Q7LGC8 (CHST3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Carbohydrate sulfotransferase 3
EC=2.8.2.17

Alternative name(s):
Chondroitin 6-O-sulfotransferase 1
Short name=C6ST-1
Chondroitin 6-sulfotransferase
Galactose/N-acetylglucosamine/N-acetylglucosamine 6-O-sulfotransferase 0
Short name=GST-0

Gene names

Name:

CHST3

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	479 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 the N-acetylgalactosamine (GalNAc) residue of chondroitin. Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage and is distributed on the surfaces of many cells and extracellular matrices. Can also sulfate Gal residues of keratan sulfate, another glycosaminoglycan, and the Gal residues in sialyl N-acetyllactosamine (sialyl LacNAc) oligosaccharides. May play a role in the maintenance of naive T-lymphocytes in the spleen. Ref.1 Ref.2
Catalytic activity	3'-phosphoadenylyl sulfate + chondroitin = adenosine 3',5'-bisphosphate + chondroitin 6'-sulfate.
Subcellular location	Golgi apparatus membrane; Single-pass type II membrane protein By similarity.
Tissue specificity	Widely expressed in adult tissues. Expressed in heart, placenta, skeletal muscle and pancreas. Also expressed in various immune tissues such as spleen, lymph node, thymus and appendix. Ref.1
Involvement in disease	Spondyloepiphyseal dysplasia with congenital joint dislocations (SEDC-JD) [MIM:143095]: A bone dysplasia clinically characterized by dislocation of the knees and/or hips at birth, clubfoot, elbow joint dysplasia with subluxation and limited extension, short stature, and progressive kyphosis developing in late childhood. The disorder is usually evident at birth, with short stature and multiple joint dislocations or subluxations that dominate the neonatal clinical and radiographic picture. During childhood, the dislocations improve, both spontaneously and with surgical treatment, and features of spondyloepiphyseal dysplasia become apparent, leading to arthritis of the hips and spine with intervertebral disk degeneration, rigid kyphoscoliosis, and trunk shortening by late childhood. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.5
Sequence similarities	Belongs to the sulfotransferase 1 family. Gal/GlcNAc/GalNAc subfamily.

Ontologies

Keywords
Biological process	Carbohydrate metabolism
Cellular component	Golgi apparatus Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Transferase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T cell homeostasis Inferred from electronic annotation. Source: Compara carbohydrate metabolic process Traceable author statement. Source: Reactome chondroitin sulfate biosynthetic process Inferred from direct assay Ref.2. Source: UniProtKB
Cellular_component	Golgi membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	chondroitin 6-sulfotransferase activity Inferred from direct assay Ref.2. Source: UniProtKB proteoglycan sulfotransferase activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 479	479	Carbohydrate sulfotransferase 3		PRO_0000085188
Regions
	Topological domain	1 – 20	20	Cytoplasmic Potential
	Transmembrane	21 – 38	18	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	39 – 479	441	Lumenal Potential
	Nucleotide binding	141 – 147	7	PAPS By similarity
	Nucleotide binding	301 – 309	9	PAPS By similarity
Amino acid modifications
	Glycosylation	63	1	N-linked (GlcNAc...) Potential
	Glycosylation	74	1	N-linked (GlcNAc...) Potential
	Glycosylation	96	1	N-linked (GlcNAc...) Potential
	Glycosylation	256	1	N-linked (GlcNAc...) Potential
	Glycosylation	420	1	N-linked (GlcNAc...) Potential
	Glycosylation	464	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	222	1	R → W in SEDC-JD; severely impairs or abolishes the enzyme function. Ref.5		VAR_047856
	Natural variant	259	1	L → P in SEDC-JD; severely impairs or abolishes the enzyme function. Ref.5		VAR_047857
	Natural variant	304	1	R → Q in SEDC-JD; reduced enzyme activity. Ref.4 Corresponds to variant rs28937593 [ dbSNP | Ensembl ].		VAR_021413
	Natural variant	307	1	L → P in SEDC-JD. Ref.5		VAR_047858
	Natural variant	348	1	I → M. Corresponds to variant rs3740128 [ dbSNP | Ensembl ].		VAR_021414
	Natural variant	357	1	R → Q. Ref.3 Ref.5 Corresponds to variant rs3740129 [ dbSNP | Ensembl ].		VAR_021415
	Natural variant	372	1	E → K in SEDC-JD. Ref.5		VAR_047859
Experimental info
	Sequence conflict	387	1	R → P in BAA32576. Ref.1
	Sequence conflict	443	1	A → P in BAA32576. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q7LGC8 [UniParc]. Last modified October 17, 2006. Version 3. Checksum: 7C290DC4970F66E0	FASTA	479	54,706
	10 20 30 40 50 60 MEKGLTLPQD CRDFVHSLKM RSKYALFLVF VVIVFVFIEK ENKIISRVSD KLKQIPQALA 70 80 90 100 110 120 DANSTDPALI LAENASLLSL SELDSAFSQL QSRLRNLSLQ LGVEPAMEAA GEEEEEQRKE 130 140 150 160 170 180 EEPPRPAVAG PRRHVLLMAT TRTGSSFVGE FFNQQGNIFY LFEPLWHIER TVSFEPGGAN 190 200 210 220 230 240 AAGSALVYRD VLKQLFLCDL YVLEHFITPL PEDHLTQFMF RRGSSRSLCE DPVCTPFVKK 250 260 270 280 290 300 VFEKYHCKNR RCGPLNVTLA AEACRRKEHM ALKAVRIRQL EFLQPLAEDP RLDLRVIQLV 310 320 330 340 350 360 RDPRAVLASR MVAFAGKYKT WKKWLDDEGQ DGLREEEVQR LRGNCESIRL SAELGLRQPA 370 380 390 400 410 420 WLRGRYMLVR YEDVARGPLQ KAREMYRFAG IPLTPQVEDW IQKNTQAAHD GSGIYSTQKN 430 440 450 460 470 SSEQFEKWRF SMPFKLAQVV QAACGPAMRL FGYKLARDAA ALTNRSVSLL EERGTFWVT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of human chondroitin 6-sulfotransferase." Fukuta M., Kobayashi Y., Uchimura K., Kimata K., Habuchi O. Biochim. Biophys. Acta 1399:57-61(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY. Tissue: Fetal brain.
[2]	"Functional expression and genomic structure of human chondroitin 6-sulfotransferase." Tsutsumi K., Shimakawa H., Kitagawa H., Sugahara K. FEBS Lett. 441:235-241(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Tissue: Placenta.
[3]	"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], VARIANT GLN-357. Tissue: Liver.
[4]	"Loss of chondroitin 6-O-sulfotransferase-1 function results in severe human chondrodysplasia with progressive spinal involvement." Thiele H., Sakano M., Kitagawa H., Sugahara K., Rajab A., Hoehne W., Ritter H., Leschik G., Nuernberg P., Mundlos S. Proc. Natl. Acad. Sci. U.S.A. 101:10155-10160(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SEDC-JD GLN-304.
[5]	"Congenital joint dislocations caused by carbohydrate sulfotransferase 3 deficiency in recessive Larsen syndrome and humero-spinal dysostosis." Hermanns P., Unger S., Rossi A., Perez-Aytes A., Cortina H., Bonafe L., Boccone L., Setzu V., Dutoit M., Sangiorgi L., Pecora F., Reicherter K., Nishimura G., Spranger J., Zabel B., Superti-Furga A. Am. J. Hum. Genet. 82:1368-1374(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SEDC-JD TRP-222; PRO-259; PRO-307 AND LYS-372, VARIANT GLN-357, CHARACTERIZATION OF VARIANTS SEDC-JD TRP-222 AND PRO-259.
[6]	Erratum Hermanns P., Unger S., Rossi A., Perez-Aytes A., Cortina H., Bonafe L., Boccone L., Setzu V., Dutoit M., Sangiorgi L., Pecora F., Reicherter K., Nishimura G., Spranger J., Zabel B., Superti-Furga A. Am. J. Hum. Genet. 83:293-293(2008)
+	Additional computationally mapped references.

