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Information on EC 2.4.1.212 - hyaluronan synthase
for references in articles please use BRENDA:EC2.4.1.212
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EC Tree 2 Transferases
2.4 Glycosyltransferases
2.4.1 Hexosyltransferases
2.4.1.212 hyaluronan synthase
IUBMB Comments
The enzyme from Streptococcus Group A and Group C requires Mg2+. The enzyme adds GlcNAc to nascent hyaluronan when the non-reducing end is GlcA, but it adds GlcA when the non-reducing end is GlcNAc . The enzyme is highly specific for UDP-GlcNAc and UDP-GlcA; no copolymerization is observed if either is replaced by UDP-Glc, UDP-Gal, UDP-GalNAc or UDP-GalA. Similar enzymes have been found in a variety of organisms.
The enzyme appears in viruses and cellular organisms
- 2.4.1.212
- glycosaminoglycans
- collagen
- polysaccharide
- keratinocytes
- cartilage
- 4-methylumbelliferone
- proteoglycans
- hyaluronidases
- chondrocytes
-
dermal
- mesenchymal
-
pericellular
- pasteurella
-
udp-glucuronic
-
hyals
- versican
-
cumulus
- synovial
-
vocal
-
articular
- aggrecan
- osteoarthritis
- streptococcal
- udp-n-acetylglucosamine
- multocida
-
rhamm
- pyogenes
- udp-sugars
- chondroitin
-
glucuronic
- procollagen
- synoviocytes
-
cumulus-oocyte
- decorin
- udp-glcua
-
photoaging
- filaggrin
- equisimilis
-
ha-binding
-
temporomandibular
-
glcua
-
perineuronal
- ophthalmopathy
- zooepidemicus
-
uvb-irradiated
-
ha-mediated
-
tnfaip6
- medicine
-
hyaluronan-binding
- fibromodulin
- biglycan
- analysis
- synthesis
- drug development
- biotechnology
Reaction Schemes
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Synonyms
hyaluronan synthase, ha synthase, hyaluronan synthase 2, has-2, hyaluronic acid synthase, sehas, has-1, pmhas, hyaluronan synthase-2, hyaluronate synthase, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CHAS2
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CHAS3
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-
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DG42 protein
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-
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HA synthase
HA synthase 3
HA2
HA3
HAS
HAS-1
HAS1
Has2
Has3
HASs
HuHAS1
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-
-
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hyaluronan synthase
hyaluronan synthase 1
hyaluronan synthase 2
hyaluronan synthase 3
hyaluronan synthase-1
hyaluronan synthase-2
hyaluronan synthases 2
hyaluronan synthethase
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-
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hyaluronate synthase
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hyaluronate synthetase
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hyaluronic acid synthase
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-
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hyaluronic acid synthetase
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PmHAS
XHAS1
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-
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XHAS2
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-
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XHAS3
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-
-
-
additional information
HA synthase
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-
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HAS
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Has2
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additional information
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the enzyme of Pasteurella multocida belongs to the group of class II hyaluronan synthases
additional information
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enzyme belongs to class I of hyaluronan synthases
additional information
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the enzyme belongs to the class I hyaluronan synthases
additional information
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the enzyme belongs to the group of class I hyaluronan synthases
additional information
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enzyme belongs to class I of hyaluronan synthases
additional information
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the enzyme of Streptococcus pyogenes belongs to the group of class I hyaluronan synthases
additional information
the enzyme belongs to the group of class I hyaluronan synthases
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan] = UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
UDP-N-acetyl-alpha-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan] = UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan] = UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
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UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan] = UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
a mechanistic shift from a steady-state ordered bi-bi to rapid equilibrium ordered bi-bi mechanism is observed at the NAc-site between the HA6 and HA8 elongation
UDP-N-acetyl-alpha-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan] = UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
highly specific
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UDP-N-acetyl-alpha-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan] = UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
addition of monosaccharides to the reducing end to form a linear heteropolysaccharide chain
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UDP-N-acetyl-alpha-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan] = UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
addition of monosaccharides to the reducing end to form a linear heteropolysaccharide chain
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UDP-N-acetyl-alpha-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan] = UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
catalytically relevant Cys226 and Cys262 are located near the UDP-binding site and might be cross-linked, structural and functional role of cysteine residues, overview
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UDP-N-acetyl-alpha-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan] = UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
catalytic mechanism, no covalent intermediates
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UDP-N-acetyl-alpha-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan] = UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
catalytic mechanism
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UDP-N-acetyl-alpha-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan] = UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
Cys307 might be a catalytic residue or be involved in maintaining structure, Cys337 is involved in UDP-sugar substrate binding, enzyme amino acid residues involved in interactions with the substrate, overview
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UDP-N-acetyl-alpha-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan] = UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
2 active sites, the 2 DXD motifs of the transferase sites in the C-terminus, residues 686-703, are essential for activity
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UDP-N-acetyl-alpha-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan] = UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
The enzyme from Streptococcus Group A and Group C requires Mg2+. It is highly specific for UDP-GlcNAc and UDP-GlcA
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UDP-N-acetyl-alpha-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan] = UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
no copolymerization is observed if either is replaced by UDP-Glc, UDP-Gal, UDP-GalNAc or UDP-GalA. Similar enzymes have been found in a variety of organisms
-
-
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UDP-N-acetyl-alpha-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan] = UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
a mechanistic shift from a steady-state ordered bi-bi to rapid equilibrium ordered bi-bi mechanism is observed at the NAc-site between the HA6 and HA8 elongation
UDP-N-acetyl-alpha-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan] = UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
2 active sites, the 2 DXD motifs of the transferase sites in the C-terminus, residues 686-703, are essential for activity
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hexosyl group transfer
hexosyl group transfer
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SYSTEMATIC NAME
IUBMB Comments
Alternating UDP-alpha-N-acetyl-D-glucosamine:beta-D-glucuronosyl-(1->3)-[nascent hyaluronan] 4-N-acetyl-beta-D-glucosaminyltransferase and UDP-alpha-D-glucuronate:N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan] 3-beta-D-glucuronosyltransferase
The enzyme from Streptococcus Group A and Group C requires Mg2+. The enzyme adds GlcNAc to nascent hyaluronan when the non-reducing end is GlcA, but it adds GlcA when the non-reducing end is GlcNAc [3]. The enzyme is highly specific for UDP-GlcNAc and UDP-GlcA; no copolymerization is observed if either is replaced by UDP-Glc, UDP-Gal, UDP-GalNAc or UDP-GalA. Similar enzymes have been found in a variety of organisms.
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CAS REGISTRY NUMBER
COMMENTARY
39346-43-5
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
hyaluronic acid tetrasaccharide + UDP-alpha-D-glucuronate
?
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Substrates: -
Products: -
Products: -
?
hyaluronic acid tetrasaccharide + UDP-alpha-N-acetyl-D-glucosamine
?
-
Substrates: -
Products: -
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?
UDP-alpha-D-glucuronate + hyaluronan oligomer HA5
UDP + beta-D-glucuronosyl-(1->3)-hyaluronan oligomer HA5
Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP-alpha-N-acetyl-D-glucosamine + hyaluronan oligomer HA4
UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-hyaluronan oligomer HA4
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + hyaluronan oligomer HA6
UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-hyaluronan oligomer HA6
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + hyaluronan oligomer HA8
UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-hyaluronan oligomer HA8
Substrates: -
Products: -
Products: -
?
UDP-D-glucosamine + UDP-D-glucuronate
[beta-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + n UDP
UDP-D-glucosamine + UDP-D-glucuronate
[beta-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
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Substrates: -
Products: -
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?
UDP-D-glucuronate + chondroitin 4-sulfate trisaccharide
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Substrates: 3.6% of the activity with hyaluronan
Products: -
Products: -
?
UDP-D-glucuronate + chondroitin 6-sulfate pentasaccharide
?
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Substrates: 61% of the activity with hyaluronan
Products: -
Products: -
?
UDP-D-glucuronate + chondroitin 6-sulfate trisaccharide
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Substrates: 80% of the activity with hyaluronan
Products: -
Products: -
?
UDP-D-glucuronate + chondroitin sulfate
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Substrates: 12% of the activity with hyaluronan
Products: -
Products: -
?
UDP-D-glucuronate + unsulfated chondroitin
?
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Substrates: 54% of the activity with hyaluronan
Products: -
Products: -
?
UDP-N-acetyl-alpha-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
[hyaluronan](n) + UDP-alpha-D-glucuronate
H+ + beta-D-glucuronosyl-(1->4)-[hyaluronan](n) + UDP
Substrates: -
Products: -
Products: -
?
[hyaluronan](n) + UDP-N-acetyl-alpha-D-glucosamine
H+ + N-acetyl-beta-D-glucosaminyl-(1->4)-[hyaluronan](n) + UDP
Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
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Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
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Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
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Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
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Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
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Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
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Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
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Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
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Substrates: -
Products: -
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?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
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Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
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Substrates: -
Products: -
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?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
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Substrates: -
Products: -
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?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
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Substrates: -
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Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-D-glucosamine + UDP-D-glucuronate
[beta-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + n UDP
-
Substrates: -
Products: -
Products: -
?
UDP-D-glucosamine + UDP-D-glucuronate
[beta-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + n UDP
-
Substrates: -
Products: -
Products: -
?
UDP-D-glucosamine + UDP-D-glucuronate
[beta-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + n UDP
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-alpha-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-alpha-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: addition of monosaccharides to the linear heteropolysaccharide chain
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: addition of monosaccharides to the linear heteropolysaccharide chain, recombinant isozyme HAS2 prefers the production of a mixture of 8mers and 16mers
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: chains growth at the non-reducing end, which is terminated by lack of substrate with a non-reducing end, active with exogenously added acceptors substrates
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: formation of linear hyaluronan polymers composed of alternating beta3-N-acetylglucosamine-beta4-glucuronic acid
Products: the product chain length can grow at the reducing end up to 40000 monosaccharides with a MW of over 8 million Da before it is released by the class I enzyme
Products: the product chain length can grow at the reducing end up to 40000 monosaccharides with a MW of over 8 million Da before it is released by the class I enzyme
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: formation of linear hyaluronan polymers composed of alternating beta3-N-acetylglucosamine-beta4-glucuronic acid
Products: the product chain length can grow at the reducing end up to 40000 monosaccharides with a MW of over 8 million Da before it is released by the class I enzyme
Products: the product chain length can grow at the reducing end up to 40000 monosaccharides with a MW of over 8 million Da before it is released by the class I enzyme
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
Substrates: -
Products: product is a linear chain
Products: product is a linear chain
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: addition of monosaccharides to the reducing end to form a linear heteropolysaccharide chain
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: biosynthesis of hyaluronan
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: highly specific for UDP-N-acetyl-D-glucosamine and UDP-D-glucuronate, addition of monosaccharides to the heteropolysaccharide chain consisting of repeated disaccharides up to 25000
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: addition of monosaccharides to the reducing end to form a linear heteropolysaccharide chain
Products: product chain length depends on reaction conditions, overview
Products: product chain length depends on reaction conditions, overview
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: addition of monosaccharides to the linear heteropolysaccharide chain composed of repeating disaccharides
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: addition of monosaccharides to the reducing end to form a linear heteropolysaccharide chain
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
Substrates: biosynthesis of hyaluronan
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: addition of monosaccharides to the reducing end to form a linear heteropolysaccharide chain
Products: product chain length depends on reaction conditions, overview
Products: product chain length depends on reaction conditions, overview
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: addition of monosaccharides to the reducing end of the acceptor substrate, no binding and activity with exogenously added hyaluronan chains
Products: the product chain length can grow at the reducing end up to 40000 monosaccharides with a MW of over 8 million Da before it is released by the class I enzyme
Products: the product chain length can grow at the reducing end up to 40000 monosaccharides with a MW of over 8 million Da before it is released by the class I enzyme
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: addition of monosaccharides to the linear heteropolysaccharide chain
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: -
Products: -
Products: -
?
additional information
?
-
-
Substrates: hyaluronic acid synthase contributes to the pathogenesis of Cryptococcus neoformans infection
Products: -
Products: -
?
additional information
?
-
-
Substrates: regulation mechanism of hyaluronan biosynthesis, stimulation of cells by cytokines effects the different expression patterns of the isoforms, especially during embryonic development, the isozymes have different roles in hyaluronan biosynthesis
Products: -
Products: -
?
additional information
?
-
-
Substrates: the isozymes form products of different size, HA synthesis modeling, active site and substrate binding site are located on the big cytoplasmic loop
Products: -
Products: -
?
additional information
?
-
Substrates: isozyme HAS1 requires higher cellular UDP-GlcNAc concentration than isozymes HAS2 and HAS3. HAS1 is almost inactive in cells with low UDP-sugar supply, HAS2 activity increases with UDP-sugars, and HAS3 produces hyaluronan at high speed even with minimum substrate content. HAS works on the cytosolic pool of the UDPsugars
Products: -
Products: -
?
additional information
?
-
Substrates: isozyme HAS1 requires higher cellular UDP-GlcNAc concentration than isozymes HAS2 and HAS3. HAS1 is almost inactive in cells with low UDP-sugar supply, HAS2 activity increases with UDP-sugars, and HAS3 produces hyaluronan at high speed even with minimum substrate content. HAS works on the cytosolic pool of the UDPsugars
Products: -
Products: -
?
additional information
?
-
Substrates: isozyme HAS1 requires higher cellular UDP-GlcNAc concentration than isozymes HAS2 and HAS3. HAS1 is almost inactive in cells with low UDP-sugar supply, HAS2 activity increases with UDP-sugars, and HAS3 produces hyaluronan at high speed even with minimum substrate content. HAS works on the cytosolic pool of the UDPsugars
Products: -
Products: -
?
additional information
?
-
-
Substrates: isozyme HAS1 requires higher cellular UDP-GlcNAc concentration than isozymes HAS2 and HAS3. HAS1 is almost inactive in cells with low UDP-sugar supply, HAS2 activity increases with UDP-sugars, and HAS3 produces hyaluronan at high speed even with minimum substrate content. HAS works on the cytosolic pool of the UDPsugars
Products: -
Products: -
?
additional information
?
-
-
Substrates: HAS2, localized in the plasma membrane, uses cytoplasmic UDP-glucuronic acid and UDP-N-acetylglucosamine as substrates
Products: -
Products: -
?
additional information
?
-
Substrates: two glycosyltransferase activities in HAS that add glucuronic acid and N-acetylglucosamine into their alternating positions in the chain, using UDP-glucuronic acid (UDP-GlcUA) and UDP-N-acetylglucosamine (UDP-GlcNAc) as substrates. Sufficient supply of both UDP-GlcUA and UDP-GlcNAc is important for hyaluronan synthesis
Products: -
Products: -
?
additional information
?
-
Substrates: two glycosyltransferase activities in HAS that add glucuronic acid and N-acetylglucosamine into their alternating positions in the chain, using UDP-glucuronic acid (UDP-GlcUA) and UDP-N-acetylglucosamine (UDP-GlcNAc) as substrates. Sufficient supply of both UDP-GlcUA and UDP-GlcNAc is important for hyaluronan synthesis
Products: -
Products: -
?
additional information
?
-
Substrates: two glycosyltransferase activities in HAS that add glucuronic acid and N-acetylglucosamine into their alternating positions in the chain, using UDP-glucuronic acid (UDP-GlcUA) and UDP-N-acetylglucosamine (UDP-GlcNAc) as substrates. Sufficient supply of both UDP-GlcUA and UDP-GlcNAc is important for hyaluronan synthesis
Products: -
Products: -
?
additional information
?
-
-
Substrates: two glycosyltransferase activities in HAS that add glucuronic acid and N-acetylglucosamine into their alternating positions in the chain, using UDP-glucuronic acid (UDP-GlcUA) and UDP-N-acetylglucosamine (UDP-GlcNAc) as substrates. Sufficient supply of both UDP-GlcUA and UDP-GlcNAc is important for hyaluronan synthesis
Products: -
Products: -
?
additional information
?
