P43155 (CACP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Carnitine O-acetyltransferase
Short name=Carnitine acetylase
EC=2.3.1.7

Alternative name(s):
Carnitine acetyltransferase
Short name=CAT
Short name=CrAT

Gene names

Name:	CRAT
Synonyms:	CAT1

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	626 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Carnitine acetylase is specific for short chain fatty acids. Carnitine acetylase seems to affect the flux through the pyruvate dehydrogenase complex. It may be involved as well in the transport of acetyl-CoA into mitochondria.
Catalytic activity	Acetyl-CoA + carnitine = CoA + O-acetylcarnitine.
Subunit structure	Monomer. Ref.7
Subcellular location	Endoplasmic reticulum Potential. Peroxisome Potential. Mitochondrion inner membrane; Peripheral membrane protein; Matrix side Potential. Isoform 1: Mitochondrion Potential. Isoform 2: Peroxisome Potential.
Tissue specificity	Mostly in skeletal muscle, less in heart, liver and pancreas, only weakly detectable in brain, placenta, lung and kidney.
Sequence similarities	Belongs to the carnitine/choline acetyltransferase family.

Ontologies

Keywords
Biological process	Fatty acid metabolism Lipid metabolism Transport
Cellular component	Endoplasmic reticulum Membrane Mitochondrion Mitochondrion inner membrane Peroxisome
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Acyltransferase Transferase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	carnitine metabolic process, CoA-linked Inferred from direct assay Ref.8PubMed 2351134. Source: UniProtKB fatty acid beta-oxidation using acyl-CoA oxidase Traceable author statement. Source: Reactome transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrial inner membrane Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from direct assay PubMed 2351134. Source: UniProtKB peroxisomal matrix Traceable author statement. Source: Reactome
Molecular_function	carnitine O-acetyltransferase activity Inferred from direct assay Ref.8PubMed 2351134. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P43155-1)

Also known as: SM-1400;

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 2 (identifier: P43155-2)

Also known as: SM-1200;

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: P43155-3)

The sequence of this isoform differs from the canonical sequence as follows:
     282-363: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 626

626

Carnitine O-acetyltransferase

PRO_0000210172

Regions

Region

418 – 430

13

Coenzyme A binding By similarity

Motif

624 – 626

3

Microbody targeting signal Potential

Sites

Active site

343

1

Proton acceptor Probable

Binding site

452

1

Carnitine

Binding site

454

1

Carnitine

Binding site

465

1

Carnitine

Amino acid modifications

Modified residue

261

1

N6-acetyllysine Ref.6

Modified residue

268

1

N6-acetyllysine Ref.6

Natural variations

Alternative sequence

1 – 21

21

Missing in isoform 2.

VSP_000792

Alternative sequence

282 – 363

82

Missing in isoform 3.

VSP_012798

Natural variant

372

1

L → M. Ref.1 Ref.3 Ref.5
Corresponds to variant rs3118635 [ dbSNP | Ensembl ].

VAR_047780

Natural variant

624

1

A → P.
Corresponds to variant rs17459086 [ dbSNP | Ensembl ].

VAR_047781

Experimental info

Mutagenesis

452

1

Y → A: Increases the KM for carnitine 100-fold. Ref.8

Mutagenesis

452

1

Y → F: Increases the KM for carnitine 320-fold and reduces enzyme activity 10000-fold. Ref.8

Mutagenesis

465

1

T → A: Increases the KM for carnitine almost 70-fold and reduces enzyme activity 450-fold. Ref.8

Mutagenesis

518

1

R → Q: Increases the KM for carnitine 230-fold and reduces enzyme activity almost 100-fold. Ref.8

Mutagenesis

566

1

F → A: Increases the KM for carnitine 18-fold and reduces enzyme activity 100-fold. Ref.8

Mutagenesis

566

1

F → Y: No effect. Ref.8

Sequence conflict

88

1

E → G in CAA55359. Ref.5

Sequence conflict

349

1

P → F in CAA55359. Ref.5

Sequence conflict

517

1

D → G in CAA55359. Ref.5

Sequence conflict

534

1

M → T in CAA55359. Ref.5

Secondary structure

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626

Helix Strand Turn

Details...

