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Details on Person UniProt:P12235 SLC25A4
| Class:Id | ReferenceGeneProduct:49742 |
|---|---|
| _chainChangeLog | initiator methionine:1 added on Fri February 6 2015;chain:2-298 added on Fri February 6 2015;initiator methionine:1 for 49742 removed on Fri Nov 03 2023;initiator methionine: for 49742 added on Fri Nov 03 2023;initiator methionine: for 49742 removed on Fri Aug 15 2025;initiator methionine:1 for 49742 added on Fri Aug 15 2025 |
| _displayName | UniProt:P12235 SLC25A4 |
| _timestamp | 2026-02-20 21:36:50 |
| chain | initiator methionine:1 chain:2-298 |
| checksum | 59F0DFAEC4E7CFBB |
| comment | 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).CATALYTIC ACTIVITY ADP(in) + ATP(out) = ADP(out) + ATP(in)CATALYTIC ACTIVITY H(+)(in) = H(+)(out)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).BIOPHYSICOCHEMICAL PROPERTIES Monomer (By similarity). Found in a complex with ARL2, ARL2BP and SLC25A4/ANT1 (By similarity). Interacts with ARL2BP (By similarity). Interacts with ARHGAP11B, thereby inhibiting the mitochondrial permeability transition pore (mPTP) (PubMed:31883789). Interacts with TIMM44; leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1 (By similarity).SUBUNIT (Microbial infection) Interacts with HIV-1 Vpr.INTERACTION The complex formed with ARL2BP, ARL2 and SLC25A4/ANT1 is expressed in mitochondria (By similarity). May localize to non-mitochondrial membranes (PubMed:27641616).TISSUE SPECIFICITY Expressed in erythrocytes (at protein level).DOMAIN 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.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.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the mitochondrial carrier (TC 2.A.29) family. |
| description | recommendedName: fullName evidence="27"ADP/ATP translocase 1 alternativeName: fullName evidence="3"ADP,ATP carrier protein 1 alternativeName: fullName evidence="24"ADP,ATP carrier protein, heart/skeletal muscle isoform T1 alternativeName: fullName evidence="26"Adenine nucleotide translocator 1 shortName evidence="26"ANT 1 alternativeName: fullName evidence="27"Solute carrier family 25 member 4 |
| geneName | SLC25A4 AAC1 ANT1 |
| identifier | P12235 |
| isSequenceChanged | FALSE |
| keyword | Acetylation Antiport ATP-binding Cardiomyopathy Direct protein sequencing Disease variant Host-virus interaction Membrane Methylation Mitochondrion Mitochondrion inner membrane Nucleotide-binding Phosphoprotein Primary mitochondrial disease Progressive external ophthalmoplegia Proteomics identification Reference proteome Repeat S-nitrosylation Transmembrane Transmembrane helix Transport |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | SLC25A4 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8994037] ENSEMBL:ENSG00000151729 SLC25A4 [Homo sapiens] |
| secondaryIdentifier | ADT1_HUMAN D3DP59 |
| sequenceLength | 298 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:49741] AAC1 [mitochondrial inner membrane] [Homo sapiens] [EntityWithAccessionedSequence:1267975] SLC25A4 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:1267984] SLC25A4 [mitochondrial intermembrane space] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:P12235 SLC25A4 (49742)
