CHST1_HUMAN
ID CHST1_HUMAN Reviewed; 411 AA.
AC O43916; D3DQP2;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Carbohydrate sulfotransferase 1;
DE AltName: Full=Galactose/N-acetylglucosamine/N-acetylglucosamine 6-O-sulfotransferase 1;
DE Short=GST-1;
DE AltName: Full=Keratan sulfate Gal-6 sulfotransferase;
DE Short=KS6ST;
DE Short=KSGal6ST;
DE Short=KSST;
DE EC=2.8.2.21 {ECO:0000269|PubMed:17690104, ECO:0000269|PubMed:9405439};
GN Name=CHST1 {ECO:0000312|HGNC:HGNC:1969};
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], FUNCTION, CATALYTIC ACTIVITY, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Fetal brain;
RX PubMed=9405439; DOI=10.1074/jbc.272.51.32321;
RA Fukuta M., Inazawa J., Torii T., Tsuzuki K., Shimada E., Habuchi O.;
RT "Molecular cloning and characterization of human keratan sulfate Gal-6-
RT sulfotransferase.";
RL J. Biol. Chem. 272:32321-32328(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9639683; DOI=10.1016/s0925-4439(98)00028-3;
RA Mazany K.D., Peng T., Watson C.E., Tabas I., Williams K.J.;
RT "Human chondroitin 6-sulfotransferase: cloning, gene structure, and
RT chromosomal localization.";
RL Biochim. Biophys. Acta 1407:92-97(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Umbilical vein endothelial cell;
RX PubMed=10049591; DOI=10.1006/geno.1998.5653;
RA Li X., Tedder T.F.;
RT "CHST1 and CHST2 sulfotransferases expressed by human vascular endothelial
RT cells: cDNA cloning, expression, and chromosomal localization.";
RL Genomics 55:345-347(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
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].
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 [7]
RP FUNCTION, SUBSTRATE SPECIFICITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10642612; DOI=10.1093/glycob/10.2.203;
RA Torii T., Fukuta M., Habuchi O.;
RT "Sulfation of sialyl N-acetyllactosamine oligosaccharides and fetuin
RT oligosaccharides by keratan sulfate Gal-6-sulfotransferase.";
RL Glycobiology 10:203-211(2000).
RN [8]
RP FUNCTION.
RX PubMed=10330415; DOI=10.1083/jcb.145.4.899;
RA Bistrup A., Bhakta S., Lee J.K., Belov Y.Y., Gunn M.D., Zuo F.-R.,
RA Huang C.-C., Kannagi R., Rosen S.D., Hemmerich S.;
RT "Sulfotransferases of two specificities function in the reconstitution of
RT high endothelial cell ligands for L-selectin.";
RL J. Cell Biol. 145:899-910(1999).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=11310842;
RA Li X., Tu L., Murphy P.G., Kadono T., Steeber D.A., Tedder T.F.;
RT "CHST1 and CHST2 sulfotransferase expression by vascular endothelial cells
RT regulates shear-resistant leukocyte rolling via L-selectin.";
RL J. Leukoc. Biol. 69:565-574(2001).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=17690104; DOI=10.1074/jbc.m703695200;
RA Kitayama K., Hayashida Y., Nishida K., Akama T.O.;
RT "Enzymes responsible for synthesis of corneal keratan sulfate
RT glycosaminoglycans.";
RL J. Biol. Chem. 282:30085-30096(2007).
CC -!- FUNCTION: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate
CC (PAPS) as sulfonate donor to catalyze the transfer of sulfate to
CC position 6 of internal galactose (Gal) residues of keratan. Cooperates
CC with B4GALT4 and B3GNT7 glycosyltransferases and CHST6 sulfotransferase
CC to construct and elongate disulfated disaccharide unit [->3(6-
CC sulfoGalbeta)1->4(6-sulfoGlcNAcbeta)1->] within keratan sulfate polymer
CC (PubMed:17690104, PubMed:9405439, PubMed:10642612). Has a preference
CC for sulfating keratan sulfate, but it also transfers sulfate to the
CC unsulfated polymer (PubMed:9405439). Involved in biosynthesis of
CC phosphacan, a major keratan sulfate proteoglycan in the developing
CC brain (By similarity). Involved in biosynthesis of 6-sulfoGalbeta-
CC containing O-linked glycans in high endothelial venules of lymph nodes.
CC May act in a synergistic manner with CHST4 to generate sialyl 6',6-
CC disulfo Lewis X motif, a recognition determinant for immune cell
CC receptors implicated in leukocyte trafficking (PubMed:10330415).
