Gene Symbol: HYAL2
Description: hyaluronoglucosaminidase 2
Alias: LUCA2, hyaluronidase-2, PH-20 homolog, PH20 homolog, hyal-2, lung carcinoma protein 2, lysosomal hyaluronidase
Species: human
Products:     HYAL2

Top Publications

  1. Harada H, Takahashi M. CD44-dependent intracellular and extracellular catabolism of hyaluronic acid by hyaluronidase-1 and -2. J Biol Chem. 2007;282:5597-607 pubmed
    ..Based on these findings, Hyal-1 and -2 contribute to intracellular and extracellular catabolism of HA, respectively, in a CD44-dependent manner, and their HA degradation occurs independently from one another. ..
  2. Nykopp T, Rilla K, Sironen R, Tammi M, Tammi R, Hamalainen K, et al. Expression of hyaluronan synthases (HAS1-3) and hyaluronidases (HYAL1-2) in serous ovarian carcinomas: inverse correlation between HYAL1 and hyaluronan content. BMC Cancer. 2009;9:143 pubmed publisher
    ..hyaluronan, we examined the expression of hyaluronan synthases (HAS1, HAS2 and HAS3) and hyaluronidases (HYAL1 and HYAL2), correlated with hyaluronidase enzyme activity hyaluronan content and HAS1-3 immunoreactivity...
  3. Rai S, Duh F, Vigdorovich V, Danilkovitch Miagkova A, Lerman M, Miller A. Candidate tumor suppressor HYAL2 is a glycosylphosphatidylinositol (GPI)-anchored cell-surface receptor for jaagsiekte sheep retrovirus, the envelope protein of which mediates oncogenic transformation. Proc Natl Acad Sci U S A. 2001;98:4443-8 pubmed
    ..HYAL2 was previously described as a lysosomal hyaluronidase, but we show that HYAL2 is actually a glycosylphosphatidylinositol (GPI)-anchored cell-surface protein...
  4. Vigdorovich V, Strong R, Miller A. Expression and characterization of a soluble, active form of the jaagsiekte sheep retrovirus receptor, Hyal2. J Virol. 2005;79:79-86 pubmed
    ..The jaagsiekte sheep retrovirus (JSRV) receptor, hyaluronidase 2 (Hyal2), is a glycosylphosphatidylinositol (GPI)-anchored molecule containing no peptide transmembrane ..
  5. Junker N, Latini S, Petersen L, Kristjansen P. Expression and regulation patterns of hyaluronidases in small cell lung cancer and glioma lines. Oncol Rep. 2003;10:609-16 pubmed
    ..Three hyaluronidases, HYAL1, HYAL2 and HYAL3, are located at the chromosomal region 3p21...
  6. Wang F, Grigorieva E, Li J, Senchenko V, Pavlova T, Anedchenko E, et al. HYAL1 and HYAL2 inhibit tumour growth in vivo but not in vitro. PLoS ONE. 2008;3:e3031 pubmed publisher
    ..The effect of expression HYAL1 and HYAL2 was studied by colony formation inhibition, growth curve and cell proliferation tests in vitro and tumour growth ..
  7. Berdiaki A, Nikitovic D, Tsatsakis A, Katonis P, Karamanos N, Tzanakakis G. bFGF induces changes in hyaluronan synthase and hyaluronidase isoform expression and modulates the migration capacity of fibrosarcoma cells. Biochim Biophys Acta. 2009;1790:1258-65 pubmed publisher
    ..bFGF regulates, in a cell-specific manner the migration capability of fibrosarcoma cells by modulating their HA metabolism. HA metabolism is suggested to be a potential therapeutic target in fibrosarcoma. ..
  8. Lerman M, Minna J. The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium. Cancer Res. 2000;60:6116-33 pubmed
  9. Liu S, Duh F, Lerman M, Miller A. Role of virus receptor Hyal2 in oncogenic transformation of rodent fibroblasts by sheep betaretrovirus env proteins. J Virol. 2003;77:2850-8 pubmed
    ..the Env proteins encoded by these viruses, which require the putative lung and breast cancer tumor suppressor hyaluronidase 2 (Hyal2) to promote virus entry into cells...

More Information


  1. Danilkovitch Miagkova A, Duh F, Kuzmin I, Angeloni D, Liu S, Miller A, et al. Hyaluronidase 2 negatively regulates RON receptor tyrosine kinase and mediates transformation of epithelial cells by jaagsiekte sheep retrovirus. Proc Natl Acad Sci U S A. 2003;100:4580-5 pubmed
    The candidate tumor-suppressor gene hyaluronidase 2 (HYAL2) encodes a glycosylphosphatidylinositol-anchored cell-surface protein that serves as an entry receptor for jaagsiekte sheep retrovirus, a virus that causes contagious lung cancer ..