-
Substrates: HAS1 produces hyaluronan of about 2000 kDa
Products: -
Products: -
-
additional information
?
-
Substrates: HAS1 produces hyaluronan of about 2000 kDa
Products: -
Products: -
-
additional information
?
-
Substrates: HAS1 produces hyaluronan of about 2000 kDa
Products: -
Products: -
-
additional information
?
-
Substrates: HAS2 produces hyaluronan of about 2000 kDa
Products: -
Products: -
-
additional information
?
-
Substrates: HAS2 produces hyaluronan of about 2000 kDa
Products: -
Products: -
-
additional information
?
-
Substrates: HAS2 produces hyaluronan of about 2000 kDa
Products: -
Products: -
-
additional information
?
-
Substrates: HAS2 produces hyaluronan of about 1000-2000 kDa
Products: -
Products: -
-
additional information
?
-
Substrates: HAS2 produces hyaluronan of about 1000-2000 kDa
Products: -
Products: -
-
additional information
?
-
Substrates: HAS2 produces hyaluronan of about 1000-2000 kDa
Products: -
Products: -
-
additional information
?
-
-
Substrates: a single protein exerts many functions as binding of two distinct UDP-sugars and binding of two distinct HA acceptor or donor species. The enzyme transfers two different sugars in two different linkages, catalyzes repetitive sugar polymerization, and transfers hyaluronan across the membrane
Products: -
Products: -
?
additional information
?
-
-
Substrates: regulation mechanism of hyaluronan biosynthesis, stimulation of cells by cytokines effects the different expression patterns of the isoforms, especially during embryonic development, the isozymes have different roles in hyaluronan biosynthesis, isozymes exhibit different functions in tumor growth, progression, and determination of malignancy
Products: -
Products: -
?
additional information
?
-
-
Substrates: isozyme expression and regulation by interleukin-1beta, progesterone, and low-molecular-weight hyaluronan in pregnant mouse uterine cervix, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: the isozymes form products of different size, HA synthesis modeling, active site and substrate binding site are located on the big cytoplasmic loop
Products: -
Products: -
?
additional information
?
-
-
Substrates: HA made by the has-1 transduced arterial smooth muscle cells is larger or part of a larger complex that resists proteolytic degradation when compared to the has-3 tansduced ASMCs. There is evidence that the different has enzymes have an inherent ability to regulate hyaluronan size
Products: -
Products: -
?
additional information
?
-
Substrates: hyaluronan synthase 1 and hyaluronan synthase 2 synthesize high molecular weight hyaluronan, while hyaluronan synthase 3 synthesizes low lecular weight hyaluronan
Products: -
Products: -
?
additional information
?
-
Substrates: hyaluronan synthase 1 and hyaluronan synthase 2 synthesize high molecular weight hyaluronan, while hyaluronan synthase 3 synthesizes low lecular weight hyaluronan
Products: -
Products: -
?
additional information
?
-
Substrates: hyaluronan synthase 1 and hyaluronan synthase 2 synthesize high molecular weight hyaluronan, while hyaluronan synthase 3 synthesizes low lecular weight hyaluronan
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme is responsible for hyaluronan biosynthesis, the hyaluronan capsule is an important, but not the only, virulence factor, physiological role of the enzyme
Products: -
Products: -
?
additional information
?
-
-
Substrates: the produced hyaluronan capsule enhances infection
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme is not processive, enzyme requires other proteins for hyaluronan translocation
Products: -
Products: -
?
additional information
?
-
-
Substrates: substrate specificity, the GlcNAc-transferase, but not the GlcUA-transferase activity depends on the WGGED motif, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: PmHAS elongates a range of acceptor molecules in addition to the cognate sugars. Certain glycosaminoglycans are very poor acceptors in comparison to the cognate molecules, but elongated products are detected. The interaction between the acceptor and the enzyme (a) the orientation of the hydroxyl at the C-4 position of the hexosamine is not critical, (b) the conformation of C-5 of the hexuronic acid (glucuronic versus iduronic) is not crucial, and (c) additional negative sulfate groups are well tolerated in certain cases, such as on C-6 of the hexosamine, but others, including C-4 sulfates, are not or are poorly tolerated
Products: -
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additional information
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Substrates: Pasteurella multocida hyaluronan synthase encompasses two transferase domains that elongate a growing hyaluronan oligosaccharide chain by addition of either GlcNAc or GlcUA residues from a corresponding UDP-sugar
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additional information
?
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Substrates: a monodispersed hyaluronan chain can be obtained by finely tuning the reaction stoichiometry. The molar ratio of precursors and acceptor molecules has an important role in enzyme kinetics
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additional information
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Substrates: initial velocity studies of single-step elongations are conducted for both domains by independently varying the concentrations of the hyaluronan oligosaccharide and the UDP-sugar. Two-substrate models are discriminated by their goodness-of-fit parameters and by dead-end inhibition studies. Coupled-enzyme assay using LDH, PK; NADH and phosphoenolpyruvate, as well as hyaluronan oligosaccharides, UDP-GlcNAc and UDP-GlcUA, overview
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additional information
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Substrates: the produced hyaluronan capsule enhances infection
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additional information
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Substrates: substrate specificity, the GlcNAc-transferase, but not the GlcUA-transferase activity depends on the WGGED motif, overview
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additional information
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Substrates: isozyme expression and effects on tumor development and growth in rats, overview, repression of HAS2 expression leads to reduced hyaluronan synthesis and reduced tumorigenicity in the peritoneum
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additional information
?
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Substrates: isozyme expression and effects on tumor development and growth in rats, overview, repression of HAS2 expression leads to reduced hyaluronan synthesis and reduced tumorigenicity in the peritoneum
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additional information
?
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Substrates: isozyme expression and effects on tumor development and growth in rats, overview, repression of HAS2 expression leads to reduced hyaluronan synthesis and reduced tumorigenicity in the peritoneum
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additional information
?
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Substrates: isozyme expression and effects on tumor development and growth in rats, overview
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additional information
?
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Substrates: isozyme expression and effects on tumor development and growth in rats, overview
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?
additional information
?
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Substrates: isozyme expression and effects on tumor development and growth in rats, overview
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additional information
?
-
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Substrates: the enzyme is inactive without bound cardiolipins
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additional information
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Substrates: determination of polymer synthesis progression direction, overview
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additional information
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Substrates: conserved cysteine residues are not essential for enzyme function
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additional information
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Substrates: a catalysis-transformation-translocation model is proposed for the hyaluronic acid synthesis and translocation processes. The residue R406 and R413 are primarily involved in catalysis, while the residues between 414 and 417 are involved in hyaluronic acid translocation
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additional information
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Substrates: a catalysis-transformation-translocation model is proposed for the hyaluronic acid synthesis and translocation processes. The residue R406 and R413 are primarily involved in catalysis, while the residues between 414 and 417 are involved in hyaluronic acid translocation
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additional information
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Substrates: the enzyme uses chitin-UDPs as primers to initiate hyaluronan synthesis, leaving the non-hyaluronan primer at the nonreducing end. chitin-UDP functions in vitro and in live cells as a primer to initiate synthesis of all HA chains and these primers remain at the nonreducing-ends of hyaluronan chains as residual chitin
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additional information
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Substrates: the enzyme uses chitin-UDPs as primers to initiate hyaluronan synthesis, leaving the non-hyaluronan primer at the nonreducing end. chitin-UDP functions in vitro and in live cells as a primer to initiate synthesis of all HA chains and these primers remain at the nonreducing-ends of hyaluronan chains as residual chitin
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additional information
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Substrates: a three-dimensional atomic scale model of class I hyaluronan synthase enzymes is presented to gain insights on functional features. 9 hyaluronan synthase-specific sub-structural elements are identified. Docking studies with UDP-substrates in the enzyme show highly overlapping single binding sites for the two UDP-substrates. In-silico and mutation studies identify functional elements implicated in polymer binding and influencing hyaluronic acid production. The studies indicate a substrate binding role for Lys139, and a critical role for Gln248 and Thr283. Anisotropic Network Modeling (ANM)-based model is analysed to assess collective global dynamics in the enzyme. Based on ligand binding landscape and architecture of functional elements, a plausible three-step molecular mechanism to extend hyaluronic acid polymer from its reducing end is proposed. The release of UDP from polymeric end may be required for glycosyltransferase reaction
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additional information
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Substrates: enzyme is responsible for hyaluronan biosynthesis, the hyaluronan capsule is an important, but not the only, virulence factor, physiological role of the enzyme
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additional information
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Substrates: determination of polymer synthesis progression direction, overview
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additional information
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Substrates: enzyme acts processive, the enzyme is active as a complex with cardiolipin, a bacterial membrane lipid
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additional information
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Substrates: conserved cysteine residues are not essential for enzyme function
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additional information
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Substrates: conserved cysteine residues are not essential for enzyme function
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additional information
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Substrates: the substrate binding selectivity is more relaxed than the specificity of catalytic transfer, a nucleotide with 2 phosphate groups and complexed with a Mg2+ ion is absolutely required for activity
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Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP-N-acetyl-alpha-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
-
Substrates: -
Products: -
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?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
-
Substrates: -
Products: -
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?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
Substrates: -
Products: -
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?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
-
Substrates: -
Products: -
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?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
-
Substrates: -
Products: -
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?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
Substrates: -
Products: -
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?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
-
Substrates: -
Products: -
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?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
Substrates: -
Products: -
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?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
-
Substrates: -
Products: -
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?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
-
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-alpha-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-alpha-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: addition of monosaccharides to the linear heteropolysaccharide chain
Products: -
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?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
Substrates: -
Products: -
Products: -
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UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: -
Products: -
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?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: addition of monosaccharides to the reducing end to form a linear heteropolysaccharide chain
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UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: -
Products: -
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?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: biosynthesis of hyaluronan
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: -
Products: -
Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: addition of monosaccharides to the reducing end to form a linear heteropolysaccharide chain
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Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
Substrates: biosynthesis of hyaluronan
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Products: -
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: -
Products: -
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?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
Substrates: -
Products: -
Products: -
?
additional information
?
-
-
Substrates: hyaluronic acid synthase contributes to the pathogenesis of Cryptococcus neoformans infection
Products: -
Products: -
?
additional information
?
-
-
Substrates: regulation mechanism of hyaluronan biosynthesis, stimulation of cells by cytokines effects the different expression patterns of the isoforms, especially during embryonic development, the isozymes have different roles in hyaluronan biosynthesis
Products: -
Products: -
?
additional information
?
-
Substrates: isozyme HAS1 requires higher cellular UDP-GlcNAc concentration than isozymes HAS2 and HAS3. HAS1 is almost inactive in cells with low UDP-sugar supply, HAS2 activity increases with UDP-sugars, and HAS3 produces hyaluronan at high speed even with minimum substrate content. HAS works on the cytosolic pool of the UDPsugars
Products: -
Products: -
?
additional information
?
-
Substrates: isozyme HAS1 requires higher cellular UDP-GlcNAc concentration than isozymes HAS2 and HAS3. HAS1 is almost inactive in cells with low UDP-sugar supply, HAS2 activity increases with UDP-sugars, and HAS3 produces hyaluronan at high speed even with minimum substrate content. HAS works on the cytosolic pool of the UDPsugars
Products: -
Products: -
?
additional information
?
-
Substrates: isozyme HAS1 requires higher cellular UDP-GlcNAc concentration than isozymes HAS2 and HAS3. HAS1 is almost inactive in cells with low UDP-sugar supply, HAS2 activity increases with UDP-sugars, and HAS3 produces hyaluronan at high speed even with minimum substrate content. HAS works on the cytosolic pool of the UDPsugars
Products: -
Products: -
?
additional information
?
-
-
Substrates: isozyme HAS1 requires higher cellular UDP-GlcNAc concentration than isozymes HAS2 and HAS3. HAS1 is almost inactive in cells with low UDP-sugar supply, HAS2 activity increases with UDP-sugars, and HAS3 produces hyaluronan at high speed even with minimum substrate content. HAS works on the cytosolic pool of the UDPsugars
Products: -
Products: -
?
additional information
?
-
-
Substrates: HAS2, localized in the plasma membrane, uses cytoplasmic UDP-glucuronic acid and UDP-N-acetylglucosamine as substrates
Products: -
Products: -
?
additional information
?
-
-
Substrates: regulation mechanism of hyaluronan biosynthesis, stimulation of cells by cytokines effects the different expression patterns of the isoforms, especially during embryonic development, the isozymes have different roles in hyaluronan biosynthesis, isozymes exhibit different functions in tumor growth, progression, and determination of malignancy
Products: -
Products: -
?
additional information
?
-
-
Substrates: isozyme expression and regulation by interleukin-1beta, progesterone, and low-molecular-weight hyaluronan in pregnant mouse uterine cervix, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: HA made by the has-1 transduced arterial smooth muscle cells is larger or part of a larger complex that resists proteolytic degradation when compared to the has-3 tansduced ASMCs. There is evidence that the different has enzymes have an inherent ability to regulate hyaluronan size
Products: -
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?
additional information
?
-
-
Substrates: enzyme is responsible for hyaluronan biosynthesis, the hyaluronan capsule is an important, but not the only, virulence factor, physiological role of the enzyme
Products: -
Products: -
?
additional information
?
-
-
Substrates: the produced hyaluronan capsule enhances infection
Products: -
Products: -
?
additional information
?
-
Substrates: Pasteurella multocida hyaluronan synthase encompasses two transferase domains that elongate a growing hyaluronan oligosaccharide chain by addition of either GlcNAc or GlcUA residues from a corresponding UDP-sugar
Products: -
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?
additional information
?
-
-
Substrates: the produced hyaluronan capsule enhances infection
Products: -
Products: -
?
additional information
?
-
Substrates: isozyme expression and effects on tumor development and growth in rats, overview, repression of HAS2 expression leads to reduced hyaluronan synthesis and reduced tumorigenicity in the peritoneum
Products: -
Products: -
?
additional information
?
-
Substrates: isozyme expression and effects on tumor development and growth in rats, overview, repression of HAS2 expression leads to reduced hyaluronan synthesis and reduced tumorigenicity in the peritoneum
Products: -
Products: -
?
additional information
?
-
Substrates: isozyme expression and effects on tumor development and growth in rats, overview, repression of HAS2 expression leads to reduced hyaluronan synthesis and reduced tumorigenicity in the peritoneum
Products: -
Products: -
?
additional information
?
-
Substrates: isozyme expression and effects on tumor development and growth in rats, overview
Products: -
Products: -
?
additional information
?
-
Substrates: isozyme expression and effects on tumor development and growth in rats, overview
Products: -
Products: -
?
additional information
?
