FANCG (also known as XRCC9) is a 622-residue tetratricopeptide-repeat (TPR) protein that forms an all-alpha-helical solenoid and is a subunit of the multiprotein Fanconi anemia (FA) core complex (FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL and FANCM, together with FAAP20/FAAP100/FAAP24). The FA core complex is a nuclear, chromatin-associated E3 ubiquitin ligase (with FANCL as the catalytic RING subunit) that, in response to DNA damage and replication stress, monoubiquitinates the FANCD2-FANCI heterodimer to promote repair of DNA interstrand crosslinks during S phase and to channel lesions into translesion synthesis and homologous recombination. FANCG itself has no known catalytic or DNA-binding activity; it acts as a protein-protein adaptor/scaffold, binding FANCA directly and being required for the assembly, stability and nuclear accumulation of the core complex. Loss of FANCG causes chromosomal instability, hypersensitivity to crosslinking agents (e.g. mitomycin C) and Fanconi anemia complementation group G, a bone-marrow-failure and cancer-predisposition syndrome. Beyond the nuclear core complex, FANCG participates in a phosphorylation(Ser7)-dependent complex with BRCA2/FANCD1, FANCD2 and XRCC3, and a minor fraction localizes to mitochondria where it interacts with peroxiredoxin-3 (PRDX3) and influences resistance to oxidative stress.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006974 DNA damage response | IBA GO_REF:0000033 | ACCEPT | Summary: FANCG is a subunit of the FA core complex that acts within the cellular response to DNA damage / replication stress; the phylogenetically inferred DNA damage response annotation is well supported and captures a core biological role. Reason: The FA core complex is required for DNA damage recognition at stalled replication forks and for the damage-induced monoubiquitination of FANCD2-FANCI. FANCG is one of the eight core subunits and FANCG-deficient cells are defective in the DNA damage response, consistent with this IBA call at an appropriate level of generality. Supporting Evidence: PMID:22266823 Eight of the FA proteins comprise the FA core complex, a multisubunit complex required for DNA damage recognition at a stalled replication fork PMID:9256465 that partially corrected the hypersensitivity of UV40 to mitomycin C, cisplatin, ethyl methanesulfonate, UV, and |
| GO:0043240 Fanconi anaemia nuclear complex | IBA GO_REF:0000033 | ACCEPT | Summary: FANCG is a bona fide subunit of the FA nuclear core complex; this is the best-supported cellular-component annotation and represents a core function. Reason: Multiple independent experimental studies place FANCG in the multiprotein nuclear FA core complex with FANCA, FANCC, FANCE, FANCF, FANCL and FANCM. The phylogenetic (IBA) call is concordant with this experimental consensus. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus, where it complexes with FANCA, FANCC and FANCG |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: The major form of FANCG is nuclear, where it functions as part of the FA core complex; the electronic subcellular-location annotation is correct though generic. Reason: UniProt records the major form as nuclear (minor form cytoplasmic), and FANCG operates in a nuclear FA complex. Nucleus is a correct if broad location; more specific nucleoplasm and chromatin annotations also exist. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus, where it complexes with FANCA, FANCC and FANCG |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A minor cytoplasmic form of FANCG is documented, but the functionally important pool is nuclear; the cytoplasm location is retained as a non-core localization. Reason: UniProt notes that the minor form is cytoplasmic, and FANCA/FANCG are reported to be cytoplasmic in G1 and G2-M and nuclear during S phase. The annotation is not wrong but is peripheral to the core nuclear ICL-repair function. Supporting Evidence: PMID:17060495 FANCA and FANCG are cytoplasmic in G1 and G2-M phase but are predominantly nuclear during S phase |