Helix

43 – 54

12

Turn

55 – 57

3

Helix

60 – 74

15

Helix

79 – 93

15

Beta strand

94 – 96

3

Helix

99 – 106

8

Turn

107 – 109

3

Turn

116 – 118

3

Beta strand

121 – 123

3

Helix

132 – 154

23

Helix

171 – 175

5

Beta strand

179 – 182

4

Beta strand

185 – 187

3

Beta strand

189 – 192

4

Beta strand

196 – 198

3

Beta strand

202 – 207

6

Beta strand

210 – 215

6

Helix

226 – 238

13

Helix

248 – 253

6

Helix

256 – 266

11

Helix

270 – 281

12

Beta strand

285 – 289

5

Beta strand

297 – 299

3

Helix

300 – 310

11

Turn

314 – 319

6

Beta strand

325 – 332

8

Beta strand

337 – 341

5

Helix

348 – 363

16

Beta strand

379 – 381

3

Helix

387 – 406

20

Beta strand

407 – 414

8

Helix

420 – 424

5

Helix

429 – 445

17

Beta strand

451 – 456

6

Beta strand

465 – 469

5

Helix

473 – 482

10

Helix

489 – 511

23

Helix

517 – 529

13

Helix

536 – 539

4

Helix

541 – 546

6

Beta strand

550 – 555

6

Beta strand

559 – 561

3

Beta strand

563 – 565

3

Beta strand

574 – 580

7

Beta strand

585 – 592

8

Helix

600 – 619

20

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (SM-1400) [UniParc]. Last modified November 25, 2008. Version 5. Checksum: 51B65E7C94E458D7	FASTA	626	70,858
	10 20 30 40 50 60 MLAFAARTVV KPLGFLKPFS LMKASSRFKA HQDALPRLPV PPLQQSLDHY LKALQPIVSE 70 80 90 100 110 120 EEWAHTKQLV DEFQASGGVG ERLQKGLERR ARKTENWLSE WWLKTAYLQY RQPVVIYSSP 130 140 150 160 170 180 GVMLPKQDFV DLQGQLRFAA KLIEGVLDFK VMIDNETLPV EYLGGKPLCM NQYYQILSSC 190 200 210 220 230 240 RVPGPKQDTV SNFSKTKKPP THITVVHNYQ FFELDVYHSD GTPLTADQIF VQLEKIWNSS 250 260 270 280 290 300 LQTNKEPVGI LTSNHRNSWA KAYNTLIKDK VNRDSVRSIQ KSIFTVCLDA TMPRVSEDVY 310 320 330 340 350 360 RSHVAGQMLH GGGSRLNSGN RWFDKTLQFI VAEDGSCGLV YEHAAAEGPP IVTLLDYVIE 370 380 390 400 410 420 YTKKPELVRS PLVPLPMPKK LRFNITPEIK SDIEKAKQNL SIMIQDLDIT VMVFHHFGKD 430 440 450 460 470 480 FPKSEKLSPD AFIQMALQLA YYRIYGQACA TYESASLRMF HLGRTDTIRS ASMDSLTFVK 490 500 510 520 530 540 AMDDSSVTEH QKVELLRKAV QAHRGYTDRA IRGEAFDRHL LGLKLQAIED LVSMPDIFMD 550 560 570 580 590 600 TSYAIAMHFH LSTSQVPAKT DCVMFFGPVV PDGYGVCYNP MEAHINFSLS AYNSCAETNA 610 620 ARLAHYLEKA LLDMRALLQS HPRAKL
	Isoform 2 (SM-1200) [UniParc]. Checksum: 915540218D46D9C7	FASTA	605	68,569
	10 20 30 40 50 60 MKASSRFKAH QDALPRLPVP PLQQSLDHYL KALQPIVSEE EWAHTKQLVD EFQASGGVGE 70 80 90 100 110 120 RLQKGLERRA RKTENWLSEW WLKTAYLQYR QPVVIYSSPG VMLPKQDFVD LQGQLRFAAK 130 140 150 160 170 180 LIEGVLDFKV MIDNETLPVE YLGGKPLCMN QYYQILSSCR VPGPKQDTVS NFSKTKKPPT 190 200 210 220 230 240 HITVVHNYQF FELDVYHSDG TPLTADQIFV QLEKIWNSSL QTNKEPVGIL TSNHRNSWAK 250 260 270 280 290 300 AYNTLIKDKV NRDSVRSIQK SIFTVCLDAT MPRVSEDVYR SHVAGQMLHG GGSRLNSGNR 310 320 330 340 350 360 WFDKTLQFIV AEDGSCGLVY EHAAAEGPPI VTLLDYVIEY TKKPELVRSP LVPLPMPKKL 370 380 390 400 410 420 RFNITPEIKS DIEKAKQNLS IMIQDLDITV MVFHHFGKDF PKSEKLSPDA FIQMALQLAY 430 440 450 460 470 480 YRIYGQACAT YESASLRMFH LGRTDTIRSA SMDSLTFVKA MDDSSVTEHQ KVELLRKAVQ 490 500 510 520 530 540 AHRGYTDRAI RGEAFDRHLL GLKLQAIEDL VSMPDIFMDT SYAIAMHFHL STSQVPAKTD 550 560 570 580 590 600 CVMFFGPVVP DGYGVCYNPM EAHINFSLSA YNSCAETNAA RLAHYLEKAL LDMRALLQSH PRAKL
