Information on EC 2.4.1.212 - hyaluronan synthase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY
2.4.1.212
-
RECOMMENDED NAME
GeneOntology No.
hyaluronan synthase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
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]
show the reaction diagram
-
-
-
-
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]
show the reaction diagram
highly specific; 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 from Streptococcus Group A and Group C requires Mg2+. It is highly specific for UDP-GlcNAc and UDP-GlcA
-
-
-
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]
show the reaction diagram
2 active sites, the 2 DXD motifs of the transferase sites in the C-terminus, residues 686-703, are essential for activity
-
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]
show the reaction diagram
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
-
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]
show the reaction diagram
catalytic mechanism
-
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]
show the reaction diagram
catalytic mechanism, no covalent intermediates
-
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]
show the reaction diagram
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
-
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]
show the reaction diagram
addition of monosaccharides to the reducing end to form a linear heteropolysaccharide chain
-
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]
show the reaction diagram
2 active sites, the 2 DXD motifs of the transferase sites in the C-terminus, residues 686-703, are essential for activity
Pasteurella multocida type A
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
hexosyl group transfer
-
-
-
-
hexosyl group transfer
-
-
hexosyl group transfer
-
-
hexosyl group transfer
-, Q27J86, Q27J87, Q27J88
-
hexosyl group transfer
-
-
hexosyl group transfer
-
-
hexosyl group transfer
-
-
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.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
CHAS2
-
-
-
-
CHAS3
-
-
-
-
DG42 protein
-
-
-
-
HA synthase
-
-
-
-
HA synthase
-
-
HA synthase
Q92819
-
HA synthase
-
-
HA synthase
Pasteurella multocida type A
-
-
-
HA synthase
-
-
HA synthase
-
-
HAS
-
three isoforms, HAS1, HAS2, HAS3
HAS
-
-
HAS
Q27J86, Q27J87, Q27J88
-
HAS
Pasteurella multocida type A
-
-
-
HAS
O35776, Q8CH92, Q8CH93
-
HAS-1
-
-
HAS-1
Mus musculus C57Bl/6
-
-
-
HAS1
Q61647
-
HAS1
Q27J88
-
Has2
-
-
Has2
P70312
-
Has2
Q27J87
-
Has2
-
-
Has3
Q96RV2
-
Has3
-
-
Has3
O08650
-
Has3
Q27J86
-
HsHAS1
-
-
HuHAS1
-
-
-
-
hyaluronan synthase
Q92819, Q92839, Q96RV2
-
hyaluronan synthase
-
-
hyaluronan synthase
-
-
hyaluronan synthase
Q7BLV3
-
hyaluronan synthase
-
-
hyaluronan synthase
-
-
hyaluronan synthase 1
-
-
hyaluronan synthase 1
Q92839
-
hyaluronan synthase 2
-
-
hyaluronan synthase 2
Q92819
-
hyaluronan synthase 2
-
-
hyaluronan synthase 3
O00219
-
hyaluronan synthase-1
-
-
hyaluronan synthase-1
Mus musculus C57Bl/6
-
-
-
hyaluronan synthase-2
Q92819
-
hyaluronan synthases
Q27J86, Q27J87, Q27J88
-
hyaluronan synthethase
-
-
-
-
hyaluronate synthase
-
-
-
-
hyaluronate synthetase
-
-
-
-
hyaluronic acid synthase
-
-
-
-
PmHAS
Q7BLV3
-
XHAS1
-
-
-
-
XHAS2
-
-
-
-
XHAS3
-
-
-
-
hyaluronic acid synthetase
-
-
-
-
additional information
-
the enzyme of Pasteurella multocida belongs to the group of class II hyaluronan synthases
additional information
-
enzyme belongs to class I of hyaluronan synthases
additional information
-
the enzyme belongs to the class I hyaluronan synthases
additional information
-
the enzyme belongs to the group of class I hyaluronan synthases
additional information
-
enzyme belongs to class I of hyaluronan synthases
additional information
-
the enzyme belongs to the group of class I hyaluronan synthases
additional information
-
the enzyme of Streptococcus pyogenes belongs to the group of class I hyaluronan synthases
CAS REGISTRY NUMBER
COMMENTARY
39346-43-5
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
3 isozymes HAS1, HAS2, and HAS3 encoded by genes HAS1, HAS2, and HAS3
-
-
Manually annotated by BRENDA team
isoform HAS1
SwissProt
Manually annotated by BRENDA team
isoform HAS1; patients with multiple myeloma and Waldenstrom macroglobulinemia
SwissProt
Manually annotated by BRENDA team
isozyme HAS1
SwissProt
Manually annotated by BRENDA team
isozyme HAS2
-
-
Manually annotated by BRENDA team
isozyme HAS2
SwissProt
Manually annotated by BRENDA team
isozyme HAS3
SwissProt
Manually annotated by BRENDA team
isozymes HAS1, HAS2 and HAS3
-
-
Manually annotated by BRENDA team
recombinant
SwissProt
Manually annotated by BRENDA team
sequence used for preparation of siRNA
SwissProt
Manually annotated by BRENDA team
sequence used for preparation of siRNA
Q96RV2
UniProt
Manually annotated by BRENDA team
3 isozymes HAS1, HAS2, and HAS3 encoded by genes HAS1, HAS2, and HAS3
-
-
Manually annotated by BRENDA team
isozymes HAS2 and HAS3
-
-
Manually annotated by BRENDA team
pregnant mice, 3 isozymes HAS1, HAS2, and HAS3
-
-
Manually annotated by BRENDA team
Mus musculus C57Bl/6
-
-
-
Manually annotated by BRENDA team
HAS1 fragment; Spinifex hopping mouse
Q27J88
UniProt
Manually annotated by BRENDA team
HAS2 fragment; Spinifex hopping mouse
UniProt
Manually annotated by BRENDA team
HAS3 fragment; Spinifex hopping mouse
UniProt
Manually annotated by BRENDA team
avian pathogen, class II enzyme
-
-
Manually annotated by BRENDA team
Pasteurella multocida type A
type A
-
-
Manually annotated by BRENDA team
female Sprague-Dawley rat
-
-
Manually annotated by BRENDA team
isoform HAS2
SwissProt
Manually annotated by BRENDA team
isozyme HAS1; 3 isozymes HAS1, HAS2, and HAS3
SwissProt
Manually annotated by BRENDA team
isozyme HAS2; isozyme HAS2
SwissProt
Manually annotated by BRENDA team
isozyme HAS3
SwissProt
Manually annotated by BRENDA team
class I enzyme
-
-
Manually annotated by BRENDA team
human pathogen, single gene hasA in the has operon, class I enzyme
-
-
Manually annotated by BRENDA team
isozyme HAS1
-
-
Manually annotated by BRENDA team
Xenopus laevis protein DG42
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
HAS-1 overexpression in dermal wounds decreases elements of scar formation
malfunction
-
catalytically inactive mutant K190R HAS2 forms dimers with wild-type HAS2 and quenches the activity of wild-type HAS2
