ID HYAL3_HUMAN Reviewed; 417 AA. AC O43820; O60540; Q8NFK2; Q8NFK3; Q8NFK4; Q96E56; Q9BRW9; DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1998, sequence version 1. DT 13-FEB-2019, entry version 148. DE RecName: Full=Hyaluronidase-3; DE Short=Hyal-3; DE EC=3.2.1.35 {ECO:0000269|PubMed:12084718}; DE AltName: Full=Hyaluronoglucosaminidase-3; DE AltName: Full=Lung carcinoma protein 3; DE Short=LuCa-3; DE Flags: Precursor; GN Name=HYAL3; Synonyms=LUCA3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RX PubMed=10493834; DOI=10.1006/geno.1999.5876; RA Csoka A.B., Scherer S.W., Stern R.; RT "Expression analysis of six paralogous human hyaluronidase genes RT clustered on chromosomes 3p21 and 7q31."; RL Genomics 60:356-361(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), CATALYTIC RP ACTIVITY, AND ALTERNATIVE SPLICING. RX PubMed=12084718; DOI=10.1074/jbc.M203821200; RA Lokeshwar V.B., Schroeder G.L., Carey R.I., Soloway M.S., Iida N.; RT "Regulation of hyaluronidase activity by alternative mRNA splicing."; RL J. Biol. Chem. 277:33654-33663(2002). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Fong K., Bader S., Lee C.-C., Latif F., Sekido Y., Duh F.-M., RA Wei M.-H., Cundiff S., Lerman M.I., Minna J.D.; RT "LUCA-3 a third hyaluronidase gene and candidate tumor suppressor gene RT located in the 3p21.3 homozygous deletion region."; RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., RA Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT RP TYR-113. RC TISSUE=Bone marrow, and Ovary; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP TISSUE SPECIFICITY. RX PubMed=20586096; DOI=10.1002/mrd.21217; RA Reese K.L., Aravindan R.G., Griffiths G.S., Shao M., Wang Y., RA Galileo D.S., Atmuri V., Triggs-Raine B.L., Martin-Deleon P.A.; RT "Acidic hyaluronidase activity is present in mouse sperm and is RT reduced in the absence of SPAM1: evidence for a role for hyaluronidase RT 3 in mouse and human sperm."; RL Mol. Reprod. Dev. 77:759-772(2010). RN [7] RP TISSUE SPECIFICITY, AND INDUCTION. RX PubMed=21699545; DOI=10.1111/j.1751-1097.2011.00959.x; RA Kurdykowski S., Mine S., Bardey V., Danoux L., Jeanmaire C., Pauly G., RA Brabencova E., Wegrowski Y., Maquart F.X.; RT "Ultraviolet-B irradiation induces differential regulations of RT hyaluronidase expression and activity in normal human keratinocytes."; RL Photochem. Photobiol. 87:1105-1112(2011). CC -!- FUNCTION: Facilitates sperm penetration into the layer of cumulus CC cells surrounding the egg by digesting hyaluronic acid. Involved CC in induction of the acrosome reaction in the sperm. Involved in CC follicular atresia, the breakdown of immature ovarian follicles CC that are not selected to ovulate. Induces ovarian granulosa cell CC apoptosis, possibly via apoptotic signaling pathway involving CC CASP8 and CASP3 activation, and poly(ADP-ribose) polymerase (PARP) CC cleavage. Has no hyaluronidase activity in embryonic fibroblasts CC in vitro. Has no hyaluronidase activity in granulosa cells in CC vitro. {ECO:0000250|UniProtKB:Q8VEI3}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Random hydrolysis of (1->4)-linkages between N-acetyl- CC beta-D-glucosamine and D-glucuronate residues in hyaluronate.; CC EC=3.2.1.35; Evidence={ECO:0000269|PubMed:12084718}; CC -!