  2. Lepperdinger G, Müllegger J, Kreil G. Hyal2--less active, but more versatile?. Matrix Biol. 2001;20:509-14 pubmed
    b>Hyal2 is one of several hyaluronidases present in vertebrates. The human gene encoding this enzyme is present on chromosome 3p.21.3, close to two additional hyaluronidase genes...
  3. Takabe P, Kärnä R, Rauhala L, Tammi M, Tammi R, Pasonen Seppänen S. Melanocyte hyaluronan coat fragmentation enhances the UVB-induced TLR-4 receptor signaling and expression of proinflammatory mediators IL-6, IL-8, CXCL-1 and CXCL-10 via NF-κB activation. J Invest Dermatol. 2019;: pubmed publisher
    ..and the expression of hyaluronan synthases HAS2, HAS3, the hyaluronan receptor CD44 and the hyaluronidase HYAL2, as well as induced the expression of inflammatory mediators IL-6, IL-8, CXCL-1 and CXCL-10...
  4. Sukowati C, Anfuso B, Fiore E, Ie S, Raseni A, Vascotto F, et al. Hyaluronic acid inhibition by 4-methylumbelliferone reduces the expression of cancer stem cells markers during hepatocarcinogenesis. Sci Rep. 2019;9:4026 pubmed publisher
    ..We observed that 4MU treatments in animal model down-regulated the mRNA expressions of HA-related genes Has3 and Hyal2 only in HBV-TG but not in normal WT...
  5. Colombaro V, Jadot I, Declèves A, Voisin V, Giordano L, Habsch I, et al. Hyaluronidase 1 and hyaluronidase 2 are required for renal hyaluronan turnover. Acta Histochem. 2015;117:83-91 pubmed publisher
    Hyaluronidase 1 (HYAL1) and hyaluronidase 2 (HYAL2) are the major hyaluronidases acting synergistically to degrade hyaluronan (HA). In the kidney, HA is distributed heterogeneously...
  6. Midgley A, Duggal L, Jenkins R, Hascall V, Steadman R, Phillips A, et al. Hyaluronan regulates bone morphogenetic protein-7-dependent prevention and reversal of myofibroblast phenotype. J Biol Chem. 2015;290:11218-34 pubmed publisher
    ..Endosomal HA co-localized with the HA-degrading enzymes, hyaluronidase-1 and hyaluronidase-2 (Hyal2)...
  7. Pedicino D, Vinci R, Giglio A, Pisano E, Porto I, Vergallo R, et al. Alterations of Hyaluronan Metabolism in Acute Coronary Syndrome: Implications for Plaque Erosion. J Am Coll Cardiol. 2018;72:1490-1503 pubmed publisher
    ..The authors evaluated: 1) gene expression of hyaluronidase 2 (HYAL2) (enzyme degrading high-molecular-weight HA to its proinflammatory 20-kDa isoform) and of CD44v1, ..
  8. Guan Z, Yu H, Cuk K, Zhang Y, Brenner H. Whole-Blood DNA Methylation Markers in Early Detection of Breast Cancer: A Systematic Literature Review. Cancer Epidemiol Biomarkers Prev. 2019;28:496-505 pubmed publisher
    ..was relatively modest, with only six markers showing sensitivity >40% at specificity >75% [only 2 (HYAL2 and S100P) were independently validated]. Although relatively strong associations (OR ≤0...
  9. Briggs A, Rosenberg L, Buie J, Rizvi H, Bertagnolli M, Cho N. Antitumor effects of hyaluronan inhibition in desmoid tumors. Carcinogenesis. 2015;36:272-9 pubmed publisher
    ..Fluorescent immunohistochemistry showed that MSCs in DTs coexpressed HA, HAS2, HYAL2, as well as the major HA receptor CD44 and HA coreceptor TLR4...
  10. Yao H, Sun L, Luo S, Ji X. [Changes in the Expression of AKT and ERK after the JSRV-Env-Induced Transfection of TC-1 and TC-1-Hyal2 Cells]. Bing Du Xue Bao. 2016;32:283-91 pubmed
    ..transfected mouse lung epithelial cells (TC-1) and mouse lung epithelial cells stably expressing sheep Hyal-2(TC-1-Hyal2)with JSRV-Env eukaryotic expression vector, measured the changes in the mRNA and protein expression of AKT(serine/..
  11. Colombaro V, Jadot I, Declèves A, Voisin V, Giordano L, Habsch I, et al. Lack of hyaluronidases exacerbates renal post-ischemic injury, inflammation, and fibrosis. Kidney Int. 2015;88:61-71 pubmed publisher
    ..Here we tested whether Hyal1-/- and Hyal2-/- mice display exacerbated renal damage following unilateral IRI due to a higher HA accumulation in the post-..
  12. Onclinx C, Dogne S, Jadin L, Andris F, Grandfils C, Jouret F, et al. Deficiency in mouse hyaluronidase 2: a new mechanism of chronic thrombotic microangiopathy. Haematologica. 2015;100:1023-30 pubmed publisher
    ..We generated hyaluronidase 2-deficient mice...