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
Mus musculus C57Bl/6
-
HAS-1 overexpression in dermal wounds decreases elements of scar formation
-
physiological function
-
mainly high molecular weight hyaluronan synthesized by isoform HAS1 regulates HT-1080 cell motility
physiological function
-
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
-
the reduction of hyaluronan caused by enzyme downregulation through 4-methylumbelliferone is associated with a significant inhibition of cell migration, proliferation and invasion; 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; 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
-
hyaluronan synthase mediates dye translocation across liposomal membranes
physiological function
-
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
-
hyaluronan synthesis is inhibited by adenosine monophosphate-activated protein kinase through the regulation of HAS2 activity in human aortic smooth muscle cells
physiological function
-
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
O00219, Q92819, Q92839
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
-
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
Mus musculus C57Bl/6
-
HAS-1 treatment of wounds promotes a more organized extracellular matrix with the regeneration of dermal appendages, including hair follicles, increased regenerative healing, overview
-
metabolism
-
regulation of hexosamine biosynthetic pathway, biosynthesis of hyaluronan and other glycoconjugates, and protein O-GlcNAcylation, overview
additional information
-
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
O00219, Q92819, Q92839
product hyaluronan is secreted to the cell surface or the into the growth medium by HAS-containing cell culture, respectively; product hyaluronan is secreted to the cell surface or the into the growth medium by HAS-containing cell culture, respectively; product hyaluronan is secreted to the cell surface or the into the growth medium by HAS-containing cell culture, respectively
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
hyaluronic acid tetrasaccharide + UDP-alpha-D-glucuronate
?
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
Q92819, Q92839, Q96RV2
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-, Q27J86, Q27J87, Q27J88
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-?-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]
show the reaction diagram
O00219, Q92819, Q92839
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
Q92819, Q92839, Q96RV2
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-, Q27J86, Q27J87, Q27J88
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
O00219, Q92819, Q92839
-
-
-
?
UDP-D-glucosamine + UDP-D-glucuronate
[beta-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
-
-
-
?
UDP-D-glucosamine + UDP-D-glucuronate
[beta-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + n UDP
show the reaction diagram
-
-
-
-
?
UDP-D-glucuronate + chondroitin 4-sulfate trisaccharide
?
show the reaction diagram
-
3.6% of the activity with hyaluronan
-
-
?
UDP-D-glucuronate + chondroitin 6-sulfate pentasaccharide
?
show the reaction diagram
-
61% of the activity with hyaluronan
-
-
?
UDP-D-glucuronate + chondroitin 6-sulfate trisaccharide
?
show the reaction diagram
-
80% of the activity with hyaluronan
-
-
?
UDP-D-glucuronate + chondroitin sulfate
?
show the reaction diagram
-
12% of the activity with hyaluronan
-
-
?
UDP-D-glucuronate + unsulfated chondroitin
?
show the reaction diagram
-
54% of the activity with hyaluronan
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
P70312
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
Q5X9A9
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
Q7BLV3
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
O35776, Q8CH92, Q8CH93
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
O35776, Q8CH92, Q8CH93
-
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
show the reaction diagram
-
addition of monosaccharides to the linear heteropolysaccharide chain
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
addition of monosaccharides to the linear heteropolysaccharide chain
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
addition of monosaccharides to the reducing end to form a linear heteropolysaccharide chain
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
addition of monosaccharides to the reducing end to form a linear heteropolysaccharide chain
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
show the reaction diagram
-
biosynthesis of hyaluronan
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
Q5X9A9
biosynthesis of hyaluronan
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
addition of monosaccharides to the linear heteropolysaccharide chain composed of repeating disaccharides
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
addition of monosaccharides to the linear heteropolysaccharide chain, recombinant isozyme HAS2 prefers the production of a mixture of 8mers and 16mers
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
addition of monosaccharides to the reducing end of the acceptor substrate, no binding and activity with exogenously added hyaluronan chains
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
show the reaction diagram
-
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
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
formation of linear hyaluronan polymers composed of alternating beta3-N-acetylglucosamine-beta4-glucuronic acid
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
show the reaction diagram
-
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
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
Xenopus laevis protein DG42
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
Pasteurella multocida type A
-
formation of linear hyaluronan polymers composed of alternating beta3-N-acetylglucosamine-beta4-glucuronic acid
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
-
?
hyaluronic acid tetrasaccharide + UDP-alpha-N-acetyl-D-glucosamine
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
enzyme is responsible for hyaluronan biosynthesis, the hyaluronan capsule is an important, but not the only, virulence factor, physiological role of the enzyme
-
-
-
additional information
?
