ID CPT1A_MOUSE Reviewed; 773 AA.
AC P97742; O35288; Q80SW3; Q8BP98; Q8C7H8;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 4.
DT 27-MAR-2024, entry version 190.
DE RecName: Full=Carnitine O-palmitoyltransferase 1, liver isoform;
DE Short=CPT1-L;
DE EC=2.3.1.21 {ECO:0000269|PubMed:16169268, ECO:0000269|PubMed:17030509};
DE AltName: Full=Carnitine O-palmitoyltransferase I, liver isoform;
DE Short=CPT I;
DE Short=CPTI-L;
DE AltName: Full=Carnitine palmitoyltransferase 1A;
GN Name=Cpt1a; Synonyms=Cpt-1, Cpt1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver, and Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 10-773.
RC STRAIN=ICR; TISSUE=Liver;
RX PubMed=9680378; DOI=10.1007/s003359900830;
RA Cox K.B., Johnson K.R., Wood P.A.;
RT "Chromosomal locations of the mouse fatty acid oxidation genes Cpt1a,
RT Cpt1b, Cpt2, Acadvl, and metabolically related Crat gene.";
RL Mamm. Genome 9:608-610(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 734-773.
RC TISSUE=Heart;
RX PubMed=8830050; DOI=10.1093/oxfordjournals.jbchem.a021274;
RA Uenaka R., Kuwajima M., Ono A., Matsuzawa Y., Hayakawa J., Inohara N.,
RA Kagawa Y., Ohta S.;
RT "Increased expression of carnitine palmitoyltransferase I gene is repressed
RT by administering L-carnitine in the hearts of carnitine-deficient juvenile
RT visceral steatosis mice.";
RL J. Biochem. 119:533-540(1996).
RN [5]
RP DISRUPTION PHENOTYPE, FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY
RP REGULATION.
RX PubMed=16169268; DOI=10.1016/j.ymgme.2005.07.021;
RA Nyman L.R., Cox K.B., Hoppel C.L., Kerner J., Barnoski B.L., Hamm D.A.,
RA Tian L., Schoeb T.R., Wood P.A.;
RT "Homozygous carnitine palmitoyltransferase 1a (liver isoform) deficiency is
RT lethal in the mouse.";
RL Mol. Genet. Metab. 86:179-187(2005).
RN [6]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=17030509; DOI=10.1074/jbc.m608372200;
RA Deberardinis R.J., Lum J.J., Thompson C.B.;
RT "Phosphatidylinositol 3-kinase-dependent modulation of carnitine
RT palmitoyltransferase 1A expression regulates lipid metabolism during
RT hematopoietic cell growth.";
RL J. Biol. Chem. 281:37372-37380(2006).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP DISRUPTION PHENOTYPE.
RX PubMed=22229081; DOI=10.1038/nutd.2011.11;
RA Nyman L.R., Tian L., Hamm D.A., Schoeb T.R., Gower B.A., Nagy T.R.,
RA Wood P.A.;
RT "Long term effects of high fat or high carbohydrate diets on glucose
RT tolerance in mice with heterozygous carnitine palmitoyltransferase-1a (CPT-
RT 1a) deficiency: Diet influences on CPT1a deficient mice.";
RL Nutr. Diabetes 1:E14-E14(2011).
CC -!- FUNCTION: Catalyzes the transfer of the acyl group of long-chain fatty
CC acid-CoA conjugates onto carnitine, an essential step for the
CC mitochondrial uptake of long-chain fatty acids and their subsequent
CC beta-oxidation in the mitochondrion (PubMed:16169268, PubMed:17030509).
CC Plays an important role in hepatic triglyceride metabolism (By
CC similarity). {ECO:0000250|UniProtKB:P32198,
CC ECO:0000269|PubMed:16169268, ECO:0000269|PubMed:17030509}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-carnitine + hexadecanoyl-CoA = CoA + O-hexadecanoyl-(R)-
CC carnitine; Xref=Rhea:RHEA:12661, ChEBI:CHEBI:16347,
CC ChEBI:CHEBI:17490, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379; EC=2.3.1.21;
CC Evidence={ECO:0000269|PubMed:16169268, ECO:0000269|PubMed:17030509};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12662;
CC Evidence={ECO:0000305|PubMed:16169268};
CC -!- ACTIVITY REGULATION: Inhibited by malonyl-CoA.
CC {ECO:0000269|PubMed:16169268}.
CC -!- PATHWAY: Lipid metabolism; fatty acid beta-oxidation.
CC -!- SUBUNIT: Homohexamer and homotrimer (By similarity). Identified in a
CC complex that contains at least CPT1A, ACSL1 and VDAC1 (By similarity).
CC Also identified in complexes with ACSL1 and VDAC2 and VDAC3 (By
CC similarity). {ECO:0000250|UniProtKB:P32198}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:P50416}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- DOMAIN: A conformation change in the N-terminal region spanning the
CC first 42 residues plays an important role in the regulation of enzyme
CC activity by malonyl-CoA. {ECO:0000250|UniProtKB:P50416}.
