HS3S5_HUMAN
ID HS3S5_HUMAN Reviewed; 346 AA.
AC Q8IZT8; A8K1J2; Q52LI2; Q8N285;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Heparan sulfate glucosamine 3-O-sulfotransferase 5;
DE EC=2.8.2.23;
DE AltName: Full=Heparan sulfate D-glucosaminyl 3-O-sulfotransferase 5;
DE Short=3-OST-5;
DE Short=Heparan sulfate 3-O-sulfotransferase 5;
DE Short=h3-OST-5;
GN Name=HS3ST5; Synonyms=3OST5, HS3OST5;
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, CHARACTERIZATION, AND
RP FUNCTION IN HSV-1 ENTRY.
RC TISSUE=Placenta;
RX PubMed=12138164; DOI=10.1074/jbc.m204209200;
RA Xia G., Chen J., Tiwari V., Ju W., Li J.-P., Malmstroem A., Shukla D.,
RA Liu J.;
RT "Heparan sulfate 3-O-sulfotransferase isoform 5 generates both an
RT antithrombin-binding site and an entry receptor for herpes simplex virus,
RT type 1.";
RL J. Biol. Chem. 277:37912-37919(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Caudate nucleus, and Corpus callosum;
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP CHARACTERIZATION, AND TISSUE SPECIFICITY.
RX PubMed=12740361; DOI=10.1074/jbc.m301861200;
RA Mochizuki H., Yoshida K., Gotoh M., Sugioka S., Kikuchi N., Kwon Y.-D.,
RA Tawada A., Maeyama K., Inaba N., Hiruma T., Kimata K., Narimatsu H.;
RT "Characterization of a heparan sulfate 3-O-sulfotransferase-5, an enzyme
RT synthesizing a tetrasulfated disaccharide.";
RL J. Biol. Chem. 278:26780-26787(2003).
RN [6]
RP CHARACTERIZATION.
RX PubMed=15026143; DOI=10.1016/j.bbagen.2003.12.010;
RA Duncan M.B., Chen J., Krise J.P., Liu J.;
RT "The biosynthesis of anticoagulant heparan sulfate by the heparan sulfate
RT 3-O-sulfotransferase isoform 5.";
RL Biochim. Biophys. Acta 1671:34-43(2004).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 88-346 IN COMPLEX WITH
RP ADENOSINE-3'-5'-DIPHOSPHATE, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ARG-99;
RP ARG-104; LYS-155; GLN-195; LYS-309 AND ARG-311.
RX PubMed=18223645; DOI=10.1038/nchembio.66;
RA Xu D., Moon A.F., Song D., Pedersen L.C., Liu J.;
RT "Engineering sulfotransferases to modify heparan sulfate.";
RL Nat. Chem. Biol. 4:200-202(2008).
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. Catalyzes the rate limiting step in
CC the biosynthesis of heparan sulfate (HSact). This modification is a
CC crucial step in the biosynthesis of anticoagulant heparan sulfate as it
CC completes the structure of the antithrombin pentasaccharide binding
CC site. Also generates GlcUA-GlcNS or IdoUA-GlcNS and IdoUA2S-GlcNH2. The
CC substrate-specific O-sulfation generates an enzyme-modified heparan
CC sulfate which acts as a binding receptor to Herpes simplex virus-1
CC (HSV-1) and permits its entry. {ECO:0000269|PubMed:12138164}.
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:18223645};
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000305}; Single-
CC pass type II membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Highly expressed in skeletal muscle and fetal
CC brain, and also found in adult brain, spinal cord, cerebellum and
CC colon. {ECO:0000269|PubMed:12138164, ECO:0000269|PubMed:12740361}.
CC -!- SIMILARITY: Belongs to the sulfotransferase 1 family. {ECO:0000305}.
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DR EMBL; AF503292; AAN37737.1; -; mRNA.
DR EMBL; AK091074; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK289907; BAF82596.1; -; mRNA.
DR EMBL; CH471051; EAW48251.1; -; Genomic_DNA.
DR EMBL; BC093911; AAH93911.1; -; mRNA.
DR EMBL; BC093913; AAH93913.1; -; mRNA.
DR CCDS; CCDS34517.1; -.
DR RefSeq; NP_705840.2; NM_153612.3.
DR RefSeq; XP_006715442.1; XM_006715379.2.
DR RefSeq; XP_011533890.1; XM_011535588.2.
