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P50416 (CPT1A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Carnitine O-palmitoyltransferase 1, liver isoform

Short name=CPT1-L
EC=2.3.1.21
Alternative name(s):
Carnitine O-palmitoyltransferase I, liver isoform
Short name=CPT I
Short name=CPTI-L
Carnitine palmitoyltransferase 1A
Gene names
Name:CPT1A
Synonyms:CPT1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length773 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Catalytic activity

Palmitoyl-CoA + L-carnitine = CoA + L-palmitoylcarnitine. Ref.11 Ref.13

Enzyme regulation

Inhibited by malonyl-CoA. Ref.13

Pathway

Lipid metabolism; fatty acid beta-oxidation.

Subunit structure

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 By similarity.

Subcellular location

Mitochondrion outer membrane; Multi-pass membrane protein Ref.11 Ref.13.

Tissue specificity

Strong expression in kidney and heart, and lower in liver and skeletal muscle.

Induction

Up-regulated by fatty acids. Ref.5 Ref.13

Domain

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. Ref.8

Involvement in disease

Carnitine palmitoyltransferase 1A deficiency (CPT1AD) [MIM:255120]: Rare autosomal recessive metabolic disorder of long-chain fatty acid oxidation characterized by severe episodes of hypoketotic hypoglycemia usually occurring after fasting or illness. Onset is in infancy or early childhood.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15

Sequence similarities

Belongs to the carnitine/choline acetyltransferase family.

Ontologies

Keywords
   Biological processFatty acid metabolism
Lipid metabolism
Transport
   Cellular componentMembrane
Mitochondrion
Mitochondrion outer membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainTransmembrane
Transmembrane helix
   Molecular functionAcyltransferase
Transferase
   PTMAcetylation
Nitration
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcarnitine metabolic process

Inferred from direct assay Ref.11. Source: UniProtKB

carnitine shuttle

Traceable author statement. Source: Reactome

cellular lipid metabolic process

Traceable author statement. Source: Reactome

cellular response to fatty acid

Inferred from electronic annotation. Source: Ensembl

eating behavior

Inferred from electronic annotation. Source: Ensembl

epithelial cell differentiation

Inferred from expression pattern PubMed 21492153. Source: UniProt

fatty acid beta-oxidation

Traceable author statement Ref.1. Source: ProtInc

glucose metabolic process

Inferred from electronic annotation. Source: Ensembl

long-chain fatty acid metabolic process

Inferred from direct assay Ref.11. Source: UniProtKB

positive regulation of fatty acid beta-oxidation

Inferred from electronic annotation. Source: Ensembl

protein homooligomerization

Inferred from electronic annotation. Source: Ensembl

regulation of insulin secretion

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to organic cyclic compound

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

triglyceride metabolic process

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentintegral component of mitochondrial outer membrane

Inferred from sequence or structural similarity. Source: UniProtKB

mitochondrial inner membrane

Inferred from electronic annotation. Source: Ensembl

mitochondrial outer membrane

Traceable author statement. Source: Reactome

mitochondrion

Inferred from direct assay Ref.11. Source: UniProtKB

   Molecular_functioncarnitine O-palmitoyltransferase activity

Inferred from direct assay Ref.11. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P50416-1)

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: P50416-2)

The sequence of this isoform differs from the canonical sequence as follows:
     746-773: DSHRFGRHLKEAMTDIITLFGLSSNSKK → GIISQGPSSDT

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 773772Carnitine O-palmitoyltransferase 1, liver isoform
PRO_0000210159

Regions

Topological domain2 – 4746Cytoplasmic Potential
Transmembrane48 – 7326Helical; Potential
Topological domain74 – 10229Mitochondrial intermembrane Potential
Transmembrane103 – 12220Helical; Potential
Topological domain123 – 773651Cytoplasmic Potential
Region555 – 56713Coenzyme A binding By similarity

Sites

Active site4731Proton acceptor By similarity
Binding site5891Carnitine By similarity
Binding site6021Carnitine By similarity

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue2821Nitrated tyrosine By similarity
Modified residue5881Phosphothreonine By similarity
Modified residue5891Nitrated tyrosine By similarity
Modified residue6041Phosphothreonine By similarity
Modified residue7411Phosphoserine By similarity
Modified residue7471Phosphoserine By similarity

