FANCA is one of the Fanconi anemia (FA) proteins and an essential structural subunit of the multiprotein FA core complex (also called the Fanconi anaemia nuclear complex), which is composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9 and FANCM together with associated FAAP proteins (FAAP20, FAAP24, FAAP100). The FA core complex is a nuclear multisubunit E3 ubiquitin ligase (with FANCL as the catalytic RING subunit and UBE2T/FANCT as the E2) that, in response to DNA interstrand crosslinks encountered during replication, monoubiquitinates the FANCD2-FANCI (ID2) heterodimer. Monoubiquitinated ID2 is loaded onto chromatin and coordinates downstream nucleolytic incision, translesion synthesis and homologous-recombination repair of the crosslink. FANCA is not the catalytic subunit; it is a large, predominantly alpha-helical scaffolding and protein-interaction hub that binds FANCG and FANCF and directly anchors FAAP20, and it is required for the assembly, stability, nuclear accumulation and chromatin loading of the core complex. The functional form of FANCA is nuclear (a minor pool is cytoplasmic), and its nuclear accumulation depends on FANCC binding and phosphorylation. Biallelic loss-of-function mutations in FANCA are the most common cause of Fanconi anemia (complementation group A, ~60-65% of cases), a chromosomal-instability syndrome with bone-marrow failure, congenital malformations, cellular hypersensitivity to DNA crosslinking agents, and cancer predisposition.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0043240 Fanconi anaemia nuclear complex | IBA GO_REF:0000033 | ACCEPT | Summary: FANCA is a core structural subunit of the multiprotein FA nuclear (core) complex. This is the central, well-established cellular-component annotation for FANCA and is supported phylogenetically, electronically, and by multiple experimental studies. Reason: FANCA is definitively a component of the FA core complex (FANCA/B/C/E/F/G/L/M plus FAAP proteins), which monoubiquitinates FANCD2-FANCI. The IBA call is consistent with direct experimental evidence. Supporting Evidence: PMID:12649160 proteins form a nuclear complex required for the monoubiquination of the |
| GO:0045589 regulation of regulatory T cell differentiation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (PANTHER/GO_Central) inference seeded from a mouse Fanca annotation (MGI:1341823). This reflects a peripheral/pleiotropic immunological role rather than the core DNA-repair scaffolding function of FANCA. Reason: FA proteins have been implicated in immune phenotypes in mouse models, so this is not clearly wrong, but regulation of regulatory T cell differentiation is not a core molecular activity of a DNA interstrand-crosslink-repair core-complex subunit. It is a context-specific, non-core process derived from a single ortholog annotation. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: FANCA localizes to the nucleus, which is the compartment where the functional FA core complex acts. Electronic mapping from the UniProt subcellular-location vocabulary is consistent with experimental data. Reason: The major, functional form of FANCA is nuclear (UniProt SUBCELLULAR LOCATION; the FAA-FAC complex is found in the nucleus). Correct location annotation. Supporting Evidence: PMID:9398857 is found in similar abundance in both cytoplasm and nucleus |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A minor pool of FANCA is cytoplasmic; unbound FANCA/FANCC localize predominantly to the cytoplasm before assembly/nuclear import. This represents a non-core (inactive/pre-assembly) location rather than the functional nuclear site of action. Reason: UniProt notes the major form is nuclear and the minor form cytoplasmic. Cytoplasmic localization is real but is not where FANCA performs its DNA-repair function; keep as non-core. Supporting Evidence: PMID:9398857 unbound FAA and FAC localize predominantly to the cytoplasm, the FAA-FAC complex |
| GO:0036297 interstrand cross-link repair | IEA GO_REF:0000002 | ACCEPT | Summary: FANCA is a core-complex subunit essential for the FA pathway that repairs DNA interstrand crosslinks via monoubiquitination of FANCD2-FANCI. This is a core biological process for FANCA. Reason: InterPro2GO mapping (IPR003516, FANCA family) to interstrand cross-link repair is biologically accurate and matches experimental and pathway knowledge. Supporting Evidence: PMID:19965384 central event in the activation of the Fanconi anemia pathway is the |
