GO Term	Evidence	Action	Reason
GO:0005524 ATP binding	IBA GO_REF:0000033	ACCEPT	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. 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. Supporting Evidence: file:human/ABCF2/ABCF2-uniprot.txt DOMAIN 86..325 file:human/ABCF2/ABCF2-uniprot.txt BINDING 118..125
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based ATP-binding annotation is consistent with the two ABC-transporter-like nucleotide-binding domains in ABCF2. Reason: The domain architecture supports ATP binding. The annotation is generic but appropriate for ABCF2's molecular-function model. Supporting Evidence: file:human/ABCF2/ABCF2-uniprot.txt DOMAIN 396..613 file:human/ABCF2/ABCF2-uniprot.txt BINDING 430..437
GO:0016887 ATP hydrolysis activity	IEA GO_REF:0000002	ACCEPT	Summary: ABCF2 is an ABCF-family protein with two ABC nucleotide-binding domains, supporting annotation as an ATP-hydrolyzing ABC-family ATPase. 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. Supporting Evidence: file:human/ABCF2/ABCF2-uniprot.txt Belongs to the ABC transporter superfamily. ABCF family. PMID:28112439 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
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: Cytosol localization is consistent with ABCF2 being a soluble ABCF-family protein lacking transmembrane domains. Reason: The HPA-derived cytosol annotation matches the published description of ABCF2 as cytosolic and the UniProt caution that it lacks transmembrane domains. Supporting Evidence: PMID:28112439 Among these genes, ABCF2, a cytosolic member of the ABC superfamily of transporters file:human/ABCF2/ABCF2-uniprot.txt Lacks transmembrane domains and is probably not involved in transport.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9796042	REMOVE	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. 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. Supporting Evidence: Reactome:R-HSA-9796042 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. PMID:28112439 Unlike other subgroups, ABCF members have NBDs but not TMDs, and thus do not function as transporters of molecules across the membrane. file:human/ABCF2/ABCF2-uniprot.txt Lacks transmembrane domains and is probably not involved in transport.
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	REMOVE	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. 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. Supporting Evidence: PMID:19946888 The remaining species were largely involved in cellular processes and molecular functions that could be predicted to be transiently associated with membranes. PMID:28112439 Among these genes, ABCF2, a cytosolic member of the ABC superfamily of transporters file:human/ABCF2/ABCF2-uniprot.txt Lacks transmembrane domains and is probably not involved in transport.

Deep Research

Falcon

(ABCF2-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 32 citations 2 artifacts 2026-06-07T03:43:12.152275

Edison artifact artifact-00 (text/markdown)

## Context ID: pqac-00000008 The document provides several visual summaries of human ABCF proteins. Figure 1B (cropped) illustrates the domain architecture of h (image/png)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Comprehensive research report: human ABCF2 (UniProt Q9UG63) — functional annotation and evidence synthesis

1) Key concepts and definitions (current understanding)

1.1. Target verification and nomenclature

ABCF2 (UniProt Q9UG63; gene symbol ABCF2; Homo sapiens) is an ATP-binding cassette (ABC) superfamily protein in the ABCF subfamily. Unlike canonical ABC transporters that couple ATP hydrolysis to substrate translocation across membranes, ABCF proteins are primarily soluble/cytosolic ABC ATPases that act on ribosomes/translation, rather than as transmembrane pumps. This distinction is emphasized in ABCF-focused reviews that note the ABC_tran_Xtn/PtIM linker has not been associated with transmembrane transport and that ABCF proteins operate as translation factors binding the ribosome (fostier2021abc‐ftranslationfactors pages 4-6, fostier2021abc‐ftranslationfactors pages 1-4).

1.2. ABCF family architecture and mechanistic model

ABCF proteins are described as soluble proteins built around two tandem ABC nucleotide-binding domains (NBDs) (ATPase cassettes) connected by a conserved PtIM (P-site tRNA interaction motif)-containing linker (also termed ABC_tran_Xtn). Across structurally characterized ABCF proteins, the PtIM forms an α-helical hairpin that can contact peptidyl-tRNA and the peptidyl transferase center (PTC) when the ABCF protein binds the ribosome near the E site. The prevailing family-level model is that ATP binding/hydrolysis drives conformational cycling that modulates translation (initiation/elongation/termination, rescue of stalled ribosomes, or protection of the PTC from inhibitors) (fostier2021abc‐ftranslationfactors pages 4-6, fostier2021abc‐ftranslationfactors pages 1-4, saha2023decipheringthestructural pages 2-3).

Important evidence gap for ABCF2 specifically: while family-level evidence strongly supports that ABCF paralogs are ATP-driven translation factors, the retrieved literature did not include a direct biochemical demonstration (e.g., ribosome-binding assay, ATPase kinetics on ribosome, cryo-EM structure) for human ABCF2 itself. Therefore, translation-factor function for ABCF2 should currently be stated as family-informed inference, unless additional ABCF2-specific ribosome studies are identified (fostier2021abc‐ftranslationfactors pages 28-30, ousalem2019abcfproteinsin pages 6-10).

1.3. Visual domain/function context for human ABCF proteins

A review figure set provides a schematic of human ABCF protein architectures and E-site ribosome-binding geometry, and summarizes known/proposed roles across ABCF1/2/3 (fostier2021abc‐ftranslationfactors media dd376791, fostier2021abc‐ftranslationfactors media 33fe9305). These visuals support the interpretation that ABCF2 is best conceptualized within the ABCF “translation factor” framework rather than as a membrane transporter.

2) Primary function, pathways, and localization for ABCF2 (evidence-weighted)

2.1. Best-supported ABCF2-specific function: modulation of intrinsic (mitochondrial) apoptosis during bacterial infection

The strongest direct functional evidence for human ABCF2 comes from enteropathogenic E. coli (EPEC) infection studies showing ABCF2 is a host factor that counteracts mitochondrial apoptosis and is antagonized by a bacterial effector.

Physical interaction partner (direct): EPEC effector EspF
Nougayrède et al. (Cellular Microbiology, 2007-03; https://doi.org/10.1111/j.1462-5822.2006.00820.x) identified human ABCF2 as an EspF-binding protein by affinity purification/mass spectrometry and confirmed interaction by yeast two-hybrid and co-immunoprecipitation from infected cells (nougayrede2007enteropathogenicescherichiacoli pages 1-2, nougayrede2007enteropathogenicescherichiacoli pages 2-4).

Functional consequence: EspF delivery reduces host ABCF2 levels and promotes caspase activation
Infection reduced cellular ABCF2 levels in an EspF dose-dependent manner, and ABCF2 depletion sensitized cells to caspase activation during infection—consistent with an anti-apoptotic role for ABCF2 that EspF counteracts (nougayrede2007enteropathogenicescherichiacoli pages 10-11, nougayrede2007enteropathogenicescherichiacoli pages 7-8).

