ID CHST6_HUMAN Reviewed; 395 AA. AC Q9GZX3; DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 1. DT 13-NOV-2007, entry version 45. DE Carbohydrate sulfotransferase 6 (EC 2.8.2.-) (N-acetylglucosamine 6-O- DE sulfotransferase 5) (GlcNAc6ST-5) (Corneal N-acetylglucosamine-6-O- DE sulfotransferase) (C-GlcNAc6ST) (hCGn6ST) (Galactose/N- DE acetylglucosamine/N-acetylglucosamine 6-O-sulfotransferase 4-beta) DE (GST4-beta). GN Name=CHST6; 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 [GENOMIC DNA / MRNA], TISSUE SPECIFICITY, AND RP VARIANTS MCD CYS-50; ARG-174; GLU-203; TRP-211 AND LYS-274. RX MEDLINE=20472330; PubMed=11017086; DOI=10.1038/79987; RA Akama T.O., Nishida K., Nakayama J., Watanabe H., Ozaki K., RA Nakamura T., Dota A., Kawasaki S., Inoue Y., Maeda N., Yamamoto S., RA Fujiwara T., Thonar E.J.-M.A., Shimomura Y., Kinoshita S., RA Tanigami A., Fukuda M.N.; RT "Macular corneal dystrophy type I and type II are caused by distinct RT mutations in a new sulphotransferase gene."; RL Nat. Genet. 26:237-241(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RX MEDLINE=21096027; PubMed=11181564; DOI=10.1093/glycob/11.1.75; RA Hemmerich S., Lee J.K., Bhakta S., Bistrup A., Ruddle N.R., RA Rosen S.D.; RT "Chromosomal localization and genomic organization for the galactose/ RT N-acetylgalactosamine/N-acetylglucosamine 6-O-sulfotransferase gene RT family."; RL Glycobiology 11:75-87(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=11352640; DOI=10.1006/bbrc.2001.4668; RA Bartes A., Bhakta S., Hemmerich S.; RT "Sulfation of endothelial mucin by corneal keratan N-acetylglucosamine RT 6-O-sulfotransferase (GST-4beta)."; RL Biochem. Biophys. Res. Commun. 282:928-933(2001). RN [5] RP FUNCTION, SUBSTRATE SPECIFICITY, AND VARIANTS MCD CYS-50; ARG-174; RP GLU-203; TRP-211; THR-217 AND LYS-274. RX PubMed=12218059; DOI=10.1074/jbc.M207412200; RA Akama T.O., Misra A.K., Hindsgaul O., Fukuda M.N.; RT "Enzymatic synthesis in vitro of the disulfated disaccharide unit of RT corneal keratan sulfate."; RL J. Biol. Chem. 277:42505-42513(2002). RN [6] RP VARIANTS MCD VAL-128 AND PRO-166. RX PubMed=11139648; RA Liu N.-P., Dew-Knight S., Rayner M., Jonasson F., Akama T.O., RA Fukuda M.N., Bao W., Gilbert J.R., Vance J.M., Klintworth G.K.; RT "Mutations in corneal carbohydrate sulfotransferase 6 gene (CHST6) RT cause macular corneal dystrophy in Iceland."; RL Mol. Vis. 6:261-264(2000). RN [7] RP VARIANTS MCD SER-31; SER-72; SER-107; ARG-200 AND VAL-206. RX PubMed=11818380; RA El-Ashry M.F., El-Aziz M.M., Wilkins S., Cheetham M.E., Wilkie S.E., RA Hardcastle A.J., Halford S., Bayoumi A.Y., Ficker L.A., Tuft S., RA Bhattacharya S.S., Ebenezer N.D.; RT "Identification of novel mutations in the carbohydrate RT sulfotransferase gene (CHST6) causing macular corneal