HS3S1_HUMAN
ID HS3S1_HUMAN Reviewed; 307 AA.
AC O14792; B3KUA6; Q6PEY8;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Heparan sulfate glucosamine 3-O-sulfotransferase 1;
DE EC=2.8.2.23 {ECO:0000269|PubMed:8900198, ECO:0000269|PubMed:9988768};
DE AltName: Full=Heparan sulfate D-glucosaminyl 3-O-sulfotransferase 1 {ECO:0000303|PubMed:9988768};
DE Short=3-OST-1 {ECO:0000303|PubMed:9988768};
DE Short=Heparan sulfate 3-O-sulfotransferase 1;
DE Short=h3-OST-1;
DE Flags: Precursor;
GN Name=HS3ST1; Synonyms=3OST, 3OST1;
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 FUNCTION.
RC TISSUE=Brain;
RX PubMed=9346953; DOI=10.1074/jbc.272.44.28008;
RA Shworak N.W., Liu J., Fritze L.M.S., Schwartz J.J., Zhang L., Logeart D.,
RA Rosenberg R.D.;
RT "Molecular cloning and expression of mouse and human cDNAs encoding heparan
RT sulfate D-glucosaminyl 3-O-sulfotransferase.";
RL J. Biol. Chem. 272:28008-28019(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-22.
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 [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8900198; DOI=10.1074/jbc.271.43.27072;
RA Liu J., Shworak N.W., Fritze L.M., Edelberg J.M., Rosenberg R.D.;
RT "Purification of heparan sulfate D-glucosaminyl 3-O-sulfotransferase.";
RL J. Biol. Chem. 271:27072-27082(1996).
RN [6]
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).
RN [7]
RP TISSUE SPECIFICITY.
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 [8]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 36-307 IN COMPLEX WITH SUBSTRATE
RP ANALOG, DISULFIDE BOND, AND BINDING SITES.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human heparan sulfate glucosamine 3-o-
RT sulfotransferase 1 in complex with PAP.";
RL Submitted (JUN-2005) to the PDB data bank.
CC -!- FUNCTION: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate
CC (PAPS) to catalyze the transfer of a sulfo group to position 3 of
CC glucosamine residues in heparan (PubMed:9346953, PubMed:8900198,
CC PubMed:9988768). Catalyzes the rate limiting step in the biosynthesis
CC of heparan sulfate (HSact) (PubMed:8900198, PubMed:9988768). This
CC modification is a crucial step in the biosynthesis of anticoagulant
CC heparan sulfate as it completes the structure of the antithrombin
CC pentasaccharide binding site (PubMed:8900198, PubMed:9988768).
CC {ECO:0000269|PubMed:8900198, ECO:0000269|PubMed:9346953,
CC 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=2.8.2.23;
CC Evidence={ECO:0000269|PubMed:8900198, ECO:0000269|PubMed:9988768};
CC -!- SUBCELLULAR LOCATION: Golgi apparatus lumen {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the brain and kidney and weakly
CC expressed in the heart, lung and placenta.
CC {ECO:0000269|PubMed:9988767}.
CC -!- SIMILARITY: Belongs to the sulfotransferase 1 family. {ECO:0000305}.
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DR EMBL; AF019386; AAB84388.1; -; mRNA.
DR EMBL; AK096823; BAG53368.1; -; mRNA.
DR EMBL; CH471069; EAW92699.1; -; Genomic_DNA.
DR EMBL; BC057803; AAH57803.1; -; mRNA.
DR CCDS; CCDS3408.1; -.
DR RefSeq; NP_005105.1; NM_005114.2.
DR RefSeq; XP_011512215.1; XM_011513913.2.
DR PDB; 1ZRH; X-ray; 2.10 A; A=36-307.
DR PDBsum; 1ZRH; -.
DR AlphaFoldDB; O14792; -.
DR SMR; O14792; -.
DR BioGRID; 115282; 120.
DR STRING; 9606.ENSP00000002596; -.
DR DrugBank; DB01812; Adenosine 3',5'-diphosphate.
DR GlyGen; O14792; 4 sites.
DR iPTMnet; O14792; -.
DR PhosphoSitePlus; O14792; -.
DR BioMuta; HS3ST1; -.
DR MassIVE; O14792; -.
DR PaxDb; O14792; -.
DR PeptideAtlas; O14792; -.
DR PRIDE; O14792; -.
DR ProteomicsDB; 48242; -.
DR Antibodypedia; 1208; 128 antibodies from 26 providers.
DR DNASU; 9957; -.
DR Ensembl; ENST00000002596.6; ENSP00000002596.5; ENSG00000002587.10.
DR GeneID; 9957; -.
DR KEGG; hsa:9957; -.
DR MANE-Select; ENST00000002596.6; ENSP00000002596.5; NM_005114.4; NP_005105.1.
DR UCSC; uc003gmq.4; human.
DR CTD; 9957; -.
DR DisGeNET; 9957; -.
DR GeneCards; HS3ST1; -.
DR HGNC; HGNC:5194; HS3ST1.
DR HPA; ENSG00000002587; Tissue enhanced (brain, ovary).
DR MIM; 603244; gene.
DR neXtProt; NX_O14792; -.
DR OpenTargets; ENSG00000002587; -.
DR PharmGKB; PA29467; -.
DR VEuPathDB; HostDB:ENSG00000002587; -.
DR eggNOG; KOG3704; Eukaryota.
