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)

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	Lipid metabolism; fatty acid beta-oxidation.
Subcellular location	Mitochondrion outer membrane; Multi-pass membrane protein.
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-oxidation Traceable author statement. Source: ProtInc
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial outer membrane Traceable 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

	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: 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

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.

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

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	December 7, 2004
Last modified:	January 25, 2012
This is version 110 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.