ID   HYAL3_MOUSE             Reviewed;         412 AA.
AC   Q8VEI3; B1AV95; Q8VBX7; Q8VI77;
DT   05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   24-JAN-2024, entry version 151.
DE   RecName: Full=Hyaluronidase-3;
DE            Short=Hyal-3;
DE            EC=3.2.1.35;
DE   AltName: Full=Hyaluronoglucosaminidase-3;
DE   Flags: Precursor;
GN   Name=Hyal3; Synonyms=Hyl3;
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 [MRNA], AND TISSUE SPECIFICITY.
RC   STRAIN=CD-1;
RX   PubMed=11929860; DOI=10.1074/jbc.m108991200;
RA   Shuttleworth T.L., Wilson M.D., Wicklow B.A., Wilkins J.A.,
RA   Triggs-Raine B.L.;
RT   "Characterization of the murine hyaluronidase gene region reveals complex
RT   organization and cotranscription of Hyal1 with downstream genes, Fus2 and
RT   Hyal3.";
RL   J. Biol. Chem. 277:23008-23018(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Csoka A.B.;
RT   "Cloning and characterization of human and mouse HYAL3, a third somatic
RT   hyaluronidase paralog.";
RL   Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Csoka A.B.;
RT   "Genomic sequence of the mouse Hyal1 locus encoding the mouse Hyal1, Fus2,
RT   and Hyal3 genes.";
RL   Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Mammary tumor;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX   PubMed=18653706; DOI=10.1210/en.2008-0175;
RA   Orimoto A.M., Dumaresq-Doiron K., Jiang J.Y., Tanphaichitr N., Tsang B.K.,
RA   Carmona E.;
RT   "Mammalian hyaluronidase induces ovarian granulosa cell apoptosis and is
RT   involved in follicular atresia.";
RL   Endocrinology 149:5835-5847(2008).
RN   [7]
RP   FUNCTION, SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX   PubMed=18234732; DOI=10.1093/glycob/cwn006;
RA   Hemming R., Martin D.C., Slominski E., Nagy J.I., Halayko A.J., Pind S.,
RA   Triggs-Raine B.;
RT   "Mouse Hyal3 encodes a 45- to 56-kDa glycoprotein whose overexpression
RT   increases hyaluronidase 1 activity in cultured cells.";
RL   Glycobiology 18:280-289(2008).
RN   [8]
RP   TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX   PubMed=18762256; DOI=10.1016/j.matbio.2008.07.006;
RA   Atmuri V., Martin D.C., Hemming R., Gutsol A., Byers S., Sahebjam S.,
RA   Thliveris J.A., Mort J.S., Carmona E., Anderson J.E., Dakshinamurti S.,
RA   Triggs-Raine B.;
RT   "Hyaluronidase 3 (HYAL3) knockout mice do not display evidence of
RT   hyaluronan accumulation.";
RL   Matrix Biol. 27:653-660(2008).
RN   [9]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP   LOCATION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX   PubMed=20586096; DOI=10.1002/mrd.21217;
RA   Reese K.L., Aravindan R.G., Griffiths G.S., Shao M., Wang Y., Galileo D.S.,
RA   Atmuri V., Triggs-Raine B.L., Martin-Deleon P.A.;
RT   "Acidic hyaluronidase activity is present in mouse sperm and is reduced in
RT   the absence of SPAM1: evidence for a role for hyaluronidase 3 in mouse and
RT   human sperm.";
RL   Mol. Reprod. Dev. 77:759-772(2010).
CC   -!- FUNCTION: Facilitates sperm penetration into the layer of cumulus cells
CC       surrounding the egg by digesting hyaluronic acid. Involved in induction
CC       of the acrosome reaction in the sperm (PubMed:20586096). Involved in
CC       follicular atresia, the breakdown of immature ovarian follicles that
CC       are not selected to ovulate. Induces ovarian granulosa cell apoptosis,
CC       possibly via apoptotic signaling pathway involving CASP8 and CASP3
CC       activation, and poly(ADP-ribose) polymerase (PARP) cleavage
CC       (PubMed:18653706). Has no hyaluronidase activity in embryonic
CC       fibroblasts in vitro (PubMed:18234732). Has no hyaluronidase activity
CC       in granulosa cells in vitro (PubMed:18653706).