DR RefSeq; XP_016865959.1; XM_017010470.1.
DR RefSeq; XP_016865960.1; XM_017010471.1.
DR RefSeq; XP_016865961.1; XM_017010472.1.
DR RefSeq; XP_016865962.1; XM_017010473.1.
DR RefSeq; XP_016865963.1; XM_017010474.1.
DR PDB; 3BD9; X-ray; 2.30 A; A=88-346.
DR PDB; 7SCD; X-ray; 2.90 A; A=86-346.
DR PDB; 7SCE; X-ray; 2.75 A; A=86-346.
DR PDBsum; 3BD9; -.
DR PDBsum; 7SCD; -.
DR PDBsum; 7SCE; -.
DR AlphaFoldDB; Q8IZT8; -.
DR SMR; Q8IZT8; -.
DR BioGRID; 128801; 5.
DR STRING; 9606.ENSP00000427888; -.
DR GlyGen; Q8IZT8; 1 site.
DR iPTMnet; Q8IZT8; -.
DR PhosphoSitePlus; Q8IZT8; -.
DR BioMuta; HS3ST5; -.
DR DMDM; 61214369; -.
DR MassIVE; Q8IZT8; -.
DR PaxDb; Q8IZT8; -.
DR PeptideAtlas; Q8IZT8; -.
DR PRIDE; Q8IZT8; -.
DR ProteomicsDB; 71426; -.
DR Antibodypedia; 50950; 42 antibodies from 15 providers.
DR DNASU; 222537; -.
DR Ensembl; ENST00000312719.10; ENSP00000427888.1; ENSG00000249853.9.
DR GeneID; 222537; -.
DR KEGG; hsa:222537; -.
DR MANE-Select; ENST00000312719.10; ENSP00000427888.1; NM_153612.4; NP_705840.2.
DR UCSC; uc003pwg.4; human.
DR CTD; 222537; -.
DR DisGeNET; 222537; -.
DR GeneCards; HS3ST5; -.
DR HGNC; HGNC:19419; HS3ST5.
DR HPA; ENSG00000249853; Tissue enhanced (brain, skeletal muscle).
DR MIM; 609407; gene.
DR neXtProt; NX_Q8IZT8; -.
DR OpenTargets; ENSG00000249853; -.
DR PharmGKB; PA164741639; -.
DR VEuPathDB; HostDB:ENSG00000249853; -.
DR eggNOG; KOG3704; Eukaryota.
DR GeneTree; ENSGT00940000158991; -.
DR HOGENOM; CLU_017703_0_0_1; -.
DR InParanoid; Q8IZT8; -.
DR OMA; MHRWLEV; -.
DR OrthoDB; 712400at2759; -.
DR PhylomeDB; Q8IZT8; -.
DR TreeFam; TF350755; -.
DR BRENDA; 2.8.2.23; 2681.
DR PathwayCommons; Q8IZT8; -.
DR Reactome; R-HSA-2022928; HS-GAG biosynthesis.
DR BioGRID-ORCS; 222537; 5 hits in 1067 CRISPR screens.
DR ChiTaRS; HS3ST5; human.
DR EvolutionaryTrace; Q8IZT8; -.
DR GenomeRNAi; 222537; -.
DR Pharos; Q8IZT8; Tbio.
DR PRO; PR:Q8IZT8; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q8IZT8; protein.
DR Bgee; ENSG00000249853; Expressed in cortical plate and 94 other tissues.
DR Genevisible; Q8IZT8; HS.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0050656; F:3'-phosphoadenosine 5'-phosphosulfate binding; NAS:UniProtKB.
DR GO; GO:0008467; F:[heparan sulfate]-glucosamine 3-sulfotransferase 1 activity; IDA:UniProtKB.
DR GO; GO:0006024; P:glycosaminoglycan biosynthetic process; TAS:Reactome.
DR GO; GO:0015015; P:heparan sulfate proteoglycan biosynthetic process, enzymatic modification; IDA:UniProtKB.
DR GO; GO:0050819; P:negative regulation of coagulation; IDA:UniProtKB.
DR GO; GO:0006477; P:protein sulfation; IDA:UniProtKB.