| GO:0043240 Fanconi anaemia nuclear complex | IEA GO_REF:0000002 | ACCEPT | Summary: Electronic (InterPro) support for FANCA membership in the FA nuclear complex, consistent with the IBA/IDA/NAS evidence. Reason: Correct and central cellular-component annotation; FANCA is a defining subunit of the FA core complex. |
| GO:0005515 protein binding | IPI PMID:10627486 Strong FANCA/FANCG but weak FANCA/FANCC interaction in the y... | MARK AS OVER ANNOTATED | Summary: Yeast two-hybrid interaction between FANCA and FANCG. FANCA-FANCG is one of the strongest and most direct interactions within the FA core complex, but the GO term captured (protein binding) is uninformative. Reason: The underlying interaction is real and biologically meaningful (FANCA-FANCG), but GO:0005515 protein binding is an uninformative molecular-function term. FANCA's scaffold/adaptor role is captured in core_functions. Supporting Evidence: PMID:10627486 found a strong interaction between FANCA and FANCG proteins |
| GO:0005515 protein binding | IPI PMID:10652215 Investigation of Fanconi anemia protein interactions by yeas... | MARK AS OVER ANNOTATED | Summary: Yeast two-hybrid evidence for a strong, direct FANCA-FANCG interaction. Real interaction but uninformative MF term. Reason: GO:0005515 protein binding is uninformative. The FANCA-FANCG interaction is captured in the description/core_functions as part of the core-complex scaffold. Supporting Evidence: PMID:10652215 indicating strong, direct interaction between these proteins |
| GO:0005515 protein binding | IPI PMID:11063725 The Fanconi anemia protein FANCF forms a nuclear complex wit... | MARK AS OVER ANNOTATED | Summary: FANCA co-complexes with FANCC, FANCF and FANCG in the nucleus. Real complex membership but annotated only as generic protein binding. Reason: Uninformative MF term; the FANCA-FANCF/FANCG/FANCC associations are core-complex relationships better captured by the FA nuclear complex CC annotation and core_functions. Supporting Evidence: PMID:11063725 where it complexes with FANCA, FANCC and |
| GO:0005515 protein binding | IPI PMID:12649160 Fanconi anemia protein complex: mapping protein interactions... | MARK AS OVER ANNOTATED | Summary: Yeast two/three-hybrid mapping showing FANCG interacts with the amino-terminus of FANCA and that FANCG bridges FANCA-FANCF. Real interactions, uninformative MF term. Reason: GO:0005515 protein binding is uninformative; the mapped FANCA-FANCG/FANCF contacts define core-complex architecture and are captured elsewhere. Supporting Evidence: PMID:12649160 FANCG was shown to interact with both |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | MARK AS OVER ANNOTATED | Summary: Large-scale (proteome-scale) human protein-protein interaction mapping; the recorded FANCA partner is FANCG. High-throughput evidence for generic protein binding. Reason: High-throughput interactome data annotated as generic protein binding is uninformative for molecular function. The FANCA-FANCG interaction itself is already well established. |
| GO:0005515 protein binding | IPI PMID:17289582 Identification of FAAP24, a Fanconi anemia core complex prot... | MARK AS OVER ANNOTATED | Summary: Study identifying FAAP24 as an FA core-complex protein that (via FANCM) links the complex to damaged DNA; the recorded FANCA interactant here is FANCG. Annotated as generic protein binding. Reason: The interaction is genuine core-complex biology, but GO:0005515 is uninformative. Captured in core_functions/CC annotations. |
| GO:0005515 protein binding | IPI PMID:17396147 FAAP100 is essential for activation of the Fanconi anemia-as... | MARK AS OVER ANNOTATED | Summary: FAAP100 (and FANCG) interactions; FAAP100 is essential for activation of the FA DNA-damage-response pathway and is an integral core-complex protein. Annotated as generic protein binding. Reason: Real core-complex interaction but uninformative MF term. FANCA's role as an interaction hub is captured in core_functions. Supporting Evidence: PMID:17396147 FAAP100 is essential for activation of the Fanconi anemia-associated DNA damage |
| GO:0005515 protein binding | IPI PMID:17474147 Systematic identification of SH3 domain-mediated human prote... | MARK AS OVER ANNOTATED | Summary: SH3-domain peptide-array screen recording a FANCA-GRB2 interaction. This is a systematic domain-ligand screen, peripheral to FANCA's core function. Reason: High-throughput peptide-array interaction annotated as generic protein binding; uninformative and peripheral (GRB2 is not part of the FA core complex). |