  13. Chowdhury B, Xiang B, Liu M, Hemming R, Dolinsky V, Triggs Raine B. Hyaluronidase 2 Deficiency Causes Increased Mesenchymal Cells, Congenital Heart Defects, and Heart Failure. Circ Cardiovasc Genet. 2017;10: pubmed publisher
    ..Heart abnormalities in hyaluronidase 2 (HYAL2)-deficient (Hyal2-/- ) mice and humans suggested removal of ..
  14. Valkonen M, Haapasalo H, Rilla K, Tyynelä Korhonen K, Soini Y, Pasonen Seppänen S. Elevated expression of hyaluronan synthase 2 associates with decreased survival in diffusely infiltrating astrocytomas. BMC Cancer. 2018;18:664 pubmed publisher
    ..The TMA sections were stained for hyaluronan, CD44, hyaluronan synthases 1-3 (HAS1-3) and hyaluronidase 2 (HYAL2)...
  15. Shimizu H, Shimoda M, Mochizuki S, Miyamae Y, Abe H, Chijiiwa M, et al. Hyaluronan-Binding Protein Involved in Hyaluronan Depolymerization Is Up-Regulated and Involved in Hyaluronan Degradation in Human Osteoarthritic Cartilage. Am J Pathol. 2018;188:2109-2119 pubmed publisher
    ..These data are the first to demonstrate that HYBID is up-regulated in OA cartilage, and suggest that tumor necrosis factor ?-stimulated HYBID plays a role in HA degradation in OA cartilage. ..
  16. Bourguignon V, Flamion B. Respective roles of hyaluronidases 1 and 2 in endogenous hyaluronan turnover. FASEB J. 2016;30:2108-14 pubmed publisher
    We studied the physiologic roles of the hyaluronidase (HYAL) 1 and HYAL2 in hyaluronan (HA) turnover...
  17. Wu M, Cao M, He Y, Liu Y, Yang C, Du Y, et al. A novel role of low molecular weight hyaluronan in breast cancer metastasis. FASEB J. 2015;29:1290-8 pubmed publisher
    ..LMW-HA level was accompanied by the overexpression of hyaluronan synthase (HAS2) and hyaluronidase (both HYAL1 and HYAL2)...
  18. Jokela T, Kärnä R, Rauhala L, Bart G, Pasonen Seppänen S, Oikari S, et al. Human Keratinocytes Respond to Extracellular UTP by Induction of Hyaluronan Synthase 2 Expression and Increased Hyaluronan Synthesis. J Biol Chem. 2017;292:4861-4872 pubmed publisher
    ..expression, although the other hyaluronan synthases (HAS1, HAS3) and hyaluronidases (HYAL1, HYAL2) were not affected. The HAS2 response was rapid and transient, with the maximum stimulation at 1.5 h...
  19. Nykopp T, Pasonen Seppänen S, Tammi M, Tammi R, Kosma V, Anttila M, et al. Decreased hyaluronidase 1 expression is associated with early disease recurrence in human endometrial cancer. Gynecol Oncol. 2015;137:152-9 pubmed publisher
    Hyaluronidases (HYAL1 and HYAL2) are key enzymes in the degradation of hyaluronan, and their expression has been altered in various cancer types...
  20. Yamamoto H, Tobisawa Y, Inubushi T, Irie F, Ohyama C, Yamaguchi Y. A mammalian homolog of the zebrafish transmembrane protein 2 (TMEM2) is the long-sought-after cell-surface hyaluronidase. J Biol Chem. 2017;292:7304-7313 pubmed publisher
    ..HYAL1 and HYAL2 have properties more consistent with lysosomal hyaluronidases, whereas CEMIP/KIAA1199, a recently identified HA-..
  21. van den Berg L, Cardinaud S, van der Aar A, Sprokholt J, de Jong M, Zijlstra Willems E, et al. Langerhans Cell-Dendritic Cell Cross-Talk via Langerin and Hyaluronic Acid Mediates Antigen Transfer and Cross-Presentation of HIV-1. J Immunol. 2015;195:1763-73 pubmed publisher
    ..These data underscore the importance of LCs and DCs in orchestrating adaptive immunity to HIV-1. Novel strategies might be developed to harness this mechanism for vaccination. ..
  22. Yoshino Y, Ishisaka M, Tsuruma K, Shimazawa M, Yoshida H, Inoue S, et al. Distribution and function of hyaluronan binding protein involved in hyaluronan depolymerization (HYBID, KIAA1199) in the mouse central nervous system. Neuroscience. 2017;347:1-10 pubmed publisher
    ..In real-time PCR, Hyal1 and Hyal2 mRNA levels, which code hyaluronidases 1 and 2, respectively, did not differ between the Hybid KO and wild-type ..
