HYAL2

Hyaluronidase-2 is an enzyme that in humans is encoded by the HYAL2 gene.[5][6][7]

HYAL2
Identifiers
Aliases	HYAL2, LUCA2, hyaluronoglucosaminidase 2, hyaluronidase 2
External IDs	OMIM: 603551 MGI: 1196334 HomoloGene: 7776 GeneCards: HYAL2
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3p21.31 Start 50,317,790 bp[1] End 50,322,782 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9 F1|9 58.12 cM Start 107,567,945 bp[2] End 107,572,779 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001105 transcription coactivator activity • hyaluronoglucuronidase activity • catalytic activity • virus receptor activity • hyalurononglucosaminidase activity • receptor tyrosine kinase binding • hydrolase activity, acting on glycosyl bonds • GO:0001948 protein binding • hyaluronic acid binding • enzyme binding • receptor signaling protein tyrosine kinase inhibitor activity • hydrolase activity • transforming growth factor beta binding Cellular component • cytoplasm • cytosol • membrane • anchored component of plasma membrane • Golgi membrane • cell membrane • endocytic vesicle • microvilli • cell surface • RNA polymerase II transcription factor complex • apical plasma membrane • endoplasmic reticulum • anchored component of external side of plasma membrane • perinuclear region of cytoplasm • membrane raft • anchored component of membrane • lysosome • cytoplasmic vesicle Biological process • cellular response to transforming growth factor beta stimulus • negative regulation of protein kinase B signaling • negative regulation of fibroblast migration • positive regulation of inflammatory response • hyaluronan catabolic process • positive regulation of urine volume • kidney development • response to reactive oxygen species • response to antibiotic • cellular response to tumor necrosis factor • skeletal system morphogenesis • cellular response to fibroblast growth factor stimulus • monocyte activation • multicellular organismal iron ion homeostasis • cartilage development • negative regulation of protein tyrosine kinase activity • cellular response to UV-B • glycosaminoglycan catabolic process • negative regulation of MAP kinase activity • negative regulation of cell growth • hematopoietic progenitor cell differentiation • multicellular organism aging • cellular response to interleukin-1 • positive regulation of protein import into nucleus • positive regulation of extrinsic apoptotic signaling pathway • metabolism • renal water absorption • positive regulation of transcription from RNA polymerase II promoter • defense response to virus • viral entry • carbohydrate metabolic process • response to virus • transformation of host cell by virus • transcription from RNA polymerase II promoter Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	8692	15587
Ensembl	ENSG00000068001	ENSMUSG00000010047
UniProt	Q12891	O35632
RefSeq (mRNA)	NM_003773 NM_033158	NM_010489
RefSeq (protein)	NP_003764 NP_149348	NP_034619
Location (UCSC)	Chr 3: 50.32 – 50.32 Mb	Chr 9: 107.57 – 107.57 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

This gene encodes a protein which is similar in structure to hyaluronidases. Hyaluronidases intracellularly degrade hyaluronan, one of the major glycosaminoglycans of the extracellular matrix. Hyaluronan is thought to be involved in cell proliferation, migration and differentiation.

Varying functions have been described for this protein. It has been described as a lysosomal hyaluronidase which is active at a pH below 4 and specifically hydrolyzes high molecular weight hyaluronan. It has also been described as a GPI-anchored cell surface protein which does not display hyaluronidase activity but does serve as a receptor for the oncogenic virus Jaagsiekte sheep retrovirus. The gene is one of several related genes in a region of chromosome 3p21.3 associated with tumor suppression. This gene encodes two alternatively spliced transcript variants which differ only in the 5' UTR.[7]

One study found associations between cleft lip and palate and mutations in the HYAL2 gene.[8]

An investigation published in 2017, attributed an additional function to the Hyaluronidase 2 (HYAL2) protein. The study found interactions between HYAL2 and proteins involved in the alternative splicing of CD44 pre-mRNA,[9] suggesting a broader regulatory role for the HYAL2 protein in cell biology.