CC Catalyzes sulfation of N-acetyllactosamine (LacNAc) oligosaccharides
CC with highest efficiency for sialylated LacNAc structures
CC (PubMed:10642612). {ECO:0000250|UniProtKB:Q9EQC0,
CC ECO:0000269|PubMed:10330415, ECO:0000269|PubMed:10642612,
CC ECO:0000269|PubMed:17690104, ECO:0000269|PubMed:9405439}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3'-phosphoadenylyl sulfate + keratan = adenosine 3',5'-
CC bisphosphate + keratan 6'-sulfate.; EC=2.8.2.21;
CC Evidence={ECO:0000269|PubMed:17690104, ECO:0000269|PubMed:9405439};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10.4 mM for Galbeta1->4(6-sulfo)GlcNAcbeta1->3(6-
CC sulfo)Galbeta1->4(6-sulfo)GlcNAc (L2L4)
CC {ECO:0000269|PubMed:10642612};
CC KM=0.65 mM for NeuAcalpha2->3Galbeta1->4(6-sulfo)GlcNAcbeta1->3(6-
CC sulfo)Galbeta1->4(6-sulfo)GlcNAc (SL2L4)
CC {ECO:0000269|PubMed:10642612};
CC KM=0.38 mM for keratan sulfate {ECO:0000269|PubMed:10642612};
CC Vmax=85 pmol/min/mg enzyme toward Galbeta1->4(6-
CC sulfo)GlcNAcbeta1->3(6-sulfo)Galbeta1->4(6-sulfo)GlcNAc (L2L4)
CC {ECO:0000269|PubMed:10642612};
CC Vmax=20 pmol/min/mg enzyme toward NeuAcalpha2->3Galbeta1->4(6-
CC sulfo)GlcNAcbeta1->3(6-sulfo)Galbeta1->4(6-sulfo)GlcNAc (SL2L4)
CC {ECO:0000269|PubMed:10642612};
CC Vmax=6.1 pmol/min/mg enzyme toward keratan sulfate
CC {ECO:0000269|PubMed:10642612};
CC -!- PATHWAY: Glycan metabolism. {ECO:0000269|PubMed:17690104}.
CC -!- INTERACTION:
CC O43916; Q8TED1: GPX8; NbExp=3; IntAct=EBI-748017, EBI-11721746;
CC O43916; P27105: STOM; NbExp=3; IntAct=EBI-748017, EBI-1211440;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250}; Single-
CC pass type II membrane protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Widely expressed at low level. Expressed in brain
CC and skeletal muscle. Expressed by high endothelial cells (HEVs) and
CC leukocytes. {ECO:0000269|PubMed:11310842, ECO:0000269|PubMed:9405439}.
CC -!- SIMILARITY: Belongs to the sulfotransferase 1 family. Gal/GlcNAc/GalNAc
CC subfamily. {ECO:0000305}.
CC -!- CAUTION: Was originally (PubMed:9639683) thought to be the ortholog of
CC chicken CHST3 and therefore named C6ST. However, it has no strong
CC chondroitin 6-sulfotransferase activity. {ECO:0000305|PubMed:9639683}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/chst1/";
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DR EMBL; AB003791; BAA24840.1; -; mRNA.
DR EMBL; U65637; AAC28776.1; -; mRNA.
DR EMBL; AF090137; AAD19878.1; -; mRNA.
DR EMBL; AY339617; AAP88041.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68035.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68038.1; -; Genomic_DNA.
DR EMBL; BC022567; AAH22567.1; -; mRNA.
DR EMBL; BC028235; AAH28235.1; -; mRNA.
DR CCDS; CCDS7913.1; -.
DR RefSeq; NP_003645.1; NM_003654.5.
DR AlphaFoldDB; O43916; -.
DR BioGRID; 114104; 5.
DR IntAct; O43916; 4.
DR STRING; 9606.ENSP00000309270; -.
DR GlyGen; O43916; 4 sites.
DR iPTMnet; O43916; -.
DR PhosphoSitePlus; O43916; -.
DR BioMuta; CHST1; -.
DR jPOST; O43916; -.
DR MassIVE; O43916; -.
DR PaxDb; O43916; -.
DR PeptideAtlas; O43916; -.
DR PRIDE; O43916; -.
DR ProteomicsDB; 49232; -.
DR Antibodypedia; 13251; 208 antibodies from 29 providers.
DR DNASU; 8534; -.
DR Ensembl; ENST00000308064.7; ENSP00000309270.2; ENSG00000175264.8.