  23. van der Heijden A, Mengual L, Lozano J, Ingelmo Torres M, Ribal M, Fernandez P, et al. A five-gene expression signature to predict progression in T1G3 bladder cancer. Eur J Cancer. 2016;64:127-36 pubmed publisher
    ..A five-gene expression signature (ANXA10, DAB2, HYAL2, SPOCD1, and MAP4K1) discriminated progressive from non-progressive T1G3 BC patients with a sensitivity of 79% and ..
  24. Saito N, Adachi H, Tanaka H, Nakata S, Kawada N, Oofusa K, et al. Interstitial fluid flow-induced growth potential and hyaluronan synthesis of fibroblasts in a fibroblast-populated stretched collagen gel culture. Biochim Biophys Acta Gen Subj. 2017;1861:2261-2273 pubmed publisher
    ..synthase 2 (HAS2) and matrix metalloprotease 1 (MMP1) gene expressions but not of the other genes (MMP2, HYAL1, HYAL2, HYAL3, COL1A1, COL3A1, and CD44)...
  25. Edjekouane L, Benhadjeba S, Jangal M, Fleury H, Gévry N, Carmona E, et al. Proximal and distal regulation of the HYAL1 gene cluster by the estrogen receptor α in breast cancer cells. Oncotarget. 2016;7:77276-77290 pubmed publisher
    ..Genes encoded in the 3p21.3 cluster include HYAL1, HYAL2 and HYAL3 members of hyaluronidases involved in the breakdown of hyaluronan, an abundant component of the ..
  26. Eicher J, Chen M, Pitsillides A, Lin H, Veeraraghavan N, Brody J, et al. Whole exome sequencing in the Framingham Heart Study identifies rare variation in HYAL2 that influences platelet aggregation. Thromb Haemost. 2017;117:1083-1092 pubmed publisher
    ..Using gene-based association tests of rare and low-frequency variants, we found significant associations of HYAL2 with increased ADP-induced aggregation (p = 1...
  27. Pavan M, Galesso D, Secchieri C, Guarise C. Hyaluronic acid alkyl derivative: A novel inhibitor of metalloproteases and hyaluronidases. Int J Biol Macromol. 2016;84:221-6 pubmed publisher
    ..This study demonstrates the unique properties of Hyadd-C16, including its remarkable enzymatic inhibitory activity, which is conferred by the hydrophobic chain, and its high biocompatibility and water solubility of the HA backbone. ..
  28. Della Colleta H, Carvalho H. Hyaluronan Content and Distribution in the Rat Ventral Prostate after Castration. Biochem Cell Biol. 2018;: pubmed publisher
    ..In conclusion, castration results in increased non-lysosomal hyaluronidase activity in concert with higher Has1 and Has2 mRNA abundance, resulting in decreased HA absolute content, ..
  29. Mohey Elsaeed O, Marei W, Fouladi Nashta A, El Saba A. Histochemical structure and immunolocalisation of the hyaluronan system in the dromedary oviduct. Reprod Fertil Dev. 2016;28:936-947 pubmed publisher
    ..dromedarius), focusing on the immnolocalisation of hyaluronic acid (HA) synthases (HAS2 and HAS3), hyaluronidases (HYAL2 and HYAL1) and the HA receptor CD44 in the ampulla and isthmus...
  30. Marei W, Raheem K, Salavati M, Tremaine T, Khalid M, Fouladi Nashta A. Hyaluronan and hyaluronidase, which is better for embryo development?. Theriogenology. 2016;86:940-948 pubmed publisher
    ..the size produced by HA synthase-3, which is abundant in the oviduct), or HA treated with Hyaluronidase-2 (Hyal2; also expressed in the oviduct that breaks down HA into 20 kDa fragments)...
  31. Chowdhury B, Hemming R, Faiyaz S, Triggs Raine B. Hyaluronidase 2 (HYAL2) is expressed in endothelial cells, as well as some specialized epithelial cells, and is required for normal hyaluronan catabolism. Histochem Cell Biol. 2016;145:53-66 pubmed publisher
    b>Hyaluronidase 2 (HYAL2) is a membrane-anchored protein that is proposed to initiate the degradation of hyaluronan (HA) in the extracellular matrix...
  32. Gaucherand L, Falk B, Evanko S, Workman G, Chan C, Wight T. Crosstalk Between T Lymphocytes and Lung Fibroblasts: Generation of a Hyaluronan-Enriched Extracellular Matrix Adhesive for Monocytes. J Cell Biochem. 2017;118:2118-2130 pubmed publisher
    ..stimulated the expression of mRNA for hyaluronan synthase 2 (HAS2) and decreased the expression of hyaluronidase 2 (HYAL2)...
  33. Puissant E, Boonen M. Monocytes/Macrophages Upregulate the Hyaluronidase HYAL1 and Adapt Its Subcellular Trafficking to Promote Extracellular Residency upon Differentiation into Osteoclasts. PLoS ONE. 2016;11:e0165004 pubmed publisher
    ..Interestingly, the expression of the other main hyaluronidase, HYAL2, and of lysosomal exoglycosidases involved in HA degradation, does not increase similarly to HYAL1 upon ..
  34. Shaheen R, Patel N, Shamseldin H, Alzahrani F, Al Yamany R, Almoisheer A, et al. Accelerating matchmaking of novel dysmorphology syndromes through clinical and genomic characterization of a large cohort. Genet Med. 2016;18:686-95 pubmed publisher
    ..genes are published here for the first time as novel candidates (CDK9, NEK9, ZNF668, TTC28, MBL2, CADPS, CACNA1H, HYAL2, CTU2, and C3ORF17)...
  35. Kramer P, Lausch V, Volkwein A, Hanke K, Hohn O, Bannert N. The human endogenous retrovirus K(HML-2) has a broad envelope-mediated cellular tropism and is prone to inhibition at a post-entry, pre-integration step. Virology. 2016;487:121-8 pubmed publisher
    ..an initial effort to identify a receptor for HERV-K(HML-2) we investigated whether transferrin receptor 1 and hyaluronidase 2, known cellular receptors of the closely related betaretroviruses mouse mammary tumor virus (MMTV) and ..
  36. Stridh S, Palm F, Takahashi T, Ikegami Kawai M, Friederich Persson M, Hansell P. Hyaluronan Production by Renomedullary Interstitial Cells: Influence of Endothelin, Angiotensin II and Vasopressin. Int J Mol Sci. 2017;18: pubmed publisher
    ..HAS2 and Hyal2 mRNA did not alter, while Hyal1 mRNA was increased at all ET-1 concentrations tested...
  37. Saito T, Kawana H, Azuma K, Toyoda A, Fujita H, Kitagawa M, et al. Fragmented hyaluronan is an autocrine chemokinetic motility factor supported by the HAS2-HYAL2/CD44 system on the plasma membrane. Int J Oncol. 2011;39:1311-20 pubmed publisher
    Hyaluronan (HA) is synthesized by HA synthase (HAS) 1, HAS2 and HAS3, and degraded by hyaluronidase (HYAL) 1 and HYAL2 in a CD44-dependent manner. HA and HYALs are intricately involved in tumor growth and metastasis...
  38. Nykopp T, Rilla K, Tammi M, Tammi R, Sironen R, Hamalainen K, et al. Hyaluronan synthases (HAS1-3) and hyaluronidases (HYAL1-2) in the accumulation of hyaluronan in endometrioid endometrial carcinoma. BMC Cancer. 2010;10:512 pubmed publisher
    ..we examined the expression levels of the hyaluronan synthases (HAS1, HAS2 and HAS3) and hyaluronidases (HYAL1 and HYAL2), and correlated them with hyaluronan content and HAS1-3 immunoreactivity...
  39. Monzon M, Fregien N, Schmid N, Falcon N, Campos M, Casalino Matsuda S, et al. Reactive oxygen species and hyaluronidase 2 regulate airway epithelial hyaluronan fragmentation. J Biol Chem. 2010;285:26126-34 pubmed publisher
    b>Hyaluronidase 2 (Hyal2) is a hyaluronan (HA)-degrading enzyme found intracellularly or/and anchored to the plasma membrane through glycosylphosphatidylinositol (GPI)...
  40. Monzon M, Manzanares D, Schmid N, Casalino Matsuda S, Forteza R. Hyaluronidase expression and activity is regulated by pro-inflammatory cytokines in human airway epithelial cells. Am J Respir Cell Mol Biol. 2008;39:289-95 pubmed publisher
    ..Confocal microscopy showed that Hyals 1, 2, and 3 were localized intracellularly, while Hyal2 was also expressed at the apical pole associated with the plasma membrane, and in a soluble form on the apical ..
  41. Kong X, Chen L, Ye P, Wang Z, Zhang J, Ye F, et al. The role of HYAL2 in LSS-induced glycocalyx impairment and the PKA-mediated decrease in eNOS-Ser-633 phosphorylation and nitric oxide production. Mol Biol Cell. 2016;27:3972-3979 pubmed
    ..Here we focus on the possible role of hyaluronidase 2 (HYAL2) in LSS-induced glycocalyx impairment and the resulting alterations in eNOS phosphorylation and NO ..
  42. Vigdorovich V, Miller A, Strong R. Ability of hyaluronidase 2 to degrade extracellular hyaluronan is not required for its function as a receptor for jaagsiekte sheep retrovirus. J Virol. 2007;81:3124-9 pubmed
    Jaagsiekte sheep retrovirus (JSRV) uses hyaluronidase 2 (Hyal2) as a cell entry receptor...
  43. Pfütze K, Benner A, Hoffmeister M, Jansen L, Yang R, Bläker H, et al. Methylation status at HYAL2 predicts overall and progression-free survival of colon cancer patients under 5-FU chemotherapy. Genomics. 2015;106:348-54 pubmed publisher
  44. Sun L, Feusi E, Sibalic A, Beck Schimmer B, Wuthrich R. Expression profile of hyaluronidase mRNA transcripts in the kidney and in renal cells. Kidney Blood Press Res. 1998;21:413-8 pubmed
    ..We found that transcripts for the lysosomal-type hyaluronidases Hyal1 and Hyal2 were constitutively expressed in normal and autoimmune kidneys as well as in tubular epithelial cells and in a ..
