Any feedback?
Information on EC 2.4.1.212 - hyaluronan synthase and Organism(s) Mus musculus and UniProt Accession P70312
for references in articles please use BRENDA:EC2.4.1.212Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
2.4.1.212 hyaluronan synthaseIUBMB Comments
The enzyme from Streptococcus Group A and Group C requires Mg2+. The enzyme adds GlcNAc to nascent hyaluronan when the non-reducing end is GlcA, but it adds GlcA when the non-reducing end is GlcNAc . The enzyme is highly specific for UDP-GlcNAc and UDP-GlcA; no copolymerization is observed if either is replaced by UDP-Glc, UDP-Gal, UDP-GalNAc or UDP-GalA. Similar enzymes have been found in a variety of organisms.
Specify your search results
Word Map
- 2.4.1.212
- glycosaminoglycans
- collagen
- polysaccharide
- keratinocytes
- cartilage
- 4-methylumbelliferone
- proteoglycans
- hyaluronidases
- chondrocytes
-
dermal
- mesenchymal
-
pericellular
- pasteurella
-
udp-glucuronic
-
hyals
- versican
-
cumulus
- synovial
-
vocal
-
articular
- aggrecan
- osteoarthritis
- streptococcal
- udp-n-acetylglucosamine
- multocida
-
rhamm
- pyogenes
- udp-sugars
- chondroitin
-
glucuronic
- procollagen
- synoviocytes
-
cumulus-oocyte
- decorin
- udp-glcua
-
photoaging
- filaggrin
- equisimilis
-
ha-binding
-
temporomandibular
-
glcua
-
perineuronal
- ophthalmopathy
- zooepidemicus
-
uvb-irradiated
-
ha-mediated
-
tnfaip6
- medicine
-
hyaluronan-binding
- fibromodulin
- biglycan
- analysis
- synthesis
- drug development
- biotechnology
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
hyaluronan synthase, ha synthase, hyaluronan synthase 2, has-2, hyaluronic acid synthase, sehas, has-1, pmhas, hyaluronan synthase-2, hyaluronate synthase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CHAS2
-
-
-
-
CHAS3
-
-
-
-
DG42 protein
-
-
-
-
HA synthase
HA synthase 3
HAS-1
Has3
HuHAS1
-
-
-
-
hyaluronan synthase 3
hyaluronan synthethase
-
-
-
-
hyaluronate synthase
-
-
-
-
hyaluronate synthetase
-
-
-
-
hyaluronic acid synthase
-
-
-
-
hyaluronic acid synthetase
-
-
-
-
XHAS1
-
-
-
-
XHAS2
-
-
-
-
XHAS3
-
-
-
-
HA synthase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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.
CAS REGISTRY NUMBER
COMMENTARY
39346-43-5
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
-
-
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
-
-
-
-
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
-
-
-
?
additional information
?
-
hyaluronan synthase 1 and hyaluronan synthase 2 synthesize high molecular weight hyaluronan, while hyaluronan synthase 3 synthesizes low lecular weight hyaluronan
-
-
-
additional information
?
-
hyaluronan synthase 1 and hyaluronan synthase 2 synthesize high molecular weight hyaluronan, while hyaluronan synthase 3 synthesizes low lecular weight hyaluronan
-
-
-
additional information
?
-
hyaluronan synthase 1 and hyaluronan synthase 2 synthesize high molecular weight hyaluronan, while hyaluronan synthase 3 synthesizes low lecular weight hyaluronan
-
-
-
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, isozymes exhibit different functions in tumor growth, progression, and determination of malignancy
-
-
?
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
?
-
-
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
?
-
hyaluronan synthase 1 and hyaluronan synthase 2 synthesize high molecular weight hyaluronan, while hyaluronan synthase 3 synthesizes low lecular weight hyaluronan
-
-
-
additional information
?
-
hyaluronan synthase 1 and hyaluronan synthase 2 synthesize high molecular weight hyaluronan, while hyaluronan synthase 3 synthesizes low lecular weight hyaluronan
-
-
-
additional information
?
