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Q86X52 (CHSS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 105. 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:
Chondroitin sulfate synthase 1

EC=2.4.1.175
EC=2.4.1.226
Alternative name(s):
Chondroitin glucuronyltransferase 1
Chondroitin synthase 1
Short name=ChSy-1
Glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase 1
N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase 1
N-acetylgalactosaminyltransferase 1
Gene names
Name:CHSY1
Synonyms:CHSY, CSS1, KIAA0990
ORF Names:UNQ756/PRO1487
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length802 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Has both beta-1,3-glucuronic acid and beta-1,4-N-acetylgalactosamine transferase activity. Transfers glucuronic acid (GlcUA) from UDP-GlcUA and N-acetylgalactosamine (GalNAc) from UDP-GalNAc to the non-reducing end of the elongating chondroitin polymer. Involved in the negative control of osteogenesis likely through the modulation of NOTCH signaling. Ref.1 Ref.7

Catalytic activity

UDP-N-acetyl-alpha-D-galactosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-galactosaminyl-proteoglycan = UDP + N-acetyl-beta-D-galactosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-galactosaminyl-proteoglycan.

UDP-alpha-D-glucuronate + N-acetyl-beta-D-galactosaminyl-(1->4)-beta-D-glucuronosyl-proteoglycan = UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-galactosaminyl-(1->4)-beta-D-glucuronosyl-proteoglycan.

Cofactor

Divalent cations. Highest activities are measured with cobalt, manganese and cadmium. Ref.6

Subunit structure

Binds CHPF.

Subcellular location

Golgi apparatusGolgi stack membrane; Single-pass type II membrane protein Probable. Secreted Ref.1 Ref.7.

Tissue specificity

Ubiquitous, with the highest levels in placenta. Detected at low levels in brain, heart, skeletal muscle, colon, thymus, spleen, kidney, liver, adrenal gland, mammary gland, stomach, small intestine, lung and peripheral blood leukocytes. Ref.1 Ref.6

Involvement in disease

Temtamy preaxial brachydactyly syndrome (TPBS) [MIM:605282]: A syndrome characterized by multiple congenital anomalies, mental retardation, sensorineural deafness, talon cusps of upper central incisors, growth retardation, and bilateral symmetric digital anomalies mainly in the form of preaxial brachydactyly and hyperphalangism.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.8

Sequence similarities

Belongs to the chondroitin N-acetylgalactosaminyltransferase family.

Sequence caution

The sequence BAA76834.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Cellular componentGolgi apparatus
Membrane
Secreted
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   LigandMetal-binding
   Molecular functionTransferase
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcarbohydrate metabolic process

Traceable author statement. Source: Reactome

chondroitin sulfate biosynthetic process

Inferred from direct assay Ref.1. Source: MGI

chondroitin sulfate metabolic process

Traceable author statement. Source: Reactome

glycosaminoglycan metabolic process

Traceable author statement. Source: Reactome

negative regulation of ossification

Inferred from mutant phenotype Ref.7. Source: UniProtKB

response to nutrient levels

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentGolgi cisterna membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

Golgi membrane

Traceable author statement. Source: Reactome

extracellular region

Inferred from direct assay Ref.7. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionN-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase activity

Inferred from electronic annotation. Source: UniProtKB-EC

glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase activity

Inferred from direct assay Ref.1. Source: MGI

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 802802Chondroitin sulfate synthase 1
PRO_0000189558

Regions

Topological domain1 – 77Cytoplasmic Potential
Transmembrane8 – 2821Helical; Signal-anchor for type II membrane protein; Potential
Topological domain29 – 802774Lumenal Potential
Compositional bias449 – 4546Poly-Leu

Sites

Metal binding6331Divalent metal cation Potential
Metal binding7471Divalent metal cation Potential

Amino acid modifications

Glycosylation1891N-linked (GlcNAc...) Potential
Glycosylation6231N-linked (GlcNAc...) Potential
Glycosylation7961N-linked (GlcNAc...) Potential

