UniProtKB - P05141 (ADT2_HUMAN)
ADP/ATP translocase 2
SLC25A5
Functioni
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 (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 SLC25A5/ANT2 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).
Probably mediates mitochondrial uncoupling in tissues that do not express UCP1 (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:31883789).
It is however unclear if SLC25A5/ANT2 constitutes a pore-forming component of mPTP or regulates it (By similarity).
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 (By similarity).
As part of the mitotic spindle-associated MMXD complex it may play a role in chromosome segregation (PubMed:20797633).
By similarity2 PublicationsCatalytic activityi
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 80 | ADPBy similarity | 1 | |
Binding sitei | 92 | ADPBy similarity | 1 | |
Binding sitei | 235 | ADPBy similarity | 1 |
GO - Molecular functioni
- adenine nucleotide transmembrane transporter activity Source: UniProtKB
- adenine transmembrane transporter activity Source: ProtInc
- ATP:ADP antiporter activity Source: UniProtKB
- oxidative phosphorylation uncoupler activity Source: UniProtKB
- proton transmembrane transporter activity Source: Ensembl
- RNA binding Source: UniProtKB
- ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
GO - Biological processi
- adaptive thermogenesis Source: UniProtKB
- adenine nucleotide transport Source: UniProtKB
- B cell differentiation Source: UniProtKB
- cellular response to leukemia inhibitory factor Source: Ensembl
- chromosome segregation Source: UniProtKB-KW
- erythrocyte differentiation Source: UniProtKB
- mitochondrial ADP transmembrane transport Source: UniProtKB
- mitochondrial ATP transmembrane transport Source: UniProtKB
- negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway Source: UniProtKB
- positive regulation of cell population proliferation Source: UniProtKB
- positive regulation of mitophagy Source: UniProtKB
- regulation of mitochondrial membrane permeability Source: UniProtKB
Keywordsi
Biological process | Antiport, Chromosome partition, Host-virus interaction, Transport |
Enzyme and pathway databases
PathwayCommonsi | P05141 |
Reactomei | R-HSA-180897, Vpr-mediated induction of apoptosis by mitochondrial outer membrane permeabilization R-HSA-83936, Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane |
SignaLinki | P05141 |
Protein family/group databases
TCDBi | 2.A.29.1.1, the mitochondrial carrier (mc) family |
Names & Taxonomyi
Protein namesi | Recommended name: ADP/ATP translocase 2CuratedAlternative name(s): ADP,ATP carrier protein 21 Publication ADP,ATP carrier protein, fibroblast isoform1 Publication Adenine nucleotide translocator 21 Publication Short name: ANT 2 Solute carrier family 25 member 5Curated Cleaved into the following chain: |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:10991, SLC25A5 |
MIMi | 300150, gene |
neXtProti | NX_P05141 |
VEuPathDBi | HostDB:ENSG00000005022 |
Subcellular locationi
Mitochondrion
- Mitochondrion inner membrane By similarity; Multi-pass membrane protein Sequence analysis
Other locations
- Membrane 1 Publication; Multi-pass membrane protein Sequence analysis
Note: May localize to non-mitochondrial membranes.1 Publication
Cytoskeleton
- MMXD complex Source: UniProtKB
Mitochondrion
- mitochondrial inner membrane Source: Reactome
- mitochondrial nucleoid Source: BHF-UCL
- mitochondrial permeability transition pore complex Source: UniProtKB
- mitochondrion Source: HPA
Nucleus
- nucleus Source: UniProtKB
Plasma Membrane
- integral component of plasma membrane Source: ProtInc
Other locations
- membrane Source: UniProtKB
- membrane raft Source: Ensembl
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 7 | Mitochondrial intermembraneCurated | 7 | |
Transmembranei | 8 – 37 | Helical; Name=1By similarityAdd BLAST | 30 | |
Topological domaini | 38 – 74 | Mitochondrial matrixCuratedAdd BLAST | 37 | |
Transmembranei | 75 – 99 | Helical; Name=2By similarityAdd BLAST | 25 | |
