ID CHSTB_HUMAN Reviewed; 352 AA. AC Q9NPF2; A8K4F8; Q9NXY6; Q9NY36; DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 02-SEP-2026, entry version 177. DE RecName: Full=Carbohydrate sulfotransferase 11; DE EC=2.8.2.5; DE AltName: Full=Chondroitin 4-O-sulfotransferase 1; DE AltName: Full=Chondroitin 4-sulfotransferase 1; DE Short=C4S-1; DE Short=C4ST-1; DE Short=C4ST1; GN Name=CHST11; 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), ENZYME ACTIVITY, AND TISSUE RP SPECIFICITY. RC TISSUE=Fetal brain; RX PubMed=11056388; DOI=10.1093/oxfordjournals.jbchem.a022813; RA Okuda T., Mita S., Yamauchi S., Matsubara T., Yagi F., Yamamori D., RA Fukuta M., Kuroiwa A., Matsuda Y., Habuchi O.; RT "Molecular cloning, expression, and chromosomal mapping of human RT chondroitin 4-sulfotransferase, whose expression pattern in human tissues RT is different from that of chondroitin 6-sulfotransferase."; RL J. Biochem. 128:763-770(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ENZYME ACTIVITY, AND TISSUE RP SPECIFICITY. RX PubMed=10781601; DOI=10.1074/jbc.m002443200; RA Hiraoka N., Nakagawa H., Ong E., Akama O.T., Fukuda N.M., Fukuda M.; RT "Molecular cloning and expression of two distinct human chondroitin 4-O- RT sulfotransferases that belong to the HNK-1 sulfotransferase gene family."; RL J. Biol. Chem. 275:20188-20196(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RA Xia G., Evers M.R., Schachner M.; RT "Cloning and expression of a human chondroitin-4-sulfotransferase similar RT to members of the HNK-1 sulfotransferase family."; RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=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 [7] RP SUBSTRATE SPECIFICITY. RX PubMed=12847091; DOI=10.1074/jbc.m306044200; RA Mikami T., Mizumoto S., Kago N., Kitagawa H., Sugahara K.; RT "Specificities of three distinct human chondroitin/dermatan N- RT acetylgalactosamine 4-O-sulfotransferases demonstrated using partially RT desulfated dermatan sulfate as an acceptor. Implication of differential RT roles in dermatan sulfate biosynthesis."; RL J. Biol. Chem. 278:36115-36127(2003). RN [8] RP DISEASE, AND CHROMOSOMAL TRANSLOCATION WITH IGH. RX PubMed=15273723; DOI=10.1038/sj.onc.1207934; RA Schmidt H.H., Dyomin V.G., Palanisamy N., Itoyama T., Nanjangud G., RA Pirc-Danoewinata H., Haas O.A., Chaganti R.S.K.; RT "Deregulation of the carbohydrate (chondroitin 4) sulfotransferase 11 RT (CHST11) gene in a B-cell chronic lymphocytic leukemia with a RT t(12;14)(q23;q32)."; RL Oncogene 23:6991-6996(2004). RN [9] RP BIOPHYSICOCHEMICAL PROPERTIES, GLYCOSYLATION, AND MUTAGENESIS OF LYS-125; RP ASN-205; ASN-223 AND ASN-342. RX PubMed=15628971; DOI=10.1042/bj20041573; RA Yusa A., Kitajima K., Habuchi O.; RT "N-linked oligosaccharides are required to produce and stabilize the active RT form of chondroitin 4-sulphotransferase-1."; RL Biochem. J. 388:115-121(2005). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [11] RP INVOLVEMENT IN OCBMD, AND VARIANT OCBMD 161-LEU--ASN-165 DEL. RX PubMed=29514872; DOI=10.1136/jmedgenet-2017-105003; RA Shabbir R.M.K., Nalbant G., Ahmad N., Malik S., Tolun A.; RT "Homozygous CHST11 mutation in chondrodysplasia, brachydactyly, overriding RT digits, clino-symphalangism and synpolydactyly."; RL J. Med. Genet. 55:489-496(2018). CC -!- FUNCTION: Catalyzes the transfer of sulfate to position 4 of the N- CC acetylgalactosamine (GalNAc) residue of chondroitin. Chondroitin CC sulfate constitutes the predominant proteoglycan present in cartilage CC and is distributed on the surfaces of many cells and extracellular CC matrices. Can also sulfate Gal residues in desulfated dermatan sulfate. CC Preferentially sulfates in GlcA->GalNAc unit than in IdoA->GalNAc unit. CC Does not form 4, 6-di-O-sulfated GalNAc when chondroitin sulfate C is CC used as an acceptor. CC -!- CATALYTIC ACTIVITY: CC Reaction=chondroitin beta-D-glucuronate + n 3'-phosphoadenylyl sulfate CC = chondroitin 4'-sulfate + n adenosine 3',5'-bisphosphate + n H(+); CC Xref=Rhea:RHEA:16101, Rhea:RHEA-COMP:9827, Rhea:RHEA-COMP:9829, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57652, ChEBI:CHEBI:58339, CC ChEBI:CHEBI:58343, ChEBI:CHEBI:58422; EC=2.8.2.5; CC Evidence={ECO:0000269|PubMed:10781601, ECO:0000269|PubMed:11056388}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.5 uM for PAPS {ECO:0000269|PubMed:15628971}; CC KM=2.1 mM for chondroitin {ECO:0000269|PubMed:15628971}; 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=2; CC Name=1; CC IsoId=Q9NPF2-1; Sequence=Displayed; CC Name=2; Synonyms=C4S-1A; CC IsoId=Q9NPF2-2; Sequence=VSP_012992; CC -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in spleen, CC thymus, bone marrow, peripheral blood leukocytes, lymph node, heart, CC brain, lung and placenta. {ECO:0000269|PubMed:10781601, CC ECO:0000269|PubMed:11056388}. CC -!- PTM: N-glycosylated; required for activity and stability. CC {ECO:0000269|PubMed:15628971}. CC -!- DISEASE: Note=A chromosomal aberration involving CHST11 is found in B- CC cell chronic lymphocytic leukemias. Translocation t(12;14)(q23;q32) CC with IgH. {ECO:0000269|PubMed:15273723}. CC -!- DISEASE: Osteochondrodysplasia, brachydactyly, and overlapping CC malformed digits (OCBMD) [MIM:618167]: An autosomal recessive disorder CC characterized by bilateral symmetric skeletal defects that primarily CC affect the limbs. Affected individuals have mild short stature due to CC shortening of the lower leg bones, as well as hand and foot CC malformations, predominantly brachydactyly and overlapping digits. CC Other skeletal defects include scoliosis, dislocated patellae and CC fibulae, and pectus excavatum. {ECO:0000269|PubMed:29514872}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the sulfotransferase 2 family. {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; AB042326; BAA95485.1; -; mRNA. DR EMBL; AF239820; AAF81691.1; -; mRNA. DR EMBL; AJ269537; CAB87380.1; -; mRNA. DR EMBL; AJ289134; CAB92134.1; -; mRNA. DR EMBL; AK290923; BAF83612.1; -; mRNA. DR EMBL; CH471054; EAW97748.1; -; Genomic_DNA. DR EMBL; BC013315; AAH13315.1; -; mRNA. DR