RNF168
entrez
165918
canonical
uniprot
Q8IYW5
canonical
ensembl
ENSG00000163961
resolver
ensp
ENSP00000320898
resolver
enst
ENST00000318037
resolver
genesymbol
RNF168
resolver
hgnc
HGNC:26661
resolver
uniprot
Q8NA67
resolver
uniprot
Q96NS4
resolver
uniprot_entry
RN168_HUMAN
resolver
uniprot_sec
Q8NA67
resolver
uniprot_sec
Q96NS4
resolver
amino_acid_sequence
MALPKDAIPSLSECQCGICMEILVEPVTLPCNHTLCKPCFQSTVEKASLCCPFCRRRVSSWTRYHTRRNSLVNVELWTIIQKHYPRECKLRASGQESEEVADDYQPVRLLSKPGELRREYEEEISKVAAERRASEEEENKASEEYIQRLLAEEEEEEKRQAEKRRRAMEEQLKSDEELARKLSIDINNFCEGSISASPLNSRKSDPVTPKSEKKSKNKQRNTGDIQKYLTPKSQFGSASHSEAVQEVRKDSVSKDIDSSDRKSPTGQDTEIEDMPTLSPQISLGVGEQGADSSIESPMPWLCACGAEWYHEGNVKTRPSNHGKELCVLSHERPKTRVPYSKETAVMPCGRTESGCAPTSGVTQTNGNNTGETENEESCLLISKEISKRKNQESSFEAVKDPCFSAKRRKVSPESSPDQEETEINFTQKLIDLEHLLFERHKQEEQDRLLALQLQKEVDKEQMVPNRQKGSPDEYHLRATSSPPDKVLNGQRKNPKDGNFKRQTHTKHPTPERGSRDKNRQVSLKMQLKQSVNRRKMPNSTRDHCKVSKSAHSLQPSISQKSVFQMFQRCTK
uniprot
proteins
disease_involvement
DISEASE: Riddle syndrome (RIDL) [MIM:611943]: An autosomal recessive disorder characterized by increased radiosensitivity, immunodeficiency, mild motor control and learning difficulties, facial dysmorphism, and short stature. {ECO:0000269|PubMed:19203578}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.3.2.27
uniprot
proteins
function
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:0000255|HAMAP-Rule:MF_03066, ECO:0000269|PubMed:19203578, ECO:0000269|PubMed:19203579, ECO:0000269|PubMed:20550933, ECO:0000269|PubMed:22373579, ECO:0000269|PubMed:22705371, ECO:0000269|PubMed:22713238, ECO:0000269|PubMed:22742833, ECO:0000269|PubMed:22980979, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538}.
uniprot
proteins
mass_dalton
65020
uniprot
proteins
mutagenesis
MUTAGEN 16; /note="C->S: Does not affect ability to bind ubiquitin and localization to DSBs sites, while it abolishes E3 ligase activity; when associated with S-19."; /evidence="ECO:0000269|PubMed:19500350"; MUTAGEN 18; /note="I->A: Abolishes ability to ubiquitinate KDM4A."; /evidence="ECO:0000269|PubMed:22373579"; MUTAGEN 19; /note="C->S: Does not affect ability to bind ubiquitin and localization to DSBs sites, while it abolishes E3 ligase activity; when associated with S-16."; /evidence="ECO:0000269|PubMed:19500350"; MUTAGEN 57; /note="R->D: Does not affect the monomeric structure but abolishes ability to monoubiquitinate H2A in nucleosomes."; /evidence="ECO:0000269|PubMed:22980979"; MUTAGEN 149..150; /note="LL->AA: Impaired ability to bind ubiquitin."; /evidence="ECO:0000269|PubMed:21041483"; MUTAGEN 179; /note="A->G: Impairs ability to form foci following ionizing radiation and impaired binding to 'Lys-63'-linked ubiquitin."; /evidence="ECO:0000269|PubMed:19203578, ECO:0000269|PubMed:19500350, ECO:0000269|PubMed:21041483"; MUTAGEN 450; /note="A->G: Still able to bind 'Lys-63'-linked ubiquitin."; /evidence="ECO:0000269|PubMed:19203578, ECO:0000269|PubMed:19500350, ECO:0000269|PubMed:21041483"; MUTAGEN 476..477; /note="LR->AA: Does not affect ubiquitin-binding but impairs recruitment to DSBs."; /evidence="ECO:0000269|PubMed:22742833
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000255|HAMAP-Rule:MF_03066}.
uniprot
proteins
post_translational_modification
PTM: Sumoylated with SUMO1 by PIAS4 in response to double-strand breaks (DSBs). {ECO:0000255|HAMAP-Rule:MF_03066, ECO:0000269|PubMed:22508508}.; PTM: Ubiquitinated. {ECO:0000255|HAMAP-Rule:MF_03066, ECO:0000269|PubMed:19500350, ECO:0000269|PubMed:21041483}.
uniprot
proteins
protein_family
RNF168 family
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16641997
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19203578
uniprot
proteins
pubmed
19203579
uniprot
proteins
pubmed
19500350
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20550933
uniprot
proteins
pubmed
21041483
uniprot
proteins
pubmed
22373579
uniprot
proteins
pubmed
22508508
uniprot
proteins
pubmed
22589545
uniprot
proteins
pubmed
22705371
uniprot
proteins
pubmed
22713238
uniprot
proteins
pubmed
22742833
uniprot
proteins
pubmed
22980979
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23760478
uniprot
proteins
pubmed
27153538
uniprot
proteins
pubmed
28112733
uniprot
proteins
sequence_length
571
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03066, ECO:0000269|PubMed:19203578, ECO:0000269|PubMed:19203579, ECO:0000269|PubMed:19500350, ECO:0000269|PubMed:21041483, ECO:0000269|PubMed:22742833}. Note=Localizes to double-strand breaks (DSBs) sites of DNA damage. {ECO:0000255|HAMAP-Rule:MF_03066}.
uniprot
proteins