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   24-JAN-2024, entry version 185.
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.ENSMUSP00000141280; -.
DR   CAZy; GH56; Glycoside Hydrolase Family 56.
DR   GlyConnect; 2375; 1 N-Linked glycan (1 site).
DR   GlyCosmos; O35632; 5 sites, 1 glycan.
DR   GlyGen; O35632; 5 sites, 1 N-linked glycan (1 site).
DR   iPTMnet; O35632; -.
DR   PhosphoSitePlus; O35632; -.
DR   jPOST; O35632; -.
DR   PaxDb; 10090-ENSMUSP00000010191; -.
DR   PeptideAtlas; O35632; -.
DR   ProteomicsDB; 273333; -.
DR   Pumba; O35632; -.
DR   Antibodypedia; 30889; 308 antibodies from 32 providers.
DR   DNASU; 15587; -.
DR   Ensembl; ENSMUST00000010191.13; ENSMUSP00000010191.8; ENSMUSG00000010047.13.
DR   Ensembl; ENSMUST00000195752.6; ENSMUSP00000141280.2; ENSMUSG00000010047.13.
DR   GeneID; 15587; -.
DR   KEGG; mmu:15587; -.
DR   UCSC; uc009rlu.1; mouse.
DR   AGR; MGI:1196334; -.
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; TKNRESC; -.
DR   OrthoDB; 5344684at2759; -.
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 80 CRISPR screens.
DR   PRO; PR:O35632; -.
DR   Proteomes; UP000000589; Chromosome 9.
DR   RNAct; O35632; Protein.
DR   Bgee; ENSMUSG00000010047; Expressed in right kidney and 206 other cell types or tissues.
DR   ExpressionAtlas; O35632; baseline and differential.
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:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA:BHF-UCL.
DR   GO; GO:0098552; C:side of membrane; IEA:UniProtKB-KW.
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:0060586; P:multicellular organismal-level 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 phosphatidylinositol 3-kinase/protein kinase B signal transduction; 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; Aldolase class I; 1.
DR   InterPro; IPR013785; Aldolase_TIM.
DR   InterPro; IPR017853; Glycoside_hydrolase_SF.
DR   InterPro; IPR018155; Hyaluronidase.
DR   PANTHER; PTHR11769; HYALURONIDASE; 1.
DR   PANTHER; PTHR11769:SF6; HYALURONIDASE-2; 1.
DR   Pfam; PF01630; Glyco_hydro_56; 1.
DR   PIRSF; PIRSF038193; Hyaluronidase; 1.
DR   PRINTS; PR00846; GLHYDRLASE56.
DR   SUPFAM; SSF51445; (Trans)glycosidases; 1.
DR   PROSITE; PS00022; EGF_1; 1.
DR   PROSITE; PS01186; EGF_2; 1.
DR   Genevisible; O35632; MM.
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
//