HS3S4_HUMAN
ID HS3S4_HUMAN Reviewed; 456 AA.
AC Q9Y661; Q5QI42; Q8NDC2;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2013, sequence version 3.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Heparan sulfate glucosamine 3-O-sulfotransferase 4;
DE EC=2.8.2.23;
DE AltName: Full=Heparan sulfate D-glucosaminyl 3-O-sulfotransferase 4;
DE Short=3-OST-4;
DE Short=Heparan sulfate 3-O-sulfotransferase 4;
DE Short=h3-OST-4;
GN Name=HS3ST4; Synonyms=3OST4;
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], TISSUE SPECIFICITY, AND VARIANT ARG-136.
RC TISSUE=Brain;
RX PubMed=9988767; DOI=10.1074/jbc.274.8.5170;
RA Shworak N.W., Liu J., Petros L.M., Zhang L., Kobayashi M., Copeland N.G.,
RA Jenkins N.A., Rosenberg R.D.;
RT "Multiple isoforms of heparan sulfate D-glucosaminyl 3-O-sulfotransferase.
RT Isolation, characterization, and expression of human cDNAs and
RT identification of distinct genomic loci.";
RL J. Biol. Chem. 274:5170-5184(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-136.
RA Lawrence R., Yabe T., Hajmohammadi S., Rhodes J., McNeely M., Liu J.,
RA Lamperti E.D., Toselli P.A., Spear P.G., Rosenberg R.D., Shworak N.W.;
RT "Neuronal 3-O-sulfotransferases exhibit trigeminal ganglion expression,
RT confer entry of HSV-1, and may explain disease patterns.";
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 122-456, AND VARIANT ARG-136.
RC TISSUE=Brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
CC -!- FUNCTION: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate
CC (PAPS) to catalyze the transfer of a sulfo group to an N-unsubstituted
CC glucosamine linked to a 2-O-sulfo iduronic acid unit on heparan
CC sulfate. Unlike 3-OST-1, does not convert non-anticoagulant heparan
CC sulfate to anticoagulant heparan sulfate (By similarity).
CC {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3'-phosphoadenylyl sulfate + alpha-D-glucosaminyl-[heparan
CC sulfate](n) = 3-sulfo-alpha-D-glucosaminyl-[heparan sulfate](n) +
CC adenosine 3',5'-bisphosphate + H(+); Xref=Rhea:RHEA:15461, Rhea:RHEA-
CC COMP:9830, Rhea:RHEA-COMP:9831, ChEBI:CHEBI:15378, ChEBI:CHEBI:58339,
CC ChEBI:CHEBI:58343, ChEBI:CHEBI:58388, ChEBI:CHEBI:70975; EC=2.8.2.23;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000305}; Single-
CC pass type II membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Brain-specific. {ECO:0000269|PubMed:9988767}.
CC -!- SIMILARITY: Belongs to the sulfotransferase 1 family. {ECO:0000305}.
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DR EMBL; AF105378; AAD30210.2; -; mRNA.
DR EMBL; AY476736; AAS58324.1; -; Genomic_DNA.
DR EMBL; AC092141; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093511; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL834283; CAD38957.1; -; mRNA.
DR CCDS; CCDS53995.1; -.
DR RefSeq; NP_006031.2; NM_006040.2.
DR AlphaFoldDB; Q9Y661; -.
DR SMR; Q9Y661; -.
DR BioGRID; 115276; 105.
DR STRING; 9606.ENSP00000330606; -.
DR GlyGen; Q9Y661; 4 sites.
DR BioMuta; HS3ST4; -.
DR DMDM; 527504083; -.
DR MassIVE; Q9Y661; -.
DR PaxDb; Q9Y661; -.
DR PeptideAtlas; Q9Y661; -.
DR PRIDE; Q9Y661; -.
DR ProteomicsDB; 86604; -.
DR Antibodypedia; 66573; 21 antibodies from 9 providers.
DR DNASU; 9951; -.
DR Ensembl; ENST00000331351.6; ENSP00000330606.5; ENSG00000182601.7.
DR GeneID; 9951; -.
DR KEGG; hsa:9951; -.
DR MANE-Select; ENST00000331351.6; ENSP00000330606.5; NM_006040.3; NP_006031.2.