-
Substrates: isozyme expression and effects on tumor development and growth in rats, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme is responsible for hyaluronan biosynthesis, the hyaluronan capsule is an important, but not the only, virulence factor, physiological role of the enzyme
Products: -
Products: -
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
K+
coactivation occurs if K+ is applied together with Mn2+ or Mg2+. With Mn2+, a high UDP reaction rate and high molecular mass of hyaluronic acid (2.45 MDa after 8 h) are achieved. With Mg2+, a low reaction rate and low molecular mass (1.55 MDa after 8 h) are reached. If 10 mM K+ are added to 15 mM Mg2+, a significant increase of the reaction rate by a factor of 2.7 is observed, and the molecular mass is doubled (3.11 MDa after 8 h). The coactivating effect of K+ together with Mn2+ is less pronounced
KCl
-
activates at 50 mM, slightly more effective than NaCl
Mg2+
Mn2+
NaCl
-
activates at 50 mM, slightly less effective than KCl
additional information
-
metal requirements of mutant enzymes, overview
Co2+
-
2% as effective as Mn2+ at similar concentrations
Co2+
-
18% and 39% of the wild-type GlcUA-transferase and GlcNAc-transferase activity with Mn2+, respectively, 0.2 mM
Mg2+
-
20% as effective as Mn2+ at similar concentrations
Mg2+
-
66% and 77% of the wild-type GlcUA-transferase and GlcNAc-transferase activity with Mn2+, respectively, 0.2 mM
Mg2+
Mg2+ activates with an optimum of 15-20 mM leading to about half of the yield obtained with Mn2+ after 8 h
Mg2+
-
a nucleotide with 2 phosphate groups and complexed with a Mg2+ ion is absolutely required for activity
Mn2+
Mn2+ is the preferred metal ion with an optimum of 10 mM. Presence of Mn2+ induces a concentration-dependent decomposition of UDP-GlcA to its 1,2-cyclic phosphate and UMP, especially promoted at basic pH
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside
modulates aortic smooth muscle cell motility and adhesive properties through AMP-activated protein kinase, AMPK
AG825
ErbB2 inhibitor, blocks the heregulin-mediated HAS isozyme phosphorylation/activation; ErbB2 inhibitor, blocks the heregulin-mediated HAS isozyme phosphorylation/activation; ErbB2 inhibitor, blocks the heregulin-mediated HAS isozyme phosphorylation/activation
mannose
inhibits HAS because it depletes UDP-GlcNAc in cells; inhibits HAS because it depletes UDP-GlcNAc in cells; inhibits HAS because it depletes UDP-GlcNAc in cells
metformin
modulates aortic smooth muscle cell motility and adhesive properties through AMP-activated protein kinase, AMPK
PEG
-
increasing MW increases the inhibitory effect on the enzyme, overview
thiazolidinedione
ERK inhibitor, blocks the heregulin-mediated HAS isozyme phosphorylation/activation; ERK inhibitor, blocks the heregulin-mediated HAS isozyme phosphorylation/activation; ERK inhibitor, blocks the heregulin-mediated HAS isozyme phosphorylation/activation
UDP-glucuronate
The substrate UDP-GlcA inhibits pmHAS in concentrations above 8 mM
4-Methylumbelliferone
inhibits HAS because it depletes UDPGlcUA in cells; inhibits HAS because it depletes UDPGlcUA in cells; inhibits HAS because it depletes UDPGlcUA in cells
4-Methylumbelliferone
-
changes the localization of the enzyme by preventing its association with the plasma membrane
iodoacetamide
-
15% inhibition at 5 mM, biphasic inhibition
methylmethanethiosulfonate
-
93% reduced activity at 0.05 mM
N-ethylmaleimide
-
reacts with the Cys residues C226, C262, and C281, but not with C367, binding of substrates UDP-N-acetyl-D-glucosamine, UDP-D-glucuronate, or of product UDP protects the enzyme from inhibition by NEM, level of inhibition of wild-type and mutant enzymes, overview
N-ethylmaleimide
-
biphasic inhibition, about 50% reduced reaction velocity, unaltered Km-value, 70% inhibition at 5 mM
N-ethylmaleimide
-
inhibits wild-type and mutant enzymes by about 90% at 0.2 mM, UDP-N-acetyl-D-glucosamine protects the enzyme best against inactivation by NEM compared to diverse other nucleotide compounds, overview
sodium arsenite
-
inhibition of wild-type and mutant enzymes, no inhibition of C262 deletion mutant, overview
sulfhydryl reagents
-
enzyme is inhibited by sulfhydryl-modifying reagents, inhibition mode and mechanism
sulfhydryl reagents
enzyme is inhibited by sulfhydryl-modifying reagents, inhibition mode and mechanism
additional information
-
using inhibitors for MEK1/2, U0126, and for PI3K, LY294002, and the SN50 inhibitor, a complete inhibition of HAS2 transcriptional activity and hyaluronan sythesis is observed
-
additional information
AMP-activated protein kinase, AMPK, phosphorylates HAS2 at Thr110, which inhibits its enzymatic activity, and is itself inhibit by Compound C. Isoenzymes HAS1 and HAS3 are not modified by the kinase
-
additional information
-
interleukin-1beta augmented the expression of all 3 isozymes in the uterine cervix of pregnant mice, progesterone inhibited expression of isozymes HAS1 and HAS2
-
additional information
-
using inhibitors for MEK1/2, U0126, and for PI3K, LY294002, and the SN50 inhibitor, a complete inhibition of HAS2 transcriptional activity and hyaluronan sythesis is observed
-
additional information
M1H2Q1
activity and structure of HAS are only minimally affected by 350 mM urea
-
additional information
-
enzyme is more active in 25 mM phosphate buffer than in 50 mM, enzyme is inhibited by increasing viscosity via addition of PEG, glycerol, sucrose or ethylene glycol
-
additional information
-
heating, oxidization or cysteine modification with N-ethylmaleimide inhibit the enzyme
-
additional information
-
HA product size is decreased by increasing concentrations of glycerol
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
black rice hydrolized peptides
BRP from germinated Oryza sativa L. var. japonica
-
dioleoyl phosphatidic acid
-
stimulates about 10fold
ERK
heregulin-mediated HAS isozyme phosphorylation/activation
-
O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate
-
increases O-GlcNAcylation and HA synthesis
phorbol 12-myristate 13-acetate
-
activation of enzyme in plasma membrane fraction
platelet-derived growth factor BB
-
activation of enzyme in plasma membrane fraction
-
tunicamycin
-
significant increase in HAS activity in the cytosolic membrane fraction after tunicamycin treatment
cardiolipin
the bacterial enzyme is strictly associated with cardiolipin and the catalytic activity is dependent on such lipid
cardiolipin
-
required for full activity, activates up to 10fold, 14-18 molecules of cardiolipin are bound to one molecule of enzyme
cardiolipin
-
the bacterial enzyme is strictly associated with cardiolipin and the catalytic activity is dependent on such lipid
tetraoleoyl cardiolipin
-
strong activation, same pattern of lipid preference between pH 6 and 10.5. Lipid-independent activity at pH 11.5
additional information
-
the activity is independent of cardiolipin
-
additional information
-
HAS2 can be O-GlcNAcylated on serine 221, which strongly increases its activity and its stability to half-life of over 5 h versus 17 min without O-GlcNAcylation
-
additional information
-
the isozymes use cytoplasmic UDP-GlcNAc and UDP-GlcUA as precursors to polymerize the hyaluronan chain and to extrude it out of the cell without the necessity of a primer or an anchor protein or lipid
-
additional information
-
progesterone activates the expression of HAS3, low-molecular-weight hyaluronan activates the expression of isozyme HAS1
-
additional information
-
enzyme is more active in 25 mM phosphate buffer than in 50 mM
-
additional information
-
tetramyristoyl cardiolipin is ineffective in activation
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.7
hyaluronan oligomer HA4
with UDP-alpha-N-acetyl-D-glucosamine, pH 8.0, 35°C, recombinant enzyme
-
0.6
hyaluronan oligomer HA5
with UDP-alpha-D-glucuronate, pH 8.0, 35°C, recombinant enzyme
-
1
hyaluronan oligomer HA6
with UDP-alpha-N-acetyl-D-glucosamine, pH 8.0, 35°C, recombinant enzyme
-
0.7
hyaluronan oligomer HA8
with UDP-alpha-N-acetyl-D-glucosamine, pH 8.0, 35°C, recombinant enzyme
-
23.4
UDP-N-acetyl-alpha-D-glucosamine
pH 7.0, 25 °C, 10 mM MnCl2 and 5 mM UDP-GlcA (in absence of HA oligosaccharide as acceptor substrate)
0.8
UDP-alpha-D-glucuronate
pH 7.0, 25 °C, 10 mM MnCl2 and 15 mM UDP-GlcNAc (in absence of HA oligosaccharide as acceptor substrate)
0.04
UDP-D-glucuronate
-
pH 7.0, 30°C, recombinant mutant C281A
0.044
UDP-D-glucuronate
-
pH 7.0, 30°C, recombinant mutant C226S
0.056
UDP-D-glucuronate
-
pH 7.0, 30°C, recombinant mutant C281S
0.077
UDP-D-glucuronate
-
pH 7.0, 30°C, recombinant wild-type enzyme
0.079
UDP-D-glucuronate
-
pH 7.0, 30°C, recombinant mutant C367S
0.085
UDP-D-glucuronate
-
pH 7.0, 30°C, recombinant mutant C367A
0.088
UDP-D-glucuronate
-
pH 7.0, 30°C, recombinant mutant C226A
0.096
UDP-D-glucuronate
-
pH 7.0, 30°C, recombinant mutant C262S
0.11
UDP-D-glucuronate
-
pH 7.5, 30°C, recombinant wild-type enzyme at low UDP-N-acetyl-D-glucosamine concentration, and mutant C239S
0.146
UDP-D-glucuronate
-
pH 7.0, 30°C, recombinant mutant C262A
0.053
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30°C, recombinant mutant C226A/C281A
0.065
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30°C, recombinant mutant C281A/C367A
0.074
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30°C, recombinant wild-type enzyme
0.079
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30°C, recombinant mutant C226A/C367A
0.09
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30°C, recombinant mutant C367A
0.091
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30°C, recombinant mutant C367S
0.098
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30°C, recombinant mutant C281S
0.113
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30°C, recombinant mutant C262A/C281A
0.121
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30°C, recombinant mutant C262A/C367A
0.13
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30°C, recombinant mutant C281A
0.134
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30°C, recombinant mutant C226A/C262A
0.153
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30°C, recombinant mutant C262S
0.154
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30°C, recombinant mutant C226A
0.186
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30°C, recombinant mutant C262A
0.232
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30°C, recombinant mutant C226S
0.26
UDP-N-acetyl-D-glucosamine
-
pH 7.5, 30°C, recombinant wild-type enzyme at low UDP-glucuronate concentration
0.4
UDP-N-acetyl-D-glucosamine
-
pH 7.5, 30°C, recombinant wild-type enzyme and mutants C210S, C337S at low UDP-glucuronate concentration
0.88
UDP-N-acetyl-D-glucosamine
-
pH 7.5, 30°C, recombinant mutant C337S at higher UDP-glucuronate concentration
additional information
additional information
-
values for other substrate concentrations
-
additional information
additional information
-
recombinant enzyme, kinetics at different pH, thermodynamics
-
additional information
additional information
-
kinetics, kinetic analysis of Cys-deletion mutants, overview
-
additional information
additional information
-
Km values of the enzyme in standard reaction in presence of diverse protecting nucleotide compounds, overview
-
additional information
additional information
-
kinetics, wild-type and mutant enzymes
-
additional information
additional information
structural and kinetic analysis and modeling, both NAc- and UA-transferase domains follow a sequential kinetic mechanism, most likely an ordered one in which the UDP-sugar donor binds first, followed by the HA oligosaccharide. After transfer of the sugar moiety, both products are released, first the elongated HA oligosaccharide and then the UDP sugar. A mechanistic shift from a steady-state ordered bi-bi to rapid equilibrium ordered bi-bi mechanism is observed at the NAc-site between the HA6 and HA8 elongation, detailed overview
-
additional information
additional information
availability of substrate UDP-GlcNAc does not considerably influence the Km of Has1 toward UDP-GlcUA, whereas levels of UDP-GlcUA have a significant effect of the Km toward UDP-GlcNAc
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
7.9
hyaluronan oligomer HA4
with UDP-alpha-N-acetyl-D-glucosamine, pH 8.0, 35°C, recombinant enzyme
-
7.9
hyaluronan oligomer HA5
with UDP-alpha-D-glucuronate, pH 8.0, 35°C, recombinant enzyme
-
13.5
hyaluronan oligomer HA6
with UDP-alpha-N-acetyl-D-glucosamine, pH 8.0, 35°C, recombinant enzyme
-
8.8
hyaluronan oligomer HA8
with UDP-alpha-N-acetyl-D-glucosamine, pH 8.0, 35°C, recombinant enzyme
-
120
UDP-D-glucuronate
-
recombinant enzyme, pH 7.0, 30°C
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4.5
ethylene glycol
-
recombinant enzyme, pH 7.0, 30°C
3.3
glycerol
-
recombinant enzyme, pH 7.0, 30°C
3.5
PEG 20000
-
recombinant enzyme, pH 7.0, 30°C
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0000000062
HAS activity, HAS1siRNA + HAS2siRNA + HAS3siRNA treatment, plus heregulin
0.0000000092
HAS activity, HAS1siRNA + HAS2siRNA + HAS3siRNA treatment
0.0000000227
HAS activity, HAS2siRNA treatment, plus heregulin
0.0000000237
HAS activity, scrambled sequence treatment, control
0.0000000248
HAS activity, HAS1siRNA treatment, plus heregulin
0.000000025
HAS activity, HAS3siRNA treatment, plus heregulin
0.0000000257
HAS activity, AG825 treatment, plus heregulin
0.0000000263
HAS activity, thiazolidinedione treatment, plus heregulin
0.0000000583
HAS activity, scrambled sequence treatment, control, plus heregulin
0.0000000627
HAS activity, no treatment, control, plus heregulin
31.6
-
deletion mutant DELTA3-C262, pH 7.0, 30°C
38.6
-
deletion mutant DELTA3-C226, pH 7.0, 30°C
additional information
additional information
-
nonradioactive method to quantify the HAS enzymatic activity in crude cellular membrane preparations. The method uses nonradioactive UDP-sugar precursors, the newly synthesized hyaluronic acid is then digested to obtain unsaturated disaccharides which are quantified by HPLC. pH 7.1, 37°C
additional information
activity in wild-type cells and their oncogenic transformants
additional information
activity in wild-type cells and their oncogenic transformants
additional information
activity in wild-type cells and their oncogenic transformants
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.1
7.4
7.5
additional information
highest activity in MES, MOPS and HEPES buffers and lower activity in TRIS-buffer
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22
30
37
60
22
-
HAS capture assay, overnight at room temperature
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
3 isozymes HAS1, HAS2, and HAS3 encoded by genes HAS1, HAS2, and HAS3
-
-
brenda
isoform HAS1; patients with multiple myeloma and Waldenstrom macroglobulinemia
SwissProt
brenda
3 isozymes HAS1, HAS2, and HAS3 encoded by genes HAS1, HAS2, and HAS3
-
-
brenda
-
-
-
brenda
human pathogen, single gene hasA in the has operon, class I enzyme
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
expression of HAS1 splice variants is absent from B cells of healthy donors and in multiple myeloma and monoclonal gammopathy of undetermined significance (MGUS) is restricted to the B-cell compartment
brenda
tumorigenic cell line, 3-5fold higher hyaluronan accumulation than in the parental cell line 3Y1
brenda
MDA-MB-231 and Hs-578T breast cancer cell line express higher levels of HAS2 mRNA and synthesize higher amounts of HA than breast cancer cell lines with a less aggressive phenotype, like MCF-7
brenda
-
HAS1 expression is shown in 55.7% of SIRPA-positive macrophages in stage III follicles
brenda
MDA-MB-231 and Hs-578T breast cancer cell line express higher levels of HAS2 mRNA and synthesize higher amounts of HA than breast cancer cell lines with a less aggressive phenotype, like MCF-7. HAS2 is dramatically increased in bone metastases compared to the parental MDA-MB-231 cells
brenda
embryonic mouse molar. Difference in the distribution and expression of the three hyaluronan synthases at different developmental stages. Hyaluronan synthase 1 and hyaluronan synthase 2, but not hyaluronan synthase 3, are highly expressed in the bud stage
brenda
-
expression of isoform HAS1 in theca cells of healthy and early atretic follicles of stage I and stage II and in progressing atretic stage III follicles
brenda
serous epithelial ovarian tumor
brenda
platelet-derived growth factor BB exerts dominant influence on HAS2 isoform expression by osteoblasts
brenda
metastatic cell line, 3-5fold higher hyaluronan accumulation than in the parental cell line 3Y1
brenda
-
35 endometrial tissue biopsies from 35 patients, including proliferative and secretory endometrium, post-menopausal proliferative endometrium, complex atypical hyperplasia, grade 1 and grade 2 + 3 endometrioid adenocarcinomas. Immunoreactivity of all HAS proteins is increased in the cancer epithelium
brenda
additional information
fibroblast, expression of isozymes HAS1 and HAS2 is increased after oncogenic malignant transformation with v-sre and/or v-fos, while only the expression of isozyme HAS2 is increased by transformation with v-HA-ras
brenda
fibroblast, oncogenic malignant transformation with v-sre and/or v-fos, and v-HA-ras
brenda
-
HAS2 is the main synthase in aortic smooth muscle cells
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double Has2/Hyal-1 immunohistochemistry reveals partial co-localization of Has2 and Hyal-2 (EC 3.2.1.36) two proteins in protoplasmic astrocytes
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double Has2/Hyal-1 immunohistochemistry reveals partial co-localization of Has2 and Hyal-2 (EC 3.2.1.36) two proteins in protoplasmic astrocytes
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at embryonic day 7.5, Has2 is expressed throughout the gastrulating embryo. After ambryonic day 8.5, Has2 continues to be strongly, albeit transiently, expressed in numerous tissues, including the branchial arches and craniofacial structures such as the palatal shelves and lens pit. Has2 is also expressed during cardiac, skeletal, and tail development
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Has3 transcripts are first detected at embryonic day 10.5 in the maxillary and mandibular components of the first branchial arch. Has3 expression in the developing teeth, vibrissae hair follicles, nasal cavity, and inner ear complements the expression pattern of Has2
