TCDB is operated by the Saier Lab Bioinformatics Group
« See all members of the family


2.A.29.1.2
Mitochondrial ADP/ATP carrier 1 (AAC1); ADP/ATP translocase 1; adenine nucleotide translocator 1 (ANT1); adPEO, Sengers syndrome (SLC25A4).  Valine 181 is critical for the nucleotide exchange activity (De Marcos Lousa et al. 2005). Mice have three ANTs, and if all three are knocked out, the mitochondrial permeability transition pore (MPTP) can not form, although with only two eliminated, it still can, suggesting the an ANT is an essential constituent of the MPTP  (Karch et al. 2019). Upon protein kinase C (PKC) inactivation, the cytoprotective compound, bisindolylpyrrole, can induce prolonged transient MPTP, causing apoptosis in a cyclophilin D (CypD)-dependent manner through the VDAC1/2-regulated ANT-associated pore (Koushi et al. 2020). ANT1 mediates H+ transport, but only in the presence of long-chain fatty acids (FA), as already known for UCPs. It depends on FA chain length and saturation, implying that FA transport is confined to the lipid-protein interface. Purine nucleotides with the preference for ATP and ADP inhibited H+ transport, as do inhibitors of ATP/ADP transport, carboxyatractyloside or bongkrekic acid (Kreiter et al. 2021).

Accession Number:P12235
Protein Name:Mitochondrial ADP/ATP carrier 1 (AAC1) aka ADP/ATP translocase 1 aka adenine nucleotide translocator 1 (ANT1) aka adPEO, Sengers syndrome (SLC25A4)
Length:298
Molecular Weight:33064.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:6
Location1 / Topology2 / Orientation3: Mitochondrion inner membrane1 / Multi-pass membrane protein2
Substrate ATP, ADP

Cross database links:

Genevestigator: P12235 P12235 P12235
eggNOG: prNOG12573 NOG238123 NOG238123
HEGENOM: HBG610399 HOG000165727 HOG000165727
RefSeq: NP_001142.2   
Entrez Gene ID: 291   
Pfam: PF00153   
Drugbank: Drugbank Link   
OMIM: 103220  gene
609283  phenotype
KEGG: hsa:291    hsa:291    hsa:291   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0005743 C:mitochondrial inner membrane
GO:0015207 F:adenine transmembrane transporter activity
GO:0005515 F:protein binding
GO:0006091 P:generation of precursor metabolites and energy
GO:0044419 P:interspecies interaction between organisms
GO:0000002 P:mitochondrial genome maintenance
GO:0060547 P:negative regulation of necrotic cell death
GO:0055085 P:transmembrane transport
GO:0006112 P:energy reserve metabolic process
GO:0050796 P:regulation of insulin secretion
GO:0044281 P:small molecule metabolic process
GO:0016032 P:viral reproduction
GO:0005741 C:mitochondrial outer membrane
GO:0005471 F:ATP:ADP antiporter activity
GO:0015866 P:ADP transport
GO:0015867 P:ATP transport
GO:0051935 P:glutamate uptake involved in synaptic transmission

References (48)

