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P28329 (CLAT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Choline O-acetyltransferase

Short name=CHOACTase
Short name=ChAT
Short name=Choline acetylase
EC=2.3.1.6
Gene names
Name:CHAT
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length748 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the reversible synthesis of acetylcholine (ACh) from acetyl CoA and choline at cholinergic synapses.

Catalytic activity

Acetyl-CoA + choline = CoA + O-acetylcholine.

Involvement in disease

Myasthenic syndrome, congenital, associated with episodic apnea (CMSEA) [MIM:254210]: An autosomal recessive congenital myasthenic syndrome. Patients have myasthenic symptoms since birth or early infancy, negative tests for anti-AChR antibodies, and abrupt episodic crises with increased weakness, bulbar paralysis, and apnea precipitated by undue exertion, fever, or excitement.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.11

Sequence similarities

Belongs to the carnitine/choline acetyltransferase family.

Ontologies

Keywords
   Biological processNeurotransmitter biosynthesis
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseCongenital myasthenic syndrome
Disease mutation
   Molecular functionAcyltransferase
Transferase
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processadult walking behavior

Inferred from electronic annotation. Source: Ensembl

dendrite development

Inferred from electronic annotation. Source: Ensembl

establishment of synaptic specificity at neuromuscular junction

Inferred from electronic annotation. Source: Ensembl

glycerophospholipid biosynthetic process

Traceable author statement. Source: Reactome

muscle organ development

Inferred from electronic annotation. Source: Ensembl

neuromuscular synaptic transmission

Inferred from electronic annotation. Source: Ensembl

neurotransmitter biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

neurotransmitter secretion

Traceable author statement. Source: Reactome

phosphatidylcholine biosynthetic process

Traceable author statement. Source: Reactome

phospholipid metabolic process

Traceable author statement. Source: Reactome

rhythmic behavior

Inferred from electronic annotation. Source: Ensembl

rhythmic excitation

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

synaptic transmission

Traceable author statement. Source: Reactome

   Cellular_componentaxon

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Traceable author statement PubMed 10861222. Source: ProtInc

cytosol

Traceable author statement. Source: Reactome

mitochondrion

Inferred from electronic annotation. Source: Ensembl

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

nucleus

Traceable author statement PubMed 10861222. Source: ProtInc

   Molecular_functioncholine O-acetyltransferase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform M (identifier: P28329-1)

Also known as: 83 kDa;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform S (identifier: P28329-2)

Also known as: 74 kDa;

The sequence of this isoform differs from the canonical sequence as follows:
     1-95: MGLRTAKKRG...SAEAAEPRRA → MWPECRDEALSTV
Isoform R (identifier: P28329-3)

Also known as: 70 kDa;

The sequence of this isoform differs from the canonical sequence as follows:
     1-118: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 748748Choline O-acetyltransferase
PRO_0000210154

Regions

Region520 – 53213Coenzyme A binding

Sites

Active site4421Proton acceptor
Binding site5581Coenzyme A
Binding site6591Coenzyme A