  45. Maierthaler M, Kriegsmann M, Peng C, Jauch S, SZABO A, Wallwiener M, et al. S100P and HYAL2 as prognostic markers for patients with triple-negative breast cancer. Exp Mol Pathol. 2015;99:180-7 pubmed publisher
    ..Here we have analysed the expression of S100P and HYAL2 using immunohistochemistry (IHC) in a TNBC cohort of 98 patients with a follow-up for recurrence and death...
  46. Albeiroti S, Ayasoufi K, Hill D, Shen B, De La Motte C. Platelet hyaluronidase-2: an enzyme that translocates to the surface upon activation to function in extracellular matrix degradation. Blood. 2015;125:1460-9 pubmed publisher
    ..We also showed that human platelets contain the enzyme hyaluronidase-2 (HYAL2), one of two major hyaluronidases that digest HA in somatic tissues...
  47. Miller A, de las Heras M, Yu J, Zhang F, Liu S, Vaughan A, et al. Evidence against a role for jaagsiekte sheep retrovirus in human lung cancer. Retrovirology. 2017;14:3 pubmed publisher
    ..entry into cells is initiated by binding of the viral envelope (Env) protein to a specific cell-surface receptor, Hyal2. Unlike almost all other retroviruses, the JSRV Env protein is also a potent oncoprotein and is responsible for ..
  48. Lepperdinger G, Strobl B, Kreil G. HYAL2, a human gene expressed in many cells, encodes a lysosomal hyaluronidase with a novel type of specificity. J Biol Chem. 1998;273:22466-70 pubmed
    ..Expression of this cDNA yielded a polypeptide termed HYAL2, which is located in lysosomes. The HYAL2 protein was shown to have hyaluronidase activity below pH 4...
  49. Strobl B, Wechselberger C, Beier D, Lepperdinger G. Structural organization and chromosomal localization of Hyal2, a gene encoding a lysosomal hyaluronidase. Genomics. 1998;53:214-9 pubmed
    The human HYAL2 gene encodes a lysosomal hyaluronidase that is related to the testicular PH-20 hyaluronidase...
  50. Nicoll S, Barak O, Csoka A, Bhatnagar R, Stern R. Hyaluronidases and CD44 undergo differential modulation during chondrogenesis. Biochem Biophys Res Commun. 2002;292:819-25 pubmed
    ..Marked increase in HYAL1 expression was observed, with only moderate increases occurring in HYAL2 and HYAL3. No expression of HYAL4 and PH-20, the sperm-associated hyaluronidase, was detected...
  51. Chow G, Knudson W. Characterization of promoter elements of the human HYAL-2 gene. J Biol Chem. 2005;280:26904-12 pubmed
    ..As such, it appears that the expression of lysosomal hyaluronidase participates little in the overall regulation of hyaluronan catabolism.
  52. Chow G, Knudson C, Knudson W. Expression and cellular localization of human hyaluronidase-2 in articular chondrocytes and cultured cell lines. Osteoarthritis Cartilage. 2006;14:849-58 pubmed
    ..Thus, local turnover of HA is dependent on receptor-mediated endocytosis and delivery to low pH intracellular organelles for its complete degradation. ..
  53. Fiszer Szafarz B, Litynska A, Zou L. Human hyaluronidases: electrophoretic multiple forms in somatic tissues and body fluids. Evidence for conserved hyaluronidase potential N-glycosylation sites in different mammalian species. J Biochem Biophys Methods. 2000;45:103-16 pubmed
    ..1) with similar tripeptide patterns was observed at the same position in human plasma (HYAL1), human lysosomes (HYAL2) and in two newly reported hyaluronidases (HYAL4 and HYALP1)...
  54. Modelski M, Menlah G, Wang Y, Dash S, Wu K, Galileo D, et al. Hyaluronidase 2: a novel germ cell hyaluronidase with epididymal expression and functional roles in mammalian sperm. Biol Reprod. 2014;91:109 pubmed publisher
    ..Here we report that the ~57 kDa hyaluronidase 2 (HYAL2) that in somatic tissues has been highly characterized to be acid-active is present in mouse and human ..
  55. Petrey A, Obery D, Kessler S, Flamion B, De La Motte C. Hyaluronan Depolymerization by Megakaryocyte Hyaluronidase-2 Is Required for Thrombopoiesis. Am J Pathol. 2016;186:2390-403 pubmed publisher
    ..Together, our data uncover a previously unsuspected mechanism of how hyaluronan and Hyal-2 control platelet generation. ..