Natural variations

Natural variant19 – 2810Missing in TPBS.
VAR_065821
Natural variant3591P → S.
Corresponds to variant rs3743193 [ dbSNP | Ensembl ].
VAR_021173
Natural variant5391P → R in TPBS. Ref.8
VAR_065822
Natural variant6521Q → H.
Corresponds to variant rs4426333 [ dbSNP | Ensembl ].
VAR_028009

Experimental info

Sequence conflict2741Q → R in AAQ88893. Ref.3
Sequence conflict5881R → T in BAB64936. Ref.1
Sequence conflict5881R → T in BAA76834. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q86X52 [UniParc].

Last modified October 17, 2006. Version 3.
Checksum: 5B4C02670332FA0E

FASTA80291,784
        10         20         30         40         50         60 
MAARGRRAWL SVLLGLVLGF VLASRLVLPR ASELKRAGPR RRASPEGCRS GQAAASQAGG 

        70         80         90        100        110        120 
ARGDARGAQL WPPGSDPDGG PRDRNFLFVG VMTAQKYLQT RAVAAYRTWS KTIPGKVQFF 

       130        140        150        160        170        180 
SSEGSDTSVP IPVVPLRGVD DSYPPQKKSF MMLKYMHDHY LDKYEWFMRA DDDVYIKGDR 

       190        200        210        220        230        240 
LENFLRSLNS SEPLFLGQTG LGTTEEMGKL ALEPGENFCM GGPGVIMSRE VLRRMVPHIG 

       250        260        270        280        290        300 
KCLREMYTTH EDVEVGRCVR RFAGVQCVWS YEMQQLFYEN YEQNKKGYIR DLHNSKIHQA 

       310        320        330        340        350        360 
ITLHPNKNPP YQYRLHSYML SRKISELRHR TIQLHREIVL MSKYSNTEIH KEDLQLGIPP 

       370        380        390        400        410        420 
SFMRFQPRQR EEILEWEFLT GKYLYSAVDG QPPRRGMDSA QREALDDIVM QVMEMINANA 

       430        440        450        460        470        480 
KTRGRIIDFK EIQYGYRRVN PMYGAEYILD LLLLYKKHKG KKMTVPVRRH AYLQQTFSKI 

       490        500        510        520        530        540 
QFVEHEELDA QELAKRINQE SGSLSFLSNS LKKLVPFQLP GSKSEHKEPK DKKINILIPL 

       550        560        570        580        590        600 
SGRFDMFVRF MGNFEKTCLI PNQNVKLVVL LFNSDSNPDK AKQVELMRDY RIKYPKADMQ 

       610        620        630        640        650        660 
ILPVSGEFSR ALALEVGSSQ FNNESLLFFC DVDLVFTTEF LQRCRANTVL GQQIYFPIIF 

       670        680        690        700        710        720 
SQYDPKIVYS GKVPSDNHFA FTQKTGFWRN YGFGITCIYK GDLVRVGGFD VSIQGWGLED 

       730        740        750        760        770        780 
VDLFNKVVQA GLKTFRSQEV GVVHVHHPVF CDPNLDPKQY KMCLGSKAST YGSTQQLAEM 

