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Q9GZX3 (CHST6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length395 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 395395Carbohydrate sulfotransferase 6
PRO_0000085197

Regions

Topological domain1 – 55Cytoplasmic Potential
Transmembrane6 – 2621Helical; Signal-anchor for type II membrane protein; Potential
Topological domain27 – 395369Lumenal Potential
Nucleotide binding49 – 557PAPS By similarity
Nucleotide binding202 – 2109PAPS By similarity

Amino acid modifications

Glycosylation1161N-linked (GlcNAc...) Potential
Glycosylation2291N-linked (GlcNAc...) Potential
Glycosylation3051N-linked (GlcNAc...) Potential
Glycosylation3281N-linked (GlcNAc...) Potential

Natural variations

Natural variant151L → P in MCDC1. Ref.9
VAR_021417
Natural variant221L → R in MCDC1. Ref.13
VAR_021418
Natural variant311P → S in MCDC1. Ref.8
VAR_021419
Natural variant421H → Y in MCDC1. Ref.13
VAR_021420
Natural variant501R → C in MCDC1; abolishes ability to sulfate keratan. Ref.1 Ref.6
Corresponds to variant rs28937877 [ dbSNP | Ensembl ].
VAR_021421
Natural variant511S → L in MCDC1. Ref.12 Ref.16
VAR_021422
Natural variant521G → D in MCDC1. Ref.14
VAR_021423
Natural variant531S → L in MCDC1. Ref.13 Ref.14
VAR_021424
Natural variant591L → P in MCDC1. Ref.12
VAR_021425
Natural variant611N → T in MCDC1. Ref.9
VAR_021426
Natural variant661V → L in MCDC1. Ref.12
VAR_021427
Natural variant681Y → H in MCDC1. Ref.9
VAR_021428
Natural variant701M → L in MCDC1. Ref.9
VAR_021429
Natural variant721P → S in MCDC1. Ref.8 Ref.16
VAR_021430
Natural variant761V → M in MCDC1. Ref.12
VAR_021431
Natural variant931R → H in MCDC1. Ref.13
VAR_021432
Natural variant971R → P in MCDC1. Ref.13
VAR_021433
Natural variant981S → W in MCDC1. Ref.14
VAR_021434
Natural variant1021C → G in MCDC1. Ref.9 Ref.15 Ref.16
VAR_021435
Natural variant1021C → Y in MCDC1. Ref.13
VAR_021436
Natural variant1041M → V in MCDC1. Ref.16
VAR_021437
Natural variant1071F → S in MCDC1. Ref.8 Ref.14
VAR_021438
Natural variant1101Y → C in MCDC1. Ref.16
VAR_021439
Natural variant1211F → L in MCDC1. Ref.14
VAR_021440
Natural variant1221Q → P in MCDC1. Ref.16
VAR_021441
Natural variant1271R → C in MCDC1. Ref.13
VAR_021442
Natural variant1281A → V in MCDC1. Ref.7
VAR_021443
Natural variant1311S → P in MCDC1. Ref.9
VAR_021444
Natural variant1521L → P in MCDC1. Ref.9
VAR_021445
Natural variant1621R → G in MCDC1. Ref.15
Corresponds to variant rs117435647 [ dbSNP | Ensembl ].
VAR_021446
Natural variant1661R → P in MCDC1. Ref.7 Ref.9
VAR_021447
Natural variant1741K → R in MCDC1; abolishes ability to sulfate keratan. Ref.1 Ref.6
Corresponds to variant rs28937878 [ dbSNP | Ensembl ].
VAR_021448
Natural variant1771R → H in MCDC1. Ref.10
VAR_021449
Natural variant1981V → E in MCDC1. Ref.15
VAR_021450
Natural variant2001L → R in MCDC1. Ref.8 Ref.9 Ref.15 Ref.16 Ref.17
Corresponds to variant rs28937879 [ dbSNP | Ensembl ].
VAR_021451
Natural variant2021R → S in MCDC1. Ref.14
VAR_021452
Natural variant2031D → E in MCDC1; abolishes ability to sulfate keratan. Ref.1 Ref.6
Corresponds to variant rs28937878 [ dbSNP | Ensembl ].
VAR_021453
Natural variant2041P → Q in MCDC1. Ref.9 Ref.10 Ref.14
VAR_021454
Natural variant2051R → L in MCDC1. Ref.10
VAR_021455
Natural variant2051R → Q in MCDC1. Ref.13
VAR_021456
Natural variant2061A → T in MCDC1. Ref.13
VAR_021457
Natural variant2061A → V in MCDC1. Ref.8
VAR_021458
Natural variant2101S → F in MCDC1. Ref.14
VAR_021459
Natural variant2111R → Q in MCDC1. Ref.11 Ref.12
VAR_021460
Natural variant2111R → W in MCDC1; abolishes ability to sulfate keratan. Ref.1 Ref.6 Ref.10
Corresponds to variant rs202175444 [ dbSNP | Ensembl ].
VAR_021461
Natural variant2171A → T in MCDC1; abolishes ability to sulfate keratan. Ref.6 Ref.10
VAR_021462
Natural variant2211D → E in MCDC1. Ref.14
VAR_021463
Natural variant2211D → Y in MCDC1. Ref.14
VAR_021464
Natural variant2491H → P in MCDC1. Ref.13
VAR_021465
Natural variant2681Y → C in MCDC1. Ref.12
VAR_021466
Natural variant2741E → K in MCDC1; abolishes ability to sulfate keratan. Ref.1 Ref.6 Ref.13
VAR_021467
Natural variant2761L → P in MCDC1. Ref.16 Ref.17
VAR_021468
Natural variant3581Y → D in MCDC1. Ref.17
VAR_021469
Natural variant3691N → D.
Corresponds to variant rs35036798 [ dbSNP | Ensembl ].
VAR_033735

