HYAL3_MOUSE
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 03-AUG-2022, entry version 143.
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 GlyGen; Q8VEI3; 2 sites.
DR PaxDb; Q8VEI3; -.
DR PRIDE; Q8VEI3; -.
DR ProteomicsDB; 273289; -.
DR Antibodypedia; 34877; 198 antibodies from 27 providers.
DR DNASU; 109685; -.
DR Ensembl; ENSMUST00000040059; ENSMUSP00000042667; ENSMUSG00000036091.
DR Ensembl; ENSMUST00000148440; ENSMUSP00000119499; ENSMUSG00000036091.
DR GeneID; 109685; -.
DR KEGG; mmu:109685; -.
DR UCSC; uc009rmc.2; mouse.
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; FYRFPAC; -.
DR OrthoDB; 1096692at2759; -.
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 73 CRISPR screens.
DR PRO; PR:Q8VEI3; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8VEI3; protein.
DR Bgee; ENSMUSG00000036091; Expressed in right kidney and 45 other tissues.
DR ExpressionAtlas; Q8VEI3; baseline and differential.
DR Genevisible; Q8VEI3; MM.
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; -; 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; PTHR11769; 1.
DR PANTHER; PTHR11769:SF19; PTHR11769:SF19; 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; SSF51445; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 1.
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; AAL54883/
FT 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
