HS3S2_HUMAN
ID HS3S2_HUMAN Reviewed; 367 AA.
AC Q9Y278; Q52LZ1;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Heparan sulfate glucosamine 3-O-sulfotransferase 2;
DE EC=2.8.2.29 {ECO:0000269|PubMed:9988768};
DE AltName: Full=Heparan sulfate D-glucosaminyl 3-O-sulfotransferase 2 {ECO:0000303|PubMed:9988768};
DE Short=3-OST-2 {ECO:0000303|PubMed:9988768};
DE Short=Heparan sulfate 3-O-sulfotransferase 2;
DE Short=h3-OST-2;
GN Name=HS3ST2; Synonyms=3OST2; ORFNames=UNQ2442/PRO5004;
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.
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 [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=9988768; DOI=10.1074/jbc.274.8.5185;
RA Liu J., Shworak N.W., Sinay P., Schwartz J.J., Zhang L., Fritze L.M.S.,
RA Rosenberg R.D.;
RT "Expression of heparan sulfate D-glucosaminyl 3-O-sulfotransferase isoforms
RT reveals novel substrate specificities.";
RL J. Biol. Chem. 274:5185-5192(1999).
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 sulfate
CC (PubMed:9988768). Catalyzes the O-sulfation of glucosamine in GlcA2S-
CC GlcNS (PubMed:9988768). Unlike HS3ST1/3-OST-1, does not convert non-
CC anticoagulant heparan sulfate to anticoagulant heparan sulfate
CC (PubMed:9988768). {ECO:0000269|PubMed:9988768}.
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=2.8.2.29;
CC Evidence={ECO:0000269|PubMed:9988768};
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000305}; Single-
CC pass type II membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the brain and weakly expressed
CC in the heart, placenta, lung and skeletal muscle.
CC {ECO:0000269|PubMed:9988767}.
CC -!- SIMILARITY: Belongs to the sulfotransferase 1 family. {ECO:0000305}.
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DR EMBL; AF105374; AAD30206.1; -; mRNA.
DR EMBL; AF105375; AAD30207.1; -; mRNA.
DR EMBL; AY359095; AAQ89453.1; -; mRNA.
DR EMBL; BC093734; AAH93734.1; -; mRNA.
DR EMBL; BC093736; AAH93736.1; -; mRNA.
DR CCDS; CCDS10606.1; -.
DR RefSeq; NP_006034.1; NM_006043.1.
DR AlphaFoldDB; Q9Y278; -.
DR SMR; Q9Y278; -.
DR BioGRID; 115281; 115.
DR IntAct; Q9Y278; 11.
DR STRING; 9606.ENSP00000261374; -.
DR GlyGen; Q9Y278; 4 sites.
DR PhosphoSitePlus; Q9Y278; -.
DR BioMuta; HS3ST2; -.
DR DMDM; 61214416; -.
DR MassIVE; Q9Y278; -.
DR PaxDb; Q9Y278; -.
DR PeptideAtlas; Q9Y278; -.
DR PRIDE; Q9Y278; -.
DR ProteomicsDB; 85682; -.
DR Antibodypedia; 2393; 94 antibodies from 17 providers.
DR DNASU; 9956; -.
DR Ensembl; ENST00000261374.4; ENSP00000261374.3; ENSG00000122254.7.
DR GeneID; 9956; -.
DR KEGG; hsa:9956; -.
DR MANE-Select; ENST00000261374.4; ENSP00000261374.3; NM_006043.2; NP_006034.1.
DR UCSC; uc002dli.4; human.
DR CTD; 9956; -.
DR DisGeNET; 9956; -.
DR GeneCards; HS3ST2; -.
DR HGNC; HGNC:5195; HS3ST2.
DR HPA; ENSG00000122254; Tissue enriched (brain).
DR MIM; 604056; gene.
DR neXtProt; NX_Q9Y278; -.
DR OpenTargets; ENSG00000122254; -.
DR PharmGKB; PA29468; -.
DR VEuPathDB; HostDB:ENSG00000122254; -.
DR eggNOG; KOG3704; Eukaryota.
DR GeneTree; ENSGT00940000160498; -.
DR HOGENOM; CLU_017703_0_0_1; -.
DR InParanoid; Q9Y278; -.
DR OMA; NIIFYRG; -.
DR OrthoDB; 712400at2759; -.
DR PhylomeDB; Q9Y278; -.
DR TreeFam; TF350755; -.
DR BioCyc; MetaCyc:HS04557-MON; -.
DR BRENDA; 2.8.2.29; 2681.
DR PathwayCommons; Q9Y278; -.
DR Reactome; R-HSA-2022928; HS-GAG biosynthesis.
DR SignaLink; Q9Y278; -.
DR BioGRID-ORCS; 9956; 5 hits in 1061 CRISPR screens.
DR ChiTaRS; HS3ST2; human.
DR GeneWiki; HS3ST2; -.
DR GenomeRNAi; 9956; -.
DR Pharos; Q9Y278; Tbio.
DR PRO; PR:Q9Y278; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9Y278; protein.
DR Bgee; ENSG00000122254; Expressed in Brodmann (1909) area 46 and 129 other tissues.
DR ExpressionAtlas; Q9Y278; baseline and differential.
DR Genevisible; Q9Y278; HS.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0008467; F:[heparan sulfate]-glucosamine 3-sulfotransferase 1 activity; IDA:UniProtKB.
DR GO; GO:0033871; F:[heparan sulfate]-glucosamine 3-sulfotransferase 2 activity; IEA:UniProtKB-EC.
DR GO; GO:0008146; F:sulfotransferase activity; TAS:ProtInc.
DR GO; GO:0006024; P:glycosaminoglycan biosynthetic process; IDA: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 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Golgi apparatus; Membrane;
KW Reference proteome; Signal-anchor; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..367
FT /note="Heparan sulfate glucosamine 3-O-sulfotransferase 2"
FT /id="PRO_0000085214"
FT TOPO_DOM 1..19
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 20..39
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 40..367
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 61..110
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 76..90
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 124..128
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:Q9Y663"
FT BINDING 146..152
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y663"
FT BINDING 177..180
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y663"
FT BINDING 205
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:Q9Y663"
FT BINDING 213
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:Q9Y663"
FT BINDING 245..246
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y663"
FT BINDING 330..334
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:Q9Y663"
FT CARBOHYD 102
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 193
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 235
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 306
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 313..325
FT /evidence="ECO:0000250|UniProtKB:Q9Y663"
FT VARIANT 339
FT /note="P -> A (in dbSNP:rs17725080)"
FT /id="VAR_052530"
SQ SEQUENCE 367 AA; 41501 MW; F63EACDD4721607C CRC64;
MAYRVLGRAG PPQPRRARRL LFAFTLSLSC TYLCYSFLCC CDDLGRSRLL GAPRCLRGPS
AGGQKLLQKS RPCDPSGPTP SEPSAPSAPA AAVPAPRLSG SNHSGSPKLG TKRLPQALIV
GVKKGGTRAV LEFIRVHPDV RALGTEPHFF DRNYGRGLDW YRSLMPRTLE SQITLEKTPS
YFVTQEAPRR IFNMSRDTKL IVVVRNPVTR AISDYTQTLS KKPDIPTFEG LSFRNRTLGL
VDVSWNAIRI GMYVLHLESW LQYFPLAQIH FVSGERLITD PAGEMGRVQD FLGIKRFITD
KHFYFNKTKG FPCLKKTESS LLPRCLGKSK GRTHVQIDPE VIDQLREFYR PYNIKFYETV
GQDFRWE