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at embryonic day 7.5, Has1 is expressed throughout the gastrulating embryo. After ambryonic day 8.5, Has1 expression disappears
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expression of different HAS isoenzymes during embryonic development, overview. Intense hyaluronan staining is observed throughout the development in the tissues of mesodermal origin, like heart and cartilages, but also for example during the maturation of kidneys and stratified epithelia. In general, staining for one or several HAS isozymes correlates with hyaluronan staining. While epithelial cells are mostly negative for HASs, stratified epithelia become HAS positive during differentiation
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expression of different HAS isoenzymes during embryonic development, overview. Intense hyaluronan staining is observed throughout the development in the tissues of mesodermal origin, like heart and cartilages, but also for example during the maturation of kidneys and stratified epithelia. In general, staining for one or several HAS isozymes correlates with hyaluronan staining. While epithelial cells are mostly negative for HASs, stratified epithelia become HAS positive during differentiation
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HAS2 is suppressed in senescent fibroblasts, real time PCR enzyme expresion in fibrotic and senescent fibroblasts
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MDA-MB-231 and Hs-578T breast cancer cell line express higher levels of HAS2 mRNA and synthesize higher amounts of HA than breast cancer cell lines with a less aggressive phenotype, like MCF-7
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13fold decrease in hyaluronan synthase 3 expression in mineralising MG63 cells
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no significant change in hyaluronan synthase 2 expression in mineralising cells
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hyaluronan synthesized by HAS-2 in MG-63 plays a crucial role in osteosarcoma cell proliferation, motility, and invasion
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TGF-beta2 is the major stimulator of HAS2 isoform expression in osteosarcoma cells
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double Has2/Hyal-1 immunohistochemistry reveals partial co-localization of Has2 and Hyal-2 (EC 3.2.1.36). Has2/Hyal-2 double staining in layer V reveals three types of neurons: Has2+/Hyal-2-, Has2-/Hyal-2+ and Has2+/Hyal-2+. Of these three, the third type is the least abundant. Has2 is present in both PNN-enveloped neurons and neurons devoid of perineuronal nets (PNNs)
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double Has2/Hyal-1 immunohistochemistry reveals partial co-localization of Has2 and Hyal-2 (EC 3.2.1.36). Has2/Hyal-2 double staining in layer V reveals three types of neurons: Has2+/Hyal-2-, Has2-/Hyal-2+ and Has2+/Hyal-2+. Of these three, the third type is the least abundant. Has2 is present in both PNN-enveloped neurons and neurons devoid of perineuronal nets (PNNs)
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SKOV-3.ipl cell, the cell line is established from ascites that developed in a nu/nu mouse given an intraperitoneal injection of SK-OV-3 human ovarian carcinoma cell line
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the SK-OV-3.ipl cell line is established from ascites that developed in a nu/nu mouse given an intraperitoneal injection of SK-OV-3 human ovarian carcinoma cell line
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expression of isoform HAS1 in theca cells of healthy and early atretic follicles of stage I and stage II and in progressing atretic stage III follicles
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additional information
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while immunoreactivity for HASs increases in the cancer cells, tumor mRNA levels for HASs are not changed, suggesting that reduced turnover of HAS protein may also have contributed to the accumulation of hyaluronan, quantitative expression analysis, overview
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additional information
both full length and splice variants of HAS1 are expressed in malignancies like bladder and prostate cancers, multiple myeloma, and malignant mesothelioma
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additional information
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subcellular localization study, intracellular localization of EGFP-HAS1 and Dendra-HAS1 in MCF-7 cells, overview
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additional information
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isozyme expression profile in uterine cervix of pregnant mice
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additional information
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immunohistochemic localization, highest content in the granulosa layer
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additional information
immunohistochemic localization, highest content in the granulosa layer
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additional information
immunohistochemic localization, highest content in the granulosa layer
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
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bound, enzyme possesses a cysteine cluster localized at the inner surface of the cell membrane near the substrate/product-binding sites
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most parts of the enzyme, except the transmembrane region, are cytoplasmic including the active site
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isozyme HAS2 has the brightest signal in the endoplasmic reticulum
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isozyme HAS3 has the brightest signal in the Golgi and microvillous protrusions
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isozyme HAS1 has the brightest signal in the Golgi network
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fraction containing membrane proteins from the endoplasmic reticulum and Golgi apparatus
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are integral membrane proteins with transmembrane domains in addition to membrane-associated domains
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presence of five trans-membrane domains at positions 7-28, 33-54, 319-341, 351-370 and 377-395
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enzyme is predicted to be an integral membrane protein
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integral, plasma membrane residence of hyaluronan synthase is coupled to its enzymatic activity
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in natural membrane extensions
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the hyaluronan polymer is synthesized on the cytosolic side of the cell membrane by the membrane-embedded hyaluronan synthase
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additional information
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sequence contains no transmembrane region
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additional information
the intracellular distribution pattern of HAS1 is distinct from other isoenzymes. In all cell types studied so far, a high proportion of HAS1 is accumulated intracellularly, with a faint signal detected on the plasma membrane and its protrusions. The recombinant GFP-HAS1 signal is mainly cytoplasmic, rather than on the plasma membrane, being distributed either diffusely or in cytoplasmic patches, and partially co-localizing with the Golgi apparatus. Transfected HAS1V-GFP constructs localize with cytoskeletal structures like microtubules
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additional information
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the HAS1 enzymatic activity depends on the endoplasmic reticulum-Golgi-plasma membrane traffic, like reported for isozymes HAS2 and HAS3
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additional information
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recombinant isozymes GFP-HAS2 and GFP-HAS3 travel through endoplasmic reticulum, Golgi, plasma membrane, and endocytic vesicles in keratinocytes
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Highest Expressing Human Cell Lines
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
the three HAS isoenzymes, HAS1, HAS2, and HAS3, expressed in mammalian cells differ in their enzymatic properties and regulation by external stimuli
malfunction
metabolism
physiological function
additional information
malfunction
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catalytically inactive mutant K190R HAS2 forms dimers with wild-type HAS2 and quenches the activity of wild-type HAS2
malfunction
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HAS-1 overexpression in dermal wounds decreases elements of scar formation
malfunction
reduction of HA due to decreased HAS activity, caused by phosphorylation at Thr110 through AMP-activated protein kinase, decreases the ability of aortic smooth muscle cells to proliferate, migrate, and recruit immune cells, thereby reducing the pro-atherosclerotic AoSMC phenotype. AMP-activated protein kinase can block the pro-atherosclerotic signals driven by HA by interaction with its receptors
malfunction
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the regulation of isozyme HAS2 by O-GlcNAcylation can have important therapeutic consequences considering that the excess of glucose can lead to a dramatic increase of UDP-GlcNAc and hyaluronan (in particular in cells where the uptake of glucose is insulin-independent). Clinical and experimental evidences show that in hyperglycemic patients and in streptozotocin-induced diabetes animals there is evidence of hyaluronan accumulation both in plasma and in vascular wall
malfunction
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embryonic lethality of genetic deletion of HAS2, some HAS2-specific functions are not compensated for by isozyme HAS1 or HAS3
malfunction
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in a ligation-induced carotid artery injury model, attenuated neointimal hyperplasia occurs in HAS3-null animals compared with wild-type control C57BL/6J mice. No changes are observed in medial and neointimal cell density, proliferation, or apoptosis. A lack of compensatory upregulation of isozymes HAS1 or HAS2, HAS3 deletion is associated with a reduction in vascular hyaluronan content, most dramatically in the media rather than the neointima. Transcriptome analysis of injured vessels from wild-type and HAS3-null mice reveals differential activation of pathways associated with a migratory VSMC phenotype. Isozyme HAS3 overexpression in VSMCs supports a migratory phenotype in response to platelet-derived growth factor BB (PDGF-BB), whereas knockdown of HAS3 results in reduced PDGF-BB-induced migration. Isozyme HAS3 knockdown also leads to a decrease in PDGF-B mRNA levels
malfunction
downregulation of HAS2 initiates and regulates fibroblast senescence through a p27-CDK2-SKP2 pathway. Deletion of HAS2 in mouse mesenchymal cells increases the cellular senescence of fibroblasts in bleomycin-induced mouse lung fibrosis in vivo. Overexpression of HAS2 in mesenchymal cells promotes an invasive phenotype resulting in severe fibrosis and downregulation of HAS2 promotes resolution. HAS2 deficiency leads to embryonic lethality. Downregulation of HAS2 increases p27 protein stability. p27 inhibits cell proliferation by regulating CDK2 activity. HAS2 deletion enhances cell stress responses. Phenotypes, detailed overview
malfunction
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isozyme HAS3 overexpression downregulates MV3 melanoma cell proliferation, migration and adhesion. Overexpression of isozyme HAS3 decreases cell proliferation, directional and random cell migration, and promotes cell cycle arrest at G1/G0 and decreases ERK1/2 phosphorylation suggesting that inhibition of MAP-kinase signaling is responsible for the suppressive effects on the malignant phenotype of MV3 melanoma cells. EGFP-HAS3 overexpression downregulates several signaling pathways in MV3 melanoma cells
malfunction
Has2-/- mice are embryonic lethal. Has2-/- embryos die between embryonic day 9.5 and 10.5 and exhibit severe cardiac and vascular abnormalities, in addition to yolk sac and somite deformities
malfunction
Has3/Apoe double deficient mice develop less atherosclerosis characterized by decreased Th1-cell responses, decreased IL-12 release, and decreased macrophage-driven inflammation
malfunction
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in a ligation-induced carotid artery injury model, attenuated neointimal hyperplasia occurs in HAS3-null animals compared with wild-type control C57BL/6J mice. No changes are observed in medial and neointimal cell density, proliferation, or apoptosis. A lack of compensatory upregulation of isozymes HAS1 or HAS2, HAS3 deletion is associated with a reduction in vascular hyaluronan content, most dramatically in the media rather than the neointima. Transcriptome analysis of injured vessels from wild-type and HAS3-null mice reveals differential activation of pathways associated with a migratory VSMC phenotype. Isozyme HAS3 overexpression in VSMCs supports a migratory phenotype in response to platelet-derived growth factor BB (PDGF-BB), whereas knockdown of HAS3 results in reduced PDGF-BB-induced migration. Isozyme HAS3 knockdown also leads to a decrease in PDGF-B mRNA levels
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malfunction
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HAS-1 overexpression in dermal wounds decreases elements of scar formation
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metabolism
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regulation of hexosamine biosynthetic pathway, biosynthesis of hyaluronan and other glycoconjugates, and protein O-GlcNAcylation, overview
metabolism
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the most general sensor of cellular nutritional status is the hexosamine biosynthetic pathway that brings to the formation of UDP-GlcNAc and intracellular protein glycosylation by O-linked attachment of the monosaccharide beta-N-acetylglucosamine (O-GlcNAcylation) to specific aminoacid residues. Such highly dynamic and ubiquitous protein modification affects residue Ser221 residue of isozyme HAS2 that lead to a dramatic stabilization of the enzyme in the membrane
metabolism
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role of hyaluronan in vascular disease, a multitude of synthases (HAS1, HAS2, and HAS3) and multiple hyaluronidases are involved in its metabolism
metabolism
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role of hyaluronan in vascular disease, a multitude of synthases (HAS1, HAS2, and HAS3) and multiple hyaluronidases are involved in its metabolism
metabolism
hyaluronan synthase 2 expression is elevated in both human and murine liver fibrosis. The enzyme actively synthesizes hyaluronan in hepatic stellate cells and promotes activation of hepatic stellate cells and liver fibrosis through Notch1
metabolism
histamine controls hyaluronan metabolism by up-regulating HYBID (hyaluronan-binding protein) and down-regulating hyaluronan synthase 2 (HAS2) via distinct signaling pathways downstream of histamine receptor H1
metabolism
hyaluronan is expressed in a temporal-spatial expression pattern and may play a role in embryonic tooth morphogenesis. The difference in the distribution and expression of the three hyaluronan synthases at different developmental stages also supports their roles in cell proliferation, cell differentiation and cell migration
metabolism
hyaluronan synthase 2 expression is elevated in both human and murine liver fibrosis. The enzyme actively synthesizes hyaluronan in hepatic stellate cells and promotes activation of hepatic stellate cells and liver fibrosis through Notch1
metabolism
after stroke, a substantial reorganization of polysaccharide content occurs, and interfering with this process at early time has a beneficial effect on recovery. Simultaneous upregulation of mRNA of hyaluronan (HA) synthesizing and degrading enzymes in the perilesional area early after stroke are observed with acceleration of HA turnover in ischaemic animals. Statistical analysis do not reveal significant changes in expression of isozymes Has1 or Has3 in the perilesional area, whereas Has2 expression is significantly altered. However, Bonferroni post hoc analysis shows increased Has1 expression in contralateral cortex 3 months post-stroke. The expression of Has3 is altered in the remote area bilaterally at 3 months
metabolism
after stroke, a substantial reorganization of polysaccharide content occurs, and interfering with this process at early time has a beneficial effect on recovery. Simultaneous upregulation of mRNA of hyaluronan (HA) synthesizing and degrading enzymes in the perilesional area early after stroke are observed with acceleration of HA turnover in ischaemic animals. Differential cellular localization of enzymes, with hyaluronidase 1 (EC 3.2.1.36) in astrocytes and hyaluronan synthase 2 in astrocytes and neurons, and poststroke upregulation of both of them in astrocytes. beta-glucuronidase is observed in neurons but post-stroke upregulation occurs in microglia. Inhibition of hyaluronidase activity early after stroke results in improved performance in skilled reaching test, without affecting the numbers of perineuronal nets (PNNs). Statistical analysis do not reveal significant changes in expression of isozymes Has1 or Has3 in the perilesional area, whereas Has2 expression is significantly altered. However, Bonferroni post hoc analysis shows increased Has1 expression in contralateral cortex 3 months post-stroke. The expression of Has3 is altered in the remote area bilaterally at 3 months
metabolism
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role of hyaluronan in vascular disease, a multitude of synthases (HAS1, HAS2, and HAS3) and multiple hyaluronidases are involved in its metabolism
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metabolism