| GO:0006974 DNA damage response | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA electronic annotation to DNA damage response; concordant with the IBA and with experimental evidence for FANCG in the FA damage-response pathway. Reason: Duplicates the well-supported DNA damage response role (see the IBA row). The electronic inference is at an appropriate level and is not an over-annotation. Supporting Evidence: PMID:22266823 the FA proteins cooperate in a DNA damage response (DDR) pathway required for DNA interstrand crosslink repair |
| GO:0036297 interstrand cross-link repair | IEA GO_REF:0000002 | ACCEPT | Summary: FANCG, as a core-complex subunit required for FANCD2 monoubiquitination, is required for replication-coupled interstrand crosslink repair; this is a core biological process. Reason: InterPro-based electronic annotation matches the experimental consensus that the FA pathway promotes replication-dependent ICL repair and that FANCG-null cells are hypersensitive to crosslinkers. Supporting Evidence: PMID:19965384 FANCI-FANCD2 is required for replication-coupled ICL repair in S phase PMID:9256465 that partially corrected the hypersensitivity of UV40 to mitomycin C, cisplatin |
| GO:0043240 Fanconi anaemia nuclear complex | IEA GO_REF:0000002 | ACCEPT | Summary: Electronic (InterPro) assignment of FANCG to the FA nuclear complex, concordant with experimental IDA/IBA/NAS evidence. Reason: Duplicates the experimentally well-established FA nuclear complex membership; the InterPro family model correctly maps FANCG into the complex. Supporting Evidence: PMID:22266823 Eight of the FA proteins comprise the FA core complex |
| GO:0005515 protein binding | IPI PMID:10627486 Strong FANCA/FANCG but weak FANCA/FANCC interaction in the y... | KEEP AS NON CORE | Summary: FANCG binds FANCA strongly (yeast two-hybrid). This is a biologically central interaction that underlies FANCG's scaffold role, but the generic 'protein binding' term is uninformative as a molecular function. Reason: The FANCA-FANCG interaction is real and functionally important (it seeds core-complex assembly), but GO:0005515 does not convey the adaptor/scaffold function. The informative molecular function is captured by a proposed NEW protein-macromolecule adaptor activity term and in core_functions. Supporting Evidence: PMID:10627486 the authors found a strong interaction between FANCA and FANCG proteins |
| GO:0005515 protein binding | IPI PMID:10652215 Investigation of Fanconi anemia protein interactions by yeas... | KEEP AS NON CORE | Summary: Yeast two-hybrid mapping of FA protein interactions (FANCA partner). Real interaction but uninformative MF term; retained as non-core. Reason: Supports FANCG's participation in the FA protein-interaction network (FANCA), but the generic protein binding term does not describe FANCG's molecular activity. Supporting Evidence: PMID:10652215 Investigation of Fanconi anemia protein interactions by yeast two-hybrid analysis |
| GO:0005515 protein binding | IPI PMID:11063725 The Fanconi anemia protein FANCF forms a nuclear complex wit... | KEEP AS NON CORE | Summary: FANCG complexes with FANCA, FANCC and FANCF in the nucleus (IntAct rows for FANCA and FANCF). Central to complex assembly but uninformative as an MF term. Reason: Documents FANCG-FANCA and FANCG-FANCF interactions within the nuclear FA complex; complex membership is better captured by the FA nuclear complex CC term, and the scaffold activity by core_functions. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus, where it complexes with FANCA, FANCC and FANCG |
| GO:0005515 protein binding | IPI PMID:12649160 Fanconi anemia protein complex: mapping protein interactions... | KEEP AS NON CORE | Summary: Yeast 2-/3-hybrid mapping of FA complex protein interactions (FANCA, FANCF partners). Real but uninformative MF; kept as non-core. Reason: Corroborates FANCG interactions within the FA complex; the generic term does not describe a molecular activity. Supporting Evidence: PMID:12649160 Fanconi anemia protein complex: mapping protein interactions in the yeast |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | KEEP AS NON CORE | Summary: Proteome-scale interactome mapping capturing a FANCG-FANCA interaction; retained as non-core given the uninformative MF term. Reason: The FANCA partner is biologically plausible and consistent with complex membership, but protein binding is uninformative and high-throughput. Supporting Evidence: PMID:16189514 Towards a proteome-scale map of the human protein-protein interaction network |
| GO:0005515 protein binding | IPI PMID:17289582 Identification of FAAP24, a Fanconi anemia core complex prot... | KEEP AS NON CORE | Summary: Interaction detected in the study identifying FAAP24 as an FA core-complex protein interacting with FANCM (FANCA partner row); retained as non-core. Reason: Consistent with FANCG being embedded in the FA core complex, but the generic MF term is uninformative. Supporting Evidence: PMID:17289582 Identification of FAAP24, a Fanconi anemia core complex protein that interacts with FANCM |
| GO:0005515 protein binding | IPI PMID:17396147 FAAP100 is essential for activation of the Fanconi anemia-as... | KEEP AS NON CORE | Summary: Interaction detected in the FAAP100 study (FANCA partner). Consistent with core-complex membership; non-core due to uninformative MF term. Reason: FAAP100 is essential for FA-pathway activation and this row supports FANCG's presence in the complex, but protein binding conveys no molecular activity. Supporting Evidence: PMID:17396147 FAAP100 is essential for activation of the Fanconi anemia-associated DNA damage response pathway |
| GO:0005515 protein binding | IPI PMID:19102630 The SH3 domain of alphaII spectrin is a target for the Fanco... | KEEP AS NON CORE | Summary: FANCG binds the SH3 domain of alphaII-spectrin (SPTAN1) via an SH3-binding motif. A specific, documented interaction but peripheral to the core FA-complex function. Reason: Direct, mapped interaction (SH3-binding motif in FANCG), proposed to stabilize alphaII-spectrin for ICL repair. Real but a secondary scaffold interaction; the MF term itself is uninformative. Supporting Evidence: PMID:19102630 The site of interaction in FANCG was mapped to a motif that binds to SH3 domains and contains a consensus sequence with preference for the SH3 domain of alphaIISp |
| GO:0005515 protein binding | IPI PMID:22458338 Host-pathogen interactome mapping for HTLV-1 and -2 retrovir... | MARK AS OVER ANNOTATED | Summary: Interaction with HTLV Tax reported in a host-pathogen interactome screen; not a physiological human FANCG function. Reason: This IntAct row is a xeno (viral Tax) interaction from a large host-pathogen mapping effort and does not inform FANCG's endogenous molecular function. Supporting Evidence: PMID:22458338 Host-pathogen interactome mapping for HTLV-1 and -2 retroviruses |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: Interaction (FANCA partner) from a large-scale interactome/protein-communities study; consistent with complex membership, retained non-core. Reason: FANCA partner is plausible and matches known biology, but the term is uninformative and the evidence is high-throughput. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks |
| GO:0005515 protein binding | IPI PMID:31467278 Maximizing binary interactome mapping with a minimal number ... | KEEP AS NON CORE | Summary: Binary interactome mapping capturing a FANCG-FANCA interaction (isoform O15360-3); retained as non-core. Reason: Consistent with FANCA binding but uninformative as a molecular function and high-throughput. Supporting Evidence: PMID:31467278 Maximizing binary interactome mapping with a minimal number of assays |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Rows from a reference binary interactome map pairing FANCG with several unrelated proteins (SUOX, ZNF329, TPRX1, TCEANC, CCHCR1, PRPF18); these are non-specific high-throughput hits. Reason: The partners in this screen are not part of the FA pathway and no functional relationship is established; treated as over-annotation of the generic protein-binding term. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: A neurodegeneration protein-aggregation interactome screen linking FANCG to many unrelated proteins (VIM, GFAP, CYP3A4, RAB5A, HSPB1, etc.); mostly non-specific aggregation-driven hits. Reason: Aside from FANCA, the partners are not FA-pathway related and the assay context (widespread protein aggregation) is prone to non-specific associations; over-annotation of protein binding. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BioPlex dual proteome-scale network capturing a FANCG-FANCA interaction; retained as non-core. Reason: FANCA partner is consistent with known biology, but the term is uninformative and evidence is high-throughput. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome |
| GO:0005515 protein binding | IPI PMID:37398436 AI-guided pipeline for protein-protein interaction drug disc... | KEEP AS NON CORE | Summary: FANCG-FANCA interaction reported within an AI-guided PPI drug-discovery pipeline; consistent with complex membership, retained non-core. Reason: The FANCA partner is plausible, but the generic term is uninformative and the study context is unrelated to FANCG's function. Supporting Evidence: PMID:37398436 AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: FANCG-FANCA interaction from a multimodal cell-maps study; retained as non-core. Reason: Consistent with FANCA binding/complex membership, but protein binding is uninformative as an MF. Supporting Evidence: PMID:40205054 Multimodal cell maps as a foundation for structural and functional genomics |
| GO:0030674 protein-macromolecule adaptor activity | IPI PMID:10627486 Strong FANCA/FANCG but weak FANCA/FANCC interaction in the y... | NEW | Summary: Proposed informative molecular function to replace the uninformative 'protein binding' rows: FANCG is a TPR scaffold that binds FANCA directly and acts as an adaptor bridging FANCA into the FA core complex, required for complex assembly, stability and nuclear accumulation. Reason: FANCG has no catalytic or DNA-binding activity; its molecular role within the FA core complex is that of a protein-protein adaptor/scaffold. The strong direct FANCA-FANCG interaction, together with FANCG's requirement for FANCA stability/nuclear localization and for core-complex integrity, supports an adaptor activity that better captures FANCG's molecular function than GO:0005515. Supporting Evidence: PMID:10627486 the authors found a strong interaction between FANCA and FANCG proteins PMID:11063725 a model in which a multi-protein FA complex serves a nuclear function to maintain genomic integrity |
| GO:0016607 nuclear speck | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: HPA immunofluorescence localizes FANCG to nuclear speckles; a specific sub-nuclear location that is peripheral to the core chromatin-associated FA-complex function. Reason: The nuclear speck localization comes from a single immunofluorescence dataset and does not correspond to the established chromatin/replication-fork site of FA-complex action; retained as a non-core location rather than removed. Supporting Evidence: GO_REF:0000052 Gene Ontology annotation based on curation of immunofluorescence data |
| GO:0000785 chromatin | IDA PMID:22343915 FAAP20: a novel ubiquitin-binding FA nuclear core-complex pr... | ACCEPT | Summary: The FA core complex (including FANCA, stabilized by FANCG) is loaded onto chromatin in a DNA-damage-induced manner; chromatin localization is a core-relevant location for FANCG. Reason: Damage-induced chromatin loading of the FA core complex is central to FA-pathway activation, and the ComplexPortal IDA annotation reflects the functional site of action. Supporting Evidence: PMID:22343915 required for DNA-damage-induced chromatin loading of FANCA and the functional integrity of the FA pathway |
| GO:0036297 interstrand cross-link repair | NAS PMID:19965384 The Fanconi anemia pathway promotes replication-dependent DN... | ACCEPT | Summary: Interstrand crosslink repair is a core FANCG process; the NAS annotation is supported by the demonstration that the FA pathway drives replication-coupled ICL repair. Reason: FANCG is required for FANCD2/FANCI monoubiquitination, which the cited work shows is required for replication-coupled ICL repair; ICL repair is the canonical FA-pathway function. Supporting Evidence: PMID:19965384 FANCI-FANCD2 is required for replication-coupled ICL repair in S phase |
