Overview
| Uniprot ID | Q8IYW5 |
|---|
| Protein Name | E3 ubiquitin-protein ligase RNF168 |
|---|
| Gene Name | RNF168 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 227 |
RNTGDIQKYLTPKSQ |
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)
Protein Sequence
10
MALPKDAIPS
20
LSECQCGICM
30
EILVEPVTLP
40
CNHTLCKPCF
50
QSTVEKASLC
60
CPFCRRRVSS
70
WTRYHTRRNS
80
LVNVELWTII
90
QKHYPRECKL
100
RASGQESEEV
110
ADDYQPVRLL
120
SKPGELRREY
130
EEEISKVAAE
140
RRASEEEENK
150
ASEEYIQRLL
160
AEEEEEEKRQ
170
AEKRRRAMEE
180
QLKSDEELAR
190
KLSIDINNFC
200
EGSISASPLN
210
SRKSDPVTPK
220
SEKKSKNKQR
230
NTGDIQKYLT
240
PKSQFGSASH
250
SEAVQEVRKD
260
SVSKDIDSSD
270
RKSPTGQDTE
280
IEDMPTLSPQ
290
ISLGVGEQGA
300
DSSIESPMPW
310
LCACGAEWYH
320
EGNVKTRPSN
330
HGKELCVLSH
340
ERPKTRVPYS
350
KETAVMPCGR
360
TESGCAPTSG
370
VTQTNGNNTG
380
ETENEESCLL
390
ISKEISKRKN
400
QESSFEAVKD
410
PCFSAKRRKV
420
SPESSPDQEE
430
TEINFTQKLI
440
DLEHLLFERH
450
KQEEQDRLLA
460
LQLQKEVDKE
470
QMVPNRQKGS
480
PDEYHLRATS
490
SPPDKVLNGQ
500
RKNPKDGNFK
510
RQTHTKHPTP
520
ERGSRDKNRQ
530
VSLKMQLKQS
540
VNRRKMPNST
550
RDHCKVSKSA
560
HSLQPSISQK
570
SVFQMFQRCT
K
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0035861 |
site of double-strand break |
| Cellular Component |
GO:0016604 |
nuclear body |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:0032991 |
protein-containing complex |
| Cellular Component |
GO:0000151 |
ubiquitin ligase complex |
| Molecular Function |
GO:0003682 |
chromatin binding |
| Molecular Function |
GO:0042393 |
histone binding |
| Molecular Function |
GO:0140858 |
histone H2AK15 ubiquitin ligase activity |
| Molecular Function |
GO:0140852 |
histone ubiquitin ligase activity |
| Molecular Function |
GO:0070530 |
K63-linked polyubiquitin modification-dependent protein binding |
| Molecular Function |
GO:0031491 |
nucleosome binding |
| Molecular Function |
GO:0043130 |
ubiquitin binding |
| Molecular Function |
GO:0004842 |
ubiquitin-protein transferase activity |
| Molecular Function |
GO:0008270 |
zinc ion binding |
| Biological Process |
GO:0006974 |
DNA damage response |
| Biological Process |
GO:0140861 |
DNA repair-dependent chromatin remodeling |
| Biological Process |
GO:0006302 |
double-strand break repair |
| Biological Process |
GO:0097680 |
double-strand break repair via classical nonhomologous end joining |
| Biological Process |
GO:0006303 |
double-strand break repair via nonhomologous end joining |
| Biological Process |
GO:0040029 |
epigenetic regulation of gene expression |
| Biological Process |
GO:0036297 |
interstrand cross-link repair |
| Biological Process |
GO:0045190 |
isotype switching |
| Biological Process |
GO:0034244 |
negative regulation of transcription elongation by RNA polymerase II |
| Biological Process |
GO:0045739 |
positive regulation of DNA repair |
| Biological Process |
GO:0070534 |
protein K63-linked ubiquitination |
| Biological Process |
GO:0016567 |
protein ubiquitination |
| Biological Process |
GO:0010212 |
response to ionizing radiation |
| Biological Process |
GO:0006511 |
ubiquitin-dependent protein catabolic process |
Reference
PMID: N/A