Q8BGD5 · CPT1C_MOUSE
- ProteinPalmitoyl thioesterase CPT1C
- GeneCpt1c
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids798 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Palmitoyl thioesterase specifically expressed in the endoplasmic reticulum of neurons. Modulates the trafficking of the glutamate receptor, AMPAR, to plasma membrane through depalmitoylation of GRIA1 (By similarity).
Also regulates AMPR trafficking through the regulation of SACM1L phosphatidylinositol-3-phosphatase activity by interaction in a malonyl-CoA dependent manner (PubMed:32931550).
Binds malonyl-CoA and couples malonyl-CoA to ceramide levels, necessary for proper spine maturation and contributing to systemic energy homeostasis and appetite control (PubMed:16651524, PubMed:22539351, PubMed:37309891).
Binds to palmitoyl-CoA, but does not have carnitine palmitoyltransferase 1 catalytic activity or at very low levels (PubMed:12376098, PubMed:25751282, PubMed:30135643).
Also regulates AMPR trafficking through the regulation of SACM1L phosphatidylinositol-3-phosphatase activity by interaction in a malonyl-CoA dependent manner (PubMed:32931550).
Binds malonyl-CoA and couples malonyl-CoA to ceramide levels, necessary for proper spine maturation and contributing to systemic energy homeostasis and appetite control (PubMed:16651524, PubMed:22539351, PubMed:37309891).
Binds to palmitoyl-CoA, but does not have carnitine palmitoyltransferase 1 catalytic activity or at very low levels (PubMed:12376098, PubMed:25751282, PubMed:30135643).
Catalytic activity
- H2O + S-hexadecanoyl-L-cysteinyl-[protein] = H+ + hexadecanoate + L-cysteinyl-[protein]This reaction proceeds in the forward direction.
Features
Showing features for active site, binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 469 | Proton acceptor | ||||
Sequence: H | ||||||
Binding site | 551-563 | CoA (UniProtKB | ChEBI) | ||||
Sequence: GKSFIKCCHVSSD | ||||||
Binding site | 585 | (R)-carnitine (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 587 | (R)-carnitine (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 598 | (R)-carnitine (UniProtKB | ChEBI) | ||||
Sequence: T |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | AMPA glutamate receptor complex | |
Cellular Component | axon | |
Cellular Component | dendrite | |
Cellular Component | dendritic spine | |
Cellular Component | endoplasmic reticulum | |
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | glutamatergic synapse | |
Cellular Component | mitochondrion | |
Cellular Component | postsynapse | |
Molecular Function | carnitine O-palmitoyltransferase activity | |
Molecular Function | palmitoyl-(protein) hydrolase activity | |
Biological Process | carnitine metabolic process | |
Biological Process | fatty acid metabolic process | |
Biological Process | regulation of postsynaptic membrane neurotransmitter receptor levels |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePalmitoyl thioesterase CPT1C
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ8BGD5
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Multi-pass membrane protein
Note: Localized in the soma and dendritic and axonal projections.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-52 | Cytoplasmic | ||||