Topological domaini | 100 – 109 | Mitochondrial intermembraneCurated | 10 | |
Transmembranei | 110 – 130 | Helical; Name=3By similarityAdd BLAST | 21 | |
Topological domaini | 131 – 178 | Mitochondrial matrixCuratedAdd BLAST | 48 | |
Transmembranei | 179 – 199 | Helical; Name=4By similarityAdd BLAST | 21 | |
Topological domaini | 200 – 210 | Mitochondrial intermembraneCuratedAdd BLAST | 11 | |
Transmembranei | 211 – 231 | Helical; Name=5By similarityAdd BLAST | 21 | |
Topological domaini | 232 – 273 | Mitochondrial matrixCuratedAdd BLAST | 42 | |
Transmembranei | 274 – 291 | Helical; Name=6By similarityAdd BLAST | 18 | |
Topological domaini | 292 – 298 | Mitochondrial intermembraneCurated | 7 |
Keywords - Cellular componenti
Membrane, Mitochondrion, Mitochondrion inner membranePathology & Biotechi
Organism-specific databases
DisGeNETi | 292 |
OpenTargetsi | ENSG00000005022 |
PharmGKBi | PA35867 |
Miscellaneous databases
Pharosi | P05141, Tchem |
Chemistry databases
ChEMBLi | CHEMBL3709670 |
DrugBanki | DB00720, Clodronic acid DB01077, Etidronic acid |
DrugCentrali | P05141 |
Genetic variation databases
BioMutai | SLC25A5 |
DMDMi | 317373597 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000423220 | 1 – 298 | ADP/ATP translocase 2Add BLAST | 298 | |
Initiator methioninei | Removed; alternateCombined sources2 Publications | |||
ChainiPRO_0000090579 | 2 – 298 | ADP/ATP translocase 2, N-terminally processedAdd BLAST | 297 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineCombined sources | 1 | |
Modified residuei | 2 | N-acetylthreonine; in ADP/ATP translocase 2, N-terminally processedCombined sources2 Publications | 1 | |
Modified residuei | 7 | PhosphoserineBy similarity | 1 | |
Modified residuei | 23 | N6-malonyllysine1 Publication | 1 | |
Modified residuei | 43 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 52 | N6,N6,N6-trimethyllysine; alternateCombined sources1 Publication | 1 | |
Modified residuei | 52 | N6,N6-dimethyllysine; alternate1 Publication | 1 | |
Modified residuei | 52 | N6-methyllysine; alternate1 Publication | 1 | |
Modified residuei | 92 | N6-malonyllysine1 Publication | 1 | |
Modified residuei | 96 | N6-malonyllysine1 Publication | 1 | |
Modified residuei | 105 | N6-acetyllysine; alternateCombined sources | 1 | |
Modified residuei | 105 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 147 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 147 | N6-malonyllysine; alternate1 Publication | 1 | |
Modified residuei | 147 | N6-methyllysine; alternateCombined sources | 1 | |
Modified residuei | 147 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 163 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 166 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 268 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 268 | N6-succinyllysine; alternateBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Methylation, PhosphoproteinProteomic databases
EPDi | P05141 |
jPOSTi | P05141 |
MassIVEi | P05141 |
MaxQBi | P05141 |
PaxDbi | P05141 |
PeptideAtlasi | P05141 |
PRIDEi | P05141 |
ProteomicsDBi | 51804 |
TopDownProteomicsi | P05141 |
PTM databases
GlyGeni | P05141, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P05141 |
MetOSitei | P05141 |
PhosphoSitePlusi | P05141 |
SwissPalmi | P05141 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000005022, Expressed in cortex of kidney and 248 other tissues |
Genevisiblei | P05141, HS |
Organism-specific databases
HPAi | ENSG00000005022, Low tissue specificity |
Interactioni
Subunit structurei
Monomer (By similarity).
Component of the MMXD complex, which includes CIAO1, ERCC2, CIAO2B, MMS19 and SLC25A5/ANT2 (PubMed:20797633).
Interacts with AK4 (PubMed:19130895).
Interacts with ARHGAP11B, thereby inhibiting the mitochondrial permeability transition pore (mPTP) (PubMed:31883789).
Interacts with TIMM44; leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1 (By similarity).
By similarity3 Publications(Microbial infection) Interacts with HIV-1 Vpr.
