RFWD3 (RING finger and WD repeat domain-containing protein 3; also RNF201; Fanconi anemia complementation group W, FANCW) is a nuclear RING-type E3 ubiquitin-protein ligase (EC 2.3.2.27). It combines an N-terminal region bearing ATM/ATR phosphorylation sites (Ser46, Ser63), a degenerate RING zinc finger that provides the catalytic ligase activity (active-site Cys315), a coiled-coil, and a C-terminal WD40 Ξ²-propeller that mediates protein-protein interactions. RFWD3 is recruited, through its WD40 domain binding the RPA32 (RPA2) subunit of the single-stranded-DNA-binding replication protein A (RPA) complex, to stalled replication forks and sites of DNA damage. There it polyubiquitinates RPA (all three subunits) and RAD51, promoting their VCP/p97-dependent turnover and timely removal from DNA damage sites so that the RPA-to-RAD51 exchange, homologous recombination and interstrand crosslink (ICL) repair can proceed. RFWD3 also promotes ubiquitination of proteins on single-stranded DNA, driving PCNA ubiquitination and translesion DNA synthesis. It additionally participates in replication-checkpoint signaling (ATR-dependent CHK1 activation) and, as a secondary activity, cooperates with MDM2 to ubiquitinate and stabilize p53 in the late DNA-damage response, contributing to the G1 checkpoint. Biallelic loss-of-function mutations cause Fanconi anemia, and Rfwd3-knockout mice show embryonic lethality, subfertility and reduced lifespan.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0061630 ubiquitin protein ligase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred RING-type ubiquitin ligase activity. This is the core molecular function of RFWD3 and is strongly corroborated by direct biochemistry. Reason: RFWD3 is a RING-finger E3 ligase (EC 2.3.2.27) with catalytic Cys315; multiple IDA studies demonstrate ligase activity toward RPA, RAD51 and p53. The IBA is at the correct level of specificity and represents the central evolved function. Supporting Evidence: PMID:26474068 We demonstrate that the E3 ligase RFWD3 mediates RPA ubiquitination. |
| GO:0016567 protein ubiquitination | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred involvement in protein ubiquitination, the process carried out by the RFWD3 ligase activity. Reason: Directly supported: RFWD3 ubiquitinates RPA, RAD51 and p53 and promotes ubiquitination of proteins on ssDNA. Correct and well-supported. Supporting Evidence: PMID:33321094 the E3 ubiquitin ligase RFWD3 promotes ubiquitylation of proteins on ssDNA |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred nuclear localization; RFWD3 acts in the nucleus at replication forks and DNA damage sites. Reason: RFWD3 functions in the nucleus where it ubiquitinates RPA/RAD51 at chromatin; is_active_in nucleus is the correct core location. Supporting Evidence: PMID:28691929 impaired relocation of mutant RFWD3 to chromatin |
| GO:0031297 replication fork processing | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred role at stalled replication forks, consistent with RFWD3 promoting fork restart and repair at stalled forks. Reason: RFWD3 is recruited to stalled replication forks and is required for fork restart and repair at stalled forks (Elia et al. 2015). Supporting Evidence: PMID:26474068 RFWD3 is necessary for replication fork restart, normal repair kinetics during |
| GO:0090734 site of DNA damage | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred activity at sites of DNA damage; RFWD3 is recruited to and functions at DNA damage sites. Reason: RFWD3 translocates to tracks of laser micro-irradiation and to MMC-induced foci that co-localize with RPA and gamma-H2AX; this is a core functional location. Supporting Evidence: PMID:28575657 translocates to tracks of laser micro-irradiation and co-localizes with the phosphorylated form of histone variant H2AX |