Natural variations

Alternative sequence1 – 118118Missing in isoform R.
VSP_000791
Alternative sequence1 – 9595MGLRT…EPRRA → MWPECRDEALSTV in isoform S.
VSP_000790
Natural variant471D → E.
Corresponds to variant rs3810948 [ dbSNP | Ensembl ].
VAR_046683
Natural variant1201A → T. Ref.2 Ref.6
Corresponds to variant rs3810950 [ dbSNP | Ensembl ].
VAR_011675
Natural variant2101L → P in CMSEA; impaired activity. Ref.2
Corresponds to variant rs28930071 [ dbSNP | Ensembl ].
VAR_011666
Natural variant2111P → A in CMSEA; impaired activity. Ref.2
VAR_011667
Natural variant2221R → P.
Corresponds to variant rs8178989 [ dbSNP | Ensembl ].
VAR_046684
Natural variant2431L → F.
Corresponds to variant rs8178990 [ dbSNP | Ensembl ].
VAR_046685
Natural variant2991P → L.
Corresponds to variant rs868749 [ dbSNP | Ensembl ].
VAR_046686
Natural variant3051I → T in CMSEA; impaired activity. Ref.2
Corresponds to variant rs28929482 [ dbSNP | Ensembl ].
VAR_011668
Natural variant3361I → T in CMSEA. Ref.11
VAR_038605
Natural variant3921A → G. Ref.1 Ref.2
VAR_011676
Natural variant4001D → N.
Corresponds to variant rs8178991 [ dbSNP | Ensembl ].
VAR_046687
Natural variant4201R → C in CMSEA; impaired activity. Ref.2
VAR_011669
Natural variant4411E → K in CMSEA; completely lack activity. Ref.2
Corresponds to variant rs28930070 [ dbSNP | Ensembl ].
VAR_011670
Natural variant4611V → M. Ref.1 Ref.2 Ref.6
Corresponds to variant rs4838544 [ dbSNP | Ensembl ].
VAR_046688
Natural variant4821R → G in CMSEA; impaired activity. Ref.2
Corresponds to variant rs28929481 [ dbSNP | Ensembl ].
VAR_011671
Natural variant4981S → L in CMSEA; impaired activity. Ref.2
VAR_011672
Natural variant5061V → L in CMSEA; impaired activity. Ref.2
VAR_011673
Natural variant5601R → H in CMSEA; impaired activity. Ref.2
VAR_011674

Experimental info

Sequence conflict1511R → Q in CAA39923. Ref.7
Sequence conflict261 – 2622GQ → PE in AAA14245. Ref.1
Sequence conflict3961V → L in AAB23557. Ref.6
Sequence conflict4341G → A in AAA14245. Ref.1
Sequence conflict5291C → S in AAB23557. Ref.6
Sequence conflict5671V → L in AAB23557. Ref.6
Sequence conflict629 – 6302EL → DV in AAB23557. Ref.6
Sequence conflict6641T → M in AAB23557. Ref.6

Secondary structure

............................................................................................. 748
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform M (83 kDa) [UniParc].

Last modified December 15, 2009. Version 4.
Checksum: A902364081915391

FASTA74882,536
        10         20         30         40         50         60 
MGLRTAKKRG LGGGGKWKRE EGGGTRGRRE VRPACFLQSG GRGDPGDVGG PAGNPGCSPH 

        70         80         90        100        110        120 
PRAATRPPPL PAHTPAHTPE WCGAASAEAA EPRRAGPHLC IPAPGLTKTP ILEKVPRKMA 

       130        140        150        160        170        180 
AKTPSSEESG LPKLPVPPLQ QTLATYLQCM RHLVSEEQFR KSQAIVQQFG APGGLGETLQ 

       190        200        210        220        230        240 
QKLLERQEKT ANWVSEYWLN DMYLNNRLAL PVNSSPAVIF ARQHFPGTDD QLRFAASLIS 

       250        260        270        280        290        300 
GVLSYKALLD SHSIPTDCAK GQLSGQPLCM KQYYGLFSSY RLPGHTQDTL VAQNSSIMPE 

       310        320        330        340        350        360 
PEHVIVACCN QFFVLDVVIN FRRLSEGDLF TQLRKIVKMA SNEDERLPPI GLLTSDGRSE 

       370        380        390        400        410        420 
WAEARTVLVK DSTNRDSLDM IERCICLVCL DAPGGVELSD THRALQLLHG GGYSKNGANR 

       430        440        450        460        470        480 
WYDKSLQFVV GRDGTCGVVC EHSPFDGIVL VQCTEHLLKH VTQSSRKLIR ADSVSELPAP 

       490        500        510        520        530        540 
RRLRWKCSPE IQGHLASSAE KLQRIVKNLD FIVYKFDNYG KTFIKKQKCS PDAFIQVALQ 

       550        560        570        580        590        600 
LAFYRLHRRL VPTYESASIR RFQEGRVDNI RSATPEALAF VRAVTDHKAA VPASEKLLLL 

       610        620        630        640        650        660 
KDAIRAQTAY TVMAITGMAI DNHLLALREL ARAMCKELPE MFMDETYLMS NRFVLSTSQV 

       670        680        690        700        710        720 
PTTTEMFCCY GPVVPNGYGA CYNPQPETIL FCISSFHSCK ETSSSKFAKA VEESLIDMRD 

       730        740 
LCSLLPPTES KPLATKEKAT RPSQGHQP 

« Hide

Isoform S (74 kDa) [UniParc].