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after stroke, a substantial reorganization of polysaccharide content occurs, and interfering with this process at early time has a beneficial effect on recovery. Simultaneous upregulation of mRNA of hyaluronan (HA) synthesizing and degrading enzymes in the perilesional area early after stroke are observed with acceleration of HA turnover in ischaemic animals. Statistical analysis do not reveal significant changes in expression of isozymes Has1 or Has3 in the perilesional area, whereas Has2 expression is significantly altered. However, Bonferroni post hoc analysis shows increased Has1 expression in contralateral cortex 3 months post-stroke. The expression of Has3 is altered in the remote area bilaterally at 3 months
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metabolism
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after stroke, a substantial reorganization of polysaccharide content occurs, and interfering with this process at early time has a beneficial effect on recovery. Simultaneous upregulation of mRNA of hyaluronan (HA) synthesizing and degrading enzymes in the perilesional area early after stroke are observed with acceleration of HA turnover in ischaemic animals. Differential cellular localization of enzymes, with hyaluronidase 1 (EC 3.2.1.36) in astrocytes and hyaluronan synthase 2 in astrocytes and neurons, and poststroke upregulation of both of them in astrocytes. beta-glucuronidase is observed in neurons but post-stroke upregulation occurs in microglia. Inhibition of hyaluronidase activity early after stroke results in improved performance in skilled reaching test, without affecting the numbers of perineuronal nets (PNNs). Statistical analysis do not reveal significant changes in expression of isozymes Has1 or Has3 in the perilesional area, whereas Has2 expression is significantly altered. However, Bonferroni post hoc analysis shows increased Has1 expression in contralateral cortex 3 months post-stroke. The expression of Has3 is altered in the remote area bilaterally at 3 months
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physiological function
the reduction of hyaluronan caused by enzyme downregulation through 4-methylumbelliferone is associated with a significant inhibition of cell migration, proliferation and invasion
physiological function
inhibition of HAS2 expression by siRNA decreases matrix metalloprotein MMP-7 expression by about 20%, and dramaticlly decreases MMP-7 protein, and enzymatic activity. HAS isoforms and hyaluronan may mediate cellular invasion via changes in matrix metalloprotein MMP-7 expression
physiological function
inhibition of HAS2 expression by siRNA decreases matrix metalloprotein MMP-7 expression by about 30%, and dramaticlly decreases MMP-7 protein, and enzymatic activity. HAS isoforms and hyaluronan may mediate cellular invasion via changes in matrix metalloprotein MMP-7 expression
physiological function
mainly high molecular weight hyaluronan synthesized by isoform HAS1 regulates HT-1080 cell motility
physiological function
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hyaluronan concentration in follicular fluids increases during atresia. Isoform HAS1 may be the dominant HAS protein in theca cells to produce hyaluronan in pig ovaries
physiological function
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the hyaluronan synthase catalyzes the synthesis and membrane translocation of hyaluronan, it is both necessary and sufficient to translocate hyaluronan in a reaction that is tightly coupled to hyaluronan elongation. Hyaluronan synthesis and translocation are spatially coupled events, which allow hyaluronan synthesis even in the presence of a large excess of hyaluronan-degrading enzyme
physiological function
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hyaluronan synthase mediates dye translocation across liposomal membranes
physiological function
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HAS-1 treatment of wounds promotes a more organized extracellular matrix with the regeneration of dermal appendages, including hair follicles, increased regenerative healing, overview
physiological function
the expression of the Has1 isoenzyme, most dependent on high UDP-sugar contents, is coordinated with a metabolic state that maintains a high level of these substrates
physiological function
hyaluronan synthesis is inhibited by adenosine monophosphate-activated protein kinase through the regulation of HAS2 activity in human aortic smooth muscle cells
physiological function
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the role of UDP-N-acetylglucosamine and O-GlcNAc-acylation of hyaluronan synthase 2 in the control of chondroitin sulfate and hyaluronan synthesis, overview. O-linked GlcNAc (O-GlcNAcylation) is regulated by the action of two enzymes, O-GlcNAc transferase and O-GlcNAc hydrolase. The HA increase due to O-GlcNAcylation regulates inflammatory cell adhesion, the number of monocytes that adhere on AoSMC monolayer cultures is increased
physiological function
hyaluronan is the largest and one of the most abundant glycosaminoglycans of the extracellular space. Hyaluronan synthases are glycosyltransferases acting on the inner face of plasma membrane, adding alternately glucuronic acid and N-acetylglucosamine to the reducing end of the growing chain. Hyaluronan synthase forms a reserve that is transported to the plasma membrane for rapid activation of hyaluronan synthesis. The levels and localizations of HAS isoforms are likely to be highly important in processes like embryonic development, wound healing, inflammation, and malignant growth
physiological function
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hyaluronan is a glycosaminoglycan composed by repeating units of D-glucuronic acid and N-acetylglucosamine that is ubiquitously present in the extracellular matrix where it has a critical role in the physiology and pathology of several mammalian tissues. Hyaluronan represents a perfect environment in which cells can migrate and proliferate. Several receptors can interact with hyaluronan at cellular level triggering multiple signal transduction responses. The control of the hyaluronan synthesis is therefore critical in extracellular matrix assembly and cell biology, analysis of metabolic regulation of hyaluronan synthesis, overview. In contrast with other glycosaminoglycans, which are synthesized in the Golgi apparatus, hyaluronan is produced at the plasma membrane by hyaluronan synthases (HAS1-3), which use cytoplasmic UDP-glucuronic acid and UDP-N-acetylglucosamine as substrates. UDP-GlcUA and UDP-hexosamine availability is critical for the synthesis of glycosaminoglycans, an energy consuming process
physiological function
recombinant hyaluronan synthase-2 upregulation protects smpd3-deficient fibroblasts against cell death induced by nutrient deprivation, but not against apoptosis evoked by human oxidized LDL. Resistance of fro/fro cells to starvation-induced apoptosis is associated with an increased expression of hyaluronan synthase 2 (HAS2) mRNAs and protein, which is inhibited by ceramide. The protective mechanism of HAS2 involves an increased expression of the heat-shock protein Hsp72, a chaperone with antiapoptotic activity. Antiapoptotic properties of HAS2 , overview
physiological function
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hyaluronan synthase isozymes are involved in hyaluronan biosynthesis. Each HAS isoform produces structurally identical hyaluronan, thus, hyaluronan function is independent of the HAS by which it is synthesized. Hyaluronan is an essential component of the pericellular matrix, or alternatively, it can be released in a soluble form and be released and incorporated as part of the extracellular matrix. The composition and architecture of the matrix affect hyaluronan-dependent biochemical signaling, as well as the biophysical and biomechanical properties of tissues. The temporal and spatial relationship of hyaluronan with cells that express hyaluronidases that modify the molecular weight of hyaluronan is another determinant of hyaluronan function. Hyaluronan synthases may affect vascular disease independent of hyaluronan. HAS isoform-specific functions in tissue homeostasis and disease
physiological function
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hyaluronan synthase isozymes are involved in hyaluronan biosynthesis. Each HAS isoform produces structurally identical hyaluronan, thus, hyaluronan function is independent of the HAS by which it is synthesized. Hyaluronan is an essential component of the pericellular matrix, or alternatively, it can be released in a soluble form and be released and incorporated as part of the extracellular matrix. The composition and architecture of the matrix affect hyaluronan-dependent biochemical signaling, as well as the biophysical and biomechanical properties of tissues. The temporal and spatial relationship of hyaluronan with cells that express hyaluronidases that modify the molecular weight of hyaluronan is another determinant of hyaluronan function. Hyaluronan synthases may affect vascular disease independent of hyaluronan. HAS isoform-specific functions in tissue homeostasis and disease. Apotential autocrine loop involving isoyzme HAS3, PDGF-B expression, and PDGF-BB-induced migration. Isoform-specific role for HAS3 in promoting neointimal hyperplasia after carotid artery ligation
physiological function
hyaluronan synthase 1 (HAS1) is one of three isoenzymes responsible for cellular hyaluronan synthesis. The role of HAS1 in hyaluronan production seems to be insignificant compared to the two other isoenzymes, HAS2 and HAS3, which have higher enzymatic activity. Isozyme Has1 is upregulated in states associated with inflammation, like atherosclerosis, osteoarthritis, and infectious lung disease. Both full length and splice variants of HAS1 are expressed in malignancies like bladder and prostate cancers, multiple myeloma, and malignant mesothelioma. The pericellular hyaluronan coat produced by HAS1 is usually thin without induction by inflammatory agents or glycemic stress and depends on CD44HA interactions. These specific interactions regulate the organization of hyaluronan into a leukocyte recruiting matrix during inflammatory responses. Despite the apparently minor enzymatic activity of HAS1 under normal conditions, it may be an important factor under conditions associated with glycemic stress like metabolic syndrome, inflammation, and cancer. HAS1 expression is transcriptionally regulated by transforming growth factor-beta in synoviocytes and by the pro-inflammatory cytokine interleukin-1beta in fibroblasts, while these factors may have similar or opposite effects on other HASs, depending on the cell type. Has1 is associated with breast tumor and with estrogen receptor negativity, HER2 positivity, high relapse rate, and short overall survival
physiological function
hyaluronan synthase 2 regulates fibroblast senescence in pulmonary fibrosis. Senescence is implicated in development, cancer, and tissue fibrosis. The chronic inflammation caused by cellular senescence may be related to the pathogenesis of various chronic diseases. Isozyme HAS2 may be a critical regulator of the fate of pulmonary fibrosis. Isozyme HAS2 is the major isoform responsible for hyaluronan production in mesenchymal cells
physiological function
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hyaluronan is a ubiquitous glycosaminoglycan involved in embryonic development, inflammation and cancer. In mammals, three hyaluronan synthase isoenzymes (HAS1-3) inserted in the plasma membrane produce hyaluronan directly on the cell surface. Isozyme hyaluronan synthase 1 (HAS1) produces a cytokine-and glucose-inducible, CD44-dependent cell surface coat
physiological function
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the enzyme is involved in synthesis of hyaluronan that may have anti-cancer like effects in melanoma progression
physiological function
hyaluronan synthase 3 promotes plaque inflammation and atheroprogression. Hyaluronan synthase 3 expression in vascular smooth muscle cells is found to be regulated by interleukin 1 beta (IL-1beta) in an NFkappaB dependent manner
physiological function
enzyme expression has a pivotal role in cell motility and invasion. The enzyme regulates tumor progression and cell aggressiveness. Mammary tumor biopsies in which the enzyme (HAS2) is overexpressed display enhanced angiogenesis and inflammatory cells recruitment. HAS2 is a critical factor that induces epithelial-mesenchymal transition
physiological function
the mean length of protrusions in bone-marrow derived mesenchymal stem cells is significantly increased by the application of fluid shear stress, the overexpression of HAS2-eGFP or a combination of both conditions. Fluid shear stress significantly increases the density of protrusions in bone-marrow derived mesenchymal stem cells, but not in immortalised HAS2-eGFP cells
physiological function
siRNA-mediated knockdown of HAS3 in epidermal equivalents results in a significant reduction in epidermal hyaluronan content and thickness, accompanied by decreased keratinocyte proliferation and differentiation
physiological function
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hyaluronan synthase isozymes are involved in hyaluronan biosynthesis. Each HAS isoform produces structurally identical hyaluronan, thus, hyaluronan function is independent of the HAS by which it is synthesized. Hyaluronan is an essential component of the pericellular matrix, or alternatively, it can be released in a soluble form and be released and incorporated as part of the extracellular matrix. The composition and architecture of the matrix affect hyaluronan-dependent biochemical signaling, as well as the biophysical and biomechanical properties of tissues. The temporal and spatial relationship of hyaluronan with cells that express hyaluronidases that modify the molecular weight of hyaluronan is another determinant of hyaluronan function. Hyaluronan synthases may affect vascular disease independent of hyaluronan. HAS isoform-specific functions in tissue homeostasis and disease. Apotential autocrine loop involving isoyzme HAS3, PDGF-B expression, and PDGF-BB-induced migration. Isoform-specific role for HAS3 in promoting neointimal hyperplasia after carotid artery ligation
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physiological function
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HAS-1 treatment of wounds promotes a more organized extracellular matrix with the regeneration of dermal appendages, including hair follicles, increased regenerative healing, overview
-
physiological function
-
recombinant hyaluronan synthase-2 upregulation protects smpd3-deficient fibroblasts against cell death induced by nutrient deprivation, but not against apoptosis evoked by human oxidized LDL. Resistance of fro/fro cells to starvation-induced apoptosis is associated with an increased expression of hyaluronan synthase 2 (HAS2) mRNAs and protein, which is inhibited by ceramide. The protective mechanism of HAS2 involves an increased expression of the heat-shock protein Hsp72, a chaperone with antiapoptotic activity. Antiapoptotic properties of HAS2 , overview
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additional information
product hyaluronan is secreted to the cell surface or the into the growth medium by HAS-containing cell culture, respectively
additional information
product hyaluronan is secreted to the cell surface or the into the growth medium by HAS-containing cell culture, respectively
additional information
product hyaluronan is secreted to the cell surface or the into the growth medium by HAS-containing cell culture, respectively
additional information
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product hyaluronan is secreted to the cell surface or the into the growth medium by HAS-containing cell culture, respectively
additional information
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HA product size is decreased by increasing concentrations of glycerol. The four Cys residues in SeHAS are clustered close together and are located at the membrane-HAS interface within the enzyme active site. Involvement of these Cys residues in HAS activity, overview
additional information
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the mechanism of HAS2 proteasomal degradation is complex and requires additional processes considering the several transmembrane domains of HAS2 and its localization in the plasma membrane
additional information
An important factor affecting activity of all HAS enzymes is the cytoplasmic availability of substrates, namely, UDP-GlcUA and UDP-GlcNAc. This role of substrates is particularly interesting in regulation of HAS1 as its activity of hyaluronan production in many cell models is low or absent unless stimulated
additional information
the synergistic combination of carnosine and retinol increases hyaluronan production in normal human epidermal keratinocytes by upregulating hyaluronan synthase 2 (HAS2) gene transcription. The combined treatment of carnosine and retinol significantly attenuates UVB-induced prostaglandin E2 (PGE2) synthesis in normal human epidermal keratinocytes
additional information
in vitro, a minimum of 67 % cardiolipin is necessary for hyaluronan synthesis. The anionic cardiolipin stabilizes the cationic transmembrane regions and thereby maintains the conformation of HAS. Cardiolipin is required to modulate the catalysis-relevant motions in HAS and thus facilitate hyaluronan synthesis
additional information
M1H2Q1
the enzyme either binds to UDP-GlcNAc at the active site or GlcNAc at the acceptor position, but not simultaneously. Either the donor or acceptor GlcNAc, but not both, is able to bind the pocket. The GlcNAc and GlcA acceptors are differently coordinated and positioned at the acceptor site
Show AA Sequence and Transmembrane Helices (1816 entries)
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PDB
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
42000
47780
48000
49000
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x * 49000, recombinant enzyme, SDS-PAGE
48000
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1 * 48000, without cardiolipin, radiation inactivation analysis
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
additional information
?
x * 108000, SDS-PAGE of recombinant protein including MBP tag
?
x * 107000, SDS-PAGE of recombinant protein including MBP tag
?