CCDS; CCDS55878.1; -. [Q9NPF2-2] DR CCDS; CCDS9099.1; -. [Q9NPF2-1] DR PIR; JC7525; JC7525. DR RefSeq; NP_001167453.1; NM_001173982.2. [Q9NPF2-2] DR RefSeq; NP_060883.1; NM_018413.6. [Q9NPF2-1] DR AlphaFoldDB; Q9NPF2; -. DR BioGRID; 119084; 23. DR FunCoup; Q9NPF2; 481. DR IntAct; Q9NPF2; 15. DR NDEx; IQUERY-CP-CHST11; 3 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000305725; -. DR GlyCosmos; Q9NPF2; 4 sites, No reported glycans. DR GlyGen; Q9NPF2; 5 sites, 2 N-linked glycans (2 sites), 1 O-linked glycan (1 site). DR iPTMnet; Q9NPF2; -. DR PhosphoSitePlus; Q9NPF2; -. DR SwissPalm; Q9NPF2; -. DR BioMuta; CHST11; -. DR DMDM; 61212137; -. DR jPOST; Q9NPF2; -. DR MassIVE; Q9NPF2; -. DR PaxDb; 9606-ENSP00000305725; -. DR PeptideAtlas; Q9NPF2; -. DR ProteomicsDB; 81982; -. [Q9NPF2-1] DR ProteomicsDB; 81983; -. [Q9NPF2-2] DR Antibodypedia; 30604; 175 antibodies from 25 providers. DR DNASU; 50515; -. DR Ensembl; ENST00000303694.6; ENSP00000305725.5; ENSG00000171310.11. [Q9NPF2-1] DR Ensembl; ENST00000549260.5; ENSP00000450004.1; ENSG00000171310.11. [Q9NPF2-2] DR GeneID; 50515; -. DR KEGG; hsa:50515; -. DR MANE-Select; ENST00000303694.6; ENSP00000305725.5; NM_018413.6; NP_060883.1. DR UCSC; uc001tky.4; human. [Q9NPF2-1] DR AGR; HGNC:17422; -. DR ClinPGx; PA134875681; -. DR CTD; 50515; -. DR DisGeNET; 50515; -. DR GeneCards; CHST11; -. DR HGNC; HGNC:17422; CHST11. DR HPA; ENSG00000171310; Tissue enhanced (bone marrow, choroid plexus). DR MalaCards; CHST11; -. DR MIM; 610128; gene. DR MIM; 618167; phenotype. DR OpenTargets; ENSG00000171310; -. DR VEuPathDB; HostDB:ENSG00000171310; -. DR eggNOG; KOG4651; Eukaryota. DR GeneTree; ENSGT00940000159167; -. DR HOGENOM; CLU_043398_1_1_1; -. DR InParanoid; Q9NPF2; -. DR OMA; ISMEHQT; -. DR OrthoDB; 2019940at2759; -. DR PAN-GO; Q9NPF2; 2 GO annotations based on evolutionary models. DR PhylomeDB; Q9NPF2; -. DR BioCyc; MetaCyc:HS10284-MONOMER; -. DR BRENDA; 2.8.2.5; 2681. DR PathwayCommons; Q9NPF2; -. DR Reactome; R-HSA-2022870; CS-GAG biosynthesis. DR SignaLink; Q9NPF2; -. DR Agora; ENSG00000171310; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 50515; 11 hits in 1159 CRISPR screens. DR ChiTaRS; CHST11; human. DR GeneWiki; CHST11; -. DR GenomeRNAi; 50515; -. DR Pharos; Q9NPF2; Tbio. DR PRO; PR:Q9NPF2; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q9NPF2; protein. DR Bgee; ENSG00000171310; Expressed in tibia and 163 other cell types or tissues. DR ExpressionAtlas; Q9NPF2; baseline and differential. DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0047756; F:chondroitin 4-sulfotransferase activity; IDA:UniProtKB. DR GO; GO:0001537; F:dermatan 4-sulfotransferase activity; IDA:UniProtKB. DR GO; GO:0050659; F:N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase activity; IEA:Ensembl. DR GO; GO:0008146; F:sulfotransferase activity; IBA:GO_Central. DR GO; GO:0016051; P:carbohydrate biosynthetic process; IEA:InterPro. DR GO; GO:0050650; P:chondroitin sulfate proteoglycan biosynthetic process; IDA:UniProtKB. DR GO; GO:0030166; P:proteoglycan biosynthetic process; IBA:GO_Central. DR