CHSTE_HUMAN
ID CHSTE_HUMAN Reviewed; 376 AA.
AC Q8NCH0; Q6PJ31; Q6UXA0; Q96P94;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Carbohydrate sulfotransferase 14;
DE EC=2.8.2.35;
DE AltName: Full=Dermatan 4-sulfotransferase 1;
DE Short=D4ST-1;
DE Short=hD4ST1;
GN Name=CHST14; Synonyms=D4ST1; ORFNames=UNQ1925/PRO4400;
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], ENZYME ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=11470797; DOI=10.1074/jbc.m105848200;
RA Evers M.R., Xia G., Kang H.-G., Schachner M., Baenziger J.U.;
RT "Molecular cloning and characterization of a dermatan-specific N-
RT acetylgalactosamine 4-O-sulfotransferase.";
RL J. Biol. Chem. 276:36344-36353(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND 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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Hiraoka N., Fukuda M.;
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Teratocarcinoma;
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 MRNA].
RC TISSUE=Lung, and Uterus;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 36-376.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [7]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=19661164; DOI=10.1093/glycob/cwp110;
RA Pacheco B., Maccarana M., Malmstrom A.;
RT "Dermatan 4-O-sulfotransferase 1 is pivotal in the formation of iduronic
RT acid blocks in dermatan sulfate.";
RL Glycobiology 19:1197-1203(2009).
RN [8]
RP INVOLVEMENT IN EDSMC1.
RX PubMed=20842734; DOI=10.1002/humu.21355;
RA Malfait F., Syx D., Vlummens P., Symoens S., Nampoothiri S.,
RA Hermanns-Le T., Van Laer L., De Paepe A.;
RT "Musculocontractural Ehlers-Danlos syndrome (former EDS type VIB) and
RT adducted thumb clubfoot syndrome (ATCS) represent a single clinical entity
RT caused by mutations in the dermatan-4-sulfotransferase 1 encoding CHST14
RT gene.";
RL Hum. Mutat. 31:1233-1239(2010).
RN [9]
RP VARIANTS EDSMC1 GLY-135; GLN-137; PRO-213 AND CYS-293, AND CHARACTERIZATION
RP OF VARIANTS EDSMC1 GLY-135; GLN-137; PRO-213 AND CYS-293.
RX PubMed=20004762; DOI=10.1016/j.ajhg.2009.11.010;
RA Dundar M., Muller T., Zhang Q., Pan J., Steinmann B., Vodopiutz J.,
RA Gruber R., Sonoda T., Krabichler B., Utermann G., Baenziger J.U., Zhang L.,
RA Janecke A.R.;
RT "Loss of dermatan-4-sulfotransferase 1 function results in adducted thumb-
RT clubfoot syndrome.";
RL Am. J. Hum. Genet. 85:873-882(2009).
RN [10]
RP VARIANTS EDSMC1 LEU-281; SER-289 AND CYS-293, AND CHARACTERIZATION OF
RP VARIANTS EDSMC1 LEU-281; SER-289 AND CYS-293.
RX PubMed=20533528; DOI=10.1002/humu.21300;
RA Miyake N., Kosho T., Mizumoto S., Furuichi T., Hatamochi A., Nagashima Y.,
RA Arai E., Takahashi K., Kawamura R., Wakui K., Takahashi J., Kato H.,
RA Yasui H., Ishida T., Ohashi H., Nishimura G., Shiina M., Saitsu H.,
RA Tsurusaki Y., Doi H., Fukushima Y., Ikegawa S., Yamada S., Sugahara K.,
RA Matsumoto N.;
RT "Loss-of-function mutations of CHST14 in a new type of Ehlers-Danlos
RT syndrome.";
RL Hum. Mutat. 31:966-974(2010).
CC -!- FUNCTION: Catalyzes the transfer of sulfate to position 4 of the N-
CC acetylgalactosamine (GalNAc) residue of dermatan sulfate. Plays a
CC pivotal role in the formation of 4-0-sulfated IdoA blocks in dermatan
CC sulfate. Transfers sulfate to the C-4 hydroxyl of beta1,4-linked GalNAc
CC that is substituted with an alpha-linked iduronic acid (IdoUA) at the
CC C-3 hydroxyl. Transfers sulfate more efficiently to GalNAc residues in
CC -IdoUA-GalNAc-IdoUA- than in -GlcUA-GalNAc-GlcUA-sequences. Has
CC preference for partially desulfated dermatan sulfate. Addition of
CC sulfate to GalNAc may occur immediately after epimerization of GlcUA to
CC IdoUA. Appears to have an important role in the formation of the
CC cerebellar neural network during postnatal brain development.
