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Database: UniProt
Entry: HYAL4_HUMAN
LinkDB: HYAL4_HUMAN
Original site: HYAL4_HUMAN 
ID   HYAL4_HUMAN             Reviewed;         481 AA.
AC   Q2M3T9; D0VXG1; Q9UL99; Q9Y6T9;
DT   11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT   11-SEP-2007, sequence version 2.
DT   08-MAY-2019, entry version 112.
DE   RecName: Full=Hyaluronidase-4;
DE            Short=Hyal-4;
DE            EC=3.2.1.35;
DE   AltName: Full=Chondroitin sulfate endo-beta-N-acetylgalactosaminidase;
DE   AltName: Full=Chondroitin sulfate hydrolase;
DE            Short=CSHY;
DE   AltName: Full=Hyaluronoglucosaminidase-4;
GN   Name=HYAL4;
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], 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], FUNCTION, AND BIOPHYSICOCHEMICAL
RP   PROPERTIES.
RX   PubMed=19889881; DOI=10.1093/glycob/cwp174;
RA   Kaneiwa T., Mizumoto S., Sugahara K., Yamada S.;
RT   "Identification of human hyaluronidase-4 as a novel chondroitin
RT   sulfate hydrolase that preferentially cleaves the galactosaminidic
RT   linkage in the trisulfated tetrasaccharide sequence.";
RL   Glycobiology 20:300-309(2010).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
RA   Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA   Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA   Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA   Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA   Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA   Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA   Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA   Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA   Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA   Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA   Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA   Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
RA   Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA   Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA   Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA   Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA   Waterston R.H., Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12690205; DOI=10.1126/science.1083423;
RA   Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA   Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA   Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA   Kanematsu E., Gentles S., Christopoulos C.C., Choufani S.,
RA   Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
RA   Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
RA   Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
RA   Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
RA   Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
RA   Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
RA   Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
RA   Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
RA   Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
RA   Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
RA   Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
RA   Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA   Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W.,
RA   Mural R.J., Adams M.D., Tsui L.-C.;
RT   "Human chromosome 7: DNA sequence and biology.";
RL   Science 300:767-772(2003).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-346.
RC   TISSUE=Cerebellum;
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   [7]
RP   FUNCTION, AND 3D-STRUCTURE MODELING.
RX   PubMed=16104017; DOI=10.1002/prot.20592;
RA   Jedrzejas M.J., Stern R.;
RT   "Structures of vertebrate hyaluronidases and their unique enzymatic
RT   mechanism of hydrolysis.";
RL   Proteins 61:227-238(2005).
RN   [8]
RP   GLYCOSYLATION AT ASN-177.
RX   PubMed=19139490; DOI=10.1074/mcp.M800504-MCP200;
RA   Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F.,
RA   Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y.,
RA   Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.;
RT   "A strategy for precise and large scale identification of core
RT   fucosylated glycoproteins.";
RL   Mol. Cell. Proteomics 8:913-923(2009).
CC   -!- FUNCTION: Endo-hyaluronidase that degrades hyaluronan to smaller
CC       oligosaccharide fragments. Has also chondroitin sulfate hydrolase
CC       activity, The best substrate being the galactosaminidic linkage in
CC       the sequence of a trisulfated tetrasaccharide.
CC       {ECO:0000269|PubMed:16104017, ECO:0000269|PubMed:19889881}.
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;
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 4.5-5 (for chondroitin sulfate hydrolase
CC         activity). {ECO:0000269|PubMed:19889881};
CC       Temperature dependence:
CC         Optimum temperature is 37 degrees Celsius.
CC         {ECO:0000269|PubMed:19889881};
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC       protein {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Detected in placenta and skeletal muscle.
CC       {ECO:0000269|PubMed:10493834}.
CC   -!- SIMILARITY: Belongs to the glycosyl hydrolase 56 family.
CC       {ECO:0000305}.
DR   EMBL; AF009010; AAC98883.1; -; mRNA.
DR   EMBL; AB470346; BAI49593.1; -; mRNA.
DR   EMBL; AC006029; AAD43186.1; -; Genomic_DNA.
DR   EMBL; CH236947; EAL24331.1; -; Genomic_DNA.
DR   EMBL; CH471070; EAW83603.1; -; Genomic_DNA.
DR   EMBL; BC104788; AAI04789.1; -; mRNA.
DR   EMBL; BC104790; AAI04791.1; -; mRNA.
DR   CCDS; CCDS5789.1; -.
DR   RefSeq; NP_036401.2; NM_012269.2.
DR   RefSeq; XP_011514292.1; XM_011515990.2.
DR   RefSeq; XP_016867400.1; XM_017011911.1.
DR   SMR; Q2M3T9; -.
DR   BioGrid; 117097; 5.
DR   IntAct; Q2M3T9; 1.
DR   MINT; Q2M3T9; -.
DR   STRING; 9606.ENSP00000223026; -.
DR   CAZy; GH56; Glycoside Hydrolase Family 56.
DR   GlyConnect; 1382; -.
DR   iPTMnet; Q2M3T9; -.
DR   PhosphoSitePlus; Q2M3T9; -.
DR   BioMuta; HYAL4; -.