1 PublicationBinary interactionsi
P05141
With | #Exp. | IntAct |
---|---|---|
ADCK2 [Q7Z695] | 4 | EBI-355133,EBI-21505425 |
LRRK2 [Q5S007] | 2 | EBI-355133,EBI-5323863 |
SIRT4 [Q9Y6E7] | 2 | EBI-355133,EBI-2606540 |
SLC35F6 [Q8N357] | 2 | EBI-355133,EBI-713484 |
GO - Molecular functioni
- ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
Protein-protein interaction databases
BioGRIDi | 106789, 314 interactors |
CORUMi | P05141 |
DIPi | DIP-33873N |
IntActi | P05141, 184 interactors |
MINTi | P05141 |
STRINGi | 9606.ENSP00000360671 |
Miscellaneous databases
RNActi | P05141, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 6 – 98 | Solcar 1Add BLAST | 93 | |
Repeati | 111 – 201 | Solcar 2Add BLAST | 91 | |
Repeati | 212 – 297 | Solcar 3Add BLAST | 86 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 235 – 240 | Important for transport activityBy similarity | 6 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 235 – 240 | Nucleotide carrier signature motifBy similarity | 6 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Repeat, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0749, Eukaryota |
GeneTreei | ENSGT00940000154400 |
HOGENOMi | CLU_015166_12_0_1 |
InParanoidi | P05141 |
OMAi | GYGKWLA |
OrthoDBi | 870903at2759 |
PhylomeDBi | P05141 |
TreeFami | TF300743 |
Family and domain databases
Gene3Di | 1.50.40.10, 1 hit |
InterProi | View protein in InterPro IPR002113, ADT_euk_type IPR002067, Mit_carrier IPR018108, Mitochondrial_sb/sol_carrier IPR023395, Mt_carrier_dom_sf |
PANTHERi | PTHR45635, PTHR45635, 1 hit |
Pfami | View protein in Pfam PF00153, Mito_carr, 3 hits |
PRINTSi | PR00927, ADPTRNSLCASE PR00926, MITOCARRIER |
SUPFAMi | SSF103506, SSF103506, 1 hit |
PROSITEi | View protein in PROSITE PS50920, SOLCAR, 3 hits |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MTDAAVSFAK DFLAGGVAAA ISKTAVAPIE RVKLLLQVQH ASKQITADKQ
60 70 80 90 100
YKGIIDCVVR IPKEQGVLSF WRGNLANVIR YFPTQALNFA FKDKYKQIFL
110 120 130 140 150
GGVDKRTQFW LYFAGNLASG GAAGATSLCF VYPLDFARTR LAADVGKAGA
160 170 180 190 200
EREFRGLGDC LVKIYKSDGI KGLYQGFNVS VQGIIIYRAA YFGIYDTAKG
210 220 230 240 250
MLPDPKNTHI VISWMIAQTV TAVAGLTSYP FDTVRRRMMM QSGRKGTDIM
260 270 280 290
YTGTLDCWRK IARDEGGKAF FKGAWSNVLR GMGGAFVLVL YDEIKKYT
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 6 | V → L in AAA35579 (PubMed:3031073).Curated | 1 | |
Sequence conflicti | 43 | K → M in BAG37698 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 66 | G → E in AAA35579 (PubMed:3031073).Curated | 1 | |
Sequence conflicti | 162 | V → G in AAA36749 (PubMed:2829183).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_030039 | 111 | L → R4 PublicationsCorresponds to variant dbSNP:rs371749Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M57424 Genomic DNA Translation: AAA51737.1 J02683 mRNA Translation: AAA35579.1 L78810 Genomic DNA Translation: AAB39266.1 AK315292 mRNA Translation: BAG37698.1 AC004000 Genomic DNA Translation: AAB96347.1 BC056160 mRNA Translation: AAH56160.1 J03591 mRNA Translation: AAA36749.1 |
CCDSi | CCDS14578.1 |
PIRi | A29132 |
RefSeqi | NP_001143.2, NM_001152.4 |
Genome annotation databases
Ensembli | ENST00000317881.9; ENSP00000360671.4; ENSG00000005022.6 |
GeneIDi | 292 |
KEGGi | hsa:292 |
MANE-Selecti | ENST00000317881.9; ENSP00000360671.4; NM_001152.5; NP_001143.2 |
UCSCi | uc004erh.5, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M57424 Genomic DNA Translation: AAA51737.1 J02683 mRNA Translation: AAA35579.1 L78810 Genomic DNA Translation: AAB39266.1 AK315292 mRNA Translation: BAG37698.1 AC004000 Genomic DNA Translation: AAB96347.1 BC056160 mRNA Translation: AAH56160.1 J03591 mRNA Translation: AAA36749.1 |
