InnateDB Protein
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IDBP-71205.6
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Last Modified
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2014-10-13 [Report errors or provide feedback]
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Gene Symbol
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RNF168
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Protein Name
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ring finger protein 168
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Synonyms
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Species
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Homo sapiens
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Ensembl Protein
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ENSP00000320898
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InnateDB Gene
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IDBG-71203 (RNF168)
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Protein Structure
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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). {ECO:0000269PubMed:19203578, ECO:0000269PubMed:19203579, ECO:0000269PubMed:20550933, ECO:0000269PubMed:22373579, ECO:0000269PubMed:22705371, ECO:0000269PubMed:22713238, ECO:0000269PubMed:22742833, ECO:0000269PubMed:22980979}.
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Subcellular Localization |
Nucleus {ECO:0000269PubMed:19203578, ECO:0000269PubMed:19203579, ECO:0000269PubMed:19500350, ECO:0000269PubMed:21041483, ECO:0000269PubMed:22742833}. Note=Localizes to double-strand breaks (DSBs) sites of DNA damage.
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Disease Associations |
Riddle syndrome (RIDDLES) [MIM:611943]: Characterized by increased radiosensitivity, immunodeficiency, mild motor control and learning difficulties, facial dysmorphism, and short stature. Defects are probably due to impaired localization of TP53BP1 and BRCA1 at DNA lesions. {ECO:0000269PubMed:19203578}. Note=The disease is caused by mutations affecting the gene represented in this entry.
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Tissue Specificity |
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Comments |
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Number of Interactions
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This gene and/or its encoded proteins are associated with 41 experimentally validated interaction(s) in this database.
Experimentally validated |
Total |
41
[view]
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Protein-Protein |
40
[view]
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Protein-DNA |
1
[view]
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Protein-RNA |
0
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DNA-DNA |
0
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RNA-RNA |
0
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DNA-RNA |
0
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Molecular Function |
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Biological Process |
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Cellular Component |
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PDB ID |
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InterPro |
IPR001841
Zinc finger, RING-type
IPR018957
Zinc finger, C3HC4 RING-type
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PFAM |
PF13639
PF14634
PF00097
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PRINTS |
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PIRSF |
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SMART |
SM00184
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TIGRFAMs |
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Modification |
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SwissProt |
Q8IYW5
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PhosphoSite |
PhosphoSite-Q8IYW5
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TrEMBL |
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UniProt Splice Variant |
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Entrez Gene |
165918
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UniGene |
Hs.727426
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RefSeq |
NP_689830
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HUGO |
HGNC:26661
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OMIM |
612688
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CCDS |
CCDS3317
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HPRD |
08190
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IMGT |
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EMBL |
AC092933
AC117490
AK054732
AK093113
BC033791
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GenPept |
AAH33791
BAB70801
BAC04060
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