Checksum: 3A521459434FF919
Show »

FASTA66674,361
Isoform R (70 kDa) [UniParc].

Checksum: 0BF3CC8F56518326
Show »

FASTA63070,394

References

« Hide 'large scale' references
[1]"A complementary DNA for human choline acetyltransferase induces two forms of enzyme with different molecular weights in cultured cells."
Oda Y., Nakanishi I., Deguchi T.
Brain Res. Mol. Brain Res. 16:287-294(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS GLY-392 AND MET-461.
Tissue: Spinal cord.
[2]"Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans."
Ohno K., Tsujino A., Brengman J.M., Harper C.M., Bajzer Z., Udd B., Beyring R., Robb S., Kirkham F.J., Engel A.G.
Proc. Natl. Acad. Sci. U.S.A. 98:2017-2022(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], ALTERNATIVE SPLICING, VARIANTS CMSEA PRO-210; ALA-211; THR-305; CYS-420; LYS-441; GLY-482; LEU-498; LEU-506 AND HIS-560, VARIANTS THR-120; GLY-392 AND MET-461.
[3]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]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].
[5]"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] (ISOFORM R).
[6]"Two mRNAs are transcribed from the human gene for choline acetyltransferase."
Lorenzi M.V., Trinidad A.C., Zhang R., Strauss W.L.
DNA Cell Biol. 11:593-603(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 111-669, VARIANTS THR-120 AND MET-461.
[7]"Human choline acetyltransferase (CHAT): partial gene sequence and potential control regions."
Toussaint J.L., Geoffroy V., Schmitt M., Werner A., Garnier J.-M., Simoni P., Kempf J.
Genomics 12:412-416(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 109-232.
[8]"Conservation of amino acid sequences between human and porcine choline acetyltransferase."
Hersh L.B., Takane K., Gylys K., Moomaw C., Slaughter C.
J. Neurochem. 51:1843-1845(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 161-182; 271-295; 340-352; 376-382; 404-415; 550-559; 572-583; 620-632; 644-648; 650-662 AND 739-748.
Tissue: Placenta.
[9]"Isolation and sub-chromosomal localization of a DNA fragment of the human choline acetyltransferase gene."
Cervini R., Rocchi M., DiDonato S., Finocchiaro G.
Neurosci. Lett. 132:191-194(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 688-738.
Tissue: Lymphocyte.
[10]"Substrate binding and catalytic mechanism of human choline acetyltransferase."
Kim A.-R., Rylett R.J., Shilton B.H.
Biochemistry 45:14621-14631(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 120-733 IN COMPLEXES WITH CHOLINE AND ACETYL COENZYME A.
[11]"Congenital myasthenic syndrome with episodic apnea in patients homozygous for a CHAT missense mutation."
Kraner S., Laufenberg I., Strassburg H.M., Sieb J.P., Steinlein O.K.
Arch. Neurol. 60:761-763(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CMSEA THR-336.
+Additional computationally mapped references.

