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Protein

Carnitine O-palmitoyltransferase 1, liver isoform

Gene

Cpt1a

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion. Plays an important role in triglyceride metabolism.1 Publication

Catalytic activityi

Palmitoyl-CoA + L-carnitine = CoA + L-palmitoylcarnitine.2 Publications

Enzyme regulationi

Inhibited by malonyl-CoA.2 Publications

Pathwayi: fatty acid beta-oxidation

This protein is involved in the pathway fatty acid beta-oxidation, which is part of Lipid metabolism.
View all proteins of this organism that are known to be involved in the pathway fatty acid beta-oxidation and in Lipid metabolism.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei473 – 4731Proton acceptor
Binding sitei589 – 5891CarnitineBy similarity
Binding sitei602 – 6021CarnitineBy similarity

GO - Molecular functioni

  • carnitine O-palmitoyltransferase activity Source: UniProtKB
  • identical protein binding Source: RGD
  • palmitoleoyltransferase activity Source: Ensembl

GO - Biological processi

  • carnitine metabolic process Source: UniProtKB
  • cellular response to fatty acid Source: RGD
  • eating behavior Source: RGD
  • epithelial cell differentiation Source: Ensembl
  • fatty acid beta-oxidation Source: UniProtKB-UniPathway
  • glucose metabolic process Source: RGD
  • long-chain fatty acid metabolic process Source: UniProtKB
  • positive regulation of fatty acid beta-oxidation Source: RGD
  • protein homooligomerization Source: RGD
  • regulation of fatty acid beta-oxidation Source: RGD
  • regulation of fatty acid oxidation Source: RGD
  • regulation of insulin secretion Source: RGD
  • response to drug Source: RGD
  • response to organic cyclic compound Source: RGD
  • transport Source: UniProtKB-KW
  • triglyceride metabolic process Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Acyltransferase, Transferase

Keywords - Biological processi

Fatty acid metabolism, Lipid metabolism, Transport

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-14439.
BRENDAi2.3.1.21. 5301.
ReactomeiR-RNO-200425. Import of palmitoyl-CoA into the mitochondrial matrix.
R-RNO-5362517. Signaling by Retinoic Acid.
SABIO-RKP32198.
UniPathwayiUPA00659.

Chemistry

SwissLipidsiSLP:000000777.

Names & Taxonomyi

Protein namesi
Recommended name:
Carnitine O-palmitoyltransferase 1, liver isoform (EC:2.3.1.21)
Short name:
CPT1-L
Alternative name(s):
Carnitine O-palmitoyltransferase I, liver isoform
Short name:
CPT I
Short name:
CPTI-L
Carnitine palmitoyltransferase 1A
Gene namesi
Name:Cpt1a
Synonyms:Cpt-1, Cpt1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi2396. Cpt1a.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini2 – 4746CytoplasmicSequence analysisAdd
BLAST
Transmembranei48 – 7326HelicalSequence analysisAdd
BLAST
Topological domaini74 – 10229Mitochondrial intermembraneSequence analysisAdd
BLAST
Transmembranei103 – 12220HelicalSequence analysisAdd
BLAST
Topological domaini123 – 773651CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • integral component of membrane Source: RGD
  • integral component of mitochondrial outer membrane Source: UniProtKB
  • intracellular membrane-bounded organelle Source: RGD
  • mitochondrial inner membrane Source: Ensembl
  • mitochondrial outer membrane Source: RGD
  • mitochondrion Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi3 – 31E → R: Decreases susceptibility to inhibition by malonyl-CoA. 1 Publication
Mutagenesisi9 – 91A → G: Increases susceptibility to inhibition by malonyl-CoA. 1 Publication
Mutagenesisi18 – 181G → A: Increases susceptibility to inhibition by malonyl-CoA. 1 Publication
Mutagenesisi381 – 3811A → D: Reduces activity by 86%. No effect on inhibition by malonyl-coenzyme A. 1 Publication
Mutagenesisi473 – 4731H → A: Loss of activity. 1 Publication
Mutagenesisi477 – 4771D → A: Reduces activity by 98%. 1 Publication
Mutagenesisi560 – 5601K → A: Reduces activity by 50%. 1 Publication
Mutagenesisi567 – 5671D → A: Reduces activity by 97%.
Mutagenesisi590 – 5901E → D: Reduces activity by over 60%. 1 Publication
Mutagenesisi593 – 5931M → A, E or S: Almost abolishes inhibition by malonyl-coenzyme A. 1 Publication
Mutagenesisi608 – 6081C → A: Slightly lowers inhibition by malonyl-coenzyme A. 1 Publication
Mutagenesisi685 – 6851S → A: Reduces activity by 50%. 1 Publication
Mutagenesisi686 – 6861T → A: Loss of activity. 1 Publication
Mutagenesisi687 – 6871S → A: Loss of activity. 1 Publication

