Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
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Curator-judged ISS transfer from the well-characterised paralogue SLC25A4 (P51881), the source of the core ADP/ATP antiporter molecular function, inner-membrane location and adenine-nucleotide transport processes for SLC25A5.
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The same ISS transfer also supplies the secondary uncoupling, permeability transition pore and mitophagy-related annotations; these are by-similarity assertions from the paralogue rather than direct evidence for ANT2.
Annotation inferences using phylogenetic trees
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PAN-GO/GO_Central phylogenetically-inferred (IBA) annotations, which correctly propagate the ADP/ATP antiporter activity, mitochondrial inner-membrane location and ATP transport process across the deeply conserved ANT clade.
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
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Ensembl Compara orthology projection from the mouse orthologue, the source of the secondary proton-transport/uncoupling, permeability transition pore, mitophagy, thermogenesis and differentiation annotations; all are By-similarity and are treated as non-core here.
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
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Inter-ontology logical inference propagated "adenine transport" from an upstream "adenine transmembrane transporter activity" assertion. ANT2 exchanges ADP for ATP, i.e. adenine nucleotides, not free adenine, so this inferred term carries the wrong substrate.
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
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Combined multi-method IEA pipeline; for SLC25A5 it converges on the core ADP/ATP antiporter activity, mitochondrial inner-membrane location and mitochondrial ADP and ATP transport processes, in agreement with the manual and phylogenetic evidence.
Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase.
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ANT2 and ANT3 were recovered by mass spectrometry as SIRT4 co-immunoprecipitating proteins, the source of the SIRT4-SLC25A5 interaction record.
"Mass spectrometry analysis of proteins that coimmunoprecipitate with SIRT4 identified insulindegrading enzyme and the ADP/ATP carrier proteins, ANT2 and ANT3."
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The study's focus is SIRT4 and insulin secretion; the ANT2 association is an interaction data point and supports only an uninformative protein-binding assignment for SLC25A5.
"These observations define a new role for mitochondrial SIRT4 in the regulation of insulin secretion."
The layered structure of human mitochondrial DNA nucleoids.
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Formaldehyde cross-linking distinguished core nucleoid proteins in direct contact with mtDNA from metabolic proteins merely co-purifying with native nucleoids; ANT2's presence in the native preparation is therefore association, not nucleoid membership.
"Several other metabolic proteins and chaperones identified in native nucleoids, including ATAD3, were not observed to cross-link to mtDNA."
Capsaicin binds to prohibitin 2 and displaces it from the mitochondria to the nucleus.
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The cached record is abstract-only. The abstract reports identification of prohibitin 2 as the capsaicin target and its displacement from the mitochondria to the nucleus, and does not mention ANT2 or any nucleotide-transport assay; the full text was not available for this review, so the nucleotide-transport activity attributed to this reference could not be verified from the cached record.
"We show that capsaicin binds to prohibitin (PHB) 2, which is normally localized to the inner mitochondrial membrane, and induces its translocation to the nucleus."
Enzymatically inactive adenylate kinase 4 interacts with mitochondrial ADP/ATP translocase.
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Proteomic and co-precipitation experiments showed that the mitochondrial ADP/ATP translocases interact with adenylate kinase 4, a physiologically plausible adenine-nucleotide-handling partner.
"Proteomic studies revealed that the mitochondrial ADP/ATP translocases (ANTs) interacted with AK4 and higher amount of ANT was co-precipitated with AK4 when cells were exposed to H(2)O(2) treatment."
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The authors propose that the ANT interaction underlies the cytoprotective effect of AK4 under stress; the evidence nevertheless supports only protein binding as a molecular function for ANT2.
"It is likely that the interaction with the mitochondrial inner membrane protein ANT is important for AK4 to exert the protective benefits to cells under stress."
Identification of C2orf18, termed ANT2BP (ANT2-binding protein), as one of the key molecules involved in pancreatic carcinogenesis.
