id: Q9UG63 gene_symbol: ABCF2 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: >- ABCF2 encodes ATP-binding cassette sub-family F member 2, a soluble member of the ABCF family with two ABC nucleotide-binding domains and no transmembrane domains. It is best described as a cytosolic ABC-family ATPase rather than a membrane transporter. ABCF2 expression is regulated by NFE2L2/NRF2 through a promoter antioxidant-response element in ovarian cancer cells, where altered ABCF2 abundance affects cisplatin sensitivity, but the direct molecular mechanism linking ABCF2 to drug resistance remains unresolved. ABCF2 has also been reported as a putative anti-apoptotic host factor that is bound and destabilized by the enteropathogenic Escherichia coli type III effector EspF, with cytoplasmic and partial mitochondrial localization, consistent with a role in restraining the intrinsic (mitochondrial) apoptotic pathway. alternative_products: - name: '1' id: Q9UG63-1 - name: '2' id: Q9UG63-2 sequence_note: VSP_054715 existing_annotations: - term: id: GO:0005524 label: ATP binding evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables review: summary: >- ABCF2 has two ABC nucleotide-binding domains and conserved ATP-binding motifs. ATP binding is therefore well supported as a core molecular property of the protein. action: ACCEPT reason: >- The phylogenetic annotation is consistent with UniProt feature annotation of two ABC transporter domains and two ATP-binding sites. This does not imply that ABCF2 is a membrane transporter. supported_by: - reference_id: file:human/ABCF2/ABCF2-uniprot.txt supporting_text: >- DOMAIN 86..325 - reference_id: file:human/ABCF2/ABCF2-uniprot.txt supporting_text: >- BINDING 118..125 - term: id: GO:0005524 label: ATP binding evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: enables review: summary: >- InterPro-based ATP-binding annotation is consistent with the two ABC-transporter-like nucleotide-binding domains in ABCF2. action: ACCEPT reason: >- The domain architecture supports ATP binding. The annotation is generic but appropriate for ABCF2's molecular-function model. supported_by: - reference_id: file:human/ABCF2/ABCF2-uniprot.txt supporting_text: >- DOMAIN 396..613 - reference_id: file:human/ABCF2/ABCF2-uniprot.txt supporting_text: >- BINDING 430..437 - term: id: GO:0016887 label: ATP hydrolysis activity evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: enables review: summary: >- ABCF2 is an ABCF-family protein with two ABC nucleotide-binding domains, supporting annotation as an ATP-hydrolyzing ABC-family ATPase. action: ACCEPT reason: >- ATP hydrolysis activity is the most informative existing molecular function term for ABCF2. The biological process coupled to this ATPase activity remains uncertain; the ribosome-associated quality-control projection was not accepted without direct ABCF2 evidence. supported_by: - reference_id: file:human/ABCF2/ABCF2-uniprot.txt supporting_text: >- Belongs to the ABC transporter superfamily. ABCF family. - reference_id: PMID:28112439 supporting_text: >- ABCF2 possesses nucleotide-binding domains, but has no transmembrane domains, which makes it different from other members of the ATP binding cassette family since it cannot function as a membrane transporter - term: id: GO:0005829 label: cytosol evidence_type: IDA original_reference_id: GO_REF:0000052 qualifier: located_in review: summary: >- Cytosol localization is consistent with ABCF2 being a soluble ABCF-family protein lacking transmembrane domains. action: ACCEPT reason: >- The HPA-derived cytosol annotation matches the published description of ABCF2 as cytosolic and the UniProt caution that it lacks transmembrane domains. supported_by: - reference_id: PMID:28112439 supporting_text: >- Among these genes, ABCF2, a cytosolic member of the ABC superfamily of transporters - reference_id: file:human/ABCF2/ABCF2-uniprot.txt supporting_text: >- Lacks transmembrane domains and is probably not involved in transport. - term: id: GO:0005886 label: plasma membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-9796042 qualifier: located_in review: summary: >- Reactome models NFE2L2-dependent ABCF2 expression, but the primary evidence supports ABCF2 as a cytosolic, non-transmembrane ABCF protein rather than a plasma membrane transporter. action: REMOVE reason: >- The Reactome event is useful as NFE2L2 target-gene context, but plasma membrane localization is not supported by the cited primary literature and conflicts with the soluble ABCF-domain architecture. additional_reference_ids: - PMID:28112439 supported_by: - reference_id: Reactome:R-HSA-9796042 supporting_text: >- ABCF2 is an NFE2L2 target gene that contains a functional ARE sequence in the promoter which is confirmed through ChIP assay in Human Ovarian cancer cell lines. - reference_id: PMID:28112439 supporting_text: >- Unlike other subgroups, ABCF members have NBDs but not TMDs, and thus do not function as transporters of molecules across the membrane. - reference_id: file:human/ABCF2/ABCF2-uniprot.txt supporting_text: >- Lacks transmembrane domains and is probably not involved in transport. - term: id: GO:0016020 label: membrane evidence_type: HDA original_reference_id: PMID:19946888 qualifier: located_in review: summary: >- ABCF2 was identified in a high-throughput NK-cell membrane-proteome study, but the same study notes that many identified proteins were transient or nonintegral membrane-associated species. action: REMOVE reason: >- ABCF2 lacks transmembrane domains and is described in primary literature as cytosolic. The broad HDA membrane row is likely a fractionation or transient-association result rather than a defining localization. supported_by: - reference_id: PMID:19946888 supporting_text: >- The remaining species were largely involved in cellular processes and molecular functions that could be predicted to be transiently associated with membranes. - reference_id: PMID:28112439 supporting_text: >- Among these genes, ABCF2, a cytosolic member of the ABC superfamily of transporters - reference_id: file:human/ABCF2/ABCF2-uniprot.txt supporting_text: >- Lacks transmembrane domains and is probably not involved in transport. references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000052 title: Gene Ontology annotation based on curation of immunofluorescence data findings: [] - id: PMID:10944468 title: cDNA cloning by amplification of circularized first strand cDNAs reveals non-IRE-regulated iron-responsive mRNAs. findings: - statement: >- ABCF2 was identified in a cloning study of mRNAs responsive to cellular iron levels, but this does not establish a GO process or transporter function. supporting_text: >- We tested this new method on eight mRNAs that we have previously shown to respond to cellular iron levels. - id: PMID:16203778 title: Identification of overexpression and amplification of ABCF2 in clear cell ovarian adenocarcinomas by cDNA microarray analyses. findings: - statement: >- ABCF2 copy number and expression are elevated in ovarian clear cell adenocarcinoma relative to serous cases, and cytoplasmic staining was higher in chemotherapy nonresponders. supporting_text: >- The results showed significantly higher ABCF2 DNA and mRNA copy number and protein levels in clear cell cases compared with those in serous cases. - id: PMID:19946888 title: Defining the membrane proteome of NK cells. findings: - statement: >- The high-throughput NK-cell membrane-proteome study identified many nonintegral or transiently membrane-associated proteins, making the broad ABCF2 membrane row weak. supporting_text: >- The remaining species were largely involved in cellular processes and molecular functions that could be predicted to be transiently associated with membranes. - id: PMID:28112439 title: ABCF2, an Nrf2 target gene, contributes to cisplatin resistance in ovarian cancer cells. findings: - statement: >- ABCF2 is a cytosolic ABCF protein with nucleotide-binding domains but no transmembrane domains, distinguishing it from membrane transporters. supporting_text: >- ABCF2 possesses nucleotide-binding domains, but has no transmembrane domains, which makes it different from other members of the ATP binding cassette family since it cannot function as a membrane transporter - statement: >- NFE2L2/NRF2 regulates ABCF2 expression through a functional promoter ARE in ovarian cancer cells. supporting_text: >- To further confirm that NRF2 binds to the putative ARE of the ABCF2 promoter, a CHIP assay was performed in A2780cp cells. - statement: >- Manipulating ABCF2 abundance changes cisplatin response in ovarian cancer cell-line assays, but the mechanism remains unresolved. supporting_text: >- ABCF2 overexpression rendered A2780 cells more resistant to cisplatin and ABCF2 knockdown rendered resistant A2780 cells more sensitive to cisplatin - id: PMID:17064289 title: Enteropathogenic Escherichia coli effector EspF interacts with host protein Abcf2. full_text_unavailable: true findings: - statement: >- ABCF2 (Abcf2) was identified by affinity purification as a binding partner of the