DR   DMDM; 158564281; -.
DR   PaxDb; Q2M3T9; -.
DR   PRIDE; Q2M3T9; -.
DR   ProteomicsDB; 61382; -.
DR   DNASU; 23553; -.
DR   Ensembl; ENST00000223026; ENSP00000223026; ENSG00000106302.
DR   Ensembl; ENST00000476325; ENSP00000417186; ENSG00000106302.
DR   GeneID; 23553; -.
DR   KEGG; hsa:23553; -.
DR   UCSC; uc003vlc.4; human.
DR   CTD; 23553; -.
DR   DisGeNET; 23553; -.
DR   GeneCards; HYAL4; -.
DR   H-InvDB; HIX0033519; -.
DR   HGNC; HGNC:5323; HYAL4.
DR   HPA; HPA029453; -.
DR   MIM; 604510; gene.
DR   neXtProt; NX_Q2M3T9; -.
DR   OpenTargets; ENSG00000106302; -.
DR   PharmGKB; PA29574; -.
DR   eggNOG; ENOG410IECJ; Eukaryota.
DR   eggNOG; ENOG410XPZT; LUCA.
DR   GeneTree; ENSGT00950000182708; -.
DR   HOGENOM; HOG000015133; -.
DR   InParanoid; Q2M3T9; -.
DR   KO; K01197; -.
DR   OMA; CHNYNVY; -.
DR   OrthoDB; 1096692at2759; -.
DR   PhylomeDB; Q2M3T9; -.
DR   TreeFam; TF321598; -.
DR   BioCyc; MetaCyc:HS02883-MONOMER; -.
DR   BRENDA; 3.2.1.35; 2681.
DR   GenomeRNAi; 23553; -.
DR   PRO; PR:Q2M3T9; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   Bgee; ENSG00000106302; Expressed in 67 organ(s), highest expression level in triceps brachii.
DR   ExpressionAtlas; Q2M3T9; baseline and differential.
DR   Genevisible; Q2M3T9; HS.
DR   GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0004415; F:hyalurononglucosaminidase activity; TAS:ProtInc.
DR   GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR   GO; GO:0030207; P:chondroitin sulfate catabolic process; IEA:Ensembl.
DR   GO; GO:0006027; P:glycosaminoglycan catabolic process; TAS:ProtInc.
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   Complete proteome; Disulfide bond; EGF-like domain; Glycoprotein;
KW   Glycosidase; Hydrolase; Membrane; Polymorphism; Reference proteome;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN         1    481       Hyaluronidase-4.
FT                                /FTId=PRO_0000301999.
FT   TOPO_DOM      1      8       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM      9     29       Helical. {ECO:0000255}.
FT   TOPO_DOM     30    453       Extracellular. {ECO:0000255}.
FT   TRANSMEM    454    474       Helical. {ECO:0000255}.
FT   TOPO_DOM    475    481       Cytoplasmic. {ECO:0000255}.
FT   ACT_SITE    147    147       Proton donor. {ECO:0000250}.
FT   CARBOHYD     86     86       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    115    115       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    177    177       N-linked (GlcNAc...) (complex)
FT                                asparagine.
FT                                {ECO:0000269|PubMed:19139490}.
FT   CARBOHYD    343    343       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID     59    351       {ECO:0000250}.
FT   DISULFID    223    237       {ECO:0000250}.
FT   DISULFID    376    387       {ECO:0000250}.
FT   DISULFID    381    435       {ECO:0000250}.
FT   DISULFID    437    446       {ECO:0000250}.
FT   VARIANT     346    346       A -> S (in dbSNP:rs6949082).
FT                                {ECO:0000269|PubMed:15489334}.
FT                                /FTId=VAR_034936.
FT   CONFLICT    263    263       G -> C (in Ref. 1; AAC98883).
FT                                {ECO:0000305}.
SQ   SEQUENCE   481 AA;  54249 MW;  9D530009AA898D1F CRC64;
     MKVLSEGQLK LCVVQPVHLT SWLLIFFILK SISCLKPARL PIYQRKPFIA AWNAPTDQCL
     IKYNLRLNLK MFPVIGSPLA KARGQNVTIF YVNRLGYYPW YTSQGVPING GLPQNISLQV
     HLEKADQDIN YYIPAEDFSG LAVIDWEYWR PQWARNWNSK DVYRQKSRKL ISDMGKNVSA
     TDIEYLAKVT FEESAKAFMK ETIKLGIKSR PKGLWGYYLY PDCHNYNVYA PNYSGSCPED
     EVLRNNELSW LWNSSAALYP SIGVWKSLGD SENILRFSKF RVHESMRIST MTSHDYALPV
     FVYTRLGYRD EPLFFLSKQD LVSTIGESAA LGAAGIVIWG DMNLTASKAN CTKVKQFVSS
     DLGSYIANVT RAAEVCSLHL CRNNGRCIRK MWNAPSYLHL NPASYHIEAS EDGEFTVKGK
     ASDTDLAVMA DTFSCHCYQG YEGADCREIK TADGCSGVSP SPGSLMTLCL LLLASYRSIQ
     L
//
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