| GO:0043240 Fanconi anaemia nuclear complex | NAS PMID:22343915 FAAP20: a novel ubiquitin-binding FA nuclear core-complex pr... | ACCEPT | Summary: FANCG is a subunit of the FA nuclear core complex; NAS annotation concordant with the experimental consensus. Reason: The FAAP20 study characterizes the FA nuclear core complex of which FANCG is an integral subunit. Supporting Evidence: PMID:22343915 FAAP20 is an integral component of the FA nuclear core complex |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9835411 | KEEP AS NON CORE | Summary: Reactome places a FA core complex:HSP70 species (binding PKR) in the cytosol; corresponds to the minor cytoplasmic pool of FANCG rather than its core nuclear function. Reason: A minor cytoplasmic/cytosolic form of FANCG exists and is captured by this Reactome cytosolic reaction, but the functionally central pool is nuclear/chromatin-associated. Supporting Evidence: PMID:17060495 FANCA and FANCG are cytoplasmic in G1 and G2-M phase but are predominantly nuclear during S phase |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785126 | ACCEPT | Summary: Reactome localizes FANCG to the nucleoplasm as part of FA-pathway ICL-repair reactions; a correct core location for the nuclear FA complex. Reason: Nucleoplasm is consistent with the nuclear FA core complex acting on chromatin/DNA in the ICL-repair pathway modeled by Reactome. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus, where it complexes with FANCA, FANCC and FANCG |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785342 | ACCEPT | Summary: Reactome nucleoplasm localization within the FA ICL-repair pathway; correct core location. Reason: Consistent with the nuclear FA core complex; duplicate of the nucleoplasm annotation from another Reactome reaction in the same pathway. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus, where it complexes with FANCA, FANCC and FANCG |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785361 | ACCEPT | Summary: Reactome nucleoplasm localization (Monoubiquitination of FANCD2:FANCI reaction); correct core location. Reason: Consistent with the nuclear FA core complex acting in the ICL-repair pathway. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus, where it complexes with FANCA, FANCC and FANCG |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785732 | ACCEPT | Summary: Reactome nucleoplasm localization within the FA ICL-repair pathway; correct core location. Reason: Consistent with the nuclear FA core complex; Reactome pathway localization. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus, where it complexes with FANCA, FANCC and FANCG |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785986 | ACCEPT | Summary: Reactome nucleoplasm localization within the FA ICL-repair pathway; correct core location. Reason: Consistent with the nuclear FA core complex; Reactome pathway localization. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus, where it complexes with FANCA, FANCC and FANCG |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6786155 | ACCEPT | Summary: Reactome nucleoplasm localization within the FA ICL-repair pathway; correct core location. Reason: Consistent with the nuclear FA core complex; Reactome pathway localization. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus, where it complexes with FANCA, FANCC and FANCG |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6786166 | ACCEPT | Summary: Reactome nucleoplasm localization within the FA ICL-repair pathway; correct core location. Reason: Consistent with the nuclear FA core complex; Reactome pathway localization. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus, where it complexes with FANCA, FANCC and FANCG |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6786171 | ACCEPT | Summary: Reactome nucleoplasm localization (FANCD2 deubiquitination by USP1:WDR48); correct core location. Reason: Consistent with the nuclear FA core complex; Reactome pathway localization. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus, where it complexes with FANCA, FANCC and FANCG |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6788385 | ACCEPT | Summary: Reactome nucleoplasm localization within the FA ICL-repair pathway; correct core location. Reason: Consistent with the nuclear FA core complex; Reactome pathway localization. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus, where it complexes with FANCA, FANCC and FANCG |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6788392 | ACCEPT | Summary: Reactome nucleoplasm localization within the FA ICL-repair pathway; correct core location. Reason: Consistent with the nuclear FA core complex; Reactome pathway localization. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus, where it complexes with FANCA, FANCC and FANCG |
