RNF168 — Ring finger protein 168
RNF168 belongs to a gene co-expression module in 5 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.
RNF168's module in each cell type
| Cell type | Module | Shares the module with | |
|---|---|---|---|
| CD4⁺ T cells | DNA damage response DNA/chromatin regulation | ATP2B1, CENPC, DEAF1, FBXO34, HAX1, HECTD1, KMT5C, MRPL50 +7 more | View in SCUBA |
| Gamma-delta T cells | DNA Damage Ubiquitin DNA/chromatin regulation | ACBD3, CDADC1, CTPS1, CWC25, FNIP1, ING3, KLHL18, RALGAPA1 +7 more | |
| Innate lymphoid cells | NR4A Activation Response activation | ALG13, ARL4A, BCAS2, CASP3, CHMP1B, CREM, DDX24, DLL1 +16 more | View in SCUBA |
| Macrophages | ER Stress Response Stress | ARHGEF12, ATXN7, BTBD7, CD2AP, CLIP2, DAPK1, DST, ERN1 +14 more | View in SCUBA |
| Mucosal-associated invariant T cell | Transcriptional Repression Immune regulation | ANKRD11, CMIP, MXI1, NR3C1, PELI2, PROSER1, RB1CC1, RCOR1 +7 more |
About the gene
| Synonyms | FLJ35794 |
|---|---|
| Chromosome | 3: 196468783-196503768 |
| Predicted location | Intracellular |
| Essential gene | Yes |
| Protein class | Disease related genes, Enzymes, Essential proteins, Human disease related genes, Potential drug targets, Predicted intracellular proteins |
| Molecular function | Chromatin regulator, Transferase |
| Biological process | DNA damage, DNA repair, Ubl conjugation pathway |
Function
E3 ubiquitin-protein ligase required for accumulation of repair proteins to sites of DNA damage. Acts with UBE2N/UBC13 to amplify the RNF8-dependent histone ubiquitination. Recruited to sites of DNA damage at double-strand breaks (DSBs) by binding to ubiquitinated histone H2A and H2AX and amplifies the RNF8-dependent H2A ubiquitination, promoting the formation of 'Lys-63'-linked ubiquitin conjugates. This leads to concentrate ubiquitinated histones H2A and H2AX at DNA lesions to the threshold required for recruitment of TP53BP1 and BRCA1. Also recruited at DNA interstrand cross-links (ICLs) sites and promotes accumulation of 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. Following DNA damage, promotes the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF8, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. Not able to initiate 'Lys-63'-linked ubiquitination in vitro; possibly due to partial occlusion of the UBE2N/UBC13-binding region. Catalyzes monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub, respectively).
Human Protein Atlas · Open Targets · UniProt
Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.