-
hyaluronan synthase 1 and hyaluronan synthase 2 synthesize high molecular weight hyaluronan, while hyaluronan synthase 3 synthesizes low lecular weight hyaluronan
-
-
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
-
-
?
UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
UDP + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-[nascent hyaluronan]
-
-
-
-
?
UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
UDP + N-acetyl-beta-D-glucosaminyl-(1-4)-beta-D-glucuronosyl-(1-3)-N-acetyl-beta-D-glucosaminyl-(1-4)-[nascent hyaluronan]
-
-
-
-
?
UDP-N-acetyl-D-glucosamine + UDP-D-glucuronate
[beta-N-acetyl-D-glucosaminyl(1-4)beta-D-glucuronosyl(1-3)]n + UDP
-
-
-
-
?
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, isozymes exhibit different functions in tumor growth, progression, and determination of malignancy
-
-
?
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
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4-Methylumbelliferone
-
changes the localization of the enzyme by preventing its association with the plasma membrane
additional information
-
interleukin-1beta augmented the expression of all 3 isozymes in the uterine cervix of pregnant mice, progesterone inhibited expression of isozymes HAS1 and HAS2
-
additional information
-
using inhibitors for MEK1/2, U0126, and for PI3K, LY294002, and the SN50 inhibitor, a complete inhibition of HAS2 transcriptional activity and hyaluronan sythesis is observed
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
progesterone activates the expression of HAS3, low-molecular-weight hyaluronan activates the expression of isozyme HAS1
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
values for other substrate concentrations
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
embryonic mouse molar. Difference in the distribution and expression of the three hyaluronan synthases at different developmental stages. Hyaluronan synthase 1 and hyaluronan synthase 2, but not hyaluronan synthase 3, are highly expressed in the bud stage
embryonic mouse molar. Difference in the distribution and expression of the three hyaluronan synthases at different developmental stages. Hyaluronan synthase 1 and hyaluronan synthase 2, but not hyaluronan synthase 3, are highly expressed in the bud stage
additional information
-
isozyme expression profile in uterine cervix of pregnant mice
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
expression of different HAS isoenzymes during embryonic development, overview. Intense hyaluronan staining is observed throughout the development in the tissues of mesodermal origin, like heart and cartilages, but also for example during the maturation of kidneys and stratified epithelia. In general, staining for one or several HAS isozymes correlates with hyaluronan staining. While epithelial cells are mostly negative for HASs, stratified epithelia become HAS positive during differentiation
HAS2 is suppressed in senescent fibroblasts, real time PCR enzyme expresion in fibrotic and senescent fibroblasts
at embryonic day 7.5, Has1 is expressed throughout the gastrulating embryo. After ambryonic day 8.5, Has1 expression disappears
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
expression of different HAS isoenzymes during embryonic development, overview. Intense hyaluronan staining is observed throughout the development in the tissues of mesodermal origin, like heart and cartilages, but also for example during the maturation of kidneys and stratified epithelia. In general, staining for one or several HAS isozymes correlates with hyaluronan staining. While epithelial cells are mostly negative for HASs, stratified epithelia become HAS positive during differentiation
expression of different HAS isoenzymes during embryonic development, overview. Intense hyaluronan staining is observed throughout the development in the tissues of mesodermal origin, like heart and cartilages, but also for example during the maturation of kidneys and stratified epithelia. In general, staining for one or several HAS isozymes correlates with hyaluronan staining. While epithelial cells are mostly negative for HASs, stratified epithelia become HAS positive during differentiation
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