| GO:0043240 Fanconi anaemia nuclear complex | IDA PMID:22266823 Regulation of Rev1 by the Fanconi anemia core complex. | ACCEPT | Summary: Direct experimental identification of FANCG within the FA core complex; core cellular-component annotation. Reason: The study defines the eight-subunit FA core complex (including FANCG) and its role in FANCD2/FANCI monoubiquitination and Rev1 regulation. Supporting Evidence: PMID:22266823 Eight of the FA proteins comprise the FA core complex, a multisubunit complex required for DNA damage recognition at a stalled replication fork |
| GO:0043240 Fanconi anaemia nuclear complex | IDA PMID:22343915 FAAP20: a novel ubiquitin-binding FA nuclear core-complex pr... | ACCEPT | Summary: Direct identification of FANCG in the FA nuclear core complex; core cellular-component annotation. Reason: FAAP20 is characterized as an integral component of the FA nuclear core complex, which includes FANCG; supports core-complex membership. Supporting Evidence: PMID:22343915 FAAP20 is an integral component of the FA nuclear core complex |
| GO:0043240 Fanconi anaemia nuclear complex | IDA PMID:22705371 A ubiquitin-binding protein, FAAP20, links RNF8-mediated ubi... | ACCEPT | Summary: FANCG identified within the FA core complex in the study linking RNF8 ubiquitin signaling to the FA network via FAAP20; core CC annotation. Reason: The work characterizes FAAP20 as a component of the FA core complex (which contains FANCG) recruited to interstrand crosslinks. Supporting Evidence: PMID:22705371 mediated by FAAP20, a component of the FA core 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 associates with the FA core complex (containing FANCG) and promotes FANCD2 monoubiquitination; supports core-complex membership. Reason: The DNA-remodeling FANCM-MHF module is shown to associate with the vertebrate FA core complex, of which FANCG is a subunit. Supporting Evidence: PMID:20347428 FANCM-MHF associates with the Fanconi anemia (FA) core complex, promotes FANCD2 monoubiquitination in response to DNA damage |
| GO:0005515 protein binding | IPI PMID:17060495 Defective mitochondrial peroxiredoxin-3 results in sensitivi... | KEEP AS NON CORE | Summary: FANCG physically interacts with the mitochondrial peroxidase peroxiredoxin-3 (PRDX3); a specific but non-core interaction linked to oxidative-stress resistance rather than the nuclear FA pathway. Reason: The wild-type (but not G546R) FANCG-PRDX3 interaction is well documented by Y2H and co-IP, but it reflects a secondary mitochondrial/oxidative-stress role; the generic protein binding term is also uninformative as an MF. Supporting Evidence: PMID:17060495 Wild-type but not G546R mutant FANCG physically interacts with the mitochondrial peroxidase peroxiredoxin-3 (PRDX3) |
| GO:0005739 mitochondrion | IDA PMID:17060495 Defective mitochondrial peroxiredoxin-3 results in sensitivi... | KEEP AS NON CORE | Summary: A fraction of FANCG localizes to mitochondria (immunofluorescence, subcellular fractionation). Experimentally supported but a minor/secondary localization relative to the core nuclear function. Reason: Immunofluorescence and mitochondrial-fractionation data support a mitochondrial pool of FANCG, but this is a moonlighting localization tied to oxidative-stress biology and not the canonical chromatin-associated FA-complex function. Supporting Evidence: PMID:17060495 both the immunofluorescent and Western blot assays are consistent with a portion of FANCG protein localizing to the mitochondria |
| GO:0007005 mitochondrion organization | IMP PMID:17060495 Defective mitochondrial peroxiredoxin-3 results in sensitivi... | KEEP AS NON CORE | Summary: FA-G mutant cells show distorted mitochondrial structures, implicating FANCG in mitochondrial integrity; a secondary role likely downstream of oxidative-stress/PRDX3 biology. Reason: The IMP is based on abnormal mitochondrial morphology in FANCG-deficient cells (via PRDX3 deregulation). It is experimentally supported and retained, but is peripheral to the core nuclear ICL-repair function rather than a primary FANCG activity. Supporting Evidence: PMID:17060495 FA-G cells demonstrate distorted mitochondrial structures |