-
O35776, Q8CH92, Q8CH93
isozyme expression and effects on tumor development and growth in rats, overview
-
-
-
additional information
?
-
O35776, Q8CH92, Q8CH93
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
-
-
-
additional information
?
-
-
isozyme expression and regulation by interleukin-1beta, progesterone, and low-molecular-weight hyaluronan in pregnant mouse uterine cervix, overview
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
the produced hyaluronan capsule enhances infection
-
-
-
additional information
?
-
-
conserved cysteine residues are not essential for enzyme function
-
-
-
additional information
?
-
Q5X9A9
conserved cysteine residues are not essential for enzyme function
-
-
-
additional information
?
-
-
determination of polymer synthesis progression direction, overview
-
-
-
additional information
?
-
-
enzyme acts processive, the enzyme is active as a complex with cardiolipin, a bacterial membrane lipid
-
-
-
additional information
?
-
-
enzyme is not processive, enzyme requires other proteins for hyaluronan translocation
-
-
-
additional information
?
-
-
substrate specificity, the GlcNAc-transferase, but not the GlcUA-transferase activity depends on the WGGED motif, overview
-
-
-
additional information
?
-
-
the enzyme is inactive without bound cardiolipins
-
-
-
additional information
?
-
-
the isozymes form products of different size, HA synthesis modeling, active site and substrate binding site are located on the big cytoplasmic loop
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
hyaluronic acid synthase contributes to the pathogenesis of Cryptococcus neoformans infection
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
HAS2, localized in the plasma membrane, uses cytoplasmic UDP-glucuronic acid and UDP-N-acetylglucosamine as substrates
-
-
-
additional information
?
-
O00219, Q92819, Q92839
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
-
-
-
additional information
?
-
O00219, Q92819, Q92839
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
-
-
-
additional information
?
-
Pasteurella multocida type A
-
the produced hyaluronan capsule enhances infection, substrate specificity, the GlcNAc-transferase, but not the GlcUA-transferase activity depends on the WGGED motif, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
Q92819, Q92839, Q96RV2
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-, Q27J86, Q27J87, Q27J88
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-?-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]
show the reaction diagram
O00219, Q92819, Q92839
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
Q92819, Q92839, Q96RV2
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-, Q27J86, Q27J87, Q27J88
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
-
-
-
-
?
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]
show the reaction diagram
O00219, Q92819, Q92839
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
P70312
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
Q7BLV3
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
O35776, Q8CH92, Q8CH93
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
addition of monosaccharides to the linear heteropolysaccharide chain
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
addition of monosaccharides to the reducing end to form a linear heteropolysaccharide chain
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
-
biosynthesis of hyaluronan
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
Q5X9A9
biosynthesis of hyaluronan
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
show the reaction diagram
Xenopus laevis protein DG42
-
-
-
-
?
additional information
?
-
-
enzyme is responsible for hyaluronan biosynthesis, the hyaluronan capsule is an important, but not the only, virulence factor, physiological role of the enzyme
-
-
-
additional information
?
-
O35776, Q8CH92, Q8CH93
isozyme expression and effects on tumor development and growth in rats, overview
-
-
-
additional information
?
-
O35776, Q8CH92, Q8CH93
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
-
-
-
additional information
?
-
-
isozyme expression and regulation by interleukin-1beta, progesterone, and low-molecular-weight hyaluronan in pregnant mouse uterine cervix, overview
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
the produced hyaluronan capsule enhances infection
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
hyaluronic acid synthase contributes to the pathogenesis of Cryptococcus neoformans infection
-
-
-
additional information
?
-
-
HAS2, localized in the plasma membrane, uses cytoplasmic UDP-glucuronic acid and UDP-N-acetylglucosamine as substrates
-
-
-
additional information
?
-
O00219, Q92819, Q92839
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
-
-
-
additional information
?