enteropathogenic E. coli (EPEC) type III effector EspF, with the interaction confirmed by yeast two-hybrid, colocalization, and co-immunoprecipitation from infected cells. This is direct experimental evidence for an ABCF2 protein-protein interaction, surfaced by the Falcon deep research report. - statement: >- EPEC infection decreased ABCF2 levels in an EspF dose-dependent manner, and RNAi knockdown of ABCF2 increased EspF-induced caspase-9 and caspase-3 cleavage and increased staurosporine-induced caspase-3 cleavage, indicating a putative anti-apoptotic (cytoprotective) function for ABCF2 that EspF antagonizes via the intrinsic/mitochondrial death pathway. - statement: >- ABCF2 was described as primarily cytoplasmic with partial mitochondrial localization in this study; this is consistent with influence on mitochondrial apoptosis but does not by itself justify a stable mitochondrial GO localization annotation without further evidence. - id: Reactome:R-HSA-9796042 title: NFE2L2 dependent ABCF2 expression findings: - statement: >- Reactome models ABCF2 as an NFE2L2 target gene with evidence from Bao et al. 2017; this supports transcriptional-regulation context, not plasma membrane localization. supporting_text: >- ABCF2 is an NFE2L2 target gene that contains a functional ARE sequence in the promoter which is confirmed through ChIP assay in Human Ovarian cancer cell lines. - id: file:human/ABCF2/ABCF2-uniprot.txt title: UniProt record for ABCF2 findings: - statement: >- UniProt annotates ABCF2 as an ABCF-family protein with two ABC transporter domains, two ATP-binding sites, and no transmembrane-domain transporter role. supporting_text: >- Lacks transmembrane domains and is probably not involved in transport. - id: file:human/ABCF2/ABCF2-notes.md title: Manual notes for ABCF2 Proteostasis PN review findings: [] core_functions: - molecular_function: id: GO:0016887 label: ATP hydrolysis activity description: >- ABCF2 is a soluble ABCF-family ATPase with two ABC nucleotide-binding domains. Current evidence supports ATP binding and inferred ATP hydrolysis as the core molecular features, with cytosolic localization. ABCF-family members are reported to have translation/elongation roles, and UniProt places ABCF2 in the EF3 subfamily, but a direct biological process for the ABCF2 ATPase cycle is not established. The ribosome-associated quality-control projection is retained as a question rather than a new GO annotation. locations: - id: GO:0005829 label: cytosol supported_by: - reference_id: file:human/ABCF2/ABCF2-uniprot.txt supporting_text: >- DOMAIN 86..325 - reference_id: file:human/ABCF2/ABCF2-uniprot.txt supporting_text: >- DOMAIN 396..613 - reference_id: PMID:28112439 supporting_text: >- Unlike other subgroups, ABCF members have NBDs but not TMDs, and thus do not function as transporters of molecules across the membrane. - reference_id: PMID:28112439 supporting_text: >- Instead, they are reported to be involved in protein translation and elongation - reference_id: file:human/ABCF2/ABCF2-uniprot.txt supporting_text: >- EF3 subfamily. proposed_new_terms: [] suggested_questions: - question: >- Does ABCF2 directly bind ribosomes or participate in ribosome-associated protein quality control, or is its PN placement under "other RQC processes" based on family/context inference? - question: >- What substrates or client complexes are coupled to ABCF2 ATP hydrolysis in cytosol? - question: >- By what molecular mechanism does ABCF2 abundance alter cisplatin sensitivity in ovarian cancer cells if it is not a membrane transporter? - question: >- Does ABCF2 have a bona fide anti-apoptotic function at mitochondria, as suggested by the EspF-interaction study (PMID:17064289), and is the EspF-driven decrease in ABCF2 mediated by ubiquitin-dependent degradation? suggested_experiments: - description: >- Test endogenous ABCF2 association with translating ribosomes, collided ribosomes, and RQC factors by polysome profiling or ribosome co-sedimentation before and after ribosome-stalling treatments, followed by ABCF2 immunoblot or targeted mass spectrometry. hypothesis: >- ABCF2 will only justify a protein-quality-control GO annotation if it reproducibly associates with stalled-ribosome/RQC complexes. - description: >- Purify ABCF2 and test ATPase activity with and without ribosomes, eIF factors, and candidate stress-response interactors, including ATPase-dead Walker motif mutants. hypothesis: >- ABCF2 is an active soluble ABC ATPase whose hydrolysis rate is stimulated by a specific cytosolic client complex.