isozyme HAS2 has the brightest signal in the endoplasmic reticulum
additional information
-
recombinant isozymes GFP-HAS2 and GFP-HAS3 travel through endoplasmic reticulum, Golgi, plasma membrane, and endocytic vesicles in keratinocytes
-
isozyme HAS1 has the brightest signal in the Golgi network
isozyme HAS3 has the brightest signal in the Golgi and microvillous protrusions
-
integral, plasma membrane residence of hyaluronan synthase is coupled to its enzymatic activity
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
the three HAS isoenzymes, HAS1, HAS2, and HAS3, expressed in mammalian cells differ in their enzymatic properties and regulation by external stimuli
malfunction
metabolism
physiological function
evolution
the three HAS isoenzymes, HAS1, HAS2, and HAS3, expressed in mammalian cells differ in their enzymatic properties and regulation by external stimuli
malfunction
metabolism
physiological function
malfunction
downregulation of HAS2 initiates and regulates fibroblast senescence through a p27-CDK2-SKP2 pathway. Deletion of HAS2 in mouse mesenchymal cells increases the cellular senescence of fibroblasts in bleomycin-induced mouse lung fibrosis in vivo. Overexpression of HAS2 in mesenchymal cells promotes an invasive phenotype resulting in severe fibrosis and downregulation of HAS2 promotes resolution. HAS2 deficiency leads to embryonic lethality. Downregulation of HAS2 increases p27 protein stability. p27 inhibits cell proliferation by regulating CDK2 activity. HAS2 deletion enhances cell stress responses. Phenotypes, detailed overview
malfunction
Has2-/- mice are embryonic lethal. Has2-/- embryos die between embryonic day 9.5 and 10.5 and exhibit severe cardiac and vascular abnormalities, in addition to yolk sac and somite deformities
metabolism
hyaluronan is expressed in a temporal-spatial expression pattern and may play a role in embryonic tooth morphogenesis. The difference in the distribution and expression of the three hyaluronan synthases at different developmental stages also supports their roles in cell proliferation, cell differentiation and cell migration
metabolism
hyaluronan synthase 2 expression is elevated in both human and murine liver fibrosis. The enzyme actively synthesizes hyaluronan in hepatic stellate cells and promotes activation of hepatic stellate cells and liver fibrosis through Notch1
physiological function
hyaluronan is the largest and one of the most abundant glycosaminoglycans of the extracellular space. Hyaluronan synthases are glycosyltransferases acting on the inner face of plasma membrane, adding alternately glucuronic acid and N-acetylglucosamine to the reducing end of the growing chain. Hyaluronan synthase forms a reserve that is transported to the plasma membrane for rapid activation of hyaluronan synthesis. The levels and localizations of HAS isoforms are likely to be highly important in processes like embryonic development, wound healing, inflammation, and malignant growth
physiological function
hyaluronan synthase 2 regulates fibroblast senescence in pulmonary fibrosis. Senescence is implicated in development, cancer, and tissue fibrosis. The chronic inflammation caused by cellular senescence may be related to the pathogenesis of various chronic diseases. Isozyme HAS2 may be a critical regulator of the fate of pulmonary fibrosis. Isozyme HAS2 is the major isoform responsible for hyaluronan production in mesenchymal cells
physiological function
recombinant hyaluronan synthase-2 upregulation protects smpd3-deficient fibroblasts against cell death induced by nutrient deprivation, but not against apoptosis evoked by human oxidized LDL. Resistance of fro/fro cells to starvation-induced apoptosis is associated with an increased expression of hyaluronan synthase 2 (HAS2) mRNAs and protein, which is inhibited by ceramide. The protective mechanism of HAS2 involves an increased expression of the heat-shock protein Hsp72, a chaperone with antiapoptotic activity. Antiapoptotic properties of HAS2 , overview
malfunction
-
catalytically inactive mutant K190R HAS2 forms dimers with wild-type HAS2 and quenches the activity of wild-type HAS2
malfunction
-
HAS-1 overexpression in dermal wounds decreases elements of scar formation
malfunction
