ADP/ATP translocase 1

Details

Name
ADP/ATP translocase 1
Synonyms
  • AAC1
  • Adenine nucleotide translocator 1
  • ADP,ATP carrier protein 1
  • ADP,ATP carrier protein, heart/skeletal muscle isoform T1
  • ANT 1
  • ANT1
  • Solute carrier family 25 member 4
Gene Name
SLC25A4
UniProtKB Entry
P12235Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0010417|ADP/ATP translocase 1
MGDHAWSFLKDFLAGGVAAAVSKTAVAPIERVKLLLQVQHASKQISAEKQYKGIIDCVVR
IPKEQGFLSFWRGNLANVIRYFPTQALNFAFKDKYKQLFLGGVDRHKQFWRYFAGNLASG
GAAGATSLCFVYPLDFARTRLAADVGKGAAQREFHGLGDCIIKIFKSDGLRGLYQGFNVS
VQGIIIYRAAYFGVYDTAKGMLPDPKNVHIFVSWMIAQSVTAVAGLVSYPFDTVRRRMMM
QSGRKGADIMYTGTVDCWRKIAKDEGAKAFFKGAWSNVLRGMGGAFVLVLYDEIKKYV
Number of residues
298
Molecular Weight
33064.265
Theoretical pI
10.27
GO Classification
Functions
ATP / oxidative phosphorylation uncoupler activity / proton transmembrane transporter activity
Processes
adaptive thermogenesis / ADP transport / mitochondrial ADP transmembrane transport / mitochondrial ATP transmembrane transport / negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / positive regulation of mitophagy / regulation of mitochondrial membrane permeability
Components
membrane / mitochondrial membrane / mitochondrial permeability transition pore complex / plasma membrane
General Function
ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell (PubMed:21586654, PubMed:27693233). Cycles between the cytoplasmic-open state (c-state) and the matrix-open state (m-state): operates by the alternating access mechanism with a single substrate-binding site intermittently exposed to either the cytosolic (c-state) or matrix (m-state) side of the inner mitochondrial membrane (By similarity). In addition to its ADP:ATP antiporter activity, also involved in mitochondrial uncoupling and mitochondrial permeability transition pore (mPTP) activity (PubMed:31883789). Plays a role in mitochondrial uncoupling by acting as a proton transporter: proton transport uncouples the proton flows via the electron transport chain and ATP synthase to reduce the efficiency of ATP production and cause mitochondrial thermogenesis (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity, suggesting that SLC25A4/ANT1 acts as a master regulator of mitochondrial energy output by maintaining a delicate balance between ATP production (ADP:ATP antiporter activity) and thermogenesis (proton transporter activity) (By similarity). Proton transporter activity requires free fatty acids as cofactor, but does not transport it (By similarity). Also plays a key role in mPTP opening, a non-specific pore that enables free passage of the mitochondrial membranes to solutes of up to 1.5 kDa, and which contributes to cell death (PubMed:31883789). It is however unclear if SLC25A4/ANT1 constitutes a pore-forming component of mPTP or regulates it (By similarity). Acts as a regulator of mitophagy independently of ADP:ATP antiporter activity: promotes mitophagy via interaction with TIMM44, leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1 (By similarity)
Specific Function
Adenine transmembrane transporter activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
8-37 75-99 110-130 179-199 211-231 274-291
Cellular Location
Mitochondrion inner membrane
Gene sequence
>lcl|BSEQ0010418|ADP/ATP translocase 1 (SLC25A4)
ATGGGTGATCACGCTTGGAGCTTCCTAAAGGACTTCCTGGCCGGGGGCGTCGCCGCTGCC
GTCTCCAAGACCGCGGTCGCCCCCATCGAGAGGGTCAAACTGCTGCTGCAGGTCCAGCAT
GCCAGCAAACAGATCAGTGCTGAGAAGCAGTACAAAGGGATCATTGATTGTGTGGTGAGA
ATCCCTAAGGAGCAGGGCTTCCTCTCCTTCTGGAGGGGTAACCTGGCCAACGTGATCCGT
TACTTCCCCACCCAAGCTCTCAACTTCGCCTTCAAGGACAAGTACAAGCAGCTCTTCTTA
GGGGGTGTGGATCGGCATAAGCAGTTCTGGCGCTACTTTGCTGGTAACCTGGCGTCCGGT
GGGGCCGCTGGGGCCACCTCCCTTTGCTTTGTCTACCCGCTGGACTTTGCTAGGACCAGG
TTGGCTGCTGATGTGGGCAAGGGCGCCGCCCAGCGTGAGTTCCATGGTCTGGGCGACTGT
ATCATCAAGATCTTCAAGTCTGATGGCCTGAGGGGGCTCTACCAGGGTTTCAACGTCTCT
GTCCAAGGCATCATTATCTATAGAGCTGCCTACTTCGGAGTCTATGATACTGCCAAGGGG
ATGCTGCCTGACCCCAAGAACGTGCACATTTTTGTGAGCTGGATGATTGCCCAGAGTGTG
ACGGCAGTCGCAGGGCTGGTGTCCTACCCCTTTGACACTGTTCGTCGTAGAATGATGATG
CAGTCCGGCCGGAAAGGGGCCGATATTATGTACACGGGGACAGTTGACTGCTGGAGGAAG
ATTGCAAAAGACGAAGGAGCCAAGGCCTTCTTCAAAGGTGCCTGGTCCAATGTGCTGAGA
GGCATGGGCGGTGCTTTTGTATTGGTGTTGTATGATGAGATCAAAAAATATGTCTAA
Chromosome Location
4
Locus
4q35.1
External Identifiers
ResourceLink
UniProtKB IDP12235
UniProtKB Entry NameADT1_HUMAN
GenBank Protein ID339920
GenBank Gene IDJ02966
GeneCard IDSLC25A4
GenAtlas IDSLC25A4
