HYAL2_MOUSE
ID HYAL2_MOUSE Reviewed; 473 AA.
AC O35632; O35631; Q99MS9; Q99MT0;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 15-NOV-2002, sequence version 2.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Hyaluronidase-2;
DE Short=Hyal-2;
DE EC=3.2.1.35;
DE AltName: Full=Hyaluronoglucosaminidase-2;
DE Flags: Precursor;
GN Name=Hyal2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=129/SvJ;
RX PubMed=9790770; DOI=10.1006/geno.1998.5472;
RA Strobl B., Wechselberger C., Beier D., Lepperdinger G.;
RT "Structural organization and chromosomal localization of Hyal2, a gene
RT encoding a lysosomal hyaluronidase.";
RL Genomics 53:214-219(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C3H/HeJ, and Czech II;
RX PubMed=11296287; DOI=10.1073/pnas.071572898;
RA Rai S.K., Duh F.-M., Vigdorovich V., Danilkovitch-Miagkova A., Lerman M.I.,
RA Miller A.D.;
RT "Candidate tumor suppressor HYAL2 is a glycosylphosphatidylinositol (GPI)-
RT anchored cell-surface receptor for jaagsiekte sheep retrovirus, the
RT envelope protein of which mediates oncogenic transformation.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:4443-4448(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Czech II;
RX PubMed=11960552; DOI=10.1186/1471-2121-3-8;
RA Chang N.-S.;
RT "Transforming growth factor-beta1 blocks the enhancement of tumor necrosis
RT factor cytotoxicity by hyaluronidase Hyal-2 in L929 fibroblasts.";
RL BMC Cell Biol. 3:8-8(2002).
RN [4]
RP REVIEW.
RX PubMed=11731268; DOI=10.1016/s0945-053x(01)00170-6;
RA Lepperdinger G., Mullegger J., Kreil G.;
RT "Hyal2 -- less active, but more versatile?";
RL Matrix Biol. 20:509-514(2001).
RN [5]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-74 AND ASN-390.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
CC -!- FUNCTION: Hydrolyzes high molecular weight hyaluronic acid to produce
CC an intermediate-sized product which is further hydrolyzed by sperm
CC hyaluronidase to give small oligosaccharides. Displays very low levels
CC of activity. Associates with and negatively regulates MST1R (By
CC similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Random hydrolysis of (1->4)-linkages between N-acetyl-beta-D-
CC glucosamine and D-glucuronate residues in hyaluronate.; EC=3.2.1.35;
CC -!- SUBUNIT: Interacts with MST1R. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Lipid-anchor, GPI-
CC anchor {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Widely expressed. In the brain, expressed during
CC embryonic stages but expression decreases after birth and is barely
CC detectable in adult brain. {ECO:0000269|PubMed:9790770}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 56 family. {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be lysosomal. {ECO:0000305}.
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DR EMBL; AJ000059; CAA03888.1; -; mRNA.
DR EMBL; AJ000060; CAA03889.1; -; Genomic_DNA.
DR EMBL; AF302843; AAK28481.1; -; mRNA.
DR EMBL; AF302844; AAK28482.1; -; mRNA.
DR EMBL; AF422177; AAL17823.1; -; mRNA.
DR CCDS; CCDS23496.1; -.
DR RefSeq; NP_034619.2; NM_010489.2.
DR RefSeq; XP_006511706.1; XM_006511643.3.
DR RefSeq; XP_006511707.1; XM_006511644.3.
DR RefSeq; XP_006511708.1; XM_006511645.3.
DR AlphaFoldDB; O35632; -.
DR SMR; O35632; -.
DR STRING; 10090.ENSMUSP00000010191; -.
DR CAZy; GH56; Glycoside Hydrolase Family 56.
DR GlyConnect; 2375; 1 N-Linked glycan (1 site).
DR GlyGen; O35632; 5 sites, 1 N-linked glycan (1 site).
DR iPTMnet; O35632; -.
DR PhosphoSitePlus; O35632; -.
DR jPOST; O35632; -.
DR PaxDb; O35632; -.
DR PeptideAtlas; O35632; -.
DR PRIDE; O35632; -.
DR ProteomicsDB; 273333; -.
DR Antibodypedia; 30889; 281 antibodies from 32 providers.
DR DNASU; 15587; -.
DR Ensembl; ENSMUST00000010191; ENSMUSP00000010191; ENSMUSG00000010047.
DR Ensembl; ENSMUST00000195752; ENSMUSP00000141280; ENSMUSG00000010047.
DR GeneID; 15587; -.
DR KEGG; mmu:15587; -.
DR UCSC; uc009rlu.1; mouse.
DR CTD; 8692; -.
DR MGI; MGI:1196334; Hyal2.
DR VEuPathDB; HostDB:ENSMUSG00000010047; -.
DR eggNOG; ENOG502QUYI; Eukaryota.
DR GeneTree; ENSGT01020000230364; -.
DR HOGENOM; CLU_036366_0_0_1; -.
DR InParanoid; O35632; -.
DR OMA; FHCHCYQ; -.
DR OrthoDB; 1096692at2759; -.
DR PhylomeDB; O35632; -.
DR TreeFam; TF321598; -.
DR BRENDA; 3.2.1.35; 3474.
DR Reactome; R-MMU-2160916; Hyaluronan uptake and degradation.
DR BioGRID-ORCS; 15587; 3 hits in 75 CRISPR screens.
DR PRO; PR:O35632; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; O35632; protein.
DR Bgee; ENSMUSG00000010047; Expressed in right kidney and 202 other tissues.
DR ExpressionAtlas; O35632; baseline and differential.
DR Genevisible; O35632; MM.
DR GO; GO:0046658; C:anchored component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0030139; C:endocytic vesicle; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0005902; C:microvillus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA:BHF-UCL.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0005540; F:hyaluronic acid binding; ISS:UniProtKB.
DR GO; GO:0033906; F:hyaluronoglucuronidase activity; ISS:UniProtKB.
DR GO; GO:0004415; F:hyalurononglucosaminidase activity; IMP:MGI.
DR GO; GO:0030294; F:receptor signaling protein tyrosine kinase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:MGI.
DR GO; GO:0050431; F:transforming growth factor beta binding; IPI:BHF-UCL.
DR GO; GO:0001618; F:virus receptor activity; IDA:UniProtKB.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0051216; P:cartilage development; ISS:UniProtKB.
DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0071347; P:cellular response to interleukin-1; ISS:UniProtKB.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:BHF-UCL.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR GO; GO:0071493; P:cellular response to UV-B; ISS:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; ISS:UniProtKB.
DR GO; GO:0006027; P:glycosaminoglycan catabolic process; ISS:UniProtKB.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IMP:MGI.
DR GO; GO:0030214; P:hyaluronan catabolic process; IMP:MGI.
DR GO; GO:0042117; P:monocyte activation; ISS:UniProtKB.
DR GO; GO:0010259; P:multicellular organism aging; IMP:MGI.
DR GO; GO:0060586; P:multicellular organismal iron ion homeostasis; IMP:MGI.
DR GO; GO:0030308; P:negative regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0010764; P:negative regulation of fibroblast migration; ISS:UniProtKB.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; ISS:UniProtKB.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0061099; P:negative regulation of protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IDA:MGI.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:UniProtKB.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISS:UniProtKB.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IDA:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0035810; P:positive regulation of urine volume; ISS:UniProtKB.
DR GO; GO:0070295; P:renal water absorption; ISS:UniProtKB.
DR GO; GO:0046677; P:response to antibiotic; IEA:Ensembl.
DR GO; GO:0000302; P:response to reactive oxygen species; ISS:UniProtKB.