-
in a ligation-induced carotid artery injury model, attenuated neointimal hyperplasia occurs in HAS3-null animals compared with wild-type control C57BL/6J mice. No changes are observed in medial and neointimal cell density, proliferation, or apoptosis. A lack of compensatory upregulation of isozymes HAS1 or HAS2, HAS3 deletion is associated with a reduction in vascular hyaluronan content, most dramatically in the media rather than the neointima. Transcriptome analysis of injured vessels from wild-type and HAS3-null mice reveals differential activation of pathways associated with a migratory VSMC phenotype. Isozyme HAS3 overexpression in VSMCs supports a migratory phenotype in response to platelet-derived growth factor BB (PDGF-BB), whereas knockdown of HAS3 results in reduced PDGF-BB-induced migration. Isozyme HAS3 knockdown also leads to a decrease in PDGF-B mRNA levels
malfunction
Has3/Apoe double deficient mice develop less atherosclerosis characterized by decreased Th1-cell responses, decreased IL-12 release, and decreased macrophage-driven inflammation
metabolism
-
role of hyaluronan in vascular disease, a multitude of synthases (HAS1, HAS2, and HAS3) and multiple hyaluronidases are involved in its metabolism
metabolism
hyaluronan is expressed in a temporal-spatial expression pattern and may play a role in embryonic tooth morphogenesis. The difference in the distribution and expression of the three hyaluronan synthases at different developmental stages also supports their roles in cell proliferation, cell differentiation and cell migration
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 is the largest and one of the most abundant glycosaminoglycans of the extracellular space. Hyaluronan synthases are glycosyltransferases acting on the inner face of plasma membrane, adding alternately glucuronic acid and N-acetylglucosamine to the reducing end of the growing chain. Hyaluronan synthase forms a reserve that is transported to the plasma membrane for rapid activation of hyaluronan synthesis. The levels and localizations of HAS isoforms are likely to be highly important in processes like embryonic development, wound healing, inflammation, and malignant growth
physiological function
-
hyaluronan synthase isozymes are involved in hyaluronan biosynthesis. Each HAS isoform produces structurally identical hyaluronan, thus, hyaluronan function is independent of the HAS by which it is synthesized. Hyaluronan is an essential component of the pericellular matrix, or alternatively, it can be released in a soluble form and be released and incorporated as part of the extracellular matrix. The composition and architecture of the matrix affect hyaluronan-dependent biochemical signaling, as well as the biophysical and biomechanical properties of tissues. The temporal and spatial relationship of hyaluronan with cells that express hyaluronidases that modify the molecular weight of hyaluronan is another determinant of hyaluronan function. Hyaluronan synthases may affect vascular disease independent of hyaluronan. HAS isoform-specific functions in tissue homeostasis and disease. Apotential autocrine loop involving isoyzme HAS3, PDGF-B expression, and PDGF-BB-induced migration. Isoform-specific role for HAS3 in promoting neointimal hyperplasia after carotid artery ligation
physiological function
hyaluronan synthase 3 promotes plaque inflammation and atheroprogression. Hyaluronan synthase 3 expression in vascular smooth muscle cells is found to be regulated by interleukin 1 beta (IL-1beta) in an NFkappaB dependent manner
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). HYAS2_MOUSE
552
6
63510
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
HAS2 is ubiquitinated on Lys190, HAS2 is both mono- and polyubiquitinated
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
additional information
-
site-directed mutagenesis of residues of the cytoplasmic loop of isozyme HAS1 for determining the residues required for glycosyltransferase activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene has2, quantitative real time PCR enzyme expression analysis, HAS2 expression is dependent on ceramide generated by neutral type 2 sphingomyelinase, nSMase2, as shown by treatment with C2-ceramide that decreases HAS2 expression in murine fro/fro fibroblasts