  56. Miller A, Vigdorovich V, Strong R, Fernandes R, Lerman M. Hyal2, where are you?. Osteoarthritis Cartilage. 2006;14:1315-7 pubmed
  57. Schott S, Yang R, Stöcker S, Canzian F, Giese N, Bugert P, et al. HYAL2 methylation in peripheral blood as a potential marker for the detection of pancreatic cancer: a case control study. Oncotarget. 2017;8:67614-67625 pubmed publisher
    ..Early detection markers are urgently needed to improve diagnosis. Altered hyaluronoglucosaminidase 2 gene (HYAL2) DNA methylation in peripheral blood is known to be associated with malignancy at early stage but has not been ..
  58. Andre B, Duterme C, Van Moer K, Mertens Strijthagen J, Jadot M, Flamion B. Hyal2 is a glycosylphosphatidylinositol-anchored, lipid raft-associated hyaluronidase. Biochem Biophys Res Commun. 2011;411:175-9 pubmed publisher
    ..One of them, hyaluronidase-2 (Hyal2), degrades HA into smaller fragments endowed with specific biological activities such as inflammation and ..
  59. Marei W, Wathes D, Raheem K, Mohey Elsaeed O, Ghafari F, Fouladi Nashta A. Influence of hyaluronan on endometrial receptivity and embryo attachment in sheep. Reprod Fertil Dev. 2017;29:1763-1773 pubmed publisher
    ..uterine horns were infused with either (n=4 each): PBS (control), HA (1mg mL-1), HA+hyaluronidase 2 (Hyal2; 300IU mL-1) or 4-methyl-umbelliferone (HA-synthesis inhibitor; 4MU, 1mM)...
  60. Muggenthaler M, Chowdhury B, Hasan S, Cross H, Mark B, Harlalka G, et al. Mutations in HYAL2, Encoding Hyaluronidase 2, Cause a Syndrome of Orofacial Clefting and Cor Triatriatum Sinister in Humans and Mice. PLoS Genet. 2017;13:e1006470 pubmed publisher
    ..Here, we describe mutations in the HYAL2 gene as a cause of syndromic orofacial clefting. HYAL2, encoding hyaluronidase 2, degrades extracellular hyaluronan, a critical component of the developing heart and palatal shelf matrix...
  61. Anedchenko E, Dmitriev A, Krasnov G, Kondrat eva T, Kopantsev E, Vinogradova T, et al. [Down-regulation of RBSP3/CTDSPL, NPRL2/G21, RASSF1A, ITGA9, HYAL1 and HYAL2 genes in non-small cell lung cancer]. Mol Biol (Mosk). 2008;42:965-76 pubmed
    ..3 (RBSP3/CTDSPL, NPRL2/G21, RASSF1A, ITGA9, HYAL1 and HYAL2 in basic types of non-small cell lung cancer (NSCLC)--squamous cell lung cancer (SCC) and lung adenocarcinoma (AC)...
  62. Midgley A, Oltean S, Hascall V, Woods E, Steadman R, Phillips A, et al. Nuclear hyaluronidase 2 drives alternative splicing of CD44 pre-mRNA to determine profibrotic or antifibrotic cell phenotype. Sci Signal. 2017;10: pubmed publisher
    ..We identified an unexpected function for the ubiquitous hyaluronan-degrading enzyme, hyaluronidase 2 (HYAL2), as a regulator of CD44 splicing...
  63. Higuchi Y, Nishida Y, Kozawa E, Zhuo L, Arai E, Hamada S, et al. Conditional knockdown of hyaluronidase 2 in articular cartilage stimulates osteoarthritic progression in a mice model. Sci Rep. 2017;7:7028 pubmed publisher
    ..The aims of this study were to investigate the effects of hyaluronidase 2 (Hyal2) knockdown in articular cartilage on the development of osteoarthritis (OA) using genetic manipulated ..
  64. Bouga H, Tsouros I, Bounias D, Kyriakopoulou D, Stavropoulos M, Papageorgakopoulou N, et al. Involvement of hyaluronidases in colorectal cancer. BMC Cancer. 2010;10:499 pubmed publisher
    ..The results provided new evidence on the mechanisms involved in the progression of colorectal cancer. ..
  65. Duh F, Dirks C, Lerman M, Miller A. Amino acid residues that are important for Hyal2 function as a receptor for jaagsiekte sheep retrovirus. Retrovirology. 2005;2:59 pubmed
    ..and by enzootic nasal tumor virus (ENTV) depends on cell-surface expression of the virus entry receptor, hyaluronidase 2 (Hyal2)...
  66. Hsu L, Schultz L, Hong Q, Van Moer K, Heath J, Li M, et al. Transforming growth factor beta1 signaling via interaction with cell surface Hyal-2 and recruitment of WWOX/WOX1. J Biol Chem. 2009;284:16049-59 pubmed publisher
    ..Together, TGF-beta1 invokes a novel signaling by engaging cell surface Hyal-2 and recruiting WOX1 for regulating the activation of Smad-driven promoter, thereby controlling cell growth and death. ..
