P12236 · ADT3_HUMAN
- ProteinADP/ATP translocase 3
- GeneSLC25A6
- 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 (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).
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).
Miscellaneous
The gene coding for this protein is located in the pseudoautosomal region 1 (PAR1) of X and Y chromosomes and escapes X-inactivation.
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). 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 (By similarity).
Proton transporter activity is inhibited by ADP:ATP antiporter activity (By similarity).
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | membrane | |
Cellular Component | mitochondrial inner membrane | |
Cellular Component | mitochondrion | |
Cellular Component | nucleus | |
Cellular Component | TIM23 mitochondrial import inner membrane translocase complex | |
Molecular Function | ATP:ADP antiporter activity | |
Biological Process | apoptotic process | |
Biological Process | mitochondrial ADP transmembrane transport | |
Biological Process | mitochondrial ATP transmembrane transport | |
Biological Process | negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway |
Keywords
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameADP/ATP translocase 3
- Alternative names
- Cleaved into 1 chains
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP12236
- 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 SLC25A6/ANT3 is expressed in mitochondria (By similarity).
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 | 1-7 | Mitochondrial intermembrane | ||||
Sequence: MTEQAIS | ||||||
Transmembrane | 8-37 | Helical; Name=1 | ||||
Sequence: FAKDFLAGGIAAAISKTAVAPIERVKLLLQ | ||||||
Topological domain | 38-74 | Mitochondrial matrix | ||||
Sequence: VQHASKQIAADKQYKGIVDCIVRIPKEQGVLSFWRGN | ||||||
Transmembrane | 75-99 | Helical; Name=2 | ||||
Sequence: LANVIRYFPTQALNFAFKDKYKQIF | ||||||
Topological domain | 100-109 | Mitochondrial intermembrane | ||||
Sequence: LGGVDKHTQF | ||||||
Transmembrane | 110-130 | Helical; Name=3 | ||||
Sequence: WRYFAGNLASGGAAGATSLCF | ||||||
Topological domain | 131-178 | Mitochondrial matrix | ||||
Sequence: VYPLDFARTRLAADVGKSGTEREFRGLGDCLVKITKSDGIRGLYQGFS | ||||||
Transmembrane | 179-199 | Helical; Name=4 | ||||
Sequence: VSVQGIIIYRAAYFGVYDTAK | ||||||
Topological domain | 200-210 | Mitochondrial intermembrane | ||||
Sequence: GMLPDPKNTHI | ||||||
Transmembrane | 211-231 | Helical; Name=5 | ||||
Sequence: VVSWMIAQTVTAVAGVVSYPF | ||||||
Topological domain | 232-273 | Mitochondrial matrix | ||||
Sequence: DTVRRRMMMQSGRKGADIMYTGTVDCWRKIFRDEGGKAFFKG | ||||||
Transmembrane | 274-291 | Helical; Name=6 | ||||
Sequence: AWSNVLRGMGGAFVLVLY | ||||||
Topological domain | 292-298 | Mitochondrial intermembrane | ||||
Sequence: DELKKVI |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_054819 | 242 | ||||
Sequence: S → F |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 363 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed; alternate | ||||
Sequence: M | |||||||
Modified residue | 1 | UniProt | N-acetylmethionine | ||||
Sequence: M | |||||||
Chain | PRO_0000425781 | 1-298 | UniProt | ADP/ATP translocase 3 | |||
Sequence: MTEQAISFAKDFLAGGIAAAISKTAVAPIERVKLLLQVQHASKQIAADKQYKGIVDCIVRIPKEQGVLSFWRGNLANVIRYFPTQALNFAFKDKYKQIFLGGVDKHTQFWRYFAGNLASGGAAGATSLCFVYPLDFARTRLAADVGKSGTEREFRGLGDCLVKITKSDGIRGLYQGFSVSVQGIIIYRAAYFGVYDTAKGMLPDPKNTHIVVSWMIAQTVTAVAGVVSYPFDTVRRRMMMQSGRKGADIMYTGTVDCWRKIFRDEGGKAFFKGAWSNVLRGMGGAFVLVLYDELKKVI | |||||||
Modified residue | 2 | UniProt | N-acetylthreonine; in ADP/ATP translocase 3, N-terminally processed | ||||
Sequence: T | |||||||
Chain | PRO_0000090584 | 2-298 | UniProt | ADP/ATP translocase 3, N-terminally processed | |||
Sequence: TEQAISFAKDFLAGGIAAAISKTAVAPIERVKLLLQVQHASKQIAADKQYKGIVDCIVRIPKEQGVLSFWRGNLANVIRYFPTQALNFAFKDKYKQIFLGGVDKHTQFWRYFAGNLASGGAAGATSLCFVYPLDFARTRLAADVGKSGTEREFRGLGDCLVKITKSDGIRGLYQGFSVSVQGIIIYRAAYFGVYDTAKGMLPDPKNTHIVVSWMIAQTVTAVAGVVSYPFDTVRRRMMMQSGRKGADIMYTGTVDCWRKIFRDEGGKAFFKGAWSNVLRGMGGAFVLVLYDELKKVI | |||||||
Modified residue (large scale data) | 22 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 42 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 52 | UniProt | N6,N6,N6-trimethyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 81 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 105 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 148 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 191 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 195 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 268 | UniProt | N6-acetyllysine | ||||
Sequence: K |
Post-translational modification
Trimethylated by ANTKMT at Lys-52.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in erythrocytes (at protein level).