Chemistry

ChEMBLiCHEMBL3858.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved1 Publication
Chaini2 – 773772Carnitine O-palmitoyltransferase 1, liver isoformPRO_0000210161Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine1 Publication
Modified residuei282 – 2821Nitrated tyrosine1 Publication
Modified residuei588 – 5881Phosphothreonine1 Publication
Modified residuei589 – 5891Nitrated tyrosine1 Publication
Modified residuei604 – 6041Phosphothreonine1 Publication
Modified residuei741 – 7411Phosphoserine1 Publication
Modified residuei747 – 7471Phosphoserine1 Publication

Keywords - PTMi

Acetylation, Nitration, Phosphoprotein

Proteomic databases

PaxDbiP32198.
PRIDEiP32198.

PTM databases

iPTMnetiP32198.
PhosphoSiteiP32198.

Expressioni

Tissue specificityi

Liver and kidney.

Gene expression databases

GenevisibleiP32198. RN.

Interactioni

Subunit structurei

Homohexamer and homotrimer. Identified in a complex that contains at least CPT1A, ACSL1 and VDAC1. Also identified in complexes with ACSL1 and VDAC2 and VDAC3.2 Publications

GO - Molecular functioni

  • identical protein binding Source: RGD

Protein-protein interaction databases

IntActiP32198. 1 interaction.
MINTiMINT-4590667.
STRINGi10116.ENSRNOP00000019652.

Chemistry

BindingDBiP32198.

Structurei

3D structure databases

ProteinModelPortaliP32198.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni555 – 56713Coenzyme A bindingBy similarityAdd
BLAST

Domaini

A conformation change in the N-terminal region spanning the first 42 residues plays an important role in the regulation of enzyme activity by malonyl-CoA.1 Publication

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3717. Eukaryota.
ENOG410XNZ9. LUCA.
GeneTreeiENSGT00760000119220.
HOGENOMiHOG000233542.
HOVERGENiHBG003458.
InParanoidiP32198.
KOiK08765.
OMAiHIVVFHK.
OrthoDBiEOG7J17ZQ.
PhylomeDBiP32198.
TreeFamiTF313836.