recombinant expression of EGFP-tagged isozyme HAS2 in MCF-7 cells and localization to the endoplasmic reticulum
ectopic expression of Flag- and 6myc-HAS2 in COS-1 cells as homodimers, co-expression with Flag-HAS3 leads to formation of heterodimers
-
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
-
recombinant expression of EGFP-tagged isozyme HAS1 in MCF-7 cells and localization to the Golgi apparatus
recombinant expression of EGFP-tagged isozyme HAS3 in MCF-7 cells and localization to the Golgi apparatus
retroviral transduction system is used to overexpress the three murine hyaluronan synthase enzymes in arterial smooth muscle cells. Overexpression of hyaluronan synthases alters vascular smooth muscle cell phenotype and promotes monocyte adhesion
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
hyaluronan synthase 2 expression is elevated in both human and murine liver fibrosis. The enzyme is transcriptionally up-regulated by transforming growth factor-beta through Wilms tumor 1 to promote fibrogenic, proliferative, and invasive properties of HSCs via CD44, Toll-like receptor 4, and newly identified downstream effector Notch1
Has3 expression is increased early during lesion formation when macrophages enter atherosclerotic plaques
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
the enzyme actively synthesizes hyaluronan in hepatic stellate cells and promotes hepatic stellate cells activation and liver fibrosis through Notch1. Targeted hyaluronan inhibition may have potential to be an effective therapy for liver fibrosis
medicine
targeting HAS2 to induce fibroblast senescence can be an attractive approach to resolve tissue fibrosis
drug development
inhibition of hyaluronan synthase 3-dependent synthesis of hyaluronan dampens systemic Th1 cell polarization and reduces plaque inflammation. Hyaluronan synthase 3 might be a promising therapeutic target in atherosclerosis. Because hyaluronan synthase 3 is regulated by IL-1beta, therapeutic anti-IL-1beta antibodies, may exert their beneficial effects on inflammation in post-myocardial infarction patients in part via effects on hyaluronan synthase 3
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Spicer, A.P.; Augustine, M.L.; McDonald, J.A.
Molecular cloning and characterization of a putative mouse hyaluronan synthase
J. Biol. Chem.
271
23400-23406
1996
Mus musculus (P70312), Mus musculus
Itano, N.; Sawai, T.; Yoshida, M.; Lenas, P.; Yamada, Y.; Imagawa, M.; Shinomura, T.; Hamaguchi, M.; Yoshida, Y.; Ohnuki, Y.; Miyauchi, S.; Spicer, A.P.; McDonald, J.A.; Kimata, K.
Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties
J. Biol. Chem.
274
25085-25092
1999
Mus musculus
Klewes, L.; Prehm, P.
Intracellular signal transduction for serum activation of the hyaluronan synthase in eukaryotic cell lines
J. Cell. Physiol.
160
539-544
1994
Mus musculus
Uchiyama, T.; Sakuta, T.; Kanayama, T.
Regulation of hyaluronan synthases in mouse uterine cervix
Biochem. Biophys. Res. Commun.
327
927-932
2005
Mus musculus
Itano, N.; Kimata, K.
Mammalian hyaluronan synthases
IUBMB Life
54
195-199
2002
Homo sapiens, Mus musculus
Rilla, K.; Siiskonen, H.; Spicer, A.P.; Hyttinen, J.M.; Tammi, M.I.; Tammi, R.H.
Plasma membrane residence of hyaluronan synthase is coupled to its enzymatic activity
J. Biol. Chem.
280
31890-31897
2005
Mus musculus
Tien, J.Y.; Spicer, A.P.
Three vertebrate hyaluronan synthases are expressed during mouse development in distinct spatial and temporal patterns
Dev. Dyn.
233
130-141
2005
Mus musculus (O08650), Mus musculus (P70312), Mus musculus (Q61647), Mus musculus
Wilkinson, T.S.; Bressler, S.L.; Evanko, S.P.; Braun, K.R.; Wight, T.N.
Overexpression of hyaluronan synthases alters vascular smooth muscle cell phenotype and promotes monocyte adhesion
J. Cell. Physiol.
206
378-385
2006
Mus musculus
Li, L.; Asteriou, T.; Bernert, B.; Heldin, C.H.; Heldin, P.
Growth factor regulation of hyaluronan synthesis and degradation in human dermal fibroblasts: importance of hyaluronan for the mitogenic response of PDGF-BB
Biochem. J.
404
327-336
2007
Homo sapiens, Mus musculus
Caskey, R.C.; Allukian, M.; Lind, R.C.; Herdrich, B.J.; Xu, J.; Radu, A.; Mitchell, M.E.; Liechty, K.W.