| GO:0004842 ubiquitin-protein transferase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based electronic annotation of ubiquitin-protein transferase activity, a parent/equivalent of the demonstrated RING ligase activity. Reason: Correct: RFWD3 is a ubiquitin transferase (RING E3). Slightly more general than GO:0061630 but not wrong; the specific ligase activity is captured by the IDA annotations. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation of nuclear localization, consistent with experimental data. Reason: Nuclear localization is experimentally established (multiple EXP/IDA annotations); the IEA is correct. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic subcellular-location annotation of cytoplasm; RFWD3 is found in the cytoplasm of undamaged cells before nuclear recruitment upon damage. Reason: A cytoplasmic pool is documented in undamaged cells, but the functional site of RFWD3 is the nucleus/chromatin; cytoplasmic localization is peripheral to its DNA-repair function. Supporting Evidence: PMID:21558276 RFWD3 associates with replication protein |
| GO:0016567 protein ubiquitination | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation of protein ubiquitination, matching experimental evidence. Reason: RFWD3 ubiquitinates multiple substrates; the process annotation is correct. |
| GO:0016605 PML body | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic subcellular-location annotation of PML nuclear body, from the reported partial association of RFWD3 with PML bodies in undamaged cells. Reason: RFWD3 is partially associated with PML nuclear bodies in undamaged cells, but this is not the site of its characterized DNA-repair ligase activity. Supporting Evidence: PMID:21558276 RFWD3 associates with replication protein |
| GO:0036297 interstrand cross-link repair | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based annotation of interstrand cross-link repair, a core RFWD3 process confirmed experimentally. Reason: RFWD3-deficient cells are profoundly hypersensitive to ICL-inducing agents; ICL repair is a major RFWD3 function (FANCW). Supporting Evidence: PMID:28575657 show profound defects in ICL repair |
| GO:0061630 ubiquitin protein ligase activity | IEA GO_REF:0000003 | ACCEPT | Summary: EC-mapping-based annotation of ubiquitin ligase activity (EC 2.3.2.27). Reason: Consistent with the RecName EC 2.3.2.27 and direct biochemical demonstration of RING E3 ligase activity. |
| GO:0005515 protein binding | IPI PMID:19549727 Analysis of the human E2 ubiquitin conjugating enzyme protei... | MARK AS OVER ANNOTATED | Summary: IntAct-curated interaction with the E2 conjugating enzyme UBE2N (UBC13) from a systematic E2 interaction-network screen. Reason: GO:0005515 protein binding is uninformative as a molecular function. The biologically relevant interaction (RFWD3 partnering with the K63-forming E2 UBE2N) is better captured by the ligase activity core function; no specific MF term is warranted from this high-throughput screen. |
| GO:0005515 protein binding | IPI PMID:20173098 RFWD3-Mdm2 ubiquitin ligase complex positively regulates p53... | MARK AS OVER ANNOTATED | Summary: IntAct-curated interactions with p53 (TP53) and MDM2 from the RFWD3-MDM2-p53 study. Reason: Generic protein binding is uninformative; the specific and informative interactions are separately annotated as p53 binding (GO:0002039) and MDM2/MDM4 family protein binding (GO:0097371). |
| GO:0005515 protein binding | IPI PMID:24126761 hPrimpol1/CCDC111 is a human DNA primase-polymerase required... | MARK AS OVER ANNOTATED | Summary: IntAct-curated RFWD3-RPA2 (P15927) interaction detected in a PRIMPOL study. Reason: Uninformative generic binding term; the functionally important RPA2 interaction underlies the core RFWD3 recruitment/ubiquitination function and is captured there. |
| GO:0005515 protein binding | IPI PMID:25260751 The MEKK1 PHD ubiquitinates TAB1 to activate MAPKs in respon... | MARK AS OVER ANNOTATED | Summary: IntAct-curated RFWD3-UBE2N (P61088) interaction detected in a MEKK1/TAB1 study. Reason: Generic protein binding is uninformative; the UBE2N (E2) partnership is subsumed by the ligase activity annotation. |
