O43772 (MCAT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitochondrial carnitine/acylcarnitine carrier protein

Alternative name(s):
Carnitine/acylcarnitine translocase
Short name=CAC
Solute carrier family 25 member 20

Gene names

Name:	SLC25A20
Synonyms:	CAC, CACT

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	301 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mediates the transport of acylcarnitines of different length across the mitochondrial inner membrane from the cytosol to the mitochondrial matrix for their oxidation by the mitochondrial fatty acid-oxidation pathway.
Subcellular location	Mitochondrion inner membrane; Multi-pass membrane protein.
Involvement in disease	Carnitine-acylcarnitine translocase deficiency (CACT deficiency) [MIM:212138]: A rare long-chain fatty acid oxidation disorder. Metabolic consequences include hypoketotic hypoglycemia under fasting conditions, hyperammonemia, elevated creatine kinase and transaminases, dicarboxylic aciduria, very low free carnitine and abnormal acylcarnitine profile with marked elevation of the long-chain acylcarnitines. Clinical features include neurologic abnormalities, cardiomyopathy, arrythmias, skeletal muscle damage, liver dysfunction and episodes of life-threatening coma, which eventually lead to death. Most patients become symptomatic in the neonatal period with a rapidly progressive deterioration and a high mortality rate. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1
Sequence similarities	Belongs to the mitochondrial carrier (TC 2.A.29) family. [View classification] Contains 3 Solcar repeats.