CCDSi | CCDS14578.1 |
PIRi | A29132 |
RefSeqi | NP_001143.2, NM_001152.4 |
3D structure databases
AlphaFoldDBi | P05141 |
SMRi | P05141 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 106789, 314 interactors |
CORUMi | P05141 |
DIPi | DIP-33873N |
IntActi | P05141, 184 interactors |
MINTi | P05141 |
STRINGi | 9606.ENSP00000360671 |
Chemistry databases
ChEMBLi | CHEMBL3709670 |
DrugBanki | DB00720, Clodronic acid DB01077, Etidronic acid |
DrugCentrali | P05141 |
Protein family/group databases
TCDBi | 2.A.29.1.1, the mitochondrial carrier (mc) family |
PTM databases
GlyGeni | P05141, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P05141 |
MetOSitei | P05141 |
PhosphoSitePlusi | P05141 |
SwissPalmi | P05141 |
Genetic variation databases
BioMutai | SLC25A5 |
DMDMi | 317373597 |
Proteomic databases
EPDi | P05141 |
jPOSTi | P05141 |
MassIVEi | P05141 |
MaxQBi | P05141 |
PaxDbi | P05141 |
PeptideAtlasi | P05141 |
PRIDEi | P05141 |
ProteomicsDBi | 51804 |
TopDownProteomicsi | P05141 |
Protocols and materials databases
Antibodypediai | 29785, 106 antibodies from 24 providers |
DNASUi | 292 |
Genome annotation databases
Ensembli | ENST00000317881.9; ENSP00000360671.4; ENSG00000005022.6 |
GeneIDi | 292 |
KEGGi | hsa:292 |
MANE-Selecti | ENST00000317881.9; ENSP00000360671.4; NM_001152.5; NP_001143.2 |
UCSCi | uc004erh.5, human |
Organism-specific databases
CTDi | 292 |
DisGeNETi | 292 |
GeneCardsi | SLC25A5 |
HGNCi | HGNC:10991, SLC25A5 |
HPAi | ENSG00000005022, Low tissue specificity |
MIMi | 300150, gene |
neXtProti | NX_P05141 |
OpenTargetsi | ENSG00000005022 |
PharmGKBi | PA35867 |
VEuPathDBi | HostDB:ENSG00000005022 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0749, Eukaryota |
GeneTreei | ENSGT00940000154400 |
HOGENOMi | CLU_015166_12_0_1 |
InParanoidi | P05141 |
OMAi | GYGKWLA |
OrthoDBi | 870903at2759 |
PhylomeDBi | P05141 |
TreeFami | TF300743 |
Enzyme and pathway databases
PathwayCommonsi | P05141 |
Reactomei | R-HSA-180897, Vpr-mediated induction of apoptosis by mitochondrial outer membrane permeabilization R-HSA-83936, Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane |
SignaLinki | P05141 |
Miscellaneous databases
BioGRID-ORCSi | 292, 180 hits in 704 CRISPR screens |
ChiTaRSi | SLC25A5, human |
GenomeRNAii | 292 |
Pharosi | P05141, Tchem |
PROi | PR:P05141 |
RNActi | P05141, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000005022, Expressed in cortex of kidney and 248 other tissues |
Genevisiblei | P05141, HS |
Family and domain databases
Gene3Di | 1.50.40.10, 1 hit |
InterProi | View protein in InterPro IPR002113, ADT_euk_type IPR002067, Mit_carrier IPR018108, Mitochondrial_sb/sol_carrier IPR023395, Mt_carrier_dom_sf |
PANTHERi | PTHR45635, PTHR45635, 1 hit |
Pfami | View protein in Pfam PF00153, Mito_carr, 3 hits |
PRINTSi | PR00927, ADPTRNSLCASE PR00926, MITOCARRIER |
SUPFAMi | SSF103506, SSF103506, 1 hit |
PROSITEi | View protein in PROSITE PS50920, SOLCAR, 3 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | ADT2_HUMAN | |
Accessioni | P05141Primary (citable) accession number: P05141 Secondary accession number(s): B2RCV1, O43350 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 13, 1987 |
Last sequence update: | January 11, 2011 | |
Last modified: | May 25, 2022 | |
This is version 234 of the entry and version 7 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- Human chromosome X
Human chromosome X: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families