| GO:0005515 protein binding | IPI PMID:28691929 Biallelic mutations in the ubiquitin ligase RFWD3 cause Fanc... | MARK AS OVER ANNOTATED | Summary: IntAct-curated RFWD3-RPA2 (P15927) interaction from the FANCW paper. Reason: Uninformative generic term; the RPA2 interaction that recruits RFWD3 to chromatin is central and captured by the core function rather than by GO:0005515. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: IntAct-curated RFWD3-RPA2 (P15927) interaction from a systems-level multimodal cell-mapping study. Reason: Generic protein binding is uninformative; the RPA2 interaction is already represented functionally elsewhere. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence localization to the nucleoplasm. Reason: Consistent with the established nuclear localization; nucleoplasm is an accurate sub-nuclear location. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: HPA immunofluorescence localization to the cytosol. Reason: A cytosolic pool is consistent with cytoplasmic localization in undamaged cells, but is peripheral to the nuclear DNA-repair function. |
| GO:0005634 nucleus | EXP PMID:21504906 E3 ligase RFWD3 participates in replication checkpoint contr... | ACCEPT | Summary: Experimental nuclear localization; RFWD3 is recruited to the nucleus/stalled forks upon replication stress. Reason: Nuclear localization is well established experimentally. Supporting Evidence: PMID:21504906 RFWD3 is recruited to stalled replication forks and co-localizes with RPA2 in response to replication stress |
| GO:0005634 nucleus | EXP PMID:21558276 RING finger and WD repeat domain 3 (RFWD3) associates with r... | ACCEPT | Summary: Experimental nuclear localization from the RFWD3-RPA association study. Reason: Consistent with established nuclear localization. |
| GO:0005634 nucleus | EXP PMID:28575657 RPA-Mediated Recruitment of the E3 Ligase RFWD3 Is Vital for... | ACCEPT | Summary: Experimental nuclear localization; GFP-RFWD3 forms nuclear foci/tracks at DNA damage sites. Reason: Nuclear localization at DNA damage sites is directly demonstrated. Supporting Evidence: PMID:28575657 translocates to tracks of laser micro-irradiation |
| GO:0005737 cytoplasm | EXP PMID:21558276 RING finger and WD repeat domain 3 (RFWD3) associates with r... | KEEP AS NON CORE | Summary: Experimental cytoplasmic localization; RFWD3 is found in the cytoplasm of undamaged cells. Reason: Real localization in undamaged cells but peripheral to the nuclear repair function. |
| GO:0005737 cytoplasm | EXP PMID:28691929 Biallelic mutations in the ubiquitin ligase RFWD3 cause Fanc... | KEEP AS NON CORE | Summary: Experimental cytoplasmic localization reported in the FANCW study. Reason: Cytoplasmic pool documented; the functionally critical relocation is to chromatin/nucleus. |
| GO:0036297 interstrand cross-link repair | IDA PMID:33321094 The ubiquitin ligase RFWD3 is required for translesion DNA s... | ACCEPT | Summary: Direct demonstration of RFWD3's role in the crosslink/lesion-bypass response; RFWD3 promotes ssDNA-protein ubiquitination required for TLS during ICL repair. Reason: RFWD3 is required for translesion synthesis, an integral gap-filling step of ICL repair; ICL repair involvement is a core function. Supporting Evidence: PMID:33321094 TLS across different DNA lesions is drastically impaired |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:20173098 RFWD3-Mdm2 ubiquitin ligase complex positively regulates p53... | ACCEPT | Summary: Direct demonstration of RFWD3 E3 ligase activity toward p53 (in the RFWD3-MDM2 complex). Reason: In vitro experiments show RFWD3 acts as a p53 E3 ligase; supports the core RING ligase activity. (The p53 process context is secondary.) Supporting Evidence: PMID:20173098 RFWD3 is a p53 E3 ubiquitin ligase |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:26474068 RFWD3-Dependent Ubiquitination of RPA Regulates Repair at St... | ACCEPT | Summary: Direct demonstration that RFWD3 ligase activity ubiquitinates RPA. Reason: Core catalytic function; RFWD3 mediates RPA ubiquitination. Supporting Evidence: PMID:26474068 the E3 ligase RFWD3 is responsible for RPA ubiquitination |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:28575657 RPA-Mediated Recruitment of the E3 Ligase RFWD3 Is Vital for... | ACCEPT | Summary: Direct demonstration of RFWD3 ligase activity; the recombinant C315A active-site mutant is inactive in vitro. Reason: Confirms catalytic RING E3 activity dependent on Cys315; core molecular function. Supporting Evidence: PMID:28575657 which renders the recombinant protein inactive in vitro |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:28575658 RFWD3-Mediated Ubiquitination Promotes Timely Removal of Bot... | ACCEPT | Summary: Direct demonstration that RFWD3 polyubiquitinates both RPA and RAD51 in vitro and in vivo. Reason: Core catalytic function toward the physiological substrates RPA and RAD51. Supporting Evidence: PMID:28575658 RFWD3 polyubiquitinates both RPA and RAD51 in vitro and in vivo |