-
Pasteurella multocida type A
-
the produced hyaluronan capsule enhances infection
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
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
KCl
-
activates at 50 mM, slightly more effective than NaCl
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+
-
required by class II enzyme
Mg2+
-
required
Mg2+
-
a nucleotide with 2 phosphate groups and complexed with a Mg2+ ion is absolutely required for activity
Mg2+
-
-
Mg2+
-
required
Mg2+
O00219, Q92819, Q92839
required; required; required
Mn2+
-
essential for activity
NaCl
-
activates at 50 mM, slightly less effective than KCl
Mn2+
-
absolutely required, best metal cofactor, 0.2 mM
additional information
-
metal requirements of mutant enzymes, overview
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2-deoxyglucose
-
-
4-methylesculetin
-
-
4-Methylumbelliferone
-
changes the localization of the enzyme by preventing its association with the plasma membrane
4-Methylumbelliferone
-
-
4-Methylumbelliferone
O00219, Q92819, Q92839
inhibits HAS because it depletes UDPGlcUA in cells; inhibits HAS because it depletes UDPGlcUA in cells; inhibits HAS because it depletes UDPGlcUA in cells
5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside
-
modulates aortic smooth muscle cell motility and adhesive properties through AMP-activated protein kinase, AMPK
AG825
Q92819, Q92839, Q96RV2
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
DTNB
Q5X9A9
52% inhibition at 0.5 mM
HAS1 siRNA
-
-
-
iodoacetamide
-
15% inhibition at 5 mM, biphasic inhibition
iodoacetamide
Q5X9A9
13% inhibition at 5 mM, biphasic inhibition
Mannose
O00219, Q92819, Q92839
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
methylmethanethiosulfonate
-
93% reduced activity at 0.05 mM
N-ethylmaleimide
-
-
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
Q5X9A9
60% inhibition at 5 mM, biphasic inhibition
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
PEG
-
increasing MW increases the inhibitory effect on the enzyme, overview
siRNA
Q92819, Q92839, Q96RV2
-
-
Sodium arsenite
-
inhibition of wild-type and mutant enzymes, no inhibition of C262 deletion mutant, overview
Sodium arsenite
-
40% inhibition at 10 mM
Sodium arsenite
Q5X9A9
46% inhibition at 10 mM
sodium salicylate
-
sodium salicylate is a potent suppressor of HAS1 activation
-
sulfhydryl reagents
-
enzyme is inhibited by sulfhydryl-modifying reagents, inhibition mode and mechanism
sulfhydryl reagents
Q5X9A9
enzyme is inhibited by sulfhydryl-modifying reagents, inhibition mode and mechanism
tetramyristoyl cardiolipin
-
inactivating
thiazolidinedione
Q92819, Q92839, Q96RV2
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
methylmethanethiosulfonate
Q5X9A9
89% reduced activity at 0.05 mM
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
-
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
-
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
-
not inhibitory: 4-methylumbeliferone
-
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
-
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
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
black rice hydrolized peptides
-
BRP from germinated Oryza sativa L. var. japonica
-
carbocyclic thromboxane A2
-
-
cardiolipin
-
required for full activity, activates up to 10fold, 14-18 molecules of cardiolipin are bound to one molecule of enzyme
dioleoyl phosphatidic acid
-
stimulates about 10fold
Epidermal growth factor
-
EGF
Epstein-Barr virus
-
-
-
ERK
Q92819, Q92839, Q96RV2
heregulin-mediated HAS isozyme phosphorylation/activation; heregulin-mediated HAS isozyme phosphorylation/activation; heregulin-mediated HAS isozyme phosphorylation/activation
-
interleukin 1beta
-
activation of enzyme in plasma membrane fraction
-
Interleukin-1beta
-
-
-
O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate
-
increases O-GlcNAcylation and HA synthesis
PDGF-BB
-
-
-
phorbol 12-myristate 13-acetate
-
activation of enzyme in plasma membrane fraction
pinane thromboxane A2
-
-
platelet derived growth factor BB
-
PDGF-BB
-
platelet derived growth factor BB
-
PDGF-BB
-
platelet derived growth factor-BB
-
PDGF-BB
-
platelet-derived growth factor BB
-
activation of enzyme in plasma membrane fraction
-
prostacyclin
-
-
prostaglandin E2
-
-
prostaglandin E2
-
-
prostaglandin F2alpha
-
-
prostaglandin I2
-
-
prostaglandin I2
-
-
synthetic single-stranded poly(A)
-
-
-
synthetic single-stranded poly(C)
-
-
-
synthetic viral RNA analog poly(I,C)
-
-
-
tetraoleoyl cardiolipin
-
highly activating
tetraoleoyl cardiolipin
-
strong activation, same pattern of lipid preference between pH 6 and 10.5. Lipid-independent activity at pH 11.5
TGFbeta1
-
-
-
TNFalpha
-
-
-
Transforming growth factor
-
TGF-1beta
-
transforming growth factor-beta
-
TGF-beta
-
transforming growth factor-beta1
-
TGF-beta1
-
Tunicamycin
-
significant increase in HAS activity in the cytosolic membrane fraction after tunicamycin treatment
UVB irradiation
-
UVB increases HAS2 mRNA expression; UVB increases HAS3 mRNA expression
-
Interleukin-1beta
-
-
-
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
-
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
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.014
-
UDP-alpha-D-glucuronate
-
25C, pH 7.5
0.66
-
UDP-alpha-N-acetyl-D-glucosamine
-
25C, pH 7.5
0.032
-
UDP-D-glucuronate
-
HAS2
0.034
-
UDP-D-glucuronate
-
HAS3
0.04
-
UDP-D-glucuronate
-
-
0.04
-
UDP-D-glucuronate
-
pH 7.0, 30C, recombinant mutant C281A
0.044
-
UDP-D-glucuronate
-
pH 7.0, 30C, recombinant mutant C226S
0.056
-
UDP-D-glucuronate
-
pH 7.0, 30C, recombinant mutant C281S
0.06
-
UDP-D-glucuronate
-
-
0.073
-
UDP-D-glucuronate
-
HAS1
0.077
-
UDP-D-glucuronate
-
pH 7.0, 30C, recombinant wild-type enzyme
0.079
-
UDP-D-glucuronate
-
pH 7.0, 30C, recombinant mutant C367S
0.085
-
UDP-D-glucuronate
-
pH 7.0, 30C, recombinant mutant C367A
0.088
-
UDP-D-glucuronate
-
pH 7.0, 30C, recombinant mutant C226A
0.096
-
UDP-D-glucuronate
-
pH 7.0, 30C, recombinant mutant C262S
