Search Results

Overview

Uniprot ID	P12236
Protein Name	ADP/ATP translocase 3
Gene Name	SLC25A6
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
105	IFLGGVDKHTQFWRY
147	RLAADVGKSGTEREF
163	GLGDCLVKITKSDGI
166	DCLVKITKSDGIRGL
199	FGVYDTAKGMLPDPK
23	GIAAAISKTAVAPIE
272	EGGKAFFKGAWSNVL
43	LQVQHASKQIAADKQ
63	DCIVRIPKEQGVLSF
92	QALNFAFKDKYKQIF
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 (By similarity). 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). In addition to its ADP:ATP antiporter activity, also involved in mitochondrial uncoupling and mitochondrial permeability transition pore (mPTP) activity (PubMed:15033708). 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 SLC25A6/ANT3 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:15033708). It is however unclear if SLC25A6/ANT3 constitutes a pore-forming component of mPTP or regulates it (By similarity)

Protein Sequence

10 MTEQAISFAK 20 DFLAGGIAAA 30 ISKTAVAPIE 40 RVKLLLQVQH 50 ASKQIAADKQ 60 YKGIVDCIVR 70 IPKEQGVLSF 80 WRGNLANVIR 90 YFPTQALNFA 100 FKDKYKQIFL 110 GGVDKHTQFW 120 RYFAGNLASG 130 GAAGATSLCF 140 VYPLDFARTR 150 LAADVGKSGT 160 EREFRGLGDC 170 LVKITKSDGI 180 RGLYQGFSVS 190 VQGIIIYRAA 200 YFGVYDTAKG 210 MLPDPKNTHI 220 VVSWMIAQTV 230 TAVAGVVSYP 240 FDTVRRRMMM 250 QSGRKGADIM 260 YTGTVDCWRK 270 IFRDEGGKAF 280 FKGAWSNVLR 290 GMGGAFVLVL YDELKKVI

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0016020	membrane
Cellular Component	GO:0005743	mitochondrial inner membrane
Cellular Component	GO:0005757	mitochondrial permeability transition pore complex
Cellular Component	GO:0005739	mitochondrion
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0005744	TIM23 mitochondrial import inner membrane translocase complex
Molecular Function	GO:0005524	ATP binding
Molecular Function	GO:0005471	ATP:ADP antiporter activity
Biological Process	GO:0006915	apoptotic process
Biological Process	GO:0140021	mitochondrial ADP transmembrane transport
Biological Process	GO:1990544	mitochondrial ATP transmembrane transport
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] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[5] 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.

[6] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[7] 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.