Sequence: MAEAHQASSLLSSLSSDGAEVELSSPVWQEIYLCALRSWKRHLWRVWNDFLA | ||||||
Transmembrane | 53-75 | Helical | ||||
Sequence: GVVPATPLSWLFLFSTIQLACLL | ||||||
Topological domain | 76-103 | Lumenal | ||||
Sequence: QLDPSLGLMEKIKELLPDWGGQHHQLQG | ||||||
Transmembrane | 104-126 | Helical | ||||
Sequence: FLSAAVFASCLWGALIFTLHVAL | ||||||
Topological domain | 127-798 | Cytoplasmic | ||||
Sequence: RLLLSHHGWLLEPHGAMSSPTKTWLALVRIFSGRHPRLFSFQRALPRQPVPSAQETVRKYLESVRPVLGDDAFDRATALANDFLRLHAPRLQLYLQLKSWCTSNYVSDWWEEFVYLRSRGSLINSTYYMMDFLYVTPTPLQAARAGNAVHTLLLYRHLLNRQEISPTLLMGMRPLCSAQYERMFNTTRIPGVEKDHLRHLQDSRHVAVFHRGRFFRVGTHSPNGLLSPRALEQQFQDILDDPSPACPLEEHLAALTAAPRSMWAQVRESVKTHAATALEAVEGAAFFVSLDSEPAGLTREDPAASLDAYAHALLAGRGHDRWFDKSFTLIVFSNGKLGLSVEHSWADCPVSGHLWEFTLATECFQLGYATDGHCKGHPDPTLPQPQRLQWDLPEQIQPSISLALRGAKTLSGNIDCHVFPFSHFGKSFIKCCHVSSDSFIQLVLQLAHFRDRGQFCLTYESAMTRLFLEGRTETVRSCTREACQFVRAMDNKETDQHCLALFRVAVDKHQALLKAAMSGQGIDRHLFALYIMSRLLHMQSPFLTQVQSQQWLLSTSQVPVQQTHLIDVHNYPDYVSSGGGFGPAHDHGYGISYIFMGENAITFHISSKKSSTETDSHRLGQHIENALLDVASLFRVGQHFKRQFRGENSDYRYNFLSCKTVDPNTPTSSTNL |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Knockout mice show decreased food intake but higher susceptibility to obesity and diabetes when fed a high fat diet (PubMed:16651524).
Mutant mice show extensive learning and memory deficits, they exhibit impaired motor and instrumental learning as well as detrimental hippocampus-dependent spatial and habituation memory (PubMed:37309891).
Mutant mice show extensive learning and memory deficits, they exhibit impaired motor and instrumental learning as well as detrimental hippocampus-dependent spatial and habituation memory (PubMed:37309891).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 589 | Loss of binding to malonyl-CoA. Loss of regulation of SACM1L phosphatidylinositol-3-phosphatase activity. No effect on interaction with GRIA1. | ||||
Sequence: M → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 55 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000210167 | 1-798 | Palmitoyl thioesterase CPT1C | |||
Sequence: MAEAHQASSLLSSLSSDGAEVELSSPVWQEIYLCALRSWKRHLWRVWNDFLAGVVPATPLSWLFLFSTIQLACLLQLDPSLGLMEKIKELLPDWGGQHHQLQGFLSAAVFASCLWGALIFTLHVALRLLLSHHGWLLEPHGAMSSPTKTWLALVRIFSGRHPRLFSFQRALPRQPVPSAQETVRKYLESVRPVLGDDAFDRATALANDFLRLHAPRLQLYLQLKSWCTSNYVSDWWEEFVYLRSRGSLINSTYYMMDFLYVTPTPLQAARAGNAVHTLLLYRHLLNRQEISPTLLMGMRPLCSAQYERMFNTTRIPGVEKDHLRHLQDSRHVAVFHRGRFFRVGTHSPNGLLSPRALEQQFQDILDDPSPACPLEEHLAALTAAPRSMWAQVRESVKTHAATALEAVEGAAFFVSLDSEPAGLTREDPAASLDAYAHALLAGRGHDRWFDKSFTLIVFSNGKLGLSVEHSWADCPVSGHLWEFTLATECFQLGYATDGHCKGHPDPTLPQPQRLQWDLPEQIQPSISLALRGAKTLSGNIDCHVFPFSHFGKSFIKCCHVSSDSFIQLVLQLAHFRDRGQFCLTYESAMTRLFLEGRTETVRSCTREACQFVRAMDNKETDQHCLALFRVAVDKHQALLKAAMSGQGIDRHLFALYIMSRLLHMQSPFLTQVQSQQWLLSTSQVPVQQTHLIDVHNYPDYVSSGGGFGPAHDHGYGISYIFMGENAITFHISSKKSSTETDSHRLGQHIENALLDVASLFRVGQHFKRQFRGENSDYRYNFLSCKTVDPNTPTSSTNL |
Proteomic databases
PTM databases
Expression
Tissue specificity
Predominantly expressed in brain (at protein level) and testis, highly expressed in the hippocampus, amygdala and cerebellum (PubMed:12376098, PubMed:18192268, PubMed:22539351, PubMed:22632720, PubMed:25751282, PubMed:37309891).
