| UniProt ID | RNF8_HUMAN | |
|---|---|---|
| UniProt AC | O76064 | |
| Protein Name | E3 ubiquitin-protein ligase RNF8 {ECO:0000255|HAMAP-Rule:MF_03067} | |
| Gene Name | RNF8 {ECO:0000255|HAMAP-Rule:MF_03067} | |
| Organism | Homo sapiens (Human). | |
| Sequence Length | 485 | |
| Subcellular Localization | Nucleus . Cytoplasm . Midbody . Chromosome, telomere . Recruited at uncapped telomeres (By similarity). Following DNA damage, such as double-strand breaks, recruited to the sites of damage (PubMed:18001824, PubMed:18077395, PubMed:22266820, PubMed:23 | |
| Protein Description | E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: by mediating the 'Lys-63'-linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing 'Lys-48'-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the 'Lys-63'-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF). Also controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and PAXIP1/PTIP to DNA damage sites. Also recruited at DNA interstrand cross-links (ICLs) sites and catalyzes '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. Promotes the formation of 'Lys-63'-linked polyubiquitin chains via interactions with the specific ubiquitin-conjugating UBE2N/UBC13 and ubiquitinates non-histone substrates such as PCNA. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation. Also catalyzes the formation of 'Lys-48'-linked polyubiquitin chains via interaction with the ubiquitin-conjugating UBE2L6/UBCH8, leading to degradation of substrate proteins such as CHEK2, JMJD2A/KDM4A and KU80/XRCC5: it is still unclear how the preference toward 'Lys-48'- versus 'Lys-63'-linked ubiquitination is regulated but it could be due to RNF8 ability to interact with specific E2 specific ligases. For instance, interaction with phosphorylated HERC2 promotes the association between RNF8 and UBE2N/UBC13 and favors the specific formation of 'Lys-63'-linked ubiquitin chains. Promotes non-homologous end joining (NHEJ) by promoting the 'Lys-48'-linked ubiquitination and degradation the of KU80/XRCC5. Following DNA damage, mediates the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF168, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. [PubMed: 11322894] | |
| Protein Sequence | MGEPGFFVTGDRAGGRSWCLRRVGMSAGWLLLEDGCEVTVGRGFGVTYQLVSKICPLMISRNHCVLKQNPEGQWTIMDNKSLNGVWLNRARLEPLRVYSIHQGDYIQLGVPLENKENAEYEYEVTEEDWETIYPCLSPKNDQMIEKNKELRTKRKFSLDELAGPGAEGPSNLKSKINKVSCESGQPVKSQGKGEVASTPSDNLDPKLTALEPSKTTGAPIYPGFPKVTEVHHEQKASNSSASQRSLQMFKVTMSRILRLKIQMQEKHEAVMNVKKQTQKGNSKKVVQMEQELQDLQSQLCAEQAQQQARVEQLEKTFQEEEQHLQGLEIAQGEKDLKQQLAQALQEHWALMEELNRSKKDFEAIIQAKNKELEQTKEEKEKMQAQKEEVLSHMNDVLENELQCIICSEYFIEAVTLNCAHSFCSYCINEWMKRKIECPICRKDIKSKTYSLVLDNCINKMVNNLSSEVKERRIVLIRERKAKRLF | |
| Overview of Protein Modification Sites with Functional and Structural Information | ||
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* ASA = Accessible Surface Area
| Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
|---|---|---|---|---|---|
| 67 | Ubiquitination | SRNHCVLKQNPEGQW HCCCEEEECCCCCCE | 27.86 | 29967540 | |
| 80 | Ubiquitination | QWTIMDNKSLNGVWL CEEEECCCCCCCEEE | 52.64 | 32015554 | |
| 155 | Ubiquitination | KELRTKRKFSLDELA HHHHHHCCCCHHHHC | 40.64 | 29967540 | |
| 157 | Phosphorylation | LRTKRKFSLDELAGP HHHHCCCCHHHHCCC | 37.64 | 29255136 | |
| 167 (in isoform 2) | Ubiquitination | - | 77.03 | 21906983 | |
| 170 | Phosphorylation | GPGAEGPSNLKSKIN CCCCCCCCCHHHHCC | 66.70 | 24719451 | |
| 173 | Ubiquitination | AEGPSNLKSKINKVS CCCCCCHHHHCCEEE | 54.69 | 32015554 | |
| 192 | Ubiquitination | QPVKSQGKGEVASTP CCCCCCCCCCCCCCC | 44.24 | - | |
| 198 | Phosphorylation | GKGEVASTPSDNLDP CCCCCCCCCCCCCCC | 19.64 | - | |
| 206 | Ubiquitination | PSDNLDPKLTALEPS CCCCCCCCCCCCCCC | 59.13 | 29967540 | |
| 214 | Ubiquitination | LTALEPSKTTGAPIY CCCCCCCCCCCCCCC | 61.90 | 29967540 | |
| 235 | Ubiquitination | TEVHHEQKASNSSAS CHHCCCHHCCCCCHH | 51.28 | 21906983 | |
| 235 (in isoform 1) | Ubiquitination | - | 51.28 | 21906983 | |
| 284 | Ubiquitination | TQKGNSKKVVQMEQE HCCCCHHHHHHHHHH | 47.67 | 29967540 | |
| 316 | Phosphorylation | RVEQLEKTFQEEEQH HHHHHHHHHHHHHHH | 22.60 | 28555341 | |
| 334 | Ubiquitination | LEIAQGEKDLKQQLA HHHHCCCHHHHHHHH | 75.16 | 29967540 | |
| 368 | Ubiquitination | FEAIIQAKNKELEQT HHHHHHHHHHHHHHH | 52.77 | 32015554 | |
| 459 | Ubiquitination | VLDNCINKMVNNLSS HHHHHHHHHHHCCCH | 25.06 | 32015554 |
* Distance = the distance between SAP position and PTM sites.
| Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
|---|---|---|---|---|---|---|
Oops, there are no SNP-PTM records of RNF8_HUMAN !! | ||||||
| Kegg Disease | ||||||
|---|---|---|---|---|---|---|
| There are no disease associations of PTM sites. | ||||||
| OMIM Disease | ||||||
| There are no disease associations of PTM sites. | ||||||
| Kegg Drug | ||||||
| There are no disease associations of PTM sites. | ||||||
| DrugBank | ||||||
| There are no disease associations of PTM sites. | ||||||
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| Phosphorylation | |
| Reference | PubMed |
| "Quantitative phosphoproteomic analysis of T cell receptor signalingreveals system-wide modulation of protein-protein interactions."; Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,Rodionov V., Han D.K.; Sci. Signal. 2:RA46-RA46(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-157, AND MASSSPECTROMETRY. | |
| "A quantitative atlas of mitotic phosphorylation."; Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-157, AND MASSSPECTROMETRY. | |
