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.

1. hyaluron synthase 2 has a role in stem cell senescence PMID: 27339908
2. COX-2, GREM1, and HAS2 are cumulus cell genes that potentially determine oocyte and embryo developmental competence. (Review) PMID: 29537212
3. HAS2 may be a critical regulator of the fate of pulmonary fibrosis and we propose a model where over-expression of HAS2 promotes an invasive phenotype resulting in severe fibrosis and down-regulation of HAS2 promotes resolution. PMID: 26987798
4. Results show that cancer-associated fibroblasts (CAFs) expresses higher levels of HAS2 and suggest that HAS2 is one of the key regulators responsible for CAF-mediated oral squamous cell carcinoma progression by modulating the balance of MMP1 and TIMP1. PMID: 27884164
5. Results demonstrate that hypoxia induces HAS2 expression and thereby HA production, which contributes to EMT of oral squamous cell carcinoma. This process is mediated by HAS2-AS1, which can bind to HAS2 gene inducing its transcription. PMID: 28485478
6. We identified HAS2, tumor cell-derived hyaluronic acid (HA) and ZEB1 to form a positive feedback loop as ZEB1, elevated by HA, directly activates HAS2 expression in breast cancer PMID: 28086235
7. The present data reveal a selective up-regulation of HAS2 expression by extracellular Uridine Triphosphate, which is likely to contribute to the previously reported rapid activation of hyaluronan metabolism in response to tissue trauma or ultraviolet radiation. PMID: 28188289
8. HAS2 and HAS3 were the only hyaluronan synthases detected, the expression of which was almost similar in NPs and NM. PMID: 26661071
9. HAS2 has been proposed to be a target for therapeutic intervention in cancer. Our findings suggested a possible antagonistic role of androgen receptor (AR) pathway on HAS2 function. PMID: 27169756
10. HAS-2 gene silencing may inhibit proliferation and promote apoptosis in the MCF-7 human breast cancer cell line. PMID: 27915342
11. Our study establishes HAS2-mediated HA synthesis as a driver of growth of bladder cancer with low AGL and provides preclinical rationale for personalized targeting of HAS2/HA signaling in patients with low amylo-alpha-1-6-glucosidase-4-alpha-glucanotransferase -expressing tumors. PMID: 26490312
12. HAS2-HA system influences the biological characteristics of human breast cancer cells PMID: 26722395
13. Our study identified HAS2 as a novel candidate gene for susceptibility to adult asthma. PMID: 25251750
14. In 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. PMID: 24527698
15. review of the roles of HAS2 and CD44 in breast tumorigenesis [review] PMID: 25081531
16. mir-23a-3p causes cellular senescence by targeting hyaluronan synthase 2: possible implication for skin aging. PMID: 25264594
17. HAS2 may be involved in the etiology of non-syndromic VSD and have the vital function in the development of heart septum PMID: 24558368
18. Stimulation 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 enzymes PMID: 24472738
19. UDP-glucose activates P2Y14 receptor and JAK2, increases STAT3 Tyr705 phosphorylation, and enhances transcription of HAS2. PMID: 24847057
20. Melanoma cell-derived factors stimulate hyaluronan synthesis in dermal fibroblasts by upregulating HAS2 through PDGFR-PI3K-AKT and p38 signaling PMID: 22825838
21. findings suggested that rs2046571 of the HSA2 has marginal association with PD in Chinese population. PMID: 23916661
22. HAS2 knockdown sensitizes cancer cells to radiation via persistent DNA damage. PMID: 24333416
23. Inhibition of miR-21 has no effect on thrombospondin (TSP)-1-stimulated expression of HAS2. PMID: 24314882
24. Data 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. PMID: 23806178
25. Data indicate that oxLDL doubled the transcripts of hyaluronan synthases HAS2 and HAS3 and hyaluronan deposition via the scavenger receptor LOX-1. PMID: 23979132
26. The 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. PMID: 23397370
27. HAS 2 may be a potential therapeutic target for the treatment of oral cavity cancer PMID: 22473523
28. COL6A1 and COL6A2 silencing downregulates HAS2 expression in Down syndrome fibroblasts. PMID: 23452080
29. no significant difference (P > 0.05) was found between the level of HAS2 synthesized by control cells and NCTC 2544 cells treated with Plantaricin A preparations PMID: 22742591
30. polymorphisms in HAS2 are potentially involved in glaucomatous neurodegeneration. PMID: 22960332
31. Role of UDP-N-acetylglucosamine (GlcNAc) and O-GlcNAcylation of hyaluronan synthase 2 in the control of chondroitin sulfate and hyaluronan synthesis. PMID: 22887999
32. We identified a previously unknown downstream target of beta-catenin, HAS2, in prostate cancer PMID: 22298898
33. Findings show a critical role of HAS2 in the development of a prometastatic microenvironment. PMID: 22113945
34. The 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. PMID: 22162480
35. Hyaluronan synthase 2 (HAS2) promotes breast cancer cell invasion by suppression of tissue metalloproteinase inhibitor 1 (TIMP-1) PMID: 22016393
36. HAS2-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. PMID: 21743962
37. pulsatile, 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. PMID: 21551265
38. Altered binding of SP1 and YY1 to the promoter correlated with cellular UDP-N-acetylhexosamines content and inhibition of HAS2 expression. PMID: 21795679
39. transcriptional 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. PMID: 21357421
40. The combined HAS2-HYAL-1 biomarker detected bladder cancer and significantly predicted its recurrence. PMID: 20960509
41. Hyaluronan synthesis is inhibited by adenosine monophosphate-activated protein kinase through the regulation of HAS2 activity in human aortic smooth muscle cells. PMID: 21228273
42. interleukin 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 2 PMID: 20522558
43. Upregulation 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. PMID: 14752026
44. Base sequence of this gene's promoter is sequenced. PMID: 14988410
45. Fusion with PLAG1 protein in lipoblastoma. PMID: 15642402
46. IL-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 cells PMID: 15677552
47. Has2 gene is a potent primary EGF and all-trans-RA responding gene with a complex regulation PMID: 15722343
48. natural antisense mRNAs of HAS2 may have an important and novel regulatory role in the control of HAS2, hyaluronan biosynthesis, and HA-dependent cell functions PMID: 15843373
49. Antisense inhibition of HAS2 in osteosarcoma cells inhibits hyaluronan retention and tumorigenicity. PMID: 15922739
50. Sp1 and Sp3 are principal mediators of HAS2 constitutive transcription PMID: 16603733

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Membrane; Multi-pass membrane protein.

NodC/HAS family

Expressed in fibroblasts.

HGNC: 4819

OMIM: 601636

KEGG: hsa:3037

STRING: 9606.ENSP00000306991

UniGene: Hs.159226