DR UCSC; uc002dof.3; human.
DR CTD; 9951; -.
DR DisGeNET; 9951; -.
DR GeneCards; HS3ST4; -.
DR HGNC; HGNC:5200; HS3ST4.
DR HPA; ENSG00000182601; Tissue enriched (brain).
DR MIM; 604059; gene.
DR neXtProt; NX_Q9Y661; -.
DR OpenTargets; ENSG00000182601; -.
DR PharmGKB; PA29473; -.
DR VEuPathDB; HostDB:ENSG00000182601; -.
DR eggNOG; KOG3704; Eukaryota.
DR GeneTree; ENSGT00940000161466; -.
DR HOGENOM; CLU_017703_0_1_1; -.
DR InParanoid; Q9Y661; -.
DR OMA; EGAADTW; -.
DR OrthoDB; 712400at2759; -.
DR PhylomeDB; Q9Y661; -.
DR TreeFam; TF350755; -.
DR BRENDA; 2.8.2.23; 2681.
DR PathwayCommons; Q9Y661; -.
DR Reactome; R-HSA-2022928; HS-GAG biosynthesis.
DR BioGRID-ORCS; 9951; 10 hits in 1060 CRISPR screens.
DR ChiTaRS; HS3ST4; human.
DR GenomeRNAi; 9951; -.
DR Pharos; Q9Y661; Tbio.
DR PRO; PR:Q9Y661; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9Y661; protein.
DR Bgee; ENSG00000182601; Expressed in cortical plate and 95 other tissues.
DR Genevisible; Q9Y661; HS.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0008467; F:[heparan sulfate]-glucosamine 3-sulfotransferase 1 activity; IBA:GO_Central.
DR GO; GO:0030201; P:heparan sulfate proteoglycan metabolic process; NAS:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR037359; NST/OST.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000863; Sulfotransferase_dom.
DR PANTHER; PTHR10605; PTHR10605; 1.
DR Pfam; PF00685; Sulfotransfer_1; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 2: Evidence at transcript level;
KW Disulfide bond; Glycoprotein; Golgi apparatus; Membrane;
KW Reference proteome; Signal-anchor; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..456
FT /note="Heparan sulfate glucosamine 3-O-sulfotransferase 4"
FT /id="PRO_0000085221"
FT TOPO_DOM 1..34
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 35..59
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 60..456
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 68..139
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 154..192
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..28
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 72..119
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 207..211
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 229..235
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 260..263
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 288
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 296
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 328..329
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 413..417
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT CARBOHYD 105
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 318
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 389
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 396..408
FT /evidence="ECO:0000250"
FT VARIANT 136
FT /note="Q -> R (in dbSNP:rs2943336)"
FT /evidence="ECO:0000269|PubMed:17974005,
FT ECO:0000269|PubMed:9988767, ECO:0000269|Ref.2"
FT /id="VAR_069580"
FT CONFLICT 383
FT /note="E -> K (in Ref. 1; AAD30210 and 2; AAS58324)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 456 AA; 49799 MW; A1BA47F9817F6B38 CRC64;
MARWPAPPPP PPPPPPLAAP PPPGASAKGP PARKLLFMCT LSLSVTYLCY SLLGGSGSLQ
FPLALQESPG AAAEPPPSPP PPSLLPTPVR LGAPSQPPAP PPLDNASHGE PPEPPEQPAA
PGTDGWGLPS GGGGAQDAWL RTPLAPSEMI TAQSALPERE AQESSTTDED LAGRRAANGS
SERGGAVSTP DYGEKKLPQA LIIGVKKGGT RALLEAIRVH PDVRAVGVEP HFFDRNYEKG
LEWYRNVMPK TLDGQITMEK TPSYFVTNEA PKRIHSMAKD IKLIVVVRNP VTRAISDYTQ
TLSKKPEIPT FEVLAFKNRT LGLIDASWSA IRIGIYALHL ENWLQYFPLS QILFVSGERL
IVDPAGEMAK VQDFLGLKRV VTEKHFYFNK TKGFPCLKKP EDSSAPRCLG KSKGRTHPRI
DPDVIHRLRK FYKPFNLMFY QMTGQDFQWE QEEGDK
