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 03-AUG-2022, entry version 128.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 clustered
RT on chromosomes 3p21 and 7q31.";
RL Genomics 60:356-361(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND BIOPHYSICOCHEMICAL 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 sulfate
RT hydrolase that preferentially cleaves the galactosaminidic linkage in the
RT 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., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., 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., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA 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., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., 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., Mural R.J.,
RA 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT 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., Zheng Z.B.,
RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L.,
RA Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core fucosylated
RT 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 the
CC 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-beta-D-
CC glucosamine and D-glucuronate residues in hyaluronate.; EC=3.2.1.35;
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 4.5-5 (for chondroitin sulfate hydrolase activity).
CC {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. {ECO:0000305}.
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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 AlphaFoldDB; Q2M3T9; -.
DR SMR; Q2M3T9; -.
DR BioGRID; 117097; 11.
DR IntAct; Q2M3T9; 2.
DR MINT; Q2M3T9; -.
DR STRING; 9606.ENSP00000223026; -.
DR DrugBank; DB08818; Hyaluronic acid.
DR CAZy; GH56; Glycoside Hydrolase Family 56.
DR GlyConnect; 1382; 3 N-Linked glycans (1 site).
DR GlyGen; Q2M3T9; 5 sites, 3 N-linked glycans (1 site).
DR iPTMnet; Q2M3T9; -.
DR PhosphoSitePlus; Q2M3T9; -.
DR BioMuta; HYAL4; -.
DR DMDM; 158564281; -.
DR PaxDb; Q2M3T9; -.
DR PeptideAtlas; Q2M3T9; -.
DR PRIDE; Q2M3T9; -.
DR ProteomicsDB; 61382; -.
DR Antibodypedia; 31779; 86 antibodies from 18 providers.
DR DNASU; 23553; -.
DR Ensembl; ENST00000223026.9; ENSP00000223026.4; ENSG00000106302.10.
DR Ensembl; ENST00000476325.5; ENSP00000417186.1; ENSG00000106302.10.
DR GeneID; 23553; -.
DR KEGG; hsa:23553; -.
DR MANE-Select; ENST00000223026.9; ENSP00000223026.4; NM_012269.3; NP_036401.2.
DR UCSC; uc003vlc.4; human.
DR CTD; 23553; -.
DR DisGeNET; 23553; -.
DR GeneCards; HYAL4; -.
DR HGNC; HGNC:5323; HYAL4.
DR HPA; ENSG00000106302; Tissue enhanced (placenta, skeletal muscle).
DR MIM; 604510; gene.
DR neXtProt; NX_Q2M3T9; -.
DR OpenTargets; ENSG00000106302; -.
DR PharmGKB; PA29574; -.
DR VEuPathDB; HostDB:ENSG00000106302; -.
DR eggNOG; ENOG502QPZH; Eukaryota.
DR GeneTree; ENSGT01020000230364; -.
DR HOGENOM; CLU_036366_0_0_1; -.
DR InParanoid; Q2M3T9; -.
DR OMA; CVVQPIH; -.
DR OrthoDB; 1096692at2759; -.
DR PhylomeDB; Q2M3T9; -.
DR TreeFam; TF321598; -.
DR BioCyc; MetaCyc:HS02883-MON; -.
DR BRENDA; 3.2.1.35; 2681.
DR PathwayCommons; Q2M3T9; -.
DR SignaLink; Q2M3T9; -.
DR BioGRID-ORCS; 23553; 17 hits in 1066 CRISPR screens.
DR ChiTaRS; HYAL4; human.
DR GenomeRNAi; 23553; -.
DR Pharos; Q2M3T9; Tbio.
DR PRO; PR:Q2M3T9; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q2M3T9; protein.
DR Bgee; ENSG00000106302; Expressed in triceps brachii and 80 other tissues.
DR ExpressionAtlas; Q2M3T9; baseline and differential.
DR Genevisible; Q2M3T9; HS.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004415; F:hyalurononglucosaminidase activity; IBA:GO_Central.
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 GO; GO:0030214; P:hyaluronan catabolic process; IBA:GO_Central.
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 Disulfide bond; EGF-like domain; Glycoprotein; Glycosidase; Hydrolase;
KW Membrane; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..481
FT /note="Hyaluronidase-4"
FT /id="PRO_0000301999"
FT TOPO_DOM 1..8
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..453
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 454..474
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 475..481
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ACT_SITE 147
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT CARBOHYD 86
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 115
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 177
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:19139490"
FT CARBOHYD 343
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 59..351
FT /evidence="ECO:0000250"
FT DISULFID 223..237
FT /evidence="ECO:0000250"
FT DISULFID 376..387
FT /evidence="ECO:0000250"
FT DISULFID 381..435
FT /evidence="ECO:0000250"
FT DISULFID 437..446
FT /evidence="ECO:0000250"
FT VARIANT 346
FT /note="A -> S (in dbSNP:rs6949082)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_034936"
FT CONFLICT 263
FT /note="G -> C (in Ref. 1; AAC98883)"
FT /evidence="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
