Overview
| Uniprot ID | A0A286XI80 |
|---|
| Protein Name | E3 ubiquitin-protein ligase RNF168 |
|---|
| Gene Name | RNF168 |
|---|
| Organism | Cavia porcellus |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 127 |
EYEEEICKVEAERRA |
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. 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
MAVSRDAVPA
20
LSECQCPICM
30
EILVEPVTLP
40
CRHTLCNPCF
50
RATVEKASLY
60
CPFCRRRVSS
70
WTRYHTRRNS
80
LINVELWDLI
90
QKHYPAECKR
100
RASGQESEEI
110
AGEACQPIRL
120
LSQPGELRRE
130
YEEEICKVEA
140
ERRASEEEEN
150
KASEEYIQRL
160
LAEEEEEERR
170
RAQKRRSEME
180
EQLKSDEALA
190
RRLSININNF
200
HEKSVLASPS
210
NSRKSDPVTA
220
KLQPKNKNKQ
230
TNIGDIQKYL
240
SPKSQFVSSS
250
QSATGQEVRR
260
NSISKEVGSN
270
DSKSPGWQDV
280
EAEDRPALSP
290
QMCLEIQQPS
300
ARSSMDSAMP
310
RPCAYDADQC
320
LESKVKTRSH
330
NHDGELCVAN
340
HASPKATVPS
350
EAISAEFGDK
360
AGNGGSLPGG
370
THLTADSTAE
380
TENEEAGLLL
390
SKDVSKRKHL
400
EPAPETARGA
410
ACSVKRKKMF
420
PNSSSSEEET
430
ERNFTQKLMD
440
LEHLLFERHK
450
QEEQDRLLAL
460
QLQEEEEKEQ
470
KSRQNGSHKE
480
YELRAASTAP
490
SKPWSTQTAA
500
LGQAETAGDH
510
NPKRQPTTKH
520
PRAQRGSRDE
530
NRQPFKVQPR
540
PSDNKKKMPK
550
SSRDHRSVAR
560
SAQSLLPRDS
570
QKSIFEMFPR
CAK
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0016604 |
nuclear body |
| Cellular Component |
GO:0035861 |
site of double-strand break |
| Cellular Component |
GO:0000151 |
ubiquitin ligase complex |
| Molecular Function |
GO:0042393 |
histone binding |
| Molecular Function |
GO:0140858 |
histone H2AK15 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:0008270 |
zinc ion binding |
| Biological Process |
GO:0140861 |
DNA repair-dependent chromatin remodeling |
| Biological Process |
GO:0097680 |
double-strand break repair via classical nonhomologous end joining |
| Biological Process |
GO:0040029 |
epigenetic regulation of gene expression |
| 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:0010212 |
response to ionizing radiation |
| Biological Process |
GO:0006511 |
ubiquitin-dependent protein catabolic process |
Reference
[1] Feng J, Chen X, Li R, Xie Y, Zhang X et al.. Lactylome analysis reveals potential target modified proteins in the retina of form-deprivation myopia.. iScience 27(9):110606. 2024 Sep 20. PMID: 39246443.