Q9GZX3 (CHST6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Carbohydrate sulfotransferase 6
EC=2.8.2.-

Alternative name(s):
Corneal N-acetylglucosamine-6-O-sulfotransferase
Short name=C-GlcNAc6ST
Short name=hCGn6ST
Galactose/N-acetylglucosamine/N-acetylglucosamine 6-O-sulfotransferase 4-beta
Short name=GST4-beta
N-acetylglucosamine 6-O-sulfotransferase 5
Short name=GlcNAc6ST-5
Short name=Gn6st-5

Gene names

Name:

CHST6

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	395 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of non-reducing N-acetylglucosamine (GlcNAc) residues of keratan. Mediates sulfation of keratan in cornea. Keratan sulfate plays a central role in maintaining corneal transparency. Acts on the non-reducing terminal GlcNAc of short and long carbohydrate substrates that have poly-N-acetyllactosamine structures. Ref.5 Ref.6
Subcellular location	Golgi apparatus membrane; Single-pass type II membrane protein By similarity.
Tissue specificity	Expressed in cornea. Mainly expressed in brain. Also expressed in spinal cord and trachea. Ref.1 Ref.2 Ref.5
Involvement in disease	Macular dystrophy, corneal, 1 (MCDC1) [MIM:217800]: An ocular disease characterized by bilateral, progressive corneal opacification, and reduced corneal sensitivity. Onset occurs in the first decade, usually between ages 5 and 9. Painful attacks with photophobia, foreign body sensations, and recurrent erosions occur in most patients. The disease is due to deposition of an unsulfated keratan sulfate both within the intracellular space (within the keratocytes and endothelial cells) and in the extracellular corneal stroma. Macular corneal dystrophy is divided into the clinically indistinguishable types I, IA, and II based on analysis of the normally sulfated, or antigenic, keratan sulfate levels in serum and immunohistochemical evaluation of the cornea. Patients with types I and IA macular corneal dystrophy have undetectable serum levels of antigenic keratan sulfate, whereas those with type II macular corneal dystrophy have normal or low levels, depending on the population examined. Note: The disease is caused by mutations affecting the gene represented in this entry. CHST6 homozygous missense mutations have been observed in patients with macular corneal dystrophy type I, while type II patients show a large deletion and replacement in the upstream region of CHST6. The only missense mutation for type II is Cys-50, which is heterozygous with a replacement in the upstream region on the other allele of CHST6. Ref.1 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17
Sequence similarities	Belongs to the sulfotransferase 1 family. Gal/GlcNAc/GalNAc subfamily.
Caution	Ref.9 reported a Gly-204 variant, however according to their results reported in figure 1, it is a Gln-204 variant.