CC       {ECO:0000269|PubMed:18234732, ECO:0000269|PubMed:18653706,
CC       ECO:0000269|PubMed:20586096}.
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         Evidence={ECO:0000269|PubMed:20586096};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 7. Higher activity at pH 4 than at pH 7 in sperm.
CC         {ECO:0000269|PubMed:20586096};
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:20586096}. Cell
CC       membrane {ECO:0000269|PubMed:20586096}. Cytoplasmic vesicle, secretory
CC       vesicle, acrosome {ECO:0000269|PubMed:20586096}. Endoplasmic reticulum
CC       {ECO:0000269|PubMed:18234732}. Early endosome
CC       {ECO:0000269|PubMed:18234732}. Note=Mostly present in low-density
CC       vesicles. Low levels in higher density vesicles of late endosomes and
CC       lysosomes. Localized in punctate cytoplasmic vesicles and in
CC       perinuclear structures, but does not colocalize with LAMP1
CC       (PubMed:18234732). Localized on the plasma membrane over the acrosome
CC       and on the surface of the midpiece of the sperm tail (PubMed:20586096).
CC       {ECO:0000269|PubMed:18234732, ECO:0000269|PubMed:20586096}.
CC   -!- TISSUE SPECIFICITY: Expressed in testis, epididymal tissue, epididymal
CC       luminal fluid (ELF), acrosome-intact (AI) sperm and caput (CAP), corpus
CC       (COR) and caudal (CAU) sperm. Higher expression in sperm than testis
CC       (at protein level) (PubMed:20586096). Liver, kidney, skin, brain,
CC       stomach and testis (PubMed:11929860). Expressed mainly in granulosa
CC       cells of the ovaries. Expressed in small and large antral follicles.
CC       Not present in theca or stroma cells (PubMed:18653706). Expressed in
CC       testis and liver (PubMed:18762256). Expressed in testis and CAP, COR,
CC       and CAU epididymis tissue (PubMed:20586096).
CC       {ECO:0000269|PubMed:11929860, ECO:0000269|PubMed:18653706,
CC       ECO:0000269|PubMed:18762256, ECO:0000269|PubMed:20586096}.
CC   -!- INDUCTION: Up-regulated expression in apoptotic granulosa cells and in
CC       atretic follicles of the ovaries (PubMed:18653706).
CC       {ECO:0000269|PubMed:18653706}.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:18234732}.
CC   -!- DISRUPTION PHENOTYPE: No visible phenotype. Both male and female mice
CC       are viable. Skeletal features, joints, whole-body weights, organ
CC       weights, organ morphologies and the serum hyaluronic acid (HA) levels
CC       are normal. No evidence of glycosaminoglycan accumulation, including
CC       vacuolization, in tissues analyzed including liver, lung, kidney,
CC       spleen, skin, fat, testes and seminal vesicles at 12-14 months of age.
CC       No difference in tissue organization or connective tissue thickness.
CC       Only a subtle change in the alveolar structure and extracellular matrix
CC       thickness in lung tissue sections at 12-14 months of age. Lungs have
CC       larger alveoli and more areas of thickened interstitium. Lung tissues
CC       from 6 months old mice show more immature alveoli compared to wild-type
CC       (PubMed:18762256). Mice are fully fertile (PubMed:18762256,
CC       PubMed:20586096). Sperm show delayed cumulus penetration and reduced
CC       acrosomal exocytosis (PubMed:20586096). {ECO:0000269|PubMed:18762256,
CC       ECO:0000269|PubMed:20586096}.
CC   -!- SIMILARITY: Belongs to the glycosyl hydrolase 56 family. {ECO:0000305}.
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DR   EMBL; AY048681; AAL06145.1; -; mRNA.