Gene expression databases
Organism-specific databases
Interaction
Subunit
Monomer (By similarity).
Found in a complex with ARL2, ARL2BP and SLC25A6/ANT3 (By similarity).
Found in a complex with ARL2, ARL2BP and SLC25A6/ANT3 (By similarity).
(Microbial infection) Interacts with influenza A virus PB1-F2 protein.
(Microbial infection) Interacts with HIV-1 Vpr.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P12236 | AP2B1 P63010 | 4 | EBI-356254, EBI-432924 | |
BINARY | P12236 | KRT31 Q15323 | 3 | EBI-356254, EBI-948001 | |
BINARY | P12236 | LRRK2 Q5S007 | 2 | EBI-356254, EBI-5323863 | |
BINARY | P12236 | LZTS2 Q9BRK4 | 3 | EBI-356254, EBI-741037 | |
BINARY | P12236 | MID2 Q9UJV3-2 | 3 | EBI-356254, EBI-10172526 | |
BINARY | P12236 | MTUS2 Q5JR59 | 4 | EBI-356254, EBI-742948 | |
BINARY | P12236 | NOTCH2NLA Q7Z3S9 | 3 | EBI-356254, EBI-945833 | |
XENO | P12236 | PB1 P0C0U1 | 5 | EBI-356254, EBI-12579807 | |
BINARY | P12236 | TEKT4 Q8WW24 | 3 | EBI-356254, EBI-750487 | |
BINARY | P12236 | TRAF1 Q13077 | 3 | EBI-356254, EBI-359224 | |
BINARY | P12236 | TRIM23 P36406 | 3 | EBI-356254, EBI-740098 | |
BINARY | P12236 | TRIP6 Q15654 | 3 | EBI-356254, EBI-742327 | |
BINARY | P12236 | VDAC1 P21796 | 4 | EBI-356254, EBI-354158 |
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: ISFAKDFLAGGIAAAISKTAVAPIERVKLLLQVQHASKQIAADKQYKGIVDCIVRIPKEQGVLSFWRGNLANVIRYFPTQALNFAFKDKYKQI | ||||||
Repeat | 111-201 | Solcar 2 | ||||
Sequence: RYFAGNLASGGAAGATSLCFVYPLDFARTRLAADVGKSGTEREFRGLGDCLVKITKSDGIRGLYQGFSVSVQGIIIYRAAYFGVYDTAKGM | ||||||
Repeat | 212-297 | Solcar 3 | ||||
Sequence: VSWMIAQTVTAVAGVVSYPFDTVRRRMMMQSGRKGADIMYTGTVDCWRKIFRDEGGKAFFKGAWSNVLRGMGGAFVLVLYDELKKV | ||||||
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)32,866
- Last updated2007-01-23 v4
- Checksum18534E9F0E49672F
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 105-108 | in Ref. 5; AAA36750 | ||||
Sequence: KHTQ → RHA |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY007135 EMBL· GenBank· DDBJ | AAG01998.1 EMBL· GenBank· DDBJ | mRNA | ||
BC007295 EMBL· GenBank· DDBJ | AAH07295.1 EMBL· GenBank· DDBJ | mRNA | ||
BC007850 EMBL· GenBank· DDBJ | AAH07850.1 EMBL· GenBank· DDBJ | mRNA | ||
BC008737 EMBL· GenBank· DDBJ | AAH08737.1 EMBL· GenBank· DDBJ | mRNA | ||
BC008935 EMBL· GenBank· DDBJ | AAH08935.1 EMBL· GenBank· DDBJ | mRNA | ||
BC014775 EMBL· GenBank· DDBJ | AAH14775.1 EMBL· GenBank· DDBJ | mRNA | ||
BC031912 EMBL· GenBank· DDBJ | AAH31912.1 EMBL· GenBank· DDBJ | mRNA | ||
J03592 EMBL· GenBank· DDBJ | AAA36750.1 EMBL· GenBank· DDBJ | mRNA |