  67. Wei M, Latif F, Bader S, Kashuba V, Chen J, Duh F, et al. Construction of a 600-kilobase cosmid clone contig and generation of a transcriptional map surrounding the lung cancer tumor suppressor gene (TSG) locus on human chromosome 3p21.3: progress toward the isolation of a lung cancer TSG. Cancer Res. 1996;56:1487-92 pubmed
    ..This large cosmid clone contig and high resolution maps will prove crucial in the identification of the lung cancer TSG(s). ..
  68. Jiang F, Todd N, Li R, Zhang H, Fang H, Stass S. A panel of sputum-based genomic marker for early detection of lung cancer. Cancer Prev Res (Phila). 2010;3:1571-8 pubmed publisher
    ..A logistic regression model with the best prediction was built on the basis of 6 genes, ENO1, FHIT, HYAL2, SKP2, p16, and 14-3-3zeta. The composite of the 6 genes produced 86.7% sensitivity and 93...
  69. de la Motte C, Nigro J, Vasanji A, Rho H, Kessler S, Bandyopadhyay S, et al. Platelet-derived hyaluronidase 2 cleaves hyaluronan into fragments that trigger monocyte-mediated production of proinflammatory cytokines. Am J Pathol. 2009;174:2254-64 pubmed publisher
    ..as well as their megakaryocyte precursors, are unusual among somatic cells in that they contain only hyaluronidase 2 (HYAL2) but not HYAL1...
  70. Tzuman Y, Sapoznik S, Granot D, Nevo N, Neeman M. Peritoneal adhesion and angiogenesis in ovarian carcinoma are inversely regulated by hyaluronan: the role of gonadotropins. Neoplasia. 2010;12:51-60 pubmed
    ..Accordingly, angiogenesis of the adhered spheroids was significantly elevated in DON-treated tumors. These results can explain the selective pressure that can lead to simultaneously increased tumor expression of both HASs and Hyals...
  71. Kurdykowski S, Mine S, Bardey V, Danoux L, Jeanmaire C, Pauly G, et al. Ultraviolet-B irradiation induces differential regulations of hyaluronidase expression and activity in normal human keratinocytes. Photochem Photobiol. 2011;87:1105-12 pubmed publisher
    ..The mRNA expression of HYAL1, HYAL2 and HYAL3 and the hyaluronidase enzymatic activity were quantified using real-time PCR and a microtiter-based ..
  72. Al Qteishat A, Gaffney J, Krupinski J, Slevin M. Hyaluronan expression following middle cerebral artery occlusion in the rat. Neuroreport. 2006;17:1111-4 pubmed
    ..Hyaluronan synthesis and degradation in the stroke hemisphere might have an impact on neuronal survival, angiogenesis and general tissue remodelling after stroke. ..
  73. Yang R, Pfütze K, Zucknick M, Sutter C, Wappenschmidt B, Marme F, et al. DNA methylation array analyses identified breast cancer-associated HYAL2 methylation in peripheral blood. Int J Cancer. 2015;136:1845-55 pubmed publisher
    ..identified a BC-associated differentially methylated CpG site cg27091787 in the hyaluronoglucosaminidase 2 gene (HYAL2) (discovery round with 72 BC case and 24 controls: p = 2.61 × 10(-9) adjusted for cell-type proportions)...
  74. Delpech B, Laquerriere A, Maingonnat C, Bertrand P, Freger P. Hyaluronidase is more elevated in human brain metastases than in primary brain tumours. Anticancer Res. 2002;22:2423-7 pubmed
    ..These results suggest that hyaluronidase is associated with the more aggressive cancer cells and is directly or indirectly involved in brain metastasis phenotype. ..
  75. Ohnuma S, Miura K, Horii A, Fujibuchi W, Kaneko N, Gotoh O, et al. Cancer-associated splicing variants of the CDCA1 and MSMB genes expressed in cancer cell lines and surgically resected gastric cancer tissues. Surgery. 2009;145:57-68 pubmed publisher
    ..Among these variants, M-RIP, HYAL2, CDCA1, and MSMB genes showed differential expressions between cancer cell lines and corresponding normal tissues...
  76. Siiskonen H, Poukka M, Tyynelä Korhonen K, Sironen R, Pasonen Seppänen S. Inverse expression of hyaluronidase 2 and hyaluronan synthases 1-3 is associated with reduced hyaluronan content in malignant cutaneous melanoma. BMC Cancer. 2013;13:181 pubmed publisher
    ..The immunopositivity of hyaluronidase 2 was significantly increased in the premalignant and malignant lesions indicating its specific role in the ..
  77. Hida D, Danielson B, Knudson C, Knudson W. CD44 knock-down in bovine and human chondrocytes results in release of bound HYAL2. Matrix Biol. 2015;48:42-54 pubmed publisher
    ..Previous work of others has suggested that the hyaluronidase isoform HYAL2 has the capacity to bind to CD44, a binding that may itself induce CD44 cleavage...