0.11
-
UDP-D-glucuronate
-
pH 7.5, 30C, recombinant wild-type enzyme at low UDP-N-acetyl-D-glucosamine concentration, and mutant C239S
0.12
-
UDP-D-glucuronate
-
pH 7.5, 30C, recombinant mutants C117S and C210S
0.14
-
UDP-D-glucuronate
-
-
0.146
-
UDP-D-glucuronate
-
pH 7.0, 30C, recombinant mutant C262A
0.16
-
UDP-D-glucuronate
-
pH 7.5, 30C, recombinant mutant C298S
0.18
-
UDP-D-glucuronate
-
pH 7.5, 30C, recombinant mutant C304S
0.19
-
UDP-D-glucuronate
-
pH 7.5, 30C, recombinant wild-type enzyme
0.7
-
UDP-D-glucuronate
-
pH 7.5, 30C, recombinant mutant C337S
0.89
-
UDP-D-glucuronate
-
pH 7.5, 30C, recombinant mutant C304S/C337S
0.93
-
UDP-D-glucuronate
-
pH 7.5, 30C, recombinant mutant C239S/C337S
0.053
-
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30C, recombinant mutant C226A/C281A
0.06
-
UDP-N-acetyl-D-glucosamine
-
-
0.065
-
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30C, recombinant mutant C281A/C367A
0.074
-
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30C, recombinant wild-type enzyme
0.079
-
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30C, recombinant mutant C226A/C367A
0.08
-
UDP-N-acetyl-D-glucosamine
-
HAS3
0.09
-
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30C, recombinant mutant C367A
0.091
-
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30C, recombinant mutant C367S
0.098
-
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30C, recombinant mutant C281S
0.11
-
UDP-N-acetyl-D-glucosamine
-
HAS2
0.113
-
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30C, recombinant mutant C262A/C281A
0.121
-
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30C, recombinant mutant C262A/C367A
0.13
-
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30C, recombinant mutant C281A
0.134
-
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30C, recombinant mutant C226A/C262A
0.149
-
UDP-N-acetyl-D-glucosamine
-
-
0.153
-
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30C, recombinant mutant C262S
0.154
-
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30C, recombinant mutant C226A
0.16
-
UDP-N-acetyl-D-glucosamine
-
-
0.186
-
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30C, recombinant mutant C262A
0.23
-
UDP-N-acetyl-D-glucosamine
-
-
0.232
-
UDP-N-acetyl-D-glucosamine
-
pH 7.0, 30C, recombinant mutant C226S
0.26
-
UDP-N-acetyl-D-glucosamine
-
pH 7.5, 30C, recombinant wild-type enzyme at low UDP-glucuronate concentration
0.32
-
UDP-N-acetyl-D-glucosamine
-
pH 7.5, 30C, recombinant mutant C239S
0.34
-
UDP-N-acetyl-D-glucosamine
-
pH 7.5, 30C, recombinant mutant C117S
0.4
-
UDP-N-acetyl-D-glucosamine
-
pH 7.5, 30C, recombinant wild-type enzyme and mutants C210S, C337S at low UDP-glucuronate concentration
0.43
-
UDP-N-acetyl-D-glucosamine
-
pH 7.5, 30C, recombinant mutant C298S
0.47
-
UDP-N-acetyl-D-glucosamine
-
pH 7.5, 30C, recombinant mutant C304S
0.79
-
UDP-N-acetyl-D-glucosamine
-
HAS1
0.88
-
UDP-N-acetyl-D-glucosamine
-
pH 7.5, 30C, recombinant mutant C337S at higher UDP-glucuronate concentration
1
-
UDP-N-acetyl-D-glucosamine
-
pH 7.5, 30C, recombinant mutant C239S/C337S
1.1
-
UDP-N-acetyl-D-glucosamine
-
pH 7.5, 30C, recombinant mutant C304S/C337S
0.91
-
hyaluronic acid tetrasaccharide
-
25C, pH 7.5
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, wild-type and mutant enzymes
-
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
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
120
-
UDP-D-glucuronate
-
recombinant enzyme, pH 7.0, 30C
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
4.5
-
ethylene glycol
-
recombinant enzyme, pH 7.0, 30C
3.3
-
glycerol
-
recombinant enzyme, pH 7.0, 30C
3.5
-
PEG 20000
-
recombinant enzyme, pH 7.0, 30C
1.2
-
Sucrose
-
recombinant enzyme, pH 7.0, 30C
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.0000000062
-
Q92819, Q92839, Q96RV2
HAS activity, HAS1siRNA + HAS2siRNA + HAS3siRNA treatment, plus heregulin; HAS activity, HAS1siRNA + HAS2siRNA + HAS3siRNA treatment, plus heregulin; HAS activity, HAS1siRNA + HAS2siRNA + HAS3siRNA treatment, plus heregulin
0.0000000092
-
Q92819, Q92839, Q96RV2
HAS activity, HAS1siRNA + HAS2siRNA + HAS3siRNA treatment; HAS activity, HAS1siRNA + HAS2siRNA + HAS3siRNA treatment; HAS activity, HAS1siRNA + HAS2siRNA + HAS3siRNA treatment
0.000000017
-
Q92819, Q92839, Q96RV2
HAS activity, HAS2siRNA treatment; HAS activity, HAS2siRNA treatment; HAS activity, HAS2siRNA treatment
0.0000000175
-
Q92819, Q92839, Q96RV2
HAS activity, HAS1siRNA treatment; HAS activity, HAS1siRNA treatment; HAS activity, HAS1siRNA treatment
0.0000000188
-
Q92819, Q92839, Q96RV2
HAS activity, HAS3siRNA treatment; HAS activity, HAS3siRNA treatment; HAS activity, HAS3siRNA treatment
0.0000000222
-
Q92819, Q92839, Q96RV2
HAS activity, AG825 treatment; HAS activity, AG825 treatment; HAS activity, AG825 treatment
0.0000000227
-
Q92819, Q92839, Q96RV2
HAS activity, HAS2siRNA treatment, plus heregulin; HAS activity, HAS2siRNA treatment, plus heregulin; HAS activity, HAS2siRNA treatment, plus heregulin
0.000000023
-
Q92819, Q92839, Q96RV2
HAS activity, thiazolidinedione treatment; HAS activity, thiazolidinedione treatment; HAS activity, thiazolidinedione treatment
0.0000000233
-
Q92819, Q92839, Q96RV2
HAS activity, no treatment, control; HAS activity, no treatment, control; HAS activity, no treatment, control
0.0000000237
-
Q92819, Q92839, Q96RV2
HAS activity, scrambled sequence treatment, control; HAS activity, scrambled sequence treatment, control; HAS activity, scrambled sequence treatment, control
0.0000000248
-
Q92819, Q92839, Q96RV2
HAS activity, HAS1siRNA treatment, plus heregulin; HAS activity, HAS1siRNA treatment, plus heregulin; HAS activity, HAS1siRNA treatment, plus heregulin
0.000000025
-
Q92819, Q92839, Q96RV2
HAS activity, HAS3siRNA treatment, plus heregulin; HAS activity, HAS3siRNA treatment, plus heregulin; HAS activity, HAS3siRNA treatment, plus heregulin
0.0000000257
-
Q92819, Q92839, Q96RV2
