ABCF2

Gene 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 Annotations Review

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.

Core Functions

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.

Molecular Function:

ATP hydrolysis activity

Cellular Locations:

cytosol

Supporting Evidence:

file:human/ABCF2/ABCF2-uniprot.txt
DOMAIN 86..325
file:human/ABCF2/ABCF2-uniprot.txt
DOMAIN 396..613
PMID:28112439
Unlike other subgroups, ABCF members have NBDs but not TMDs, and thus do not function as transporters of molecules across the membrane.
PMID:28112439
Instead, they are reported to be involved in protein translation and elongation
file:human/ABCF2/ABCF2-uniprot.txt
EF3 subfamily.

References

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Suggested Experiments

Experiment: 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.

Experiment: 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.

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

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Notes

Pn Notes

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