HAMAP rule MF_03066
General rule information
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| Accession | MF_03066 |
| Dates | 5-MAR-2009 (Created)
23-MAY-2024 (Last updated, Version 7) |
| Name | RNF168 |
| Scope(s) |
Eukaryota Vertebrata |
| Template(s) | Q8IYW5 (RN168_HUMAN); [ Recover all ] |
| Triggered by |
HAMAP; MF_03066 (Get profile general information and statistics) |
Propagated annotation
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Identifier, protein and gene names
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| Identifier | RN168 |
| case <OC:Mammalia> | |
| Protein name | RecName: Full=E3 ubiquitin-protein ligase RNF168; EC=2.3.2.27; AltName: Full=RING finger protein 168; AltName: Full=RING-type E3 ubiquitin transferase RNF168; |
| else | |
| Protein name | RecName: Full=E3 ubiquitin-protein ligase EC=2.3.2.27; AltName: Full=RING finger protein 168; AltName: Full=RING-type E3 ubiquitin transferase |
| end case | |
| Gene name | Name=RNF168; |
Comments
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| case <OC:Mammalia> | |
| FUNCTION | E3 ubiquitin-protein ligase required for accumulation of repair proteins to sites of DNA damage. Acts with @gn(UBE2N)/@gn(UBC13) to amplify the @gn(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 @gn(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 @gn(TP53BP1) and @gn(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 @gn(FAAP20) 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 @gn(JMJD2A)/@gn(KDM4A) in collaboration with @gn(RNF8), leading to unmask H4K20me2 mark and promote the recruitment of @gn(TP53BP1) at DNA damage sites. Not able to initiate 'Lys-63'-linked ubiquitination in vitro; possibly due to partial occlusion of the @gn(UBE2N)/@gn(UBC13)- binding region. Catalyzes monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub, respectively). |
| SUBUNIT | Monomer. Interacts with UBE2N/UBC13. |
| else | |
| FUNCTION | E3 ubiquitin-protein ligase required for accumulation of repair proteins to sites of DNA damage. Acts with @gn(UBE2N)/@gn(UBC13) to amplify the @gn(RNF8)-dependent histone ubiquitination. Recruited to sites of DNA damage at double-strand breaks (DSBs) by binding to ubiquitinated histone H2A and ubiquitinates histone H2A and H2AX, leading to amplify the @gn(RNF8)-dependent H2A ubiquitination and 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 @gn(TP53BP1) and @gn(BRCA1). Catalyzes monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub, respectively). |
| SUBUNIT | Monomer. |
| end case | |
| CATALYTIC ACTIVITY | Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27; |
| PATHWAY | Protein modification; protein ubiquitination. |
| SUBCELLULAR LOCATION | Nucleus. Note=Localizes to double-strand breaks (DSBs) sites of DNA damage. |
| DOMAIN | The MIU motif (motif interacting with ubiquitin) mediates the interaction with both 'Lys-48'- and 'Lys-63'-linked ubiquitin chains. The UMI motif mediates interaction with ubiquitin with a preference for 'Lys-63'-linked ubiquitin. The specificity for different types of ubiquitin is mediated by juxtaposition of ubiquitin-binding motifs (MIU and UMI motifs) with LR motifs (LRMs). |
| case <OC:Mammalia> | |
| PTM | Sumoylated with @gn(SUMO1) by @gn(PIAS4) in response to double- strand breaks (DSBs). |
| PTM | Ubiquitinated. |
| CAUTION | According to a well-established model, @gn(RNF168) cannot initiate H2A 'Lys-63'-linked ubiquitination and is recruited following @gn(RNF8)-dependent histone ubiquitination to amplify H2A 'Lys-63'- linked ubiquitination. However, other data suggest that @gn(RNF168) is the priming ubiquitin ligase by mediating monoubiquitination of 'Lys- 13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub respectively). These data suggest that @gn(RNF168) might be recruited to DSBs sites in a @gn(RNF8)-dependent manner by binding to non-histone proteins ubiquitinated via 'Lys-63'-linked and initiates monoubiquitination of H2A, which is then amplified by @gn(RNF8). Additional evidences are however required to confirm these data. |
| end case | |
| SIMILARITY | Belongs to the RNF168 family. |
Keywords
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| Chromatin regulator | |
| DNA damage | |
| DNA repair | |
| Metal-binding | |
| Nucleus | |
| Transferase | |
| case <OC:Mammalia> | |
| Ubl conjugation | |
| end case | |
| Ubl conjugation pathway | |
| Zinc | |
| Zinc-finger | |
Gene Ontology
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| GO:0003682; Molecular function:chromatin binding |
| GO:0042393; Molecular function:histone binding |
| GO:0043130; Molecular function:ubiquitin binding |
| GO:0004842; Molecular function:ubiquitin-protein transferase activity |
| GO:0016567; Biological process:protein ubiquitination |
| GO:0045739; Biological process:positive regulation of DNA repair |
| GO:0010212; Biological process:response to ionizing radiation |
| GO:0006302; Biological process:double-strand break repair |
| GO:0000151; Cellular component:ubiquitin ligase complex |
| GO:0005634; Cellular component:nucleus |
Cross-references
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| PROSITE | PS00518; ZF_RING_1; 1; |
| PROSITE | PS50089; ZF_RING_2; 1; |
| PROSITE | PS50313; GLU_RICH; 0-unlimited; |
Features
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| From: RN168_HUMAN (Q8IYW5) | ||||||||||||
| Key | From | To | Description | Tag | Condition | FTGroup | ||||||
| MOTIF | 110 | 128 | /note="LR motif 1" | [ILV]-[SC]-[KQE]-P-G-E-[ILV]-R-[RQK]-E-Y-E-x-[EQ]-[ILV]-x-[RK]-x(2) | ||||||||
| MOTIF | 143 | 151 | /note="UMI motif" | E-[EDQ]-Y-I-[RQ]-[RK]-L-L-A | ||||||||
| MOTIF | 168 | 191 | /note="MIU motif 1" | x-E-[EKQR]-Q-[LM]-[KRLE]-x-D-E-x-L-A-[RW]-x-[LIV]-S-x-[DSNKEQ]-[LMI]-[DN]-x(1,4) | ||||||||
| MOTIF | 439 | 462 | /note="MIU motif 2" | R-[RHYWQ]-[RKQ]-Q-E-[EK]-[QHED]-D-[RH]-x-[LF]-A-L-[QER]-[LI]-Q-[RKE]-[EQ]-x-[DNEK]-[KQR]-[ER]-x(2) | ||||||||
| MOTIF | 466 | 477 | /note="LR motif 2" | R-x-[KN]-G-S-x(3)-Y-x-L-R | ||||||||
Additional information
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| Size range | 422-577 amino acids |
| Related rules |
None |
| Fusion | Nter: None Cter: None |