P50416 · CPT1A_HUMAN
- ProteinCarnitine O-palmitoyltransferase 1, liver isoform
- GeneCPT1A
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids773 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Possesses also a lysine succinyltransferase activity that can regulate enzymatic activity of substrate proteins such as ENO1 and metabolism independent of its classical carnitine O-palmitoyltransferase activity (PubMed:29425493).
Plays an important role in hepatic triglyceride metabolism (By similarity).
Plays also a role in inducible regulatory T-cell (iTreg) differentiation once activated by butyryl-CoA that antagonizes malonyl-CoA-mediated CPT1A repression (By similarity).
Sustains the IFN-I response by recruiting ZDHCC4 to palmitoylate MAVS at the mitochondria leading to MAVS stabilization and activation (PubMed:38016475).
Promotes ROS-induced oxidative stress in liver injury via modulation of NFE2L2 and NLRP3-mediated signaling pathways (By similarity).
Catalytic activity
- (R)-carnitine + hexadecanoyl-CoA = CoA + O-hexadecanoyl-(R)-carnitineThis reaction proceeds in the forward direction.
- L-lysyl-[protein] + succinyl-CoA = CoA + H+ + N6-succinyl-L-lysyl-[protein]
Activity regulation
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
89 μM | carnitine | |||||
106.5 μM | carnitine | |||||
43 μM | palmitoyl-CoA | |||||
82.8 μM | palmitoyl-CoA |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
15 nmol/min/mg | toward carnitine | ||||
147.8 nmol/min/mg | toward carnitine | ||||
40 nmol/min/mg | toward palmitoyl-CoA | ||||
88.6 nmol/min/mg | toward palmitoyl-CoA |
Pathway
Features
Showing features for active site, binding site.
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameCarnitine O-palmitoyltransferase 1, liver isoform
- EC number
- Short namesCPT1-L
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP50416
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 2-47 | Cytoplasmic | ||||
Sequence: AEAHQAVAFQFTVTPDGIDLRLSHEALRQIYLSGLHSWKKKFIRFK | ||||||
Transmembrane | 48-73 | Helical | ||||
Sequence: NGIITGVYPASPSSWLIVVVGVMTTM | ||||||
Topological domain | 74-102 | Mitochondrial intermembrane | ||||
Sequence: YAKIDPSLGIIAKINRTLETANCMSSQTK | ||||||
Transmembrane | 103-122 | Helical | ||||
Sequence: NVVSGVLFGTGLWVALIVTM | ||||||
Topological domain | 123-773 | Cytoplasmic | ||||
Sequence: RYSLKVLLSYHGWMFTEHGKMSRATKIWMGMVKIFSGRKPMLYSFQTSLPRLPVPAVKDTVNRYLQSVRPLMKEEDFKRMTALAQDFAVGLGPRLQWYLKLKSWWATNYVSDWWEEYIYLRGRGPLMVNSNYYAMDLLYILPTHIQAARAGNAIHAILLYRRKLDREEIKPIRLLGSTIPLCSAQWERMFNTSRIPGEETDTIQHMRDSKHIVVYHRGRYFKVWLYHDGRLLKPREMEQQMQRILDNTSEPQPGEARLAALTAGDRVPWARCRQAYFGRGKNKQSLDAVEKAAFFVTLDETEEGYRSEDPDTSMDSYAKSLLHGRCYDRWFDKSFTFVVFKNGKMGLNAEHSWADAPIVAHLWEYVMSIDSLQLGYAEDGHCKGDINPNIPYPTRLQWDIPGECQEVIETSLNTANLLANDVDFHSFPFVAFGKGIIKKCRTSPDAFVQLALQLAHYKDMGKFCLTYEASMTRLFREGRTETVRSCTTESCDFVRAMVDPAQTVEQRLKLFKLASEKHQHMYRLAMTGSGIDRHLFCLYVVSKYLAVESPFLKEVLSEPWRLSTSQTPQQQVELFDLENNPEYVSSGGGFGPVADDGYGVSYILVGENLINFHISSKFSCPETDSHRFGRHLKEAMTDIITLFGLSSNSKK |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Carnitine palmitoyltransferase 1A deficiency (CPT1AD)
- Note
- DescriptionRare 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.
