UIMC1
UIMC1, also known as RAP80, is a nuclear ubiquitin-binding protein and a subunit of the BRCA1-A complex. It recognises 'Lys-63'-linked ubiquitin on histones at DNA lesions and helps direct BRCA1-BARD1 to sites of DNA damage. Browse Assay Genie's current range of UIMC1 research reagents below, or read on for the biology behind the target.
UIMC1 is a ubiquitin-binding protein that specifically recognises and binds 'Lys-63'-linked ubiquitin. It plays a central role in the BRCA1-A complex by binding 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesion sites. This recruits the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also has deubiquitinase activity that removes 'Lys-63'-linked ubiquitin from histones H2A and H2AX.
The protein binds monoubiquitin only weakly, with much less affinity than 'Lys-63'-linked ubiquitin, and it does not bind 'Lys-48'-linked ubiquitin. It may interact with monoubiquitinated histones H2A and H2B, although the relevance of this in vivo is unclear. UIMC1 may also act indirectly as a transcriptional repressor, by inhibiting the interaction of NR6A1 with the corepressor NCOR1. The UIMC1 protein localises to the nucleus and belongs to the RAP80 family.
In HGNC, the UIMC1 gene is placed in the BRCA1 A complex group and in the group of UBZ4 CCHC-type zinc fingers. As RefSeq summarises, the gene encodes a nuclear protein that interacts with BRCA1 (breast cancer 1) in a complex to recognise and repair DNA lesions, and alternative splicing gives multiple transcript variants. RAP80 is the common alias, and orthologous genes are annotated in mouse and rat as Uimc1. These features make UIMC1 a useful subject for studies of ubiquitin signalling and the cellular response to DNA damage.
UIMC1 targets the BRCA1-BARD1 heterodimer to double-strand break sites, making it central to studies of how cells recognise and repair DNA lesions.
UIMC1 selectively reads 'Lys-63'-linked ubiquitin but not 'Lys-48'-linked chains, which makes it a model for ubiquitin-linkage specificity.
UIMC1 binds 'Lys-63'-linked ubiquitinated histones H2A and H2AX, linking histone ubiquitination to the assembly of repair complexes.
UIMC1 may indirectly repress transcription by inhibiting the interaction of NR6A1 with the corepressor NCOR1.
UIMC1 binds 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesion sites as part of the BRCA1-A complex. This targets the BRCA1-BARD1 heterodimer to double-strand breaks. It may also indirectly repress transcription by affecting NR6A1 and NCOR1 interaction.
Yes. RAP80 is an alias of UIMC1, whose HGNC name is ubiquitin interaction motif containing 1. UniProt lists the protein as BRCA1-A complex subunit RAP80 and places it in the RAP80 family. RefSeq notes that alternative splicing produces multiple transcript variants.
Orthologues of the human UIMC1 gene are annotated in both mouse and rat, and each is named Uimc1. This allows the DNA damage response role of the protein to be studied in rodent systems; check the datasheet of any product for its validated reactivity.
BRCA1-A complex partners, histone substrates and transcriptional corepressor pathway members related to UIMC1.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q96RL1; product specifications from Assay Genie datasheets.