HGNC IDHGNC:10990
KEGG IDhsa:291
NCBI Gene ID291
General References
  1. Neckelmann N, Li K, Wade RP, Shuster R, Wallace DC: 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. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7580-4. [Article]
  2. Cozens AL, Runswick MJ, Walker JE: DNA sequences of two expressed nuclear genes for human mitochondrial ADP/ATP translocase. J Mol Biol. 1989 Mar 20;206(2):261-80. [Article]
  3. Li K, Warner CK, Hodge JA, Minoshima S, Kudoh J, Fukuyama R, Maekawa M, Shimizu Y, Shimizu N, Wallace DC: A human muscle adenine nucleotide translocator gene has four exons, is located on chromosome 4, and is differentially expressed. J Biol Chem. 1989 Aug 25;264(24):13998-4004. [Article]
  4. Wang W, Shen P, Thiyagarajan S, Lin S, Palm C, Horvath R, Klopstock T, Cutler D, Pique L, Schrijver I, Davis RW, Mindrinos M, Speed TP, Scharfe C: Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing. Nucleic Acids Res. 2011 Jan;39(1):44-58. doi: 10.1093/nar/gkq750. Epub 2010 Sep 15. [Article]
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  6. Houldsworth J, Attardi G: Two distinct genes for ADP/ATP translocase are expressed at the mRNA level in adult human liver. Proc Natl Acad Sci U S A. 1988 Jan;85(2):377-81. [Article]
  7. Deniaud A, Brenner C, Kroemer G: Mitochondrial membrane permeabilization by HIV-1 Vpr. Mitochondrion. 2004 Jul;4(2-3):223-33. [Article]
  8. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [Article]
  9. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  10. Echaniz-Laguna A, Chassagne M, Ceresuela J, Rouvet I, Padet S, Acquaviva C, Nataf S, Vinzio S, Bozon D, Mousson de Camaret B: Complete loss of expression of the ANT1 gene causing cardiomyopathy and myopathy. J Med Genet. 2012 Feb;49(2):146-50. doi: 10.1136/jmedgenet-2011-100504. Epub 2011 Dec 20. [Article]
  11. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
  12. Kaukonen J, Juselius JK, Tiranti V, Kyttala A, Zeviani M, Comi GP, Keranen S, Peltonen L, Suomalainen A: Role of adenine nucleotide translocator 1 in mtDNA maintenance. Science. 2000 Aug 4;289(5480):782-5. [Article]
  13. Napoli L, Bordoni A, Zeviani M, Hadjigeorgiou GM, Sciacco M, Tiranti V, Terentiou A, Moggio M, Papadimitriou A, Scarlato G, Comi GP: A novel missense adenine nucleotide translocator-1 gene mutation in a Greek adPEO family. Neurology. 2001 Dec 26;57(12):2295-8. [Article]
  14. Komaki H, Fukazawa T, Houzen H, Yoshida K, Nonaka I, Goto Y: A novel D104G mutation in the adenine nucleotide translocator 1 gene in autosomal dominant progressive external ophthalmoplegia patients with mitochondrial DNA with multiple deletions. Ann Neurol. 2002 May;51(5):645-8. [Article]
  15. Agostino A, Valletta L, Chinnery PF, Ferrari G, Carrara F, Taylor RW, Schaefer AM, Turnbull DM, Tiranti V, Zeviani M: Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO). Neurology. 2003 Apr 22;60(8):1354-6. [Article]
  16. 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: Complete loss-of-function of the heart/muscle-specific adenine nucleotide translocator is associated with mitochondrial myopathy and cardiomyopathy. Hum Mol Genet. 2005 Oct 15;14(20):3079-88. Epub 2005 Sep 9. [Article]
  17. Deschauer M, Hudson G, Muller T, Taylor RW, Chinnery PF, Zierz S: A novel ANT1 gene mutation with probable germline mosaicism in autosomal dominant progressive external ophthalmoplegia. Neuromuscul Disord. 2005 Apr;15(4):311-5. Epub 2005 Jan 28. [Article]
  18. Virgilio R, Ronchi D, Hadjigeorgiou GM, Bordoni A, Saladino F, Moggio M, Adobbati L, Kafetsouli D, Tsironi E, Previtali S, Papadimitriou A, Bresolin N, Comi GP: Novel Twinkle (PEO1) gene mutations in mendelian progressive external ophthalmoplegia. J Neurol. 2008 Sep;255(9):1384-91. doi: 10.1007/s00415-008-0926-3. Epub 2008 Jun 30. [Article]

Associated Data

Bio-Entities
Bio-EntityType
ADP/ATP translocase 1 (Humans)protein
primary
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
ATPinvestigational, nutraceuticalunknowntargetDetails
Clodronic acidapproved, investigational, vet_approvedyestargetinhibitorDetails
CarboxyatractylosideexperimentalunknowntargetDetails
Tetrastearoyl cardiolipinexperimentalunknowntargetDetails
Di-Stearoyl-3-Sn-PhosphatidylcholineexperimentalyestargetinhibitorDetails
[3-(Dodecanoylamino)Propyl](Hydroxy)DimethylammoniumexperimentalunknowntargetDetails
Etidronic acidapprovedunknowntargetinhibitorDetails