HAS activity, AG825 treatment, plus heregulin; HAS activity, AG825 treatment, plus heregulin; HAS activity, AG825 treatment, plus heregulin
0.0000000263
-
Q92819, Q92839, Q96RV2
HAS activity, thiazolidinedione treatment, plus heregulin; HAS activity, thiazolidinedione treatment, plus heregulin; HAS activity, thiazolidinedione treatment, plus heregulin
0.0000000583
-
Q92819, Q92839, Q96RV2
HAS activity, scrambled sequence treatment, control, plus heregulin; HAS activity, scrambled sequence treatment, control, plus heregulin; HAS activity, scrambled sequence treatment, control, plus heregulin
0.0000000627
-
Q92819, Q92839, Q96RV2
HAS activity, no treatment, control, plus heregulin; HAS activity, no treatment, control, plus heregulin; HAS activity, no treatment, control, plus heregulin
13.4
-
-
mutant C226A/C262A, pH 7.0, 30C
14
-
-
deletion mutant DELTA3-C281, pH 7.0, 30C
16.4
-
-
mutant C226A, pH 7.0, 30C
16.5
-
-
mutant C226S, pH 7.0, 30C
21.2
-
-
mutant C281S, pH 7.0, 30C
22.9
-
-
deletion mutant C-Null, pH 7.0, 30C
25.3
-
-
mutant C226A/C281A, pH 7.0, 30C
27
-
-
deletion mutant DELTA3-C367, pH 7.0, 30C
29.1
-
-
mutant C262A, pH 7.0, 30C
29.5
-
-
mutant C367S, pH 7.0, 30C
30.2
-
-
mutant C262A/C281A, pH 7.0, 30C
31.4
-
-
mutant C262S, pH 7.0, 30C
31.6
-
-
deletion mutant DELTA3-C262, pH 7.0, 30C
33.7
-
-
mutant C281A, pH 7.0, 30C
37
-
-
wild-type enzyme, pH 7.0, 30C
37.8
-
-
mutant C226A/C367A, pH 7.0, 30C
38.6
-
-
deletion mutant DELTA3-C226, pH 7.0, 30C
39.5
-
-
mutant C281A/C367A, pH 7.0, 30C
46.7
-
-
mutant C367A, pH 7.0, 30C
additional information
-
O35776, Q8CH92, Q8CH93
activity in wild-type cells and their oncogenic transformants; activity in wild-type cells and their oncogenic transformants; activity in wild-type cells and their oncogenic transformants
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.1
-
O35776, Q8CH92, Q8CH93
assay at; assay at; assay at
7.1
-
O00219, Q92819, Q92839
assay at; assay at; assay at
7.4
-
-
assay at
7.5
-
-
assay at
7.5
-
-
assay at
7.6
8.1
-
-
9
10
-
recombinant enzyme, pH-profile
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
11.5
-
recombinant enzyme, pH-profile
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
22
-
-
HAS capture assay, overnight at room temperature
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
standard assay for HAS activity
37
-
O35776, Q8CH92, Q8CH93
assay at; assay at; assay at
37
-
-
assay at
37
-
-
standard assay for HAS activity
37
-
O00219, Q92819, Q92839
assay at; assay at; assay at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
O35776, Q8CH92, Q8CH93
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; fibroblast, oncogenic malignant transformation with v-sre and/or v-fos, and v-HA-ras
Manually annotated by BRENDA team
-
HAS2 is the main synthase in aortic smooth muscle cells
Manually annotated by BRENDA team
Q92839
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
Manually annotated by BRENDA team
O00219, Q92819, Q92839
-
Manually annotated by BRENDA team
-
skin dermal fibroblast cell
Manually annotated by BRENDA team
O08650, Q61647
at embryonic day 7.5, Has1 is expressed throughout the gastrulating embryo. After ambryonic day 8.5, Has1 expression disappears; 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; 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
Manually annotated by BRENDA team
-
vitreous body
Manually annotated by BRENDA team
-
uterine cervical
Manually annotated by BRENDA team
O35776, Q8CH92, Q8CH93
;
Manually annotated by BRENDA team
-
dermal fibroblast
Manually annotated by BRENDA team
-
oral and dermal fibroblast
Manually annotated by BRENDA team
Mus musculus C57Bl/6
-
dermal
-
Manually annotated by BRENDA team
O35776, Q8CH92, Q8CH93
tumorigenic cell line, 3-5fold higher hyaluronan accumulation than in the parental cell line 3Y1; tumorigenic cell line, 3-5fold higher hyaluronan accumulation than in the parental cell line 3Y1
Manually annotated by BRENDA team
-
epidermal keratinocyte, NHEK(F) cell
Manually annotated by BRENDA team
-
epidermal keratinocyte
Manually annotated by BRENDA team
-, Q27J86, Q27J87, Q27J88
-
Manually annotated by BRENDA team
O35776
strong expression of HAS2 mRNA; weak expression of HAS1 and HAS3 mRNA
Manually annotated by BRENDA team
-
HAS1 expression is shown in 55.7% of SIRPA-positive macrophages in stage III follicles
Manually annotated by BRENDA team
-
hyaluronan synthesized by HAS-2 in MG-63 plays a crucial role in osteosarcoma cell proliferation, motility, and invasion
Manually annotated by BRENDA team
-
TGF-beta2 is the major stimulator of HAS2 isoform expression in osteosarcoma cells
Manually annotated by BRENDA team
-
mouse epithelial cell line
Manually annotated by BRENDA team
-
platelet-derived growth factor BB exerts dominant influence on HAS2 isoform expression by osteoblasts
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
serous epithelial ovarian tumor
Manually annotated by BRENDA team
-
serous epithelial ovarian tumor; serous epithelial ovarian tumor
Manually annotated by BRENDA team
Q92819, Q92839, Q96RV2
-
Manually annotated by BRENDA team
-
serous epithelial ovarian tumor
Manually annotated by BRENDA team
O35776, Q8CH92, Q8CH93
-
Manually annotated by BRENDA team
-
type DPK-SKDF-H
Manually annotated by BRENDA team
Q92819, Q92839, Q96RV2
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; 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; 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
Manually annotated by BRENDA team
O35776, Q8CH92, Q8CH93
metastatic cell line, 3-5fold higher hyaluronan accumulation than in the parental cell line 3Y1; metastatic cell line, 3-5fold higher hyaluronan accumulation than in the parental cell line 3Y1
Manually annotated by BRENDA team
-
type-B-synoviocyte
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
O00219
13fold decrease in hyaluronan synthase 3 expression in mineralising MG63 cells; no significant change in hyaluronan synthase 2 expression in mineralising cells
Manually annotated by BRENDA team
additional information
-
