CHSTF_HUMAN
ID CHSTF_HUMAN Reviewed; 561 AA.
AC Q7LFX5; O60338; O60474; Q86VM4;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Carbohydrate sulfotransferase 15;
DE EC=2.8.2.33;
DE AltName: Full=B-cell RAG-associated gene protein;
DE Short=hBRAG;
DE AltName: Full=N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase;
DE Short=GalNAc4S-6ST;
GN Name=CHST15; Synonyms=BRAG, GALNAC4S6ST, KIAA0598;
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), AND TISSUE SPECIFICITY.
RC TISSUE=Pre-B cell;
RX PubMed=9754571;
RX DOI=10.1002/(sici)1521-4141(199809)28:09<2839::aid-immu2839>3.0.co;2-6;
RA Verkoczy L.K., Marsden P.A., Berinstein N.L.;
RT "hBRAG, a novel B cell lineage cDNA encoding a type II transmembrane
RT glycoprotein potentially involved in the regulation of recombination
RT activating gene 1 (RAG1).";
RL Eur. J. Immunol. 28:2839-2853(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11032940; DOI=10.3892/or.7.6.1339;
RA Yuki M., Yoshinaga K., Yamakawa H., Sakurada K., Sato S., Yajima A.,
RA Horii A.;
RT "Structure, expression and mutational analysis of the hBRAG gene on 10q in
RT the frequently deleted region in human endometrial cancer.";
RL Oncol. Rep. 7:1339-1342(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RC TISSUE=Brain;
RX PubMed=11572857; DOI=10.1074/jbc.m104922200;
RA Ohtake S., Ito Y., Fukuta M., Habuchi O.;
RT "Human N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase cDNA is related
RT to human B cell recombination activating gene-associated gene.";
RL J. Biol. Chem. 276:43894-43900(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Blood, Duodenum, and Lung;
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 [8]
RP POSSIBLE FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, GLYCOSYLATION, DISULFIDE
RP BOND, AND INTERACTION WITH HCK.
RX PubMed=10749872; DOI=10.1074/jbc.m001866200;
RA Verkoczy L.K., Guinn B.-A., Berinstein N.L.;
RT "Characterization of the human B cell RAG-associated gene, hBRAG, as a B
RT cell receptor signal-enhancing glycoprotein dimer that associates with
RT phosphorylated proteins in resting B cells.";
RL J. Biol. Chem. 275:20967-20979(2000).
RN [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=12874280; DOI=10.1074/jbc.m306132200;
RA Ohtake S., Kimata K., Habuchi O.;
RT "A unique nonreducing terminal modification of chondroitin sulfate by N-
RT acetylgalactosamine 4-sulfate 6-o-sulfotransferase.";
RL J. Biol. Chem. 278:38443-38452(2003).
RN [10]
RP ACTIVITY REGULATION.
RX PubMed=16024005; DOI=10.1016/j.carres.2005.06.010;
RA Sawada T., Fujii S., Nakano H., Ohtake S., Kimata K., Habuchi O.;
RT "Synthesis of sulfated phenyl 2-acetamido-2-deoxy-D--D-galactopyranosides.
RT 4-O-Sulfated phenyl 2-acetamido-2-deoxy-beta-D-galactopyranoside is a
RT competitive acceptor that decreases sulfation of chondroitin sulfate by N-
RT acetylgalactosamine 4-sulfate 6-O-sulfotransferase.";
RL Carbohydr. Res. 340:1983-1996(2005).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
CC -!- FUNCTION: Sulfotransferase that transfers sulfate from 3'-
CC phosphoadenosine 5'-phosphosulfate (PAPS) to the C-6 hydroxyl group of
CC the GalNAc 4-sulfate residue of chondroitin sulfate A and forms
CC chondroitin sulfate E containing GlcA-GalNAc(4,6-SO(4)) repeating
CC units. It also transfers sulfate to a unique non-reducing terminal
CC sequence, GalNAc(4SO4)-GlcA(2SO4)-GalNAc(6SO4), to yield a highly
CC sulfated structure similar to the structure found in thrombomodulin
CC chondroitin sulfate. May also act as a B-cell receptor involved in BCR
CC ligation-mediated early activation that mediate regulatory signals key
CC to B-cell development and/or regulation of B-cell-specific RAG
CC expression; however such results are unclear in vivo.