	Isoform 3 [UniParc]. Checksum: 2AD5B9AA49773E5C	FASTA	544	61,870
	10 20 30 40 50 60 MLAFAARTVV KPLGFLKPFS LMKASSRFKA HQDALPRLPV PPLQQSLDHY LKALQPIVSE 70 80 90 100 110 120 EEWAHTKQLV DEFQASGGVG ERLQKGLERR ARKTENWLSE WWLKTAYLQY RQPVVIYSSP 130 140 150 160 170 180 GVMLPKQDFV DLQGQLRFAA KLIEGVLDFK VMIDNETLPV EYLGGKPLCM NQYYQILSSC 190 200 210 220 230 240 RVPGPKQDTV SNFSKTKKPP THITVVHNYQ FFELDVYHSD GTPLTADQIF VQLEKIWNSS 250 260 270 280 290 300 LQTNKEPVGI LTSNHRNSWA KAYNTLIKDK VNRDSVRSIQ KKPELVRSPL VPLPMPKKLR 310 320 330 340 350 360 FNITPEIKSD IEKAKQNLSI MIQDLDITVM VFHHFGKDFP KSEKLSPDAF IQMALQLAYY 370 380 390 400 410 420 RIYGQACATY ESASLRMFHL GRTDTIRSAS MDSLTFVKAM DDSSVTEHQK VELLRKAVQA 430 440 450 460 470 480 HRGYTDRAIR GEAFDRHLLG LKLQAIEDLV SMPDIFMDTS YAIAMHFHLS TSQVPAKTDC 490 500 510 520 530 540 VMFFGPVVPD GYGVCYNPME AHINFSLSAY NSCAETNAAR LAHYLEKALL DMRALLQSHP RAKL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANT MET-372.
[2]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] (ISOFORM 3), VARIANT MET-372. Tissue: Placenta.
[4]	"Divergent sequences in the 5' region of cDNA suggest alternative splicing as a mechanism for the generation of carnitine acetyltransferases with different subcellular localizations." Corti O., DiDonato S., Finocchiaro G. Biochem. J. 303:37-41(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-52 (ISOFORMS 1 AND 2), ALTERNATIVE SPLICING.
[5]	"Molecular cloning of cDNAs encoding human carnitine acetyltransferase and mapping of the corresponding gene to chromosome 9q34.1." Corti O., Finocchiaro G., Rossi E., Zuffardi O., Didonato S. Genomics 23:94-99(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3-626 (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, VARIANT MET-372.
[6]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-261 AND LYS-268, MASS SPECTROMETRY.
[7]	"Structure of human carnitine acetyltransferase. Molecular basis for fatty acyl transfer." Wu D., Govindasamy L., Lian W., Gu Y., Kukar T., Agbandje-McKenna M., McKenna R. J. Biol. Chem. 278:13159-13165(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 35-626, SUBUNIT.
[8]	"Structural and mutational characterization of L-carnitine binding to human carnitine acetyltransferase." Govindasamy L., Kukar T., Lian W., Pedersen B., Gu Y., Agbandje-McKenna M., Jin S., McKenna R., Wu D. J. Struct. Biol. 146:416-424(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 35-626 IN COMPLEX WITH CARNITINE, MUTAGENESIS OF TYR-452; THR-465; ARG-518 AND PHE-566.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