InterPro; IPR018011; Carb_sulfotrans_8-10. DR InterPro; IPR005331; Sulfotransferase. DR PANTHER; PTHR12137; CARBOHYDRATE SULFOTRANSFERASE; 1. DR PANTHER; PTHR12137:SF32; CARBOHYDRATE SULFOTRANSFERASE 11; 1. DR Pfam; PF03567; Sulfotransfer_2; 1. PE 1: Evidence at protein level; KW Alternative splicing; Carbohydrate metabolism; Chromosomal rearrangement; KW Disease variant; Dwarfism; Glycoprotein; Golgi apparatus; Membrane; KW Proteomics identification; Reference proteome; Signal-anchor; Transferase; KW Transmembrane; Transmembrane helix. FT CHAIN 1..352 FT /note="Carbohydrate sulfotransferase 11" FT /id="PRO_0000189664" FT TOPO_DOM 1..16 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 17..37 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255" FT TOPO_DOM 38..352 FT /note="Lumenal" FT /evidence="ECO:0000255" FT BINDING 124..130 FT /ligand="3'-phosphoadenylyl sulfate" FT /ligand_id="ChEBI:CHEBI:58339" FT /evidence="ECO:0000250" FT BINDING 186..194 FT /ligand="3'-phosphoadenylyl sulfate" FT /ligand_id="ChEBI:CHEBI:58339" FT /evidence="ECO:0000250" FT CARBOHYD 205 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 223 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 321 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 342 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000305|PubMed:15628971" FT VAR_SEQ 35..40 FT /note="SMLHPV -> I (in isoform 2)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_012992" FT VARIANT 161..165 FT /note="Missing (in OCBMD)" FT /evidence="ECO:0000269|PubMed:29514872" FT /id="VAR_081477" FT MUTAGEN 125 FT /note="K->Q: Abolishes enzyme activity but does not affect FT stability of the protein." FT /evidence="ECO:0000269|PubMed:15628971" FT MUTAGEN 205 FT /note="N->S: Induces a weak decrease in enzyme activity but FT has no effect on stability of the protein. Unstable FT protein; when associated with S-223 and S-321." FT /evidence="ECO:0000269|PubMed:15628971" FT MUTAGEN 223 FT /note="N->S: Induces a weak decrease in enzyme activity but FT has no effect on stability of the protein. Unstable FT protein; when associated with S-205 and S-321." FT /evidence="ECO:0000269|PubMed:15628971" FT MUTAGEN 321 FT /note="N->S: Induces a strong decrease in enzyme activity FT but has no effect on stability of the protein. Unstable FT protein; when associated with S-205 and S-223." FT MUTAGEN 342 FT /note="N->S: Induces a strong decrease in enzyme activity FT has no effect on stability of the protein." FT /evidence="ECO:0000269|PubMed:15628971" FT CONFLICT 289 FT /note="V -> F (in Ref. 3; CAB87380)" FT /evidence="ECO:0000305" SQ SEQUENCE 352 AA; 41555 MW; 55DF1D29D6703307 CRC64; MKPALLEVMR MNRICRMVLA TCLGSFILVI FYFQSMLHPV MRRNPFGVDI CCRKGSRSPL QELYNPIQLE LSNTAVLHQM RRDQVTDTCR ANSATSRKRR VLTPNDLKHL VVDEDHELIY CYVPKVACTN WKRLMMVLTG RGKYSDPMEI PANEAHVSAN LKTLNQYSIP EINHRLKSYM KFLFVREPFE RLVSAYRNKF TQKYNISFHK RYGTKIIKRQ RKNATQEALR KGDDVKFEEF VAYLIDPHTQ REEPFNEHWQ TVYSLCHPCH IHYDLVGKYE TLEEDSNYVL QLAGVGSYLK FPTYAKSTRT TDEMTTEFFQ NISSEHQTQL YEVYKLDFLM FNYSVPSYLK LE //