CC {ECO:0000269|PubMed:11572857, ECO:0000269|PubMed:12874280}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=n 3'-phosphoadenylyl sulfate + dermatan 4'-sulfate = n
CC adenosine 3',5'-bisphosphate + dermatan 4',6'-bissulfate + n H(+);
CC Xref=Rhea:RHEA:54304, Rhea:RHEA-COMP:9965, Rhea:RHEA-COMP:13850,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58339, ChEBI:CHEBI:58343,
CC ChEBI:CHEBI:58465, ChEBI:CHEBI:138121; EC=2.8.2.33;
CC Evidence={ECO:0000269|PubMed:12874280};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=n 3'-phosphoadenylyl sulfate + chondroitin 4'-sulfate = n
CC adenosine 3',5'-bisphosphate + chondroitin 4',6'-bissulfate + n H(+);
CC Xref=Rhea:RHEA:54300, Rhea:RHEA-COMP:9829, Rhea:RHEA-COMP:13849,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58339, ChEBI:CHEBI:58343,
CC ChEBI:CHEBI:58422, ChEBI:CHEBI:138112; EC=2.8.2.33;
CC Evidence={ECO:0000269|PubMed:12874280};
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000250};
CC -!- COFACTOR:
CC Name=glutathione; Xref=ChEBI:CHEBI:57925; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by phenyl beta-GalNAc(4,6-SO(4)).
CC {ECO:0000269|PubMed:16024005}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (Potential). The relevance of
CC homodimerization is however unsure. May interact with phosphorylated
CC proteins in resting B-cells, including HCK.
CC {ECO:0000269|PubMed:10749872, ECO:0000305}.
CC -!- INTERACTION:
CC Q7LFX5; P27824: CANX; NbExp=2; IntAct=EBI-11123530, EBI-355947;
CC Q7LFX5; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-11123530, EBI-16439278;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000305|PubMed:10749872}; Single-pass type II membrane protein
CC {ECO:0000305|PubMed:10749872}. Note=A small fraction may also be
CC present at the cell surface, where it acts as a B-cell receptor.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q7LFX5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7LFX5-2; Sequence=VSP_017387;
CC -!- TISSUE SPECIFICITY: Expressed in B-cell-enriched tissues but not in
CC fetal or adult thymus. Expressed in fetal and adult spleen, lymph node,
CC tonsil, bone marrow and peripheral leukocytes. Not expressed in T-
CC cells. In pro-B, pre-B, and mature B-cell lines, it colocalizes with
CC RAG1. {ECO:0000269|PubMed:9754571}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:10749872}.
CC -!- SIMILARITY: Belongs to the sulfotransferase 1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC71691.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAH50540.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA25524.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF026477; AAC71691.1; ALT_FRAME; mRNA.
DR EMBL; AB025341; BAA83686.1; -; Genomic_DNA.
DR EMBL; AB062423; BAB72145.1; -; mRNA.
DR EMBL; AB011170; BAA25524.2; ALT_INIT; mRNA.
DR EMBL; CR749804; CAH18664.1; -; mRNA.
DR EMBL; AL683842; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC027908; AAH27908.1; -; mRNA.
DR EMBL; BC050540; AAH50540.1; ALT_FRAME; mRNA.
DR EMBL; BC075813; AAH75813.1; -; mRNA.
DR CCDS; CCDS55731.1; -. [Q7LFX5-2]
DR CCDS; CCDS7638.1; -. [Q7LFX5-1]
DR RefSeq; NP_001257693.1; NM_001270764.1. [Q7LFX5-1]
DR RefSeq; NP_001257694.1; NM_001270765.1. [Q7LFX5-2]
DR RefSeq; NP_056976.2; NM_015892.4. [Q7LFX5-1]
DR RefSeq; XP_005269948.1; XM_005269891.3. [Q7LFX5-1]
DR RefSeq; XP_006717954.1; XM_006717891.3. [Q7LFX5-1]
DR RefSeq; XP_016871808.1; XM_017016319.1. [Q7LFX5-1]
DR AlphaFoldDB; Q7LFX5; -.
DR BioGRID; 119498; 76.
DR IntAct; Q7LFX5; 23.
DR STRING; 9606.ENSP00000402394; -.
DR GlyGen; Q7LFX5; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q7LFX5; -.
DR PhosphoSitePlus; Q7LFX5; -.
DR BioMuta; CHST15; -.
DR DMDM; 74749920; -.
DR jPOST; Q7LFX5; -.
DR MassIVE; Q7LFX5; -.
DR PaxDb; Q7LFX5; -.
DR PeptideAtlas; Q7LFX5; -.
DR PRIDE; Q7LFX5; -.
DR ProteomicsDB; 68858; -. [Q7LFX5-1]
DR ProteomicsDB; 68859; -. [Q7LFX5-2]
DR Antibodypedia; 2663; 72 antibodies from 24 providers.
DR DNASU; 51363; -.
DR Ensembl; ENST00000346248.7; ENSP00000333947.6; ENSG00000182022.18. [Q7LFX5-1]
DR Ensembl; ENST00000435907.6; ENSP00000402394.1; ENSG00000182022.18. [Q7LFX5-1]
DR Ensembl; ENST00000628426.1; ENSP00000485905.1; ENSG00000182022.18. [Q7LFX5-2]
DR GeneID; 51363; -.
