Slc25a4
entrez
11739
canonical
uniprot
P48962
canonical
ensembl
ENSMUSG00000031633
resolver
ensp
ENSMUSP00000034049
resolver
enst
ENSMUST00000034049
resolver
genesymbol
Slc25a4
resolver
genesymbol_syn
Aac1
resolver
genesymbol_syn
Anc1
resolver
genesymbol_syn
Ant1
resolver
uniprot
Q62164
resolver
uniprot_entry
ADT1_MOUSE
resolver
uniprot_sec
Q62164
resolver
activity_regulation
ACTIVITY REGULATION: The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA) (By similarity). The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR) (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity (PubMed:31341297). {ECO:0000250|UniProtKB:G2QNH0, ECO:0000269|PubMed:31341297}.
uniprot
proteins
amino_acid_sequence
MGDQALSFLKDFLAGGIAAAVSKTAVAPIERVKLLLQVQHASKQISAEKQYKGIIDCVVRIPKEQGFLSFWRGNLANVIRYFPTQALNFAFKDKYKQIFLGGVDRHKQFWRYFAGNLASGGAAGATSLCFVYPLDFARTRLAADVGKGSSQREFNGLGDCLTKIFKSDGLKGLYQGFSVSVQGIIIYRAAYFGVYDTAKGMLPDPKNVHIIVSWMIAQSVTAVAGLVSYPFDTVRRRMMMQSGRKGADIMYTGTLDCWRKIAKDEGANAFFKGAWSNVLRGMGGAFVLVLYDEIKKYV
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:31341297, PubMed:31618756). 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 (By similarity) In addition to its ADP:ATP antiporter activity, also involved in mitochondrial uncoupling and mitochondrial permeability transition pore (mPTP) activity (PubMed:31341297, PubMed:31489369). 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 (PubMed:31341297). 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) (PubMed:31341297). Proton transporter activity requires free fatty acids as cofactor, but does not transport it (PubMed:31341297). Probably mediates mitochondrial uncoupling in tissues that do not express UCP1 (PubMed:31341297). 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:31489369). It is however unclear if SLC25A4/ANT1 constitutes a pore-forming component of mPTP or regulates it (PubMed:31489369). 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 (PubMed:31618756). {ECO:0000250|UniProtKB:G2QNH0, ECO:0000250|UniProtKB:P12235, ECO:0000269|PubMed:31341297, ECO:0000269|PubMed:31489369, ECO:0000269|PubMed:31618756}.
uniprot
proteins
mass_dalton
32904
uniprot
proteins
mutagenesis
MUTAGEN 43; /note="K->E: Abolished ADP:ATP antiporter activity without affecting ability to regulate mitophagy; when associated with E-244."; /evidence="ECO:0000269|PubMed:31618756"; MUTAGEN 90; /note="A->D: Abolished ability to regulate mitophagy."; /evidence="ECO:0000269|PubMed:31618756"; MUTAGEN 123; /note="A->D: Abolished ability to regulate mitophagy."; /evidence="ECO:0000269|PubMed:31618756"; MUTAGEN 146..147; /note="GK->ED: Abolished interaction with TIMM4, thereby abolishing ability to regulate mitophagy."; /evidence="ECO:0000269|PubMed:31618756"; MUTAGEN 244; /note="R->E: Abolished ADP:ATP antiporter activity without affecting ability to regulate mitophagy; when associated with E-43."; /evidence="ECO:0000269|PubMed:31618756
uniprot
proteins
post_translational_modification
PTM: Under cell death induction, transglutaminated by TGM2 (PubMed:19644512). Transglutamination leads to formation of covalent cross-links between a glutamine and the epsilon-amino group of a lysine residue, forming polymers (PubMed:19644512). {ECO:0000269|PubMed:19644512}.
uniprot
proteins
protein_family
Mitochondrial carrier (TC 2.A.29) family
uniprot
proteins
pubmed
10974536
uniprot
proteins
pubmed
11809823
uniprot
proteins
pubmed
14749836
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16303948
uniprot
proteins
pubmed
18034455
uniprot
proteins
pubmed
19644512
uniprot
proteins
pubmed
20671283
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
23806337
uniprot
proteins
pubmed
31341297
uniprot
proteins
pubmed
31489369
uniprot
proteins
pubmed
31618756
uniprot
proteins
pubmed
8903724
uniprot
proteins
pubmed
9207786
uniprot
proteins
sequence_length
298
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000305|PubMed:19644512}; Multi-pass membrane protein {ECO:0000255}. Membrane {ECO:0000250|UniProtKB:P12235}; Multi-pass membrane protein {ECO:0000255}. Note=The complex formed with ARL2BP, ARL2 and SLC25A4/ANT1 is expressed in mitochondria (PubMed:11809823). May localize to non-mitochondrial membranes (By similarity). {ECO:0000250|UniProtKB:P12235, ECO:0000269|PubMed:11809823}.
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