HS3S6_HUMAN
ID HS3S6_HUMAN Reviewed; 342 AA.
AC Q96QI5; Q96RX7;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Heparan sulfate glucosamine 3-O-sulfotransferase 6;
DE EC=2.8.2.23;
DE AltName: Full=Heparan sulfate D-glucosaminyl 3-O-sulfotransferase 6;
DE Short=3-OST-6;
DE Short=Heparan sulfate 3-O-sulfotransferase 6;
DE Short=h3-OST-6;
GN Name=HS3ST6; Synonyms=HS3ST5;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=11157797; DOI=10.1093/hmg/10.4.339;
RA Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., Tufarelli C.,
RA Kearney L., Buckle V.J., Doggett N.A., Flint J., Higgs D.R.;
RT "Sequence, structure and pathology of the fully annotated terminal 2 Mb of
RT the short arm of human chromosome 16.";
RL Hum. Mol. Genet. 10:339-352(2001).
RN [2]
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 [3]
RP FUNCTION IN HSV-1 ENTRY.
RX PubMed=15303968; DOI=10.1042/bj20040908;
RA Xu D., Tiwari V., Xia G., Clement C., Shukla D., Liu J.;
RT "Characterization of heparan sulphate 3-O-sulphotransferase isoform 6 and
RT its role in assisting the entry of herpes simplex virus type 1.";
RL Biochem. J. 385:451-459(2005).
RN [4]
RP VARIANT HAE8 SER-144, AND INVOLVEMENT IN HAE8.
RX PubMed=33508266; DOI=10.1016/j.jaci.2021.01.011;
RA Bork K., Wulff K., Moehl B.S., Steinmueller-Magin L., Witzke G., Hardt J.,
RA Meinke P.;
RT "Novel hereditary angioedema linked with a heparan sulfate 3-O-
RT sulfotransferase 6 gene mutation.";
RL J. Allergy Clin. Immunol. 148:1041-1048(2021).
CC -!- FUNCTION: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate
CC (PAPS) to catalyze the transfer of a sulfo group to heparan sulfate.
CC The 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. Unlike 3-OST-1, does not convert non-
CC anticoagulant heparan sulfate to anticoagulant heparan sulfate.
CC {ECO:0000269|PubMed:15303968}.
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 -!- DISEASE: Angioedema, hereditary, 8 (HAE8) [MIM:619367]: A form of
CC angioedema, a disorder characterized by episodic local swelling
CC involving subcutaneous or submucous tissue of the upper respiratory and
CC gastrointestinal tracts, face, extremities, and genitalia. HAE8
CC inheritance is autosomal dominant. {ECO:0000269|PubMed:33508266}.
CC Note=The disease may be caused by variants affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the sulfotransferase 1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK61299.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AE006640; AAK61299.1; ALT_INIT; Genomic_DNA.
DR EMBL; AL031723; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS45381.2; -.
DR RefSeq; NP_001009606.3; NM_001009606.3.
DR AlphaFoldDB; Q96QI5; -.
DR SMR; Q96QI5; -.
DR BioGRID; 122239; 7.
DR STRING; 9606.ENSP00000416741; -.
DR GlyGen; Q96QI5; 1 site.
DR iPTMnet; Q96QI5; -.
DR PhosphoSitePlus; Q96QI5; -.
DR BioMuta; HS3ST6; -.
DR DMDM; 61214397; -.
DR MassIVE; Q96QI5; -.
DR PaxDb; Q96QI5; -.
DR PeptideAtlas; Q96QI5; -.
DR PRIDE; Q96QI5; -.
DR ProteomicsDB; 77881; -.
DR Antibodypedia; 23316; 27 antibodies from 14 providers.
DR DNASU; 64711; -.
DR Ensembl; ENST00000293937.5; ENSP00000293937.3; ENSG00000276333.2.
DR Ensembl; ENST00000454677.3; ENSP00000416741.3; ENSG00000162040.7.
DR GeneID; 64711; -.
DR KEGG; hsa:64711; -.
DR MANE-Select; ENST00000454677.3; ENSP00000416741.3; NM_001009606.4; NP_001009606.3.
DR UCSC; uc032epu.2; human.
DR CTD; 64711; -.
DR DisGeNET; 64711; -.
DR GeneCards; HS3ST6; -.
DR HGNC; HGNC:14178; HS3ST6.
DR HPA; ENSG00000162040; Tissue enriched (skin).
DR MIM; 619210; gene.
DR MIM; 619367; phenotype.
DR neXtProt; NX_Q96QI5; -.
DR OpenTargets; ENSG00000162040; -.
DR Orphanet; 599418; Hereditary angioedema with normal C1Inh not related to F12 or PLG variant.
DR VEuPathDB; HostDB:ENSG00000162040; -.
DR eggNOG; KOG3704; Eukaryota.
DR GeneTree; ENSGT00940000154768; -.
DR InParanoid; Q96QI5; -.
DR OMA; RVCTMNC; -.
DR OrthoDB; 712400at2759; -.
DR PhylomeDB; Q96QI5; -.
DR BRENDA; 2.8.2.23; 2681.
DR PathwayCommons; Q96QI5; -.
DR Reactome; R-HSA-2022928; HS-GAG biosynthesis.
DR BioGRID-ORCS; 64711; 23 hits in 1034 CRISPR screens.
DR GenomeRNAi; 64711; -.
DR Pharos; Q96QI5; Tdark.
DR PRO; PR:Q96QI5; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q96QI5; protein.
DR Bgee; ENSG00000162040; Expressed in skin of leg and 44 other tissues.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0008467; F:[heparan sulfate]-glucosamine 3-sulfotransferase 1 activity; ISS:UniProtKB.
DR GO; GO:0001835; P:blastocyst hatching; IEA:Ensembl.
DR GO; GO:0006024; P:glycosaminoglycan biosynthetic process; TAS:Reactome.
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..342
FT /note="Heparan sulfate glucosamine 3-O-sulfotransferase 6"
FT /id="PRO_0000085224"
FT TOPO_DOM 1..31
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 32..49
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 50..342
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 55..85
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 153..156
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 181
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 189
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 220..221
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 305..309
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT CARBOHYD 281
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 288..300
FT /evidence="ECO:0000250"
FT VARIANT 144
FT /note="T -> S (in HAE8; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:33508266"
FT /id="VAR_085820"
FT CONFLICT 192
FT /note="A -> T (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 316
FT /note="L -> V (in Ref. 1)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 342 AA; 37186 MW; 3CB8FFD4AFA7F9DC CRC64;
MAGSGGLGGG AGGGQGAGAG QGAALRASRA PMLLVALVLG AYCLCALPGR CPPAARAPAP
APAPSEPSSS VHRPGAPGLP LASGPGRRRF PQALIVGVKK GGTRALLEFL RLHPDVRALG
SEPHFFDRCY ERGLAWYRSL MPRTLDGQIT MEKTPSYFVT REAPRRIHAM SPDTKLIVVV
RNPVTRAISD YAQTLSKTPG LPSFRALAFR HGLGPVDTAW SAVRIGLYAQ HLDHWLRYFP
LSHFLFVSGE RLVSDPAGEV GRVQDFLGLK RVVTDKHFYF NATKGFPCLK KAQGGSRPRC
LGKSKGRPHP RVPQALVRRL QEFYRPFNRR FYQMTGQDFG WG