DR GO; GO:0009615; P:response to virus; IDA:UniProtKB.
DR GO; GO:0048705; P:skeletal system morphogenesis; IMP:MGI.
DR GO; GO:0046718; P:viral entry into host cell; ISS:UniProtKB.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR InterPro; IPR018155; Hyaluronidase.
DR PANTHER; PTHR11769; PTHR11769; 1.
DR Pfam; PF01630; Glyco_hydro_56; 1.
DR PIRSF; PIRSF038193; Hyaluronidase; 1.
DR PRINTS; PR00846; GLHYDRLASE56.
DR SUPFAM; SSF51445; SSF51445; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; EGF-like domain; Glycoprotein; Glycosidase;
KW GPI-anchor; Hydrolase; Lipoprotein; Membrane; Receptor; Reference proteome;
KW Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..448
FT /note="Hyaluronidase-2"
FT /id="PRO_0000012101"
FT PROPEP 449..473
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000012102"
FT DOMAIN 361..439
FT /note="EGF-like"
FT ACT_SITE 135
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT LIPID 448
FT /note="GPI-anchor amidated asparagine; alternate"
FT /evidence="ECO:0000255"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 357
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 390
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 448
FT /note="N-linked (GlcNAc...) asparagine; alternate"
FT /evidence="ECO:0000255"
FT DISULFID 47..340
FT /evidence="ECO:0000250"
FT DISULFID 211..227
FT /evidence="ECO:0000250"
FT DISULFID 365..376
FT /evidence="ECO:0000250"
FT DISULFID 370..427
FT /evidence="ECO:0000250"
FT DISULFID 429..438
FT /evidence="ECO:0000250"
FT CONFLICT 26..27
FT /note="TA -> KP (in Ref. 1; CAA03888/CAA03889)"
FT /evidence="ECO:0000305"
FT CONFLICT 193..199
FT /note="YVKAVRP -> LRQGSQT (in Ref. 1; CAA03888)"
FT /evidence="ECO:0000305"
FT CONFLICT 250
FT /note="Missing (in Ref. 1; CAA03888)"
FT /evidence="ECO:0000305"
FT CONFLICT 269..272
FT /note="SFRV -> RFGG (in Ref. 1; CAA03888)"
FT /evidence="ECO:0000305"
FT CONFLICT 355
FT /note="I -> V (in Ref. 2; AAK28481)"
FT /evidence="ECO:0000305"
FT CONFLICT 383
FT /note="A -> V (in Ref. 1; CAA03888/CAA03889)"
FT /evidence="ECO:0000305"
FT CONFLICT 416..422
FT /note="ADLNYLQ -> RDRQLPE (in Ref. 1; CAA03888)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 473 AA; 53618 MW; DD433C9FFCF8147C CRC64;
MRAGLGPIIT LALVLEVAWA GELKPTAPPI FTGRPFVVAW NVPTQECAPR HKVPLDLRAF
DVKATPNEGF FNQNITTFYY DRLGLYPRFD AAGTSVHGGV PQNGSLCAHL PMLKESVERY
IQTQEPGGLA VIDWEEWRPV WVRNWQEKDV YRQSSRQLVA SRHPDWPSDR VMKQAQYEFE
FAARQFMLNT LRYVKAVRPQ HLWGFYLFPD CYNHDYVQNW ESYTGRCPDV EVARNDQLAW
LWAESTALFP SVYLDETLAS SVHSRNFVSF RVREALRVAH THHANHALPV YVFTRPTYTR
GLTGLSQVDL ISTIGESAAL GSAGVIFWGD SEDASSMETC QYLKNYLTQL LVPYIVNVSW
ATQYCSWTQC HGHGRCVRRN PSANTFLHLN ASSFRLVPGH TPSEPQLRPE GQLSEADLNY
LQKHFRCQCY LGWGGEQCQR NYKGAAGNAS RAWAGSHLTS LLGLVAVALT WTL