Ontologies

Keywords
Biological process	Transport
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Disease	Disease mutation
Domain	Repeat Transmembrane Transmembrane helix
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	carnitine shuttle Traceable author statement. Source: Reactome cellular lipid metabolic process Traceable author statement. Source: Reactome regulation of fatty acid oxidation Traceable author statement. Source: Reactome small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial inner membrane Traceable author statement. Source: Reactome
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 301	301	Mitochondrial carnitine/acylcarnitine carrier protein		PRO_0000090628
Regions
	Topological domain	1 – 12	12	Cytoplasmic Potential
	Transmembrane	13 – 31	19	Helical; Name=1; Potential
	Topological domain	32 – 73	42	Mitochondrial matrix Potential
	Transmembrane	74 – 93	20	Helical; Name=2; Potential
	Topological domain	94 – 112	19	Cytoplasmic Potential
	Transmembrane	113 – 131	19	Helical; Name=3; Potential
	Topological domain	132 – 170	39	Mitochondrial matrix Potential
	Transmembrane	171 – 190	20	Helical; Name=4; Potential
	Topological domain	191 – 211	21	Cytoplasmic Potential
	Transmembrane	212 – 230	19	Helical; Name=5; Potential
	Topological domain	231 – 267	37	Mitochondrial matrix Potential
	Transmembrane	268 – 287	20	Helical; Name=6; Potential
	Topological domain	288 – 301	14	Cytoplasmic Potential
	Repeat	8 – 99	92	Solcar 1
	Repeat	108 – 196	89	Solcar 2
	Repeat	207 – 293	87	Solcar 3
Amino acid modifications
	Modified residue	148	1	N6-acetyllysine By similarity
	Modified residue	244	1	N6-acetyllysine By similarity
Natural variations
	Natural variant	133	1	R → W in CACT deficiency. Ref.8		VAR_021818
	Natural variant	231	1	D → H in CACT deficiency. Ref.8		VAR_021819
	Natural variant	238	1	Q → R in CACT deficiency. Ref.6 Ref.7 Corresponds to variant rs28934589 [ dbSNP | Ensembl ].		VAR_021820
Experimental info
	Sequence conflict	203	1	R → S in CAB55356. Ref.2
	Sequence conflict	240	1	A → G in CAB55356. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O43772 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: AEB34E4E335102B0	FASTA	301	32,944
	10 20 30 40 50 60 MADQPKPISP LKNLLAGGFG GVCLVFVGHP LDTVKVRLQT QPPSLPGQPP MYSGTFDCFR 70 80 90 100 110 120 KTLFREGITG LYRGMAAPII GVTPMFAVCF FGFGLGKKLQ QKHPEDVLSY PQLFAAGMLS 130 140 150 160 170 180 GVFTTGIMTP GERIKCLLQI QASSGESKYT GTLDCAKKLY QEFGIRGIYK GTVLTLMRDV 190 200 210 220 230 240 PASGMYFMTY EWLKNIFTPE GKRVSELSAP RILVAGGIAG IFNWAVAIPP DVLKSRFQTA 250 260 270 280 290 300 PPGKYPNGFR DVLRELIRDE GVTSLYKGFN AVMIRAFPAN AACFLGFEVA MKFLNWATPN L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the human carnitine-acylcarnitine carrier cDNA and identification of the molecular defect in a patient." Huizing M., Iacobazzi V., Ijlst L., Savelkoul P., Ruitenbeek W., van den Heuvel L., Indiveri C., Smeitink J., Trijbels F., Wanders R., Palmieri F. Am. J. Hum. Genet. 61:1239-1245(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], DISEASE. Tissue: Liver.
[2]	"The structure and organization of the human carnitine/acylcarnitine translocase (CACT) gene." Iacobazzi V., Naglieri M.A., Stanley C.A., Wanders R.J.A., Palmieri F. Biochem. Biophys. Res. Commun. 252:770-774(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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]. Tissue: Skin.
[5]	"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].
[6]	"A novel molecular defect of the carnitine acylcarnitine translocase gene in a Saudi patient." Al-Aqeel A.I., Rashid M.S., Ruiter J.P., Ijlst L., Wanders R.J.A. Clin. Genet. 64:163-165(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CACT DEFICIENCY ARG-238.
[7]	"Response to therapy in carnitine/acylcarnitine translocase (CACT) deficiency due to a novel missense mutation." Iacobazzi V., Pasquali M., Singh R., Matern D., Rinaldo P., Amat di San Filippo C., Palmieri F., Longo N. Am. J. Med. Genet. A 126:150-155(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CACT DEFICIENCY ARG-238.
[8]	"Molecular and functional analysis of SLC25A20 mutations causing carnitine-acylcarnitine translocase deficiency." Iacobazzi V., Invernizzi F., Baratta S., Pons R., Chung W., Garavaglia B., Dionisi-Vici C., Ribes A., Parini R., Huertas M.D., Roldan S., Lauria G., Palmieri F., Taroni F. Hum. Mutat. 24:312-320(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CACT DEFICIENCY TRP-133 AND HIS-231.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	Y10319 mRNA. Translation: CAA71367.1. Y17775 , Y17776, Y17777, Y17778, Y17779 Genomic DNA. Translation: CAB55356.1. AK312962 mRNA. Translation: BAG35801.1. BC001689 mRNA. Translation: AAH01689.1.
IPI	IPI00013957.
RefSeq	NP_000378.1. NM_000387.5.
UniGene	Hs.13845.
3D structure databases
ProteinModelPortal	O43772.
ModBase	Search...
Protein-protein interaction databases
IntAct	O43772. 1 interaction.
MINT	MINT-1370660.
STRING	9606.ENSP00000326305.
Protein family/group databases
TCDB	2.A.29.8.3. mitochondrial carrier (MC) family.
PTM databases
PhosphoSite	O43772.
Proteomic databases
PaxDb	O43772.
PeptideAtlas	O43772.
PRIDE	O43772.
Protocols and materials databases
DNASU	788.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000319017; ENSP00000326305; ENSG00000178537.
GeneID	788.
KEGG	hsa:788.
UCSC	uc003cva.4. human.
Organism-specific databases
CTD	788.
GeneCards	GC03M048869.
HGNC	HGNC:1421. SLC25A20.
HPA	HPA016862. HPA029863.
MIM	212138. phenotype. 613698. gene.
neXtProt	NX_O43772.
Orphanet	159. Carnitine-acylcarnitine translocase deficiency.
PharmGKB	PA35031.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG245605.
HOGENOM	HOG000168307.
HOVERGEN	HBG003500.
InParanoid	O43772.
KO	K15109.
OMA	IYRGTGA.
OrthoDB	EOG4WM4V6.
PhylomeDB	O43772.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism. REACT_11163. Activated AMPK stimulates fatty-acid oxidation in muscle.
Gene expression databases
ArrayExpress	O43772.
Bgee	O43772.
CleanEx	HS_SLC25A20.
Genevestigator	O43772.
GermOnline	ENSG00000178537. Homo sapiens.
Family and domain databases
Gene3D	1.50.40.10. 1 hit.
InterPro	IPR018108. Mitochondrial_sb/sol_carrier. IPR023395. Mt_carrier_dom. [Graphical view]
Pfam	PF00153. Mito_carr. 3 hits. [Graphical view]
SUPFAM	SSF103506. Mitoch_carrier. 1 hit.
PROSITE	PS50920. SOLCAR. 3 hits. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00583. L-Carnitine.
GenomeRNAi	788.
NextBio	3206.
SOURCE	Search...

Entry information

Entry name

MCAT_HUMAN

Accession

Primary (citable) accession number: O43772
Secondary accession number(s): B2R7F4, Q9UIQ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	June 1, 1998
Last modified:	May 1, 2013
This is version 120 of the entry and version 1 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.