HAS2:Hyaluronan synthase 2

Gene Name
Hyaluronan synthase 2
Protein ID
Chromosome ID
HPP Status
Protein Name
Hyaluronan synthase 2

Hyaluronic acid synthase 2

Hyaluronate synthase 2

hyaluronic acid synthase 2

hyaluronan synthase 2

HA synthase 2

hyaluronate synthase 2


[Reference: http://www.genecards.org/cgi-bin/carddisp.pl?gene=HAS2 ]
Chromosomal Position
8q24.13 | Start:121612116 End:121612116

Entrez Gene Summary for HAS2
Hyaluronan or hyaluronic acid (HA) is a high molecular weight unbranched polysaccharide synthesized by a wide variety of organisms from bacteria to mammals, and is a constituent of the extracellular matrix. It consists of alternating glucuronic acid and N-acetylglucosamine residues that are linked by beta-1-3 and beta-1-4 glycosidic bonds. HA is synthesized by membrane-bound synthase at the inner surface of the plasma membrane, and the chains are extruded through pore-like structures into the extracellular space. It serves a variety of functions, including space filling, lubrication of joints, and provision of a matrix through which cells can migrate. HA is actively produced during wound healing and tissue repair to provide a framework for ingrowth of blood vessels and fibroblasts. Changes in the serum concentration of HA are associated with inflammatory and degenerative arthropathies such as rheumatoid arthritis. In addition, the interaction of HA with the leukocyte receptor CD44 is important in tissue-specific homing by leukocytes, and overexpression of HA receptors has been correlated with tumor metastasis. HAS2 is a member of the newly identified vertebrate gene family encoding putative hyaluronan synthases, and its amino acid sequence shows significant homology to glycosaminoglycan synthetase (DG42) from Xenopus laevis, and human and murine hyaluronan synthase 1. (provided by RefSeq, Jul 2008)

UniProtKB Summary for HAS2
Function: Catalyzes the addition of GlcNAc or GlcUA monosaccharides to the nascent hyaluronan polymer. Therefore, it is essential to hyaluronan synthesis a major component of most extracellular matrices that has a structural role in tissues architectures and regulates cell adhesion, migration and differentiation. This is one of the isozymes catalyzing that reaction and it is particularly responsible for the synthesis of high molecular mass hyaluronan. Required for the transition of endocardial cushion cells into mesenchymal cells, a process crucial for heart development. May also play a role in vasculogenesis. High molecular mass hyaluronan also play a role in early contact inhibition a process which stops cell growth when cells come into contact with each other or the extracellular matrix (By similarity)

[Reference: http://www.genecards.org/cgi-bin/carddisp.pl?gene=HAS2 ]
External IDs
Hgnc ID: 4819 EntrezGene ID: 3037 Ensembl ID: ENSG00000170961
[Reference: http://www.genecards.org/cgi-bin/carddisp.pl?gene=HAS2 ]
Reference Source

Gene Reference Into Function (GeneRIF)