x * 106000, SDS-PAGE of recombinant protein including MBP tag
monomer
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1 * 48000, without cardiolipin, radiation inactivation analysis
additional information
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determination of isozyme structures with 7 putative transmembrane regions, thereof 2 at the N-terminus and 5 at the C-terminus, and a big cytoplasmic loop harboring the active site and the substrate binding site
additional information
in co-transfected cells, full length HAS1 and HAS1 splice variants interact with themselves and with each other to form heteromeric multiprotein assemblies
additional information
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in co-transfected cells, full length HAS1 and HAS1 splice variants interact with themselves and with each other to form heteromeric multiprotein assemblies
additional information
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a single protein exerts many functions as binding of two distinct UDP-sugars and binding of two distinct hyaluronan acceptor or donor species. Class 1 mammalian isozymes have two N-terminal transmembrane domains and several of C-terminal transmembrane domains or membrane associated domains, predicted structural organization of mammalian isozymes, Class 1 mammalian HAS with 6 transmembrane domains and 2 membrane associated domains, structure comparisons, overview
additional information
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determination of isozyme structures with 7 putative transmembrane regions, 2 thereof at the N-terminus and 5 at the C-terminus, and a big cytoplasmic loop harboring the active site and the substrate binding site
additional information
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predicted enzyme topology and organization, overview
additional information
the only member of Class 2 HAS, expressed by Pasteurella multocida, has a short C-terminal domain with only 4 transmembrane regions and 2 membrane associated domains, structure comparisons, overview
additional information
-
the membrane-bound enzyme possesses a membrane-localized cysteine cluster near the substrate-binding sites
additional information
-
Streptococcal enzymes have two N-terminal transmembrane domains and several of C-terminal transmembrane domains or membrane associated domains, predicted structural organization of Streptococcal isozymes, structure comparisons, overview
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
-
HAS activity can be modulated by post-translational modification, such as phosphorylation and N-glycosylation
phosphoprotein
ubiquitination
the enzyme is regulated by post-translational modifications, including ubiquitination. The deubiquitinating enzymes USP4 and USP17 target hyaluronan synthase 2 and differentially affect its function
additional information
phosphoprotein
human HAS3 expressed in COS-7 cells is serine-phosphorylated. This phosphorylation can be enhanced by a number of effectors, most significantly by a membrane-permeable analogue of cAMP. Under non-stimulating conditions, the FLAGHAS3 is phosphorylated to a stoichiometry of approx. 0.11 in COS-7 cells and, following maximal stimulation with 8-(4-chlorophenylthio)-cAMP, phosphorylation is increased to approximately 0.32 mol of phosphate/mol of protein
phosphoprotein
-
HAS activity can be modulated by post-translational modification, such as phosphorylation and N-glycosylation
phosphoprotein
AMP-activated protein kinase, AMPK, phosphorylates HAS2 at Thr110, which inhibits its enzymatic activity. Isoenzymes HAS1 and HAS3 are not modified by the kinase
phosphoprotein
-
ERK-mediated serine phosphorylation of all the three HAS isozymes increases their specific activity. AMP activated protein kinase (AMPK) is considered a sensor of the energy status of the cell and is activated by low ATP:AMP ratio, AMPK leads to the inhibition of hyaluronan secretion by HAS2 phosphorylation at residue Thr110
additional information
-
HAS2 can be O-GlcNAcylated on serine 221, which strongly increases its activity and its stability to half-life of over 5 h versus 17 min without O-GlcNAcylation
additional information
-
the treatments of plasma membranes or microsomal membranes with phosphatases or N-glycosidase F reveals that also HAS activity in internal vesicles can be modulated
additional information
-
HAS2 is ubiquitinated on Lys190, HAS2 is both mono- and polyubiquitinated
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
cryo-electron microscopy structures of HAS in apo, UDP-bound, UDP N-acetylglucosamine-bound and GlcNAc-primed states
M1H2Q1
cryo-EM strucutre of the complex with shark variable regions of immunoglobulin new antigen receptor (VNAR)
M1H2Q1
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
S221A
-
site-directed mutation of the O-GlcNAcylable Ser-221 to alanine generated an enzyme with a calculated t1/2 of about 70 min
T110A
site-directed mutagenesis of the phosphorylation site residue, the mutant is not inhibited by AMP-activated protein kinase
K190R
-
site-directed mutagenesis, inactive mutant, K190R-mutated HAS2 forms dimers with wild-type HAS2 and quenches the activity of wild-type HAS2
D247E
-
site-directed mutagenesis, mutant possesses only GlcUA-transferase activity
D247K
-
site-directed mutagenesis, mutant possesses only GlcUA-transferase activity
D247N
-
site-directed mutagenesis, mutant possesses only GlcUA-transferase activity
D249E
-
site-directed mutagenesis, mutant possesses only GlcUA-transferase activity
D249K
-
site-directed mutagenesis, mutant possesses only GlcUA-transferase activity
D249N
-
site-directed mutagenesis, mutant possesses only GlcUA-transferase activity
D370E
-
site-directed mutagenesis, mutant possesses GlcUA-transferase activity, and very low hyaluronan synthase activity
D370K
-
site-directed mutagenesis, mutant possesses GlcUA-transferase activity, and very low GlcNAc-transferase activity
D370N
-
site-directed mutagenesis, mutant possesses GlcUA-transferase activity, and very low GlcNAc-transferase activity
D477K
-
mutants possess UDP-N-acetyl-D-glucosamine-transferase activity
D527E
-
site-directed mutagenesis, mutant possesses only GlcNAc-transferase activity
D527K
-
site-directed mutagenesis, mutant possesses only GlcNAc-transferase activity
D527N
-
site-directed mutagenesis, mutant possesses only GlcNAc-transferase activity
D529E
-
site-directed mutagenesis, mutant possesses GlcNAc-transferase activity, and low hyaluronan synthase activity
D529K
-
site-directed mutagenesis, mutant possesses GlcNAc-transferase activity, and very low hyaluronan synthase activity
D529N
-
site-directed mutagenesis, mutant possesses only GlcNAc-transferase activity
E369D
-
site-directed mutagenesis, mutant possesses GlcUA-transferase activity, and very low GlcNAc-transferase activity
E369H
-
site-directed mutagenesis, mutant possesses GlcUA-transferase activity, and very low GlcNAc-transferase activity
E369Q
-
site-directed mutagenesis, mutant possesses GlcUA-transferase activity, and very low GlcNAc-transferase activity
D247E
-
site-directed mutagenesis, mutant possesses only GlcUA-transferase activity
-
D247K
-
site-directed mutagenesis, mutant possesses only GlcUA-transferase activity
-
D247N
-
site-directed mutagenesis, mutant possesses only GlcUA-transferase activity
-
D249K
-
site-directed mutagenesis, mutant possesses only GlcUA-transferase activity
-
D249N
-
site-directed mutagenesis, mutant possesses only GlcUA-transferase activity
-
C226A
C226A/C262A
C226A/C262A/C367A
-
site-directed mutagenesis, 1.4% remaining activity and altered kinetic constants compared to the wild-type enzyme
C226A/C281A
C226A/C367A
C226S
C262A
C262A/C281A
C262A/C367A
C262S
C281A
C281A/C367A
C281S
C367A
C367S
delD409-L417
deletion of 409-DWGTRKKLL-417 causes significant decreases in hyaluronic acid titer and in vitro hyaluronan synthase activity and undetectable hyaluronic acid weight-average molecular weight. Stepping truncations from L417 to K415 have little impact on hyaluronic acid and molecular weight. The removal of L417-K414, the hyaluronic acid titer of the resulting WGTR413 variant dramatically decreased to 16.8% of the wild type, while the same hyaluronic acid molecular weight is still detectable. With the further removal of R413, the hyaluronic acid titer of the resulting WGT412 variant dropps to less than 10% of the wild-type, and no hyaluronic acid products are detectable
E327D
-
the specific enzyme activity relative to wild type enzyme is 38%. Mutant enzyme synthesizes hyaluronan of smaller weight-average molar mass than wild-type enzyme
E327K
-
the specific enzyme activity relative to wild type enzyme is 0.16%. Mutant enzyme synthesizes hyaluronan of smaller weight-average molar mass than wild-type enzyme
E327K/K48E
-
the specific enzyme activity near wild-type level. Mutant enzyme synthesizes hyaluronan of smaller weight-average molar mass than wild-type enzymel
E327Q
-
the specific enzyme activity relative to wild type enzyme is 26%. Mutant enzyme synthesizes hyaluronan of smaller weight-average molar mass than wild-type enzyme
K414A
mutation does not notably affect hyaluronic acid titer
K414R
mutation does not notably affect hyaluronic acid titer. The molecular weight of the hyaluronic acid produced by the K414R variant is significantly increased
K415A
mutation does not notably affect hyaluronic acid titer
K415R
mutation does not notably affect hyaluronic acid titer
K48E
K48F
-
site-directed mutagenesis, alteration of K48 within membrane domain 2 causes decreased activity and HA product size
K48R
-
the specific enzyme activity relative to wild type enzyme is 17%. Mutant enzyme synthesizes hyaluronan of smaller weight-average molar mass than wild-type enzyme
R406A
hyaluronic acid titer is greatly decreased
R413A
hyaluronic acid titer is greatly decreased
R413K
the variant barely produces hyaluronic acid
T412A
mutations completely deactivates the enzyme
W410A
mutations completely deactivates the enzyme
N196I/L197R/T202S/D203H/C226F/S231D/V232F/E236Q/S256N/C262S/K294T/N297H/N300K/F303C
the enzyme is engineered to increase hyaluronan production and molecular mass through structural alteration of multiple regions. As compared with other variants and wild-type enzyme, the V5 variant generates a higher hyaluronan titer (2.24 g/l) and molecular weight value (1360000 Da). Following overexpression of the genes tuaD and glmU in Bacillus subtilis V5, hyaluronan production and molecular weight increases further to 2.81 g/l and 2430000 Da, respectively. The results provide a new strategy for producing hyaluronan with higher titers and molecular mass values that could be extended to other polysaccharides, such as heparosan and chondroitin, produced in Bacillus subtilis
C117L
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme
C117S
-
site-directed mutagenesis, activity is similar to the wild-type enzyme
C210S
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme
C239S
-
site-directed mutagenesis, activity is similar to the wild-type enzyme
C239S/C337S
-
site-directed mutagenesis, reduced recombinant expression level, activity is similar to the wild-type enzyme
C298F
-
site-directed mutagenesis, poor recombinant expression level, highly reduced activity compared to the wild-type enzyme
C298L
-
site-directed mutagenesis, poor recombinant expression level, highly reduced activity compared to the wild-type enzyme
C298S
-
site-directed mutagenesis, activity is similar to the wild-type enzyme
C304S
-
site-directed mutagenesis, activity is similar to the wild-type enzyme
C304S/C337S
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme
C307S
-
site-directed mutagenesis, highly reduced activity compared to the wild-type enzyme
C307S/C337S
-
site-directed mutagenesis, reduced recombinant expression level, inactive mutant
C337S
-
site-directed mutagenesis, increased Km for UDP-N-acetylglucosamine compared to the wild-type enzyme
additional information
C226A
-
site-directed mutagenesis, increased sensitivity to inhibition by NEM
C226A
-
site-directed mutagenesis, 24% remaining activity and altered kinetic constants compared to the wild-type enzyme
C226A
-
site-directed mutagenesis, the mutant shows 44% of wild-type activity
C226A/C262A
-
site-directed mutagenesis, slightly increased sensitivity to inhibition by NEM, and reduced sensitivity to inhibition by sodium arsenite compared to the wild-type enzyme
C226A/C262A
-
site-directed mutagenesis, 3.2% remaining activity and altered kinetic constants compared to the wild-type enzyme
C226A/C262A
-
site-directed mutagenesis, the mutant shows 36% of wild-type activity, mutant kinetics compared to the wild-type enzyme
C226A/C281A
-
site-directed mutagenesis, reduced sensitivity to inhibition by NEM, and highly reduced sensitivity to inhibition by sodium arsenite compared to the wild-type enzyme
C226A/C281A
-
site-directed mutagenesis, reduced reaction velocity and altered Km values compared to the wild-type enzyme
C226A/C281A
-
site-directed mutagenesis, the mutant shows 68% of wild-type activity
C226A/C367A
-
site-directed mutagenesis, reduced sensitivity to inhibition by NEM, and slightly increased sensitivity to inhibition by sodium arsenite compared to the wild-type
C226A/C367A
-
site-directed mutagenesis, reduced reaction velocity and altered Km values compared to the wild-type enzyme
C226A/C367A
-
site-directed mutagenesis, the mutant shows 102% of wild-type activity
C226S
-
site-directed mutagenesis, reduced sensitivity to inhibition by NEM
C226S
-
site-directed mutagenesis, highly reduced reaction velocity and altered Km values compared to the wild-type enzyme
C226S
-
site-directed mutagenesis, the mutant shows 45% of wild-type activity, mutant kinetics compared to the wild-type enzyme
C262A
-
site-directed mutagenesis, increased sensitivity to inhibition by NEM
C262A
-
site-directed mutagenesis, reduced reaction velocity and increased Km values compared to the wild-type enzyme
C262A
-
site-directed mutagenesis, the mutant shows 79% of wild-type activity
C262A/C281A
-
site-directed mutagenesis, reduced sensitivity to inhibition by NEM, and highly reduced sensitivity to inhibition by sodium arsenite compared to the wild-type enzyme
C262A/C281A
-
site-directed mutagenesis, reduced reaction velocity and altered Km values compared to the wild-type enzyme
C262A/C281A
-
site-directed mutagenesis, the mutant shows 82% of wild-type activity, mutant kinetics compared to the wild-type enzyme
C262A/C367A
-
site-directed mutagenesis, increased sensitivity to inhibition by NEM, and highly reduced sensitivity to inhibition by sodium arsenite compared to the wild-type enzyme
C262A/C367A
-
site-directed mutagenesis, reduced reaction velocity and altered Km values compared to the wild-type enzyme
C262S
-
site-directed mutagenesis, increased sensitivity to inhibition by NEM
C262S
-
site-directed mutagenesis, reduced reaction velocity and increased Km values compared to the wild-type enzyme
C262S
-
site-directed mutagenesis, the mutant shows 85% of wild-type activity
C281A
-
site-directed mutagenesis, highly reduced sensitivity to inhibition by NEM
C281A
-
site-directed mutagenesis, reduced reaction velocity and altered Km values compared to the wild-type enzyme
C281A
-
site-directed mutagenesis, the mutant shows 91% of wild-type activity
C281A/C367A
-
site-directed mutagenesis, reduced sensitivity to inhibition by NEM, and highly reduced sensitivity to inhibition by sodium arsenite compared to the wild-type enzyme
C281A/C367A
-
site-directed mutagenesis, reduced reaction velocity and altered Km values compared to the wild-type enzyme
C281A/C367A
-
site-directed mutagenesis, the mutant shows 107% of wild-type activity
C281S
-
site-directed mutagenesis, increased sensitivity to inhibition by NEM
C281S
-
site-directed mutagenesis, reduced reaction velocity and altered Km values compared to the wild-type enzyme
C281S
-
site-directed mutagenesis, the mutant shows 57% of wild-type activity
C367A
-
site-directed mutagenesis, unaltered inhibition by NEM compared to the wild-type enzyme
C367A
-
site-directed mutagenesis, increased reaction velocity and Km values compared to the wild-type enzyme
C367A
-
site-directed mutagenesis, the mutant shows 126% of wild-type activity
C367S
-
site-directed mutagenesis, unaltered inhibition by NEM compared to the wild-type enzyme
C367S
-
site-directed mutagenesis, kinetics similar to the wild-type enzyme
C367S
-
site-directed mutagenesis, the mutant shows 80% of wild-type activity
K48E
-
the specific enzyme activity relative to wild type enzyme is 7%. Mutant enzyme synthesizes hyaluronan of smaller weight-average molar mass than wild-type enzyme
K48E
-
site-directed mutagenesis, alteration of K48 within membrane domain 2 causes decreased activity and HA product size
additional information
COS-1 cells, with minor endogenous hyaluronan synthesis, is transfected with Has1 isozyme. HAS1 is almost unable to secrete hyaluronan or form a hyaluronan coat. This failure of HAS1 to synthesize hyaluronan is compensated by increasing the cellular content of UDP-GlcNAc by 10fold with 1 mM glucosamine in the growth medium
additional information
COS-1 cells, with minor endogenous hyaluronan synthesis, is transfected with Has1 isozyme. HAS1 is almost unable to secrete hyaluronan or form a hyaluronan coat. This failure of HAS1 to synthesize hyaluronan is compensated by increasing the cellular content of UDP-GlcNAc by 10fold with 1 mM glucosamine in the growth medium
additional information
