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Protein

Chondroitin sulfate synthase 1

Gene

CHSY1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

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.

Cofactori

Co2+1 Publication, Mn2+1 Publication, Cd2+1 PublicationNote: Divalent metal cations. Highest activities are measured with Co(2+), Mn(2+) and Cd2+.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi633 – 6331Divalent metal cationSequence Analysis
Metal bindingi747 – 7471Divalent metal cationSequence Analysis

GO - Molecular functioni

  1. glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase activity Source: MGI
  2. metal ion binding Source: UniProtKB-KW
  3. N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase activity Source: UniProtKB-EC

GO - Biological processi

  1. bone morphogenesis Source: Ensembl
  2. carbohydrate metabolic process Source: Reactome
  3. chondrocyte development Source: Ensembl
  4. chondroitin sulfate biosynthetic process Source: MGI
  5. chondroitin sulfate metabolic process Source: Reactome
  6. glycosaminoglycan metabolic process Source: Reactome
  7. negative regulation of ossification Source: UniProtKB
  8. pathogenesis Source: Reactome
  9. positive regulation of smoothened signaling pathway Source: Ensembl
  10. proximal/distal pattern formation Source: Ensembl
  11. response to nutrient levels Source: Ensembl
  12. small molecule metabolic process Source: Reactome
  13. sulfation Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Ligandi

Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS13400-MONOMER.
BRENDAi2.4.1.175. 2681.
ReactomeiREACT_120989. Chondroitin sulfate biosynthesis.
REACT_268113. Defective CHSY1 causes TPBS.
SABIO-RKQ86X52.

Protein family/group databases

CAZyiGT31. Glycosyltransferase Family 31.
GT7. Glycosyltransferase Family 7.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:CHSY1
Synonyms:CHSY, CSS1, KIAA0990
ORF Names:UNQ756/PRO1487
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:17198. CHSY1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 77CytoplasmicSequence Analysis
Transmembranei8 – 2821Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST
Topological domaini29 – 802774LumenalSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. extracellular region Source: UniProtKB
  2. Golgi cisterna membrane Source: UniProtKB-SubCell
  3. Golgi membrane Source: Reactome
  4. integral component of membrane Source: UniProtKB-KW
  5. membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Golgi apparatus, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Temtamy preaxial brachydactyly syndrome (TPBS)2 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:605282
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti19 – 2810Missing in TPBS. 1 Publication
VAR_065821
Natural varianti539 – 5391P → R in TPBS. 1 Publication
VAR_065822

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi605282. phenotype.
Orphaneti363417. Temtamy preaxial brachydactyly syndrome.
PharmGKBiPA26509.

Polymorphism and mutation databases

BioMutaiCHSY1.
DMDMi116241296.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 802802Chondroitin sulfate synthase 1PRO_0000189558Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi189 – 1891N-linked (GlcNAc...)Sequence Analysis
Glycosylationi623 – 6231N-linked (GlcNAc...)Sequence Analysis
Glycosylationi796 – 7961N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiQ86X52.
PaxDbiQ86X52.
PRIDEiQ86X52.

PTM databases

PhosphoSiteiQ86X52.

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

BgeeiQ86X52.
CleanExiHS_CHSY1.
GenevestigatoriQ86X52.

Organism-specific databases

HPAiHPA048902.

Interactioni

Subunit structurei

Binds CHPF.

Protein-protein interaction databases

BioGridi116526. 8 interactions.
IntActiQ86X52. 1 interaction.
STRINGi9606.ENSP00000254190.

Structurei

3D structure databases

ProteinModelPortaliQ86X52.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi449 – 4546Poly-Leu

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG325444.
GeneTreeiENSGT00760000119143.
HOGENOMiHOG000220809.
HOVERGENiHBG050948.
InParanoidiQ86X52.
KOiK13499.
OMAiYRIKYPK.
OrthoDBiEOG74TWXX.
PhylomeDBiQ86X52.
TreeFamiTF318303.

Family and domain databases

Gene3Di3.90.550.10. 1 hit.
InterProiIPR008428. Chond_GalNAc.
IPR029044. Nucleotide-diphossugar_trans.
[Graphical view]
PfamiPF05679. CHGN. 1 hit.
[Graphical view]
SUPFAMiSSF53448. SSF53448. 3 hits.

Sequencei

Sequence statusi: Complete.

Q86X52-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAARGRRAWL SVLLGLVLGF VLASRLVLPR ASELKRAGPR RRASPEGCRS
60 70 80 90 100
GQAAASQAGG ARGDARGAQL WPPGSDPDGG PRDRNFLFVG VMTAQKYLQT
110 120 130 140 150
RAVAAYRTWS KTIPGKVQFF SSEGSDTSVP IPVVPLRGVD DSYPPQKKSF
160 170 180 190 200
MMLKYMHDHY LDKYEWFMRA DDDVYIKGDR LENFLRSLNS SEPLFLGQTG
210 220 230 240 250
LGTTEEMGKL ALEPGENFCM GGPGVIMSRE VLRRMVPHIG KCLREMYTTH
260 270 280 290 300
EDVEVGRCVR RFAGVQCVWS YEMQQLFYEN YEQNKKGYIR DLHNSKIHQA
310 320 330 340 350
ITLHPNKNPP YQYRLHSYML SRKISELRHR TIQLHREIVL MSKYSNTEIH
360 370 380 390 400
KEDLQLGIPP SFMRFQPRQR EEILEWEFLT GKYLYSAVDG QPPRRGMDSA
410 420 430 440 450
QREALDDIVM QVMEMINANA KTRGRIIDFK EIQYGYRRVN PMYGAEYILD
460 470 480 490 500
LLLLYKKHKG KKMTVPVRRH AYLQQTFSKI QFVEHEELDA QELAKRINQE
510 520 530 540 550
SGSLSFLSNS LKKLVPFQLP GSKSEHKEPK DKKINILIPL SGRFDMFVRF
560 570 580 590 600
MGNFEKTCLI PNQNVKLVVL LFNSDSNPDK AKQVELMRDY RIKYPKADMQ
610 620 630 640 650
ILPVSGEFSR ALALEVGSSQ FNNESLLFFC DVDLVFTTEF LQRCRANTVL
660 670 680 690 700
GQQIYFPIIF SQYDPKIVYS GKVPSDNHFA FTQKTGFWRN YGFGITCIYK
710 720 730 740 750
GDLVRVGGFD VSIQGWGLED VDLFNKVVQA GLKTFRSQEV GVVHVHHPVF
760 770 780 790 800
CDPNLDPKQY KMCLGSKAST YGSTQQLAEM WLEKNDPSYS KSSNNNGSVR

TA
Length:802
Mass (Da):91,784
Last modified:October 17, 2006 - v3
Checksum:i5B4C02670332FA0E
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti274 – 2741Q → R in AAQ88893 (PubMed:12975309).Curated
Sequence conflicti588 – 5881R → T in BAB64936 (PubMed:11514575).Curated
Sequence conflicti588 – 5881R → T in BAA76834 (PubMed:10231032).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti19 – 2810Missing in TPBS. 1 Publication
VAR_065821
Natural varianti359 – 3591P → S.
Corresponds to variant rs3743193 [ dbSNP | Ensembl ].
VAR_021173
Natural varianti539 – 5391P → R in TPBS. 1 Publication
VAR_065822
Natural varianti652 – 6521Q → H.
Corresponds to variant rs4426333 [ dbSNP | Ensembl ].
VAR_028009

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB071402 mRNA. Translation: BAB64936.1.
AB023207 mRNA. Translation: BAA76834.2. Different initiation.
AY358529 mRNA. Translation: AAQ88893.1.
BC046247 mRNA. Translation: AAH46247.1.
CCDSiCCDS10390.1.
RefSeqiNP_055733.2. NM_014918.4.
UniGeneiHs.110488.

Genome annotation databases

EnsembliENST00000254190; ENSP00000254190; ENSG00000131873.
GeneIDi22856.
KEGGihsa:22856.
UCSCiuc010usd.2. human.

Polymorphism and mutation databases

BioMutaiCHSY1.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

GGDB

GlycoGene database

Functional Glycomics Gateway - GTase

Chondroitin sulfate synthase 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB071402 mRNA. Translation: BAB64936.1.
AB023207 mRNA. Translation: BAA76834.2. Different initiation.
AY358529 mRNA. Translation: AAQ88893.1.
BC046247 mRNA. Translation: AAH46247.1.
CCDSiCCDS10390.1.
RefSeqiNP_055733.2. NM_014918.4.
UniGeneiHs.110488.

3D structure databases

ProteinModelPortaliQ86X52.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116526. 8 interactions.
IntActiQ86X52. 1 interaction.
STRINGi9606.ENSP00000254190.

Protein family/group databases

CAZyiGT31. Glycosyltransferase Family 31.
GT7. Glycosyltransferase Family 7.

PTM databases

PhosphoSiteiQ86X52.

Polymorphism and mutation databases

BioMutaiCHSY1.
DMDMi116241296.

Proteomic databases

MaxQBiQ86X52.
PaxDbiQ86X52.
PRIDEiQ86X52.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000254190; ENSP00000254190; ENSG00000131873.
GeneIDi22856.
KEGGihsa:22856.
UCSCiuc010usd.2. human.

Organism-specific databases

CTDi22856.
GeneCardsiGC15M101715.
H-InvDBHIX0172828.
HGNCiHGNC:17198. CHSY1.
HPAiHPA048902.
MIMi605282. phenotype.
608183. gene.
neXtProtiNX_Q86X52.
Orphaneti363417. Temtamy preaxial brachydactyly syndrome.
PharmGKBiPA26509.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG325444.
GeneTreeiENSGT00760000119143.
HOGENOMiHOG000220809.
HOVERGENiHBG050948.
InParanoidiQ86X52.
KOiK13499.
OMAiYRIKYPK.
OrthoDBiEOG74TWXX.
PhylomeDBiQ86X52.
TreeFamiTF318303.

Enzyme and pathway databases

BioCyciMetaCyc:HS13400-MONOMER.
BRENDAi2.4.1.175. 2681.
ReactomeiREACT_120989. Chondroitin sulfate biosynthesis.
REACT_268113. Defective CHSY1 causes TPBS.
SABIO-RKQ86X52.

Miscellaneous databases

ChiTaRSiCHSY1. human.
GeneWikiiCHSY1.
GenomeRNAii22856.
NextBioi43341.
PROiQ86X52.
SOURCEiSearch...

Gene expression databases

BgeeiQ86X52.
CleanExiHS_CHSY1.
GenevestigatoriQ86X52.

Family and domain databases

Gene3Di3.90.550.10. 1 hit.
InterProiIPR008428. Chond_GalNAc.
IPR029044. Nucleotide-diphossugar_trans.
[Graphical view]
PfamiPF05679. CHGN. 1 hit.
[Graphical view]
SUPFAMiSSF53448. SSF53448. 3 hits.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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.
    , 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.

Entry informationi

Entry nameiCHSS1_HUMAN
AccessioniPrimary (citable) accession number: Q86X52
Secondary accession number(s): Q6UX38, Q7LFU5, Q9Y2J5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 2005
Last sequence update: October 17, 2006
Last modified: April 29, 2015
This is version 116 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.