PubMed IDGeneRIF TextLast Update
11790779hyaluronan synthase expression in prostate adenocarcinoma cells2010-01-21
14636845Expression of each hyaluronan synthase isoform is regulated differently by growth factors and cytokines in vascular endothelial cells. Expressed in proliferative membranes from proliferative vitreoretinal diseases. May affect progression of diseases.2010-01-21
14752026Upregulation of HAS2 expression via EP(2) and IP receptors might contribute to the accumulation of HA during human atherosclerosis, thereby mediating proatherosclerotic functions of COX2.2010-01-21
14988410Base sequence of this gene's promoter is sequenced.2010-01-21
15642402Fusion with PLAG1 protein in lipoblastoma.2010-01-21
15677552IL-1beta induction of HAS2 expression involves multiple signaling pathways that act in concert, thus leading to an increase in expression of hyaluronan by jejunum-derived mesenchymal cells2010-01-21
15722343Has2 gene is a potent primary EGF and all-trans-RA responding gene with a complex regulation2010-01-21
15843373natural antisense mRNAs of HAS2 may have an important and novel regulatory role in the control of HAS2, hyaluronan biosynthesis, and HA-dependent cell functions2010-01-21
15922739Antisense inhibition of HAS2 in osteosarcoma cells inhibits hyaluronan retention and tumorigenicity.2010-01-21
16564133mRNA for HAS1 is undetectable but HAS3 mRNA can be readily detected in freshly isolated CD133+ as well as in CD133- umbilical cord blood (UCB) cells. mRNA for HAS2 can only be detected in CD133+ progenitor cells.2010-01-21
16603733Sp1 and Sp3 are principal mediators of HAS2 constitutive transcription2010-01-21
16687630hyaluronan synthase 2 and TSG-6 have roles in hyaluronan distribution and function in proximal tubular epithelial cells2010-01-21
16786194The aim of this study was to evaluate how TNF-alpha, IFN-gamma,IL-1beta, and exposition to oxidative stress may modulate HAS activities in normal human skin fibroblasts.2010-01-21
16807238osteopontin-transfected cells express high levels of hyaluronan synthase 2, which is associated with increased HA production and matrix retention and is necessary for tumor cell adhesion to bone marrow endothelial cells and anchorage-independent growth2010-01-21
17307735explain the induction of HAS2 mRNA by all-trans-retinoic acid and tumor necrosis factor-alpha2010-01-21
17315194RNA interference-mediated suppression of HAS2 led to a less aggressive phenotype of the breast tumor cells, as assessed by cell growth, both in anchorage-dependent and anchorage-independent cultures.2010-01-21
17611197Interleukin-1beta stimulation resulted in induction of HAS1 and HAS2 transcription but did not induce phenotypic differentiation or induce hyaluronan coat assembly2010-01-21
17872502HAS2 plays an important role in regulating hyaluronan synthesis and human embryonic stem cell differentiation.2010-01-21
18587729Observational study of gene-disease association. (HuGE Navigator)2008-07-13
19231585Hyaluronan synthase (HAS2 and HAS3) and hyaluronan may mediate cellular invasion via changes in MMP-7 expression in SW620 colon carcinoma cells.2010-01-21
19416972MED1 and NCoR1 are central for the all-trans-RA induction of the HAS2 gene and CBP dominates its forskolin response2010-01-21
19435493HAS1, HAS2 and HAS3 expression is not consistently elevated in ovarian carcinomas.2010-01-21
19577615Transfection with siHAS2 and siHAS1 showed that mainly HAS1 synthesized high molecular weight HA regulates HT1080 cell motility.2010-01-21
20072653Data show that a significant in expression levels of HA synthases (HASs) and hyaluronidases (Hyals) was observed in vitro on stimulation of epithelial ovarian carcinoma cells by gonadotropins.2010-05-31
20379614Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)2010-06-30
20522558interleukin 1beta and tumor necrosis factors alpha and beta, but not transforming growth factors alpha and beta, strongly induced HA synthesis by NF-kappaB pathway, activating hyaluronan synthase 22010-09-27
20875124Hyaluronan synthases (HAS1-3) and hyaluronidases (HYAL1-2) in the accumulation of hyaluronan in endometrioid endometrial carcinoma2011-03-26
20960509The combined HAS2-HYAL-1 biomarker detected bladder cancer and significantly predicted its recurrence.2011-05-14
21228273Hyaluronan synthesis is inhibited by adenosine monophosphate-activated protein kinase through the regulation of HAS2 activity in human aortic smooth muscle cells.2011-05-14
21357421transcriptional induction of HAS2-AS1 and HAS2 occurs simultaneously in PTCs and suggest that transcription of the antisense RNA stabilizes or augments HAS2 mRNA expression in these cells via RNA/mRNA heteroduplex formation.2011-08-06
21551265pulsatile, arterial-like shear stress conditions induced enzyme and hyaluronan effectively, while lower shear stress that continuously changed its direction did not induce any differences in comparison with control cultures not exposed to shear stress.2011-12-17
21743962HAS2-HYAL2/CD44 system may support spontaneous chemokinesis of human cancer cells through self-degradation of HMW-HA to produce LMW-HA by an autocrine mechanism.2012-01-14
21795679Altered binding of SP1 and YY1 to the promoter correlated with cellular UDP-N-acetylhexosamines content and inhibition of HAS2 expression.2011-11-26
22016393Hyaluronan synthase 2 (HAS2) promotes breast cancer cell invasion by suppression of tissue metalloproteinase inhibitor 1 (TIMP-1)2012-02-25
22113945Findings show a critical role of HAS2 in the development of a prometastatic microenvironment.2012-04-14
22162480The difference in control of HAS2 expression allows the activation of one of the mechanisms underlying Graves ophthalmopathy, adipogenesis, to be linked biologically with the second, Hyaluronan overproduction.2012-04-14
22298898We identified a previously unknown downstream target of beta-catenin, HAS2, in prostate cancer2012-05-26
22473523HAS 2 may be a potential therapeutic target for the treatment of oral cavity cancer2013-09-21
22529214analysis of changes in cervical glycosaminoglycan composition during normal pregnancy and preterm birth: Has1 is expressed in preterm birth, while Has2 is induced at term2012-09-22
22695958HA chains synthesized by HAS1 and HAS2 contribute to outflow resistance, while hyaluronan produced by HAS3 does not appear to play a significant role.2012-10-06
22742591no significant difference (P > 0.05) was found between the level of HAS2 synthesized by control cells and NCTC 2544 cells treated with Plantaricin A preparations2013-03-09
22825838Melanoma cell-derived factors stimulate hyaluronan synthesis in dermal fibroblasts by upregulating HAS2 through PDGFR-PI3K-AKT and p38 signaling2014-06-21
22887999Role of UDP-N-acetylglucosamine (GlcNAc) and O-GlcNAcylation of hyaluronan synthase 2 in the control of chondroitin sulfate and hyaluronan synthesis.2013-01-05
22960332polymorphisms in HAS2 are potentially involved in glaucomatous neurodegeneration.2013-02-02
23303191Hyaluronan synthase 1 (HAS1) requires higher cellular UDP-GlcNAc concentration than HAS2 and HAS32013-04-27
23397370The results from these experiments suggest that downregulation of HAS2 may be responsible for inhibition of hyaluronate synthesis in the self-assembled 2-nM T3 human dermal matrix.2013-09-28
23452080COL6A1 and COL6A2 silencing downregulates HAS2 expression in Down syndrome fibroblasts.2013-07-06
23560496Inverse expression of hyaluronidase 2 and hyaluronan synthases 1-3 is associated with reduced hyaluronan content in malignant cutaneous melanoma.2013-09-21
23806178Data suggest that expression of HAS2 is lower in trophoblasts from first-trimester placenta of miscarriage then of normal subjects; the products of HAS2 (high/medium MW hyaluronan) promote cell proliferation/invasion and inhibit apoptosis.2014-03-15
23916661findings suggested that rs2046571 of the HSA2 has marginal association with PD in Chinese population.2014-05-17
23979132Data indicate that oxLDL doubled the transcripts of hyaluronan synthases HAS2 and HAS3 and hyaluronan deposition via the scavenger receptor LOX-1.2013-12-14
24314882Inhibition of miR-21 has no effect on thrombospondin (TSP)-1-stimulated expression of HAS2.2014-03-22
24333416HAS2 knockdown sensitizes cancer cells to radiation via persistent DNA damage.2014-03-22
24472738Stimulation with LPS caused rapid increases in versican mRNA and protein, a rapid increase in Has1 mRNA, and concomitant inhibition of hyaluronidases 1 and 2, the major hyaluronan degrading enzymes2015-01-03
24527698In contrast to other carcinoma subtypes, HAS2 expression was observed in up to 72.7% of metaplastic carcinomas of breast, a carcinoma subtype related to the epithelial-mesenchymal transition.2015-06-27
24558368HAS2 may be involved in the etiology of non-syndromic VSD and have the vital function in the development of heart septum2015-01-17
24847057UDP-glucose activates P2Y14 receptor and JAK2, increases STAT3 Tyr705 phosphorylation, and enhances transcription of HAS2.2014-10-18
25081531review of the roles of HAS2 and CD44 in breast tumorigenesis [review]2015-04-18
25251750Our study identified HAS2 as a novel candidate gene for susceptibility to adult asthma.2015-06-27
25264594mir-23a-3p causes cellular senescence by targeting hyaluronan synthase 2: possible implication for skin aging.2015-03-28
25325984transcriptional regulation of the HAS and HAS2-antisense RNA 1 genes, was analyzed.2015-06-20
26518873Regulation of Hyaluronan (HA) Metabolism Mediated by HYBID (Hyaluronan-binding Protein Involved in HA Depolymerization, KIAA1199) and HA Synthases in Growth Factor-stimulated Fibroblasts.2016-04-23


