ID CHST3_HUMAN Reviewed; 479 AA. AC Q7LGC8; O75099; Q52M30; DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 3. DT 09-DEC-2015, entry version 115. DE RecName: Full=Carbohydrate sulfotransferase 3; DE EC=2.8.2.17; DE AltName: Full=Chondroitin 6-O-sulfotransferase 1; DE Short=C6ST-1; DE AltName: Full=Chondroitin 6-sulfotransferase; DE AltName: Full=Galactose/N-acetylglucosamine/N-acetylglucosamine 6-O-sulfotransferase 0; DE Short=GST-0; GN Name=CHST3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY. RC TISSUE=Fetal brain; RX PubMed=9714738; DOI=10.1016/S0167-4781(98)00089-X; RA Fukuta M., Kobayashi Y., Uchimura K., Kimata K., Habuchi O.; RT "Molecular cloning and expression of human chondroitin 6- RT sulfotransferase."; RL Biochim. Biophys. Acta 1399:57-61(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION. RC TISSUE=Placenta; RX PubMed=9883891; DOI=10.1016/S0014-5793(98)01532-4; RA Tsutsumi K., Shimakawa H., Kitagawa H., Sugahara K.; RT "Functional expression and genomic structure of human chondroitin 6- RT sulfotransferase."; RL FEBS Lett. 441:235-241(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-357. RC TISSUE=Liver; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP VARIANT SEDC-JD GLN-304. RX PubMed=15215498; DOI=10.1073/pnas.0400334101; RA Thiele H., Sakano M., Kitagawa H., Sugahara K., Rajab A., Hoehne W., RA Ritter H., Leschik G., Nuernberg P., Mundlos S.; RT "Loss of chondroitin 6-O-sulfotransferase-1 function results in severe RT human chondrodysplasia with progressive spinal involvement."; RL Proc. Natl. Acad. Sci. U.S.A. 101:10155-10160(2004). RN [5] RP VARIANTS SEDC-JD TRP-222; PRO-259; PRO-307 AND LYS-372, VARIANT RP GLN-357, AND CHARACTERIZATION OF VARIANTS SEDC-JD TRP-222 AND PRO-259. RX PubMed=18513679; DOI=10.1016/j.ajhg.2008.05.006; RA Hermanns P., Unger S., Rossi A., Perez-Aytes A., Cortina H., RA Bonafe L., Boccone L., Setzu V., Dutoit M., Sangiorgi L., Pecora F., RA Reicherter K., Nishimura G., Spranger J., Zabel B., Superti-Furga A.; RT "Congenital joint dislocations caused by carbohydrate sulfotransferase RT 3 deficiency in recessive Larsen syndrome and humero-spinal RT dysostosis."; RL Am. J. Hum. Genet. 82:1368-1374(2008). RN [6] RP ERRATUM. RA Hermanns P., Unger S., Rossi A., Perez-Aytes A., Cortina H., RA Bonafe L., Boccone L., Setzu V., Dutoit M., Sangiorgi L., Pecora F., RA Reicherter K., Nishimura G., Spranger J., Zabel B., Superti-Furga A.; RL Am. J. Hum. Genet. 83:293-293(2008). CC -!- FUNCTION: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl CC sulfate (PAPS) as sulfonate donor to catalyze the transfer of CC sulfate to position 6 of the N-acetylgalactosamine (GalNAc) CC residue of chondroitin. Chondroitin sulfate constitutes the CC predominant proteoglycan present in cartilage and is distributed CC on the surfaces of many cells and extracellular matrices. Can also CC sulfate Gal residues of keratan sulfate, another CC glycosaminoglycan, and the Gal residues in sialyl N- CC acetyllactosamine (sialyl LacNAc) oligosaccharides. May play a CC role in the maintenance of naive T-lymphocytes in the spleen. CC {ECO:0000269|PubMed:9714738, ECO:0000269|PubMed:9883891}. CC -!- CATALYTIC ACTIVITY: 3'-phosphoadenylyl sulfate + chondroitin = CC adenosine 3',5'-bisphosphate + chondroitin 6'-sulfate. CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250}; CC Single-pass type II membrane protein {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Widely expressed in adult tissues. Expressed CC in heart, placenta, skeletal muscle and pancreas. Also expressed CC in various immune tissues such as spleen, lymph node, thymus and CC appendix. {ECO:0000269|PubMed:9714738}. CC -!