dystrophy."; RL Invest. Ophthalmol. Vis. Sci. 43:377-382(2002). RN [8] RP VARIANTS MCD PRO-15; THR-61; HIS-68; LEU-70; GLY-102; PRO-131; RP PRO-152; PRO-166; ARG-200 AND GLN-204. RX PubMed=12824236; DOI=10.1167/iovs.02-0740; RA Niel F., Ellies P., Dighiero P., Soria J., Sabbagh C., San C., RA Renard G., Delpech M., Valleix S.; RT "Truncating mutations in the carbohydrate sulfotransferase 6 gene RT (CHST6) result in macular corneal dystrophy."; RL Invest. Ophthalmol. Vis. Sci. 44:2949-2953(2003). RN [9] RP VARIANTS MCD HIS-177; GLN-204; LEU-205; TRP-211 AND THR-217. RX PubMed=12882769; DOI=10.1167/iovs.02-0910; RA Iida-Hasegawa N., Furuhata A., Hayatsu H., Murakami A., Fujiki K., RA Nakayasu K., Kanai A.; RT "Mutations in the CHST6 gene in patients with macular corneal RT dystrophy: immunohistochemical evidence of heterogeneity."; RL Invest. Ophthalmol. Vis. Sci. 44:3272-3277(2003). RN [10] RP VARIANT MCD GLN-211. RX PubMed=12883341; DOI=10.1097/00003226-200308000-00004; RA Ha N.T., Chau H.M., Cung le X., Thanh T.K., Fujiki K., Murakami A., RA Hiratsuka Y., Hasegawa N., Kanai A.; RT "Identification of novel mutations of the CHST6 gene in Vietnamese RT families affected with macular corneal dystrophy in two generations."; RL Cornea 22:508-511(2003). RN [11] RP VARIANTS MCD LEU-51; PRO-59; LEU-66; MET-76; GLN-211; GLN-211; CYS-268 RP AND CYS-268. RX PubMed=12882775; DOI=10.1167/iovs.03-0031; RA Ha N.T., Chau H.M., Cung le X., Thanh T.K., Fujiki K., Murakami A., RA Hiratsuka Y., Kanai A.; RT "Mutation analysis of the carbohydrate sulfotransferase gene in RT Vietnamese with macular corneal dystrophy."; RL Invest. Ophthalmol. Vis. Sci. 44:3310-3316(2003). RN [12] RP VARIANTS MCD ARG-22; TYR-42; LEU-53; HIS-93; PRO-97; TYR-102; CYS-127; RP GLN-205; THR-206; PRO-249 AND LYS-274. RX PubMed=14609920; DOI=10.1001/archopht.121.11.1608; RA Warren J.F., Aldave A.J., Srinivasan M., Thonar E.J., Kumar A.B., RA Cevallos V., Whitcher J.P., Margolis T.P.; RT "Novel mutations in the CHST6 gene associated with macular corneal RT dystrophy in southern India."; RL Arch. Ophthalmol. 121:1608-1612(2003). RN [13] RP VARIANTS MCD ASP-52; LEU-53; TRP-98; SER-107; LEU-121; SER-202; RP GLN-204; PHE-210; GLU-221 AND TYR-221. RX PubMed=14735064; RA Sultana A., Sridhar M.S., Jagannathan A., Balasubramanian D., RA Kannabiran C., Klintworth G.K.; RT "Novel mutations of the carbohydrate sulfotransferase-6 (CHST6) gene RT causing macular corneal dystrophy in India."; RL Mol. Vis. 9:730-734(2003). RN [14] RP VARIANTS MCD GLY-102; GLY-162; GLU-198 AND ARG-200. RX PubMed=14984470; DOI=10.1111/j.0009-9163.2004.00191.x; RA Abbruzzese C., Kuhn U., Molina F., Rama P., De Luca M.; RT "Novel mutations in the CHST6 gene causing macular corneal RT dystrophy."; RL Clin. Genet. 