Overview
| Uniprot ID | Q99708 |
|---|
| Protein Name | DNA endonuclease RBBP8 |
|---|
| Gene Name | RBBP8 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 360 |
PGKKKHLKTLPFSNT |
Function
Endonuclease that cooperates with the MRE11-RAD50-NBN (MRN) complex in DNA-end resection, the first step of double-strand break (DSB) repair through the homologous recombination (HR) pathway (PubMed:17965729, PubMed:19202191, PubMed:19759395, PubMed:20064462, PubMed:23273981, PubMed:26721387, PubMed:27814491, PubMed:27889449, PubMed:30787182, PubMed:31802118). HR is restricted to S and G2 phases of the cell cycle and preferentially repairs DSBs resulting from replication fork collapse (PubMed:17965729, PubMed:19202191, PubMed:23273981, PubMed:27814491, PubMed:27889449, PubMed:30787182). Key determinant of DSB repair pathway choice, as it commits cells to HR by preventing classical non-homologous end-joining (NHEJ) (PubMed:19202191). Specifically promotes the endonuclease activity of the MRN complex to clear DNA ends containing protein adducts: recruited to DSBs by NBN following phosphorylation by CDK1, and promotes the endonuclease activity of MRE11 to clear protein-DNA adducts and generate clean double-strand break ends (PubMed:27814491, PubMed:27889449, PubMed:30787182, PubMed:33836577). Functions downstream of the MRN complex and ATM, promotes ATR activation and its recruitment to DSBs in the S/G2 phase facilitating the generation of ssDNA (PubMed:16581787, PubMed:17965729, PubMed:19759395, PubMed:20064462). Component of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage (PubMed:15485915, PubMed:16818604). During immunoglobulin heavy chain class-switch recombination, promotes microhomology-mediated alternative end joining (A-NHEJ) and plays an essential role in chromosomal translocations (By similarity). Binds preferentially to DNA Y-junctions and to DNA substrates with blocked ends and promotes intermolecular DNA bridging (PubMed:30601117)
Protein Sequence
10
MNISGSSCGS
20
PNSADTSSDF
30
KDLWTKLKEC
40
HDREVQGLQV
50
KVTKLKQERI
60
LDAQRLEEFF
70
TKNQQLREQQ
80
KVLHETIKVL
90
EDRLRAGLCD
100
RCAVTEEHMR
110
KKQQEFENIR
120
QQNLKLITEL
130
MNERNTLQEE
140
NKKLSEQLQQ
150
KIENDQQHQA
160
AELECEEDVI
170
PDSPITAFSF
180
SGVNRLRRKE
190
NPHVRYIEQT
200
HTKLEHSVCA
210
NEMRKVSKSS
220
THPQHNPNEN
230
EILVADTYDQ
240
SQSPMAKAHG
250
TSSYTPDKSS
260
FNLATVVAET
270
LGLGVQEESE
280
TQGPMSPLGD
290
ELYHCLEGNH
300
KKQPFEESTR
310
NTEDSLRFSD
320
STSKTPPQEE
330
LPTRVSSPVF
340
GATSSIKSGL
350
DLNTSLSPSL
360
LQPGKKKHLK
370
TLPFSNTCIS
380
RLEKTRSKSE
390
DSALFTHHSL
400
GSEVNKIIIQ
410
SSNKQILINK
420
NISESLGEQN
430
RTEYGKDSNT
440
DKHLEPLKSL
450
GGRTSKRKKT
460
EEESEHEVSC
470
PQASFDKENA
480
FPFPMDNQFS
490
MNGDCVMDKP
500
LDLSDRFSAI
510
QRQEKSQGSE
520
TSKNKFRQVT
530
LYEALKTIPK
540
GFSSSRKASD
550
GNCTLPKDSP
560
GEPCSQECII
570
LQPLNKCSPD
580
NKPSLQIKEE
590
NAVFKIPLRP
600
RESLETENVL
610
DDIKSAGSHE
620
PIKIQTRSDH
630
GGCELASVLQ
640
LNPCRTGKIK
650
SLQNNQDVSF
660
ENIQWSIDPG
670
ADLSQYKMDV
680
TVIDTKDGSQ
690
SKLGGETVDM
700
DCTLVSETVL
710
LKMKKQEQKG
720
EKSSNEERKM
730
NDSLEDMFDR
740
TTHEEYESCL
750
ADSFSQAADE
760
EEELSTATKK
770
LHTHGDKQDK
780
VKQKAFVEPY
790
FKGDERETSL
800
QNFPHIEVVR
810
KKEERRKLLG
820
HTCKECEIYY
830
ADMPAEEREK
840
KLASCSRHRF
850
RYIPPNTPEN
860
FWEVGFPSTQ
870
TCMERGYIKE
880
DLDPCPRPKR
890
RQPYNAIFSP
KGKEQKT
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:0035861 |
site of double-strand break |
| Cellular Component |
GO:0017053 |
transcription repressor complex |
| Molecular Function |
GO:0003684 |
damaged DNA binding |
| Molecular Function |
GO:0042802 |
identical protein binding |
| Molecular Function |
GO:0046872 |
metal ion binding |
| Molecular Function |
GO:0061629 |
RNA polymerase II-specific DNA-binding transcription factor binding |
| Molecular Function |
GO:0000014 |
single-stranded DNA endodeoxyribonuclease activity |
| Molecular Function |
GO:0003714 |
transcription corepressor activity |
| Biological Process |
GO:0051301 |
cell division |
| Biological Process |
GO:0010792 |
DNA double-strand break processing involved in repair via single-strand annealing |
| Biological Process |
GO:0110025 |
DNA strand resection involved in replication fork processing |
| Biological Process |
GO:0000724 |
double-strand break repair via homologous recombination |
| Biological Process |
GO:0035825 |
homologous recombination |
| Biological Process |
GO:0051321 |
meiotic cell cycle |
| Biological Process |
GO:0044818 |
mitotic G2/M transition checkpoint |
Reference
PMID: N/A