Family and domain databases

InterProiIPR000542. Carn_acyl_trans.
IPR032476. CPT_N.
[Graphical view]
PANTHERiPTHR22589. PTHR22589. 1 hit.
PfamiPF00755. Carn_acyltransf. 1 hit.
PF16484. CPT_N. 1 hit.
[Graphical view]
PROSITEiPS00439. ACYLTRANSF_C_1. 1 hit.
PS00440. ACYLTRANSF_C_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P32198-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAEAHQAVAF QFTVTPDGID LRLSHEALKQ ICLSGLHSWK KKFIRFKNGI
60 70 80 90 100
ITGVFPANPS SWLIVVVGVI SSMHAKVDPS LGMIAKISRT LDTTGRMSSQ
110 120 130 140 150
TKNIVSGVLF GTGLWVAVIM TMRYSLKVLL SYHGWMFAEH GKMSRSTKIW
160 170 180 190 200
MAMVKVLSGR KPMLYSFQTS LPRLPVPAVK DTVSRYLESV RPLMKEEDFQ
210 220 230 240 250
RMTALAQDFA VNLGPKLQWY LKLKSWWATN YVSDWWEEYI YLRGRGPLMV
260 270 280 290 300
NSNYYAMEML YITPTHIQAA RAGNTIHAIL LYRRTLDREE LKPIRLLGST
310 320 330 340 350
IPLCSAQWER LFNTSRIPGE ETDTIQHIKD SRHIVVYHRG RYFKVWLYHD
360 370 380 390 400
GRLLRPRELE QQMQQILDDP SEPQPGEAKL AALTAADRVP WAKCRQTYFA
410 420 430 440 450
RGKNKQSLDA VEKAAFFVTL DESEQGYREE DPEASIDSYA KSLLHGRCFD
460 470 480 490 500
RWFDKSITFV VFKNSKIGIN AEHSWADAPV VGHLWEYVMA TDVFQLGYSE
510 520 530 540 550
DGHCKGDTNP NIPKPTRLQW DIPGECQEVI DASLSSASLL ANDVDLHSFP
560 570 580 590 600
FDSFGKGLIK KCRTSPDAFI QLALQLAHYK DMGKFCLTYE ASMTRLFREG
610 620 630 640 650
RTETVRSCTM ESCNFVQAMM DPKSTAEQRL KLFKIACEKH QHLYRLAMTG
660 670 680 690 700
AGIDRHLFCL YVVSKYLAVD SPFLKEVLSE PWRLSTSQTP QQQVELFDFE
710 720 730 740 750
KNPDYVSCGG GFGPVADDGY GVSYIIVGEN FIHFHISSKF SSPETDSHRF
760 770
GKHLRQAMMD IITLFGLTIN SKK
Length:773
Mass (Da):88,125
Last modified:May 1, 2007 - v2
Checksum:i8C15594D45430CB8
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti266 – 2661H → D AA sequence (PubMed:8348957).Curated
Sequence conflicti374 – 3752QP → NG AA sequence (PubMed:8348957).Curated
Sequence conflicti480 – 4801V → I in AAA40876 (PubMed:8449948).Curated
Sequence conflicti531 – 5311D → Y AA sequence (PubMed:8348957).Curated
Sequence conflicti708 – 7081C → R AA sequence (PubMed:8348957).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L07736 mRNA. Translation: AAA40876.1.
U88294 mRNA. Translation: AAB48046.1.
BC072522 mRNA. Translation: AAH72522.1.
PIRiA46627.
RefSeqiNP_113747.2. NM_031559.2.
XP_006230757.1. XM_006230695.1.
UniGeneiRn.2856.

Genome annotation databases

EnsembliENSRNOT00000019652; ENSRNOP00000019652; ENSRNOG00000014254.
GeneIDi25757.
KEGGirno:25757.
UCSCiRGD:2396. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L07736 mRNA. Translation: AAA40876.1.
U88294 mRNA. Translation: AAB48046.1.
BC072522 mRNA. Translation: AAH72522.1.
PIRiA46627.
RefSeqiNP_113747.2. NM_031559.2.
XP_006230757.1. XM_006230695.1.
UniGeneiRn.2856.

3D structure databases

ProteinModelPortaliP32198.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP32198. 1 interaction.
MINTiMINT-4590667.
STRINGi10116.ENSRNOP00000019652.

Chemistry

BindingDBiP32198.
ChEMBLiCHEMBL3858.
SwissLipidsiSLP:000000777.

PTM databases

iPTMnetiP32198.
PhosphoSiteiP32198.

