HS2ST_HUMAN
ID HS2ST_HUMAN Reviewed; 356 AA.
AC Q7LGA3; D3DT22; O75036; Q32NB5; Q8TAC5; Q9H441; Q9NUJ9;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Heparan sulfate 2-O-sulfotransferase 1;
DE Short=2-O-sulfotransferase;
DE Short=2OST;
DE EC=2.8.2.-;
GN Name=HS2ST1; Synonyms=HS2ST, KIAA0448;
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] (ISOFORM 1).
RA Habuchi H.;
RT "Human heparan sulfate 2-O-sulfotransferase.";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9455484; DOI=10.1093/dnares/4.5.345;
RA Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D.,
RA Nomura N., Ohara O.;
RT "Characterization of cDNA clones in size-fractionated cDNA libraries from
RT human brain.";
RL DNA Res. 4:345-349(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain, Ovary, and Testis;
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP INVOLVEMENT IN NFSRA, AND VARIANTS NFSRA TYR-165; SER-176 AND SER-189.
RX PubMed=33159882; DOI=10.1016/j.ajhg.2020.10.007;
RA Schneeberger P.E., von Elsner L., Barker E.L., Meinecke P., Marquardt I.,
RA Alawi M., Steindl K., Joset P., Rauch A., Zwijnenburg P.J.G., Weiss M.M.,
RA Merry C.L.R., Kutsche K.;
RT "Bi-allelic pathogenic variants in HS2ST1 cause a syndrome characterized by
RT developmental delay and corpus callosum, skeletal, and renal
RT abnormalities.";
RL Am. J. Hum. Genet. 107:1044-1061(2020).
CC -!- FUNCTION: Catalyzes the transfer of sulfate to the C2-position of
CC selected hexuronic acid residues within the maturing heparan sulfate
CC (HS). 2-O-sulfation within HS, particularly of iduronate residues, is
CC essential for HS to participate in a variety of high-affinity ligand-
CC binding interactions and signaling processes. Mediates 2-O-sulfation of
CC both L-iduronyl and D-glucuronyl residues (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Homotrimer. Interacts with the C5-epimerase GLCE (By
CC similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q7LGA3-3; O14908-2: GIPC1; NbExp=3; IntAct=EBI-25887463, EBI-25913156;
CC Q7LGA3-3; Q92876: KLK6; NbExp=3; IntAct=EBI-25887463, EBI-2432309;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250}; Single-
CC pass type II membrane protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q7LGA3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7LGA3-2; Sequence=VSP_014062, VSP_014064;
CC Name=3;
CC IsoId=Q7LGA3-3; Sequence=VSP_014063;
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- DISEASE: Neurofacioskeletal syndrome with or without renal agenesis
CC (NFSRA) [MIM:619194]: An autosomal recessive syndrome characterized by
CC developmental delay and/or intellectual disability, corpus callosum
CC agenesis or hypoplasia, flexion contractures, brachydactyly of hands
CC and feet with broad fingertips and toes, and dysmorphic features such
CC as coarse face, upslanted palpebral fissures, broad nasal tip and wide
CC mouth. Some patients manifest unilateral or bilateral renal agenesis.
CC {ECO:0000269|PubMed:33159882}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the sulfotransferase 3 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA32293.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB024568; BAA89250.1; -; mRNA.
DR EMBL; AB007917; BAA32293.2; ALT_INIT; mRNA.
DR EMBL; AK002179; BAA92125.1; -; mRNA.
DR EMBL; AC093155; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL121989; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL139139; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471097; EAW73171.1; -; Genomic_DNA.
DR EMBL; CH471097; EAW73172.1; -; Genomic_DNA.
DR EMBL; BC025384; AAH25384.1; -; mRNA.
DR EMBL; BC025990; AAH25990.1; -; mRNA.
DR EMBL; BC108735; AAI08736.1; -; mRNA.
DR CCDS; CCDS44171.1; -. [Q7LGA3-3]
DR CCDS; CCDS711.1; -. [Q7LGA3-1]
DR RefSeq; NP_001127964.1; NM_001134492.1. [Q7LGA3-3]
DR RefSeq; NP_036394.1; NM_012262.3. [Q7LGA3-1]
DR AlphaFoldDB; Q7LGA3; -.
DR SMR; Q7LGA3; -.
DR BioGRID; 115011; 139.
DR IntAct; Q7LGA3; 24.
DR MINT; Q7LGA3; -.
DR STRING; 9606.ENSP00000359581; -.
DR GlyConnect; 1308; 3 N-Linked glycans (1 site).
DR GlyGen; Q7LGA3; 3 sites, 3 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; Q7LGA3; -.
DR PhosphoSitePlus; Q7LGA3; -.
DR BioMuta; HS2ST1; -.
DR DMDM; 68052326; -.
DR EPD; Q7LGA3; -.
DR jPOST; Q7LGA3; -.
DR MassIVE; Q7LGA3; -.
DR MaxQB; Q7LGA3; -.
DR PaxDb; Q7LGA3; -.
DR PeptideAtlas; Q7LGA3; -.
DR PRIDE; Q7LGA3; -.
DR ProteomicsDB; 68865; -. [Q7LGA3-1]
DR ProteomicsDB; 68866; -. [Q7LGA3-2]
DR ProteomicsDB; 68867; -. [Q7LGA3-3]
DR Antibodypedia; 33591; 221 antibodies from 26 providers.
DR DNASU; 9653; -.
DR Ensembl; ENST00000370550.10; ENSP00000359581.4; ENSG00000153936.18. [Q7LGA3-1]
DR Ensembl; ENST00000370551.8; ENSP00000359582.3; ENSG00000153936.18. [Q7LGA3-3]
DR GeneID; 9653; -.