Natural variations

Alternative sequence746 – 77328DSHRF…SNSKK → GIISQGPSSDT in isoform 2.
VSP_012167
Natural variant1231R → C in CPT1AD. Ref.10
VAR_020546
Natural variant2751A → T. Ref.2 Ref.10 Ref.13
Corresponds to variant rs2229738 [ dbSNP | Ensembl ].
VAR_020547
Natural variant3041C → W in CPT1AD. Ref.10
VAR_020548
Natural variant3141T → I in CPT1AD. Ref.14
VAR_020549
Natural variant3161R → G in CPT1AD. Ref.15
VAR_046767
Natural variant3431F → V in CPT1AD. Ref.15
VAR_046768
Natural variant3571R → W in CPT1AD; decreased stability. Ref.10
VAR_020550
Natural variant3601E → G in CPT1AD; reduced protein levels. Ref.12
Corresponds to variant rs28936372 [ dbSNP | Ensembl ].
VAR_020551
Natural variant3951Missing in CPT1AD; loss of activity. Ref.10
VAR_020552
Natural variant4141A → V in CPT1AD; decreased activity. Ref.2 Ref.13
Corresponds to variant rs28936373 [ dbSNP | Ensembl ].
VAR_020553
Natural variant4541D → G in CPT1AD. Ref.9
VAR_020554
Natural variant4651G → W in CPT1AD. Ref.15
VAR_046769
Natural variant4791P → L in CPT1AD; decreased activity. Ref.10
VAR_020555
Natural variant4841L → P in CPT1AD. Ref.10
VAR_020556
Natural variant4981Y → C in CPT1AD; decreased activity. Ref.2 Ref.13
VAR_020557
Natural variant7091G → E in CPT1AD; loss of activity. Ref.13
Corresponds to variant rs28936374 [ dbSNP | Ensembl ].
VAR_020558
Natural variant7101G → E in CPT1AD; loss of activity. Ref.11 Ref.13
VAR_020559

Experimental info

Sequence conflict4791P → Q in AAC41748. Ref.1
Sequence conflict5681A → T in AAC41748. Ref.1

Secondary structure

......... 773
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 7, 2004. Version 2.
Checksum: E5DC9141B6301947

FASTA77388,368
        10         20         30         40         50         60 
MAEAHQAVAF QFTVTPDGID LRLSHEALRQ IYLSGLHSWK KKFIRFKNGI ITGVYPASPS 

        70         80         90        100        110        120 
SWLIVVVGVM TTMYAKIDPS LGIIAKINRT LETANCMSSQ TKNVVSGVLF GTGLWVALIV 

       130        140        150        160        170        180 
TMRYSLKVLL SYHGWMFTEH GKMSRATKIW MGMVKIFSGR KPMLYSFQTS LPRLPVPAVK 

       190        200        210        220        230        240 
DTVNRYLQSV RPLMKEEDFK RMTALAQDFA VGLGPRLQWY LKLKSWWATN YVSDWWEEYI 

       250        260        270        280        290        300 
YLRGRGPLMV NSNYYAMDLL YILPTHIQAA RAGNAIHAIL LYRRKLDREE IKPIRLLGST 

       310        320        330        340        350        360 
IPLCSAQWER MFNTSRIPGE ETDTIQHMRD SKHIVVYHRG RYFKVWLYHD GRLLKPREME 

       370        380        390        400        410        420 
QQMQRILDNT SEPQPGEARL AALTAGDRVP WARCRQAYFG RGKNKQSLDA VEKAAFFVTL 

       430        440        450        460        470        480 
DETEEGYRSE DPDTSMDSYA KSLLHGRCYD RWFDKSFTFV VFKNGKMGLN AEHSWADAPI 

       490        500        510        520        530        540 
VAHLWEYVMS IDSLQLGYAE DGHCKGDINP NIPYPTRLQW DIPGECQEVI ETSLNTANLL 

       550        560        570        580        590        600 
ANDVDFHSFP FVAFGKGIIK KCRTSPDAFV QLALQLAHYK DMGKFCLTYE ASMTRLFREG 

       610        620        630        640        650        660 
RTETVRSCTT ESCDFVRAMV DPAQTVEQRL KLFKLASEKH QHMYRLAMTG SGIDRHLFCL 

       670        680        690        700        710        720 
YVVSKYLAVE SPFLKEVLSE PWRLSTSQTP QQQVELFDLE NNPEYVSSGG GFGPVADDGY 

       730        740        750        760        770 
GVSYILVGEN LINFHISSKF SCPETDSHRF GRHLKEAMTD IITLFGLSSN SKK 

« Hide

Isoform 2 [UniParc].