DR GeneID; 8534; -.
DR KEGG; hsa:8534; -.
DR MANE-Select; ENST00000308064.7; ENSP00000309270.2; NM_003654.6; NP_003645.1.
DR UCSC; uc001mys.3; human.
DR CTD; 8534; -.
DR DisGeNET; 8534; -.
DR GeneCards; CHST1; -.
DR HGNC; HGNC:1969; CHST1.
DR HPA; ENSG00000175264; Tissue enhanced (brain, thyroid gland).
DR MIM; 603797; gene.
DR neXtProt; NX_O43916; -.
DR OpenTargets; ENSG00000175264; -.
DR PharmGKB; PA26501; -.
DR VEuPathDB; HostDB:ENSG00000175264; -.
DR eggNOG; ENOG502S17I; Eukaryota.
DR GeneTree; ENSGT00940000161262; -.
DR HOGENOM; CLU_028381_3_2_1; -.
DR InParanoid; O43916; -.
DR OMA; NQHQEIF; -.
DR OrthoDB; 1246608at2759; -.
DR PhylomeDB; O43916; -.
DR TreeFam; TF342871; -.
DR BioCyc; MetaCyc:HS10902-MON; -.
DR BRENDA; 2.8.2.21; 2681.
DR PathwayCommons; O43916; -.
DR Reactome; R-HSA-2022854; Keratan sulfate biosynthesis.
DR SABIO-RK; O43916; -.
DR SignaLink; O43916; -.
DR BioGRID-ORCS; 8534; 10 hits in 1066 CRISPR screens.
DR GeneWiki; CHST1; -.
DR GenomeRNAi; 8534; -.
DR Pharos; O43916; Tbio.
DR PRO; PR:O43916; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O43916; protein.
DR Bgee; ENSG00000175264; Expressed in frontal pole and 142 other tissues.
DR Genevisible; O43916; HS.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0005802; C:trans-Golgi network; IBA:GO_Central.
DR GO; GO:0045130; F:keratan sulfotransferase activity; IDA:UniProtKB.
DR GO; GO:0001517; F:N-acetylglucosamine 6-O-sulfotransferase activity; IBA:GO_Central.
DR GO; GO:0008146; F:sulfotransferase activity; IDA:UniProtKB.
DR GO; GO:0006012; P:galactose metabolic process; IDA:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0018146; P:keratan sulfate biosynthetic process; IDA:UniProtKB.
DR GO; GO:0042339; P:keratan sulfate metabolic process; IDA:UniProtKB.
DR GO; GO:0006044; P:N-acetylglucosamine metabolic process; IBA:GO_Central.
DR GO; GO:0005976; P:polysaccharide metabolic process; TAS:ProtInc.
DR GO; GO:0006790; P:sulfur compound metabolic process; IDA:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR016469; Carbohydrate_sulfotransferase.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000863; Sulfotransferase_dom.
DR Pfam; PF00685; Sulfotransfer_1; 1.
DR PIRSF; PIRSF005883; Carbohydrate_sulfotransferase; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW Carbohydrate metabolism; Glycoprotein; Golgi apparatus;
KW Inflammatory response; Membrane; Reference proteome; Signal-anchor;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..411
FT /note="Carbohydrate sulfotransferase 1"
FT /id="PRO_0000085182"
FT TOPO_DOM 1..2
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 3..23
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 24..411
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT MOTIF 337..339
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT BINDING 69..75
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 234..242
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT CARBOHYD 56
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 145
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 189
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 334
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 411 AA; 46715 MW; F07D0A23B6338A09 CRC64;
MQCSWKAVLL LALASIAIQY TAIRTFTAKS FHTCPGLAEA GLAERLCEES PTFAYNLSRK
THILILATTR SGSSFVGQLF NQHLDVFYLF EPLYHVQNTL IPRFTQGKSP ADRRVMLGAS
RDLLRSLYDC DLYFLENYIK PPPVNHTTDR IFRRGASRVL CSRPVCDPPG PADLVLEEGD
CVRKCGLLNL TVAAEACRER SHVAIKTVRV PEVNDLRALV EDPRLNLKVI QLVRDPRGIL
ASRSETFRDT YRLWRLWYGT GRKPYNLDVT QLTTVCEDFS NSVSTGLMRP PWLKGKYMLV
RYEDLARNPM KKTEEIYGFL GIPLDSHVAR WIQNNTRGDP TLGKHKYGTV RNSAATAEKW
RFRLSYDIVA FAQNACQQVL AQLGYKIAAS EEELKNPSVS LVEERDFRPF S