- See alsoMIM:255120
Natural variants in CPT1AD
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_020546 | 123 | R>C | in CPT1AD; dbSNP:rs80356775 | |
VAR_020548 | 304 | C>W | in CPT1AD; dbSNP:rs80356789 | |
VAR_020549 | 314 | T>I | in CPT1AD; dbSNP:rs80356776 | |
VAR_046767 | 316 | R>G | in CPT1AD; dbSNP:rs80356796 | |
VAR_046768 | 343 | F>V | in CPT1AD; dbSNP:rs80356783 | |
VAR_020550 | 357 | R>W | in CPT1AD; decreased stability; dbSNP:rs80356777 | |
VAR_020551 | 360 | E>G | in CPT1AD; reduced protein levels; dbSNP:rs80356787 | |
VAR_020552 | 395 | missing | in CPT1AD; loss of activity | |
VAR_020553 | 414 | A>V | in CPT1AD; decreased activity; dbSNP:rs80356790 | |
VAR_020554 | 454 | D>G | in CPT1AD; loss of activity; dbSNP:rs80356778 | |
VAR_046769 | 465 | G>W | in CPT1AD; dbSNP:rs80356784 | |
VAR_020555 | 479 | P>L | in CPT1AD; decreased activity; dbSNP:rs80356779 | |
VAR_020556 | 484 | L>P | in CPT1AD; dbSNP:rs80356793 | |
VAR_020557 | 498 | Y>C | in CPT1AD; decreased activity; dbSNP:rs80356791 | |
VAR_020558 | 709 | G>E | in CPT1AD; loss of activity; dbSNP:rs28936374 | |
VAR_020559 | 710 | G>E | in CPT1AD; loss of activity; dbSNP:rs80356780 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_020546 | 123 | in CPT1AD; dbSNP:rs80356775 | |||
Sequence: R → C | ||||||
Natural variant | VAR_020547 | 275 | in dbSNP:rs2229738 | |||
Sequence: A → T | ||||||
Natural variant | VAR_020548 | 304 | in CPT1AD; dbSNP:rs80356789 | |||
Sequence: C → W | ||||||
Natural variant | VAR_020549 | 314 | in CPT1AD; dbSNP:rs80356776 | |||
Sequence: T → I | ||||||
Natural variant | VAR_046767 | 316 | in CPT1AD; dbSNP:rs80356796 | |||
Sequence: R → G | ||||||
Natural variant | VAR_046768 | 343 | in CPT1AD; dbSNP:rs80356783 | |||
Sequence: F → V | ||||||
Natural variant | VAR_020550 | 357 | in CPT1AD; decreased stability; dbSNP:rs80356777 | |||
Sequence: R → W | ||||||
Natural variant | VAR_020551 | 360 | in CPT1AD; reduced protein levels; dbSNP:rs80356787 | |||
Sequence: E → G | ||||||
Natural variant | VAR_020552 | 395 | in CPT1AD; loss of activity | |||
Sequence: Missing | ||||||
Natural variant | VAR_020553 | 414 | in CPT1AD; decreased activity; dbSNP:rs80356790 | |||
Sequence: A → V | ||||||
Natural variant | VAR_020554 | 454 | in CPT1AD; loss of activity; dbSNP:rs80356778 | |||
Sequence: D → G | ||||||
Natural variant | VAR_046769 | 465 | in CPT1AD; dbSNP:rs80356784 | |||
Sequence: G → W | ||||||
Mutagenesis | 473 | Loss of carnitine O-palmitoyltransferase activity. No loss of the scaffolding activity. | ||||
Sequence: H → A | ||||||
Natural variant | VAR_020555 | 479 | in CPT1AD; decreased activity; dbSNP:rs80356779 | |||
Sequence: P → L | ||||||
Natural variant | VAR_020556 | 484 | in CPT1AD; dbSNP:rs80356793 | |||
Sequence: L → P | ||||||
Natural variant | VAR_020557 | 498 | in CPT1AD; decreased activity; dbSNP:rs80356791 | |||
Sequence: Y → C | ||||||
Natural variant | VAR_020558 | 709 | in CPT1AD; loss of activity; dbSNP:rs28936374 | |||
Sequence: G → E | ||||||
Natural variant | VAR_020559 | 710 | in CPT1AD; loss of activity; dbSNP:rs80356780 | |||
