P50416 (CPT1A_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 110.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended 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 |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 773 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Catalytic activity | Palmitoyl-CoA + L-carnitine = CoA + L-palmitoylcarnitine. |
| Enzyme regulation | Inhibitors such as malonyl-CoA interact with its catalytic domain and not with an associated regulatory component. |
| Pathway | |
| Subcellular location | |
| Tissue specificity | Strong expression in kidney and heart, and lower in liver and skeletal muscle. |
| Involvement in disease | Defects in CPT1A are the cause of carnitine palmitoyltransferase 1A deficiency (CPT1AD) [MIM:255120]; also known as CPT-I deficiency or CPT1A deficiency. CPT1AD is a 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. Ref.2 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 |
| Sequence similarities | Belongs to the carnitine/choline acetyltransferase family. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Fatty acid metabolism Lipid metabolism Transport |
| Cellular component | Membrane Mitochondrion Mitochondrion outer membrane |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Disease | Disease mutation |
| Domain | Transmembrane Transmembrane helix |
| Molecular function | Acyltransferase Transferase |
| PTM | Acetylation Phosphoprotein |
| Technical term | 3D-structure Complete proteome Reference proteome |
| Gene Ontology (GO) | |
| Biological process | carnitine shuttle Traceable author statement. Source: Reactome fatty acid beta-oxidationTraceable author statement. Source: ProtInc |
| Cellular component | integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial outer membraneTraceable author statement. Source: Reactome |
| Molecular function | carnitine O-palmitoyltransferase activity Traceable author statement. Source: ProtInc |
| 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 key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Initiator methionine | 1 | 1 | Removed By similarity | ||||||
| Chain | 2 – 773 | 772 | Carnitine O-palmitoyltransferase 1, liver isoform | PRO_0000210159 | |||||
Regions | |||||||||
| Topological domain | 2 – 47 | 46 | Cytoplasmic Potential | ||||||
| Transmembrane | 48 – 73 | 26 | Helical; Potential | ||||||
| Topological domain | 74 – 102 | 29 | Mitochondrial intermembrane Potential | ||||||
| Transmembrane | 103 – 122 | 20 | Helical; Potential | ||||||
| Topological domain | 123 – 773 | 651 | Cytoplasmic Potential | ||||||
| Region | 555 – 567 | 13 | Coenzyme A binding By similarity | ||||||
Sites | |||||||||
| Active site | 473 | 1 | Proton acceptor By similarity | ||||||
| Binding site | 589 | 1 | Carnitine By similarity | ||||||
| Binding site | 602 | 1 | Carnitine By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 2 | 1 | N-acetylalanine By similarity | ||||||
| Modified residue | 588 | 1 | Phosphothreonine By similarity | ||||||
| Modified residue | 604 | 1 | Phosphothreonine By similarity | ||||||
| Modified residue | 741 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 747 | 1 | Phosphoserine By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 746 – 773 | 28 | DSHRF…SNSKK → GIISQGPSSDT in isoform 2. | VSP_012167 | |||||
| Natural variant | 123 | 1 | R → C in CPT1AD. Ref.7 | VAR_020546 | |||||
| Natural variant | 275 | 1 | A → T. Ref.2 Ref.7 Ref.10 Corresponds to variant rs2229738 [ dbSNP | Ensembl ]. | VAR_020547 | |||||
| Natural variant | 304 | 1 | C → W in CPT1AD. Ref.7 | VAR_020548 | |||||
| Natural variant | 314 | 1 | T → I in CPT1AD. Ref.11 | VAR_020549 | |||||
| Natural variant | 316 | 1 | R → G in CPT1AD. Ref.12 | VAR_046767 | |||||
| Natural variant | 343 | 1 | F → V in CPT1AD. Ref.12 | VAR_046768 | |||||
| Natural variant | 357 | 1 | R → W in CPT1AD; decreased stability. Ref.7 | VAR_020550 | |||||
| Natural variant | 360 | 1 | E → G in CPT1AD; reduced protein levels. Ref.9 Corresponds to variant rs28936372 [ dbSNP | Ensembl ]. | VAR_020551 | |||||
| Natural variant | 395 | 1 | Missing in CPT1AD; loss of activity. | VAR_020552 | |||||
| Natural variant | 414 | 1 | A → V in CPT1AD; decreased activity. Ref.2 Ref.10 Corresponds to variant rs28936373 [ dbSNP | Ensembl ]. | VAR_020553 | |||||
| Natural variant | 454 | 1 | D → G in CPT1AD. Ref.6 | VAR_020554 | |||||
| Natural variant | 465 | 1 | G → W in CPT1AD. Ref.12 | VAR_046769 | |||||
| Natural variant | 479 | 1 | P → L in CPT1AD; decreased activity. Ref.7 | VAR_020555 | |||||
| Natural variant | 484 | 1 | L → P in CPT1AD. Ref.7 | VAR_020556 | |||||
| Natural variant | 498 | 1 | Y → C in CPT1AD; decreased activity. Ref.2 Ref.10 | VAR_020557 | |||||
| Natural variant | 709 | 1 | G → E in CPT1AD; loss of activity. Ref.10 Corresponds to variant rs28936374 [ dbSNP | Ensembl ]. | VAR_020558 | |||||
| Natural variant | 710 | 1 | G → E in CPT1AD; loss of activity. Ref.8 Ref.10 | VAR_020559 | |||||