DR   EMBL; AF074489; AAL54882.1; -; mRNA.
DR   EMBL; AF075576; AAL54883.1; -; Genomic_DNA.
DR   EMBL; AF338323; AAL57175.1; -; Genomic_DNA.
DR   EMBL; AL672219; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC018457; AAH18457.1; -; mRNA.
DR   CCDS; CCDS23499.1; -.
DR   RefSeq; NP_821139.2; NM_178020.3.
DR   AlphaFoldDB; Q8VEI3; -.
DR   SMR; Q8VEI3; -.
DR   STRING; 10090.ENSMUSP00000042667; -.
DR   CAZy; GH56; Glycoside Hydrolase Family 56.
DR   GlyCosmos; Q8VEI3; 2 sites, No reported glycans.
DR   GlyGen; Q8VEI3; 2 sites.
DR   PaxDb; 10090-ENSMUSP00000042667; -.
DR   Antibodypedia; 34877; 238 antibodies from 27 providers.
DR   DNASU; 109685; -.
DR   Ensembl; ENSMUST00000040059.9; ENSMUSP00000042667.3; ENSMUSG00000036091.9.
DR   Ensembl; ENSMUST00000148440.8; ENSMUSP00000119499.2; ENSMUSG00000036091.9.
DR   GeneID; 109685; -.
DR   KEGG; mmu:109685; -.
DR   UCSC; uc009rmc.2; mouse.
DR   AGR; MGI:1330288; -.
DR   CTD; 8372; -.
DR   MGI; MGI:1330288; Hyal3.
DR   VEuPathDB; HostDB:ENSMUSG00000036091; -.
DR   eggNOG; ENOG502QTXP; Eukaryota.
DR   GeneTree; ENSGT01020000230364; -.
DR   HOGENOM; CLU_036366_0_0_1; -.
DR   InParanoid; Q8VEI3; -.
DR   OMA; GWATSWH; -.
DR   OrthoDB; 5344684at2759; -.
DR   PhylomeDB; Q8VEI3; -.
DR   TreeFam; TF321598; -.
DR   BRENDA; 3.2.1.35; 3474.
DR   Reactome; R-MMU-2024101; CS/DS degradation.
DR   Reactome; R-MMU-2160916; Hyaluronan uptake and degradation.
DR   BioGRID-ORCS; 109685; 3 hits in 78 CRISPR screens.
DR   PRO; PR:Q8VEI3; -.
DR   Proteomes; UP000000589; Chromosome 9.
DR   RNAct; Q8VEI3; Protein.
DR   Bgee; ENSMUSG00000036091; Expressed in mesodermal cell in embryo and 48 other cell types or tissues.
DR   ExpressionAtlas; Q8VEI3; baseline and differential.
DR   GO; GO:0002080; C:acrosomal membrane; IDA:UniProtKB.
DR   GO; GO:0001669; C:acrosomal vesicle; IDA:UniProtKB.
DR   GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR   GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005764; C:lysosome; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0097225; C:sperm midpiece; IDA:UniProtKB.
DR   GO; GO:0033906; F:hyaluronoglucuronidase activity; ISO:MGI.
DR   GO; GO:0004415; F:hyalurononglucosaminidase activity; IDA:UniProtKB.
DR   GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR   GO; GO:0051216; P:cartilage development; IEA:Ensembl.
DR   GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR   GO; GO:0071347; P:cellular response to interleukin-1; ISO:MGI.
DR   GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR   GO; GO:0071493; P:cellular response to UV-B; ISO:MGI.
DR   GO; GO:0030214; P:hyaluronan catabolic process; IDA:UniProtKB.
DR   GO; GO:0006954; P:inflammatory response; ISO:MGI.
DR   GO; GO:2000355; P:negative regulation of ovarian follicle development; IDA:UniProtKB.
DR   GO; GO:0001552; P:ovarian follicle atresia; IDA:UniProtKB.
DR   GO; GO:0007341; P:penetration of zona pellucida; IMP:UniProtKB.