[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.et.al.   2823266
[2] “DNA sequences of two expressed nuclear genes for human mitochondrial ADP/ATP translocase.”  Cozens A.L.et.al.   2541251
[3] “A human muscle adenine nucleotide translocator gene has four exons, is located on chromosome 4, and is differentially expressed.”  Li K.et.al.   2547778
[4] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[5] “Two distinct genes for ADP/ATP translocase are expressed at the mRNA level in adult human liver.”  Houldsworth J.et.al.   2829183
[6] “Mitochondrial membrane permeabilization by HIV-1 Vpr.”  Deniaud A.et.al.   16120388
[7] “Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer.”  Rikova K.et.al.   18083107
[8] “Lysine acetylation targets protein complexes and co-regulates major cellular functions.”  Choudhary C.et.al.   19608861
[9] “Role of adenine nucleotide translocator 1 in mtDNA maintenance.”  Kaukonen J.et.al.   10926541
[10] “A novel missense adenine nucleotide translocator-1 gene mutation in a Greek adPEO family.”  Napoli L.et.al.   11756613
[11] “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.et.al.   12112115
[12] “Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO).”  Agostino A.et.al.   12707443
[13] “Complete loss-of-function of the heart/muscle-specific adenine nucleotide translocator is associated with mitochondrial myopathy and cardiomyopathy.”  Palmieri L.et.al.   16155110
[14] “A novel ANT1 gene mutation with probable germline mosaicism in autosomal dominant progressive external ophthalmoplegia.”  Deschauer M.et.al.   15792871
[15] “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.et.al.   2823266
[16] “DNA sequences of two expressed nuclear genes for human mitochondrial ADP/ATP translocase.”  Cozens A.L.et.al.   2541251
[17] “A human muscle adenine nucleotide translocator gene has four exons, is located on chromosome 4, and is differentially expressed.”  Li K.et.al.   2547778
[18] “Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing.”  Wang W.et.al.   20843780
[19] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[20] “Two distinct genes for ADP/ATP translocase are expressed at the mRNA level in adult human liver.”  Houldsworth J.et.al.   2829183
[21] “Mitochondrial membrane permeabilization by HIV-1 Vpr.”  Deniaud A.et.al.   16120388
[22] “Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer.”  Rikova K.et.al.   18083107
[23] “Lysine acetylation targets protein complexes and co-regulates major cellular functions.”  Choudhary C.et.al.   19608861
[24] “Initial characterization of the human central proteome.”  Burkard T.R.et.al.   21269460
[25] “Role of adenine nucleotide translocator 1 in mtDNA maintenance.”  Kaukonen J.et.al.   10926541
[26] “A novel missense adenine nucleotide translocator-1 gene mutation in a Greek adPEO family.”  Napoli L.et.al.   11756613
[27] “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.et.al.   12112115
[28] “Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO).”  Agostino A.et.al.   12707443
[29] “Complete loss-of-function of the heart/muscle-specific adenine nucleotide translocator is associated with mitochondrial myopathy and cardiomyopathy.”  Palmieri L.et.al.   16155110
[30] “A novel ANT1 gene mutation with probable germline mosaicism in autosomal dominant progressive external ophthalmoplegia.”  Deschauer M.et.al.   15792871
[31] “Novel Twinkle (PEO1) gene mutations in mendelian progressive external ophthalmoplegia.”  Virgilio R.et.al.   18575922
[32] “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.et.al.   2823266
[33] “DNA sequences of two expressed nuclear genes for human mitochondrial ADP/ATP translocase.”  Cozens A.L.et.al.   2541251
[34] “A human muscle adenine nucleotide translocator gene has four exons, is located on chromosome 4, and is differentially expressed.”  Li K.et.al.   2547778
[35] “Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing.”  Wang W.et.al.   20843780
[36] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[37] “Two distinct genes for ADP/ATP translocase are expressed at the mRNA level in adult human liver.”  Houldsworth J.et.al.   2829183
[38] “Mitochondrial membrane permeabilization by HIV-1 Vpr.”  Deniaud A.et.al.   16120388
[39] “Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer.”  Rikova K.et.al.   18083107
[40] “Lysine acetylation targets protein complexes and co-regulates major cellular functions.”  Choudhary C.et.al.   19608861
[41] “Initial characterization of the human central proteome.”  Burkard T.R.et.al.   21269460
[42] “Role of adenine nucleotide translocator 1 in mtDNA maintenance.”  Kaukonen J.et.al.   10926541
[43] “A novel missense adenine nucleotide translocator-1 gene mutation in a Greek adPEO family.”  Napoli L.et.al.   11756613
[44] “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.et.al.   12112115
[45] “Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO).”  Agostino A.et.al.   12707443
[46] “Complete loss-of-function of the heart/muscle-specific adenine nucleotide translocator is associated with mitochondrial myopathy and cardiomyopathy.”  Palmieri L.et.al.   16155110
[47] “A novel ANT1 gene mutation with probable germline mosaicism in autosomal dominant progressive external ophthalmoplegia.”  Deschauer M.et.al.   15792871
[48] “Novel Twinkle (PEO1) gene mutations in mendelian progressive external ophthalmoplegia.”  Virgilio R.et.al.   18575922
Structure:
1okc     

External Searches:

  • Search: DB with
  • BLAST ExPASy (Swiss Institute of Bioinformatics (SIB) BLAST)
  • CDD Search (Conserved Domain Database)
  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

Analyze:

Predict TMSs (Predict number of transmembrane segments)
Window Size: Angle:  
FASTA formatted sequence
1:	MGDHAWSFLK DFLAGGVAAA VSKTAVAPIE RVKLLLQVQH ASKQISAEKQ YKGIIDCVVR 
61:	IPKEQGFLSF WRGNLANVIR YFPTQALNFA FKDKYKQLFL GGVDRHKQFW RYFAGNLASG 
121:	GAAGATSLCF VYPLDFARTR LAADVGKGAA QREFHGLGDC IIKIFKSDGL RGLYQGFNVS 
181:	VQGIIIYRAA YFGVYDTAKG MLPDPKNVHI FVSWMIAQSV TAVAGLVSYP FDTVRRRMMM 
241:	QSGRKGADIM YTGTVDCWRK IAKDEGAKAF FKGAWSNVLR GMGGAFVLVL YDEIKKYV