Lentiviral-mediated over-expression of hyaluronan synthase-1 (HAS-1) decreases the cellular inflammatory response and results in regenerative wound repair
Cell Tissue Res.
351
117-125
2013
Mus musculus, Mus musculus C57BL/6
Karousou, E.; Kamiryo, M.; Skandalis, S.S.; Ruusala, A.; Asteriou, T.; Passi, A.; Yamashita, H.; Hellman, U.; Heldin, C.H.; Heldin, P.
The activity of hyaluronan synthase 2 is regulated by dimerization and ubiquitination
J. Biol. Chem.
285
23647-23654
2010
Mus musculus
Pure, E.; Krolikoski, M.; Monslow, J.
Role for hyaluronan synthase 3 in the response to vascular injury
Arterioscler. Thromb. Vasc. Biol.
36
224-225
2016
Homo sapiens, Mus musculus, Mus musculus C57/BL6J
Toerroenen, K.; Nikunen, K.; Kaernae, R.; Tammi, M.; Tammi, R.; Rilla, K.
Tissue distribution and subcellular localization of hyaluronan synthase isoenzymes
Histochem. Cell Biol.
141
17-31
2014
Mus musculus (O08650), Mus musculus (P70312), Mus musculus (Q61647), Mus musculus
Li, Y.; Liang, J.; Yang, T.; Monterrosa Mena, J.; Huan, C.; Xie, T.; Kurkciyan, A.; Liu, N.; Jiang, D.; Noble, P.W.
Hyaluronan synthase 2 regulates fibroblast senescence in pulmonary fibrosis
Matrix Biol.
55
35-48
2016
Mus musculus (P70312), Mus musculus
Garoby-Salom, S.; Rouahi, M.; Mucher, E.; Auge, N.; Salvayre, R.; Negre-Salvayre, A.
Hyaluronan synthase-2 upregulation protects smpd3-deficient fibroblasts against cell death induced by nutrient deprivation, but not against apoptosis evoked by oxidized LDL
Redox Biol.
4
118-126
2015
Mus musculus (P70312), Mus musculus 129/Sv (P70312)
Passi, A.; Vigetti, D.; Buraschi, S.; Iozzo, R.V.
Dissecting the role of hyaluronan synthases in the tumor microenvironment
FEBS J.
286
2937-2949
2019
Mus musculus (P70312), Homo sapiens (Q92819)
Yang, G.; Jiang, B.; Cai, W.; Liu, S.; Zhao, S.
Hyaluronan and hyaluronan synthases expression and localization in embryonic mouse molars
J. Mol. Histol.
47
413-420
2016
Mus musculus (O08650), Mus musculus (P70312), Mus musculus (Q61647)
Homann, S.; Grandoch, M.; Kiene, L.S.; Podsvyadek, Y.; Feldmann, K.; Rabausch, B.; Nagy, N.; Lehr, S.; Kretschmer, I.; Oberhuber, A.; Bollyky, P.; Fischer, J.W.
Hyaluronan synthase 3 promotes plaque inflammation and atheroprogression
Matrix Biol.
66
67-80
2018
Mus musculus (O08650)
Yang, Y.M.; Noureddin, M.; Liu, C.; Ohashi, K.; Kim, S.Y.; Ramnath, D.; Powell, E.E.; Sweet, M.J.; Roh, Y.S.; Hsin, I.F.; Deng, N.; Liu, Z.; Liang, J.; Mena, E.; Shouhed, D.; Schwabe, R.F.; Jiang, D.; Lu, S.C.; Noble, P.W.; Seki, E.
Hyaluronan synthase 2-mediated hyaluronan production mediates Notch1 activation and liver fibrosis
Sci. Transl. Med.
11
eaat9284
2019
Mus musculus (P70312), Mus musculus, Homo sapiens (Q92819), Homo sapiens
EXTERNAL LINKS (specific for EC-Number 2.4.1.212)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