65:120-125(2004). RN [15] RP VARIANTS MCD LEU-51; SER-72; GLY-102; VAL-104; CYS-110; PRO-122; RP ARG-200 AND PRO-276. RX PubMed=15013869; DOI=10.1016/j.ajo.2003.09.036; RA Aldave A.J., Yellore V.S., Thonar E.J., Udar N., Warren J.F., RA Yoon M.K., Cohen E.J., Rapuano C.J., Laibson P.R., Margolis T.P., RA Small K.; RT "Novel mutations in the carbohydrate sulfotransferase gene (CHST6) in RT American patients with macular corneal dystrophy."; RL Am. J. Ophthalmol. 137:465-473(2004). RN [16] RP VARIANTS MCD ARG-200; PRO-276 AND ASP-358. RX PubMed=15652851; DOI=10.1016/j.ajo.2004.07.001; RA El-Ashry M.F., Abd El-Aziz M.M., Shalaby O., Wilkins S., RA Poopalasundaram S., Cheetham M., Tuft S.J., Hardcastle A.J., RA Bhattacharya S.S., Ebenezer N.D.; RT "Novel CHST6 nonsense and missense mutations responsible for macular RT corneal dystrophy."; RL Am. J. Ophthalmol. 139:192-193(2005). CC -!- FUNCTION: Catalyzes the transfer of sulfate to position 6 of non- CC reducing N-acetylglucosamine (GlcNAc) residues of keratan. CC Mediates sulfation of keratan in cornea. Keratan sulfate plays a CC central role in maintaining corneal transparency. Acts on the CC nonreducing terminal GlcNAc of short and long carbohydrate CC substrates that have poly-N-acetyllactosamine structures. CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane; Single-pass type CC II membrane protein (By similarity). CC -!- TISSUE SPECIFICITY: Expressed in cornea. Mainly expressed in CC brain. Also expressed in spinal cord and trachea. CC -!- DISEASE: Defects in CHST6 are the cause of macular corneal CC dystrophy (MCD) [MIM:217800]. MCD is an autosomal recessive CC disease characterized by corneal opacities. Onset occurs in the CC first decade, usually between ages 5 and 9. The disorder is CC progressive. Minute, gray, punctate opacities develop. Corneal CC sensitivity is usually reduced. Painful attacks with photophobia, CC foreign body sensations, and recurrent erosions occur in most CC patients. There are different types of MCD: MCD type I, in which CC there is a virtual absence of sulfated keratan sulfate (KS) in the CC serum and cornea, as determined by KS-specific antibodies; and MCD CC type II, in which the normal sulfated KS-antibody response is CC present in cornea and serum. MCD type I patients usually have a CC homozygous missense mutation, while MCD type II patients show a CC large deletion and replacement in the upstream region of CHST6. CC The only missense mutation for type II is Cys-50, which is CC heterozygous with a replacement in the upstream region on the CC other allele of CHST6. CC -!- SIMILARITY: Belongs to the sulfotransferase family. CC Gal/GlcNAc/GalNAc subfamily. CC -!- CAUTION: PubMed:12824236 reported a Gly-204 variant, however CC according to their results reported in figure 1, it is a Gln-204 CC variant. CC -!- WEB RESOURCE: Name=GGDB; Note=GlycoGene database"; CC URL="http://ggdb.muse.aist.go.jp/GGDB/index.jsp"; 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; AF219990; AAG26325.1; -; mRNA. DR EMBL; AF219991; AAG26327.1; -; Genomic_DNA. DR EMBL; AF280086; AAG48244.1; -; mRNA. DR EMBL; BC074883; AAH74883.1; -; mRNA. DR EMBL; BC074834; AAH74834.1; -; mRNA. DR RefSeq; NP_067628.1; -. DR UniGene; Hs.655622; -. DR Ensembl; ENSG00000183196; Homo sapiens. DR GeneID; 4166; -. DR KEGG; hsa:4166; -. DR HGNC; HGNC:6938; CHST6. DR MIM; 217800; phenotype. DR MIM; 605294; gene. DR Orphanet; 34533; Corneal dystrophy. DR PharmGKB; PA26506; -. DR ArrayExpress; Q9GZX3; -. DR CleanEx; HS_CHST6; -. DR GermOnline; ENSG00000183196; Homo sapiens. DR GO; GO:0005794; C:Golgi apparatus; TAS:UniProtKB. DR GO; GO:0001517; F:N-acetylglucosamine 6-O-sulfotransferase ac...; IDA:UniProtKB. DR GO; GO:0018146; P:keratan sulfate biosynthetic process; IDA:UniProtKB. DR GO; GO:0006044; P:N-acetylglucosamine metabolic process; IDA:UniProtKB. DR InterPro; IPR000863; Sulfotransferase. DR Pfam; PF00685; Sulfotransfer_1; 1. PE 1: Evidence at protein level; KW Carbohydrate metabolism; Disease mutation; Glycoprotein; KW Golgi apparatus; Membrane; Polymorphism; Signal-anchor; Transferase; KW Transmembrane. FT CHAIN 1 395 Carbohydrate sulfotransferase 6. FT /FTId=PRO_0000085197. FT TOPO_DOM 1 5 Cytoplasmic (Potential). FT TRANSMEM 6 26 Signal-anchor for type II membrane FT protein (Potential). FT TOPO_DOM 27 395 Lumenal (Potential). FT NP_BIND 49 55 PAPS (By similarity). FT NP_BIND 202 210 PAPS (By similarity). FT CARBOHYD 116 116 N-linked (GlcNAc...) (Potential). FT CARBOHYD 229 229 N-linked (GlcNAc...) (Potential). FT CARBOHYD 305 305 N-linked (GlcNAc...) (Potential). FT CARBOHYD 328 328 N-linked (GlcNAc...) (Potential). FT VARIANT 15 15 L -> P (in MCD). FT /FTId=VAR_021417. FT VARIANT 22 22 L -> R (in MCD). FT /FTId=VAR_021418. FT VARIANT 31 31 P -> S (in MCD). FT /FTId=VAR_021419. FT VARIANT 42 42 H -> Y (in MCD). FT /FTId=VAR_021420. FT VARIANT 50 50 R -> C (in MCD; abolishes ability to FT sulfate keratan). FT /FTId=VAR_021421. FT VARIANT 51 51 S -> L (in MCD). FT /FTId=VAR_021422. FT VARIANT 52 52 G -> D (in MCD). FT /FTId=VAR_021423. FT VARIANT 53 53 S -> L (in MCD). FT /FTId=VAR_021424. FT VARIANT 59 59 L -> P (in MCD). FT /FTId=VAR_021425. FT VARIANT 61 61 N -> T (in MCD). FT /FTId=VAR_021426. FT VARIANT 66 66 V -> L (in MCD). FT /FTId=VAR_021427. FT VARIANT 68 68 Y -> H (in MCD). FT /FTId=VAR_021428. FT VARIANT 70 70 M -> L (in MCD). FT /FTId=VAR_021429. FT VARIANT 72 72 P -> S (in MCD). FT /FTId=VAR_021430. FT VARIANT 76 76 V -> M (in MCD). FT /FTId=VAR_021431. FT VARIANT 93 93 R -> H (in MCD). FT /FTId=VAR_021432. FT VARIANT 97 97 R -> P (in MCD). FT /FTId=VAR_021433. FT VARIANT 