Ontologies

Keywords
Biological process	Carbohydrate metabolism
Cellular component	Golgi apparatus Membrane
Coding sequence diversity	Polymorphism
Disease	Corneal dystrophy Disease mutation
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Transferase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	N-acetylglucosamine metabolic process Inferred from direct assay Ref.5. Source: UniProtKB carbohydrate metabolic process Traceable author statement. Source: Reactome keratan sulfate biosynthetic process Inferred from direct assay PubMed 11278593. Source: UniProtKB
Cellular_component	Golgi membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	N-acetylglucosamine 6-O-sulfotransferase activity Inferred from direct assay PubMed 11278593Ref.5. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 395	395	Carbohydrate sulfotransferase 6		PRO_0000085197
Regions
	Topological domain	1 – 5	5	Cytoplasmic Potential
	Transmembrane	6 – 26	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	27 – 395	369	Lumenal Potential
	Nucleotide binding	49 – 55	7	PAPS By similarity
	Nucleotide binding	202 – 210	9	PAPS By similarity
Amino acid modifications
	Glycosylation	116	1	N-linked (GlcNAc...) Potential
	Glycosylation	229	1	N-linked (GlcNAc...) Potential
	Glycosylation	305	1	N-linked (GlcNAc...) Potential
	Glycosylation	328	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	15	1	L → P in MCDC1. Ref.9		VAR_021417
	Natural variant	22	1	L → R in MCDC1. Ref.13		VAR_021418
	Natural variant	31	1	P → S in MCDC1. Ref.8		VAR_021419
	Natural variant	42	1	H → Y in MCDC1. Ref.13		VAR_021420
	Natural variant	50	1	R → C in MCDC1; abolishes ability to sulfate keratan. Ref.1 Ref.6 Corresponds to variant rs28937877 [ dbSNP | Ensembl ].		VAR_021421
	Natural variant	51	1	S → L in MCDC1. Ref.12 Ref.16		VAR_021422
	Natural variant	52	1	G → D in MCDC1. Ref.14		VAR_021423
	Natural variant	53	1	S → L in MCDC1. Ref.13 Ref.14		VAR_021424
	Natural variant	59	1	L → P in MCDC1. Ref.12		VAR_021425
	Natural variant	61	1	N → T in MCDC1. Ref.9		VAR_021426
	Natural variant	66	1	V → L in MCDC1. Ref.12		VAR_021427
	Natural variant	68	1	Y → H in MCDC1. Ref.9		VAR_021428
	Natural variant	70	1	M → L in MCDC1. Ref.9		VAR_021429
	Natural variant	72	1	P → S in MCDC1. Ref.8 Ref.16		VAR_021430
	Natural variant	76	1	V → M in MCDC1. Ref.12		VAR_021431
	Natural variant	93	1	R → H in MCDC1. Ref.13		VAR_021432
	Natural variant	97	1	R → P in MCDC1. Ref.13		VAR_021433
	Natural variant	98	1	S → W in MCDC1. Ref.14		VAR_021434
	Natural variant	102	1	C → G in MCDC1. Ref.9 Ref.15 Ref.16		VAR_021435
	Natural variant	102	1	C → Y in MCDC1. Ref.13		VAR_021436
	Natural variant	104	1	M → V in MCDC1. Ref.16		VAR_021437
	Natural variant	107	1	F → S in MCDC1. Ref.8 Ref.14		VAR_021438
	Natural variant	110	1	Y → C in MCDC1. Ref.16		VAR_021439
	Natural variant	121	1	F → L in MCDC1. Ref.14		VAR_021440
	Natural variant	122	1	Q → P in MCDC1. Ref.16		VAR_021441
	Natural variant	127	1	R → C in MCDC1. Ref.13		VAR_021442
	Natural variant	128	1	A → V in MCDC1. Ref.7		VAR_021443
	Natural variant	131	1	S → P in MCDC1. Ref.9		VAR_021444
	Natural variant	152	1	L → P in MCDC1. Ref.9		VAR_021445
	Natural variant	162	1	R → G in MCDC1. Ref.15		VAR_021446
	Natural variant	166	1	R → P in MCDC1. Ref.7 Ref.9		VAR_021447
	Natural variant	174	1	K → R in MCDC1; abolishes ability to sulfate keratan. Ref.1 Ref.6 Corresponds to variant rs28937878 [ dbSNP | Ensembl ].		VAR_021448
	Natural variant	177	1	R → H in MCDC1. Ref.10		VAR_021449
	Natural variant	198	1	V → E in MCDC1. Ref.15		VAR_021450
	Natural variant	200	1	L → R in MCDC1. Ref.8 Ref.9 Ref.15 Ref.16 Ref.17 Corresponds to variant rs28937879 [ dbSNP | Ensembl ].		VAR_021451
	Natural variant	202	1	R → S in MCDC1. Ref.14		VAR_021452
	Natural variant	203	1	D → E in MCDC1; abolishes ability to sulfate keratan. Ref.1 Ref.6 Corresponds to variant rs28937878 [ dbSNP | Ensembl ].		VAR_021453
	Natural variant	204	1	P → Q in MCDC1. Ref.9 Ref.10 Ref.14		VAR_021454
	Natural variant	205	1	R → L in MCDC1. Ref.10		VAR_021455
	Natural variant	205	1	R → Q in MCDC1. Ref.13		VAR_021456
	Natural variant	206	1	A → T in MCDC1. Ref.13		VAR_021457
	Natural variant	206	1	A → V in MCDC1. Ref.8		VAR_021458
	Natural variant	210	1	S → F in MCDC1. Ref.14		VAR_021459
	Natural variant	211	1	R → Q in MCDC1. Ref.11 Ref.12		VAR_021460
	Natural variant	211	1	R → W in MCDC1; abolishes ability to sulfate keratan. Ref.1 Ref.6 Ref.10		VAR_021461
	Natural variant	217	1	A → T in MCDC1; abolishes ability to sulfate keratan. Ref.6 Ref.10		VAR_021462
	Natural variant	221	1	D → E in MCDC1. Ref.14		VAR_021463
	Natural variant	221	1	D → Y in MCDC1. Ref.14		VAR_021464
	Natural variant	249	1	H → P in MCDC1. Ref.13		VAR_021465
	Natural variant	268	1	Y → C in MCDC1. Ref.12		VAR_021466
	Natural variant	274	1	E → K in MCDC1; abolishes ability to sulfate keratan. Ref.1 Ref.6 Ref.13		VAR_021467
	Natural variant	276	1	L → P in MCDC1. Ref.16 Ref.17		VAR_021468
	Natural variant	358	1	Y → D in MCDC1. Ref.17		VAR_021469
	Natural variant	369	1	N → D. Corresponds to variant rs35036798 [ dbSNP | Ensembl ].		VAR_033735

