HYAL2

Hyaluronidase-2 is a multifunctional protein, previously thought to only possess acid-active hyaluronan-degrading enzymatic function. In humans it 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; OMA:HYAL2 - orthologs
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 107,445,144 bp[2] End 107,449,978 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lung spleen upper lobe of left lung right lobe of thyroid gland left uterine tube left lobe of thyroid gland pericardium gallbladder apex of heart body of uterus Top expressed in right kidney yolk sac external carotid artery proximal tubule internal carotid artery lip left lobe of liver epiblast right lung lobe neural tube More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transcription coactivator activity hyaluronoglucuronidase activity catalytic activity virus receptor activity hyalurononglucosaminidase activity receptor tyrosine kinase binding hydrolase activity, acting on glycosyl bonds 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 plasma membrane endocytic vesicle microvillus cell surface RNA polymerase II transcription regulator 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 by RNA polymerase II defense response to virus viral entry into host cell carbohydrate metabolic process response to virus transformation of host cell by virus transcription by RNA polymerase II 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: 107.45 – 107.45 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] Another study published in 2020, described roles for HYAL2 in the orchestration of cytoskeletal components involved in myofibroblast contraction.^[10] These recent discoveries suggest 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 (August 1998). "HYAL2, a human gene expressed in many cells, encodes a lysosomal hyaluronidase with a novel type of specificity". The Journal of Biological Chemistry. 273 (35): 22466–70. doi:10.1074/jbc.273.35.22466. PMID 9712871. S2CID 44868532.
6. Strobl B, Wechselberger C, Beier DR, Lepperdinger G (October 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 A (2017-01-17). "Scientists find genetic mutation that causes cleft lip and palate, heart defects". Medical News Today. Retrieved 2017-01-31.
9. Midgley AC, Oltean S, Hascall V, Woods EL, Steadman R, Phillips AO, Meran S (November 2017). "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. hdl:10871/36504. PMID 29162741. S2CID 12486942.
10. Midgley AC, Woods EL, Jenkins RH, Brown C, Khalid U, Chavez R, et al. (June 2020). "Hyaluronidase-2 Regulates RhoA Signaling, Myofibroblast Contractility, and Other Key Profibrotic Myofibroblast Functions". The American Journal of Pathology. 190 (6): 1236–1255. doi:10.1016/j.ajpath.2020.02.012. PMC 7254050. PMID 32201263.

Further reading

• Lepperdinger G, Müllegger J, Kreil G (December 2001). "Hyal2--less active, but more versatile?". Matrix Biology. 20 (8): 509–14. doi:10.1016/S0945-053X(01)00170-6. PMID 11731268.
• Maruyama K, Sugano S (January 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, Kashuba V, Chen JY, Duh FM, et al. (April 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 Research. 56 (7): 1487–92. PMID 8603390.
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (April 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, et al. (April 1997). "Large-scale concatenation cDNA sequencing". Genome Research. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 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, Beck-Schimmer B, Wüthrich RP (1999). "Expression profile of hyaluronidase mRNA transcripts in the kidney and in renal cells". Kidney & Blood Pressure Research. 21 (6): 413–8. doi:10.1159/000025893. PMID 9933825. S2CID 40489637.
• Fiszer-Szafarz B, Litynska A, Zou L (September 2000). "Human hyaluronidases: electrophoretic multiple forms in somatic tissues and body fluids. Evidence for conserved hyaluronidase potential N-glycosylation sites in different mammalian species". Journal of Biochemical and Biophysical Methods. 45 (2): 103–16. doi:10.1016/S0165-022X(00)00067-1. PMID 10989127.
• Lerman MI, Minna JD (November 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 Research. 60 (21): 6116–33. PMID 11085536.
• Rai SK, Duh FM, Vigdorovich V, Danilkovitch-Miagkova A, Lerman MI, Miller AD (April 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". Proceedings of the National Academy of Sciences of the United States of America. 98 (8): 4443–8. Bibcode:2001PNAS...98.4443R. doi:10.1073/pnas.071572898. PMC 31854. PMID 11296287.
• Delpech B, Laquerriere A, Maingonnat C, Bertrand P, Freger P (2002). "Hyaluronidase is more elevated in human brain metastases than in primary brain tumours". Anticancer Research. 22 (4): 2423–7. PMID 12174938.
• Liu SL, Duh FM, Lerman MI, Miller AD (March 2003). "Role of virus receptor Hyal2 in oncogenic transformation of rodent fibroblasts by sheep betaretrovirus env proteins". Journal of Virology. 77 (5): 2850–8. doi:10.1128/JVI.77.5.2850-2858.2003. PMC 149765. PMID 12584308.
• Danilkovitch-Miagkova A, Duh FM, Kuzmin I, Angeloni D, Liu SL, Miller AD, Lerman MI (April 2003). "Hyaluronidase 2 negatively regulates RON receptor tyrosine kinase and mediates transformation of epithelial cells by jaagsiekte sheep retrovirus". Proceedings of the National Academy of Sciences of the United States of America. 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". Oncology Reports. 10 (3): 609–16. doi:10.3892/or.10.3.609 (inactive 1 November 2024). PMID 12684632.{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link)