Sequence: G → E | ||||||
Mutagenesis | 710 | Loss of carnitine O-palmitoyltransferase activity but not the lysine succinyltransferase activity. | ||||
Sequence: G → E |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 983 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylalanine | ||||
Sequence: A | ||||||
Chain | PRO_0000210159 | 2-773 | Carnitine O-palmitoyltransferase 1, liver isoform | |||
Sequence: AEAHQAVAFQFTVTPDGIDLRLSHEALRQIYLSGLHSWKKKFIRFKNGIITGVYPASPSSWLIVVVGVMTTMYAKIDPSLGIIAKINRTLETANCMSSQTKNVVSGVLFGTGLWVALIVTMRYSLKVLLSYHGWMFTEHGKMSRATKIWMGMVKIFSGRKPMLYSFQTSLPRLPVPAVKDTVNRYLQSVRPLMKEEDFKRMTALAQDFAVGLGPRLQWYLKLKSWWATNYVSDWWEEYIYLRGRGPLMVNSNYYAMDLLYILPTHIQAARAGNAIHAILLYRRKLDREEIKPIRLLGSTIPLCSAQWERMFNTSRIPGEETDTIQHMRDSKHIVVYHRGRYFKVWLYHDGRLLKPREMEQQMQRILDNTSEPQPGEARLAALTAGDRVPWARCRQAYFGRGKNKQSLDAVEKAAFFVTLDETEEGYRSEDPDTSMDSYAKSLLHGRCYDRWFDKSFTFVVFKNGKMGLNAEHSWADAPIVAHLWEYVMSIDSLQLGYAEDGHCKGDINPNIPYPTRLQWDIPGECQEVIETSLNTANLLANDVDFHSFPFVAFGKGIIKKCRTSPDAFVQLALQLAHYKDMGKFCLTYEASMTRLFREGRTETVRSCTTESCDFVRAMVDPAQTVEQRLKLFKLASEKHQHMYRLAMTGSGIDRHLFCLYVVSKYLAVESPFLKEVLSEPWRLSTSQTPQQQVELFDLENNPEYVSSGGGFGPVADDGYGVSYILVGENLINFHISSKFSCPETDSHRFGRHLKEAMTDIITLFGLSSNSKK | ||||||
Modified residue | 282 | 3'-nitrotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 588 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 589 | 3'-nitrotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 604 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 741 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 747 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Induction
Gene expression databases
Organism-specific databases
Interaction
Subunit
Identified in a complex that contains at least CPT1A, ACSL1 and VDAC1 (By similarity).
Also identified in complexes with ACSL1 and VDAC2 and VDAC3 (By similarity).
Interacts with ZDHHC4 (PubMed:38016475).
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Domain
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
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.
- Name1
- Length773
- Mass (Da)88,368
- Last updated2004-12-07 v2
- ChecksumE5DC9141B6301947
P50416-2
- Name2
- Differences from canonical
- 746-773: DSHRFGRHLKEAMTDIITLFGLSSNSKK → GIISQGPSSDT
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 479 | in Ref. 1; AAC41748 | ||||
Sequence: P → Q | ||||||
Sequence conflict | 568 | in Ref. 1; AAC41748 | ||||
Sequence: A → T | ||||||
Alternative sequence | VSP_012167 | 746-773 | in isoform 2 | |||
Sequence: DSHRFGRHLKEAMTDIITLFGLSSNSKK → GIISQGPSSDT |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L39211 EMBL· GenBank· DDBJ | AAC41748.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ420747 EMBL· GenBank· DDBJ | CAD12625.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ420748 EMBL· GenBank· DDBJ | CAD59673.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BT009791 EMBL· GenBank· DDBJ | AAP88793.1 EMBL· GenBank· DDBJ | mRNA | ||
BC000185 EMBL· GenBank· DDBJ | AAH00185.1 EMBL· GenBank· DDBJ | mRNA |