DR GO; GO:0046596; P:regulation of viral entry into host cell; 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; Membrane;
KW Reference proteome; Signal-anchor; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..346
FT /note="Heparan sulfate glucosamine 3-O-sulfotransferase 5"
FT /id="PRO_0000085222"
FT TOPO_DOM 1..12
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 13..32
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 33..346
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT BINDING 100..104
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 122..128
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 155..158
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 183
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 191
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 226..227
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 293
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 309..313
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT CARBOHYD 287
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 294..304
FT /evidence="ECO:0000250"
FT VARIANT 247
FT /note="I -> N (in dbSNP:rs17793043)"
FT /id="VAR_052531"
FT MUTAGEN 99
FT /note="R->A: Reduces enzyme activity by over 99%."
FT /evidence="ECO:0000269|PubMed:18223645"
FT MUTAGEN 104
FT /note="R->A: Reduces enzyme activity by 93%,."
FT /evidence="ECO:0000269|PubMed:18223645"
FT MUTAGEN 155
FT /note="K->A: Reduces enzyme activity by over 99%."
FT /evidence="ECO:0000269|PubMed:18223645"
FT MUTAGEN 195
FT /note="Q->A: Reduces enzyme activity by over 99%."
FT /evidence="ECO:0000269|PubMed:18223645"
FT MUTAGEN 309
FT /note="K->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:18223645"
FT MUTAGEN 311
FT /note="R->A: Reduces enzyme activity by 98%."
FT /evidence="ECO:0000269|PubMed:18223645"
FT STRAND 92..97
FT /evidence="ECO:0007829|PDB:3BD9"
FT HELIX 103..110
FT /evidence="ECO:0007829|PDB:3BD9"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:3BD9"
FT HELIX 129..133
FT /evidence="ECO:0007829|PDB:3BD9"
FT HELIX 136..140
FT /evidence="ECO:0007829|PDB:3BD9"
FT STRAND 151..155
FT /evidence="ECO:0007829|PDB:3BD9"
FT HELIX 157..160
FT /evidence="ECO:0007829|PDB:3BD9"
FT HELIX 165..172
FT /evidence="ECO:0007829|PDB:3BD9"
FT STRAND 177..182
FT /evidence="ECO:0007829|PDB:3BD9"
FT HELIX 185..202
FT /evidence="ECO:0007829|PDB:3BD9"
FT HELIX 210..214
FT /evidence="ECO:0007829|PDB:3BD9"
FT TURN 217..219
FT /evidence="ECO:0007829|PDB:3BD9"
FT STRAND 220..222
FT /evidence="ECO:0007829|PDB:7SCE"
FT HELIX 227..231
FT /evidence="ECO:0007829|PDB:3BD9"
FT HELIX 234..242
FT /evidence="ECO:0007829|PDB:3BD9"
FT HELIX 247..249
FT /evidence="ECO:0007829|PDB:3BD9"
FT STRAND 250..254
FT /evidence="ECO:0007829|PDB:3BD9"
FT HELIX 255..260
FT /evidence="ECO:0007829|PDB:3BD9"
FT HELIX 262..272
FT /evidence="ECO:0007829|PDB:3BD9"
FT HELIX 281..283
FT /evidence="ECO:0007829|PDB:3BD9"
FT STRAND 284..287
FT /evidence="ECO:0007829|PDB:3BD9"
FT TURN 288..291
FT /evidence="ECO:0007829|PDB:3BD9"
FT STRAND 292..296
FT /evidence="ECO:0007829|PDB:3BD9"
FT STRAND 298..300
FT /evidence="ECO:0007829|PDB:3BD9"
FT HELIX 318..339
FT /evidence="ECO:0007829|PDB:3BD9"
SQ SEQUENCE 346 AA; 40408 MW; C763F70793FDB156 CRC64;
MLFKQQAWLR QKLLVLGSLA VGSLLYLVAR VGSLDRLQPI CPIEGRLGGA RTQAEFPLRA
LQFKRGLLHE FRKGNASKEQ VRLHDLVQQL PKAIIIGVRK GGTRALLEML NLHPAVVKAS
QEIHFFDNDE NYGKGIEWYR KKMPFSYPQQ ITIEKSPAYF ITEEVPERIY KMNSSIKLLI
IVREPTTRAI SDYTQVLEGK ERKNKTYYKF EKLAIDPNTC EVNTKYKAVR TSIYTKHLER
WLKYFPIEQF HVVDGDRLIT EPLPELQLVE KFLNLPPRIS QYNLYFNATR GFYCLRFNII
FNKCLAGSKG RIHPEVDPSV ITKLRKFFHP FNQKFYQITG RTLNWP
