Hyaluronidase-2 is a multifunctional protein, previously thought to only possess acid-active hyaluronan-degrading enzymatic function. In humans it is encoded by the HYAL2gene.[5][6][7]
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 CD44pre-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.
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000068001 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000010047 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^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.
^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.
^Sandoiu A (2017-01-17). "Scientists find genetic mutation that causes cleft lip and palate, heart defects". Medical News Today. Retrieved 2017-01-31.
^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. PMID 29162741. S2CID 12486942.
^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. PMC7254050. PMID 32201263.
Further readingedit
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. PMC139146. 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. PMC31854. 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. PMC149765. 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. PMC153598. 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 August 2023). PMID 12684632.{{cite journal}}: CS1 maint: DOI inactive as of August 2023 (link)
This article on a gene on human chromosome 3 is a stub. You can help Wikipedia by expanding it.
hyal2, hyaluronidase, multifunctional, protein, previously, thought, only, possess, acid, active, hyaluronan, degrading, enzymatic, function, humans, encoded, gene, identifiersaliases, luca2, hyaluronoglucosaminidase, hyaluronidase, 2external, idsomim, 603551,. 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 HYAL2IdentifiersAliasesHYAL2 LUCA2 hyaluronoglucosaminidase 2 hyaluronidase 2External IDsOMIM 603551 MGI 1196334 HomoloGene 7776 GeneCards HYAL2Gene location Human Chr Chromosome 3 human 1 Band3p21 31Start50 317 790 bp 1 End50 322 782 bp 1 Gene location Mouse Chr Chromosome 9 mouse 2 Band9 F1 9 58 12 cMStart107 445 144 bp 2 End107 449 978 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inright lungspleenupper lobe of left lungright lobe of thyroid glandleft uterine tubeleft lobe of thyroid glandpericardiumgallbladderstromal cell of endometriumsubcutaneous adipose tissueTop expressed inyolk sacexternal carotid arteryproximal tubuleinternal carotid arterylipleft lobe of liverright lung lobeneural tubecondylefossaMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functiontranscription 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 bindingCellular componentcytoplasm 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 vesicleBiological processcellular 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 IISources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez869215587EnsemblENSG00000068001ENSMUSG00000010047UniProtQ12891O35632RefSeq mRNA NM 003773NM 033158NM 010489RefSeq protein NP 003764NP 149348NP 034619Location UCSC Chr 3 50 32 50 32 MbChr 9 107 45 107 45 MbPubMed search 3 4 WikidataView Edit HumanView Edit MouseThis 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 edit a b c GRCh38 Ensembl release 89 ENSG00000068001 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000010047 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine 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 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 a b Entrez Gene HYAL2 hyaluronoglucosaminidase 2 Sandoiu A 2017 01 17 Scientists find genetic mutation that causes cleft lip and palate heart defects Medical News Today Retrieved 2017 01 31 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 PMID 29162741 S2CID 12486942 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 editLepperdinger G Mullegger 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 Wuthrich RP 1999 Expression profile of hyaluronidase mRNA transcripts in the kidney and in renal cells Kidney amp 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 August 2023 PMID 12684632 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint DOI inactive as of August 2023 link nbsp This article on a gene on human chromosome 3 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title HYAL2 amp oldid 1168150462, wikipedia, wiki, book, books, library,
