RFWD3

Entrez Summary: N/A
UniProt Summary: E3 ubiquitin-protein ligase required for the repair of DNA interstrand cross-links (ICL) in response to DNA damage (PubMed:21504906, PubMed:21558276, PubMed:26474068, PubMed:28575657, PubMed:28575658). Plays a key role in RPA- mediated DNA damage signaling and repair (PubMed:21504906, PubMed:21558276, PubMed:26474068, PubMed:28575657, PubMed:28575658). Acts by mediating ubiquitination of the RPA complex (RPA1, RPA2 and RPA3 subunits) and RAD51 at stalled replication forks, leading to remove them from DNA damage sites and promote homologous recombination (PubMed:26474068, PubMed:28575657, PubMed:28575658). Also 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 (PubMed:20173098). May act by catalyzing the formation of short polyubiquitin chains on p53/TP53 that are not targeted to the proteasome (PubMed:20173098). 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 (PubMed:20173098). {ECO:0000269|PubMed:20173098, ECO:0000269|PubMed:21504906, ECO:0000269|PubMed:21558276, ECO:0000269|PubMed:26474068, ECO:0000269|PubMed:28575657, ECO:0000269|PubMed:28575658}.

Pfam Domains GO Terms

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Global Fraction of Cell Lines Where Essential: 1/739

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	0/1
909776.0	0/1
bile duct	0/28
blood	0/28
bone	0/26
breast	0/33
central nervous system	0/56
cervix	0/4
colorectal	0/17
esophagus	0/13
fibroblast	0/1
gastric	0/16
kidney	0/21
liver	0/20
lung	0/75
lymphocyte	0/16
ovary	0/26
pancreas	0/24
peripheral nervous system	0/16
plasma cell	0/15
prostate	0/1
skin	0/24
soft tissue	0/9
thyroid	0/2
upper aerodigestive	0/22
urinary tract	0/29
uterus	0/5

Expression Distribution

Screen	Score
BI-6727 0.001μM R01 exp42	-2.12
A-366 10μM R03 exp115	2.15

zf-rbx1
zf-C3HC4

chromosome breakage
programmed DNA elimination
MDM2/MDM4 family protein binding
regulation of DNA damage checkpoint
site of DNA damage
regulation of cell cycle checkpoint
replication fork processing
DNA-dependent DNA replication maintenance of fidelity
interstrand cross-link repair
site of double-strand break
mitotic G1 DNA damage checkpoint
mitotic G1/S transition checkpoint
G1 DNA damage checkpoint
p53 binding
mitotic DNA damage checkpoint
double-strand break repair via homologous recombination
recombinational repair
PML body
negative regulation of G1/S transition of mitotic cell cycle
mitotic DNA integrity checkpoint
negative regulation of cell cycle G1/S phase transition
DNA-dependent DNA replication
DNA damage checkpoint
DNA integrity checkpoint
response to ionizing radiation
regulation of G1/S transition of mitotic cell cycle
mitotic cell cycle checkpoint
regulation of cell cycle G1/S phase transition
double-strand break repair
cell cycle checkpoint
negative regulation of mitotic cell cycle phase transition
DNA replication
regulation of response to DNA damage stimulus
DNA recombination
negative regulation of cell cycle phase transition
ubiquitin-protein transferase activity
negative regulation of mitotic cell cycle
negative regulation of cell cycle process
regulation of mitotic cell cycle phase transition
response to radiation