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C2orf18/ANT2BP was shown to localise to mitochondria and to interact with ANT2, defining the ANT2-binding protein and linking ANT2 to membrane-potential and energy homeostasis.
"We showed that C2orf18 was localized in the mitochondria and it could interact with adenine nucleotide translocase 2 (ANT2), which is involved in maintenance of the mitochondrial membrane potential and energy homeostasis, and was indicated some roles in apoptosis."
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siRNA knockdown of the ANT2 partner C2orf18 induced apoptosis and suppressed growth of pancreatic cancer cells; the phenotype is attributed to C2orf18, so proliferation/apoptosis annotations for ANT2 itself are indirect.
"Knockdown of C2orf18 by small-interfering RNA in PDAC cell lines resulted in induction of apoptosis and suppression of cancer cell growth, suggesting its essential role in maintaining viability of PDAC cells."
Proteomic analysis of increased Parkin expression and its interactants provides evidence for a role in modulation of mitochondrial function.
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SLC25A5 was recovered among 14 tandem-affinity-purified interactants of the E3 ubiquitin ligase Parkin, the basis for the specific ubiquitin protein ligase binding annotation.
"Tandem affinity purification/MS revealed 14 potential interactants of Parkin; CKB, DBT, HSPD1, HSPA9, LRPPRC, NDUFS2, PRDX6, SLC25A5, TPI1, UCHL1, UQCRC1, VCL, YWHAZ, YWHAE."
Defining the membrane proteome of NK cells.
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Large-scale membrane-proteome catalogue of an NK-like cell line; detection of the abundant ANT2 carrier here supports only the over-general membrane location and adds nothing about function.
"Mass spectrometric analysis identified 1843 proteins with high confidence scores."
MMXD, a TFIIH-independent XPD-MMS19 protein complex involved in chromosome segregation.
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ANT2 was identified as a component of the TFIIH-independent MMXD (MMS19-MIP18-XPD) complex, the basis for the GO:0071817 MMXD complex annotation.
"Instead, it included FAM96B (now designated MIP18), Ciao1, and ANT2."
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Knockdown of MMXD components caused improper chromosome segregation and abnormal nuclei, linking the complex - though not ANT2 specifically - to mitotic chromosome segregation.
"The siRNA-mediated knockdown of MMS19, MIP18, or XPD led to improper chromosome segregation and the accumulation of nuclei with abnormal shapes."
Phosphoproteome analysis of functional mitochondria isolated from resting human muscle reveals extensive phosphorylation of inner membrane protein complexes and enzymes.
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Phosphoproteomic survey of mitochondria isolated from human skeletal muscle; ANT2 is detected among phosphorylated inner-membrane transporters, which supports mitochondrial localization but not a specific function.
"We also assigned phosphorylation sites in mitochondrial proteins involved in amino acid degradation, importers and transporters, calcium homeostasis, and apoptosis."
Expression of leucine-rich repeat kinase 2 (LRRK2) inhibits the processing of uMtCK to induce cell death in a cell culture model system.
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LRRK2 was shown to interact with permeability transition pore components including ANT, the source of the LRRK2-ANT2 interaction record.
"We have identified several novel LRRK2 interacting proteins and showed that LRRK2 can interact with three components of the PTPC (permeability transition pore complex) including ANT (adenine nucleotide translocator), VDAC (voltage-dependent anion channel) and uMtCK"
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LRRK2 expression increases the ANT-VDAC association implicated in permeability transition pore opening, consistent with ANT2 participating in mPTP regulation.
"In addition, the expression of both wild-type and mutant forms of LRRK2 promotes the interaction between ANT and VDAC, which plays a role in permeabilization transition pore opening."
Proteomic characterization of the human sperm nucleus.
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Catalogue of proteins detected in isolated human sperm nuclei; a nuclear location for this abundant mitochondrial inner-membrane carrier is most parsimoniously explained as co-purification background rather than genuine nuclear residence.
"With this approach, 403 different proteins have been identified from the isolated sperm nuclei."