Sequences

	Sequence		Length	Mass (Da)
	Q9GZX3 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 433CA60248A48F67	FASTA	395	44,099
	10 20 30 40 50 60 MWLPRVSSTA VTALLLAQTF LLLFLVSRPG PSSPAGGEAR VHVLVLSSWR SGSSFVGQLF 70 80 90 100 110 120 NQHPDVFYLM EPAWHVWTTL SQGSAATLHM AVRDLVRSVF LCDMDVFDAY LPWRRNLSDL 130 140 150 160 170 180 FQWAVSRALC SPPACSAFPR GAISSEAVCK PLCARQSFTL AREACRSYSH VVLKEVRFFN 190 200 210 220 230 240 LQVLYPLLSD PALNLRIVHL VRDPRAVLRS REQTAKALAR DNGIVLGTNG TWVEADPGLR 250 260 270 280 290 300 VVREVCRSHV RIAEAATLKP PPFLRGRYRL VRFEDLAREP LAEIRALYAF TGLSLTPQLE 310 320 330 340 350 360 AWIHNITHGS GPGARREAFK TSSRNALNVS QAWRHALPFA KIRRVQELCA GALQLLGYRP 370 380 390 VYSEDEQRNL ALDLVLPRGL NGFTWASSTA SHPRN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Macular corneal dystrophy type I and type II are caused by distinct mutations in a new sulphotransferase gene." Akama T.O., Nishida K., Nakayama J., Watanabe H., Ozaki K., Nakamura T., Dota A., Kawasaki S., Inoue Y., Maeda N., Yamamoto S., Fujiwara T., Thonar E.J.-M.A., Shimomura Y., Kinoshita S., Tanigami A., Fukuda M.N. Nat. Genet. 26:237-241(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY, VARIANTS MCDC1 CYS-50; ARG-174; GLU-203; TRP-211 AND LYS-274.
[2]	"Chromosomal localization and genomic organization for the galactose/ N-acetylgalactosamine/N-acetylglucosamine 6-O-sulfotransferase gene family." Hemmerich S., Lee J.K., Bhakta S., Bistrup A., Ruddle N.R., Rosen S.D. Glycobiology 11:75-87(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[5]	"Sulfation of endothelial mucin by corneal keratan N-acetylglucosamine 6-O-sulfotransferase (GST-4beta)." Bartes A., Bhakta S., Hemmerich S. Biochem. Biophys. Res. Commun. 282:928-933(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[6]	"Enzymatic synthesis in vitro of the disulfated disaccharide unit of corneal keratan sulfate." Akama T.O., Misra A.K., Hindsgaul O., Fukuda M.N. J. Biol. Chem. 277:42505-42513(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBSTRATE SPECIFICITY, VARIANTS MCDC1 CYS-50; ARG-174; GLU-203; TRP-211; THR-217 AND LYS-274.
[7]	"Mutations in corneal carbohydrate sulfotransferase 6 gene (CHST6) cause macular corneal dystrophy in Iceland." Liu N.-P., Dew-Knight S., Rayner M., Jonasson F., Akama T.O., Fukuda M.N., Bao W., Gilbert J.R., Vance J.M., Klintworth G.K. Mol. Vis. 6:261-264(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MCDC1 VAL-128 AND PRO-166.
[8]	"Identification of novel mutations in the carbohydrate sulfotransferase gene (CHST6) causing macular corneal dystrophy." El-Ashry M.F., El-Aziz M.M., Wilkins S., Cheetham M.E., Wilkie S.E., Hardcastle A.J., Halford S., Bayoumi A.Y., Ficker L.A., Tuft S., Bhattacharya S.S., Ebenezer N.D. Invest. Ophthalmol. Vis. Sci. 43:377-382(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MCDC1 SER-31; SER-72; SER-107; ARG-200 AND VAL-206.
[9]	"Truncating mutations in the carbohydrate sulfotransferase 6 gene (CHST6) result in macular corneal dystrophy." Niel F., Ellies P., Dighiero P., Soria J., Sabbagh C., San C., Renard G., Delpech M., Valleix S. Invest. Ophthalmol. Vis. Sci. 44:2949-2953(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MCDC1 PRO-15; THR-61; HIS-68; LEU-70; GLY-102; PRO-131; PRO-152; PRO-166; ARG-200 AND GLN-204.
