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P12235 (ADT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 174. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length298 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.13 Ref.14 Ref.15 Ref.18 Ref.19

Mitochondrial DNA depletion syndrome 12, cardiomyopathic type (MTDPS12) [MIM:615418]: An autosomal recessive mitochondrial disorder characterized by childhood onset of slowly progressive hypertrophic cardiomyopathy and generalized skeletal myopathy resulting in exercise intolerance and, in some patients, muscle weakness and atrophy. Skeletal muscle biopsy shows ragged red fibers, mtDNA depletion, and accumulation of abnormal mitochondria.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12

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 processHost-virus interaction
Transport
   Cellular componentMembrane
Mitochondrion
Mitochondrion inner membrane
   DiseaseCardiomyopathy
Disease mutation
Progressive external ophthalmoplegia
   DomainRepeat
Transmembrane
Transmembrane helix
   PTMAcetylation
Isopeptide bond
S-nitrosylation
Ubl conjugation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processadenine transport

Traceable author statement Ref.1. Source: GOC

apoptotic mitochondrial changes

Inferred from electronic annotation. Source: Ensembl

energy reserve metabolic process

Traceable author statement. Source: Reactome

generation of precursor metabolites and energy

Traceable author statement Ref.1. Source: ProtInc

mitochondrial genome maintenance

Traceable author statement Ref.13. Source: ProtInc

negative regulation of necroptotic process

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

transport

Traceable author statement Ref.1. Source: ProtInc

viral process

Traceable author statement. Source: Reactome

   Cellular_componentintegral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

mitochondrial inner membrane

Traceable author statement. Source: Reactome

mitochondrion

Inferred from direct assay PubMed 20833797. Source: UniProt

nucleus

Inferred from direct assay PubMed 21630459. Source: UniProt

   Molecular_functionadenine transmembrane transporter activity

Traceable author statement Ref.1. Source: ProtInc

protein binding

Inferred from physical interaction PubMed 16507998. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.8
Chain2 – 298297ADP/ATP translocase 1
PRO_0000090574

Regions

Transmembrane5 – 3935Helical; Name=1; By similarity
Transmembrane75 – 10026Helical; Name=2; By similarity
Transmembrane109 – 14335Helical; Name=3; By similarity
Transmembrane176 – 20227Helical; Name=4; By similarity
Transmembrane207 – 24135Helical; Name=5; By similarity
Transmembrane273 – 29826Helical; Name=6; By similarity
Repeat6 – 9893Solcar 1
Repeat111 – 20191Solcar 2
Repeat212 – 29786Solcar 3
Motif235 – 2406Substrate recognition By similarity

Sites

Binding site801Nucleotide By similarity

Amino acid modifications

Modified residue21N-acetylglycine Ref.8
Modified residue1471N6-succinyllysine By similarity
Modified residue1601S-nitrosocysteine By similarity
Modified residue2451N6-succinyllysine By similarity
Modified residue2721N6-succinyllysine By similarity
Cross-link10Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Natural variations

Natural variant901A → D in PEOA2. Ref.18
VAR_038814
Natural variant981L → P in PEOA2. Ref.14 Ref.19
VAR_022459
Natural variant1041D → G in PEOA2. Ref.15
Corresponds to variant rs28999114 [ dbSNP | Ensembl ].
VAR_022460
Natural variant1141A → P in PEOA2. Ref.13 Ref.19
VAR_012111
Natural variant1231A → D in hypertrophic cardiomyopathy; sporadic patient with mild myopathy, exercise intolerance and lactic acidosis but no ophthalmoplegia. Ref.17
VAR_038815
Natural variant2891V → M in PEOA2; also found in a sporadic case affected by PEO. Ref.13 Ref.16
VAR_012112

Experimental info

Sequence conflict161G → A in AAA61223. Ref.1
Sequence conflict147 – 1493KGA → RR in AAA61223. Ref.1
Sequence conflict2271V → L in AAA61223. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P12235 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: 59F0DFAEC4E7CFBB

FASTA29833,064
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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, IDENTIFICATION BY 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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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]"Complete loss of expression of the ANT1 gene causing cardiomyopathy and myopathy."
Echaniz-Laguna A., Chassagne M., Ceresuela J., Rouvet I., Padet S., Acquaviva C., Nataf S., Vinzio S., Bozon D., Mousson de Camaret B.
J. Med. Genet. 49:146-150(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN MTDPS12.
[13]"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.
[14]"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.
[15]"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.
[16]"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.
[17]"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.
[18]"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.
[19]"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.

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.
CCDSCCDS34114.1.
PIRA44778.
RefSeqNP_001142.2. NM_001151.3.
UniGeneHs.246506.

3D structure databases

ProteinModelPortalP12235.
SMRP12235. Positions 3-294.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106788. 24 interactions.
DIPDIP-33116N.
IntActP12235. 13 interactions.
MINTMINT-196037.
STRING9606.ENSP00000281456.

Chemistry

DrugBankDB00171. Adenosine triphosphate.
DB00720. Clodronate.
GuidetoPHARMACOLOGY1062.

Protein family/group databases

TCDB2.A.29.1.2. the mitochondrial carrier (mc) family.

PTM databases

PhosphoSiteP12235.

Polymorphism databases

DMDM113455.

Proteomic databases

MaxQBP12235.
PaxDbP12235.
PRIDEP12235.

Protocols and materials databases

DNASU291.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000281456; ENSP00000281456; ENSG00000151729.
GeneID291.
KEGGhsa:291.
UCSCuc003ixd.3. human.

Organism-specific databases

CTD291.
GeneCardsGC04P186064.
HGNCHGNC:10990. SLC25A4.
MIM103220. gene.
609283. phenotype.
615418. phenotype.
neXtProtNX_P12235.
Orphanet254892. Autosomal dominant progressive external ophthalmoplegia.
1369. Congenital cataract - hypertrophic cardiomyopathy - mitochondrial myopathy.
155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBPA35866.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG238123.
HOGENOMHOG000165727.
HOVERGENHBG108348.
InParanoidP12235.
KOK05863.
OMADCIVKIF.
OrthoDBEOG7T1RBR.
PhylomeDBP12235.
TreeFamTF300743.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
REACT_17015. Metabolism of proteins.

Gene expression databases

BgeeP12235.
CleanExHS_SLC25A4.
GenevestigatorP12235.

Family and domain databases

Gene3D1.50.40.10. 1 hit.
InterProIPR002113. Aden_trnslctor.
IPR002067. Mit_carrier.
IPR018108. Mitochondrial_sb/sol_carrier.
IPR023395. Mt_carrier_dom.
[Graphical view]
PfamPF00153. Mito_carr. 3 hits.
[Graphical view]
PRINTSPR00927. ADPTRNSLCASE.
PR00926. MITOCARRIER.
SUPFAMSSF103506. SSF103506. 1 hit.
PROSITEPS50920. SOLCAR. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSLC25A4.
GenomeRNAi291.
NextBio1187.
PROP12235.
SOURCESearch...

Entry information

Entry nameADT1_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 174 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM