Search Results
Overview
| Uniprot ID | P12235 |
|---|---|
| Protein Name | ADP/ATP translocase 1 |
| Gene Name | SLC25A4 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 147 | RLAADVGKGAAQREF |
| 163 | GLGDCIIKIFKSDGL |
| 166 | DCIIKIFKSDGLRGL |
| 23 | GVAAAVSKTAVAPIE |
| 263 | DCWRKIAKDEGAKAF |
| 272 | EGAKAFFKGAWSNVL |
| 43 | LQVQHASKQISAEKQ |
| 96 | FAFKDKYKQLFLGGV |
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)
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Cellular Component | GO:0016020 | membrane |
| Cellular Component | GO:0005743 | mitochondrial inner membrane |
| Cellular Component | GO:0031966 | mitochondrial membrane |
| Cellular Component | GO:0005757 | mitochondrial permeability transition pore complex |
| Cellular Component | GO:0005739 | mitochondrion |
| Cellular Component | GO:0005886 | plasma membrane |
| Molecular Function | GO:0015207 | adenine transmembrane transporter activity |
| Molecular Function | GO:0005524 | ATP binding |
| Molecular Function | GO:0005471 | ATP:ADP antiporter activity |
| Molecular Function | GO:0017077 | oxidative phosphorylation uncoupler activity |
| Molecular Function | GO:0015078 | proton transmembrane transporter activity |
| Biological Process | GO:1990845 | adaptive thermogenesis |
| Biological Process | GO:0015866 | ADP transport |
| Biological Process | GO:0006091 | generation of precursor metabolites and energy |
| Biological Process | GO:0140021 | mitochondrial ADP transmembrane transport |
| Biological Process | GO:1990544 | mitochondrial ATP transmembrane transport |
| Biological Process | GO:0060546 | negative regulation of necroptotic process |
| Biological Process | GO:1901526 | positive regulation of mitophagy |
| Biological Process | GO:0046902 | regulation of mitochondrial membrane permeability |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.
[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.
[3] Yang YH, Wang QC, Kong J, Yang JT, Liu JF. Global profiling of lysine lactylation in human lungs.. Proteomics 23(15):e2200437. 2023 Aug. PMID: 37170646.
[4] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.
[5] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.