| GO:0005515 protein binding | IPI PMID:22266823 Regulation of Rev1 by the Fanconi anemia core complex. | MARK AS OVER ANNOTATED | Summary: FAAP20 (Q6NZ36) binds directly to the FANCA subunit and is required for stability of the core complex and FANCD2 monoubiquitination. Direct and functionally important, but annotated as generic protein binding. Reason: The FANCA-FAAP20 interaction is direct and biologically central, but GO:0005515 is uninformative. FANCA's role as the FAAP20 docking subunit is captured in core_functions. Supporting Evidence: PMID:22266823 multisubunit Fanconi anemia core complex. FAAP20 binds to FANCA subunit and is |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: Architecture-of-the-human-interactome study; recorded FANCA partner is FANCG. High-throughput protein binding. Reason: High-throughput interactome evidence annotated as generic protein binding is uninformative for molecular function. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Interactome-mapping study (neurodegenerative-disease network); recorded FANCA partner is FANCG. High-throughput protein binding. Reason: High-throughput interactome data annotated as generic protein binding; uninformative MF term. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Dual proteome-scale interaction network (BioPlex); recorded FANCA partner is FANCG. High-throughput protein binding. Reason: High-throughput interactome evidence annotated as generic protein binding; uninformative MF term. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: OpenCell endogenous-tagging cartography; recorded FANCA partner is FAAP100. High-throughput protein binding consistent with core-complex membership. Reason: High-throughput proteomics annotated as generic protein binding; uninformative MF term although the FAAP100 association is consistent with the known complex. |
| GO:0005515 protein binding | IPI PMID:37398436 AI-guided pipeline for protein-protein interaction drug disc... | MARK AS OVER ANNOTATED | Summary: AI-guided PPI drug-discovery pipeline recording a FANCA-FANCG interaction. High-throughput/computational-plus-experimental protein binding. Reason: Generic protein binding term; uninformative for molecular function. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: Multimodal cell-maps interactome study; recorded FANCA partner is FANCG. High-throughput protein binding. Reason: High-throughput interactome data annotated as generic protein binding; uninformative MF term. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence (Human Protein Atlas) localizes FANCA to the nucleoplasm, consistent with the nuclear site of action of the FA core complex. Reason: Direct immunofluorescence evidence for nucleoplasmic localization; consistent with the functional nuclear compartment of FANCA. |
| GO:0000785 chromatin | IDA PMID:22343915 FAAP20: a novel ubiquitin-binding FA nuclear core-complex pr... | ACCEPT | Summary: FANCA undergoes DNA-damage-induced chromatin loading (dependent on the FAAP20 UBZ domain), placing it at chromatin where crosslink repair is initiated. Reason: Direct evidence that FANCA is loaded onto chromatin after DNA damage; a functionally relevant location for the FA core complex. Supporting Evidence: PMID:22343915 but is required for DNA-damage-induced chromatin loading of FANCA and the |
| GO:0036297 interstrand cross-link repair | NAS PMID:19965384 The Fanconi anemia pathway promotes replication-dependent DN... | ACCEPT | Summary: The FA pathway (of which FANCA is a core-complex subunit) promotes replication-dependent repair of DNA interstrand crosslinks via monoubiquitination of FANCI-FANCD2. Core biological process. Reason: Well-supported core process for FANCA. Consistent with the IEA ICL-repair annotation and the broader DNA-repair role. Supporting Evidence: PMID:19965384 hypersensitivity to chemicals that generate DNA interstrand cross-links (ICLs) |