Checksum: C7B0ED8A26285110
Show »

FASTA75686,239

References

« Hide 'large scale' references
[1]"Human liver mitochondrial carnitine palmitoyltransferase I: characterization of its cDNA and chromosomal localization and partial analysis of the gene."
Britton C.H., Schultz R.A., Zhang B., Esser V., Foster D.W., McGarry J.D.
Proc. Natl. Acad. Sci. U.S.A. 92:1984-1988(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Liver.
[2]"Organization of the human liver carnitine palmitoyltransferase 1 gene (CPT1A) and identification of novel mutations in hypoketotic hypoglycaemia."
Gobin S., Bonnefont J.-P., Prip-Buus C., Mugnier C., Ferrec M., Demaugre F., Saudubray J.-M., Rostane H., Djouadi F., Wilcox W., Cederbaum S., Haas R., Nyhan W.L., Green A., Gray G., Girard J., Thuillier L.
Hum. Genet. 111:179-189(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CPT1AD VAL-414 AND CYS-498, VARIANT THR-275.
[3]"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 (AUG-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[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] (ISOFORM 2).
Tissue: Eye.
[5]"An intronic peroxisome proliferator-activated receptor-binding sequence mediates fatty acid induction of the human carnitine palmitoyltransferase 1A."
Napal L., Marrero P.F., Haro D.
J. Mol. Biol. 354:751-759(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION BY FATTY ACIDS.
[6]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"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: 3D-STRUCTURE MODELING.
[8]"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: STRUCTURE BY NMR OF 1-42, DOMAIN.
[9]"Molecular basis of hepatic carnitine palmitoyltransferase I deficiency."
IJlst L., Mandel H., Oostheim W., Ruiter J.P.N., Gutman A., Wanders R.J.
J. Clin. Invest. 102:527-531(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CPT1AD GLY-454.
[10]"Molecular characterization of L-CPT I deficiency in six patients: insights into function of the native enzyme."
Brown N.F., Mullur R.S., Subramanian I., Esser V., Bennett M.J., Saudubray J.-M., Feigenbaum A.S., Kobari J.A., Macleod P.M., McGarry J.D., Cohen J.C.
J. Lipid Res. 42:1134-1142(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CPT1AD CYS-123; TRP-304; TRP-357; ARG-395 DEL; LEU-479 AND PRO-484, VARIANT THR-275.
[11]"Molecular and enzymatic characterization of a unique carnitine palmitoyltransferase 1A mutation in the Hutterite community."
Prip-Buus C., Thuillier L., Abadi N., Prasad C., Dilling L., Klasing J., Demaugre F., Greenberg C.R., Haworth J.C., Droin V., Kadhom N., Gobin S., Kamoun P., Girard J., Bonnefont J.-P.
Mol. Genet. Metab. 73:46-54(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CPT1AD GLU-710, CHARACTERIZATION OF VARIANT CPT1AD GLU-710, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION.
[12]"Expression analysis of two mutations in carnitine palmitoyltransferase IA deficiency."
Ogawa E., Kanazawa M., Yamamoto S., Ohtsuka S., Ogawa A., Ohtake A., Takayanagi M., Kohno Y.
J. Hum. Genet. 47:342-347(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT CPT1AD GLY-360.
[13]"Functional and structural basis of carnitine palmitoyltransferase 1A deficiency."
Gobin S., Thuillier L., Jogl G., Faye A., Tong L., Chi M., Bonnefont J.-P., Girard J., Prip-Buus C.
J. Biol. Chem. 278:50428-50434(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CPT1AD GLU-709, CHARACTERIZATION OF VARIANTS CPT1AD THR-275; VAL-414; CYS-498; GLU-709 AND GLU-710, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, ENZYME REGULATION.
[14]"Successful long-term treatment of hepatic carnitine palmitoyltransferase I deficiency and a novel mutation."
Stoler J.M., Sabry M.A., Hanley C., Hoppel C.L., Shih V.E.
J. Inherit. Metab. Dis. 27:679-684(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CPT1AD ILE-314.
[15]"Novel mutations in CPT 1A define molecular heterogeneity of hepatic carnitine palmitoyltransferase I deficiency."
Bennett M.J., Boriack R.L., Narayan S., Rutledge S.L., Raff M.L.
Mol. Genet. Metab. 82:59-63(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CPT1AD GLY-316; VAL-343 AND TRP-465.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L39211 mRNA. Translation: AAC41748.1.
AJ420747 Genomic DNA. Translation: CAD12625.1.
AJ420748 Genomic DNA. Translation: CAD59673.1.
BT009791 mRNA. Translation: AAP88793.1.
BC000185 mRNA. Translation: AAH00185.1.
CCDSCCDS31624.1. [P50416-2]
CCDS8185.1. [P50416-1]
PIRI59351.
RefSeqNP_001027017.1. NM_001031847.2. [P50416-2]
NP_001867.2. NM_001876.3. [P50416-1]
UniGeneHs.503043.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2LE3NMR-A1-42[»]
ProteinModelPortalP50416.
SMRP50416. Positions 1-42, 180-765.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107765. 27 interactions.
IntActP50416. 12 interactions.
MINTMINT-3018357.
STRING9606.ENSP00000265641.