The human fibroblast adenine nucleotide translocator gene. Molecular cloning and sequence.
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Genomic cloning and sequencing of the human fibroblast adenine nucleotide translocator gene (ANT2/SLC25A5). The cached record is abstract-only and describes sequence-level work; no transport assay and no localization experiment are described in the abstract, and the full text was not available for this review.
"We report the cloning and sequencing of the gene expressed in human fibroblasts."
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The paper characterises the ANT2 promoter and relates promoter differences to cell-type-specific and proliferation-associated expression of the three ANT genes.
"Differences among the sequence motifs of the 5'-flanking region of the three human translocase genes could account for differences in their cell type-specific and proliferation-associated expression."
Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
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UV-crosslinking mRNA interactome capture in HeLa cells; abundant mitochondrial membrane proteins are recurrent nonspecific hits in this assay, so the resulting RNA binding assignment is not a credible molecular function for ANT2.
"We identify 860 proteins that qualify as RBPs by biochemical and statistical criteria, adding more than 300 RBPs to those previously known"
Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson's disease.
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Study of LRRK2-mediated ribosomal protein s15 phosphorylation in Parkinson's disease models; the ANT2 record derived from it is an interaction-screen by-product with no functional characterisation of ANT2.
"Here, we show that ribosomal protein s15 is a key pathogenic LRRK2 substrate in Drosophila and human neuron PD models."
Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function.
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Affinity-enrichment mass spectrometry map of mitochondrial protein interactions around uncharacterised proteins; the ADCK2-ANT2 association reported here is a high-throughput interaction data point supporting only protein binding.
"To reveal functions for these proteins (termed MXPs), we assessed condition-specific protein-protein interactions for 50 select MXPs using affinity enrichment mass spectrometry."
TSPO ligands stimulate ZnPPIX transport and ROS accumulation leading to the inhibition of P. falciparum growth in human blood.
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TSPO2 and VDAC were found together in a complex in the membranes of mature erythrocytes, which lack mitochondria; this is the observation behind the note that ANT isoforms may be present in non-mitochondrial membranes.
"TSPO2 and VDAC are present in the membranes of mature RBCs in a unique protein complex that changes the affinity of TSPO ligands after Pf infection."
Human-Specific ARHGAP11B Acts in Mitochondria to Expand Neocortical Progenitors by Glutaminolysis.
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The human-specific protein ARHGAP11B is imported into mitochondria where it binds the adenine nucleotide translocase and inhibits the mitochondrial permeability transition pore - the strongest human-cell evidence for ANT2 involvement in mPTP regulation.
"Here, we show that ARHGAP11B is imported into mitochondria, where it interacts with the adenine nucleotide translocase (ANT) and inhibits the mitochondrial permeability transition pore (mPTP)."
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Pharmacological inhibition of ANT function or of mPTP opening phenocopies ARHGAP11B-driven basal progenitor expansion, functionally linking ANT activity to the mPTP.
"BP expansion by ARHGAP11B requires its presence in mitochondria, and pharmacological inhibition of ANT function or mPTP opening mimic BP expansion by ARHGAP11B."
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
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SLC25A5 is a member of the stringently defined human mitochondrial high-confidence proteome (MitoCoP), corroborating mitochondrial localization.
"We classified >8,000 proteins in mitochondrial preparations of human cells and defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP)."
The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its localization, degradation, and toxicity.
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Quantitative interactome study of LRRK2 that identified TRIM1; an ANT2 entry arising from this dataset is a large-scale interaction hit and does not characterise ANT2 function.
"We performed quantitative mass spectrometry-based interactome studies to identify 48 novel LRRK2 interactors, including the microtubule-associated E3 ubiquitin ligase TRIM1 (tripartite motif family 1)."
SLC25A5,6 dimers exchange ATP for ADP across the mitochondrial inner membrane
Association of Vpr with ANT1
LONP1 binds mitochondrial inner membrane proteins
LONP1 degrades mitochondrial inner membrane proteins