Quantitative phenotype (key statistics):
In HeLa cells, ABCF2 knockdown increased cleaved caspase-9 levels by ~4-fold upon infection; ABCF2 knockdown also produced ~50% more cleaved caspase-3 after staurosporine treatment. Infection conditions included MOI 100:1 for 3 h (nougayrede2007enteropathogenicescherichiacoli pages 7-8).

Localization in this context:
The same work describes ABCF2 as primarily cytoplasmic with partial mitochondrial localization, while EspF is injected into the cytoplasm and sorted to mitochondria—supporting a model in which ABCF2 impacts mitochondrial/intrinsic apoptosis signaling (nougayrede2007enteropathogenicescherichiacoli pages 8-10).

Mechanistic interpretation (authoritative):
The EspF–ABCF2 binding event was proposed to inhibit ABCF2’s protective function; the route by which EspF reduces ABCF2 levels (e.g., ubiquitination-mediated degradation) was not resolved in the excerpted evidence (nougayrede2007enteropathogenicescherichiacoli pages 10-11, fostier2021abc‐ftranslationfactors pages 28-30).

2.2. ABCF2 and translation/ribosome pathways: inference from ABCF family biology

ABCF family members are experimentally established ribosome-binding translation factors that bind in similar geometry (E-site) and alter the PTC/tRNA configuration. Reviews highlight that “all biochemically characterized” ABCF proteins participate in protein synthesis and directly interact with ribosomes, with cryo-EM showing conserved binding at the E site and PtIM engagement of P-site tRNA/PTC (fostier2021abc‐ftranslationfactors pages 4-6, fostier2021abc‐ftranslationfactors pages 1-4).

However, for ABCF2 specifically, the reviewed texts note links to infection/cancer but state its role is unclear and do not supply ABCF2-specific ribosome-binding experiments (ousalem2019abcfproteinsin pages 6-10). Consequently, the most defensible statement is:
- ABCF2 is a soluble ABC ATPase with domain architecture characteristic of ribosome-binding translation-factor ABCFs; direct ABCF2 ribosome-binding evidence remains limited in the retrieved set. (fostier2021abc‐ftranslationfactors pages 28-30, ousalem2019abcfproteinsin pages 6-10)

3) Recent developments and latest research (prioritizing 2023–2024)

3.1. 2024: ABCF2 proposed as a host factor for Pasteurella multocida adhesion/invasion (preprint)

Wang et al. (bioRxiv, 2024-12; https://doi.org/10.1101/2024.12.03.626657) reported a TurboID proximity-labeling screen that nominated ABCF2 as a host interactor for three P. multocida adhesins (PlpE, PtfA, Hsf-2), with validation by co-immunoprecipitation and bio-layer interferometry (wang2024turboidbasedproximitylabeling pages 5-10, wang2024turboidbasedproximitylabeling pages 19-24).

Functional perturbation: ABCF2 gain/loss of function altered adhesion/invasion
ABCF2 knockdown/knockout reduced P. multocida adherence/invasion, whereas ABCF2 overexpression increased these outcomes (wang2024turboidbasedproximitylabeling pages 1-5).

Mechanistic signaling: p38 MAPK and NF-κB regulation; p53-dependent apoptosis
The preprint linked infection-induced ABCF2 upregulation to p38 MAPK and NF-κB signaling and connected ABCF2 to a p53-dependent apoptotic pathway during infection (wang2024turboidbasedproximitylabeling pages 5-10, wang2024turboidbasedproximitylabeling pages 10-14).

Key quantitative experimental parameters (methods/data context):
The study reports infection conditions commonly at MOI = 200, NF-κB inhibitor BAY11-7082 (5 μM), p38 inhibitor BIRB796 (40 μM), and p53 inhibitor pifithrin-α (40 μM); NF-κB and p38 activation were profiled over multi-hour time courses (wang2024turboidbasedproximitylabeling pages 19-24).

Cautionary note (expert analysis): Because this is a preprint and proposes an atypical role (“surface adhesion receptor”) for a protein generally described as cytosolic/soluble in ABCF family literature, this claim should be treated as provisional pending peer review and independent replication (fostier2021abc‐ftranslationfactors pages 4-6, fostier2021abc‐ftranslationfactors pages 1-4, wang2024turboidbasedproximitylabeling pages 5-10).

3.2. 2024: ABCF2 in amino-acid starvation/GCN2 pathway context (negative/indirect evidence)

Tatara et al. (IJMS, 2024-03; https://doi.org/10.3390/ijms25052998) reviewed GCN1/GCN2 biology and discussed ABCF paralogs as candidate orthologs of yeast GCN20. The review states ABCF3 is more similar to GCN20 than ABCF1/ABCF2 and that ABCF3 (not ABCF2) is required as the GCN20 ortholog for amino-acid-starvation–induced GCN2 activation (tatara2024emergingroleof pages 2-4). This weighs against assigning ABCF2 a primary GCN20-like role in the integrated stress response.

4) Current applications and real-world implementations

4.1. Host–pathogen interaction research

ABCF2 is used as a host factor in mechanistic studies of bacterial effectors and infection-triggered apoptosis. The EPEC EspF–ABCF2 axis provides a concrete example of how pathogens subvert host apoptotic thresholds by targeting a protective host protein (nougayrede2007enteropathogenicescherichiacoli pages 1-2, nougayrede2007enteropathogenicescherichiacoli pages 7-8).

The 2024 P. multocida preprint extends ABCF2 use into adhesion/invasion receptor discovery pipelines using proximity labeling and multi-assay validation (wang2024turboidbasedproximitylabeling pages 5-10, wang2024turboidbasedproximitylabeling pages 19-24).

4.2. Biomarker/discovery context (cancer and complex traits)

While ABCF2 has been discussed in cancer-associated contexts in reviews, the strongest retrieved evidence for ABCF2 concerns infection-apoptosis mechanisms rather than a validated cancer-driver mechanism. Database aggregations (Open Targets) connect ABCF2 to multiple diseases/traits with modest association scores, supporting exploratory biomarker hypothesis generation rather than definitive clinical implementation (OpenTargets Search: -ABCF2).

5) Expert opinions and analysis from authoritative sources

5.1. Authoritative consensus on ABCF proteins: translation factors, not transporters

Multiple authoritative reviews converge on the view that ABCF proteins are ribosome-interacting translation factors that reshape PTC/tRNA geometry and can perform translation regulation/rescue/protection functions; critically, these reviews distinguish ABCF proteins from membrane ABC exporters and do not treat ABCF proteins as substrate pumps (fostier2021abc‐ftranslationfactors pages 4-6, fostier2021abc‐ftranslationfactors pages 1-4, fostier2021abc‐ftranslationfactors pages 30-33).