Sequences

Sequence LengthMass (Da)Tools
Q9GZX3 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 433CA60248A48F67

FASTA39544,099
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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.
RefSeqNP_067628.1. NM_021615.4.
XP_005256012.1. XM_005255955.2.
UniGeneHs.655622.

3D structure databases

ProteinModelPortalQ9GZX3.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000328983.

PTM databases

PhosphoSiteQ9GZX3.

Proteomic databases

PaxDbQ9GZX3.
PRIDEQ9GZX3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000332272; ENSP00000328983; ENSG00000183196.
ENST00000390664; ENSP00000375079; ENSG00000183196.
GeneID4166.
KEGGhsa:4166.
UCSCuc002fef.3. human.

Organism-specific databases

CTD4166.
GeneCardsGC16M075508.
HGNCHGNC:6938. CHST6.
MIM217800. phenotype.
605294. gene.
neXtProtNX_Q9GZX3.
Orphanet98969. Macular corneal dystrophy.
PharmGKBPA26506.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG300333.
HOGENOMHOG000261614.
HOVERGENHBG050949.
InParanoidQ9GZX3.
KOK09671.
OMAFPRGAIS.
OrthoDBEOG7RZ5S0.
PhylomeDBQ9GZX3.
TreeFamTF342871.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.

Gene expression databases

BgeeQ9GZX3.
CleanExHS_CHST6.
GenevestigatorQ9GZX3.

Family and domain databases

Gene3D3.40.50.300. 2 hits.
InterProIPR016469. Carbohydrate_sulfotransferase.
IPR027417. P-loop_NTPase.
IPR000863. Sulfotransferase_dom.
[Graphical view]
PfamPF00685. Sulfotransfer_1. 1 hit.
[Graphical view]
PIRSFPIRSF005883. Carbohydrate_sulfotransferase. 1 hit.
SUPFAMSSF52540. SSF52540. 2 hits.
ProtoNetSearch...

Other

ChiTaRSCHST6. human.
GeneWikiCHST6.
GenomeRNAi4166.
NextBio16408.
PROQ9GZX3.
SOURCESearch...

Entry information

Entry nameCHST6_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 107 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM