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 27-MAR-2024, entry version 161. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 157. DR IntAct; Q7LGA3; 24. DR MINT; Q7LGA3; -. DR STRING; 9606.ENSP00000359581; -. DR GlyConnect; 1308; 3 N-Linked glycans (1 site). DR GlyCosmos; Q7LGA3; 2 sites, 3 glycans. DR GlyGen; Q7LGA3; 3 sites, 3 N-linked glycans (1 site), 1 O-linked glycan (1 site). DR iPTMnet; Q7LGA3; -. DR PhosphoSitePlus; Q7LGA3; -. DR SwissPalm; Q7LGA3; -. DR BioMuta; HS2ST1; -. DR DMDM; 68052326; -. DR EPD; Q7LGA3; -. DR jPOST; Q7LGA3; -. DR MassIVE; Q7LGA3; -. DR MaxQB; Q7LGA3; -. DR PaxDb; 9606-ENSP00000359581; -. DR PeptideAtlas; Q7LGA3; -. DR ProteomicsDB; 68865; -. [Q7LGA3-1] DR ProteomicsDB; 68866; -. [Q7LGA3-2] DR ProteomicsDB; 68867; -. [Q7LGA3-3] DR Pumba; Q7LGA3; -. DR Antibodypedia; 33591; 251 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 AGR; HGNC:5193; -. 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; 5401406at2759; -. DR PhylomeDB; Q7LGA3; -. DR TreeFam; TF315238; -. DR BioCyc; MetaCyc:ENSG00000153936-MONOMER; -. 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; 22 hits in 1170 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 194 other cell types or tissues. DR ExpressionAtlas; Q7LGA3; baseline and differential. DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome. 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:0010467; P:gene expression; IEA:Ensembl. 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; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR007734; Heparan_SO4_2-O-STrfase. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR005331; Sulfotransferase. DR PANTHER; PTHR12129; HEPARAN SULFATE 2-O-SULFOTRANSFERASE; 1. DR PANTHER; PTHR12129:SF17; HEPARAN SULFATE 2-O-SULFOTRANSFERASE 1; 1. DR Pfam; PF03567; Sulfotransfer_2; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR Genevisible; Q7LGA3; HS. 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; dbSNP:rs1651972168)" FT /evidence="ECO:0000269|PubMed:33159882" FT /id="VAR_085253" FT VARIANT 189 FT /note="R -> S (in NFSRA; dbSNP:rs1651973144)" 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 //