| GO:0043240 Fanconi anaemia nuclear complex | NAS PMID:22343915 FAAP20: a novel ubiquitin-binding FA nuclear core-complex pr... | ACCEPT | Summary: FAAP20 study confirming FANCA as an integral component of the FA nuclear core complex, with a defined FANCA region binding FAAP20. Reason: Directly supports FANCA membership in the FA nuclear complex; core CC annotation. Supporting Evidence: PMID:22343915 that FAAP20 is an integral component of the FA nuclear core complex. We identify |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9835411 | KEEP AS NON CORE | Summary: Reactome places FANCA (in a core-complex:HSP70 assembly binding PKR) in the cytosol. This reflects a cytoplasmic/pre-assembly pool rather than the functional nuclear site. Reason: Cytosolic localization is consistent with the known minor cytoplasmic pool of FANCA, but the core DNA-repair function occurs in the nucleus; keep as non-core. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785126 | ACCEPT | Summary: Reactome (FA core complex assembles at ICLs) localizes FANCA to the nucleoplasm, the functional compartment of the FA pathway. Reason: Consistent with the nucleoplasmic site of FA core-complex action; supported by IDA localization evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785342 | ACCEPT | Summary: Reactome nucleoplasm annotation for FANCA within the FA/ICL-repair reaction set. Reason: Correct functional location; consistent with other nucleoplasm evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785361 | ACCEPT | Summary: Reactome nucleoplasm annotation for FANCA within the FANCD2:FANCI monoubiquitination reaction context. Reason: Correct functional location; consistent with other nucleoplasm evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785732 | ACCEPT | Summary: Reactome nucleoplasm annotation for FANCA in the ICL-repair reaction set. Reason: Correct functional location; consistent with other nucleoplasm evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785986 | ACCEPT | Summary: Reactome nucleoplasm annotation for FANCA in the ICL-unhooking reaction set. Reason: Correct functional location; consistent with other nucleoplasm evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6786155 | ACCEPT | Summary: Reactome nucleoplasm annotation for FANCA in the ICL-repair reaction set. Reason: Correct functional location; consistent with other nucleoplasm evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6786166 | ACCEPT | Summary: Reactome nucleoplasm annotation for FANCA in the translesion-synthesis reaction context. Reason: Correct functional location; consistent with other nucleoplasm evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6786171 | ACCEPT | Summary: Reactome nucleoplasm annotation for FANCA in the FANCD2-deubiquitination reaction context. Reason: Correct functional location; consistent with other nucleoplasm evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6788385 | ACCEPT | Summary: Reactome nucleoplasm annotation for FANCA in the ATR/ATRIP recruitment reaction context. Reason: Correct functional location; consistent with other nucleoplasm evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6788392 | ACCEPT | Summary: Reactome nucleoplasm annotation for FANCA in the ATR-phosphorylation reaction context. Reason: Correct functional location; consistent with other nucleoplasm evidence. |
| GO:0005515 protein binding | IPI PMID:22343915 FAAP20: a novel ubiquitin-binding FA nuclear core-complex pr... | MARK AS OVER ANNOTATED | Summary: Direct interaction between FANCA and FAAP20/C1orf86; FANCA regulates FAAP20 stability. Direct and functionally important, annotated as generic protein binding. Reason: The FANCA-FAAP20 interaction is direct and central to core-complex integrity, but GO:0005515 is uninformative. Captured in core_functions. Supporting Evidence: PMID:22343915 a region on FANCA that physically interacts with FAAP20, and show that FANCA |
| GO:0005515 protein binding | IPI PMID:22705371 A ubiquitin-binding protein, FAAP20, links RNF8-mediated ubi... | MARK AS OVER ANNOTATED | Summary: FAAP20 (a component of the FA core complex, bound by FANCA) links RNF8-mediated ubiquitination to the FA network. Annotated as generic protein binding. Reason: Real, functionally important core-complex interaction, but GO:0005515 is uninformative for molecular function. Supporting Evidence: PMID:22705371 by RNF8 and its partner, UBC13, and mediated by FAAP20, a component of the FA |
| GO:0043240 Fanconi anaemia nuclear complex | IDA PMID:22266823 Regulation of Rev1 by the Fanconi anemia core complex. | ACCEPT | Summary: Direct identification of FANCA within the multisubunit FA core complex (Rev1-regulation study identifying FAAP20 as an integral subunit binding FANCA). Reason: Direct experimental evidence for FANCA membership in the FA core complex; core CC annotation. Supporting Evidence: PMID:22266823 multisubunit Fanconi anemia core complex. FAAP20 binds to FANCA subunit and is |