References

1. GRCh38: Ensembl release 89: ENSG00000068001 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000010047 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Lepperdinger G, Strobl B, Kreil G (Sep 1998). "HYAL2, a human gene expressed in many cells, encodes a lysosomal hyaluronidase with a novel type of specificity". J Biol Chem. 273 (35): 22466–70. doi:10.1074/jbc.273.35.22466. PMID 9712871. S2CID 44868532.
6. Strobl B, Wechselberger C, Beier DR, Lepperdinger G (Dec 1998). "Structural organization and chromosomal localization of Hyal2, a gene encoding a lysosomal hyaluronidase". Genomics. 53 (2): 214–9. doi:10.1006/geno.1998.5472. PMID 9790770.
7. "Entrez Gene: HYAL2 hyaluronoglucosaminidase 2".
8. Sandoiu, Ana (2017-01-17). "Scientists find genetic mutation that causes cleft lip and palate, heart defects". Medical News Today. Retrieved 2017-01-31.
9. Midgley, Adam C.; Oltean, Sebastian; Hascall, Vincent; Woods, Emma L.; Steadman, Robert; Phillips, Aled O.; Meran, Soma (2017-11-21). "Nuclear hyaluronidase 2 drives alternative splicing of CD44 pre-mRNA to determine profibrotic or antifibrotic cell phenotype". Science Signaling. 10 (506): eaao1822. doi:10.1126/scisignal.aao1822. ISSN 1937-9145. PMID 29162741. S2CID 12486942.

Further reading

• Lepperdinger G, Müllegger J, Kreil G (2002). "Hyal2--less active, but more versatile?". Matrix Biol. 20 (8): 509–14. doi:10.1016/S0945-053X(01)00170-6. PMID 11731268.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Wei MH, Latif F, Bader S, et al. (1996). "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. 56 (7): 1487–92. PMID 8603390.
• Andersson B, Wentland MA, Ricafrente JY, et al. (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
• Yu W, Andersson B, Worley KC, et al. (1997). "Large-scale concatenation cDNA sequencing". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Sun L, Feusi E, Sibalic A, et al. (1999). "Expression profile of hyaluronidase mRNA transcripts in the kidney and in renal cells". Kidney Blood Press. Res. 21 (6): 413–8. doi:10.1159/000025893. PMID 9933825. S2CID 40489637.
• Fiszer-Szafarz B, Litynska A, Zou L (2000). "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. 45 (2): 103–16. doi:10.1016/S0165-022X(00)00067-1. PMID 10989127.
• Lerman MI, Minna JD (2000). "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. 60 (21): 6116–33. PMID 11085536.
• Rai SK, Duh FM, Vigdorovich V, et al. (2001). "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. 98 (8): 4443–8. Bibcode:2001PNAS...98.4443R. doi:10.1073/pnas.071572898. PMC 31854. PMID 11296287.
• Delpech B, Laquerriere A, Maingonnat C, et al. (2002). "Hyaluronidase is more elevated in human brain metastases than in primary brain tumours". Anticancer Res. 22 (4): 2423–7. PMID 12174938.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Liu SL, Duh FM, Lerman MI, Miller AD (2003). "Role of virus receptor Hyal2 in oncogenic transformation of rodent fibroblasts by sheep betaretrovirus env proteins". J. Virol. 77 (5): 2850–8. doi:10.1128/JVI.77.5.2850-2858.2003. PMC 149765. PMID 12584308.
• Danilkovitch-Miagkova A, Duh FM, Kuzmin I, et al. (2003). "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. 100 (8): 4580–5. Bibcode:2003PNAS..100.4580D. doi:10.1073/pnas.0837136100. hdl:11382/303276. PMC 153598. PMID 12676986.
• Junker N, Latini S, Petersen LN, Kristjansen PE (2003). "Expression and regulation patterns of hyaluronidases in small cell lung cancer and glioma lines". Oncol. Rep. 10 (3): 609–16. doi:10.3892/or.10.3.609 (inactive 2021-01-13). PMID 12684632.CS1 maint: DOI inactive as of January 2021 (link)
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039. S2CID 21903526.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.