98 98 S -> W (in MCD). FT /FTId=VAR_021434. FT VARIANT 102 102 C -> G (in MCD). FT /FTId=VAR_021435. FT VARIANT 102 102 C -> Y (in MCD). FT /FTId=VAR_021436. FT VARIANT 104 104 M -> V (in MCD). FT /FTId=VAR_021437. FT VARIANT 107 107 F -> S (in MCD). FT /FTId=VAR_021438. FT VARIANT 110 110 Y -> C (in MCD). FT /FTId=VAR_021439. FT VARIANT 121 121 F -> L (in MCD). FT /FTId=VAR_021440. FT VARIANT 122 122 Q -> P (in MCD). FT /FTId=VAR_021441. FT VARIANT 127 127 R -> C (in MCD). FT /FTId=VAR_021442. FT VARIANT 128 128 A -> V (in MCD). FT /FTId=VAR_021443. FT VARIANT 131 131 S -> P (in MCD). FT /FTId=VAR_021444. FT VARIANT 152 152 L -> P (in MCD). FT /FTId=VAR_021445. FT VARIANT 162 162 R -> G (in MCD). FT /FTId=VAR_021446. FT VARIANT 166 166 R -> P (in MCD). FT /FTId=VAR_021447. FT VARIANT 174 174 K -> R (in MCD; abolishes ability to FT sulfate keratan). FT /FTId=VAR_021448. FT VARIANT 177 177 R -> H (in MCD). FT /FTId=VAR_021449. FT VARIANT 198 198 V -> E (in MCD). FT /FTId=VAR_021450. FT VARIANT 200 200 L -> R (in MCD). FT /FTId=VAR_021451. FT VARIANT 202 202 R -> S (in MCD). FT /FTId=VAR_021452. FT VARIANT 203 203 D -> E (in MCD; abolishes ability to FT sulfate keratan). FT /FTId=VAR_021453. FT VARIANT 204 204 P -> Q (in MCD). FT /FTId=VAR_021454. FT VARIANT 205 205 R -> L (in MCD). FT /FTId=VAR_021455. FT VARIANT 205 205 R -> Q (in MCD). FT /FTId=VAR_021456. FT VARIANT 206 206 A -> T (in MCD). FT /FTId=VAR_021457. FT VARIANT 206 206 A -> V (in MCD). FT /FTId=VAR_021458. FT VARIANT 210 210 S -> F (in MCD). FT /FTId=VAR_021459. FT VARIANT 211 211 R -> Q (in MCD). FT /FTId=VAR_021460. FT VARIANT 211 211 R -> W (in MCD; abolishes ability to FT sulfate keratan). FT /FTId=VAR_021461. FT VARIANT 217 217 A -> T (in MCD; abolishes ability to FT sulfate keratan). FT /FTId=VAR_021462. FT VARIANT 221 221 D -> E (in MCD). FT /FTId=VAR_021463. FT VARIANT 221 221 D -> Y (in MCD). FT /FTId=VAR_021464. FT VARIANT 249 249 H -> P (in MCD). FT /FTId=VAR_021465. FT VARIANT 268 268 Y -> C (in MCD). FT /FTId=VAR_021466. FT VARIANT 274 274 E -> K (in MCD; abolishes ability to FT sulfate keratan). FT /FTId=VAR_021467. FT VARIANT 276 276 L -> P (in MCD). FT /FTId=VAR_021468. FT VARIANT 358 358 Y -> D (in MCD). FT /FTId=VAR_021469. FT VARIANT 369 369 N -> D (in dbSNP:rs35036798). FT /FTId=VAR_033735. SQ SEQUENCE 395 AA; 44099 MW; 433CA60248A48F67 CRC64; MWLPRVSSTA VTALLLAQTF LLLFLVSRPG PSSPAGGEAR VHVLVLSSWR SGSSFVGQLF NQHPDVFYLM EPAWHVWTTL SQGSAATLHM AVRDLVRSVF LCDMDVFDAY LPWRRNLSDL FQWAVSRALC SPPACSAFPR GAISSEAVCK PLCARQSFTL AREACRSYSH VVLKEVRFFN LQVLYPLLSD PALNLRIVHL VRDPRAVLRS REQTAKALAR DNGIVLGTNG TWVEADPGLR VVREVCRSHV RIAEAATLKP PPFLRGRYRL VRFEDLAREP LAEIRALYAF TGLSLTPQLE AWIHNITHGS GPGARREAFK TSSRNALNVS QAWRHALPFA KIRRVQELCA GALQLLGYRP VYSEDEQRNL ALDLVLPRGL NGFTWASSTA SHPRN //