COS-1 cells, with minor endogenous hyaluronan synthesis, is transfected with Has1 isozyme. HAS1 is almost unable to secrete hyaluronan or form a hyaluronan coat. This failure of HAS1 to synthesize hyaluronan is compensated by increasing the cellular content of UDP-GlcNAc by 10fold with 1 mM glucosamine in the growth medium
additional information
-
COS-1 cells, with minor endogenous hyaluronan synthesis, is transfected with Has1 isozyme. HAS1 is almost unable to secrete hyaluronan or form a hyaluronan coat. This failure of HAS1 to synthesize hyaluronan is compensated by increasing the cellular content of UDP-GlcNAc by 10fold with 1 mM glucosamine in the growth medium
additional information
COS-1 cells, with minor endogenous hyaluronan synthesis, is transfected with Has2 isozyme. Hyaluronan synthesis driven by HAS2 is less affected by glucosamine addition
additional information
COS-1 cells, with minor endogenous hyaluronan synthesis, is transfected with Has2 isozyme. Hyaluronan synthesis driven by HAS2 is less affected by glucosamine addition
additional information
COS-1 cells, with minor endogenous hyaluronan synthesis, is transfected with Has2 isozyme. Hyaluronan synthesis driven by HAS2 is less affected by glucosamine addition
additional information
-
COS-1 cells, with minor endogenous hyaluronan synthesis, is transfected with Has2 isozyme. Hyaluronan synthesis driven by HAS2 is less affected by glucosamine addition
additional information
COS-1 cells, with minor endogenous hyaluronan synthesis, is transfected with Has3 isozyme. The ability of HAS3 to synthesize hyaluronan is not at all affected
additional information
COS-1 cells, with minor endogenous hyaluronan synthesis, is transfected with Has3 isozyme. The ability of HAS3 to synthesize hyaluronan is not at all affected
additional information
COS-1 cells, with minor endogenous hyaluronan synthesis, is transfected with Has3 isozyme. The ability of HAS3 to synthesize hyaluronan is not at all affected
additional information
-
COS-1 cells, with minor endogenous hyaluronan synthesis, is transfected with Has3 isozyme. The ability of HAS3 to synthesize hyaluronan is not at all affected
additional information
both COS-1 and MCF-7 cell lines have negligible endogenous hyaluronan production, and even overexpression of HAS1 enzymes does not cause prominent changes in it. Upon treatment with glucose or glucosamine, compounds that increase the amounts of hyaluronan substrates, the HAS1 enzyme is able to produce significant amounts of hyaluronan
additional information
-
HAS1-transfected MCF-7cells show very little cell surface hyaluronan, but a large hyaluronan coat is seen in cells grown in 20 mM glucose and 1 mM glucosamine, or treated with interleukin-1beta, TNF-alpha, or TGF-beta. The coats are mostly removed by the presence of hyaluronan hexasaccharides, or Hermes1 antibody, indicating that they depend on the CD44 receptor, which is, in contrast to the coat produced by HAS3, remaining attached to HAS3 itself
additional information
-
isozyme HAS3 overexpression expands the cell surface hyaluronan coat and decreases melanoma cell adhesion, migration and proliferation by cell cycle arrest at G1/G0. Melanoma cell migration is restored by removal of cell surface hyaluronan by Streptomyces hyaluronidase and by receptor blocking with hyaluronan oligosaccharides, while the effect on cell proliferation is receptor independent. Overexpression of isozyme HAS3 decreases ERK1/2 phosphorylation suggesting that inhibition of MAP-kinase signaling is responsible for the suppressive effects on the malignant phenotype of MV3 melanoma cells
additional information
the mutation in putative cyclic AMP-response element binding protein (CREB) binding sites of the promoter region in HAS2/3 genes inhibits the MgCl2 supplementation-induced elevation of promoter activity
additional information
the mutation in putative cyclic AMP-response element binding protein (CREB) binding sites of the promoter region in HAS2/3 genes inhibits the MgCl2 supplementation-induced elevation of promoter activity
additional information
-
site-directed mutagenesis of residues of the cytoplasmic loop of isozyme HAS1 for determining the residues required for glycosyltransferase activity
additional information
-
activity rescue of mutants with high substrate concentrations, overview, deletion of residues 1-117 does not affect polymerization activity, construction of different chimeric mutant enzymes comprising residues from Pasteurella multocida type A enzyme and residues of a Pasteurella multocida type F chondroitin synthase, producing an unsulfated chondroitin capsule, the chimeric mutants show different percentages of hyaluronan and chondroitin synthase ativities, overview
additional information
-
a truncated soluble form of recombinant PmHAS (residues 1703) can catalyze the glycosyl transfers in a time- and concentration-dependent manner
additional information
expression of isozyme HAS2 is increased after oncogenic malignant transformation with v-HA-ras, v-sre and/or v-fos, antisense repression of HAS2 expression leads to reduced hyaluronan synthesis and reduced tumorigenicity in the peritoneum, introduction of isozyme HAS2 promotes the growth of subcutaneous tumors dependent on hyaluronan synthesis level
additional information
expression of isozyme HAS2 is increased after oncogenic malignant transformation with v-HA-ras, v-sre and/or v-fos, antisense repression of HAS2 expression leads to reduced hyaluronan synthesis and reduced tumorigenicity in the peritoneum, introduction of isozyme HAS2 promotes the growth of subcutaneous tumors dependent on hyaluronan synthesis level
additional information
expression of isozyme HAS2 is increased after oncogenic malignant transformation with v-HA-ras, v-sre and/or v-fos, antisense repression of HAS2 expression leads to reduced hyaluronan synthesis and reduced tumorigenicity in the peritoneum, introduction of isozyme HAS2 promotes the growth of subcutaneous tumors dependent on hyaluronan synthesis level
additional information
expression of isozyme HAS1 is increased after oncogenic malignant transformation with v-sre and/or v-fos, no increase after transformation with v-HA-ras, introduction of isozyme HAS1 promotes the growth of subcutaneous tumors dependent on hyaluronan synthesis level
additional information
expression of isozyme HAS1 is increased after oncogenic malignant transformation with v-sre and/or v-fos, no increase after transformation with v-HA-ras, introduction of isozyme HAS1 promotes the growth of subcutaneous tumors dependent on hyaluronan synthesis level
additional information
expression of isozyme HAS1 is increased after oncogenic malignant transformation with v-sre and/or v-fos, no increase after transformation with v-HA-ras, introduction of isozyme HAS1 promotes the growth of subcutaneous tumors dependent on hyaluronan synthesis level
additional information
-
construction of cysteine-deletion mutants deleting either C226, C262, C281, or C367, the mutants are less sensitive or not sensisitive to sodium arsenite inhibition, overview
additional information
-
construction and kinetic analysis of Cys-deletion mutants, overview
additional information
-
purified Se-HAS is reconstituted into proteoliposomes, from total lipid extract from Escherichia coli, where it synthesizes and translocates hyaluronan, or reconstituted into synthetic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine/1,1',2,2'-tetraoleoyl cardiolipin/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (80/10/10%) proteoliposomes. In vitro synthesized, high-molecular-weight hyaluronan remains tightly associated with the intact proteoliposomes, even after proteolyticdegradation of HAS or in the presence of 1 M NaCl or 0.6 M urea to prevent nonspecific interactions of the polymer with the lipid vesicles
additional information
-
addition of purified HAS to liposomes preloaded with the fluorophore Cascade Blue, CB, which is translocated through the membrane and secreted by HAS, overview. SeHAS-mediated CB efflux is greater from liposomes made with an activating lipid, tetraoleoyl cardiolipin, compared to an inactivating lipid, tetramyristoyl cardiolipin
additional information
-
generation of several deletion mutants, DELTA3-C281, DELTA3-C226, DELTA3-C262, and DELTA3-C367, and of a C-null mutant, all show reduced activity and altered kinetics compared to the wild-type enzyme
additional information
truncation at trans-membrane domains Tr4 and Tr3, i.e. the truncation construct at Tr4 (41 amino acids deletion at C-terminus, lacks Tr5) contains amino acids 1-376. The truncated form of Tr3 without TMD4 and TMD5 consists of amino acids 1-350 (deletion of 67 amino acids at C-terminus). The removal of TMD5 and TMD4 regions does not impair the hyaluronan production and secretion process. The truncation at Tr3 produces 121% and 137% of the hyaluronan of wild-type and Tr4-truncated construct, respectively. The molecular mass of hyaluronan is about 50-60 kDa for all strains
additional information
-
dual expression of hyaluronan synthase and UDP-glucose-6-dehydrogenase in Lactococcus lactis and study of the ratios of hyaluronan synthase expression level to the precursor sugar UDP-GlcA biosynthesis ability under different induction concentration collocations with nisin and lactose on the molecular weight of hyaluronan. The final weight-average molecular weight of hyaluronan correlates with the relative ratios of hyaluronan synthase expression level to the concentration of UDP-GlcA
additional information
-
dual expression of hyaluronan synthase and UDP-glucose-6-dehydrogenase in Lactococcus lactis and study of the ratios of hyaluronan synthase expression level to the precursor sugar UDP-GlcA biosynthesis ability under different induction concentration collocations with nisin and lactose on the molecular weight of hyaluronan. The final weight-average molecular weight of hyaluronan correlates with the relative ratios of hyaluronan synthase expression level to the concentration of UDP-GlcA
-
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
the enzyme is temperature labile, but is stabilized by substrate and cardiolipin
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
HAS2 can be O-GlcNAcylated on serine 221, which strongly increases its activity and its stability to half-life of over 5 h versus 17 min without O-GlcNAcylation
-
substrate and cardiolipin stabilize the enzyme
-
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in vitro, a minimum of 67 % cardiolipin is necessary for hyaluronan synthesis. The anionic cardiolipin stabilizes the cationic transmembrane regions and thereby maintains the conformation of HAS. Cardiolipin is required to modulate the catalysis-relevant motions in HAS and thus facilitate hyaluronan synthesis
recombinant enzyme from Escherichia coli, native enzyme to homogeneity
-
recombinant enzyme from membranes of Escherichia coli, to homogeneity
-
recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography
-
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli
-
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli by nickel affinity chromatography
-
recombinant His6-tagged enzyme from Escherichia ccoli strain C43 by solubilization with detergent LysoFosCholine Ether-14, nickel affinity chromatography, and gel filtration
-
recombinant isozymes by immunoaffinity chromatography
recombinant protein, purified from membrane after solubilisation with 25 mM of HEPES (pH 8), 150 mM of NaCl, and 10% glycerol, supplemented with 1% n-dodecyl-beta-D-maltopyranoside and 0.1% CHS. Purified by affinity chromatography
recombinant protein, purified from membrane after solubilisation with a lysis buffer supplemented with 1% lauryl maltose neopentyl glycol, 0.1% cholesteryl hemisuccinate, 2 microg/ml of aprotinin. Purified by affinity chromatography
recombinant soluble C-terminally His6-tagged PmHAS1-703 by nickel affinity chromatography
recombinant synthesis of hyaluronan is carried out with Agrobacterium sp. strain ATCC 31749, hyaluronan is primarly found in the culture medium
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
a plasmid encoding FLAG epitope-tagged HAS3 for transfection of human prostate tumor cells is constructed, Tet-inducible 22Rv1 cells are generated
-
DNA and amino acid sequence determination and analysis, chromosome mapping of isozymes HAS1-3, genetic organization
-
ectopic expression of Flag- and 6myc-HAS2 in COS-1 cells as homodimers, co-expression with Flag-HAS3 leads to formation of heterodimers
-
expressed codon-optimised in HEK293F cells, with fused maltose-binding protein tags
expression in Bacillus subtilis
expression in Escherichia coli
expression of both hyaluronan synthase and UDP-glucose-6-dehydrogenase in Lactococcus lactis
-
expression of C-terminally His6-tagged Se-HAS in Escherichia coli strain C43
-
expression of His-tagged enzyme in Escherichia coli
-
expression of His-tagged wild-type and mutant enzymes in Escherichia coli
-
expression of isozyme HAS2-MBP-fusion protein in Escherichia coli strain JM109
-
expression of mutant enzymes in Escherichia coli. SeHAS(E327Q) and seHAS(E327K) are expressed at low levels, whereas seHAS(E327D) and the Lys48 mutants are expressed well
-
expression of wild-type and mutant enzymes as His-tagged proteins in Escherichia coli
-
expression of wild-type and mutant enzymes in Saccharomyces cerevisiae strain BJ5461
-
expression of wild-type FLAG-tagged human HAS1, HAS2, or HAS3, and of HAS T110A mutant enzyme in COS-7 cells
functional expression of isozymes HAS2 and HAS3 in rat epidermal keratinocytes as N-terminally GFP-tagged protein, recombinant isozymes GFP-HAS2 and GFP-HAS3 travel through endoplasmic reticulum, Golgi, plasma membrne, and endocytic vesicles, expression of inactive GFP-tagged HAS3 D216A mutant and of GFP-tagged HAS3-deletion mutants in keratinocytes
-
gene HAS1, expression analysis and recombinant expression in COS-1 cells
gene HAS1, in addition to the full-length form, HAS1 has multiple transcript variants resulting from alternative splicing
gene Has1, quantitative expression analysis by RT-qPCR analysis
gene HAS1, recombinant expression of GFP-tagged isozyme HAS1 in MCF-7 cells, MCF-7 cells transfected with Dendra-Has1 show intense fluorescence in perinuclear vesicular structures resembling the Golgi apparatus. The MCF-7 cells transfected with EGFP-Has1 produce a pericellular hyaluronan coat, which is attached the synthase itself
-
gene HAS2, expression analysis and recombinant expression in COS-1 cells
gene Has2, quantitative expression analysis by RT-qPCR analysis
gene has2, quantitative real time PCR enzyme expression analysis, HAS2 expression is dependent on ceramide generated by neutral type 2 sphingomyelinase, nSMase2, as shown by treatment with C2-ceramide that decreases HAS2 expression in murine fro/fro fibroblasts
gene HAS3, expression analysis and recombinant expression in COS-1 cells
gene Has3, quantitative expression analysis by RT-qPCR analysis
gene hyaD, recombinant expression of the soluble C-terminally His6-tagged PmHAS1-703 truncated enzyme from pET101/D-TOPO expression vector with an additional V5 epitope
genes HAS1, HAS2 and HAS3, quantitative expression analysis in benign and malign endometrial tissue
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HAS1 DNA and amino acid sequence determination and analysis, oncogenic malignant transformation of 3Y1 fibroblasts with v-sre and/or v-fos, or v-HA-ras
HAS2 DNA and amino acid sequence determination and analysis, oncogenic malignant transformation of 3Y1 fibroblasts with v-sre and/or v-fos, or v-HA-ras
Homo sapiens hyaluronan synthase 1 is cloned into the plasmid pFLAG-CMV2, for in vitro translation the pF3A WG(BYDV) Flexi vector is used
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isozyme HAS3 inducible overexpression in MV3/C8161 cells. EGFP-HAS3 overexpression rapidly induced pericellular hyaluronan coat formation and plasma membrane protrusions, induction by doxycycline
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overexpression in Escherichia coli, enzyme cannot be expressed as a soluble active protein
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overexpression of GFP-tagged HAS-1 in the wounds of lentiviral-HAS-1-treated mice
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recombinant expression of EGFP-tagged isozyme HAS1 in MCF-7 cells and localization to the Golgi apparatus
recombinant expression of EGFP-tagged isozyme HAS2 in MCF-7 cells and localization to the endoplasmic reticulum
recombinant expression of EGFP-tagged isozyme HAS3 in MCF-7 cells and localization to the Golgi apparatus
retroviral transduction system is used to overexpress the three murine hyaluronan synthase enzymes in arterial smooth muscle cells. Overexpression of hyaluronan synthases alters vascular smooth muscle cell phenotype and promotes monocyte adhesion
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stable expression of N-terminally Myc-tagged human HAS2 in NIH3T3 cells membranes, the molecular mechanism that underlies the rapid c-Myc-HAS2 turnover involves the 26 S proteasome, overview
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Streptococcus equisimilis hyaluronan synthase is cloned into the plasmid pKK223-3 for expression in Escherichia coli SURE cells
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the coding sequence of HAS1 is cloned into the vector pCR3.1 for transfection of fibroblasts
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the Escherichia coli expression vector pQE80L and the broad host range cloning vector pBBR122 are used
the human HAS2 expression plasmid is prepared by inserting its coding sequence into the vector pcDNA 3.1/CT-GFP-TOPO
expression in Escherichia coli
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