CC -!- DISRUPTION PHENOTYPE: Complete lethality during early embryogenesis.
CC Heterozygous mice are prone to liver steatosis. Compared to wild-type,
CC heterozygotes show minor differences in blood glucose levels and in
CC serum free fatty acid levels after fasting.
CC {ECO:0000269|PubMed:16169268, ECO:0000269|PubMed:22229081}.
CC -!- SIMILARITY: Belongs to the carnitine/choline acetyltransferase family.
CC {ECO:0000305}.
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DR EMBL; AK050213; BAC34126.2; -; mRNA.
DR EMBL; AK077454; BAC36808.1; -; mRNA.
DR EMBL; BC038395; AAH38395.1; -; mRNA.
DR EMBL; BC046383; AAH46383.1; -; mRNA.
DR EMBL; AF017175; AAC31641.1; -; mRNA.
DR EMBL; S82796; AAB39370.1; -; mRNA.
DR CCDS; CCDS29395.1; -.
DR RefSeq; NP_038523.2; NM_013495.2.
DR RefSeq; XP_006531717.1; XM_006531654.2.
DR RefSeq; XP_006531718.1; XM_006531655.2.
DR RefSeq; XP_006531721.1; XM_006531658.3.
DR RefSeq; XP_006531722.1; XM_006531659.2.
DR AlphaFoldDB; P97742; -.
DR SMR; P97742; -.
DR BioGRID; 198863; 7.
DR IntAct; P97742; 1.
DR STRING; 10090.ENSMUSP00000025835; -.
DR iPTMnet; P97742; -.
DR PhosphoSitePlus; P97742; -.
DR SwissPalm; P97742; -.
DR EPD; P97742; -.
DR jPOST; P97742; -.
DR PaxDb; 10090-ENSMUSP00000025835; -.
DR PeptideAtlas; P97742; -.
DR ProteomicsDB; 284111; -.
DR Pumba; P97742; -.
DR Antibodypedia; 1640; 484 antibodies from 37 providers.
DR DNASU; 12894; -.
DR Ensembl; ENSMUST00000025835.6; ENSMUSP00000025835.5; ENSMUSG00000024900.6.
DR GeneID; 12894; -.
DR KEGG; mmu:12894; -.
DR UCSC; uc008fwf.2; mouse.
DR AGR; MGI:1098296; -.
DR CTD; 1374; -.
DR MGI; MGI:1098296; Cpt1a.
DR VEuPathDB; HostDB:ENSMUSG00000024900; -.
DR eggNOG; KOG3716; Eukaryota.
DR GeneTree; ENSGT01060000248595; -.
DR HOGENOM; CLU_013513_2_1_1; -.
DR InParanoid; P97742; -.
DR OMA; NTEHSWG; -.
DR OrthoDB; 1429709at2759; -.
DR PhylomeDB; P97742; -.
DR TreeFam; TF313836; -.
DR Reactome; R-MMU-200425; Carnitine metabolism.
DR Reactome; R-MMU-5362517; Signaling by Retinoic Acid.
DR UniPathway; UPA00659; -.
DR BioGRID-ORCS; 12894; 3 hits in 78 CRISPR screens.
DR ChiTaRS; Cpt1a; mouse.
DR PRO; PR:P97742; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; P97742; Protein.
DR Bgee; ENSMUSG00000024900; Expressed in choroid plexus of fourth ventricle and 274 other cell types or tissues.
DR ExpressionAtlas; P97742; baseline and differential.
DR Genevisible; P97742; MM.
DR GO; GO:0005743; C:mitochondrial inner membrane; HDA:MGI.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0004095; F:carnitine O-palmitoyltransferase activity; IMP:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:1990698; F:palmitoleoyltransferase activity; IDA:UniProtKB.
DR GO; GO:0046222; P:aflatoxin metabolic process; IEA:Ensembl.
DR GO; GO:0009437; P:carnitine metabolic process; ISS:UniProtKB.
DR GO; GO:0071398; P:cellular response to fatty acid; IEA:Ensembl.
DR GO; GO:0042755; P:eating behavior; ISO:MGI.
DR GO; GO:0030855; P:epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IEA:UniProtKB-UniPathway.
DR GO; GO:0006631; P:fatty acid metabolic process; IBA:GO_Central.
DR GO; GO:0006006; P:glucose metabolic process; ISO:MGI.
DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl.
DR GO; GO:0001676; P:long-chain fatty acid metabolic process; ISS:UniProtKB.
DR GO; GO:0032000; P:positive regulation of fatty acid beta-oxidation; ISO:MGI.
DR GO; GO:0046320; P:regulation of fatty acid oxidation; ISO:MGI.
DR GO; GO:0050796; P:regulation of insulin secretion; ISO:MGI.
DR GO; GO:0010883; P:regulation of lipid storage; IEA:Ensembl.
DR GO; GO:0043279; P:response to alkaloid; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:1904772; P:response to tetrachloromethane; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0006641; P:triglyceride metabolic process; ISO:MGI.
