ID:RFWD3_HUMAN DESCRIPTION: RecName: Full=E3 ubiquitin-protein ligase RFWD3; EC=6.3.2.-; AltName: Full=RING finger and WD repeat domain-containing protein 3; AltName: Full=RING finger protein 201; FUNCTION: E3 ubiquitin-protein ligase that mediates the ubiquitination of p53/TP53 in the late response to DNA damage, and acts as a positive regulator of p53/TP53 stability, thereby regulating the G1/S DNA damage checkpoint. May act by catalyzing the formation of short polyubiquitin chains on p53/TP53 that are not targeted to the proteasome. In response to ionizing radiation, interacts with MDM2 and enhances p53/TP53 ubiquitination, possibly by restricting MDM2 from extending polyubiquitin chains on ubiquitinated p53/TP53. Plays a role in RPA-mediated DNA damage signaling and repair. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: Interacts with MDM2 and p53/TP53. Binds to the RPA complex via direct interaction with RPA2. SUBCELLULAR LOCATION: Nucleus. Nucleus, PML body. Cytoplasm. Note=In undamaged cells, found both in the cytoplasm and in the nucleus, partially associated with PML nuclear bodies. In response to replication block, such as that caused by hydroxyurea treatment, or to DNA damage caused by ionizing radiations or doxorubicin, recruited to the nucleus, to stalled replication forks or to sites of DNA repair. This recruitment depends upon RPA2. DEVELOPMENTAL STAGE: Up-regulated in the S-G2 phase. DOMAIN: The coiled coil domain may be involved in RPA2-binding. PTM: Phosphorylated at Ser-46 and Ser-63 upon DNA damage by ATM or ATR. ATM phosphorylation occurs at early times upon DNA damage, while ATR is the major kinase at later times. Phosphorylation by ATM and ATR is required to stabilize p53/TP53. Part of the phosphorylation depends upon RPA2 presence. SIMILARITY: Contains 1 RING-type zinc finger. SIMILARITY: Contains 3 WD repeats. SEQUENCE CAUTION: Sequence=BAA91662.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=BAF83889.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=BAG38132.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): RFWD3 CDC HuGE Published Literature: RFWD3
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q6PCD5
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.