P12235 (ADT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
ADP/ATP translocase 1

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

Gene names

Name:	SLC25A4
Synonyms:	ANT1

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	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 cytoplasmic ADP with mitochondrial ATP across the mitochondrial inner membrane.
Subunit structure	Found in a complex with ARL2, ARL2BP and SLC25A4. Interacts with ARL2BP By similarity. Homodimer. Interacts with HIV-1 Vpr. Ref.9
Subcellular location	Mitochondrion inner membrane; Multi-pass membrane protein.
Involvement in disease	Progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal dominant 2 (PEOA2) [MIM:609283]: A disorder 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Ref.13 Ref.14 Ref.17 Ref.18
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 (TC 2.A.29) family. [View classification] 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 Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic mitochondrial changes Inferred from electronic annotation. Source: Compara energy reserve metabolic process Traceable author statement. Source: Reactome mitochondrial genome maintenance Traceable author statement Ref.12. Source: ProtInc negative regulation of necrotic cell death Inferred from mutant phenotype PubMed 16507998. Source: BHF-UCL regulation of insulin secretion Traceable author statement. Source: Reactome small molecule metabolic process Traceable author statement. Source: Reactome viral reproduction Traceable author statement. Source: Reactome virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc mitochondrial inner membrane Traceable author statement. Source: Reactome
Molecular_function	adenine transmembrane transporter activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.8
	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.8
	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 By similarity
	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.17		VAR_038814
	Natural variant	98	1	L → P in PEOA2. Ref.13 Ref.18		VAR_022459
	Natural variant	104	1	D → G in PEOA2. Ref.14 Corresponds to variant rs28999114 [ dbSNP | Ensembl ].		VAR_022460
	Natural variant	114	1	A → P in PEOA2. Ref.12 Ref.18		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.16		VAR_038815
	Natural variant	289	1	V → M in PEOA2; also found in a sporadic case affected by PEO. Ref.12 Ref.15		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 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing." Wang W., Shen P., Thiyagarajan S., Lin S., Palm C., Horvath R., Klopstock T., Cutler D., Pique L., Schrijver I., Davis R.W., Mindrinos M., Speed T.P., Scharfe C. Nucleic Acids Res. 39:44-58(2011) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: Eye, Mammary gland and PNS.
[7]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-37. Tissue: Liver.
[8]	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.
[9]	"Mitochondrial membrane permeabilization by HIV-1 Vpr." Deniaud A., Brenner C., Kroemer G. Mitochondrion 4:223-233(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HIV-1 VPR.
[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.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-96, MASS SPECTROMETRY.
[11]	"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].
[12]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS PEOA2 PRO-114 AND MET-289.
[13]	"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] [Europe PMC] [Abstract] Cited for: VARIANT PEOA2 PRO-98.
[14]	"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] [Europe PMC] [Abstract] Cited for: VARIANT PEOA2 GLY-104.
[15]	"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] [Europe PMC] [Abstract] Cited for: VARIANT PEO MET-289.
[16]	"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] [Europe PMC] [Abstract] Cited for: VARIANT HYPERTROPHIC CARDIOMYOPATHY ASP-123.
[17]	"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] [Europe PMC] [Abstract] Cited for: VARIANT PEOA2 ASP-90.
[18]	"Novel Twinkle (PEO1) gene mutations in Mendelian progressive external ophthalmoplegia." Virgilio R., Ronchi D., Hadjigeorgiou G.M., Bordoni A., Saladino F., Moggio M., Adobbati L., Kafetsouli D., Tsironi E., Previtali S., Papadimitriou A., Bresolin N., Comi G.P. J. Neurol. 255:1384-1391(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PEOA2 PRO-98 AND PRO-114.