Proteomic databases

PaxDbiP32198.
PRIDEiP32198.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000019652; ENSRNOP00000019652; ENSRNOG00000014254.
GeneIDi25757.
KEGGirno:25757.
UCSCiRGD:2396. rat.

Organism-specific databases

CTDi1374.
RGDi2396. Cpt1a.

Phylogenomic databases

eggNOGiKOG3717. Eukaryota.
ENOG410XNZ9. LUCA.
GeneTreeiENSGT00760000119220.
HOGENOMiHOG000233542.
HOVERGENiHBG003458.
InParanoidiP32198.
KOiK08765.
OMAiHIVVFHK.
OrthoDBiEOG7J17ZQ.
PhylomeDBiP32198.
TreeFamiTF313836.

Enzyme and pathway databases

UniPathwayiUPA00659.
BioCyciMetaCyc:MONOMER-14439.
BRENDAi2.3.1.21. 5301.
ReactomeiR-RNO-200425. Import of palmitoyl-CoA into the mitochondrial matrix.
R-RNO-5362517. Signaling by Retinoic Acid.
SABIO-RKP32198.

Miscellaneous databases

PROiP32198.

Gene expression databases

GenevisibleiP32198. RN.

Family and domain databases

InterProiIPR000542. Carn_acyl_trans.
IPR032476. CPT_N.
[Graphical view]
PANTHERiPTHR22589. PTHR22589. 1 hit.
PfamiPF00755. Carn_acyltransf. 1 hit.
PF16484. CPT_N. 1 hit.
[Graphical view]
PROSITEiPS00439. ACYLTRANSF_C_1. 1 hit.
PS00440. ACYLTRANSF_C_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning, sequencing, and expression of a cDNA encoding rat liver carnitine palmitoyltransferase I. Direct evidence that a single polypeptide is involved in inhibitor interaction and catalytic function."
    Esser V., Britton C.H., Weis B.C., Foster D.W., McGarry J.D.
    J. Biol. Chem. 268:5817-5822(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Liver.
  2. "Functional characterization of mitochondrial carnitine palmitoyltransferases I and II expressed in the yeast Pichia pastoris."
    de Vries Y., Arvidson D.N., Waterham H.R., Cregg J.M., Woldegiorgis G.
    Biochemistry 36:5285-5292(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
    Tissue: Liver.
  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].
    Tissue: Heart.
  4. "Post-translational modifications of rat liver mitochondrial outer membrane proteins identified by mass spectrometry."
    Distler A.M., Kerner J., Hoppel C.L.
    Biochim. Biophys. Acta 1774:628-636(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 2-22; 272-283; 585-595 AND 599-606, ACETYLATION AT ALA-2, NITRATION AT TYR-282 AND TYR-589, PHOSPHORYLATION AT THR-588; THR-604; SER-741 AND SER-747, IDENTIFICATION BY MASS SPECTROMETRY.
    Tissue: Liver.
  5. "Mature carnitine palmitoyltransferase I retains the N-terminus of the nascent protein in rat liver."
    Kolodziej M.P., Zammit V.A.
    FEBS Lett. 327:294-296(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 4-21; 259-276; 361-379; 529-543 AND 696-717.
    Tissue: Liver.
  6. "Inhibitors of mitochondrial carnitine palmitoyltransferase I limit the action of proteases on the enzyme. Isolation and partial amino acid analysis of a truncated form of the rat liver isozyme."
    Esser V., Kuwajima M., Britton C.H., Krishnan K., Foster D.W., McGarry J.D.
    J. Biol. Chem. 268:5810-5816(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: PARTIAL PROTEIN SEQUENCE.
  7. "Expression of a cDNA isolated from rat brown adipose tissue and heart identifies the product as the muscle isoform of carnitine palmitoyltransferase I (M-CPT I). M-CPT I is the predominant CPT I isoform expressed in both white (epididymal) and brown adipocytes."
    Esser V., Brown N.F., Cowan A.T., Foster D.W., McGarry J.D.
    J. Biol. Chem. 271:6972-6977(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION.
    Strain: Sprague-Dawley.
    Tissue: Heart.