Experimental info | |||||||||
| Sequence conflict | 479 | 1 | P → Q in AAC41748. Ref.1 | ||||||
| Sequence conflict | 568 | 1 | A → T in AAC41748. Ref.1 | ||||||
Sequences
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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: 7892212] [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: 12189492] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Eye. |
| [5] | "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: 14711372] [Abstract] Cited for: 3D-STRUCTURE MODELING. |
| [6] | "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: 9691089] [Abstract] Cited for: VARIANT CPT1AD GLY-454. |
| [7] | "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: 11441142] [Abstract] Cited for: VARIANTS CPT1AD CYS-123; TRP-304; TRP-357; ARG-395 DEL; LEU-479 AND PRO-484, VARIANT THR-275. |
| [8] | "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: 11350182] [Abstract] Cited for: VARIANT CPT1AD GLU-710, CHARACTERIZATION OF VARIANT CPT1AD GLU-710. |
| [9] | "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: 12111367] [Abstract] Cited for: CHARACTERIZATION OF VARIANT CPT1AD GLY-360. |
| [10] | "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: 14517221] [Abstract] Cited for: VARIANT CPT1AD GLU-709, CHARACTERIZATION OF VARIANTS CPT1AD THR-275; VAL-414; CYS-498; GLU-709 AND GLU-710. |
| [11] | "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: 15669684] [Abstract] Cited for: VARIANT CPT1AD ILE-314. |
| [12] | "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: 15110323] [Abstract] Cited for: VARIANTS CPT1AD GLY-316; VAL-343 AND TRP-465. |
| + | Additional computationally mapped references. |
Web resources
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. | ||||||||||||
| IPI | IPI00032038. IPI00479108. | ||||||||||||
| PIR | I59351. | ||||||||||||
| RefSeq | NP_001027017.1. NM_001031847.2. NP_001867.2. NM_001876.3. | ||||||||||||
| UniGene | Hs.503043. | ||||||||||||
3D structure databases | |||||||||||||
| PDBe RCSB PDB PDBj |
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| ProteinModelPortal | P50416. | ||||||||||||
| SMR | P50416. Positions 169-767. | ||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| IntAct | P50416. 10 interactions. | ||||||||||||
| STRING | P50416. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | P50416. | ||||||||||||
Polymorphism databases | |||||||||||||
| DMDM | 56405343. | ||||||||||||
Proteomic databases | |||||||||||||
| PeptideAtlas | P50416. | ||||||||||||
| PRIDE | P50416. | ||||||||||||
Protocols and materials databases | |||||||||||||
| StructuralBiologyKnowledgebase | Search... | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENST00000265641; ENSP00000265641; ENSG00000110090. | ||||||||||||
| GeneID | 1374. | ||||||||||||
| KEGG | hsa:1374. | ||||||||||||
| NMPDR | fig|9606.3.peg.6174. | ||||||||||||
| UCSC | uc001oof.2. human. uc001oog.2. human. | ||||||||||||
Organism-specific databases | |||||||||||||
| CTD | 1374. | ||||||||||||
| GeneCards | GC11M068524. | ||||||||||||
| HGNC | HGNC:2328. CPT1A. | ||||||||||||
| HPA | HPA008835. | ||||||||||||
| MIM | 255120. phenotype. 600528. gene. | ||||||||||||
| neXtProt | NX_P50416. | ||||||||||||
| Orphanet | 156. Carnitine palmitoyl transferase 1A deficiency. | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| eggNOG | prNOG17203. | ||||||||||||
| HOGENOM | HBG717240. | ||||||||||||
| HOVERGEN | HBG003458. | ||||||||||||
| InParanoid | P50416. | ||||||||||||
| OMA | KGWMYES. | ||||||||||||
| PhylomeDB | P50416. | ||||||||||||
Enzyme and pathway databases | |||||||||||||
| BioCyc | MetaCyc:HS03286-MONOMER. | ||||||||||||
| BRENDA | 2.3.1.21. 2681. | ||||||||||||
| Pathway_Interaction_DB | hnf3bpathway. FOXA2 and FOXA3 transcription factor networks. | ||||||||||||
| Reactome | REACT_11163. Activated AMPK stimulates fatty-acid oxidation in muscle. REACT_22258. Metabolism of lipids and lipoproteins. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | P50416. | ||||||||||||
| Bgee | P50416. | ||||||||||||
| CleanEx | HS_CPT1A. | ||||||||||||
| Genevestigator | P50416. | ||||||||||||
| GermOnline | ENSG00000110090. Homo sapiens. | ||||||||||||
Family and domain databases | |||||||||||||
| InterPro | IPR000542. Carn_acyl_trans. [Graphical view] | ||||||||||||
| KO | K08765. | ||||||||||||
| PANTHER | PTHR22589. Carn_acyl_trans. 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 | |||||||||||||
| DrugBank | DB00583. L-Carnitine. DB01074. Perhexiline. | ||||||||||||
| NextBio | 5569. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | CPT1A_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P50416 Secondary accession number(s): Q8TCU0, Q9BWK0 | ||||||||
| Entry 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. | ||||||||
Relevant documents
| Human chromosome 11 Human chromosome 11: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PATHWAY comments Index of metabolic and biosynthesis pathways |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with