DR   GO; GO:2000368; P:positive regulation of acrosomal vesicle exocytosis; IMP:UniProtKB.
DR   GO; GO:0046677; P:response to antibiotic; IEA:Ensembl.
DR   GO; GO:0009615; P:response to virus; IDA:UniProtKB.
DR   Gene3D; 3.20.20.70; Aldolase class I; 1.
DR   InterPro; IPR013785; Aldolase_TIM.
DR   InterPro; IPR000742; EGF-like_dom.
DR   InterPro; IPR013111; EGF_extracell.
DR   InterPro; IPR017853; Glycoside_hydrolase_SF.
DR   InterPro; IPR018155; Hyaluronidase.
DR   InterPro; IPR027260; Hyaluronidase-3.
DR   PANTHER; PTHR11769; HYALURONIDASE; 1.
DR   PANTHER; PTHR11769:SF19; HYALURONIDASE-3; 1.
DR   Pfam; PF07974; EGF_2; 1.
DR   Pfam; PF01630; Glyco_hydro_56; 1.
DR   PIRSF; PIRSF038193; Hyaluronidase; 1.
DR   PIRSF; PIRSF500776; Hyaluronidase_3; 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; Q8VEI3; MM.
PE   1: Evidence at protein level;
KW   Cell adhesion; Cell membrane; Cytoplasmic vesicle; Disulfide bond;
KW   EGF-like domain; Endoplasmic reticulum; Endosome; Fertilization;
KW   Glycoprotein; Glycosidase; Hydrolase; Membrane; Reference proteome;
KW   Secreted; Signal.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   CHAIN           23..412
FT                   /note="Hyaluronidase-3"
FT                   /id="PRO_0000248201"
FT   DOMAIN          353..408
FT                   /note="EGF-like"
FT   ACT_SITE        129
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:Q12794"
FT   CARBOHYD        69
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        216
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        42..332
FT                   /evidence="ECO:0000250|UniProtKB:Q12794"
FT   DISULFID        206..221
FT                   /evidence="ECO:0000250|UniProtKB:Q12794"
FT   DISULFID        357..368
FT                   /evidence="ECO:0000250|UniProtKB:Q12794"
FT   DISULFID        362..396
FT                   /evidence="ECO:0000250|UniProtKB:Q12794"
FT   DISULFID        398..407
FT                   /evidence="ECO:0000250|UniProtKB:Q12794"
FT   CONFLICT        228
FT                   /note="R -> Q (in Ref. 1; AAL06145 and 5; AAH18457)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        296
FT                   /note="F -> S (in Ref. 3; AAL54883/AAL57175)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        354
FT                   /note="A -> D (in Ref. 1; AAL06145 and 5; AAH18457)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        397
FT                   /note="H -> R (in Ref. 2; AAL54882 and 3;
FT                   AAL54883/AAL57175)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   412 AA;  46132 MW;  B4EB888C556BE920 CRC64;
     MIMHLGLMMV VGLTLCLMHG QALLQVPEHP FSVVWNVPSA RCKAHFGVHL PLDALGIVAN
     HGQHFHGQNI SIFYKNQFGL YPYFGPRGTA HNGGIPQAVS LDHHLARAAH QILHSLGSSF
     AGLAVLDWEE WYPLWAGNWG PHRQVYLAAS WVWTQQMFPG LDPQEQLHKA HTSFEQAARA
     LMEYTLQLGR TLRPSGLWGF YRYPACGNGW HKMASNYTGH CHAAITTRNT QLRWLWAASS
     ALFPSIYLPP RLPLAYRQAF VRHRLEEAFR VALLEHSHPL PVLAYSRLTH RSSGRFLSLD
     DLMQTIGVSA ALGTAGVVLW GDLSFSSSEE KCWRLHDYLV GTLGPYVINV TKAAMACSHQ
     RCHGHGRCAR KDPGQMEAFL HLQPDDSLGA WNSFRCHCYS GWAGPTCLEP KP
//