isozyme expression profile in uterine cervix of pregnant mice
Manually annotated by BRENDA team
additional information
-
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
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
bound, enzyme possesses a cysteine cluster localized at the inner surface of the cell membrane near the substrate/product-binding sites
-
Manually annotated by BRENDA team
-
most parts of the enzyme, except the transmembrane region, are cytoplasmic including the active site
-
Manually annotated by BRENDA team
-
enzyme is predicted to be an integral membrane protein
Manually annotated by BRENDA team
-
fraction containing membrane proteins from the endoplasmic reticulum and Golgi apparatus
Manually annotated by BRENDA team
-
integral, plasma membrane residence of hyaluronan synthase is coupled to its enzymatic activity
Manually annotated by BRENDA team
-, Q27J86, Q27J87, Q27J88
-
Manually annotated by BRENDA team
-
inner surface of the plasma membrane
Manually annotated by BRENDA team
-
the hyaluronan polymer is synthesized on the cytosolic side of the cell membrane by the membrane-embedded hyaluronan synthase
Manually annotated by BRENDA team
additional information
-
probably cytoplasm or periplasm
-
Manually annotated by BRENDA team
additional information
-
recombinant isozymes GFP-HAS2 and GFP-HAS3 travel through endoplasmic reticulum, Golgi, plasma membrane, and endocytic vesicles in keratinocytes
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
42000
-
-
SDS-PAGE
47780
-
-
calculation from sequence
47780
-
-
calculation from sequence
48000
-
-
northern blot
52000
-
-
SDS-PAGE
60000
-
Q92819, Q92839, Q96RV2
determined by SDS-PAGE and Western Blot analysis; determined by SDS-PAGE and Western Blot analysis
62000
-
Q92819, Q92839, Q96RV2
determined by SDS-PAGE and Western Blot analysis
66000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 49000, recombinant enzyme, SDS-PAGE
monomer
-
1 * 48000, without cardiolipin, radiation inactivation analysis
monomer
-
enzyme functions as a monomer
additional information
-
the membrane-bound enzyme possesses a membrane-localized cysteine cluster near the substrate-binding sites
additional information
-
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
-
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
-
predicted enzyme topology and organization, overview
additional information
-
enzyme topology and organization, overview
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
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phosphoprotein
O00219
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
Q92819, Q92839, Q96RV2
ERK-mediated phosphorylation; ERK-mediated phosphorylation; ERK-mediated phosphorylation
phosphoprotein
-
HAS activity can be modulated by post-translational modification, such as phosphorylation and N-glycosylation
glycoprotein
-
HAS activity can be modulated by post-translational modification, such as phosphorylation and N-glycosylation
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
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
additional information
-
HAS2 is ubiquitinated on Lys190, HAS2 is both mono- and polyubiquitinated
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.5
-
-
1 h, at 30C, loss of 74-90% activity
11.5
-
-
1 h, at 30C, loss of 40-50% activity
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
-
the enzyme is temperature labile, but is stabilized by substrate and cardiolipin
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
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
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
4C, Na-phosphate buffer, 10% glycerol, 96 h, 18%
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
partial
-
recombinant isozymes by immunoaffinity chromatography
-
recombinant synthesis of hyaluronan is carried out with Agrobacterium sp. strain ATCC 31749, hyaluronan is primarly found in the culture medium
-
on a Ni2+-nitrilotriacetic acid resin
-
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 enzyme from Escherichia coli, native enzyme to homogeneity
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Saccharomyces cerevisiae and Escherichia coli
-
-
Q92839
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
-
expression in COS-7 cells
O00219
expression of isozyme HAS2-MBP-fusion protein in Escherichia coli strain JM109
-
expression of wild-type FLAG-tagged human HAS1, HAS2, or HAS3, and of HAS T110A mutant enzyme in COS-7 cells
-
gene HAS1, expression analysis and recombinant expression in COS-1 cells; gene HAS2, expression analysis and recombinant expression in COS-1 cells; gene HAS3, expression analysis and recombinant expression in COS-1 cells
O00219, Q92819, Q92839
genes HAS1, HAS2 and HAS3, quantitative expression analysis in benign and malign endometrial tissue
-
Homo sapiens hyaluronan synthase 1 is cloned into the plasmid pFLAG-CMV2, for in vitro translation the pF3A WG(BYDV) Flexi vector is used
-
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
-
the coding sequence of HAS1 is cloned into the vector pCR3.1 for transfection of fibroblasts
-
the human HAS2 expression plasmid is prepared by inserting its coding sequence into the vector pcDNA 3.1/CT-GFP-TOPO
Q92819, Q92839, Q96RV2
ectopic expression of Flag- and 6myc-HAS2 in COS-1 cells as homodimers, co-expression with Flag-HAS3 leads to formation of heterodimers
-
expression in COS-1 cells and rat 3Y1 fibroblasts
-
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
-
overexpression of GFP-tagged HAS-1 in the wounds of lentiviral-HAS-1-treated mice
-
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
-
into a pCR2.1 vector for sequencing; into a pCR2.1 vector for sequencing; into a pCR2.1 vector for sequencing
-, Q27J86, Q27J87, Q27J88
expression in Escherichia coli
-
expression as a soluble active protein comprising residues 1-703
-
expression in Escherichia coli
-
expression of wild-type and mutants enzymes in Escherichia coli
-
