CHSTB_HUMAN
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 03-AUG-2022, entry version 159.
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=n 3'-phosphoadenylyl sulfate + chondroitin beta-D-glucuronate
CC = n adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate + 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}.
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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_001173982.1. [Q9NPF2-2]
DR RefSeq; NP_060883.1; NM_018413.5. [Q9NPF2-1]
DR AlphaFoldDB; Q9NPF2; -.
DR BioGRID; 119084; 14.
DR IntAct; Q9NPF2; 4.
DR STRING; 9606.ENSP00000305725; -.
DR GlyGen; Q9NPF2; 4 sites.
DR iPTMnet; Q9NPF2; -.
DR PhosphoSitePlus; Q9NPF2; -.
DR SwissPalm; Q9NPF2; -.
DR BioMuta; CHST11; -.
DR DMDM; 61212137; -.
DR EPD; Q9NPF2; -.
DR MassIVE; Q9NPF2; -.
DR MaxQB; Q9NPF2; -.
DR PaxDb; Q9NPF2; -.
DR PeptideAtlas; Q9NPF2; -.
DR PRIDE; Q9NPF2; -.
DR ProteomicsDB; 81982; -. [Q9NPF2-1]
DR ProteomicsDB; 81983; -. [Q9NPF2-2]
DR Antibodypedia; 30604; 185 antibodies from 26 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 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 neXtProt; NX_Q9NPF2; -.
DR OpenTargets; ENSG00000171310; -.
DR PharmGKB; PA134875681; -.
DR VEuPathDB; HostDB:ENSG00000171310; -.
DR eggNOG; KOG4651; Eukaryota.
DR GeneTree; ENSGT00940000159167; -.
DR HOGENOM; CLU_043398_1_1_1; -.
DR InParanoid; Q9NPF2; -.
DR OMA; KMDFLMF; -.
DR PhylomeDB; Q9NPF2; -.
DR TreeFam; TF325581; -.
DR BioCyc; MetaCyc:HS10284-MON; -.
DR BRENDA; 2.8.2.5; 2681.
DR PathwayCommons; Q9NPF2; -.
DR Reactome; R-HSA-2022870; Chondroitin sulfate biosynthesis.
DR SignaLink; Q9NPF2; -.
DR BioGRID-ORCS; 50515; 9 hits in 1079 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 161 other tissues.
DR ExpressionAtlas; Q9NPF2; baseline and differential.
DR Genevisible; Q9NPF2; HS.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0047756; F:chondroitin 4-sulfotransferase activity; IDA:UniProtKB.
DR GO; GO:0001537; F:N-acetylgalactosamine 4-O-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:0006915; P:apoptotic process; IEA:Ensembl.
DR GO; GO:0016051; P:carbohydrate biosynthetic process; IEA:InterPro.
DR GO; GO:0002063; P:chondrocyte development; IEA:Ensembl.
DR GO; GO:0030206; P:chondroitin sulfate biosynthetic process; IDA:UniProtKB.
DR GO; GO:0048589; P:developmental growth; IEA:Ensembl.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl.
DR GO; GO:0048703; P:embryonic viscerocranium morphogenesis; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0033037; P:polysaccharide localization; IEA:Ensembl.
DR GO; GO:0036342; P:post-anal tail morphogenesis; IEA:Ensembl.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0030166; P:proteoglycan biosynthetic process; IBA:GO_Central.
DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0007585; P:respiratory gaseous exchange by respiratory system; IEA:Ensembl.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IEA:Ensembl.
DR InterPro; IPR018011; Carb_sulfotrans_8-10.
DR InterPro; IPR005331; Sulfotransferase.
DR PANTHER; PTHR12137; PTHR12137; 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 Reference proteome; Signal-anchor; Transferase; Transmembrane;
KW 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