| GO:0000724 double-strand break repair via homologous recombination | IMP PMID:28691929 Biallelic mutations in the ubiquitin ligase RFWD3 cause Fanc... | ACCEPT | Summary: Loss-of-function (patient/engineered mutations) disrupts homologous recombination, establishing RFWD3's role in HR. Reason: HR was disrupted in RFWD3-mutant cells; a core process for RFWD3 (FANCW). Supporting Evidence: PMID:28691929 HR was disrupted in RFWD3-mutant cells |
| GO:0005634 nucleus | IMP PMID:28691929 Biallelic mutations in the ubiquitin ligase RFWD3 cause Fanc... | ACCEPT | Summary: Mutation-based evidence that RFWD3 relocation to the nucleus/chromatin is required for function. Reason: Nuclear/chromatin relocation is impaired by FA mutations, underscoring the nucleus as the functional compartment. Supporting Evidence: PMID:28691929 impaired relocation of mutant RFWD3 to chromatin |
| GO:0000724 double-strand break repair via homologous recombination | IDA PMID:26474068 RFWD3-Dependent Ubiquitination of RPA Regulates Repair at St... | ACCEPT | Summary: RFWD3 is required for homologous recombination at stalled replication forks. Reason: Core process; RFWD3 stimulates HR at stalled forks. Supporting Evidence: PMID:26474068 homologous recombination (HR) at stalled replication forks |
| GO:0000724 double-strand break repair via homologous recombination | IDA PMID:28575657 RPA-Mediated Recruitment of the E3 Ligase RFWD3 Is Vital for... | ACCEPT | Summary: RFWD3-deficient cells show HR defects (PARP-inhibitor hypersensitivity, persistent RPA in RAD51 foci). Reason: Supports the core HR function; RFWD3 controls RPA/RAD51 dynamics required for HR. Supporting Evidence: PMID:28575657 unloading of RPA from sites of ICL induction is perturbed in RFWD3-deficient cells |
| GO:0000724 double-strand break repair via homologous recombination | IDA PMID:28575658 RFWD3-Mediated Ubiquitination Promotes Timely Removal of Bot... | ACCEPT | Summary: RFWD3-mediated removal of RPA and RAD51 facilitates late-phase homologous recombination. Reason: Core HR process, mechanistically defined via RPA/RAD51 turnover. Supporting Evidence: PMID:28575658 crucial for progression to the late-phase HR and suppression of the FA phenotype |
| GO:0005515 protein binding | IPI PMID:28575657 RPA-Mediated Recruitment of the E3 Ligase RFWD3 Is Vital for... | MARK AS OVER ANNOTATED | Summary: IntAct-curated interactions with RPA2 (P15927) and RAD51 (Q06609), the physiological RFWD3 substrates/partners. Reason: Generic protein binding is uninformative as an MF; the functionally meaningful RPA2 and RAD51 interactions underpin the core ligase/HR function and are captured there. |
| GO:0005515 protein binding | IPI PMID:28575658 RFWD3-Mediated Ubiquitination Promotes Timely Removal of Bot... | MARK AS OVER ANNOTATED | Summary: IntAct-curated RFWD3-RPA2 (P15927) interaction. Reason: Uninformative generic binding term; the RPA2 interaction is functionally represented by the core function. |
| GO:0006974 DNA damage response | IDA PMID:26474068 RFWD3-Dependent Ubiquitination of RPA Regulates Repair at St... | ACCEPT | Summary: RFWD3 acts within the DNA damage response (RPA ubiquitination upon replication stress). Reason: Accurate high-level process; RFWD3's ligase activity is part of the DDR. More specific processes (HR, ICL repair, fork processing) are also annotated. Supporting Evidence: PMID:26474068 to profile ubiquitination in the DNA damage response (DDR) |
| GO:0006974 DNA damage response | IDA PMID:28575657 RPA-Mediated Recruitment of the E3 Ligase RFWD3 Is Vital for... | ACCEPT | Summary: RFWD3 recruitment and action at DNA damage sites within the DDR. Reason: Correct high-level process annotation, consistent with damage-site recruitment. Supporting Evidence: PMID:28575657 translocates to tracks of laser micro-irradiation |
| GO:0006974 DNA damage response | IDA PMID:28575658 RFWD3-Mediated Ubiquitination Promotes Timely Removal of Bot... | ACCEPT | Summary: RFWD3 acts in the DDR via ATR/ATM-regulated ubiquitination of RPA and RAD51. Reason: Correct high-level DDR process; RFWD3 activity depends on ATR/ATM phosphorylation. Supporting Evidence: PMID:28575658 Phosphorylation by ATR and ATM kinases is required for this activity in vivo |
| GO:0016567 protein ubiquitination | IDA PMID:26474068 RFWD3-Dependent Ubiquitination of RPA Regulates Repair at St... | ACCEPT | Summary: Direct evidence of RFWD3-mediated RPA ubiquitination. Reason: Core process; RFWD3 ubiquitinates RPA on chromatin. Supporting Evidence: PMID:26474068 the E3 ligase RFWD3 is responsible for RPA ubiquitination |
| GO:0016567 protein ubiquitination | IDA PMID:28575657 RPA-Mediated Recruitment of the E3 Ligase RFWD3 Is Vital for... | ACCEPT | Summary: RFWD3 ubiquitinates RPA at sites of ICL-induced fork stalling. Reason: Core process; RFWD3 ubiquitylates RPA. Supporting Evidence: PMID:28575657 interacts with and ubiquitylates replication protein A (RPA) |
| GO:0016567 protein ubiquitination | IDA PMID:28575658 RFWD3-Mediated Ubiquitination Promotes Timely Removal of Bot... | ACCEPT | Summary: RFWD3 polyubiquitinates RPA and RAD51. Reason: Core process, defined toward physiological substrates. Supporting Evidence: PMID:28575658 RFWD3 polyubiquitinates both RPA and RAD51 in vitro and in vivo |
| GO:0031297 replication fork processing | IDA PMID:26474068 RFWD3-Dependent Ubiquitination of RPA Regulates Repair at St... | ACCEPT | Summary: RFWD3 promotes restart and remodeling of stalled replication forks and supports normal fork progression. Reason: Direct evidence that RFWD3 is necessary for fork restart and repair at stalled forks (Elia et al. 2015); further corroborated by its role in normal fork progression via PCNA binding (Lin et al. 2018) and in ZRANB3-dependent fork remodeling/reversal (Moore et al. 2023). Supporting Evidence: PMID:26474068 we found that depletion of RFWD3 decreased fork restart PMID:30530694 in unperturbed human cells, RFWD3 localizes at replication forks and associates with proliferating cell nuclear antigen (PCNA) via its PCNA-interacting protein (PIP) motif PMID:37036693 RFWD3 stimulates fork remodeling in a ZRANB3-epistatic manner |
| GO:0036297 interstrand cross-link repair | IMP PMID:28575657 RPA-Mediated Recruitment of the E3 Ligase RFWD3 Is Vital for... | ACCEPT | Summary: RFWD3-hypomorphic cells are profoundly hypersensitive to ICL-inducing agents, demonstrating an ICL-repair role. Reason: Loss-of-function evidence establishes ICL repair as a major RFWD3 function (core). Supporting Evidence: PMID:28575657 argues strongly that ICL repair is a major function of RFWD3 |
| GO:0036297 interstrand cross-link repair | IMP PMID:28575658 RFWD3-Mediated Ubiquitination Promotes Timely Removal of Bot... | ACCEPT | Summary: RFWD3 inactivation impairs ICL repair; suppression of the FA phenotype depends on RFWD3-mediated RPA/RAD51 removal. Reason: Core ICL-repair process consistent with FANCW identity. Supporting Evidence: PMID:28575658 suppression of the FA phenotype |
| GO:0090734 site of DNA damage | IDA PMID:28575657 RPA-Mediated Recruitment of the E3 Ligase RFWD3 Is Vital for... | ACCEPT | Summary: RFWD3 localizes to sites of ICL/DNA damage (laser tracks, MMC foci). Reason: Core functional location, directly imaged. Supporting Evidence: PMID:28575657 translocates to tracks of laser micro-irradiation |
| GO:0090734 site of DNA damage | IDA PMID:28575658 RFWD3-Mediated Ubiquitination Promotes Timely Removal of Bot... | ACCEPT | Summary: RFWD3 acts at DNA damage sites to remove RPA and RAD51. Reason: Consistent with damage-site localization and function; core functional location. Supporting Evidence: PMID:28575658 timely removal of RPA and RAD51 from DNA damage sites |