the Escherichia coli expression vector pQE80L and the broad host range cloning vector pBBR122 are used
-
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
O35776, Q8CH92, Q8CH93
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 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
-
Streptococcus equisimilis hyaluronan synthase is cloned into the plasmid pKK223-3 for expression in Escherichia coli SURE cells
-
expression of both hyaluronan synthase and UDP-glucose-6-dehydrogenase in Lactococcus lactis
-
expression in Escherichia coli
-
overexpression in Escherichia coli, enzyme cannot be expressed as a soluble active protein
-
expression in yeast
-
expression of wild-type and mutant enzymes in Saccharomyces cerevisiae strain BJ5461
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
transforming grwoth factor 1beta significantly inhibits HAS3 expression and protein formation
-
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; 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
-
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
-
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; 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; 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
-
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
-
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
-
reduced HAS 2 gene expression and increased excreted urinary hyaluronidase activity during dehydration contribute to the reduced amount of hyaluronan and to antidiuretic response
O35776
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
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
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
D216A
-
site-directed mutagenesis, isozyme HAS3, inactive mutant
D196N
-
mutants possess UDP-D-glucuronate-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
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
D247E
Pasteurella multocida type A
-
site-directed mutagenesis, mutant possesses only GlcUA-transferase activity
-
D247K
Pasteurella multocida type A
-
site-directed mutagenesis, mutant possesses only GlcUA-transferase activity
-
D247N
Pasteurella multocida type A
-
site-directed mutagenesis, mutant possesses only GlcUA-transferase activity
-
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/C262A/C367A
-
site-directed mutagenesis, 1.4% remaining activity and altered kinetic constants 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
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
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
K48F
-
site-directed mutagenesis, alteration of K48 within membrane domain 2 causes decreased activity and HA product size
C117F
-
site-directed mutagenesis, no expression in yeast possible
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
O00219, Q92819, Q92839
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; COS-1 cells, with minor endogenous hyaluronan synthesis, is transfected with Has2 isozyme. Hyaluronan synthesis driven by HAS2 is less affected by glucosamine addition; 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
K190R
-
site-directed mutagenesis, inactive mutant, K190R-mutated HAS2 forms dimers with wild-type HAS2 and quenches the activity of wild-type HAS2
additional information
-
site-directed mutagenesis of residues of the cytoplasmic loop of isozyme HAS1 for determining the residues required for glycosyltransferase activity
additional information
-
construction of deletion mutants of isozyme HAS3
E369Q
-
site-directed mutagenesis, mutant possesses GlcUA-transferase activity, and very low GlcNAc-transferase 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
D249N
Pasteurella multocida type A
-
site-directed mutagenesis, mutant possesses only GlcUA-transferase activity
-
additional information
Pasteurella multocida type A
-
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
O35776, Q8CH92, Q8CH93
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; 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
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
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
-
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
-
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
-
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
Streptococcus equi subsp. zooepidemicus FHA0
-
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
-
variety of cystein mutatants
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
analysis
-
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
biotechnology
-
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
medicine
Q92839
expression of HAS1Vb, an intronic splice variant, correlates with poor survival in multiple myeloma patients
medicine
Q92819, Q92839, Q96RV2
heregulin activation of ErbB2-ERK signaling modulates HAS phosphorylation/activation and hyaluronan production leading to CD-44-mediated oncogenic events and ovarian cancer progression; heregulin activation of ErbB2-ERK signaling modulates HAS phosphorylation/activation and hyaluronan production leading to CD-44-mediated oncogenic events and ovarian cancer progression; 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
-
hyaluronan synthase 3 is the most dramatically up-regulated isozyme in metastatic prostate tumor cells
medicine
Q92839
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
-
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; 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
-
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
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
analysis
-
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
synthesis
-
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
medicine
-
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
-
an in vitro model is developed to study the biomechanical effects of excess hyaluronan, which is relevant to many cardiovascular events
medicine
O35776
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; 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