DR GeneTree; ENSGT00940000160449; -.
DR HOGENOM; CLU_017703_0_0_1; -.
DR InParanoid; O14792; -.
DR OMA; RCLHDSK; -.
DR OrthoDB; 712400at2759; -.
DR PhylomeDB; O14792; -.
DR TreeFam; TF350755; -.
DR BioCyc; MetaCyc:HS00082-MON; -.
DR BRENDA; 2.8.2.23; 2681.
DR PathwayCommons; O14792; -.
DR Reactome; R-HSA-2022928; HS-GAG biosynthesis.
DR SignaLink; O14792; -.
DR BioGRID-ORCS; 9957; 5 hits in 1066 CRISPR screens.
DR ChiTaRS; HS3ST1; human.
DR EvolutionaryTrace; O14792; -.
DR GeneWiki; HS3ST1; -.
DR GenomeRNAi; 9957; -.
DR Pharos; O14792; Tbio.
DR PRO; PR:O14792; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; O14792; protein.
DR Bgee; ENSG00000002587; Expressed in nasal cavity epithelium and 167 other tissues.
DR ExpressionAtlas; O14792; baseline and differential.
DR Genevisible; O14792; HS.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0008467; F:[heparan sulfate]-glucosamine 3-sulfotransferase 1 activity; IDA:UniProtKB.
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 3D-structure; Disulfide bond; Glycoprotein; Golgi apparatus;
KW Reference proteome; Signal; Transferase.
FT SIGNAL 1..20
FT /evidence="ECO:0000250|UniProtKB:O35310"
FT CHAIN 21..307
FT /note="Heparan sulfate glucosamine 3-O-sulfotransferase 1"
FT /id="PRO_0000033451"
FT BINDING 64..68
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000305|Ref.8"
FT BINDING 147
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000305|Ref.8"
FT BINDING 155
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000305|Ref.8"
FT BINDING 255
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000305|Ref.8"
FT BINDING 270..274
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000305|Ref.8"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 192
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 242
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 249
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 256..265
FT /evidence="ECO:0000269|Ref.8"
FT VARIANT 22
FT /note="P -> T (in dbSNP:rs11559238)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_021515"
FT VARIANT 295
FT /note="K -> R (in dbSNP:rs34719057)"
FT /id="VAR_052529"
FT STRAND 56..59
FT /evidence="ECO:0007829|PDB:1ZRH"
FT HELIX 67..74
FT /evidence="ECO:0007829|PDB:1ZRH"
FT STRAND 80..82
FT /evidence="ECO:0007829|PDB:1ZRH"
FT TURN 89..91
FT /evidence="ECO:0007829|PDB:1ZRH"
FT HELIX 93..96
FT /evidence="ECO:0007829|PDB:1ZRH"
FT HELIX 99..105
FT /evidence="ECO:0007829|PDB:1ZRH"
FT STRAND 114..119
FT /evidence="ECO:0007829|PDB:1ZRH"
FT HELIX 121..125
FT /evidence="ECO:0007829|PDB:1ZRH"
FT HELIX 129..136
FT /evidence="ECO:0007829|PDB:1ZRH"
FT STRAND 141..146
FT /evidence="ECO:0007829|PDB:1ZRH"
FT HELIX 149..166
FT /evidence="ECO:0007829|PDB:1ZRH"
FT HELIX 174..178
FT /evidence="ECO:0007829|PDB:1ZRH"
FT HELIX 189..194
FT /evidence="ECO:0007829|PDB:1ZRH"
FT HELIX 196..204
FT /evidence="ECO:0007829|PDB:1ZRH"
FT HELIX 209..211
FT /evidence="ECO:0007829|PDB:1ZRH"
FT STRAND 212..216
FT /evidence="ECO:0007829|PDB:1ZRH"
FT HELIX 217..222
FT /evidence="ECO:0007829|PDB:1ZRH"
FT HELIX 224..234
FT /evidence="ECO:0007829|PDB:1ZRH"
FT HELIX 243..245
FT /evidence="ECO:0007829|PDB:1ZRH"
FT STRAND 246..249
FT /evidence="ECO:0007829|PDB:1ZRH"
FT TURN 250..253
FT /evidence="ECO:0007829|PDB:1ZRH"
FT STRAND 254..259
FT /evidence="ECO:0007829|PDB:1ZRH"
FT STRAND 262..264
FT /evidence="ECO:0007829|PDB:1ZRH"
FT HELIX 279..288
FT /evidence="ECO:0007829|PDB:1ZRH"
FT HELIX 290..300
FT /evidence="ECO:0007829|PDB:1ZRH"
SQ SEQUENCE 307 AA; 35773 MW; AA1052260633EA1C CRC64;
MAALLLGAVL LVAQPQLVPS RPAELGQQEL LRKAGTLQDD VRDGVAPNGS AQQLPQTIII
GVRKGGTRAL LEMLSLHPDV AAAENEVHFF DWEEHYSHGL GWYLSQMPFS WPHQLTVEKT
PAYFTSPKVP ERVYSMNPSI RLLLILRDPS ERVLSDYTQV FYNHMQKHKP YPSIEEFLVR
DGRLNVDYKA LNRSLYHVHM QNWLRFFPLR HIHIVDGDRL IRDPFPEIQK VERFLKLSPQ
INASNFYFNK TKGFYCLRDS GRDRCLHESK GRAHPQVDPK LLNKLHEYFH EPNKKFFELV
GRTFDWH
