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 23-FEB-2022, entry version 159. 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}; 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; 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 BioGRID; 119498; 27. 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; 70 antibodies from 24 providers. DR DNASU; 51363; -. DR Ensembl; ENST00000346248; ENSP00000333947; ENSG00000182022. DR Ensembl; ENST00000435907; ENSP00000402394; ENSG00000182022. DR Ensembl; ENST00000628426; ENSP00000485905; ENSG00000182022. [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 BRENDA; 2.8.2.33; 2681. DR PathwayCommons; Q7LFX5; -. DR Reactome; R-HSA-2022870; Chondroitin sulfate biosynthesis. DR SignaLink; Q7LFX5; -. DR BioGRID-ORCS; 51363; 10 hits in 1037 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 234 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 NP_BIND 263..267 FT /note="PAPS" FT /evidence="ECO:0000250" FT BINDING 392 FT /note="PAPS" FT /evidence="ECO:0000250" FT BINDING 400 FT /note="PAPS" 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 //