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 27-MAR-2024, entry version 157. 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 -!- INTERACTION: CC Q8NCH0; P13569: CFTR; NbExp=3; IntAct=EBI-21717278, EBI-349854; 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}; 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; 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 SMR; Q8NCH0; -. DR BioGRID; 125232; 121. DR IntAct; Q8NCH0; 9. DR MINT; Q8NCH0; -. DR STRING; 9606.ENSP00000307297; -. DR GlyCosmos; Q8NCH0; 2 sites, No reported glycans. DR GlyGen; Q8NCH0; 5 sites, 2 O-linked glycans (3 sites). DR iPTMnet; Q8NCH0; -. DR PhosphoSitePlus; Q8NCH0; -. DR SwissPalm; Q8NCH0; -. DR BioMuta; CHST14; -. DR DMDM; 61211839; -. DR EPD; Q8NCH0; -. DR jPOST; Q8NCH0; -. DR MassIVE; Q8NCH0; -. DR MaxQB; Q8NCH0; -. DR PaxDb; 9606-ENSP00000307297; -. DR PeptideAtlas; Q8NCH0; -. DR ProteomicsDB; 72895; -. DR Pumba; Q8NCH0; -. DR Antibodypedia; 23111; 125 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 AGR; HGNC:24464; -. 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; 2907043at2759; -. DR PhylomeDB; Q8NCH0; -. DR TreeFam; TF325581; -. DR BioCyc; MetaCyc:ENSG00000169105-MONOMER; -. 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; 13 hits in 1153 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 138 other cell types or 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:0016020; C: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: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; CARBOHYDRATE SULFOTRANSFERASE; 1. DR PANTHER; PTHR12137:SF33; CARBOHYDRATE SULFOTRANSFERASE 14; 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 //