| GO:0005515 protein binding | IPI PMID:21504906 E3 ligase RFWD3 participates in replication checkpoint contr... | MARK AS OVER ANNOTATED | Summary: IntAct-curated direct RFWD3-RPA2 (P15927) interaction, shown with purified proteins. Reason: Generic protein binding is uninformative; the direct RPA2 interaction that recruits RFWD3 to stalled forks is central and represented by the core function. |
| GO:0035861 site of double-strand break | IDA PMID:21504906 E3 ligase RFWD3 participates in replication checkpoint contr... | ACCEPT | Summary: RFWD3 co-localizes with RPA2 at stalled forks/damage sites in response to replication stress. Reason: Accurate colocalization annotation consistent with recruitment to damage sites; complements the site of DNA damage annotations. Supporting Evidence: PMID:21504906 RFWD3 is recruited to stalled replication forks and co-localizes with RPA2 in response to replication stress |
| GO:2000001 regulation of DNA damage checkpoint | IMP PMID:21504906 E3 ligase RFWD3 participates in replication checkpoint contr... | KEEP AS NON CORE | Summary: RFWD3 depletion decreases ATR-dependent CHK1 activation after replication stress, implicating it in replication-checkpoint control. Reason: A genuine but secondary/context-dependent role; the effect on CHK1 activation is cell-type dependent and is distinct from the core RPA/RAD51-ubiquitination repair function. Supporting Evidence: PMID:21504906 RFWD3 is important for ATR-dependent Chk1 activation in response to replication stress |
| GO:0002039 p53 binding | IPI PMID:20173098 RFWD3-Mdm2 ubiquitin ligase complex positively regulates p53... | KEEP AS NON CORE | Summary: Direct interaction with p53 (TP53) within the RFWD3-MDM2-p53 complex that regulates p53 stability. Reason: An informative, specific binding (unlike generic protein binding), but it underlies the secondary p53-stabilization role rather than the core DNA-repair ligase function. Supporting Evidence: PMID:20173098 forms a complex with Mdm2 and p53 to synergistically ubiquitinate p53 |
| GO:0005634 nucleus | IDA PMID:20173098 RFWD3-Mdm2 ubiquitin ligase complex positively regulates p53... | ACCEPT | Summary: Experimental nuclear localization in the p53-regulation study. Reason: Consistent with established nuclear localization. |
| GO:0010212 response to ionizing radiation | IDA PMID:20173098 RFWD3-Mdm2 ubiquitin ligase complex positively regulates p53... | KEEP AS NON CORE | Summary: RFWD3 is phosphorylated and stabilizes p53 in the late response to ionizing radiation. Reason: A real damage-response context, but tied to the secondary p53 role; the core RFWD3 function is better described by HR/ICL-repair processes. Supporting Evidence: PMID:20173098 p53 stabilization in the late phase after ionizing radiation correlates with active ubiquitination |
| GO:0016567 protein ubiquitination | IDA PMID:20173098 RFWD3-Mdm2 ubiquitin ligase complex positively regulates p53... | ACCEPT | Summary: RFWD3 ubiquitinates p53 (with MDM2) in the late DNA-damage response. Reason: A genuine protein-ubiquitination event catalyzed by RFWD3; correct process term, here in the secondary p53 context. Supporting Evidence: PMID:20173098 forms a complex with Mdm2 and p53 to synergistically ubiquitinate p53 |
| GO:0031571 mitotic G1 DNA damage checkpoint signaling | IMP PMID:20173098 RFWD3-Mdm2 ubiquitin ligase complex positively regulates p53... | KEEP AS NON CORE | Summary: RFWD3 positively regulates p53 stability when the G1 cell-cycle checkpoint is activated. Reason: Secondary function via p53/MDM2; distinct from the core replication-associated repair activity and supported by a single group. Supporting Evidence: PMID:20173098 a positive regulator of p53 stability when the G(1) cell cycle checkpoint is activated |
| GO:0097371 MDM2/MDM4 family protein binding | IPI PMID:20173098 RFWD3-Mdm2 ubiquitin ligase complex positively regulates p53... | KEEP AS NON CORE | Summary: Direct interaction with MDM2 in the p53-regulatory RFWD3-MDM2 complex. Reason: Informative specific binding supporting the secondary p53-stabilization role, not the core DNA-repair ligase function. Supporting Evidence: PMID:20173098 RFWD3 (RNF201/FLJ10520) forms a complex with Mdm2 and p53 |
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