Relevant citations within the PubMed literature


Putative/known Functions


Homologues, Orthologues, Paralogues and Family

Sequence Similarity and Functional Annotation

Post Translational Modifications

Protein Protein Interactions

Best Available Mass Spectra without FDR


Evidence File
Fenyö, David; Beavis, Ronald C. (2015). "The GPMDB REST interface". Bioinformatics 31 (12): 2056–2058. doi:10.1093/bioinformatics/btv107. ISSN 1367-4803.
http://gpmdb.thegpm.org/ ">Global Proteome Machine Database - THE GPM

Showing 1-5 of 5 items.


Peptide SequenceScoresPride IDSpectrum IDAnnotation
Evidence File
Vizcaino JA, et al. 2016 update of the PRIDE database and related tools. Nucleic Acids Res. 2016 Jan 1;44(D1):D447-D456.
https://www.ebi.ac.uk/pride/archive/ ">PRIDE Archive

Showing 1-4 of 4 items.

Proteomics DB

Peptide SequenceSearch EngineScoreThreshold ScoreIdentification IDExperiment IDAnnotation
Evidence File
Wilhelm, M et al. (2014) Mass-spectrometry-based draft of the human proteome. Nature. 509:582-7.
https://www.proteomicsdb.org/ ">Proteomics DB