17beta-estradiol and different combinations of estradiol, gonadotropins, insulin-like growth factor 1 and insulin iduce the enzyme expression of HAS1-3
17beta-estradiol and different combinations of estradiol, gonadotropins, insulin-like growth factor 1 and insulin iduce the expression of HAS1-3
24 h stimulation with a cocktail of 1 ng/ml of IL-1beta, IL-6, and TNF-alpha promotes the upregulation of TMEM2 and HAS2 mRNA expression levels. Enhancement of HAS2 expression by the proinflammatory cytokines is canceled by TMEM2 silencing
basic fibroblast growth factor bFGF increases HA-synthase-1 and -2 expression and enhances high molecular weight hyaluronan deposition in the pericellular matrix
both tumor necrosis factor TNFalpha and interferon INFgamma significantly induce HAS3 expression
both tumor necrosis factor TNFalpha and transforming growth factor 1beta significantly increase HAS1 expression and protein synthesis. Exposure to reactive oxygen species results in increased gene expression and protein formation of HAS1
both tumor necrosis factor TNFalpha and transforming growth factor 1beta significantly increase HAS2 expression and protein synthesis. Exposure to reactive oxygen species results in increased gene expression and protein formation of HAS2
cadmium at 2 microM upregulates hyaluronan synthesis in the medium and specifically induces HAS3 mRNA and protein expression. Cadmium-mediated HAS3 induction is abolished by the inhibition of the c-Jun N-terminal kinase pathway
chondroitin sulfate increases hyaluronan production by osteoarthritic fibroblast-like synoviocytes through up-regulation of the expression of HAS1 and HAS2 associated with activation of ERK-1/2, p38, and Akt, although to a lesser extent. Both p38 and Akt are involved in chondroitin sulfate-induced hyaluronan accumulation. IL-1 increases hyaluronan production and levels of mRNA for HAS1, HAS2, and HAS3. Chondroitin sulfate enhances the IL-1induced level of HAS2 mRNA and reduces the level of HAS3 mRNA. IL-1induced activation of p38 and JNK is slightly decreased by chondroitin sulfate, whereas that of ERK-1/2 and Akt is enhanced. More high molecular weight hyaluronan is found in chondroitin sulfate plus IL-1treated fibroblast-like synoviocytes than in fibroblast-like synoviocytes treated with IL-1 alone
comparison of full-length HAS1 isoform and its splice variants Va, Vb, and Vc. When co-expressed, the properties of HAS1 variants are dominant over those of full length HAS1. Full length HAS1 appears to be diffusely expressed in the cell, but HAS1 variants are concentrated in the cytoplasm and/or Golgi apparatus. HAS1 variants synthesize detectable de novo hyaluronan intracellularly. Each of the HAS1 variants is able to relocalize full length HAS1 protein from diffuse cytoskeleton-anchored locations to deeper cytoplasmic spaces. The HAS1-variants-mediated relocalization occurs through strong molecular interactions, which also serve to protect full length HAS1 from its otherwise high turnover kinetics
doxycycline treatment causes a strong upregulation of HAS3 expression. A distinct EGFP-HAS3 signal is observed already 2 h after starting the doxycycline induction, localized mainly at the plasma membrane and in the Golgi area. After 24 h induction EGFP-HAS3 signal has become more intense, localizing strongly at the Golgi area and at the plasma membrane
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during atresia, HAS1 mRNA and protein expression is markedly up-regulated inovary. HAS2 and HAS3 mRNA expression levels are low and very low to undetectable, respectively
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expression is inhibited by mRNA knockdown of nonimprinted in Prader-Willi/Angelman syndrome-like domain containing 4 (NIPAL4). The reporter activities and mRNA levels of HAS2/3 are inhibited by glycogen synthase kinase-3 inhibitor CHIR-99021, and by cyclic AMP-response element binding protein inhibitor naphthol AS-E
fluid shear stress upregulates the expression of genes that encode proteins belonging to the hyaluronan biosynthesis and bone mineralization pathways, including isoforms HAS1 and HAS2
Has1 is upregulated in states associated with inflammation, like atherosclerosis, osteoarthritis, and infectious lung disease. The enzyme expression is increased in transcriptional regulation by factors EGF, FGF2, FGF, forskolin, IGF, IL-1beta, PDGF, progesterone, prostaglandin D2, prostaglandin E2, and TGF-beta
HAS2 is the major isoenzyme in MCF-7 cells. The mRNA expression is lowered by 4-methylumbelliferone by 81% in MCF-7 cells, and by 88% in A2058 cells. Both HAS substrate and HAS2 and/or HAS3 mRNA are targeted by 4-methylumbelliferone. The reduction of hyaluronan caused by 4-methylumbelliferone is associated with a significant inhibition of cell migration, proliferation and invasion
Has3 expression is increased early during lesion formation when macrophages enter atherosclerotic plaques
histamine increases hyaluronan degradation by up-regulating HYBID (hyaluronan-binding protein) and down-regulating hyaluronan synthase 2 in human skin fibroblasts in a dose- and time-dependent manner and thereby decreases the total amounts and sizes of newly produced hyaluronan
hyaluronan synthase 2 expression is elevated in both human and murine liver fibrosis. The enzyme is transcriptionally up-regulated by transforming growth factor-beta through Wilms tumor 1 to promote fibrogenic, proliferative, and invasive properties of HSCs via CD44, Toll-like receptor 4, and newly identified downstream effector Notch1
in MDA-MB-361, A2058 and SKOV-3 cells, treatment with 4-methylumbelliferone decreases HAS3 mRNA by 84-60%. The reduction of hyaluronan caused by 4-methylumbelliferone is associated with a significant inhibition of cell migration, proliferation and invasion
isoform HAS2 is a primary target of the cAMP activator forskolin and the nuclear hormone alltrans-retinoic acid. Forskolin and all-trans-retinoic acid modulate the formation of complexes between transcription factor CREB1 and retinoic acid receptor with various co-regulators at the predicted sites.Mediator MED1 and co-repressor nuclear receptor co-repressor NCoR1 are central for the all-trans-retinoic acid induction of the HAS2 gene and CREB-binding protein CBP dominates its forskolin response
MDAMB-231 and HS578T breast cancer cell line express higher levels of hyaluronan synthase 2 mRNA and synthesize higher amounts of hyaluronan than breast cancer cell lines with a less aggressive phenotype, like MCF-7
poststroke upregulation of hyaluronan synthase 2 in astrocytes and neurons
reduced HAS 2 gene expression and increased excreted urinary hyaluronidase activity during dehydration contribute to the reduced amount of hyaluronan and to antidiuretic response
the combination of carnosine and retinol upregulates HAS2 gene transcription
the enzyme expression is decreased in transcriptional regulation by estradiol, 4-methylumbelliferone, and TGF-beta1
the exposure of cells to a 5.8 mM of MgCl2 induces the elevation of isoforms HAS2/3 expression
transforming grwoth factor 1beta significantly inhibits HAS3 expression and protein formation
hyaluronan synthase 2 expression is elevated in both human and murine liver fibrosis. The enzyme is transcriptionally up-regulated by transforming growth factor-beta through Wilms tumor 1 to promote fibrogenic, proliferative, and invasive properties of HSCs via CD44, Toll-like receptor 4, and newly identified downstream effector Notch1
hyaluronan synthase 2 expression is elevated in both human and murine liver fibrosis. The enzyme is transcriptionally up-regulated by transforming growth factor-beta through Wilms tumor 1 to promote fibrogenic, proliferative, and invasive properties of HSCs via CD44, Toll-like receptor 4, and newly identified downstream effector Notch1
poststroke upregulation of hyaluronan synthase 2 in astrocytes and neurons
poststroke upregulation of hyaluronan synthase 2 in astrocytes and neurons
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
biotechnology
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optimization of the recombinant enzyme expression in Escherichia coli for large scale production of hyaluronan polymers for usage in basic studies, and for biotechnological creation of functional carbohydrates in medical purposes, engineering of produced product chain length
drug development
medicine
synthesis
analysis
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a rapid, continuous, and convenient three-enzyme coupled UV absorption assay is developed to quantitate the glucuronic acid and N-acetylglucosamine transferase activities of hyaluronan synthase. Activity is measured by coupling the UDP produced from the PmHAS-catalyzed transfer of UDP-GlcNAc and UDP-GlcUA to a hyaluronic acid tetrasaccharide primer with the oxidation of NADH. Using a fluorescently labeled primer, the products are characterized by gel electrophoresis. The assay can be used to determine kinetic parameters, inhibition constants, and mechanistic aspects of this enzyme. In addition, it can be used to quantify PmHAS during purification of the enzyme from culture media
analysis
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quantification of newly synthesized hyaluronan by polyacrylamide gel electrophoresis of fluorophore-labeled saccharides and high performance liquid chromatography. The method measures HAS activity in the plasma membrane fraction and also in the cytosolic membranes. The technique is used to evaluate the effects of 4-methylumbeliferone, phorbol 12-myristate 13-acetate, interleukin 1, platelet-derived growth factor BB, and tunicamycin on HAS activities
analysis
procedure for examining the influence of membrane environment on protein dynamics, using coarse-grained MD simulations combined with UMAP dimensionality reduction
analysis
M1H2Q1
generation of specific shark variable regions of immunoglobulin new antigen receptor (VNAR) for structural analysis
analysis
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nonradioactive method to quantify the HAS enzymatic activity in crude cellular membrane preparations. The method uses nonradioactive UDP-sugar precursors, the newly synthesized hyaluronic acid is then digested to obtain unsaturated disaccharides which are quantified by HPLC
drug development
the enzyme actively synthesizes hyaluronan in hepatic stellate cells and promotes hepatic stellate cells activation and liver fibrosis through Notch1. Targeted hyaluronan inhibition may have potential to be an effective therapy for liver fibrosis
drug development
inhibition of hyaluronan synthase 3-dependent synthesis of hyaluronan dampens systemic Th1 cell polarization and reduces plaque inflammation. Hyaluronan synthase 3 might be a promising therapeutic target in atherosclerosis. Because hyaluronan synthase 3 is regulated by IL-1beta, therapeutic anti-IL-1beta antibodies, may exert their beneficial effects on inflammation in post-myocardial infarction patients in part via effects on hyaluronan synthase 3
drug development
the enzyme actively synthesizes hyaluronan in hepatic stellate cells and promotes hepatic stellate cells activation and liver fibrosis through Notch1. Targeted hyaluronan inhibition may have potential to be an effective therapy for liver fibrosis
medicine
expression of HAS1Vb, an intronic splice variant, correlates with poor survival in multiple myeloma patients
medicine
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hyaluronan synthase 3 is the most dramatically up-regulated isozyme in metastatic prostate tumor cells
medicine
heregulin activation of ErbB2-ERK signaling modulates HAS phosphorylation/activation and hyaluronan production leading to CD-44-mediated oncogenic events and ovarian cancer progression
medicine
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the overproduction of hyaluronan in soft connective tissues can transform their biological and biomechanical functionality, the results demonstrate the feasibility of using a tissue-engineering approach with genetically modified cells to study the role of individual extracellular matrix components
medicine
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an in vitro model is developed to study the biomechanical effects of excess hyaluronan, which is relevant to many cardiovascular events
medicine
HAS1 variant Vc is transforming in vitro and tumorigenic in vivo when introduced as a single oncogene to untransformed cells. In co-transfected cells, full length HAS1 and HAS1 variants interact with themselves and with each other to form heteromeric multiprotein assemblies
medicine
HAS 2 appears to be a major contributor to the baseline levels of hyaluronan. Reduced HAS 2 gene expression and increased excreted urinary hyaluronidase activity during dehydration contribute to the reduced amount of hyaluronan and to antidiuretic response. In hydrated animals, the diuretic response is followed by a 58% elevation in papillary hyaluronan and a 45% reduction in the excreted urinary hyaluronidase activity. No difference is determined in HAS 13 mRNA or HYAL 1, 34 mRNA expression. In dehydrated animals, antidiuresis is followed by a 22% reduction in papillary hyaluronan and a 62% elevation in excreted urinary hyaluronidase activity. Plasma vasopressin is 2.8-fold higher in dehydrated versus hydrated rats
medicine
in hydrated animals, the diuretic response is followed by a 58% elevation in papillary hyaluronan and a 45% reduction in the excreted urinary hyaluronidase activity. No difference is determined in HAS 13 mRNA or HYAL 1, 34 mRNA expression. In dehydrated animals, antidiuresis is followed by a 22% reduction in papillary hyaluronan and a 62% elevation in excreted urinary hyaluronidase activity. Plasma vasopressin is 2.8-fold higher in dehydrated versus hydrated rats
medicine
in serous epithelial ovarian tumors, expression of HAS1 is low or absent. The levels of HAS2 and HAS3 mRNA are not consistently increased in the carcinomas, and are not significantly correlated with HAS protein or hyaluronan accumulation in individual samples
medicine
somatic HAS1 genetic variations occur in all hematopoietic cells tested, including normal CD34 hematopoietic progenitor cells and T cells, or as tumor-specific genretic variations restricted to malignant B and plasma cells. HAS1 genetic variations direct aberrant HAS1 intronic splicing. Nearly all newly identified inherited and somatic genetic variations in multiple myeloma and/or Waldenstrom macroglobulinemia are absent from B chronic lymphocytic leukemia, nonmalignant disease, and healthy donors
medicine
the role of HAS1 as a poor predictor in breast cancer, and is correlated with high relapse rate and short overall survival
medicine
targeting HAS2 to induce fibroblast senescence can be an attractive approach to resolve tissue fibrosis
medicine
the expression of HAS2/3 and production of hyaluronan are regulated by extracellular Mg2+ concentration in HaCaT cells. The supplementation of 5.8 mM MgCl2 enhances the recovery rate in the wound-healing assay. The MSK1/GSK3/CREB pathway may be involved in the elevation of HAS2/3 expression, and hyaluronan production by MgCl2 supplementation
synthesis
-
optimization of the recombinant enzyme expression in Escherichia coli for large scale production of hyaluronan polymers for usage in basic studies, and for biotechnological creation of functional carbohydrates in medical purposes, engineering of produced product chain length
synthesis
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it may be possible to generate compounds that will selectively inhibit the binding of hyaluronan to one particular hyaladherin species without perturbing other species. Such sugar molecules may have future utility as selective therapeutics with minimal side effects for diseases such as cancer, autoimmune disease, inflammation, and infection
synthesis
multi-enzyme strategy for the in vitro one-pot synthesis of high-molecular-weight hyaluronic acid from substrates sucrose and N-acetylglucosamine (GlcNAc) with in situ regeneration of nucleotide sugars. With optimized reaction conditions, hyaluronic acid with a molecular mass above 2 MDa is synthesized from catalytic UDP concentrations and 10 mM GlcNAc in less than 10 h
synthesis
the hasA gene is cloned and expressed in Escherichia coli BL21 and the use this recombinant Escherichia coli strain BL21 is used as host in order to explore the biosynthetic capabilities for hyaluronan production (concentration and molecular weight) in batch fermentation using shake flask culture. High hyaluronan production (0.115 g/l) is achieved in nutrient rich media with 50 g/l glucose concentration. With addition of 1.0 mM isopropyl beta-D-1-thiogalactopyranoside, the highest hyaluronan production (0.532 g/l) and molecular weight at 34600 Da is achieved which is around fivefold higher compared to without isopropyl beta-D-1-thiogalactopyranoside
synthesis
immobilisation of HAS on poly(N-vinylcaprolactam-2,2'-((5-acrylamido-1-carboxypentyl)azanediyl)diacetic acid) core-shell microgels containing different amounts of nitrilotriacetic acid and Ni2+, Co2+, Mn2+, Mg2+, and Fe2+/3+. In presence of Ni2+, high yields of UDP and high-MW hyaluronan are obtained. The immobilised enzyme can be reused for three cycles over 24 h
synthesis
Nicotiana tabacum hairy roots expressing human isoform HAS2 produce hyaluronic acid up to 0.56 g/kg (wet weight) and with molecular mass of about 0.8 MDa
EXTERNAL LINKS (specific for EC-Number 2.4.1.212)
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Release 2026.1 (March 2026)
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