Expressed in neurons but not astrocytes (PubMed:18192268, PubMed:22539351, PubMed:25751282).
Expressed in the ventral horn from spinal cords (PubMed:25751282).
Expressed in neurons but not astrocytes (PubMed:18192268, PubMed:22539351, PubMed:25751282).
Expressed in the ventral horn from spinal cords (PubMed:25751282).
Gene expression databases
Interaction
Subunit
Peripherally associated with AMPAR complex. AMPAR complex consists of an inner core made of 4 pore-forming GluA/GRIA proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged in a twofold symmetry. One of the two pairs of distinct binding sites is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR complex is complemented by outer core constituents binding directly to the GluA/GRIA proteins at sites distinct from the interaction sites of the inner core constituents. Outer core constituents include at least PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the inner and outer core serve as a platform for other, more peripherally associated AMPAR constituents, including CPT1C. Alone or in combination, these auxiliary subunits control the gating and pharmacology of the AMPAR complex and profoundly impact their biogenesis and protein processing (PubMed:32931550).
Interacts with SACM1L; the interaction regulates SACM1L phosphatidylinositol-3-phosphatase activity and translocation to endoplasmic reticulum/trans Golgi network in a malonyl-CoA dependent manner (PubMed:32931550).
Interacts with ATL1 (By similarity).
Interacts with SACM1L; the interaction regulates SACM1L phosphatidylinositol-3-phosphatase activity and translocation to endoplasmic reticulum/trans Golgi network in a malonyl-CoA dependent manner (PubMed:32931550).
Interacts with ATL1 (By similarity).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 759-798 | Required for interaction with GRIA1 | ||||
Sequence: LFRVGQHFKRQFRGENSDYRYNFLSCKTVDPNTPTSSTNL |
Domain
CPT1 enzymes are comprised of an N-terminal regulatory domain and a C-terminal catalytic domain that are separated by two transmembrane helices. In CPT1A, the regulatory domain, termed N, adopts a malonyl-CoA inhibitory and non-inhibitory state, Nalpha and Nbeta, respectively, which differ in their association with the catalytic domain. In CPT1C, the inhibitory Nalpha state is structurally homolog whereas the non-inhibitory Nbeta state is severely destabilized which probably contributes to the low catalytic activity of CPT1C relative to CPT1A and makes its association with the catalytic domain unlikely.
Sequence similarities
Belongs to the carnitine/choline acetyltransferase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length798
- Mass (Da)90,030
- Last updated2003-03-01 v1
- ChecksumA4886121168E8046
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A1D5RLP8 | A0A1D5RLP8_MOUSE | Cpt1c | 112 | ||
A0A1D5RLH1 | A0A1D5RLH1_MOUSE | Cpt1c | 200 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 104 | in Ref. 3; AAH66155 | ||||
Sequence: F → L | ||||||
Sequence conflict | 195 | in Ref. 3; AAH66155 | ||||
Sequence: G → R | ||||||
Sequence conflict | 324 | in Ref. 3; AAH66155 | ||||
Sequence: R → C | ||||||
Sequence conflict | 559 | in Ref. 3; AAH66155 | ||||
Sequence: H → Q |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF320000 EMBL· GenBank· DDBJ | AAN39013.1 EMBL· GenBank· DDBJ | mRNA | ||
AK032101 EMBL· GenBank· DDBJ | BAC27700.1 EMBL· GenBank· DDBJ | mRNA | ||
AK035790 EMBL· GenBank· DDBJ | BAC29187.1 EMBL· GenBank· DDBJ | mRNA | ||
BC066155 EMBL· GenBank· DDBJ | AAH66155.1 EMBL· GenBank· DDBJ | mRNA |