  8. "Topology of carnitine palmitoyltransferase I in the mitochondrial outer membrane."
    Fraser F., Corstorphine C.G., Zammit V.A.
    Biochem. J. 323:711-718(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: TOPOLOGY.
  9. "Structural model of the catalytic core of carnitine palmitoyltransferase I and carnitine octanoyltransferase (COT): mutation of CPT I histidine 473 and alanine 381 and COT alanine 238 impairs the catalytic activity."
    Morillas M., Gomez-Puertas P., Roca R., Serra D., Asins G., Valencia A., Hegardt F.G.
    J. Biol. Chem. 276:45001-45008(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF ALA-381 AND HIS-473, 3D-STRUCTURE MODELING.
  10. "Identification of conserved amino acid residues in rat liver carnitine palmitoyltransferase I critical for malonyl-CoA inhibition. Mutation of methionine 593 abolishes malonyl-CoA inhibition."
    Morillas M., Gomez-Puertas P., Bentebibel A., Selles E., Casals N., Valencia A., Hegardt F.G., Asins G., Serra D.
    J. Biol. Chem. 278:9058-9063(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF MET-593 AND CYS-608.
  11. "Structural model of carnitine palmitoyltransferase I based on the carnitine acetyltransferase crystal."
    Morillas M., Lopez-Vinas E., Valencia A., Serra D., Gomez-Puertas P., Hegardt F.G., Asins G.
    Biochem. J. 379:777-784(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF ASP-477; LYS-560; GLU-590; SER-685; THR-686 AND SER-687, 3D-STRUCTURE MODELING.
  12. "The mitochondrial intermembrane loop region of rat carnitine palmitoyltransferase 1A is a major determinant of its malonyl-CoA sensitivity."
    Borthwick K., Jackson V.N., Price N.T., Zammit V.A.
    J. Biol. Chem. 281:32946-32952(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, ENZYME REGULATION.
  13. "A moderate increase in carnitine palmitoyltransferase 1a activity is sufficient to substantially reduce hepatic triglyceride levels."
    Stefanovic-Racic M., Perdomo G., Mantell B.S., Sipula I.J., Brown N.F., O'Doherty R.M.
    Am. J. Physiol. 294:E969-E977(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  14. "Self-association of transmembrane domain 2 (TM2), but not TM1, in carnitine palmitoyltransferase 1A: role of GXXXG(A) motifs."
    Jenei Z.A., Borthwick K., Zammit V.A., Dixon A.M.
    J. Biol. Chem. 284:6988-6997(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT, SUBCELLULAR LOCATION.
  15. "Mitochondrial carnitine palmitoyltransferase 1a (CPT1a) is part of an outer membrane fatty acid transfer complex."
    Lee K., Kerner J., Hoppel C.L.
    J. Biol. Chem. 286:25655-25662(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, IDENTIFICATION IN A COMPLEX WITH ACSL1 AND VDAC1; IDENTIFICATION IN COMPLEXES WITH ACSL1; VDAC2 AND VDAC3, IDENTIFICATION BY MASS SPECTROMETRY.
  16. "An environment-dependent structural switch underlies the regulation of carnitine palmitoyltransferase 1A."
    Rao J.N., Warren G.Z., Estolt-Povedano S., Zammit V.A., Ulmer T.S.
    J. Biol. Chem. 286:42545-42554(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION, DOMAIN, MUTAGENESIS OF GLU-3; ALA-9 AND GLY-18.

Entry informationi

Entry nameiCPT1A_RAT
AccessioniPrimary (citable) accession number: P32198
Secondary accession number(s): P97780, Q6IMZ4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: May 1, 2007
Last modified: June 8, 2016
This is version 137 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

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 one 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.