SLC25A4
entrez
291
canonical
uniprot
P12235
canonical
ensembl
ENSG00000151729
resolver
ensp
ENSP00000281456
resolver
enst
ENST00000281456
resolver
genesymbol
SLC25A4
resolver
genesymbol_syn
AAC1
resolver
genesymbol_syn
ANT1
resolver
hgnc
HGNC:10990
resolver
uniprot
A0A0S2Z3H3
resolver
uniprot
D3DP59
resolver
uniprot_entry
A0A0S2Z3H3_HUMAN
resolver
uniprot_entry
ADT1_HUMAN
resolver
uniprot_sec
D3DP59
resolver
activity_regulation
ACTIVITY REGULATION: The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA) PubMed:23173940. The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR) (PubMed:21586654, PubMed:23173940). Proton transporter activity is inhibited by ADP:ATP antiporter activity (By similarity). {ECO:0000250|UniProtKB:G2QNH0, ECO:0000250|UniProtKB:P48962, ECO:0000269|PubMed:21586654}.
uniprot
proteins
amino_acid_sequence
MGDHAWSFLKDFLAGGVAAAVSKTAVAPIERVKLLLQVQHASKQISAEKQYKGIIDCVVRIPKEQGFLSFWRGNLANVIRYFPTQALNFAFKDKYKQLFLGGVDRHKQFWRYFAGNLASGGAAGATSLCFVYPLDFARTRLAADVGKGAAQREFHGLGDCIIKIFKSDGLRGLYQGFNVSVQGIIIYRAAYFGVYDTAKGMLPDPKNVHIFVSWMIAQSVTAVAGLVSYPFDTVRRRMMMQSGRKGADIMYTGTVDCWRKIAKDEGAKAFFKGAWSNVLRGMGGAFVLVLYDEIKKYV
uniprot
proteins
disease_involvement
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. {ECO:0000269|PubMed:10926541, ECO:0000269|PubMed:11756613, ECO:0000269|PubMed:12112115, ECO:0000269|PubMed:12707443, ECO:0000269|PubMed:15792871, ECO:0000269|PubMed:18575922, ECO:0000269|PubMed:21586654, ECO:0000269|PubMed:27693233}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Mitochondrial DNA depletion syndrome 12B, cardiomyopathic type (MTDPS12B) [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. {ECO:0000269|PubMed:16155110, ECO:0000269|PubMed:22187496, ECO:0000269|PubMed:25732997, ECO:0000269|PubMed:27693233}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Mitochondrial DNA depletion syndrome 12A, cardiomyopathic type (MTDPS12A) [MIM:617184]: An autosomal dominant mitochondrial disorder characterized by severe hypotonia due to mitochondrial dysfunction apparent at birth. Affected infants have respiratory insufficiency requiring mechanical ventilation and have poor or no motor development. Many die in infancy, and those that survive have profound hypotonia with significant muscle weakness and inability to walk independently. Some patients develop hypertrophic cardiomyopathy. Muscle samples show mtDNA depletion and severe combined mitochondrial respiratory chain deficiencies. {ECO:0000269|PubMed:27693233}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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, PubMed:23173940, PubMed:30046662). 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). Substrate exchange across the membrane occurs consecutively with one substrate being transported first, then dissociating from the substrate binding site before the second substrate binds for transport in the opposite direction (PubMed:37278158). 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). {ECO:0000250|UniProtKB:G2QNH0, ECO:0000250|UniProtKB:P48962, ECO:0000269|PubMed:21586654, ECO:0000269|PubMed:23173940, ECO:0000269|PubMed:27693233, ECO:0000269|PubMed:31883789, ECO:0000269|PubMed:37278158}.
uniprot
proteins
mass_dalton
33064
uniprot
proteins
post_translational_modification
PTM: Under cell death induction, transglutaminated by TGM2. Transglutamination leads to formation of covalent cross-links between a glutamine and the epsilon-amino group of a lysine residue, forming polymers. {ECO:0000250|UniProtKB:P48962}.
uniprot
proteins
protein_family
Mitochondrial carrier (TC 2.A.29) family
uniprot
proteins
pubmed
10926541
uniprot
proteins
pubmed
11756613
uniprot
proteins
pubmed
12112115
uniprot
proteins
pubmed
12707443
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15792871
uniprot
proteins
pubmed
16120388
uniprot
proteins
pubmed
16155110
uniprot
proteins
pubmed
18575922
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
20843780
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21586654
uniprot
proteins
pubmed
22187496
uniprot
proteins
pubmed
23173940
uniprot
proteins
pubmed
2541251
uniprot
proteins
pubmed
2547778
uniprot
proteins
pubmed
25732997
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
27641616
uniprot
proteins
pubmed
27693233
uniprot
proteins
pubmed
2823266
uniprot
proteins
pubmed
2829183
uniprot
proteins
pubmed
30046662
uniprot
proteins
pubmed
31883789
uniprot
proteins
pubmed
37278158
uniprot
proteins
sequence_length
298
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:21586654}; Multi-pass membrane protein {ECO:0000255}. Membrane {ECO:0000269|PubMed:27641616}; Multi-pass membrane protein {ECO:0000255}. Note=The complex formed with ARL2BP, ARL2 and SLC25A4/ANT1 is expressed in mitochondria (By similarity). May localize to non-mitochondrial membranes (PubMed:27641616). {ECO:0000250|UniProtKB:P48962, ECO:0000269|PubMed:27641616}.
uniprot
proteins
transmembrane_region
TRANSMEM 8..37; /note="Helical; Name=1"; /evidence="ECO:0000250|UniProtKB:P02722"; TRANSMEM 75..99; /note="Helical; Name=2"; /evidence="ECO:0000250|UniProtKB:P02722"; TRANSMEM 110..130; /note="Helical; Name=3"; /evidence="ECO:0000250|UniProtKB:P02722"; TRANSMEM 179..199; /note="Helical; Name=4"; /evidence="ECO:0000250|UniProtKB:P02722"; TRANSMEM 211..231; /note="Helical; Name=5"; /evidence="ECO:0000250|UniProtKB:P02722"; TRANSMEM 274..291; /note="Helical; Name=6"; /evidence="ECO:0000250|UniProtKB:P02722
uniprot
proteins