[10]	"Mutations in the CHST6 gene in patients with macular corneal dystrophy: immunohistochemical evidence of heterogeneity." Iida-Hasegawa N., Furuhata A., Hayatsu H., Murakami A., Fujiki K., Nakayasu K., Kanai A. Invest. Ophthalmol. Vis. Sci. 44:3272-3277(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MCDC1 HIS-177; GLN-204; LEU-205; TRP-211 AND THR-217.
[11]	"Identification of novel mutations of the CHST6 gene in Vietnamese families affected with macular corneal dystrophy in two generations." Ha N.T., Chau H.M., Cung le X., Thanh T.K., Fujiki K., Murakami A., Hiratsuka Y., Hasegawa N., Kanai A. Cornea 22:508-511(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MCDC1 GLN-211.
[12]	"Mutation analysis of the carbohydrate sulfotransferase gene in Vietnamese with macular corneal dystrophy." Ha N.T., Chau H.M., Cung le X., Thanh T.K., Fujiki K., Murakami A., Hiratsuka Y., Kanai A. Invest. Ophthalmol. Vis. Sci. 44:3310-3316(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MCDC1 LEU-51; PRO-59; LEU-66; MET-76; GLN-211; GLN-211; CYS-268 AND CYS-268.
[13]	"Novel mutations in the CHST6 gene associated with macular corneal dystrophy in southern India." Warren J.F., Aldave A.J., Srinivasan M., Thonar E.J., Kumar A.B., Cevallos V., Whitcher J.P., Margolis T.P. Arch. Ophthalmol. 121:1608-1612(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MCDC1 ARG-22; TYR-42; LEU-53; HIS-93; PRO-97; TYR-102; CYS-127; GLN-205; THR-206; PRO-249 AND LYS-274.
[14]	"Novel mutations of the carbohydrate sulfotransferase-6 (CHST6) gene causing macular corneal dystrophy in India." Sultana A., Sridhar M.S., Jagannathan A., Balasubramanian D., Kannabiran C., Klintworth G.K. Mol. Vis. 9:730-734(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MCDC1 ASP-52; LEU-53; TRP-98; SER-107; LEU-121; SER-202; GLN-204; PHE-210; GLU-221 AND TYR-221.
[15]	"Novel mutations in the CHST6 gene causing macular corneal dystrophy." Abbruzzese C., Kuhn U., Molina F., Rama P., De Luca M. Clin. Genet. 65:120-125(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MCDC1 GLY-102; GLY-162; GLU-198 AND ARG-200.
[16]	"Novel mutations in the carbohydrate sulfotransferase gene (CHST6) in American patients with macular corneal dystrophy." Aldave A.J., Yellore V.S., Thonar E.J., Udar N., Warren J.F., Yoon M.K., Cohen E.J., Rapuano C.J., Laibson P.R., Margolis T.P., Small K. Am. J. Ophthalmol. 137:465-473(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MCDC1 LEU-51; SER-72; GLY-102; VAL-104; CYS-110; PRO-122; ARG-200 AND PRO-276.
[17]	"Novel CHST6 nonsense and missense mutations responsible for macular corneal dystrophy." El-Ashry M.F., Abd El-Aziz M.M., Shalaby O., Wilkins S., Poopalasundaram S., Cheetham M., Tuft S.J., Hardcastle A.J., Bhattacharya S.S., Ebenezer N.D. Am. J. Ophthalmol. 139:192-193(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MCDC1 ARG-200; PRO-276 AND ASP-358.
+	Additional computationally mapped references.