5.2. ABCF2-specific annotation confidence

High confidence: ABCF2 can act as an anti-apoptotic host factor in epithelial cells and is directly targeted by EPEC EspF, with quantitative caspase phenotypes (nougayrede2007enteropathogenicescherichiacoli pages 7-8).
Moderate confidence: ABCF2 belongs to a protein family whose members are ATP-driven ribosome/translation factors; thus ABCF2 likely shares aspects of this biology, but ABCF2-specific translation assays were not retrieved here (fostier2021abc‐ftranslationfactors pages 28-30, ousalem2019abcfproteinsin pages 6-10).
Low-to-provisional confidence: ABCF2 acting as a cell-surface adhesion receptor for P. multocida is supported by multiple assays in a 2024 preprint but is conceptually in tension with canonical ABCF family localization; this requires independent confirmation (wang2024turboidbasedproximitylabeling pages 5-10).

6) Relevant statistics and recent data

Key quantitative/statistical points extracted from primary studies and databases:
- ABCF2 knockdown increased infection-associated cleaved caspase-9 ~4-fold in HeLa cells (EPEC infection), and increased staurosporine-induced cleaved caspase-3 ~50%; infection MOI 100:1 (3 h) (Nougayrède et al., 2007-03; https://doi.org/10.1111/j.1462-5822.2006.00820.x) (nougayrede2007enteropathogenicescherichiacoli pages 7-8).
- In P. multocida infection experiments (preprint), typical infection conditions included MOI 200, with pathway inhibitors BAY11-7082 5 μM (NF-κB), BIRB796 40 μM (p38), and pifithrin-α 40 μM (p53), alongside time-course profiling of NF-κB and p38 activation (Wang et al., 2024-12; https://doi.org/10.1101/2024.12.03.626657) (wang2024turboidbasedproximitylabeling pages 19-24).
- Open Targets lists ABCF2 associations with modest scores (e.g., renal cell carcinoma score ~0.0647; neurodegenerative disease score ~0.1584; abnormality of skeletal system score ~0.2105), with evidence_size = 3 for each listed disease in the retrieved output (OpenTargets Platform; target ENSG00000033050) (OpenTargets Search: -ABCF2).

Evidence summary table

Topic	Key finding	Evidence type	System	Quantitative/statistical details (if any)	Primary citation (DOI URL + year)	PaperQA context citation ID
Function / family context	ABCF2 belongs to the ABC-F family, whose members are soluble ABC ATPases rather than membrane transporters. Family-level reviews state ABC-F proteins lack transmembrane domains, bind the ribosomal E site, and act as translation factors that modulate the peptidyl-transferase center and/or stalled-ribosome states; this supports annotation of human ABCF2 as a non-TMD ATPase with likely translation-related function, but not as a classical transporter.	Review	Cross-species ABC-F family; includes human ABCF paralogs	No ABCF2-specific activity constant reported; qualitative consensus that ABC-F proteins are cytosolic/non-membrane and ribosome-associated	Fostier et al., 2021, https://doi.org/10.1002/1873-3468.13984; Ousalem et al., 2019, https://doi.org/10.1016/j.resmic.2019.09.005; Saha et al., 2023, https://doi.org/10.29011/2577-1515.100225	(fostier2021abc‐ftranslationfactors pages 4-6, fostier2021abc‐ftranslationfactors pages 1-4, ousalem2019abcfproteinsin pages 6-10, saha2023decipheringthestructural pages 2-3, fostier2021abc‐ftranslationfactors pages 30-33, saha2023decipheringthestructural pages 3-5)
Localization / structural inference	Family-level structural summaries indicate ABC-F proteins are cytosolic and bind ribosomes in E-site geometry via tandem ABC domains plus the PtIM/ABC_tran_Xtn linker. For ABCF2 specifically, direct ribosome-binding evidence was not retrieved here, so subcellular localization is best described as inferred cytoplasmic/ribosome-associated rather than definitively proven in the available primary ABCF2 literature.	Review / inference	ABC-F proteins broadly; human ABCF2 by family inference	Qualitative only; no direct ABCF2 localization percentages reported in these family reviews	Fostier et al., 2021, https://doi.org/10.1002/1873-3468.13984; Saha et al., 2023, https://doi.org/10.29011/2577-1515.100225	(fostier2021abc‐ftranslationfactors pages 4-6, fostier2021abc‐ftranslationfactors pages 1-4, saha2023decipheringthestructural pages 2-3, saha2023decipheringthestructural pages 3-5, fostier2021abc‐ftranslationfactors media dd376791)
Pathway / apoptosis / bacterial infection	The strongest direct functional evidence for human ABCF2 is from EPEC infection studies: EspF physically binds ABCF2, lowers host ABCF2 levels, and ABCF2 depletion sensitizes cells to mitochondrial apoptosis. These data support ABCF2 as an anti-apoptotic host factor whose inhibition promotes caspase-9/-3 activation during infection.	Primary research	Human HeLa and Caco-2 cells infected with enteropathogenic E. coli	ABCF2 peptides identified in EspF pull-down (~12.4% coverage); infection experiments used MOI 100:1 for 3 h; ABCF2 siRNA increased cleaved caspase-9 ~4-fold and increased staurosporine-induced cleaved caspase-3 by ~50% versus control	Nougayrède et al., 2007, https://doi.org/10.1111/j.1462-5822.2006.00820.x	(nougayrede2007enteropathogenicescherichiacoli pages 1-2, nougayrede2007enteropathogenicescherichiacoli pages 10-11, nougayrede2007enteropathogenicescherichiacoli pages 8-10, nougayrede2007enteropathogenicescherichiacoli pages 7-8, nougayrede2007enteropathogenicescherichiacoli pages 2-4)
Localization in infection context	In the EspF study, ABCF2 was described as primarily cytoplasmic with partial mitochondrial localization, while EspF is type-III-secreted into host cells and traffics to mitochondria. This supports a model in which ABCF2 can influence intrinsic/mitochondrial apoptosis during bacterial pathogenesis.	Primary research	Human epithelial cells during EPEC infection	Qualitative localization; no compartment percentages given in retrieved text	Nougayrède et al., 2007, https://doi.org/10.1111/j.1462-5822.2006.00820.x	(nougayrede2007enteropathogenicescherichiacoli pages 8-10)
Disease / pathogen-host interaction	A 2024 preprint proposed ABCF2 as a host adhesion receptor/factor for Pasteurella multocida. TurboID proximity labeling, co-IP, BLI, overexpression, knockdown, and knockout experiments all supported a role for ABCF2 in bacterial adhesion/invasion, extending ABCF2 biology beyond apoptosis to host–pathogen interface functions.	Preprint	Human A549, HEK293T and porcine NPTr cells; mouse infection model	TurboID labeling with 50 μM biotin for 15 min; infections commonly at MOI 200; gentamicin protection 100 μg/mL for 1 h; three replicates; BLI used ABCF2 at 18.75–600 nM	Wang et al., 2024, https://doi.org/10.1101/2024.12.03.626657	(wang2024turboidbasedproximitylabeling pages 5-10, wang2024turboidbasedproximitylabeling pages 14-19, wang2024turboidbasedproximitylabeling pages 1-5, wang2024turboidbasedproximitylabeling pages 19-24, wang2024turboidbasedproximitylabeling pages 10-14)
Pathway / signaling	In the same P. multocida preprint, infection-induced ABCF2 upregulation was linked to p38 MAPK and NF-κB signaling, and ABCF2 was connected to p53-dependent apoptosis. Thus, ABCF2 was placed downstream of infection-triggered stress/inflammatory signaling and upstream of apoptosis-related outputs.	Preprint	Cell culture infection models	P-P65 increased at 6 hpi; BAY11-7082 used at 5 μM; BIRB796 at 40 μM; pifithrin-α at 40 μM; p38 assayed over 0–20 h and NF-κB over 1–12 h	Wang et al., 2024, https://doi.org/10.1101/2024.12.03.626657	(wang2024turboidbasedproximitylabeling pages 5-10, wang2024turboidbasedproximitylabeling pages 19-24, wang2024turboidbasedproximitylabeling pages 35-37, wang2024turboidbasedproximitylabeling pages 10-14, wang2024turboidbasedproximitylabeling pages 37-38, wang2024turboidbasedproximitylabeling pages 44-45)
GCN1/GCN2 / integrated stress response context	Recent review evidence does not support a direct ABCF2 role as the mammalian GCN20-like factor in amino-acid-starvation signaling. Instead, ABCF3 was described as more similar to yeast GCN20, whereas ABCF2 was explicitly noted as less similar and not assigned the GCN20-ortholog function.	Review	Mammalian/yeast comparative signaling context	Qualitative statement only; no effect size reported for ABCF2	Tatara et al., 2024, https://doi.org/10.3390/ijms25052998	(tatara2024emergingroleof pages 2-4)
Disease associations / database summary	Open Targets links ABCF2 to several diseases/traits, but the scores are modest and do not establish mechanism. Reported associations include renal cell carcinoma, multiple myeloma, smoking initiation, neurodegenerative disease, and abnormality of the skeletal system; each listed disease had evidence_size = 3 in the retrieved output.	Database	Human genetic/biomedical evidence aggregation	Scores: renal cell carcinoma 0.0647; multiple myeloma 0.0602; smoking initiation 0.1037; neurodegenerative disease 0.1584; abnormality of the skeletal system 0.2105; evidence_size = 3 for each listed disease	Open Targets Platform search result for ABCF2 (retrieved in this session), https://platform.opentargets.org/target/ENSG00000033050	(OpenTargets Search: -ABCF2)
Evidence gap / annotation confidence	Despite strong family-level support for an ATPase/ribosome-related role, direct mechanistic evidence for human ABCF2 itself in canonical translation control remains limited in the retrieved literature. The best-supported ABCF2-specific functions currently concern anti-apoptotic activity and bacterial pathogenesis, so any annotation as a ribosome-associated translation factor should be presented as family-informed rather than conclusively ABCF2-specific.	Synthesis across sources	Human ABCF2	Evidence gap is qualitative but important for functional annotation confidence	Fostier et al., 2021, https://doi.org/10.1002/1873-3468.13984; Ousalem et al., 2019, https://doi.org/10.1016/j.resmic.2019.09.005; Nougayrède et al., 2007, https://doi.org/10.1111/j.1462-5822.2006.00820.x	(fostier2021abc‐ftranslationfactors pages 28-30, ousalem2019abcfproteinsin pages 6-10, nougayrede2007enteropathogenicescherichiacoli pages 1-2)

