P48962 · ADT1_MOUSE
- ProteinADP/ATP translocase 1
- GeneSlc25a4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids298 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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).
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).
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: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).
Catalytic activity
- ADP(in) + ATP(out) = ADP(out) + ATP(in)
- H+(in) = H+(out)
Activity regulation
The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA) (By similarity).
The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR) (By similarity).
Proton transporter activity is inhibited by ADP:ATP antiporter activity (PubMed:31341297).
The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR) (By similarity).
Proton transporter activity is inhibited by ADP:ATP antiporter activity (PubMed:31341297).
Features
Showing features for binding site.
GO annotations
Keywords
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameADP/ATP translocase 1
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP48962
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Mitochondrion inner membrane ; Multi-pass membrane protein
Membrane ; Multi-pass membrane protein
Note: The complex formed with ARL2BP, ARL2 and SLC25A4/ANT1 is expressed in mitochondria (PubMed:11809823).
May localize to non-mitochondrial membranes (By similarity).
May localize to non-mitochondrial membranes (By similarity).
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 2-7 | Mitochondrial intermembrane | ||||
Sequence: GDQALS | ||||||
Transmembrane | 8-37 | Helical; Name=1 | ||||
Sequence: FLKDFLAGGIAAAVSKTAVAPIERVKLLLQ | ||||||
Topological domain | 38-74 | Mitochondrial matrix | ||||
Sequence: VQHASKQISAEKQYKGIIDCVVRIPKEQGFLSFWRGN | ||||||
Transmembrane | 75-99 | Helical; Name=2 | ||||
Sequence: LANVIRYFPTQALNFAFKDKYKQIF | ||||||
Topological domain | 100-109 | Mitochondrial intermembrane | ||||
Sequence: LGGVDRHKQF | ||||||
Transmembrane | 110-130 | Helical; Name=3 | ||||
Sequence: WRYFAGNLASGGAAGATSLCF | ||||||
Topological domain | 131-178 | Mitochondrial matrix | ||||
Sequence: VYPLDFARTRLAADVGKGSSQREFNGLGDCLTKIFKSDGLKGLYQGFS | ||||||
Transmembrane | 179-199 | Helical; Name=4 | ||||
Sequence: VSVQGIIIYRAAYFGVYDTAK | ||||||
Topological domain | 200-210 | Mitochondrial intermembrane | ||||
Sequence: GMLPDPKNVHI | ||||||
Transmembrane | 211-231 | Helical; Name=5 | ||||
Sequence: IVSWMIAQSVTAVAGLVSYPF | ||||||
Topological domain | 232-273 | Mitochondrial matrix | ||||
Sequence: DTVRRRMMMQSGRKGADIMYTGTLDCWRKIAKDEGANAFFKG | ||||||
Transmembrane | 274-291 | Helical; Name=6 | ||||
Sequence: AWSNVLRGMGGAFVLVLY | ||||||
Topological domain | 292-298 | Mitochondrial intermembrane | ||||
Sequence: DEIKKYV |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Mice display mitochondrial myopathy affecting heart and skeletal muscles (PubMed:9207786).
Hindlimb muscles exhibit abundant ragged-red fibers, characteristic of mitochondrial myopathies (PubMed:9207786).
Increased mitochondrial activity is observed, reflecting greater mitochondrial content (PubMed:9207786).
In addition, mice are exercise intolerant (PubMed:9207786).
Mice develop chronic progressive external ophthalmoplegia, but show normal ocular motility (PubMed:16303948).
In retina, while abnormalities are observed in extraocular muscles, retinal structure and function are not affected normal (PubMed:20671283).
Cells display impaired mitochondrial uncoupling (PubMed:31341297).
Cells show impaired autophagy, leading to accumulation of aberrant mitochondria (PubMed:31618756).
Mice lacking Slc25a4/Ant1 and Slc25a5/Ant2 in liver still have mitochondrial permeability transition pore (mPTP) activity, although more Ca2+ is required to activate the mPTP (PubMed:14749836).
Deletion of Slc25a4/Ant1, Slc25a5/Ant2 and Slc25a31/Ant4 in liver completely inhibits mPTP (PubMed:31489369).
Mice lacking Slc25a4/Ant1, Slc25a5/Ant2, Slc25a31/Ant4 and Ppif lack Ca2+-induced mPTP formation (PubMed:31489369).
Hindlimb muscles exhibit abundant ragged-red fibers, characteristic of mitochondrial myopathies (PubMed:9207786).
Increased mitochondrial activity is observed, reflecting greater mitochondrial content (PubMed:9207786).
In addition, mice are exercise intolerant (PubMed:9207786).
Mice develop chronic progressive external ophthalmoplegia, but show normal ocular motility (PubMed:16303948).
In retina, while abnormalities are observed in extraocular muscles, retinal structure and function are not affected normal (PubMed:20671283).
Cells display impaired mitochondrial uncoupling (PubMed:31341297).
Cells show impaired autophagy, leading to accumulation of aberrant mitochondria (PubMed:31618756).
Mice lacking Slc25a4/Ant1 and Slc25a5/Ant2 in liver still have mitochondrial permeability transition pore (mPTP) activity, although more Ca2+ is required to activate the mPTP (PubMed:14749836).
