Search Results

Overview

Uniprot ID	P48962
Protein Name	ADP/ATP translocase 1
Gene Name	Slc25a4
Organism	Mus musculus

Kla Sites from experimental identification

Position	Flanking peptide
147	RLAADVGKGSSQREF
163	GLGDCLTKIFKSDGL
166	DCLTKIFKSDGLKGL
245	MMMQSGRKGADIMYT
263	DCWRKIAKDEGANAF
33	VAPIERVKLLLQVQH
43	LQVQHASKQISAEKQ
63	DCVVRIPKEQGFLSF
96	FAFKDKYKQIFLGGV

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)

Protein Sequence

10 MGDQALSFLK 20 DFLAGGIAAA 30 VSKTAVAPIE 40 RVKLLLQVQH 50 ASKQISAEKQ 60 YKGIIDCVVR 70 IPKEQGFLSF 80 WRGNLANVIR 90 YFPTQALNFA 100 FKDKYKQIFL 110 GGVDRHKQFW 120 RYFAGNLASG 130 GAAGATSLCF 140 VYPLDFARTR 150 LAADVGKGSS 160 QREFNGLGDC 170 LTKIFKSDGL 180 KGLYQGFSVS 190 VQGIIIYRAA 200 YFGVYDTAKG 210 MLPDPKNVHI 220 IVSWMIAQSV 230 TAVAGLVSYP 240 FDTVRRRMMM 250 QSGRKGADIM 260 YTGTLDCWRK 270 IAKDEGANAF 280 FKGAWSNVLR 290 GMGGAFVLVL YDEIKKYV

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0016020	membrane
Cellular Component	GO:0045121	membrane raft
Cellular Component	GO:0005743	mitochondrial inner membrane
Cellular Component	GO:0031966	mitochondrial membrane
Cellular Component	GO:0005741	mitochondrial outer membrane
Cellular Component	GO:0005757	mitochondrial permeability transition pore complex
Cellular Component	GO:0005739	mitochondrion
Cellular Component	GO:0043209	myelin sheath
Molecular Function	GO:0005524	ATP binding
Molecular Function	GO:0005471	ATP:ADP antiporter activity
Molecular Function	GO:0019899	enzyme binding
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:0008637	apoptotic mitochondrial changes
Biological Process	GO:0140021	mitochondrial ADP transmembrane transport
Biological Process	GO:1990544	mitochondrial ATP transmembrane transport
Biological Process	GO:0010667	negative regulation of cardiac muscle cell apoptotic process
Biological Process	GO:1902109	negative regulation of mitochondrial membrane permeability involved in apoptotic process
Biological Process	GO:0060546	negative regulation of necroptotic process
Biological Process	GO:0061051	positive regulation of cell growth involved in cardiac muscle cell development
Biological Process	GO:1901526	positive regulation of mitophagy
Biological Process	GO:2000277	positive regulation of oxidative phosphorylation uncoupler activity
Biological Process	GO:0046902	regulation of mitochondrial membrane permeability

Reference

[1] Chang J, Wu W, Qian P, Lu Z, He X et al.. Multi-omics study on the effect of moderate-intensity exercise on protein lactylation in mouse muscle tissue.. Front Cell Dev Biol 12:1472338. 2024. PMID: 39935788.

[2] Zhuo W, Zhang M, Tan J, Gao Y, Wang Y et al.. Lysine lactylation analysis of proteins in the heart of the Kawasaki disease mouse model.. Front Cell Dev Biol 13:1550220. 2025. PMID: 40114965.

[3] Wu D, Tang Y, Li X, Xiong S, Zhang Z et al.. Characterization of protein lactylation in healthy and ischemic mouse hearts.. Front Cardiovasc Med 12:1644886. 2025. PMID: 41089239.