DR Gene3D; 6.10.250.1760; -; 1.
DR Gene3D; 3.30.559.10; Chloramphenicol acetyltransferase-like domain; 1.
DR Gene3D; 3.30.559.70; Choline/Carnitine o-acyltransferase, domain 2; 1.
DR InterPro; IPR000542; Carn_acyl_trans.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR039551; Cho/carn_acyl_trans.
DR InterPro; IPR042231; Cho/carn_acyl_trans_2.
DR InterPro; IPR032476; CPT_N.
DR PANTHER; PTHR22589; CARNITINE O-ACYLTRANSFERASE; 1.
DR PANTHER; PTHR22589:SF74; CARNITINE O-PALMITOYLTRANSFERASE 1, LIVER ISOFORM; 1.
DR Pfam; PF00755; Carn_acyltransf; 1.
DR Pfam; PF16484; CPT_N; 1.
DR SUPFAM; SSF52777; CoA-dependent acyltransferases; 2.
DR PROSITE; PS00439; ACYLTRANSF_C_1; 1.
DR PROSITE; PS00440; ACYLTRANSF_C_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Acyltransferase; Fatty acid metabolism; Lipid metabolism;
KW Membrane; Mitochondrion; Mitochondrion outer membrane; Nitration;
KW Phosphoprotein; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P32198"
FT CHAIN 2..773
FT /note="Carnitine O-palmitoyltransferase 1, liver isoform"
FT /id="PRO_0000210160"
FT TOPO_DOM 2..47
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 48..73
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 74..102
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT TRANSMEM 103..122
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 123..773
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ACT_SITE 473
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P18886"
FT BINDING 555..567
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250"
FT BINDING 589
FT /ligand="(R)-carnitine"
FT /ligand_id="ChEBI:CHEBI:16347"
FT /evidence="ECO:0000250|UniProtKB:P18886"
FT BINDING 602
FT /ligand="(R)-carnitine"
FT /ligand_id="ChEBI:CHEBI:16347"
FT /evidence="ECO:0000250|UniProtKB:P18886"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P32198"
FT MOD_RES 282
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P32198"
FT MOD_RES 588
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P32198"
FT MOD_RES 589
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P32198"
FT MOD_RES 604
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P32198"
FT MOD_RES 741
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P32198"
FT MOD_RES 747
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P32198"
FT CONFLICT 145
FT /note="R -> C (in Ref. 2; AAH38395/AAH46383)"
FT /evidence="ECO:0000305"
FT CONFLICT 398
FT /note="Y -> C (in Ref. 3; AAC31641)"
FT /evidence="ECO:0000305"
FT CONFLICT 531
FT /note="E -> D (in Ref. 1; BAC36808)"
FT /evidence="ECO:0000305"
FT CONFLICT 630
FT /note="F -> L (in Ref. 3; AAC31641)"
FT /evidence="ECO:0000305"
FT CONFLICT 732
FT /note="I -> T (in Ref. 3; AAC31641)"
FT /evidence="ECO:0000305"
FT CONFLICT 760
FT /note="D -> A (in Ref. 3; AAC31641)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 773 AA; 88251 MW; 85C3D386FFD97C5E CRC64;
MAEAHQAVAF QFTVTPDGID LRLSHEALKQ ICLSGLHSWK KKFIRFKNGI ITGVFPASPS
SWLIVVVGVI SSMHTKVDPS LGMIAKINRT LDTTGRMSSQ TKNIVSGVLF GTGLWVAIIM
TMRYSLKVLL SYHGWMFAEH GKMSRSTRIW MAMVKVFSGR KPMLYSFQTS LPRLPVPAVK
DTVSRYLESV RPLMKEGDFQ RMTALAQDFA VNLGPKLQWY LKLKSWWATN YVSDWWEEYI
YLRGRGPIMV NSNYYAMEML YITPTHIQAA RAGNTIHAIL LYRRTVDREE LKPIRLLGST
IPLCSAQWER LFNTSRIPGE ETDTIQHVKD SRHIVVYHRG RYFKVWLYHD GRLLRPRELE
QQMQQILDDT SEPQPGEAKL AALTAADRVP WAKCRQTYFA RGKNKQSLDA VEKAAFFVTL
DESEQGYREE DPEASIDSYA KSLLHGRCFD RWFDKSITFV VFKNSKIGIN AEHSWADAPI
VGHLWEYVMA TDVFQLGYSE DGHCKGDKNP NIPKPTRLQW DIPGECQEVI ETSLSSASFL
ANDVDLHSFP FDTFGKGLIK KCRTSPDAFI QLALQLAHYK DMGKFCLTYE ASMTRLFREG
RTETVRSCTT ESCNFVLAMM DPTTTAEQRF KLFKIACEKH QHLYRLAMTG AGIDRHLFCL
YVVSKYLAVD SPFLKEVLSE PWRLSTSQTP QQQVELFDFE KYPDYVSCGG GFGPVADDGY
GVSYIIVGEN FIHFHISSKF SSPETDSHRF GKHLRQAMMD IITLFGLTAN SKK
//