CC {ECO:0000269|PubMed:19661164}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=n 3'-phosphoadenylyl sulfate + dermatan = n adenosine 3',5'-
CC bisphosphate + dermatan 4'-sulfate + n H(+); Xref=Rhea:RHEA:48052,
CC Rhea:RHEA-COMP:9965, Rhea:RHEA-COMP:11986, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:58339, ChEBI:CHEBI:58343, ChEBI:CHEBI:58465,
CC ChEBI:CHEBI:60059; EC=2.8.2.35;
CC Evidence={ECO:0000269|PubMed:11470797, ECO:0000269|PubMed:19661164};
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250}; Single-
CC pass type II membrane protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed at high level in
CC pituitary gland, placenta, uterus and thyroid.
CC {ECO:0000269|PubMed:11470797}.
CC -!- DISEASE: Ehlers-Danlos syndrome, musculocontractural type 1 (EDSMC1)
CC [MIM:601776]: A form of Ehlers-Danlos syndrome characterized by
CC distinctive craniofacial dysmorphism, congenital contractures of thumbs
CC and fingers, clubfeet, severe kyphoscoliosis, muscular hypotonia,
CC hyperextensible thin skin with easy bruisability and atrophic scarring,
CC wrinkled palms, joint hypermobility, and ocular involvement.
CC {ECO:0000269|PubMed:20004762, ECO:0000269|PubMed:20533528,
CC ECO:0000269|PubMed:20842734}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the sulfotransferase 2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAQ88811.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF401222; AAK92532.1; -; mRNA.
DR EMBL; AB066595; BAB84097.1; -; mRNA.
DR EMBL; AF282905; AAK69530.1; -; mRNA.
DR EMBL; AK074739; BAC11172.1; -; mRNA.
DR EMBL; BC023653; AAH23653.1; -; mRNA.
DR EMBL; BC049214; AAH49214.1; -; mRNA.
DR EMBL; BC053633; AAH53633.1; -; mRNA.
DR EMBL; AY358446; AAQ88811.1; ALT_INIT; mRNA.
DR CCDS; CCDS10059.1; -.
DR RefSeq; NP_569735.1; NM_130468.3.
DR AlphaFoldDB; Q8NCH0; -.
DR BioGRID; 125232; 115.
DR IntAct; Q8NCH0; 8.
DR STRING; 9606.ENSP00000307297; -.
DR GlyGen; Q8NCH0; 2 sites.
DR iPTMnet; Q8NCH0; -.
DR PhosphoSitePlus; Q8NCH0; -.
DR BioMuta; CHST14; -.
DR DMDM; 61211839; -.
DR EPD; Q8NCH0; -.
DR jPOST; Q8NCH0; -.
DR MassIVE; Q8NCH0; -.
DR MaxQB; Q8NCH0; -.
DR PaxDb; Q8NCH0; -.
DR PeptideAtlas; Q8NCH0; -.
DR PRIDE; Q8NCH0; -.
DR ProteomicsDB; 72895; -.
DR Antibodypedia; 23111; 107 antibodies from 24 providers.
DR DNASU; 113189; -.
DR Ensembl; ENST00000306243.7; ENSP00000307297.6; ENSG00000169105.8.
DR GeneID; 113189; -.
DR KEGG; hsa:113189; -.
DR MANE-Select; ENST00000306243.7; ENSP00000307297.6; NM_130468.4; NP_569735.1.
DR UCSC; uc001zlw.4; human.
DR CTD; 113189; -.
DR DisGeNET; 113189; -.
DR GeneCards; CHST14; -.
DR HGNC; HGNC:24464; CHST14.
DR HPA; ENSG00000169105; Low tissue specificity.
DR MalaCards; CHST14; -.
DR MIM; 601776; phenotype.
DR MIM; 608429; gene.
DR neXtProt; NX_Q8NCH0; -.
DR OpenTargets; ENSG00000169105; -.
DR Orphanet; 2953; Musculocontractural Ehlers-Danlos syndrome.
DR PharmGKB; PA162382258; -.
DR VEuPathDB; HostDB:ENSG00000169105; -.
DR eggNOG; KOG4651; Eukaryota.
DR GeneTree; ENSGT00940000162640; -.
DR HOGENOM; CLU_043398_1_3_1; -.
DR InParanoid; Q8NCH0; -.
DR OMA; SQKNMPH; -.
DR OrthoDB; 1330889at2759; -.
DR PhylomeDB; Q8NCH0; -.
DR TreeFam; TF325581; -.
DR BioCyc; MetaCyc:ENSG00000169105-MON; -.
DR BRENDA; 2.8.2.35; 2681.