Deletion of Slc25a4/Ant1, Slc25a5/Ant2 and Slc25a31/Ant4 in liver completely inhibits mPTP (PubMed:31489369).
Mice lacking Slc25a4/Ant1, Slc25a5/Ant2, Slc25a31/Ant4 and Ppif lack Ca2+-induced mPTP formation (PubMed:31489369).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 43 | Abolished ADP:ATP antiporter activity without affecting ability to regulate mitophagy; when associated with E-244. | ||||
Sequence: K → E | ||||||
Mutagenesis | 90 | Abolished ability to regulate mitophagy. | ||||
Sequence: A → D | ||||||
Mutagenesis | 123 | Abolished ability to regulate mitophagy. | ||||
Sequence: A → D | ||||||
Mutagenesis | 146-147 | Abolished interaction with TIMM4, thereby abolishing ability to regulate mitophagy. | ||||
Sequence: GK → ED | ||||||
Mutagenesis | 244 | Abolished ADP:ATP antiporter activity without affecting ability to regulate mitophagy; when associated with E-43. | ||||
Sequence: R → E |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 12 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylglycine | ||||
Sequence: G | ||||||
Chain | PRO_0000090575 | 2-298 | ADP/ATP translocase 1 | |||
Sequence: GDQALSFLKDFLAGGIAAAVSKTAVAPIERVKLLLQVQHASKQISAEKQYKGIIDCVVRIPKEQGFLSFWRGNLANVIRYFPTQALNFAFKDKYKQIFLGGVDRHKQFWRYFAGNLASGGAAGATSLCFVYPLDFARTRLAADVGKGSSQREFNGLGDCLTKIFKSDGLKGLYQGFSVSVQGIIIYRAAYFGVYDTAKGMLPDPKNVHIIVSWMIAQSVTAVAGLVSYPFDTVRRRMMMQSGRKGADIMYTGTLDCWRKIAKDEGANAFFKGAWSNVLRGMGGAFVLVLYDEIKKYV | ||||||
Modified residue | 7 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 52 | N6,N6,N6-trimethyllysine | ||||
Sequence: K | ||||||
Modified residue | 147 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 149 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 150 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 160 | S-nitrosocysteine | ||||
Sequence: C | ||||||
Modified residue | 245 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 272 | N6-succinyllysine | ||||
Sequence: K |
Post-translational modification
Under cell death induction, transglutaminated by TGM2 (PubMed:19644512).
Transglutamination leads to formation of covalent cross-links between a glutamine and the epsilon-amino group of a lysine residue, forming polymers (PubMed:19644512).
Transglutamination leads to formation of covalent cross-links between a glutamine and the epsilon-amino group of a lysine residue, forming polymers (PubMed:19644512).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in heart, skeletal muscle and brain.
Gene expression databases
Interaction
Subunit
Monomer (By similarity).
Found in a complex with ARL2, ARL2BP and SLC25A4/ANT1 (PubMed:11809823).
Interacts with ARL2BP (PubMed:11809823).
Interacts with TIMM44; leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1 (PubMed:31618756).
Found in a complex with ARL2, ARL2BP and SLC25A4/ANT1 (PubMed:11809823).
Interacts with ARL2BP (PubMed:11809823).
Interacts with TIMM44; leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1 (PubMed:31618756).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for repeat, region, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Repeat | 6-98 | Solcar 1 | ||||
Sequence: LSFLKDFLAGGIAAAVSKTAVAPIERVKLLLQVQHASKQISAEKQYKGIIDCVVRIPKEQGFLSFWRGNLANVIRYFPTQALNFAFKDKYKQI | ||||||
Repeat | 111-201 | Solcar 2 | ||||
Sequence: RYFAGNLASGGAAGATSLCFVYPLDFARTRLAADVGKGSSQREFNGLGDCLTKIFKSDGLKGLYQGFSVSVQGIIIYRAAYFGVYDTAKGM | ||||||
Repeat | 212-297 | Solcar 3 | ||||
Sequence: VSWMIAQSVTAVAGLVSYPFDTVRRRMMMQSGRKGADIMYTGTLDCWRKIAKDEGANAFFKGAWSNVLRGMGGAFVLVLYDEIKKY | ||||||
Region | 235-240 | Important for transport activity | ||||
Sequence: RRRMMM | ||||||
Motif | 235-240 | Nucleotide carrier signature motif | ||||
Sequence: RRRMMM |
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.
Sequence similarities
Belongs to the mitochondrial carrier (TC 2.A.29) family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length298
- Mass (Da)32,904
- Last updated2007-01-23 v4
- Checksum3A849FEAB0981462
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 136 | in Ref. 1; AAC52837 | ||||
Sequence: F → L |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U27315 EMBL· GenBank· DDBJ | AAC52837.1 EMBL· GenBank· DDBJ | mRNA | ||
X74510 EMBL· GenBank· DDBJ | CAA52616.1 EMBL· GenBank· DDBJ | mRNA | ||
AF240002 EMBL· GenBank· DDBJ | AAF64470.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC003791 EMBL· GenBank· DDBJ | AAH03791.1 EMBL· GenBank· DDBJ | mRNA | ||
BC026925 EMBL· GenBank· DDBJ | AAH26925.1 EMBL· GenBank· DDBJ | mRNA |