- INTERACTION: CC O75553:DAB1; NbExp=3; IntAct=EBI-3913399, EBI-7875264; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q8VEI3}. CC Cell membrane {ECO:0000250|UniProtKB:Q8VEI3}. Cytoplasmic vesicle, CC secretory vesicle, acrosome {ECO:0000250|UniProtKB:Q8VEI3}. CC Endoplasmic reticulum {ECO:0000250|UniProtKB:Q8VEI3}. Early CC endosome {ECO:0000250|UniProtKB:Q8VEI3}. Note=Mostly present in CC low-density vesicles. Low levels in higher density vesicles of CC late endosomes and lysosomes. Localized in punctate cytoplasmic CC vesicles and in perinuclear structures, but does not colocalize CC with LAMP1. Localized on the plasma membrane over the acrosome and CC on the surface of the midpiece of the sperm tail. CC {ECO:0000250|UniProtKB:Q8VEI3}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=O43820-1; Sequence=Displayed; CC Name=2; Synonyms=HYAL3v1; CC IsoId=O43820-2; Sequence=VSP_020194; CC Note=Enzymatically inactive.; CC Name=3; Synonyms=HYAL3v2; CC IsoId=O43820-3; Sequence=VSP_020192, VSP_020193; CC Note=Enzymatically inactive.; CC Name=4; Synonyms=HYAL3v3; CC IsoId=O43820-4; Sequence=VSP_020192, VSP_020193, VSP_020194; CC Note=Enzymatically inactive.; CC -!- TISSUE SPECIFICITY: Expressed in sperm (PubMed:20586096). Highly CC expressed in epidermis of the skin, where it is expressed CC intracellularily in the deep horny layer (at protein level) CC (PubMed:21699545). Bone marrow, testis and kidney CC (PubMed:10493834). {ECO:0000269|PubMed:10493834, CC ECO:0000269|PubMed:20586096, ECO:0000269|PubMed:21699545}. CC -!- INDUCTION: Expression is not significantly up- or down-regulated CC by ultraviolet irradiation B (UV-B) in epidermis CC (PubMed:21699545). {ECO:0000269|PubMed:21699545}. CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q8VEI3}. CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 56 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC70915.1; Type=Frameshift; Positions=410; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; AF036035; AAD04257.1; -; mRNA. DR EMBL; AF502909; AAM60775.1; -; mRNA. DR EMBL; AF502910; AAM60776.1; -; mRNA. DR EMBL; AF502911; AAM60777.1; -; mRNA. DR EMBL; AF502912; AAM60778.1; -; mRNA. DR EMBL; AF040710; AAC70915.1; ALT_FRAME; mRNA. DR EMBL; U73167; AAC02729.1; -; Genomic_DNA. DR EMBL; BC005896; AAH05896.1; -; mRNA. DR EMBL; BC012892; AAH12892.1; -; mRNA. DR CCDS; CCDS2815.1; -. [O43820-1] DR CCDS; CCDS56257.1; -. [O43820-2] DR CCDS; CCDS56259.1; -. [O43820-4] DR CCDS; CCDS56260.1; -. [O43820-3] DR RefSeq; NP_001186958.1; NM_001200029.1. [O43820-1] DR RefSeq; NP_001186959.1; NM_001200030.1. [O43820-2] DR RefSeq; NP_001186960.1; NM_001200031.1. [O43820-3] DR RefSeq; NP_001186961.1; NM_001200032.1. [O43820-4] DR RefSeq; NP_003540.2; NM_003549.3. [O43820-1] DR UniGene; Hs.129910; -. DR UniGene; Hs.729310; -. DR ProteinModelPortal; O43820; -. DR SMR; O43820; -. DR BioGrid; 113967; 4. DR IntAct; O43820; 4. DR STRING; 9606.ENSP00000337425; -. DR CAZy; GH56; Glycoside Hydrolase Family 56. DR BioMuta; HYAL3; -. DR PaxDb; O43820; -. DR PeptideAtlas; O43820; -. DR PRIDE; O43820; -. DR ProteomicsDB; 49183; -. DR ProteomicsDB; 49184; -. [O43820-2] DR ProteomicsDB; 49185; -. [O43820-3] DR ProteomicsDB; 49186; -. [O43820-4] DR DNASU; 8372; -. DR Ensembl; ENST00000336307; ENSP00000337425; ENSG00000186792. [O43820-1] DR Ensembl; ENST00000359051; ENSP00000351946; ENSG00000186792. [O43820-2] DR Ensembl; ENST00000415204; ENSP00000401092; ENSG00000186792. [O43820-3] DR Ensembl; ENST00000450982; ENSP00000391922; ENSG00000186792. [O43820-2] DR Ensembl; ENST00000513170; ENSP00000424633; ENSG00000186792. [O43820-4] DR Ensembl; ENST00000621157; ENSP00000479935; ENSG00000186792. [O43820-1] DR GeneID; 8372; -. DR KEGG; hsa:8372; -. DR UCSC; uc003czd.3; human. [O43820-1] DR CTD; 8372; -. DR DisGeNET; 8372; -. DR EuPathDB; HostDB:ENSG00000186792.16; -. DR GeneCards; HYAL3; -. DR HGNC; HGNC:5322; HYAL3. DR HPA; HPA049402; -. DR MIM; 604038; gene. DR neXtProt; NX_O43820; -. DR OpenTargets; ENSG00000186792; -. DR PharmGKB; PA29573; -. DR eggNOG; ENOG410IH0U; Eukaryota. DR eggNOG; ENOG410XPZT; LUCA. DR GeneTree; ENSGT00940000154357; -. DR HOVERGEN; HBG052053; -. DR InParanoid; O43820; -. DR KO; K01197; -. DR OMA; FPACGNG; -. DR OrthoDB; 1096692at2759; -. DR PhylomeDB; O43820; -. DR TreeFam; TF321598; -. DR BioCyc; MetaCyc:ENSG00000114366-MONOMER; -. DR