| GO:0043240 Fanconi anaemia nuclear complex | IDA PMID:22343915 FAAP20: a novel ubiquitin-binding FA nuclear core-complex pr... | ACCEPT | Summary: Direct evidence that FANCA is an integral component of the FA nuclear core complex (FAAP20 study). Reason: Direct experimental support for the core CC annotation. Supporting Evidence: PMID:22343915 that FAAP20 is an integral component of the FA nuclear core complex. We identify |
| GO:0043240 Fanconi anaemia nuclear complex | IDA PMID:22705371 A ubiquitin-binding protein, FAAP20, links RNF8-mediated ubi... | ACCEPT | Summary: FANCA identified as part of the FA core complex whose recruitment to ICLs is regulated by the RNF8-FAAP20 ubiquitin cascade. Reason: Direct experimental support for FANCA membership in the FA nuclear complex. |
| GO:0043240 Fanconi anaemia nuclear complex | IDA PMID:20347428 A histone-fold complex and FANCM form a conserved DNA-remode... | ACCEPT | Summary: FANCM-MHF histone-fold complex study in which FANCA is identified as part of the FA core complex. Reason: Direct experimental support for the core CC annotation; consistent with all other complex-membership evidence. |
| GO:0005515 protein binding | IPI PMID:11726552 Fanconi anemia protein, FANCA, associates with BRG1, a compo... | MARK AS OVER ANNOTATED | Summary: FANCA associates with BRG1/SMARCA4 (a subunit of the SWI/SNF chromatin-remodeling complex) and co-localizes with it in the nucleus. Real interaction, uninformative MF term; a proposed link to chromatin remodeling/transcription. Reason: GO:0005515 protein binding is uninformative. The FANCA-BRG1/SWI-SNF interaction is a plausible but secondary/peripheral activity relative to the core FA-complex DNA-repair function. Supporting Evidence: PMID:11726552 FANCA was demonstrated to associate with the endogenous SWI/SNF |
| GO:0005634 nucleus | IDA PMID:11726552 Fanconi anemia protein, FANCA, associates with BRG1, a compo... | ACCEPT | Summary: Direct evidence of nuclear localization of FANCA (co-localization with BRG1 in the nucleus). Reason: Direct experimental support for the functional nuclear localization of FANCA. Supporting Evidence: PMID:11726552 between transfected FANCA and BRG1 |
| GO:0005515 protein binding | IPI PMID:12571280 Nonerythroid alphaII spectrin is required for recruitment of... | MARK AS OVER ANNOTATED | Summary: FANCA co-immunoprecipitates with nonerythroid alphaII-spectrin and ERCC4/XPF and is recruited to ICL-induced nuclear foci. Real interaction relevant to ICL repair, but annotated as generic protein binding. Reason: The FANCA-spectrin-XPF interactions are functionally relevant to recruitment at crosslink damage, but GO:0005515 is uninformative for molecular function. Supporting Evidence: PMID:12571280 alphaSpIISigma*, FANCA and XPF co-immunoprecipitate with each other from normal |
| GO:0005634 nucleus | TAS PMID:9398857 The Fanconi anaemia proteins, FAA and FAC, interact to form ... | ACCEPT | Summary: The FAA-FAC (FANCA-FANCC) complex is found in the nucleus (as well as cytoplasm); nuclear localization is essential for FA-pathway function. Reason: Supports the functional nuclear localization of FANCA; consistent with IEA/IDA nucleus evidence. Supporting Evidence: PMID:9398857 is found in similar abundance in both cytoplasm and nucleus |
| GO:0005737 cytoplasm | TAS PMID:9398857 The Fanconi anaemia proteins, FAA and FAC, interact to form ... | KEEP AS NON CORE | Summary: Unbound FANCA/FANCC localize predominantly to the cytoplasm; a minor cytoplasmic pool exists. Non-core (pre-assembly/inactive) location. Reason: Cytoplasmic localization is documented but does not represent the functional nuclear site of FANCA action; keep as non-core, consistent with the IEA cytoplasm annotation. Supporting Evidence: PMID:9398857 unbound FAA and FAC localize predominantly to the cytoplasm, the FAA-FAC complex |
| GO:0006281 DNA repair | TAS PMID:8896564 Positional cloning of the Fanconi anaemia group A gene. | ACCEPT | Summary: FANCA was cloned as an FA group A gene and proposed to belong to a class of genes associated with prevention/repair of DNA damage. Correct, broader parent of the more specific interstrand cross-link repair. Reason: DNA repair is an accurate (if general) biological-process annotation for FANCA; it is broader than but consistent with the ICL-repair annotation, and it is acceptable to retain the parent term. Supporting Evidence: PMID:8896564 new class of genes associated with the prevention or repair of DNA damage |