       790        800 
WLEKNDPSYS KSSNNNGSVR TA 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and expression of a human chondroitin synthase."
Kitagawa H., Uyama T., Sugahara K.
J. Biol. Chem. 276:38721-38726(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[2]"Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 6:63-70(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[3]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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: Brain.
[5]"Molecular cloning of a chondroitin polymerizing factor that cooperates with chondroitin synthase for chondroitin polymerization."
Kitagawa H., Izumikawa T., Uyama T., Sugahara K.
J. Biol. Chem. 278:23666-23671(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CHPF.
[6]"Chondroitin sulfate synthase-3. Molecular cloning and characterization."
Yada T., Sato T., Kaseyama H., Gotoh M., Iwasaki H., Kikuchi N., Kwon Y.-D., Togayachi A., Kudo T., Watanabe H., Narimatsu H., Kimata K.
J. Biol. Chem. 278:39711-39725(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: COFACTOR, TISSUE SPECIFICITY.
[7]"Loss of CHSY1, a secreted FRINGE enzyme, causes syndromic brachydactyly in humans via increased NOTCH signaling."
Tian J., Ling L., Shboul M., Lee H., O'Connor B., Merriman B., Nelson S.F., Cool S., Ababneh O.H., Al-Hadidy A., Masri A., Hamamy H., Reversade B.
Am. J. Hum. Genet. 87:768-778(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN TPBS.
[8]"Temtamy preaxial brachydactyly syndrome is caused by loss-of-function mutations in chondroitin synthase 1, a potential target of BMP signaling."
Li Y., Laue K., Temtamy S., Aglan M., Kotan L.D., Yigit G., Canan H., Pawlik B., Nurnberg G., Wakeling E.L., Quarrell O.W., Baessmann I., Lanktree M.B., Yilmaz M., Hegele R.A., Amr K., May K.W., Nurnberg P. expand/collapse author list , Topaloglu A.K., Hammerschmidt M., Wollnik B.
Am. J. Hum. Genet. 87:757-767(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS TPBS 19-GLY--LEU-28 DEL AND ARG-539.
+Additional computationally mapped references.

Web resources

GGDB

GlycoGene database

Functional Glycomics Gateway - GTase

Chondroitin sulfate synthase 1

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB071402 mRNA. Translation: BAB64936.1.
AB023207 mRNA. Translation: BAA76834.2. Different initiation.
AY358529 mRNA. Translation: AAQ88893.1.
BC046247 mRNA. Translation: AAH46247.1.
RefSeqNP_055733.2. NM_014918.4.
UniGeneHs.110488.

3D structure databases

ProteinModelPortalQ86X52.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116526. 1 interaction.
IntActQ86X52. 1 interaction.
STRING9606.ENSP00000254190.

Protein family/group databases

CAZyGT31. Glycosyltransferase Family 31.
GT7. Glycosyltransferase Family 7.

PTM databases

PhosphoSiteQ86X52.

Polymorphism databases

DMDM116241296.

Proteomic databases

PaxDbQ86X52.
PRIDEQ86X52.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000254190; ENSP00000254190; ENSG00000131873.
GeneID22856.
KEGGhsa:22856.
UCSCuc010usd.2. human.

Organism-specific databases

CTD22856.
GeneCardsGC15M101715.
H-InvDBHIX0172828.
HGNCHGNC:17198. CHSY1.
HPAHPA048902.
MIM605282. phenotype.
608183. gene.
neXtProtNX_Q86X52.
Orphanet363417. Temtamy preaxial brachydactyly syndrome.
PharmGKBPA26509.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG325444.
HOGENOMHOG000220809.
HOVERGENHBG050948.
InParanoidQ86X52.
KOK13499.
OMAYRIKYPK.
OrthoDBEOG74TWXX.
PhylomeDBQ86X52.
TreeFamTF318303.

Enzyme and pathway databases

BioCycMetaCyc:HS13400-MONOMER.
BRENDA2.4.1.175. 2681.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
SABIO-RKQ86X52.

Gene expression databases

BgeeQ86X52.
CleanExHS_CHSY1.
GenevestigatorQ86X52.

Family and domain databases

InterProIPR008428. Chond_GalNAc.
[Graphical view]
PANTHERPTHR12369. PTHR12369. 1 hit.
PfamPF05679. CHGN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCHSY1.
GenomeRNAi22856.
NextBio43341.
PROQ86X52.
SOURCESearch...

Entry information

Entry nameCHSS1_HUMAN
AccessionPrimary (citable) accession number: Q86X52
Secondary accession number(s): Q6UX38, Q7LFU5, Q9Y2J5
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 2005
Last sequence update: October 17, 2006
Last modified: April 16, 2014
This is version 105 of the entry and version 3 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 15

Human chromosome 15: entries, gene names and cross-references to MIM