BT006801 mRNA. Translation: AAP35447.1.
AL158151 Genomic DNA. Translation: CAI12869.1.
BC000723 mRNA. Translation: AAH00723.1.
X79825 Genomic DNA. No translation available.
X79827 Genomic DNA. No translation available.
X78706 mRNA. Translation: CAA55359.1.

IPI

IPI00016457.
IPI00029140.
IPI00514595.

PIR

A55720.

RefSeq

NP_000746.2. NM_000755.3.
NP_001244292.1. NM_001257363.1.

UniGene

Hs.12068.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NM8	X-ray	1.60	A	35-626	[»]
1S5O	X-ray	1.80	A	35-626	[»]

DisProt

DP00305.

ProteinModelPortal

P43155.

ModBase

Search...

Protein-protein interaction databases

IntAct

P43155. 3 interactions.

STRING

9606.ENSP00000315013.

Protein family/group databases

TCDB

4.C.2.1.1. carnitine O-acyl transferase (CrAT) family.

PTM databases

PhosphoSite

P43155.

Polymorphism databases

DMDM

215274265.

Proteomic databases

PaxDb

P43155.

PRIDE

P43155.

Protocols and materials databases

DNASU

1384.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000318080; ENSP00000315013; ENSG00000095321.

GeneID

1384.

KEGG

hsa:1384.

UCSC

uc004bxh.3. human.

Organism-specific databases

CTD

1384.

GeneCards

GC09M131857.

H-InvDB

HIX0169130.

HGNC

HGNC:2342. CRAT.

HPA

HPA019230.
HPA020260.
HPA022815.

MIM

600184. gene.

neXtProt

NX_P43155.

PharmGKB

PA26862.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG70127.

HOGENOM

HOG000233845.

HOVERGEN

HBG107717.

InParanoid

P43155.

KO

K00624.

OMA

FVQLEKI.

OrthoDB

EOG4933HG.

PhylomeDB

P43155.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

SABIO-RK

P43155.

Gene expression databases

ArrayExpress

P43155.

Bgee

P43155.

CleanEx

HS_CRAT.

Genevestigator

P43155.

GermOnline

ENSG00000095321. Homo sapiens.

Family and domain databases

InterPro

IPR000542. Carn_acyl_trans.
[Graphical view]

PANTHER

PTHR22589. PTHR22589. 1 hit.

Pfam

PF00755. Carn_acyltransf. 1 hit.
[Graphical view]

PROSITE

PS00439. ACYLTRANSF_C_1. 1 hit.
PS00440. ACYLTRANSF_C_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P43155.

ChEMBL

CHEMBL3184.

DrugBank

DB00583. L-Carnitine.

EvolutionaryTrace

P43155.

GenomeRNAi

1384.

NextBio

5619.

SOURCE

Search...

Entry information

Entry name

CACP_HUMAN

Accession

Primary (citable) accession number: P43155
Secondary accession number(s): Q5T952, Q9BW16

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 25, 2008
Last modified:	May 1, 2013
This is version 131 of the entry and version 5 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.