| GO:0065003 protein-containing complex assembly | TAS PMID:9398857 The Fanconi anaemia proteins, FAA and FAC, interact to form ... | ACCEPT | Summary: FANCA is required for formation and stability of the FA core complex (it binds FANCG/FANCF, anchors and stabilizes FAAP20, and the FAA-FAC complex forms only in functional cells). Assembly of the multiprotein complex is a genuine role. Reason: FANCA participates directly in assembly of the FA core complex; supported by demonstration that FANCA and FANCC bind each other and form a complex, and by FANCA-dependent stability of core-complex partners. Supporting Evidence: PMID:9398857 the FAA and FAC bind each other and form a complex |
| GO:0030674 protein-macromolecule adaptor activity | IPI PMID:22266823 Regulation of Rev1 by the Fanconi anemia core complex. | NEW | Summary: Proposed informative molecular-function annotation replacing the uninformative protein binding calls. FANCA acts as a scaffold/adaptor that brings together core-complex subunits (binds FANCG/FANCF and directly anchors FAAP20), coordinating assembly and function of the FA core complex. Reason: FANCA is a non-catalytic scaffolding subunit whose defining biochemical activity is bridging protein partners within the FA core complex; the many FANCA IPI annotations to generic protein binding (e.g. FANCG, FANCF, FAAP20) are better represented by an adaptor activity. FAAP20 binds directly to the FANCA subunit and FANCA is required for complex stability. Supporting Evidence: PMID:22266823 multisubunit Fanconi anemia core complex. FAAP20 binds to FANCA subunit and is PMID:22343915 a region on FANCA that physically interacts with FAAP20, and show that FANCA |
| GO:0003697 single-stranded DNA binding | IDA PMID:22194614 Fanconi anemia complementation group A (FANCA) protein has i... | NEW | Summary: Purified FANCA has an intrinsic nucleic-acid-binding activity with preference for single-stranded over double-stranded DNA (and RNA > ssDNA > dsDNA), mapped to its C-terminal domain where most disease mutations cluster. This activity is absent from the curated GOA set; it is added here as a well-documented but single-lab intrinsic activity surfaced by the Affinage record. Reason: Two primary papers from one group (Zhang lab) show purified FANCA directly binds ssDNA by EMSA, with a patient-derived truncation (Q772X) deficient and the C-terminal fragment C772-1455 retaining binding. This intrinsic ssDNA-binding activity is proposed to help recruit and assemble the FA core complex at stalled replication forks. It is a real biochemical activity but has not been independently replicated or adopted by GO curators, so it is treated as a non-core molecular function. Supporting Evidence: PMID:22194614 Using purified protein, we report that human FANCA has intrinsic affinity for nucleic acids. PMID:22194614 its affinity for ssDNA is significantly higher than for dsDNA in an electrophoretic mobility shift assay |
| GO:0045002 double-strand break repair via single-strand annealing | IMP PMID:30057198 FANCA Promotes DNA Double-Strand Break Repair by Catalyzing ... | NEW | Summary: Beyond its canonical core-complex scaffold role, purified FANCA catalyzes single-strand annealing and strand exchange comparable to RAD52, and cell-based DSB-repair assays (siRNA knockdown, CRISPR knockout, mutant complementation) show FANCA is specifically required for the single-strand-annealing sub-pathway of DSB repair, independently of the canonical FA pathway and RAD52. Not present in the curated GOA set. Reason: PMID:30057198 (Mol Cell) demonstrates FANCA SA/SE activity in vitro (with a homodimerization requirement, and six patient-derived mutants deficient) and a direct cellular role in the SSA sub-pathway of DSB repair that is distinct from FANCD2 monoubiquitination. GO:0045002 is a real, correctly-branched biological-process term. This is a well-documented but single-lab, non-canonical activity absent from the curated annotations; added as non-core. Supporting Evidence: PMID:30057198 The SA and SE activities of FANCA directly explain its role in homology-directed DSB repair. PMID:30057198 Our cell-based DSB repair assay further demonstrates that FANCA contributes to the repair of DNA double strand breaks independently of the FA pathway and RAD52 in human cells. |
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