P12235 (ADT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
ADP/ATP translocase 1

Alternative name(s):
Adenine nucleotide translocator 1
Short name=ANT 1
ADP,ATP carrier protein 1
Solute carrier family 25 member 4
ADP,ATP carrier protein, heart/skeletal muscle isoform T1

Gene names

Name:	SLC25A4
Synonyms:	ANT1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	298 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 exchange of ADP and ATP across the mitochondrial inner membrane.
Subunit structure	Homodimer. Interacts with HIV-1 Vpr. Ref.7
Subcellular location	Mitochondrion inner membrane; Multi-pass membrane protein.
Involvement in disease	Defects in SLC25A4 are a cause of progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal dominant type 2 (PEOA2) [MIM:609283]. Progressive external ophthalmoplegia is characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged-red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism. Ref.11 Ref.12 Ref.13 Ref.16
Miscellaneous	The transmembrane helices are not perpendicular to the plane of the membrane, but cross the membrane at an angle. Odd-numbered transmembrane helices exhibit a sharp kink, due to the presence of a conserved proline residue By similarity.
Sequence similarities	Belongs to the mitochondrial carrier family. Contains 3 Solcar repeats.

Ontologies

Keywords
Biological process	Host-virus interaction Transport
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Disease	Disease mutation Progressive external ophthalmoplegia
Domain	Repeat Transmembrane Transmembrane helix
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	generation of precursor metabolites and energy Traceable author statement. Source: ProtInc interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial genome maintenance Traceable author statement. Source: ProtInc negative regulation of necrotic cell death Inferred from mutant phenotype. Source: BHF-UCL
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc mitochondrial inner membrane Inferred from Experiment. Source: Reactome
Molecular function	adenine transmembrane transporter activity Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.6
	Chain	2 – 298	297	ADP/ATP translocase 1		PRO_0000090574
Regions
	Transmembrane	5 – 39	35	Helical; Name=1; By similarity
	Transmembrane	75 – 100	26	Helical; Name=2; By similarity
	Transmembrane	109 – 143	35	Helical; Name=3; By similarity
	Transmembrane	176 – 202	27	Helical; Name=4; By similarity
	Transmembrane	207 – 241	35	Helical; Name=5; By similarity
	Transmembrane	273 – 298	26	Helical; Name=6; By similarity
	Repeat	6 – 98	93	Solcar 1
	Repeat	111 – 201	91	Solcar 2
	Repeat	212 – 297	86	Solcar 3
	Motif	235 – 240	6	Substrate recognition By similarity
Sites
	Binding site	80	1	Nucleotide By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylglycine Ref.6
	Modified residue	96	1	N6-acetyllysine Ref.10
	Modified residue	126	1	Phosphothreonine By similarity
	Modified residue	127	1	Phosphoserine By similarity
	Modified residue	191	1	Phosphotyrosine Ref.8
	Modified residue	195	1	Phosphotyrosine By similarity
	Cross-link	10		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Natural variations
	Natural variant	90	1	A → D in PEOA2. Ref.16		VAR_038814
	Natural variant	98	1	L → P in PEOA2. Ref.12		VAR_022459
	Natural variant	104	1	D → G in PEOA2. [dbSNP:rs28999114] Ref.13		VAR_022460
	Natural variant	114	1	A → P in PEOA2. Ref.11		VAR_012111
	Natural variant	123	1	A → D in hypertrophic cardiomyopathy; sporadic patient with mild myopathy, exercise intolerance and lactic acidosis but no ophthalmoplegia. Ref.15		VAR_038815