+	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. HQ206346 Genomic DNA. Translation: ADP92294.1. HQ206347 Genomic DNA. Translation: ADP92295.1. HQ206348 Genomic DNA. Translation: ADP92296.1. HQ206349 Genomic DNA. Translation: ADP92297.1. HQ206350 Genomic DNA. Translation: ADP92298.1. HQ206351 Genomic DNA. Translation: ADP92299.1. HQ206352 Genomic DNA. Translation: ADP92300.1. HQ206353 Genomic DNA. Translation: ADP92301.1. HQ206354 Genomic DNA. Translation: ADP92302.1. HQ206355 Genomic DNA. Translation: ADP92303.1. HQ206356 Genomic DNA. Translation: ADP92304.1. HQ206357 Genomic DNA. Translation: ADP92305.1. HQ206358 Genomic DNA. Translation: ADP92306.1. HQ206359 Genomic DNA. Translation: ADP92307.1. HQ206360 Genomic DNA. Translation: ADP92308.1. HQ206361 Genomic DNA. Translation: ADP92309.1. HQ206362 Genomic DNA. Translation: ADP92310.1. HQ206363 Genomic DNA. Translation: ADP92311.1. HQ206364 Genomic DNA. Translation: ADP92312.1. HQ206365 Genomic DNA. Translation: ADP92313.1. HQ206366 Genomic DNA. Translation: ADP92314.1. HQ206367 Genomic DNA. Translation: ADP92315.1. HQ206368 Genomic DNA. Translation: ADP92316.1. HQ206369 Genomic DNA. Translation: ADP92317.1. HQ206370 Genomic DNA. Translation: ADP92318.1. HQ206371 Genomic DNA. Translation: ADP92319.1. HQ206372 Genomic DNA. Translation: ADP92320.1. HQ206373 Genomic DNA. Translation: ADP92321.1. HQ206374 Genomic DNA. Translation: ADP92322.1. HQ206375 Genomic DNA. Translation: ADP92323.1. HQ206376 Genomic DNA. Translation: ADP92324.1. HQ206377 Genomic DNA. Translation: ADP92325.1. HQ206378 Genomic DNA. Translation: ADP92326.1. HQ206379 Genomic DNA. Translation: ADP92327.1. HQ206380 Genomic DNA. Translation: ADP92328.1. HQ206381 Genomic DNA. Translation: ADP92329.1. HQ206382 Genomic DNA. Translation: ADP92330.1. HQ206383 Genomic DNA. Translation: ADP92331.1. HQ206384 Genomic DNA. Translation: ADP92332.1. HQ206385 Genomic DNA. Translation: ADP92333.1. CH471056 Genomic DNA. Translation: EAX04655.1. CH471056 Genomic DNA. Translation: EAX04656.1. 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. NM_001151.3.
UniGene	Hs.246506.
3D structure databases
ProteinModelPortal	P12235.
ModBase	Search...
Protein-protein interaction databases
IntAct	P12235. 9 interactions.
MINT	MINT-196037.
STRING	9606.ENSP00000281456.
Protein family/group databases
TCDB	2.A.29.1.2. mitochondrial carrier (MC) family.
PTM databases
PhosphoSite	P12235.
Polymorphism databases
DMDM	113455.
Proteomic databases
PaxDb	P12235.
PRIDE	P12235.
Protocols and materials databases
DNASU	291.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000281456; ENSP00000281456; ENSG00000151729.
GeneID	291.
KEGG	hsa:291.
UCSC	uc003ixd.3. human.
Organism-specific databases
CTD	291.
GeneCards	GC04P186064.
HGNC	HGNC:10990. SLC25A4.
MIM	103220. gene. 609283. phenotype.
neXtProt	NX_P12235.
Orphanet	254892. Autosomal dominant progressive external ophthalmoplegia. 1369. Cataract - cardiomyopathy. 155. Familial isolated hypertrophic cardiomyopathy.
PharmGKB	PA35866.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG238123.
HOGENOM	HOG000165727.
HOVERGEN	HBG108348.
InParanoid	P12235.
KO	K05863.
OMA	AKDEGSK.
OrthoDB	EOG49CQ86.
PhylomeDB	P12235.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism. REACT_116125. Disease. REACT_17015. Metabolism of proteins.
Gene expression databases
Bgee	P12235.
CleanEx	HS_SLC25A4.
Genevestigator	P12235.
GermOnline	ENSG00000151729. Homo sapiens.
Family and domain databases
Gene3D	1.50.40.10. 1 hit.
InterPro	IPR002113. Aden_trnslctor. IPR002067. Mit_carrier. IPR018108. Mitochondrial_sb/sol_carrier. IPR023395. Mt_carrier_dom. [Graphical view]
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
ChEMBL	CHEMBL1879.
DrugBank	DB00171. Adenosine triphosphate. DB00720. Clodronate.
GenomeRNAi	291.
NextBio	1187.
SOURCE	Search...

Entry information

Entry name

ADT1_HUMAN

Accession

Primary (citable) accession number: P12235
Secondary accession number(s): D3DP59

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 160 of the entry and version 4 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.