Web resources

Wikipedia

Choline acetyltransferase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
S56138 mRNA. Translation: AAA14245.1.
AF305907 mRNA. Translation: AAK08953.1.
AF305906 expand/collapse EMBL AC list , AF305894, AF305895, AF305896, AF305897, AF305898, AF305899, AF305900, AF305901, AF305902, AF305903, AF305904, AF305905 Genomic DNA. Translation: AAK08950.1.
AF305908 mRNA. Translation: AAK08954.1.
AF305906 expand/collapse EMBL AC list , AF305894, AF305895, AF305896, AF305897, AF305898, AF305899, AF305900, AF305901, AF305902, AF305903, AF305904, AF305905 Genomic DNA. Translation: AAK08951.1.
AF305909 mRNA. Translation: AAK08955.1.
AF305906 expand/collapse EMBL AC list , AF305894, AF305895, AF305896, AF305897, AF305898, AF305899, AF305900, AF305901, AF305902, AF305903, AF305904, AF305905 Genomic DNA. Translation: AAK08952.1.
AC073366 Genomic DNA. No translation available.
CH471187 Genomic DNA. Translation: EAW93086.1.
BC130615 mRNA. Translation: AAI30616.1.
S45018 mRNA. Translation: AAB23557.2.
X56585 Genomic DNA. Translation: CAA39923.1.
X56879 Genomic DNA. Translation: CAA40201.1.
CCDSCCDS44389.1. [P28329-2]
CCDS7232.1. [P28329-1]
CCDS7233.1. [P28329-3]
PIRA60202. I52631.
RefSeqNP_001136401.1. NM_001142929.1.
NP_001136405.1. NM_001142933.1.
NP_001136406.1. NM_001142934.1.
NP_065574.3. NM_020549.4.
NP_066264.3. NM_020984.3.
NP_066265.3. NM_020985.3.
NP_066266.3. NM_020986.3.
UniGeneHs.302002.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2FY2X-ray2.25A120-733[»]
2FY3X-ray2.27A120-733[»]
2FY4X-ray2.30A120-733[»]
2FY5X-ray2.60A120-733[»]
ProteinModelPortalP28329.
SMRP28329. Positions 126-727.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000337103.

Chemistry

ChEMBLCHEMBL4039.
DrugBankDB00122. Choline.

PTM databases

PhosphoSiteP28329.

Polymorphism databases

DMDM281185509.

Proteomic databases

PaxDbP28329.
PRIDEP28329.

Protocols and materials databases

DNASU1103.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000337653; ENSP00000337103; ENSG00000070748. [P28329-1]
ENST00000339797; ENSP00000343486; ENSG00000070748. [P28329-3]
ENST00000351556; ENSP00000345878; ENSG00000070748. [P28329-3]
ENST00000395559; ENSP00000378926; ENSG00000070748. [P28329-3]
ENST00000395562; ENSP00000378929; ENSG00000070748. [P28329-2]
GeneID1103.
KEGGhsa:1103.
UCSCuc001jhz.2. human. [P28329-1]

Organism-specific databases

CTD1103.
GeneCardsGC10P050817.
GeneReviewsCHAT.
HGNCHGNC:1912. CHAT.
HPACAB002313.
HPA048547.
MIM118490. gene.
254210. phenotype.
neXtProtNX_P28329.
Orphanet98914. Presynaptic congenital myasthenic syndromes.
PharmGKBPA26448.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG70127.
HOGENOMHOG000233845.
HOVERGENHBG107717.
InParanoidP28329.
KOK00623.
OMAHVIVACC.
OrthoDBEOG7WHH90.
PhylomeDBP28329.
TreeFamTF313836.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_13685. Neuronal System.
SABIO-RKP28329.

Gene expression databases

ArrayExpressP28329.
BgeeP28329.
CleanExHS_CHAT.
GenevestigatorP28329.

Family and domain databases

InterProIPR000542. Carn_acyl_trans.
[Graphical view]
PANTHERPTHR22589. PTHR22589. 1 hit.
PfamPF00755. Carn_acyltransf. 1 hit.
[Graphical view]
PROSITEPS00439. ACYLTRANSF_C_1. 1 hit.
PS00440. ACYLTRANSF_C_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP28329.
GeneWikiCholine_acetyltransferase.
GenomeRNAi1103.
NextBio4562.
PROP28329.
SOURCESearch...

Entry information

Entry nameCLAT_HUMAN
AccessionPrimary (citable) accession number: P28329
Secondary accession number(s): A2BDF4 expand/collapse secondary AC list , Q16488, Q9BQ23, Q9BQ35, Q9BQE1
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: December 15, 2009
Last modified: July 9, 2014
This is version 142 of the entry and version 4 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 10

Human chromosome 10: entries, gene names and cross-references to MIM