	Natural variant	289	1	V → M in PEOA2; also found in a sporadic case affected by PEO. Ref.11 Ref.14		VAR_012112
Experimental info
	Sequence conflict	16	1	G → A in AAA61223. Ref.1
	Sequence conflict	147 – 149	3	KGA → RR in AAA61223. Ref.1
	Sequence conflict	227	1	V → L in AAA61223. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P12235-1 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 59F0DFAEC4E7CFBB	FASTA	298	33,064
	10 20 30 40 50 60 MGDHAWSFLK DFLAGGVAAA VSKTAVAPIE RVKLLLQVQH ASKQISAEKQ YKGIIDCVVR 70 80 90 100 110 120 IPKEQGFLSF WRGNLANVIR YFPTQALNFA FKDKYKQLFL GGVDRHKQFW RYFAGNLASG 130 140 150 160 170 180 GAAGATSLCF VYPLDFARTR LAADVGKGAA QREFHGLGDC IIKIFKSDGL RGLYQGFNVS 190 200 210 220 230 240 VQGIIIYRAA YFGVYDTAKG MLPDPKNVHI FVSWMIAQSV TAVAGLVSYP FDTVRRRMMM 250 260 270 280 290 QSGRKGADIM YTGTVDCWRK IAKDEGAKAF FKGAWSNVLR GMGGAFVLVL YDEIKKYV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA sequence of a human skeletal muscle ADP/ATP translocator: lack of a leader peptide, divergence from a fibroblast translocator cDNA, and coevolution with mitochondrial DNA genes." Neckelmann N., Li K., Wade R.P., Shuster R., Wallace D.C. Proc. Natl. Acad. Sci. U.S.A. 84:7580-7584(1987) [PubMed: 2823266] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"DNA sequences of two expressed nuclear genes for human mitochondrial ADP/ATP translocase." Cozens A.L., Runswick M.J., Walker J.E. J. Mol. Biol. 206:261-280(1989) [PubMed: 2541251] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"A human muscle adenine nucleotide translocator gene has four exons, is located on chromosome 4, and is differentially expressed." Li K., Warner C.K., Hodge J.A., Minoshima S., Kudoh J., Fukuyama R., Maekawa M., Shimizu Y., Shimizu N., Wallace D.C. J. Biol. Chem. 264:13998-14004(1989) [PubMed: 2547778] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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]. Tissue: Eye, Mammary gland and PNS.
[5]	"Two distinct genes for ADP/ATP translocase are expressed at the mRNA level in adult human liver." Houldsworth J., Attardi G. Proc. Natl. Acad. Sci. U.S.A. 85:377-381(1988) [PubMed: 2829183] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-37. Tissue: Liver.
[6]	Bienvenut W.V. Submitted (OCT-2004) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-31; 34-43; 64-92; 141-147; 189-199 AND 273-296, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT GLY-2, MASS SPECTROMETRY. Tissue: B-cell lymphoma.
[7]	"Mitochondrial membrane permeabilization by HIV-1 Vpr." Deniaud A., Brenner C., Kroemer G. Mitochondrion 4:223-233(2004) [PubMed: 16120388] [Abstract] Cited for: INTERACTION WITH HIV-1 VPR.
[8]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-191, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-96, MASS SPECTROMETRY.
[11]	"Role of adenine nucleotide translocator 1 in mtDNA maintenance." Kaukonen J., Juselius J.K., Tiranti V., Kyttala A., Zeviani M., Comi G.P., Keranen J., Peltonen L., Suomalainen A. Science 289:782-785(2000) [PubMed: 10926541] [Abstract] Cited for: VARIANTS PEOA2 PRO-114 AND MET-289.
[12]	"A novel missense adenine nucleotide translocator-1 gene mutation in a Greek adPEO family." Napoli L., Bordoni A., Zeviani M., Hadjigeorgiou G.M., Sciacco M., Tiranti V., Terentiou A., Moggio M., Papadimitriou A., Scarlato G., Comi G.P. Neurology 57:2295-2298(2001) [PubMed: 11756613] [Abstract] Cited for: VARIANT PEOA2 PRO-98.