Table: This table summarizes the strongest family-level and ABCF2-specific evidence relevant to functional annotation of human ABCF2 (UniProt Q9UG63). It separates well-supported primary findings from family-based inferences and highlights where recent preprint and database evidence should be interpreted cautiously.

7) Conclusions for functional annotation

Molecular function (most defensible): ABCF2 is a soluble ABC ATPase-family protein whose family members act as ATP-dependent ribosome/translation factors; ABCF2 itself is best supported experimentally as an anti-apoptotic host factor targeted by bacterial effectors, rather than as a membrane transporter with a defined transported substrate (fostier2021abc‐ftranslationfactors pages 4-6, nougayrede2007enteropathogenicescherichiacoli pages 7-8).
Localization: ABCF2 is described experimentally as primarily cytoplasmic with partial mitochondrial localization in the EPEC EspF study, consistent with an influence on intrinsic apoptosis (nougayrede2007enteropathogenicescherichiacoli pages 8-10).
Pathways: The most direct pathway linkage is to intrinsic (mitochondrial) apoptosis via caspase-9/caspase-3 modulation during infection; more recent work proposes regulation by p38 MAPK/NF-κB and involvement in p53-dependent apoptosis in P. multocida infection (nougayrede2007enteropathogenicescherichiacoli pages 7-8, wang2024turboidbasedproximitylabeling pages 19-24).
Recent research (2023–2024): The most ABCF2-relevant updates are a 2024 review clarifying ABCF2 is unlikely to be the mammalian GCN20-like activator of GCN2 (ABCF3 is favored), and a 2024 preprint proposing an adhesion/invasion role in P. multocida infection (tatara2024emergingroleof pages 2-4, wang2024turboidbasedproximitylabeling pages 5-10).

URLs and publication dates (where available)

Nougayrède et al., Cellular Microbiology — 2007-03 — https://doi.org/10.1111/j.1462-5822.2006.00820.x (nougayrede2007enteropathogenicescherichiacoli pages 1-2)
Fostier et al., FEBS Letters (review) — 2021-12 — https://doi.org/10.1002/1873-3468.13984 (fostier2021abc‐ftranslationfactors pages 4-6)
Ousalem et al., Research in Microbiology (review) — 2019-11 — https://doi.org/10.1016/j.resmic.2019.09.005 (ousalem2019abcfproteinsin pages 6-10)
Tatara et al., International Journal of Molecular Sciences (review) — 2024-03 — https://doi.org/10.3390/ijms25052998 (tatara2024emergingroleof pages 2-4)
Wang et al., bioRxiv (preprint) — 2024-12 — https://doi.org/10.1101/2024.12.03.626657 (wang2024turboidbasedproximitylabeling pages 1-5)
Open Targets Platform (target ENSG00000033050 / ABCF2) — URL: https://platform.opentargets.org/target/ENSG00000033050 (retrieved during this session) (OpenTargets Search: -ABCF2)