DR KEGG; hsa:9653; -.
DR MANE-Select; ENST00000370550.10; ENSP00000359581.4; NM_012262.4; NP_036394.1.
DR UCSC; uc001dmc.5; human. [Q7LGA3-1]
DR CTD; 9653; -.
DR DisGeNET; 9653; -.
DR GeneCards; HS2ST1; -.
DR HGNC; HGNC:5193; HS2ST1.
DR HPA; ENSG00000153936; Low tissue specificity.
DR MalaCards; HS2ST1; -.
DR MIM; 604844; gene.
DR MIM; 619194; phenotype.
DR neXtProt; NX_Q7LGA3; -.
DR OpenTargets; ENSG00000153936; -.
DR OpenTargets; ENSG00000267561; -.
DR Orphanet; 528084; Non-specific syndromic intellectual disability.
DR PharmGKB; PA29466; -.
DR VEuPathDB; HostDB:ENSG00000153936; -.
DR eggNOG; KOG3922; Eukaryota.
DR GeneTree; ENSGT00530000063408; -.
DR HOGENOM; CLU_045310_1_1_1; -.
DR InParanoid; Q7LGA3; -.
DR OMA; SYLDFAX; -.
DR OrthoDB; 877221at2759; -.
DR PhylomeDB; Q7LGA3; -.
DR TreeFam; TF315238; -.
DR BioCyc; MetaCyc:ENSG00000153936-MON; -.
DR BRENDA; 2.8.2.B6; 2681.
DR PathwayCommons; Q7LGA3; -.
DR Reactome; R-HSA-2022928; HS-GAG biosynthesis.
DR SignaLink; Q7LGA3; -.
DR BioGRID-ORCS; 9653; 21 hits in 1085 CRISPR screens.
DR ChiTaRS; HS2ST1; human.
DR GeneWiki; HS2ST1; -.
DR GenomeRNAi; 9653; -.
DR Pharos; Q7LGA3; Tbio.
DR PRO; PR:Q7LGA3; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q7LGA3; protein.
DR Bgee; ENSG00000153936; Expressed in adrenal tissue and 192 other tissues.
DR ExpressionAtlas; Q7LGA3; baseline and differential.
DR Genevisible; Q7LGA3; HS.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0004394; F:heparan sulfate 2-O-sulfotransferase activity; IBA:GO_Central.
DR GO; GO:0008146; F:sulfotransferase activity; IBA:GO_Central.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0006024; P:glycosaminoglycan biosynthetic process; TAS:Reactome.
DR GO; GO:0015015; P:heparan sulfate proteoglycan biosynthetic process, enzymatic modification; IBA:GO_Central.
DR GO; GO:0015014; P:heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process; IBA:GO_Central.
DR GO; GO:0030202; P:heparin metabolic process; IEA:Ensembl.
DR GO; GO:0060676; P:ureteric bud formation; IEA:Ensembl.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR007734; Heparan_SO4_2-O-STrfase.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005331; Sulfotransferase.
DR PANTHER; PTHR12129; PTHR12129; 1.
DR Pfam; PF03567; Sulfotransfer_2; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Disulfide bond; Glycoprotein;
KW Golgi apparatus; Intellectual disability; Membrane; Reference proteome;
KW Signal-anchor; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..356
FT /note="Heparan sulfate 2-O-sulfotransferase 1"
FT /id="PRO_0000207674"
FT TOPO_DOM 1..11
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 12..28
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 29..356
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT ACT_SITE 140
FT /evidence="ECO:0000250"
FT CARBOHYD 108
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 201..209
FT /evidence="ECO:0000250"
FT DISULFID 222..228
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..41
FT /note="MGLLRIMMPPKLQLLAVVAFAVAMLFLENQIQKLEESRSKL -> MLFIKFI
FT HLEVFSMP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_014062"
FT VAR_SEQ 230..356
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_014063"
FT VAR_SEQ 282..356
FT /note="GKKSHLRKTTEKKLPTKQTIAKLQQSDIWKMENEFYEFALEQFQFIRAHAVR
FT EKDGDLYILAQNFFYEKIYPKSN -> APDTATPSHRHGPICGSKSISSLLVKVSPVCK
FT DSHCLGKCSRNGLSAV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_014064"
FT VARIANT 165
FT /note="D -> Y (in NFSRA; dbSNP:rs758990524)"
FT /evidence="ECO:0000269|PubMed:33159882"
FT /id="VAR_085252"
FT VARIANT 176
FT /note="F -> S (in NFSRA)"
FT /evidence="ECO:0000269|PubMed:33159882"
FT /id="VAR_085253"
FT VARIANT 189
FT /note="R -> S (in NFSRA)"
FT /evidence="ECO:0000269|PubMed:33159882"
FT /id="VAR_085254"
SQ SEQUENCE 356 AA; 41881 MW; 2F5BBDFC7DF50F78 CRC64;
MGLLRIMMPP KLQLLAVVAF AVAMLFLENQ IQKLEESRSK LERAIARHEV REIEQRHTMD
GPRQDATLDE EEDMVIIYNR VPKTASTSFT NIAYDLCAKN KYHVLHINTT KNNPVMSLQD
QVRFVKNITS WKEMKPGFYH GHVSYLDFAK FGVKKKPIYI NVIRDPIERL VSYYYFLRFG
DDYRPGLRRR KQGDKKTFDE CVAEGGSDCA PEKLWLQIPF FCGHSSECWN VGSRWAMDQA
KYNLINEYFL VGVTEELEDF IMLLEAALPR FFRGATELYR TGKKSHLRKT TEKKLPTKQT
IAKLQQSDIW KMENEFYEFA LEQFQFIRAH AVREKDGDLY ILAQNFFYEK IYPKSN