[13]	"A novel D104G mutation in the adenine nucleotide translocator 1 gene in autosomal dominant progressive external ophthalmoplegia patients with mitochondrial DNA with multiple deletions." Komaki H., Fukazawa T., Houzen H., Yoshida K., Nonaka I., Goto Y. Ann. Neurol. 51:645-648(2002) [PubMed: 12112115] [Abstract] Cited for: VARIANT PEOA2 GLY-104.
[14]	"Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO)." Agostino A., Valletta L., Chinnery P.F., Ferrari G., Carrara F., Taylor R.W., Schaefer A.M., Turnbull D.M., Tiranti V., Zeviani M. Neurology 60:1354-1356(2003) [PubMed: 12707443] [Abstract] Cited for: VARIANT PEO MET-289.
[15]	"Complete loss-of-function of the heart/muscle-specific adenine nucleotide translocator is associated with mitochondrial myopathy and cardiomyopathy." Palmieri L., Alberio S., Pisano I., Lodi T., Meznaric-Petrusa M., Zidar J., Santoro A., Scarcia P., Fontanesi F., Lamantea E., Ferrero I., Zeviani M. Hum. Mol. Genet. 14:3079-3088(2005) [PubMed: 16155110] [Abstract] Cited for: VARIANT HYPERTROPHIC CARDIOMYOPATHY ASP-123.
[16]	"A novel ANT1 gene mutation with probable germline mosaicism in autosomal dominant progressive external ophthalmoplegia." Deschauer M., Hudson G., Mueller T., Taylor R.W., Chinnery P.F., Zierz S. Neuromuscul. Disord. 15:311-315(2005) [PubMed: 15792871] [Abstract] Cited for: VARIANT PEOA2 ASP-90.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	J02966 mRNA. Translation: AAA61223.1. J04982 Genomic DNA. Translation: AAA51736.1. BC008664 mRNA. Translation: AAH08664.1. BC061589 mRNA. Translation: AAH61589.1. BC063643 mRNA. Translation: AAH63643.1. J03593 mRNA. Translation: AAA36751.1.
IPI	IPI00022891.
PIR	A44778.
RefSeq	NP_001142.2.
UniGene	Hs.246506.
3D structure databases
ProteinModelPortal	P12235.
SMR	P12235. Positions 3-294.
ModBase	Search...
Protein-protein interaction databases
IntAct	P12235. 2 interactions.
MINT	MINT-196037.
STRING	P12235.
Protein family/group databases
TCDB	2.A.29.1.2. mitochondrial carrier (MC) family.
PTM databases
PhosphoSite	P12235.
Proteomic databases
PRIDE	P12235.
Genome annotation databases
Ensembl	ENST00000281456; ENSP00000281456; ENSG00000151729; Homo sapiens. [Genome view]
GeneID	291.
KEGG	hsa:291.
UCSC	uc003ixd.1. human.
Organism-specific databases
CTD	291.
GeneCards	GC04P186064.
H-InvDB	HIX0004678.
HGNC	HGNC:10990. SLC25A4.
MIM	103220. gene. 609283. phenotype.
Orphanet	663. Progressive external ophthalmoplegia.
PharmGKB	PA35866.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG12573.
HOGENOM	HBG610399.
HOVERGEN	HBG108348.
InParanoid	P12235.
OMA	AKDEGSK.
OrthoDB	EOG9JMB7V.
PhylomeDB	P12235.
Enzyme and pathway databases
Reactome	REACT_1505. Integration of energy metabolism. REACT_15380. Diabetes pathways. REACT_6185. HIV Infection.
Gene expression databases
ArrayExpress	P12235.
Bgee	P12235.
CleanEx	HS_SLC25A4.
Genevestigator	P12235.
GermOnline	ENSG00000151729. Homo sapiens.
Family and domain databases
InterPro	IPR002113. Aden_trnslctor. IPR002067. Mit_carrier. IPR001993. Mitochondria_substrate_carrier. IPR018108. Mitochondrial_sb/sol_carrier. [Graphical view]
PANTHER	PTHR11896. Mitoch_carrier. 1 hit.
Pfam	PF00153. Mito_carr. 3 hits. [Graphical view]
PRINTS	PR00927. ADPTRNSLCASE. PR00926. MITOCARRIER.
SUPFAM	SSF103506. Mitoch_carrier. 1 hit.
PROSITE	PS50920. SOLCAR. 3 hits. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00171. Adenosine triphosphate. DB00720. Clodronate.
NextBio	1187.
SOURCE	Search...

Entry information

Entry name

ADT1_HUMAN

Accession

Primary (citable) accession number: P12235

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	January 23, 2007
Last modified:	August 10, 2010
This is version 132 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.