DR PathwayCommons; Q8NCH0; -.
DR Reactome; R-HSA-2022923; Dermatan sulfate biosynthesis.
DR Reactome; R-HSA-3595174; Defective CHST14 causes EDS, musculocontractural type.
DR SignaLink; Q8NCH0; -.
DR BioGRID-ORCS; 113189; 12 hits in 1077 CRISPR screens.
DR ChiTaRS; CHST14; human.
DR GeneWiki; CHST14; -.
DR GenomeRNAi; 113189; -.
DR Pharos; Q8NCH0; Tbio.
DR PRO; PR:Q8NCH0; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q8NCH0; protein.
DR Bgee; ENSG00000169105; Expressed in stromal cell of endometrium and 136 other tissues.
DR ExpressionAtlas; Q8NCH0; baseline and differential.
DR Genevisible; Q8NCH0; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0001537; F:N-acetylgalactosamine 4-O-sulfotransferase activity; IDA:UniProtKB.
DR GO; GO:0042301; F:phosphate ion binding; NAS:UniProtKB.
DR GO; GO:0008146; F:sulfotransferase activity; IBA:GO_Central.
DR GO; GO:0016051; P:carbohydrate biosynthetic process; IEA:InterPro.
DR GO; GO:0030208; P:dermatan sulfate biosynthetic process; IDA:MGI.
DR GO; GO:0050655; P:dermatan sulfate proteoglycan metabolic process; IDA:UniProtKB.
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 Carbohydrate metabolism; Disease variant; Ehlers-Danlos syndrome;
KW Glycoprotein; Golgi apparatus; Membrane; Reference proteome; Signal-anchor;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..376
FT /note="Carbohydrate sulfotransferase 14"
FT /id="PRO_0000189672"
FT TOPO_DOM 1..39
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 40..60
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 61..376
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT BINDING 155..161
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 213..221
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 368
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 135
FT /note="R -> G (in EDSMC1; associated in a complex allele
FT with Q-137; results in altered intracellular processing;
FT dbSNP:rs267606727)"
FT /evidence="ECO:0000269|PubMed:20004762"
FT /id="VAR_063754"
FT VARIANT 137
FT /note="L -> Q (in EDSMC1; associated in a complex allele
FT with G-135; results in altered intracellular processing;
FT dbSNP:rs267606728)"
FT /evidence="ECO:0000269|PubMed:20004762"
FT /id="VAR_063755"
FT VARIANT 213
FT /note="R -> P (in EDSMC1; results in altered intracellular
FT processing; dbSNP:rs121908257)"
FT /evidence="ECO:0000269|PubMed:20004762"
FT /id="VAR_063756"
FT VARIANT 281
FT /note="P -> L (in EDSMC1; loss of activity;
FT dbSNP:rs267606729)"
FT /evidence="ECO:0000269|PubMed:20533528"
FT /id="VAR_064555"
FT VARIANT 289
FT /note="C -> S (in EDSMC1; loss of activity;
FT dbSNP:rs267606731)"
FT /evidence="ECO:0000269|PubMed:20533528"
FT /id="VAR_064556"
FT VARIANT 293
FT /note="Y -> C (in EDSMC1; results in altered intracellular
FT processing; loss of activity; dbSNP:rs121908258)"
FT /evidence="ECO:0000269|PubMed:20004762,
FT ECO:0000269|PubMed:20533528"
FT /id="VAR_063757"
FT CONFLICT 195
FT /note="R -> L (in Ref. 4; BAC11172)"
FT /evidence="ECO:0000305"
FT CONFLICT 214
FT /note="E -> D (in Ref. 4; BAC11172)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 376 AA; 42997 MW; 53BF537979260188 CRC64;
MFPRPLTPLA APNGAEPLGR ALRRAPLGRA RAGLGGPPLL LPSMLMFAVI VASSGLLLMI
ERGILAEMKP LPLHPPGREG TAWRGKAPKP GGLSLRAGDA DLQVRQDVRN RTLRAVCGQP
GMPRDPWDLP VGQRRTLLRH ILVSDRYRFL YCYVPKVACS NWKRVMKVLA GVLDSVDVRL
KMDHRSDLVF LADLRPEEIR YRLQHYFKFL FVREPLERLL SAYRNKFGEI REYQQRYGAE
IVRRYRAGAG PSPAGDDVTF PEFLRYLVDE DPERMNEHWM PVYHLCQPCA VHYDFVGSYE
RLEADANQVL EWVRAPPHVR FPARQAWYRP ASPESLHYHL CSAPRALLQD VLPKYILDFS
LFAYPLPNVT KEACQQ