BRENDA; 3.2.1.35; 2681. DR Reactome; R-HSA-2024101; CS/DS degradation. DR Reactome; R-HSA-2160916; Hyaluronan uptake and degradation. DR ChiTaRS; HYAL3; human. DR GeneWiki; HYAL3; -. DR GenomeRNAi; 8372; -. DR PRO; PR:O43820; -. DR Proteomes; UP000005640; Chromosome 3. DR Bgee; ENSG00000186792; Expressed in 89 organ(s), highest expression level in caudate nucleus. DR ExpressionAtlas; O43820; baseline and differential. DR Genevisible; O43820; HS. DR GO; GO:0002080; C:acrosomal membrane; ISS:UniProtKB. DR GO; GO:0001669; C:acrosomal vesicle; ISS:UniProtKB. DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB. DR GO; GO:0005769; C:early endosome; ISS:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0005764; C:lysosome; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0097225; C:sperm midpiece; ISS:UniProtKB. DR GO; GO:0033906; F:hyaluronoglucuronidase activity; IDA:UniProtKB. 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; IEP:UniProtKB. DR GO; GO:0071347; P:cellular response to interleukin-1; IDA:UniProtKB. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:UniProtKB. DR GO; GO:0071493; P:cellular response to UV-B; IDA:UniProtKB. DR GO; GO:0030214; P:hyaluronan catabolic process; IDA:UniProtKB. DR GO; GO:0006954; P:inflammatory response; IDA:UniProtKB. DR GO; GO:2000355; P:negative regulation of ovarian follicle development; ISS:UniProtKB. DR GO; GO:0001552; P:ovarian follicle atresia; ISS:UniProtKB. DR GO; GO:0007341; P:penetration of zona pellucida; ISS:UniProtKB. DR GO; GO:2000368; P:positive regulation of acrosomal vesicle exocytosis; ISS:UniProtKB. DR GO; GO:0046677; P:response to antibiotic; IEP:UniProtKB. DR GO; GO:0009615; P:response to virus; IDA:UniProtKB. DR GO; GO:0046718; P:viral entry into host cell; IEA:GOC. DR Gene3D; 3.20.20.70; -; 1. DR InterPro; IPR013785; Aldolase_TIM. 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; 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 Alternative splicing; Cell membrane; Complete proteome; KW Cytoplasmic vesicle; Disulfide bond; EGF-like domain; KW Endoplasmic reticulum; Endosome; Fertilization; Glycoprotein; KW Glycosidase; Hydrolase; Membrane; Polymorphism; Reference proteome; KW Secreted; Signal. FT SIGNAL 1 20 {ECO:0000255}. FT CHAIN 21 417 Hyaluronidase-3. FT /FTId=PRO_0000248200. FT DOMAIN 352 407 EGF-like. FT ACT_SITE 129 129 Proton donor. FT {ECO:0000250|UniProtKB:Q12794}. FT CARBOHYD 69 69 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 215 215 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 42 331 {ECO:0000250|UniProtKB:Q12794}. FT DISULFID 205 220 {ECO:0000250|UniProtKB:Q12794}. FT DISULFID 356 367 {ECO:0000250|UniProtKB:Q12794}. FT DISULFID 361 395 {ECO:0000250|UniProtKB:Q12794}. FT DISULFID 397 406 {ECO:0000250|UniProtKB:Q12794}. FT VAR_SEQ 1 249 Missing (in isoform 3 and isoform 4). FT {ECO:0000303|PubMed:12084718}. FT /FTId=VSP_020192. FT VAR_SEQ 250 250 R -> M (in isoform 3 and isoform 4). FT {ECO:0000303|PubMed:12084718}. FT /FTId=VSP_020193. FT VAR_SEQ 299 328 Missing (in isoform 2 and isoform 4). FT {ECO:0000303|PubMed:12084718}. FT /FTId=VSP_020194. FT VARIANT 113 113 H -> Y (in dbSNP:rs13100173). FT {ECO:0000269|PubMed:15489334}. FT /FTId=VAR_027263. FT CONFLICT 54 54 A -> S (in Ref. 5; AAH05896). FT {ECO:0000305}. SQ SEQUENCE 417 AA; 46501 MW; A6E7DE5369EF2BB8 CRC64; MTTQLGPALV LGVALCLGCG QPLPQVPERP FSVLWNVPSA HCEARFGVHL PLNALGIIAN RGQHFHGQNM TIFYKNQLGL YPYFGPRGTA HNGGIPQALP LDRHLALAAY QIHHSLRPGF AGPAVLDWEE WCPLWAGNWG RRRAYQAASW AWAQQVFPDL DPQEQLYKAY TGFEQAARAL MEDTLRVAQA LRPHGLWGFY HYPACGNGWH SMASNYTGRC HAATLARNTQ LHWLWAASSA LFPSIYLPPR LPPAHHQAFV RHRLEEAFRV ALVGHRHPLP VLAYVRLTHR RSGRFLSQDD LVQSIGVSAA LGAAGVVLWG DLSLSSSEEE CWHLHDYLVD TLGPYVINVT RAAMACSHQR CHGHGRCARR DPGQMEAFLH LWPDGSLGDW KSFSCHCYWG WAGPTCQEPR PGPKEAV //