P12235 (ADT1_HUMAN)
Reviewed,
UniProtKB/Swiss-Prot
Last modified
August 10, 2010.
Version 132.
History...
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 |
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| 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 | |
| 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
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
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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: 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. 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
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 |
| ||||||||
| 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. | ||||||||
Relevant documents
| Human chromosome 4 Human chromosome 4: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