References

(fostier2021abc‐ftranslationfactors pages 4-6): Corentin R. Fostier, Laura Monlezun, Farès Ousalem, Shikha Singh, John F. Hunt, and Grégory Boël. Abc‐f translation factors: from antibiotic resistance to immune response. Dec 2021. URL: https://doi.org/10.1002/1873-3468.13984, doi:10.1002/1873-3468.13984. This article has 50 citations and is from a peer-reviewed journal.
(fostier2021abc‐ftranslationfactors pages 1-4): Corentin R. Fostier, Laura Monlezun, Farès Ousalem, Shikha Singh, John F. Hunt, and Grégory Boël. Abc‐f translation factors: from antibiotic resistance to immune response. Dec 2021. URL: https://doi.org/10.1002/1873-3468.13984, doi:10.1002/1873-3468.13984. This article has 50 citations and is from a peer-reviewed journal.
(saha2023decipheringthestructural pages 2-3): Chiranjeet Saha, Sujata Saha, Asmita Chakraborty, A. Dirisala, A. Maity, P. Bhowmik, Kunal Sikder, Soumyananda Chakraborti, and A. Basu. Deciphering the structural and functional properties of abc-f atpases. Infectious Diseases Diagnosis & Treatment, Jul 2023. URL: https://doi.org/10.29011/2577-1515.100225, doi:10.29011/2577-1515.100225. This article has 1 citations.
(fostier2021abc‐ftranslationfactors pages 28-30): Corentin R. Fostier, Laura Monlezun, Farès Ousalem, Shikha Singh, John F. Hunt, and Grégory Boël. Abc‐f translation factors: from antibiotic resistance to immune response. Dec 2021. URL: https://doi.org/10.1002/1873-3468.13984, doi:10.1002/1873-3468.13984. This article has 50 citations and is from a peer-reviewed journal.
(ousalem2019abcfproteinsin pages 6-10): Farès Ousalem, Shikha Singh, Olivier Chesneau, John F. Hunt, and Grégory Boël. Abc-f proteins in mrna translation and antibiotic resistance. Research in Microbiology, 170:435-447, Nov 2019. URL: https://doi.org/10.1016/j.resmic.2019.09.005, doi:10.1016/j.resmic.2019.09.005. This article has 42 citations and is from a peer-reviewed journal.
(fostier2021abc‐ftranslationfactors media dd376791): Corentin R. Fostier, Laura Monlezun, Farès Ousalem, Shikha Singh, John F. Hunt, and Grégory Boël. Abc‐f translation factors: from antibiotic resistance to immune response. Dec 2021. URL: https://doi.org/10.1002/1873-3468.13984, doi:10.1002/1873-3468.13984. This article has 50 citations and is from a peer-reviewed journal.
(fostier2021abc‐ftranslationfactors media 33fe9305): Corentin R. Fostier, Laura Monlezun, Farès Ousalem, Shikha Singh, John F. Hunt, and Grégory Boël. Abc‐f translation factors: from antibiotic resistance to immune response. Dec 2021. URL: https://doi.org/10.1002/1873-3468.13984, doi:10.1002/1873-3468.13984. This article has 50 citations and is from a peer-reviewed journal.
(nougayrede2007enteropathogenicescherichiacoli pages 1-2): Jean-Philippe Nougayrède, Gregory H. Foster, and Michael S. Donnenberg. Enteropathogenic escherichia coli effector espf interacts with host protein abcf2. Cellular Microbiology, 9:680-693, Mar 2007. URL: https://doi.org/10.1111/j.1462-5822.2006.00820.x, doi:10.1111/j.1462-5822.2006.00820.x. This article has 91 citations and is from a peer-reviewed journal.
(nougayrede2007enteropathogenicescherichiacoli pages 2-4): Jean-Philippe Nougayrède, Gregory H. Foster, and Michael S. Donnenberg. Enteropathogenic escherichia coli effector espf interacts with host protein abcf2. Cellular Microbiology, 9:680-693, Mar 2007. URL: https://doi.org/10.1111/j.1462-5822.2006.00820.x, doi:10.1111/j.1462-5822.2006.00820.x. This article has 91 citations and is from a peer-reviewed journal.
(nougayrede2007enteropathogenicescherichiacoli pages 10-11): Jean-Philippe Nougayrède, Gregory H. Foster, and Michael S. Donnenberg. Enteropathogenic escherichia coli effector espf interacts with host protein abcf2. Cellular Microbiology, 9:680-693, Mar 2007. URL: https://doi.org/10.1111/j.1462-5822.2006.00820.x, doi:10.1111/j.1462-5822.2006.00820.x. This article has 91 citations and is from a peer-reviewed journal.
(nougayrede2007enteropathogenicescherichiacoli pages 7-8): Jean-Philippe Nougayrède, Gregory H. Foster, and Michael S. Donnenberg. Enteropathogenic escherichia coli effector espf interacts with host protein abcf2. Cellular Microbiology, 9:680-693, Mar 2007. URL: https://doi.org/10.1111/j.1462-5822.2006.00820.x, doi:10.1111/j.1462-5822.2006.00820.x. This article has 91 citations and is from a peer-reviewed journal.
(nougayrede2007enteropathogenicescherichiacoli pages 8-10): Jean-Philippe Nougayrède, Gregory H. Foster, and Michael S. Donnenberg. Enteropathogenic escherichia coli effector espf interacts with host protein abcf2. Cellular Microbiology, 9:680-693, Mar 2007. URL: https://doi.org/10.1111/j.1462-5822.2006.00820.x, doi:10.1111/j.1462-5822.2006.00820.x. This article has 91 citations and is from a peer-reviewed journal.
(wang2024turboidbasedproximitylabeling pages 5-10): Fei Wang, Yuyao Shang, Menghan Chen, Zhihao Wang, Hanyuan Liu, Lin Hua, Wentao Li, Huanchun Chen, Qigai He, Bin Wu, and Zhong Peng. Turboid-based proximity labeling discovers abcf2 as an adhesion receptor for the zoonotic pathogen pasteurella multocida. bioRxiv, Dec 2024. URL: https://doi.org/10.1101/2024.12.03.626657, doi:10.1101/2024.12.03.626657. This article has 0 citations.
(wang2024turboidbasedproximitylabeling pages 19-24): Fei Wang, Yuyao Shang, Menghan Chen, Zhihao Wang, Hanyuan Liu, Lin Hua, Wentao Li, Huanchun Chen, Qigai He, Bin Wu, and Zhong Peng. Turboid-based proximity labeling discovers abcf2 as an adhesion receptor for the zoonotic pathogen pasteurella multocida. bioRxiv, Dec 2024. URL: https://doi.org/10.1101/2024.12.03.626657, doi:10.1101/2024.12.03.626657. This article has 0 citations.
(wang2024turboidbasedproximitylabeling pages 1-5): Fei Wang, Yuyao Shang, Menghan Chen, Zhihao Wang, Hanyuan Liu, Lin Hua, Wentao Li, Huanchun Chen, Qigai He, Bin Wu, and Zhong Peng. Turboid-based proximity labeling discovers abcf2 as an adhesion receptor for the zoonotic pathogen pasteurella multocida. bioRxiv, Dec 2024. URL: https://doi.org/10.1101/2024.12.03.626657, doi:10.1101/2024.12.03.626657. This article has 0 citations.
(wang2024turboidbasedproximitylabeling pages 10-14): Fei Wang, Yuyao Shang, Menghan Chen, Zhihao Wang, Hanyuan Liu, Lin Hua, Wentao Li, Huanchun Chen, Qigai He, Bin Wu, and Zhong Peng. Turboid-based proximity labeling discovers abcf2 as an adhesion receptor for the zoonotic pathogen pasteurella multocida. bioRxiv, Dec 2024. URL: https://doi.org/10.1101/2024.12.03.626657, doi:10.1101/2024.12.03.626657. This article has 0 citations.
(tatara2024emergingroleof pages 2-4): Yota Tatara, Shuya Kasai, Daichi Kokubu, Tadayuki Tsujita, Junsei Mimura, and Ken Itoh. Emerging role of gcn1 in disease and homeostasis. International Journal of Molecular Sciences, 25:2998, Mar 2024. URL: https://doi.org/10.3390/ijms25052998, doi:10.3390/ijms25052998. This article has 12 citations.
(OpenTargets Search: -ABCF2): Open Targets Query (-ABCF2, 5 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(fostier2021abc‐ftranslationfactors pages 30-33): Corentin R. Fostier, Laura Monlezun, Farès Ousalem, Shikha Singh, John F. Hunt, and Grégory Boël. Abc‐f translation factors: from antibiotic resistance to immune response. Dec 2021. URL: https://doi.org/10.1002/1873-3468.13984, doi:10.1002/1873-3468.13984. This article has 50 citations and is from a peer-reviewed journal.
(saha2023decipheringthestructural pages 3-5): Chiranjeet Saha, Sujata Saha, Asmita Chakraborty, A. Dirisala, A. Maity, P. Bhowmik, Kunal Sikder, Soumyananda Chakraborti, and A. Basu. Deciphering the structural and functional properties of abc-f atpases. Infectious Diseases Diagnosis & Treatment, Jul 2023. URL: https://doi.org/10.29011/2577-1515.100225, doi:10.29011/2577-1515.100225. This article has 1 citations.
(wang2024turboidbasedproximitylabeling pages 14-19): Fei Wang, Yuyao Shang, Menghan Chen, Zhihao Wang, Hanyuan Liu, Lin Hua, Wentao Li, Huanchun Chen, Qigai He, Bin Wu, and Zhong Peng. Turboid-based proximity labeling discovers abcf2 as an adhesion receptor for the zoonotic pathogen pasteurella multocida. bioRxiv, Dec 2024. URL: https://doi.org/10.1101/2024.12.03.626657, doi:10.1101/2024.12.03.626657. This article has 0 citations.
(wang2024turboidbasedproximitylabeling pages 35-37): Fei Wang, Yuyao Shang, Menghan Chen, Zhihao Wang, Hanyuan Liu, Lin Hua, Wentao Li, Huanchun Chen, Qigai He, Bin Wu, and Zhong Peng. Turboid-based proximity labeling discovers abcf2 as an adhesion receptor for the zoonotic pathogen pasteurella multocida. bioRxiv, Dec 2024. URL: https://doi.org/10.1101/2024.12.03.626657, doi:10.1101/2024.12.03.626657. This article has 0 citations.
(wang2024turboidbasedproximitylabeling pages 37-38): Fei Wang, Yuyao Shang, Menghan Chen, Zhihao Wang, Hanyuan Liu, Lin Hua, Wentao Li, Huanchun Chen, Qigai He, Bin Wu, and Zhong Peng. Turboid-based proximity labeling discovers abcf2 as an adhesion receptor for the zoonotic pathogen pasteurella multocida. bioRxiv, Dec 2024. URL: https://doi.org/10.1101/2024.12.03.626657, doi:10.1101/2024.12.03.626657. This article has 0 citations.
(wang2024turboidbasedproximitylabeling pages 44-45): Fei Wang, Yuyao Shang, Menghan Chen, Zhihao Wang, Hanyuan Liu, Lin Hua, Wentao Li, Huanchun Chen, Qigai He, Bin Wu, and Zhong Peng. Turboid-based proximity labeling discovers abcf2 as an adhesion receptor for the zoonotic pathogen pasteurella multocida. bioRxiv, Dec 2024. URL: https://doi.org/10.1101/2024.12.03.626657, doi:10.1101/2024.12.03.626657. This article has 0 citations.

Artifacts

Edison artifact artifact-00

Citations

nougayrede2007enteropathogenicescherichiacoli pages 7-8
nougayrede2007enteropathogenicescherichiacoli pages 8-10
ousalem2019abcfproteinsin pages 6-10
wang2024turboidbasedproximitylabeling pages 1-5
wang2024turboidbasedproximitylabeling pages 19-24
tatara2024emergingroleof pages 2-4
wang2024turboidbasedproximitylabeling pages 5-10
nougayrede2007enteropathogenicescherichiacoli pages 1-2
saha2023decipheringthestructural pages 2-3
nougayrede2007enteropathogenicescherichiacoli pages 2-4
nougayrede2007enteropathogenicescherichiacoli pages 10-11
wang2024turboidbasedproximitylabeling pages 10-14
saha2023decipheringthestructural pages 3-5
wang2024turboidbasedproximitylabeling pages 14-19
wang2024turboidbasedproximitylabeling pages 35-37
wang2024turboidbasedproximitylabeling pages 37-38
wang2024turboidbasedproximitylabeling pages 44-45
https://doi.org/10.1111/j.1462-5822.2006.00820.x
https://doi.org/10.1101/2024.12.03.626657
https://doi.org/10.3390/ijms25052998
https://doi.org/10.1002/1873-3468.13984;
https://doi.org/10.1016/j.resmic.2019.09.005;
https://doi.org/10.29011/2577-1515.100225
https://platform.opentargets.org/target/ENSG00000033050
https://doi.org/10.1002/1873-3468.13984
https://doi.org/10.1016/j.resmic.2019.09.005
https://doi.org/10.1002/1873-3468.13984,
https://doi.org/10.29011/2577-1515.100225,
https://doi.org/10.1016/j.resmic.2019.09.005,
https://doi.org/10.1111/j.1462-5822.2006.00820.x,
https://doi.org/10.1101/2024.12.03.626657,
https://doi.org/10.3390/ijms25052998,

📚 Additional Documentation

Notes

(ABCF2-notes.md)

ABCF2 notes

Deep research status

An initial Falcon deep research attempt on 2026-06-03 timed out at 600 seconds with no output. Falcon deep research was successfully re-run on 2026-06-07; the report is in ABCF2-deep-research-falcon.md. The earlier review used the documented manual fallback (UniProt, GOA, cached publications, the local Reactome record, PN projection reports, and targeted primary-source checks); the new Falcon report has now been incorporated (see "Falcon deep research findings" below).

Falcon deep research findings (2026-06-07)

The Falcon report reinforces the soluble-ATPase / non-transporter model and adds two functionally important strands that were not in the original review:

EspF interaction / anti-apoptotic host factor (new). ABCF2 was identified by affinity purification as a binding partner of the enteropathogenic E. coli (EPEC) type III effector EspF, confirmed by yeast two-hybrid, colocalization, and co-immunoprecipitation. EPEC infection lowered ABCF2 levels in an EspF dose-dependent manner, and ABCF2 knockdown increased EspF- and staurosporine-induced caspase-9/caspase-3 cleavage — supporting a putative cytoprotective/anti-apoptotic role acting through the intrinsic (mitochondrial) death pathway. ABCF2 was reported as primarily cytoplasmic with partial mitochondrial localization [PMID:17064289 "Enteropathogenic Escherichia coli effector EspF interacts with host protein Abcf2"; Nougayrède et al., Cell Microbiol 2006, 9(3):680-93, doi:10.1111/j.1462-5822.2006.00820.x]. This PMID has been added to the review references and a corresponding expert question added.
ABC-F translation-factor family framework. Family-level reviews (Fostier et al. 2021, FEBS Lett, doi:10.1002/1873-3468.13984; Ousalem et al. 2019, Res Microbiol, doi:10.1016/j.resmic.2019.09.005) frame ABC-F proteins as soluble, ribosome-E-site-binding translation factors with a PtIM/ABC_tran_Xtn linker, not membrane pumps. This supports (as family-informed inference, already captured in core_functions) a translation-associated role for the ABCF2 ATPase cycle, while noting that direct ABCF2-specific ribosome-binding assays were not retrieved. A 2024 GCN1/GCN2 review (Tatara et al., IJMS, doi:10.3390/ijms25052998) argues ABCF3 (not ABCF2) is the better GCN20 ortholog, weighing against an ABCF2-specific integrated-stress-response role.
Provisional / preprint (not incorporated into annotations). A 2024 bioRxiv preprint (Wang et al., doi:10.1101/2024.12.03.626657) proposes ABCF2 as a host adhesion receptor for Pasteurella multocida via TurboID proximity labeling. This is conceptually in tension with the canonical cytosolic localization and is treated as provisional pending peer review; it is recorded here only as a lead, not used to change annotations.

Function synthesis

ABCF2 is a soluble ABCF-family ATP-binding cassette protein, not a membrane transporter. UniProt records two ABC transporter domains and two ATP-binding sites, and cautions that ABCF2 "Lacks transmembrane domains and is probably not involved in transport" [file:human/ABCF2/ABCF2-uniprot.txt, "Lacks transmembrane domains and is probably not involved in transport"]. Bao et al. state the same distinction in primary literature: ABCF family proteins have nucleotide-binding domains but not transmembrane domains and "do not function as transporters of molecules across the membrane" [PMID:28112439 ABCF2, an Nrf2 target gene, contributes to cisplatin resistance in ovarian cancer cells., "Unlike other subgroups, ABCF members have NBDs but not TMDs, and thus do not function as transporters of molecules across the membrane"].

The strongest supported molecular-function model is therefore ATP binding/ATP hydrolysis activity for a cytosolic ABCF protein. There is not enough gene-level evidence to assign a specific biological process coupled to the ATPase cycle. ATP binding and ATP hydrolysis rows are retained; the cytosol row is retained because ABCF2 is described as "a cytosolic member of the ABC superfamily" [PMID:28112439 ABCF2, an Nrf2 target gene, contributes to cisplatin resistance in ovarian cancer cells., "Among these genes, ABCF2, a cytosolic member of the ABC superfamily of transporters"].

ABCF2 was originally cloned in a study of mRNAs responsive to cellular iron levels, but that paper is cloning/regulation evidence rather than direct GO function evidence [PMID:10944468 cDNA cloning by amplification of circularized first strand cDNAs reveals non-IRE-regulated iron-responsive mRNAs., "We tested this new method on eight mRNAs that we have previously shown to respond to cellular iron levels"]. ABCF2 is also overexpressed/amplified in ovarian clear cell adenocarcinoma and correlates with chemoresistance markers [PMID:16203778 Identification of overexpression and amplification of ABCF2 in clear cell ovarian adenocarcinomas by cDNA microarray analyses., "significantly higher ABCF2 DNA and mRNA copy number and protein levels in clear cell cases compared with those in serous cases"].

Bao et al. provide the key modern primary evidence: ABCF2 has a functional NRF2/NFE2L2 antioxidant-response element in its promoter, NRF2 binds the promoter region by ChIP, and manipulating ABCF2 changes cisplatin response in ovarian cancer cell lines [PMID:28112439 ABCF2, an Nrf2 target gene, contributes to cisplatin resistance in ovarian cancer cells., "To further confirm that NRF2 binds to the putative ARE of the ABCF2 promoter"; PMID:28112439 ABCF2, an Nrf2 target gene, contributes to cisplatin resistance in ovarian cancer cells., "ABCF2 overexpression rendered A2780 cells more resistant to cisplatin and ABCF2 knockdown rendered resistant A2780 cells more sensitive to cisplatin"]. This supports NFE2L2 target-gene and cancer-drug-response context, but not a precise GO molecular process for ABCF2.

Existing GOA decisions

The two ATP binding rows and the ATP hydrolysis activity row are accepted as the conserved molecular-function core of a two-NBD ABCF ATPase. The cytosol row is accepted.

The Reactome plasma membrane row is removed. The Reactome event is "NFE2L2 dependent ABCF2 expression" and supports promoter regulation, not direct plasma-membrane localization [Reactome:R-HSA-9796042 NFE2L2 dependent ABCF2 expression, "ABCF2 is an NFE2L2 target gene that contains a functional ARE sequence in the promoter"]. The primary paper and UniProt both argue against a membrane-transporter model.

The high-throughput NK-cell membrane row is also removed. The NK proteome paper explicitly notes that many identified proteins were likely transiently associated with membranes [PMID:19946888 Defining the membrane proteome of NK cells., "The remaining species were largely involved in cellular processes and molecular functions that could be predicted to be transiently associated with membranes"]. For ABCF2, a soluble cytosolic ATPase with no transmembrane domains, the row is too weak to retain.

Proteostasis PN projection

The PN projection report places ABCF2 under Translation|Cytosolic translation|Ribosome-associated QC|other RQC processes and projects GO:0006515 protein quality control for misfolded or incompletely synthesized proteins as new_to_goa. The mapping audit flags the parent RQC-group mapping as requiring manual gene-level review before changing a gene review because it is a high-level/contextual source and can lose specificity.

For ABCF2, I did not find direct evidence for stalled-ribosome recognition, ribosome rescue, collided-ribosome signaling, RQC-complex membership, or degradation of incomplete nascent chains. The PN projected GO:0006515 term is therefore not proposed. It is recorded as an expert question and experimental follow-up.