| GO:0003684 damaged DNA binding | TAS PMID:9806548 The Fanconi anaemia group G gene FANCG is identical with XRC... | MARK AS OVER ANNOTATED | Summary: FANCG has no established intrinsic DNA-binding activity; this old TAS/ProtInc molecular-function annotation appears to attribute a complex-level property to the wrong subunit and is best treated as an over-annotation. Reason: FANCG is a TPR alpha-solenoid scaffold lacking any known DNA-binding domain; within the FA core complex, DNA/branched-structure binding is contributed by the FANCM-MHF module, not FANCG. The cited reference (the FANCG=XRCC9 identification paper) makes no claim of direct damaged-DNA binding, and the annotation derives from a legacy ProtInc mapping. Per curation guidance this is not removed outright (a TAS from the era of poorly-defined FA-protein function), but flagged as an over-annotation of a subunit that does not itself enable damaged DNA binding. Supporting Evidence: PMID:9806548 We identified the gene as human XRCC9 |
| GO:0006281 DNA repair | TAS PMID:9256465 The human XRCC9 gene corrects chromosomal instability and mu... | ACCEPT | Summary: FANCG (XRCC9) is required for DNA repair, as its expression corrects the mutagen hypersensitivity and chromosomal instability of the repair-deficient CHO UV40 mutant; a correct core process (general parent of interstrand cross-link repair). Reason: The original XRCC9 cloning study established a DNA-repair role by functional complementation. DNA repair is a correct if broad process term; the more specific interstrand cross-link repair term is also annotated. Supporting Evidence: PMID:9256465 that partially corrected the hypersensitivity of UV40 to mitomycin C, cisplatin, ethyl methanesulfonate, UV, and |
| GO:0000724 double-strand break repair via homologous recombination | ISS PMID:12861027 Fanconi anemia FANCG protein in mitigating radiation- and en... | NEW | Summary: FANCG is required for efficient homologous-recombination repair of DNA double-strand breaks. FANCG-knockout DT40 cells show ~9-fold reduced HR repair of I-SceI-induced chromosomal DSBs, and FANCG additionally nucleates a Ser7-phosphorylation-dependent D1-D2-G-X3 complex (BRCA2/FANCD1, FANCD2, XRCC3) that supports HR repair. Reason: This is a genuine, experimentally supported FANCG function that the GOA set did not capture as a distinct process annotation. Both supporting studies are in CHICKEN DT40 cells, so the evidence code is ISS rather than IMP - an IMP would assert a human mutant phenotype that neither reference provides. Gene disruption in DT40 directly demonstrates a requirement for FANCG in HR-mediated DSB repair (PMID:12861027), and FANCG-dependent, Ser7-phosphorylation-gated assembly of the D1-D2-G-X3 complex with the RAD51 paralog XRCC3 links FANCG to the HR machinery independently of its core-complex role in FANCD2 monoubiquitination (PMID:18212739). Treated as a secondary (non-core) function relative to the canonical core-complex ICL-repair role. Supporting Evidence: PMID:12861027 We conclude that FANCG is required for efficient HR-mediated repair of at least some types of DSBs PMID:18212739 A role for D1-D2-G-X3 in homologous recombination repair (HRR) is supported by our finding that FANCG and the RAD51-paralog XRCC3 are epistatic for sensitivity to DNA crosslinking compounds in DT40 chicken cells |
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Download this section (compressed HTML)Q: What is the precise molecular contribution of the FANCG TPR scaffold to core-complex E3 ligase activity beyond stabilizing FANCA (e.g. does it position substrates or other subunits)?
Q: Is the Ser7-phosphorylation-dependent FANCG-BRCA2/FANCD2/XRCC3 complex a genuinely separable homologous-recombination function, or a hand-off from the core complex?
Q: How physiologically important is the mitochondrial/PRDX3 oxidative-stress role of FANCG relative to its nuclear ICL-repair function in the bone-marrow-failure phenotype?
Experiment: Structure-guided separation-of-function FANCG mutants (FANCA-binding vs core-complex-stabilizing surfaces) assayed for FANCD2 monoubiquitination and MMC/cisplatin resistance.
Type: structure-function mutagenesis
Experiment: Quantitative proteomics of the FANCG interactome under DNA-damage vs oxidative-stress conditions to delineate nuclear core-complex partners from mitochondrial/other secondary partners.
Type: affinity-proteomics
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