Web resources

GGDB

GlycoGene database

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF219990 mRNA. Translation: AAG26325.1. AF219991 Genomic DNA. Translation: AAG26327.1. AF280086 mRNA. Translation: AAG48244.1. CH471114 Genomic DNA. Translation: EAW95640.1. CH471114 Genomic DNA. Translation: EAW95641.1. BC074883 mRNA. Translation: AAH74883.1. BC074834 mRNA. Translation: AAH74834.1.
IPI	IPI00012402.
RefSeq	NP_067628.1. NM_021615.4.
UniGene	Hs.655622.
3D structure databases
ProteinModelPortal	Q9GZX3.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000328983.
PTM databases
PhosphoSite	Q9GZX3.
Polymorphism databases
DMDM	61212105.
Proteomic databases
PaxDb	Q9GZX3.
PRIDE	Q9GZX3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000332272; ENSP00000328983; ENSG00000183196. ENST00000390664; ENSP00000375079; ENSG00000183196.
GeneID	4166.
KEGG	hsa:4166.
UCSC	uc002fef.3. human.
Organism-specific databases
CTD	4166.
GeneCards	GC16M075508.
HGNC	HGNC:6938. CHST6.
MIM	217800. phenotype. 605294. gene.
neXtProt	NX_Q9GZX3.
Orphanet	98969. Macular corneal dystrophy.
PharmGKB	PA26506.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG300333.
HOGENOM	HOG000261614.
HOVERGEN	HBG050949.
InParanoid	Q9GZX3.
KO	K09671.
OMA	FSWASST.
OrthoDB	EOG4RXZ09.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism. REACT_116125. Disease.
Gene expression databases
Bgee	Q9GZX3.
CleanEx	HS_CHST6.
Genevestigator	Q9GZX3.
GermOnline	ENSG00000183196. Homo sapiens.
Family and domain databases
InterPro	IPR016469. Carbohydrate_sulfotransferase. IPR027417. P-loop_NTPase. IPR000863. Sulfotransferase_dom. [Graphical view]
Pfam	PF00685. Sulfotransfer_1. 1 hit. [Graphical view]
PIRSF	PIRSF005883. Carbohydrate_sulfotransferase. 1 hit.
SUPFAM	SSF52540. SSF52540. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	CHST6. human.
GenomeRNAi	4166.
NextBio	16408.
SOURCE	Search...

Entry information

Entry name

CHST6_HUMAN

Accession

Primary (citable) accession number: Q9GZX3
Secondary accession number(s): D3DUK3

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	March 1, 2001
Last modified:	May 29, 2013
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.