Pn Notes

(ABCF2-pn-notes.md)

ABCF2 PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: Q9UG63
AIGR review status: COMPLETE
Review batch: proteostasis-batch-2026-06-03 (PR 1326)
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/ABCF2/ABCF2-ai-review.yaml
AIGR review HTML: present - genes/human/ABCF2/ABCF2-ai-review.html
Gene notes: present - genes/human/ABCF2/ABCF2-notes.md
GOA TSV: present - genes/human/ABCF2/ABCF2-goa.tsv
UniProt record: present - genes/human/ABCF2/ABCF2-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/ABCF2.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/ABCF2.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

genes/human/ABCF2/ABCF2-deep-research-falcon.md

AIGR Review Snapshot

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.
Existing/core annotation action counts: ACCEPT: 4; REMOVE: 2

PN Consistency Summary

Consistency: Consistent in conclusions, with a deliberate divergence. Deep research and notes frame ABCF2 as a soluble two-NBD ABCF ATPase (no TMDs, not a transporter; ABC-F family = ribosome-E-site translation factors), with an NFE2L2/cisplatin angle and a putative anti-apoptotic EspF-interaction role. The review accepts ATP binding / ATP hydrolysis / cytosol and removes the membrane/plasma-membrane rows. The review explicitly declines the PN-projected GO:0006515 because no ABCF2-specific stalled-ribosome/RQC evidence exists — recording it as an open question instead. PN (RQC bucket) vs review (no RQC process) is a documented, evidence-based divergence, not an error.
PN story / NEW pressure: PN asserts a ribosome-associated QC role not in GOA. The projected GO:0006515 is verified real, but ABCF2-specific RQC evidence is absent; family/context inference alone is insufficient. Conclusion: PN over-reaches for ABCF2; correctly held as a suggested question rather than a NEW term. No defensible NEW GO term to add now.
Evidence alignment: PN dossier lists no reference titles. Review/notes cite PMID:28112439 (NRF2/cisplatin, cytosolic non-transporter), PMID:17064289 (EspF), PMID:19946888, Reactome R-HSA-9796042 — none establish RQC, so they neither support nor are cited by the PN RQC node. No citation conflict.
Verdict: Consistent (review conservatively rejects the PN RQC projection). Recommended edits: [REF] Reconcile UniProt accession — PN dossier/workbook uses A0A090N7X1 but the canonical reviewed entry and review YAML use Q9UG63; update the PN workbook to Q9UG63. [MAP] Keep GO:0006515 non-propagating for ABCF2.

Full Consistency Review

UniProt: Q9UG63 (review YAML) — dossier lists A0A090N7X1 (TrEMBL/secondary accession mismatch) · batch: proteostasis-batch-2026-06-03 · review status: COMPLETE
PN placement: Translation|Cytosolic translation|Ribosome-associated QC|other RQC processes ; PN-node mapping: type other RQC processes=no_mapping; group Ribosome-associated QC=mapped→GO:0006515 protein quality control for misfolded/incompletely synthesized proteins (new_to_goa); class/branch context_only.
Consistency: Consistent in conclusions, with a deliberate divergence. Deep research and notes frame ABCF2 as a soluble two-NBD ABCF ATPase (no TMDs, not a transporter; ABC-F family = ribosome-E-site translation factors), with an NFE2L2/cisplatin angle and a putative anti-apoptotic EspF-interaction role. The review accepts ATP binding / ATP hydrolysis / cytosol and removes the membrane/plasma-membrane rows. The review explicitly declines the PN-projected GO:0006515 because no ABCF2-specific stalled-ribosome/RQC evidence exists — recording it as an open question instead. PN (RQC bucket) vs review (no RQC process) is a documented, evidence-based divergence, not an error.
PN story / NEW pressure: PN asserts a ribosome-associated QC role not in GOA. The projected GO:0006515 is verified real, but ABCF2-specific RQC evidence is absent; family/context inference alone is insufficient. Conclusion: PN over-reaches for ABCF2; correctly held as a suggested question rather than a NEW term. No defensible NEW GO term to add now.
Mapping strategy: The group node Ribosome-associated QC→GO:0006515 is sound for bona fide RQC members but should NOT propagate to ABCF2, which sits under the other RQC processes (no_mapping) catch-all on family/context grounds only. Treat the GO:0006515 projection as non-propagating for this gene pending direct ribosome-binding/RQC evidence.
Evidence alignment: PN dossier lists no reference titles. Review/notes cite PMID:28112439 (NRF2/cisplatin, cytosolic non-transporter), PMID:17064289 (EspF), PMID:19946888, Reactome R-HSA-9796042 — none establish RQC, so they neither support nor are cited by the PN RQC node. No citation conflict.
Verdict: Consistent (review conservatively rejects the PN RQC projection). Recommended edits: [REF] Reconcile UniProt accession — PN dossier/workbook uses A0A090N7X1 but the canonical reviewed entry and review YAML use Q9UG63; update the PN workbook to Q9UG63. [MAP] Keep GO:0006515 non-propagating for ABCF2.

PN Dossier Context

review_batch: proteostasis-batch-2026-06-03
review_yaml: genes/human/ABCF2/ABCF2-ai-review.yaml
PN workbook rows: 1

PN row 1: Translation | Cytosolic translation | Ribosome-associated QC | other RQC processes

UniProt: A0A090N7X1
In branches: TR
PN-node mapping records (path + ancestors):
- [type] Translation|Cytosolic translation|Ribosome-associated QC|other RQC processes
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN category rather than a single GO class. The member genes span multiple activities, complexes, or contexts, so direct propagation from this node would overstate the shared biology.
- [group] Translation|Cytosolic translation|Ribosome-associated QC
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0006515 protein quality control for misfolded or incompletely synthesized proteins]
  rationale: The PN ribosome-associated quality-control group covers surveillance and disposal of stalled or defective nascent-chain translation products. GO lacks a dedicated ribosome-associated QC term in the local cache, so the broader protein-quality-control process is the best supported target.
- [class] Translation|Cytosolic translation
  status=context_only scope=too_broad_to_propagate GO=[GO:0002181 cytoplasmic translation]
  rationale: The PN class Cytosolic translation is centered on the cytoplasmic translation apparatus and process, but it also houses supporting machinery such as ribosome biogenesis factors. The GO process term is a useful high-level label for the class, but propagating it to all members would over-annotate genes whose PN placement is through assembly or maturation context rather than core cytoplasmic translation.
- [branch] Translation
  status=context_only scope=too_broad_to_propagate GO=[GO:0006412 translation]
  rationale: The PN Translation branch is organized around the translation apparatus and immediately associated cotranslational quality-control systems. GO translation is the closest high-level process label, but the PN branch also contains adjacent machinery such as ribosome biogenesis and nascent-chain handling. Keeping this relationship is useful for interpretation, but it is too broad to project safely onto every member.

Projected GO annotations (1)

GO:0006515 protein quality control for misfolded or incompletely synthesized proteins | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Translation|Cytosolic translation|Ribosome-associated QC

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

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.

ABCF2

Gene Description

Existing Annotations Review

Core Functions