P50416 (CPT1A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names 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

Name:	CPT1A
Synonyms:	CPT1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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)

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 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 metabolic process Inferred from direct assay Ref.11. Source: UniProtKB carnitine shuttle Traceable author statement. Source: Reactome eating behavior Inferred from electronic annotation. Source: Compara fatty acid beta-oxidation Traceable author statement Ref.1. Source: ProtInc glucose metabolic process Inferred from electronic annotation. Source: Compara 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: Compara protein homooligomerization Inferred from electronic annotation. Source: Compara regulation of fatty acid oxidation Traceable author statement. Source: Reactome regulation of insulin secretion Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to organic cyclic compound Inferred from electronic annotation. Source: Compara triglyceride metabolic process Inferred from electronic annotation. Source: Compara
Cellular_component	integral to mitochondrial outer membrane Inferred from sequence or structural similarity. Source: UniProtKB mitochondrial inner membrane Inferred from electronic annotation. Source: Compara
Molecular_function	carnitine 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 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.10

VAR_020546

Natural variant

275

1

A → T. Ref.2 Ref.10 Ref.13
Corresponds to variant rs2229738 [ dbSNP | Ensembl ].

VAR_020547

Natural variant

304

1

C → W in CPT1AD. Ref.10

VAR_020548

Natural variant

314

1

T → I in CPT1AD. Ref.14

VAR_020549

Natural variant

316

1

R → G in CPT1AD. Ref.15

VAR_046767

Natural variant

343

1

F → V in CPT1AD. Ref.15

VAR_046768

Natural variant

357

1

R → W in CPT1AD; decreased stability. Ref.10

VAR_020550

Natural variant

360

1

E → G in CPT1AD; reduced protein levels. Ref.12
Corresponds to variant rs28936372 [ dbSNP | Ensembl ].

VAR_020551

Natural variant

395

1

Missing in CPT1AD; loss of activity. Ref.10

VAR_020552

Natural variant

414

1

A → V in CPT1AD; decreased activity. Ref.2 Ref.13
Corresponds to variant rs28936373 [ dbSNP | Ensembl ].

VAR_020553

Natural variant

454

1

D → G in CPT1AD. Ref.9

VAR_020554

Natural variant

465

1

G → W in CPT1AD. Ref.15

VAR_046769

Natural variant

479

1

P → L in CPT1AD; decreased activity. Ref.10

VAR_020555

Natural variant

484

1

L → P in CPT1AD. Ref.10

VAR_020556

Natural variant

498

1

Y → C in CPT1AD; decreased activity. Ref.2 Ref.13

VAR_020557

Natural variant

709

1

G → E in CPT1AD; loss of activity. Ref.13
Corresponds to variant rs28936374 [ dbSNP | Ensembl ].

VAR_020558

Natural variant

710

1

G → E in CPT1AD; loss of activity. Ref.11 Ref.13

VAR_020559

Experimental info

Sequence conflict

479

1

P → Q in AAC41748. Ref.1

Sequence conflict

568

1

A → T in AAC41748. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

773

Helix Strand Turn

Details...

Helix

4 – 7

4

Beta strand

9 – 15

7

Beta strand

18 – 23

6

Helix

25 – 39

15

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 7, 2004. Version 2. Checksum: E5DC9141B6301947	FASTA	773	88,368
	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
	Isoform 2 [UniParc]. Checksum: C7B0ED8A26285110	FASTA	756	86,239
	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 GVSYILVGEN LINFHISSKF SCPETGIISQ GPSSDT

References

	« Hide 'large scale' referencesShow '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.

Web resources

GeneReviews

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

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2LE3	NMR	-	A	1-42	[»]

ProteinModelPortal

P50416.

ModBase

Search...

Protein-protein interaction databases

IntAct

P50416. 10 interactions.

STRING

9606.ENSP00000265641.

PTM databases

PhosphoSite

P50416.

Polymorphism databases

DMDM

56405343.

Proteomic databases

PaxDb

P50416.

PeptideAtlas

P50416.

PRIDE

P50416.

Protocols and materials databases

DNASU

1374.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000265641; ENSP00000265641; ENSG00000110090.
ENST00000376618; ENSP00000365803; ENSG00000110090.
ENST00000538308; ENSP00000446042; ENSG00000110090.
ENST00000539743; ENSP00000446108; ENSG00000110090.
ENST00000540367; ENSP00000439084; ENSG00000110090.

GeneID

1374.

KEGG

hsa:1374.

UCSC

uc001oof.4. human.
uc001oog.4. 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.

PharmGKB

PA26847.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG70127.

HOGENOM

HOG000233542.

HOVERGEN

HBG003458.

InParanoid

P50416.

KO

K08765.

OMA

KGFMKKC.

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_111217. Metabolism.
REACT_11163. Activated AMPK stimulates fatty-acid oxidation in muscle.
REACT_24941. Circadian Clock.

SABIO-RK

P50416.

UniPathway

UPA00659.

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]

PANTHER

PTHR22589. PTHR22589. 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

ChEMBL

CHEMBL1293194.

ChiTaRS

CPT1A. human.

DrugBank

DB00583. L-Carnitine.
DB01074. Perhexiline.

GenomeRNAi

1374.

NextBio

5569.

SOURCE

Search...

Entry information

Entry name

CPT1A_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 124 of the entry and version 2 of the sequence. [Complete 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.