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Overview

Uniprot IDQ9H0C2
Protein NameADP/ATP translocase 4
Gene NameSLC25A31
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
35 GVAAAVSKTAVAPIE

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) (PubMed:15670820). 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). Specifically required during spermatogenesis, probably to mediate ADP:ATP exchange in spermatocytes (PubMed:17137571). Large ATP supplies from mitochondria may be critical for normal progression of spermatogenesis during early stages of meiotic prophase I, including DNA double-strand break repair and chromosomal synapsis (By similarity). In addition to its ADP:ATP antiporter activity, also involved in mitochondrial uncoupling and mitochondrial permeability transition pore (mPTP) activity (By similarity). 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 SLC25A31/ANT4 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). Among nucleotides, may also exchange ADP for dATP and dADP (PubMed:15670820). 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 (By similarity). It is however unclear if SLC25A31/ANT4 constitutes a pore-forming component of mPTP or regulates it (By similarity)

Protein Sequence

10 MHREPAKKKA 20 EKRLFDASSF 30 GKDLLAGGVA 40 AAVSKTAVAP 50 IERVKLLLQV 60 QASSKQISPE 70 ARYKGMVDCL 80 VRIPREQGFF 90 SFWRGNLANV 100 IRYFPTQALN 110 FAFKDKYKQL 120 FMSGVNKEKQ 130 FWRWFLANLA 140 SGGAAGATSL 150 CVVYPLDFAR 160 TRLGVDIGKG 170 PEERQFKGLG 180 DCIMKIAKSD 190 GIAGLYQGFG 200 VSVQGIIVYR 210 ASYFGAYDTV 220 KGLLPKPKKT 230 PFLVSFFIAQ 240 VVTTCSGILS 250 YPFDTVRRRM 260 MMQSGEAKRQ 270 YKGTLDCFVK 280 IYQHEGISSF 290 FRGAFSNVLR 300 GTGGALVLVL 310 YDKIKEFFHI DIGGR

Gene Ontology

Classification GO ID Description
Cellular Component GO:0016020 membrane
Biological Process GO:0007283 spermatogenesis
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
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0005471 ATP:ADP antiporter activity
Biological Process GO:0030154 cell differentiation
Biological Process GO:0007141 male meiosis I
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] 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.