Chemistry

ChEMBLCHEMBL1293194.
DrugBankDB00583. L-Carnitine.
DB01074. Perhexiline.

PTM databases

PhosphoSiteP50416.

Polymorphism databases

DMDM56405343.

Proteomic databases

MaxQBP50416.
PaxDbP50416.
PeptideAtlasP50416.
PRIDEP50416.

Protocols and materials databases

DNASU1374.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265641; ENSP00000265641; ENSG00000110090. [P50416-1]
ENST00000376618; ENSP00000365803; ENSG00000110090. [P50416-2]
ENST00000539743; ENSP00000446108; ENSG00000110090. [P50416-1]
ENST00000540367; ENSP00000439084; ENSG00000110090. [P50416-2]
GeneID1374.
KEGGhsa:1374.
UCSCuc001oof.4. human. [P50416-2]
uc001oog.4. human. [P50416-1]

Organism-specific databases

CTD1374.
GeneCardsGC11M068524.
GeneReviewsCPT1A.
HGNCHGNC:2328. CPT1A.
HPAHPA008835.
MIM255120. phenotype.
600528. gene.
neXtProtNX_P50416.
Orphanet156. Carnitine palmitoyl transferase 1A deficiency.
PharmGKBPA26847.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG70127.
HOGENOMHOG000233542.
HOVERGENHBG003458.
InParanoidP50416.
KOK08765.
OMAIASEKHQ.
OrthoDBEOG7J17ZQ.
PhylomeDBP50416.
TreeFamTF313836.

Enzyme and pathway databases

BioCycMetaCyc:HS03286-MONOMER.
BRENDA2.3.1.21. 2681.
ReactomeREACT_111217. Metabolism.
REACT_24941. Circadian Clock.
SABIO-RKP50416.
UniPathwayUPA00659.

Gene expression databases

ArrayExpressP50416.
BgeeP50416.
CleanExHS_CPT1A.
GenevestigatorP50416.

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

ChiTaRSCPT1A. human.
GenomeRNAi1374.
NextBio5569.
PROP50416.
SOURCESearch...

Entry information

Entry nameCPT1A_HUMAN
AccessionPrimary (citable) accession number: P50416
Secondary accession number(s): Q8TCU0, Q9BWK0
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: December 7, 2004
Last modified: July 9, 2014
This is version 137 of the entry and version 2 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

PATHWAY comments

Index of metabolic and biosynthesis pathways

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 11

Human chromosome 11: entries, gene names and cross-references to MIM