Web resources

GGDB

GlycoGene database

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB012192 mRNA. Translation: BAA32576.1. AB017915 mRNA. Translation: BAA36348.1. BC093690 mRNA. Translation: AAH93690.1. BC104856 mRNA. Translation: AAI04857.1.
IPI	IPI00306853.
RefSeq	NP_004264.2. NM_004273.4.
UniGene	Hs.158304.
3D structure databases
ProteinModelPortal	Q7LGC8.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000362207.
PTM databases
PhosphoSite	Q7LGC8.
Polymorphism databases
DMDM	116241297.
Proteomic databases
PaxDb	Q7LGC8.
PRIDE	Q7LGC8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000373115; ENSP00000362207; ENSG00000122863.
GeneID	9469.
KEGG	hsa:9469.
UCSC	uc001jsn.3. human.
Organism-specific databases
CTD	9469.
GeneCards	GC10P073724.
HGNC	HGNC:1971. CHST3.
MIM	143095. phenotype. 603799. gene.
neXtProt	NX_Q7LGC8.
Orphanet	263463. CHST3-related skeletal dysplasia.
PharmGKB	PA26503.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG80862.
HOGENOM	HOG000261614.
HOVERGEN	HBG106811.
InParanoid	Q7LGC8.
KO	K01020.
OMA	HSLRMRS.
OrthoDB	EOG40P470.
Enzyme and pathway databases
BioCyc	MetaCyc:HS04610-MONOMER.
BRENDA	2.8.2.17. 2681.
Reactome	REACT_111217. Metabolism. REACT_116125. Disease.
Gene expression databases
Bgee	Q7LGC8.
CleanEx	HS_CHST3.
Genevestigator	Q7LGC8.
GermOnline	ENSG00000122863. Homo sapiens.
Family and domain databases
InterPro	IPR016469. Carbohydrate_sulfotransferase. IPR000863. Sulfotransferase_dom. [Graphical view]
Pfam	PF00685. Sulfotransfer_1. 1 hit. [Graphical view]
PIRSF	PIRSF005883. Carbohydrate_sulfotransferase. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	9469.
NextBio	35486.
SOURCE	Search...

Entry information

Entry name

CHST3_HUMAN

Accession

Primary (citable) accession number: Q7LGC8
Secondary accession number(s): O75099, Q52M30

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 92 of the entry and version 3 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.