InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Rnf168

Summary

InnateDB Protein

IDBP-153959.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Rnf168

Protein Name

ring finger protein 168

Synonyms

3110001H15Rik;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000014218

InnateDB Gene

IDBG-153957 (Rnf168)

Protein Structure

UniProt Annotation

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 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. 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) (By similarity). Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. {ECO:0000250, ECO:0000269PubMed:20080757}.

Subcellular Localization

Nucleus {ECO:0000250}. Note=Localizes to double-strand breaks (DSBs) sites of DNA damage. {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 3 experimentally validated interaction(s) in this database.
They are also associated with 25 interaction(s) predicted by orthology.

Experimentally validated
Total	3 [view]
Protein-Protein	3 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	25 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003682	chromatin binding
GO:0004842	ubiquitin-protein transferase activity
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0016874	ligase activity
GO:0042393	histone binding
GO:0043130	ubiquitin binding
GO:0070530	K63-linked polyubiquitin binding

Biological Process

GO:0006302	double-strand break repair
GO:0006511	ubiquitin-dependent protein catabolic process
GO:0006974	cellular response to DNA damage stimulus
GO:0010212	response to ionizing radiation
GO:0016567	protein ubiquitination
GO:0035518	histone H2A monoubiquitination
GO:0036351	histone H2A-K13 ubiquitination
GO:0036352	histone H2A-K15 ubiquitination
GO:0045190	isotype switching
GO:0045739	positive regulation of DNA repair
GO:0045900	negative regulation of translational elongation
GO:0070534	protein K63-linked ubiquitination
GO:0070535	histone H2A K63-linked ubiquitination

Cellular Component

GO:0000151	ubiquitin ligase complex
GO:0005634	nucleus
GO:0035861	site of double-strand break

Protein Structure and Domains

PDB ID

MGI:1917488

InterPro

IPR001841 Zinc finger, RING-type

PFAM

PF13639
PF14634

PRINTS

PIRSF

SMART

SM00184

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q80XJ2

PhosphoSite

PhosphoSite-Q80XJ2

TrEMBL

UniProt Splice Variant

Entrez Gene

70238

UniGene

Mm.472868

RefSeq

MGI ID

MGI Symbol

Rnf168

OMIM

CCDS

HPRD

IMGT

EMBL

AC126265 BC046815

GenPept

AAH46815