E3 ubiquitin-protein ligase RFWD3 (IPR037381)

Short name: RFWD3

Overlapping homologous superfamilies


Family relationships



RFWD3 is a RING-type E3 ubiquitin-protein ligase required for the repair of DNA interstrand cross-links (ICL) in response to DNA damage [PMID: 28575658, PMID: 21558276, PMID: 21504906].

During ICL repair, single-stranded DNA (ssDNA) is generated. The trimeric ssDNA binding protein complex RPA coats the ssDNA. Subsequently, RAD51 is loaded onto RPA-bound ssDNA and catalyzes the critical activity in homologous recombination (HR). RFWD3 polyubiquitinates both RPA and RAD5, which increases their local turnover in DNA damage-induced foci to facilitate HR [PMID: 28575658]. RFWD3-mediated ubiquitination of RPA has been shown to be essential for HR [PMID: 26474068].

GO terms

Biological Process

GO:0036297 interstrand cross-link repair
GO:0016567 protein ubiquitination

Molecular Function

GO:0004842 ubiquitin-protein transferase activity

Cellular Component

GO:0005634 nucleus

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.