DR KEGG; hsa:51363; -.
DR MANE-Select; ENST00000435907.6; ENSP00000402394.1; NM_001270764.2; NP_001257693.1.
DR UCSC; uc001lhm.5; human. [Q7LFX5-1]
DR CTD; 51363; -.
DR DisGeNET; 51363; -.
DR GeneCards; CHST15; -.
DR HGNC; HGNC:18137; CHST15.
DR HPA; ENSG00000182022; Low tissue specificity.
DR MIM; 608277; gene.
DR neXtProt; NX_Q7LFX5; -.
DR OpenTargets; ENSG00000182022; -.
DR PharmGKB; PA165548385; -.
DR VEuPathDB; HostDB:ENSG00000182022; -.
DR eggNOG; ENOG502QU6N; Eukaryota.
DR GeneTree; ENSGT00390000004719; -.
DR HOGENOM; CLU_017703_2_1_1; -.
DR InParanoid; Q7LFX5; -.
DR OMA; KYTMHMV; -.
DR OrthoDB; 356648at2759; -.
DR PhylomeDB; Q7LFX5; -.
DR TreeFam; TF333516; -.
DR BioCyc; MetaCyc:HS11694-MON; -.
DR BRENDA; 2.8.2.33; 2681.
DR PathwayCommons; Q7LFX5; -.
DR Reactome; R-HSA-2022870; Chondroitin sulfate biosynthesis.
DR SignaLink; Q7LFX5; -.
DR BioGRID-ORCS; 51363; 13 hits in 1069 CRISPR screens.
DR ChiTaRS; CHST15; human.
DR GeneWiki; GALNAC4S-6ST; -.
DR GenomeRNAi; 51363; -.
DR Pharos; Q7LFX5; Tbio.
DR PRO; PR:Q7LFX5; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q7LFX5; protein.
DR Bgee; ENSG00000182022; Expressed in blood and 200 other tissues.
DR ExpressionAtlas; Q7LFX5; baseline and differential.
DR Genevisible; Q7LFX5; HS.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0050656; F:3'-phosphoadenosine 5'-phosphosulfate binding; IDA:UniProtKB.
DR GO; GO:0050659; F:N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase activity; IDA:UniProtKB.
DR GO; GO:0030206; P:chondroitin sulfate biosynthetic process; TAS:Reactome.
DR GO; GO:0019319; P:hexose biosynthetic process; IDA:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disulfide bond; Glycoprotein; Golgi apparatus;
KW Membrane; Reference proteome; Signal-anchor; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..561
FT /note="Carbohydrate sulfotransferase 15"
FT /id="PRO_0000225623"
FT TOPO_DOM 1..80
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 81..101
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 102..561
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT BINDING 263..267
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 392
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 400
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT CARBOHYD 364
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 451..561
FT /note="RLQVGLYAVYLLDWLSVFDKQQFLILRLEDHASNVKYTMHKVFQFLNLGPLS
FT EKQEALMTKSPASNARRPEDRNLGPMWPITQKILRDFYRPFNARLAQVLADEAFAWKTT
FT -> CTPPPRTPRAGPWQKELVCCYYASGIVGLRFSIGTERSVLMCKCCSPLFMDVKAEN
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_017387"
SQ SEQUENCE 561 AA; 64926 MW; 74643A7CFF7F242D CRC64;
MRHCINCCIQ LLPDGAHKQQ VNCQGGPHHG HQACPTCKGE NKILFRVDSK QMNLLAVLEV
RTEGNENWGG FLRFKKGKRC SLVFGLIIMT LVMASYILSG AHQELLISSP FHYGGFPSNP
SLMDSENPSD TKEHHHQSSV NNISYMKDYP SIKLIINSIT TRIEFTTRQL PDLEDLKKQE
LHMFSVIPNK FLPNSKSPCW YEEFSGQNTT DPYLTNSYVL YSKRFRSTFD ALRKAFWGHL
AHAHGKHFRL RCLPHFYIIG QPKCGTTDLY DRLRLHPEVK FSAIKEPHWW TRKRFGIVRL
RDGLRDRYPV EDYLDLFDLA AHQIHQGLQA SSAKEQSKMN TIIIGEASAS TMWDNNAWTF
FYDNSTDGEP PFLTQDFIHA FQPNARLIVM LRDPVERLYS DYLYFASSNK SADDFHEKVT
EALQLFENCM LDYSLRACVY NNTLNNAMPV RLQVGLYAVY LLDWLSVFDK QQFLILRLED
HASNVKYTMH KVFQFLNLGP LSEKQEALMT KSPASNARRP EDRNLGPMWP ITQKILRDFY
RPFNARLAQV LADEAFAWKT T
