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   27-MAR-2024, entry version 162.
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; 6.
DR   STRING; 9606.ENSP00000427888; -.
DR   GlyCosmos; Q8IZT8; 1 site, No reported glycans.
DR   GlyGen; Q8IZT8; 1 site.
DR   iPTMnet; Q8IZT8; -.
DR   PhosphoSitePlus; Q8IZT8; -.
DR   BioMuta; HS3ST5; -.
DR   DMDM; 61214369; -.
DR   MassIVE; Q8IZT8; -.
DR   PaxDb; 9606-ENSP00000427888; -.
DR   PeptideAtlas; Q8IZT8; -.
DR   ProteomicsDB; 71426; -.
DR   Antibodypedia; 50950; 53 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   AGR; HGNC:19419; -.
DR   CTD; 222537; -.
DR   DisGeNET; 222537; -.
DR   GeneCards; HS3ST5; -.
DR   HGNC; HGNC:19419; HS3ST5.
DR   HPA; ENSG00000249853; Tissue enhanced (brain, skeletal muscle, urinary bladder).
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; ISLYHTY; -.
DR   OrthoDB; 10019at2759; -.
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; 7 hits in 1144 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 male germ line stem cell (sensu Vertebrata) in testis and 96 other cell types or tissues.
DR   GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR   GO; GO:0016020; C: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: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; P-loop containing nucleotide triphosphate hydrolases; 1.
DR   InterPro; IPR037359; NST/OST.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR000863; Sulfotransferase_dom.
DR   PANTHER; PTHR10605:SF46; HEPARAN SULFATE GLUCOSAMINE 3-O-SULFOTRANSFERASE 5; 1.
DR   PANTHER; PTHR10605; HEPARAN SULFATE SULFOTRANSFERASE; 1.
DR   Pfam; PF00685; Sulfotransfer_1; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   Genevisible; Q8IZT8; HS.
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
//