- DISEASE: Spondyloepiphyseal dysplasia with congenital joint CC dislocations (SEDC-JD) [MIM:143095]: A bone dysplasia clinically CC characterized by dislocation of the knees and/or hips at birth, CC clubfoot, elbow joint dysplasia with subluxation and limited CC extension, short stature, and progressive kyphosis developing in CC late childhood. The disorder is usually evident at birth, with CC short stature and multiple joint dislocations or subluxations that CC dominate the neonatal clinical and radiographic picture. During CC childhood, the dislocations improve, both spontaneously and with CC surgical treatment, and features of spondyloepiphyseal dysplasia CC become apparent, leading to arthritis of the hips and spine with CC intervertebral disk degeneration, rigid kyphoscoliosis, and trunk CC shortening by late childhood. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the sulfotransferase 1 family. CC Gal/GlcNAc/GalNAc subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=GGDB; Note=GlycoGene database; CC URL="http://jcggdb.jp/rcmg/ggdb/Homolog?cat=symbol&symbol=CHST3"; 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; AB012192; BAA32576.1; -; mRNA. DR EMBL; AB017915; BAA36348.1; -; mRNA. DR EMBL; BC093690; AAH93690.1; -; mRNA. DR EMBL; BC104856; AAI04857.1; -; mRNA. DR CCDS; CCDS7312.1; -. DR RefSeq; NP_004264.2; NM_004273.4. DR RefSeq; XP_006718138.1; XM_006718075.2. DR RefSeq; XP_011538671.1; XM_011540369.1. DR UniGene; Hs.158304; -. DR ProteinModelPortal; Q7LGC8; -. DR BioGrid; 114855; 5. DR STRING; 9606.ENSP00000362207; -. DR PhosphoSite; Q7LGC8; -. DR BioMuta; CHST3; -. DR DMDM; 116241297; -. DR MaxQB; Q7LGC8; -. DR PaxDb; Q7LGC8; -. DR PRIDE; Q7LGC8; -. DR Ensembl; ENST00000373115; ENSP00000362207; ENSG00000122863. DR GeneID; 9469; -. DR KEGG; hsa:9469; -. DR UCSC; uc001jsn.3; human. DR CTD; 9469; -. DR GeneCards; CHST3; -. DR GeneReviews; CHST3; -. DR HGNC; HGNC:1971; CHST3. DR HPA; HPA047523; -. DR HPA; HPA055704; -. DR MalaCards; CHST3; -. DR MIM; 143095; phenotype. DR MIM; 603799; gene. DR neXtProt; NX_Q7LGC8; -. DR Orphanet; 263463; CHST3-related skeletal dysplasia. DR PharmGKB; PA26503; -. DR eggNOG; ENOG410IIAV; Eukaryota. DR eggNOG; ENOG410YDA4; LUCA. DR GeneTree; ENSGT00530000062902; -. DR HOGENOM; HOG000261614; -. DR HOVERGEN; HBG106811; -. DR InParanoid; Q7LGC8; -. DR KO; K01020; -. DR OMA; SPQAREW; -. DR OrthoDB; EOG7RZ5S0; -. DR PhylomeDB; Q7LGC8; -. DR TreeFam; TF342871; -. DR BioCyc; MetaCyc:HS04610-MONOMER; -. DR BRENDA; 2.8.2.17; 2681. DR Reactome; R-HSA-2022870; Chondroitin sulfate biosynthesis. DR Reactome; R-HSA-3595172; Defective CHST3 causes SEDCJD. DR GenomeRNAi; 9469; -. DR NextBio; 35486; -. DR PRO; PR:Q7LGC8; -. DR Proteomes; UP000005640; Chromosome 10. DR Bgee; Q7LGC8; -. DR CleanEx; HS_CHST3; -. DR Genevisible; Q7LGC8; HS. DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome. DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central. DR GO; GO:0008459; F:chondroitin 6-sulfotransferase activity; IDA:UniProtKB. DR GO; GO:0001517; F:N-acetylglucosamine 6-O-sulfotransferase activity; IBA:GO_Central. DR GO; GO:0050698; F:proteoglycan sulfotransferase activity; IEA:Ensembl. DR GO; GO:0008146; F:sulfotransferase activity; TAS:ProtInc. DR GO; GO:0005975; P:carbohydrate metabolic process; TAS:Reactome. DR GO; GO:0030206; P:chondroitin sulfate biosynthetic process; IDA:UniProtKB. DR GO; GO:0030204; P:chondroitin sulfate metabolic process; TAS:Reactome. DR GO; GO:0030203; P:glycosaminoglycan metabolic process; TAS:Reactome. DR GO; GO:0098779; P:mitophagy in response to mitochondrial depolarization; IGI:ParkinsonsUK-UCL. DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IMP:ParkinsonsUK-UCL. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR GO; GO:0006790; P:sulfur compound metabolic process; IDA:UniProtKB. DR GO; GO:0043029; P:T cell homeostasis; IEA:Ensembl. DR GO; GO:0098792; P:xenophagy; IMP:ParkinsonsUK-UCL. DR Gene3D; 3.40.50.300; -; 1. DR InterPro; IPR016469; Carbohydrate_sulfotransferase. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR000863; Sulfotransferase_dom. DR Pfam; PF00685; Sulfotransfer_1; 1. DR PIRSF; PIRSF005883; Carbohydrate_sulfotransferase; 1. DR SUPFAM; SSF52540; SSF52540; 2. PE 1: Evidence at protein level; KW Carbohydrate metabolism; Complete proteome; Disease mutation; KW Glycoprotein; Golgi apparatus; Membrane; Polymorphism; KW Reference proteome; Signal-anchor; Transferase; Transmembrane; KW Transmembrane helix. FT CHAIN 1 479 Carbohydrate sulfotransferase 3. FT /FTId=PRO_0000085188. FT TOPO_DOM 1 20 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 21 38 Helical; Signal-anchor for type II FT membrane protein. {ECO:0000255}. FT TOPO_DOM 39 479 Lumenal. {ECO:0000255}. FT NP_BIND 141 147 PAPS. {ECO:0000250}. FT NP_BIND 301 309 PAPS. {ECO:0000250}. FT CARBOHYD 63 63 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 74 74 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 96 96 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 256 256 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 420 420 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 464 464 N-linked (GlcNAc...). {ECO:0000255}. FT VARIANT 222 222 R -> W (in SEDC-JD; severely impairs or FT abolishes the enzyme function). FT {ECO:0000269|PubMed:18513679}. FT /FTId=VAR_047856. FT VARIANT 259 259 L -> P (in SEDC-JD; severely impairs or FT abolishes the enzyme function). FT {ECO:0000269|PubMed:18513679}. FT /FTId=VAR_047857. FT VARIANT 304 304 R -> Q (in SEDC-JD; reduced enzyme FT activity; dbSNP:rs28937593). FT {ECO:0000269|PubMed:15215498}. FT /FTId=VAR_021413. FT VARIANT 307 307 L -> P (in SEDC-JD). FT {ECO:0000269|PubMed:18513679}. FT /FTId=VAR_047858. FT VARIANT 348 348 I -> M (in dbSNP:rs3740128). FT /FTId=VAR_021414. FT VARIANT 357 357 R -> Q (in dbSNP:rs3740129). FT {ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:18513679}. FT /FTId=VAR_021415. FT VARIANT 372 372 E -> K (in SEDC-JD). FT {ECO:0000269|PubMed:18513679}. FT /FTId=VAR_047859. FT CONFLICT 387 387 R -> P (in Ref. 1; BAA32576). FT {ECO:0000305}. FT CONFLICT 443 443 A -> P (in Ref. 1; BAA32576). FT {ECO:0000305}. SQ SEQUENCE 479 AA; 54706 MW; 7C290DC4970F66E0 CRC64; MEKGLTLPQD CRDFVHSLKM RSKYALFLVF VVIVFVFIEK ENKIISRVSD KLKQIPQALA DANSTDPALI LAENASLLSL SELDSAFSQL QSRLRNLSLQ LGVEPAMEAA GEEEEEQRKE EEPPRPAVAG PRRHVLLMAT TRTGSSFVGE FFNQQGNIFY LFEPLWHIER TVSFEPGGAN AAGSALVYRD VLKQLFLCDL YVLEHFITPL PEDHLTQFMF RRGSSRSLCE DPVCTPFVKK VFEKYHCKNR RCGPLNVTLA AEACRRKEHM ALKAVRIRQL EFLQPLAEDP RLDLRVIQLV RDPRAVLASR MVAFAGKYKT WKKWLDDEGQ DGLREEEVQR LRGNCESIRL SAELGLRQPA WLRGRYMLVR YEDVARGPLQ KAREMYRFAG IPLTPQVEDW IQKNTQAAHD GSGIYSTQKN SSEQFEKWRF SMPFKLAQVV QAACGPAMRL FGYKLARDAA ALTNRSVSLL EERGTFWVT //