RBBP8
entrez
5932
canonical
uniprot
Q99708
canonical
ensembl
ENSG00000101773
resolver
ensp
ENSP00000323050
resolver
ensp
ENSP00000382628
resolver
ensp
ENSP00000382630
resolver
ensp
ENSP00000543970
resolver
ensp
ENSP00000543971
resolver
ensp
ENSP00000543972
resolver
ensp
ENSP00000543973
resolver
ensp
ENSP00000543974
resolver
genesymbol
RBBP8
resolver
genesymbol_syn
CTIP
resolver
hgnc
HGNC:9891
resolver
uniprot
A6NKN2
resolver
uniprot
A8K8W6
resolver
uniprot
E7ETY1
resolver
uniprot
O75371
resolver
uniprot
Q8NHQ3
resolver
uniprot_entry
CTIP_HUMAN
resolver
uniprot_sec
A6NKN2
resolver
uniprot_sec
A8K8W6
resolver
uniprot_sec
E7ETY1
resolver
uniprot_sec
O75371
resolver
uniprot_sec
Q8NHQ3
resolver
amino_acid_sequence
MNISGSSCGSPNSADTSSDFKDLWTKLKECHDREVQGLQVKVTKLKQERILDAQRLEEFFTKNQQLREQQKVLHETIKVLEDRLRAGLCDRCAVTEEHMRKKQQEFENIRQQNLKLITELMNERNTLQEENKKLSEQLQQKIENDQQHQAAELECEEDVIPDSPITAFSFSGVNRLRRKENPHVRYIEQTHTKLEHSVCANEMRKVSKSSTHPQHNPNENEILVADTYDQSQSPMAKAHGTSSYTPDKSSFNLATVVAETLGLGVQEESETQGPMSPLGDELYHCLEGNHKKQPFEESTRNTEDSLRFSDSTSKTPPQEELPTRVSSPVFGATSSIKSGLDLNTSLSPSLLQPGKKKHLKTLPFSNTCISRLEKTRSKSEDSALFTHHSLGSEVNKIIIQSSNKQILINKNISESLGEQNRTEYGKDSNTDKHLEPLKSLGGRTSKRKKTEEESEHEVSCPQASFDKENAFPFPMDNQFSMNGDCVMDKPLDLSDRFSAIQRQEKSQGSETSKNKFRQVTLYEALKTIPKGFSSSRKASDGNCTLPKDSPGEPCSQECIILQPLNKCSPDNKPSLQIKEENAVFKIPLRPRESLETENVLDDIKSAGSHEPIKIQTRSDHGGCELASVLQLNPCRTGKIKSLQNNQDVSFENIQWSIDPGADLSQYKMDVTVIDTKDGSQSKLGGETVDMDCTLVSETVLLKMKKQEQKGEKSSNEERKMNDSLEDMFDRTTHEEYESCLADSFSQAADEEEELSTATKKLHTHGDKQDKVKQKAFVEPYFKGDERETSLQNFPHIEVVRKKEERRKLLGHTCKECEIYYADMPAEEREKKLASCSRHRFRYIPPNTPENFWEVGFPSTQTCMERGYIKEDLDPCPRPKRRQPYNAIFSPKGKEQKT
uniprot
proteins
disease_involvement
DISEASE: Seckel syndrome 2 (SCKL2) [MIM:606744]: A rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and intellectual disability. {ECO:0000269|PubMed:21998596, ECO:0000269|PubMed:24389050}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Jawad syndrome (JWDS) [MIM:251255]: A syndrome characterized by congenital microcephaly, moderately severe intellectual disability, and symmetrical digital anomalies. Digital malformations of variable degree include hallux valgus, syndactyly of toes 4 and 5, short fifth fingers, single flexion crease of fifth fingers, polydactyly and synpolydactyly. {ECO:0000269|PubMed:21998596}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Note=Genetic variability in RBBP8 is noted as a factor in BRCA1-associated breast cancer risk (PubMed:21799032). Associated with sensitivity to tamoxifen in certain breast cancer cell lines (PubMed:18171986). {ECO:0000269|PubMed:18171986, ECO:0000269|PubMed:21799032}.
uniprot
proteins
ec_number
3.1.-.-
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:Q80YR6, ECO:0000269|PubMed:15485915, ECO:0000269|PubMed:16581787, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:17965729, ECO:0000269|PubMed:19202191, ECO:0000269|PubMed:19759395, ECO:0000269|PubMed:20064462, ECO:0000269|PubMed:23273981, ECO:0000269|PubMed:26721387, ECO:0000269|PubMed:27814491, ECO:0000269|PubMed:27889449, ECO:0000269|PubMed:30601117, ECO:0000269|PubMed:30787182, ECO:0000269|PubMed:31802118, ECO:0000269|PubMed:33836577}.
uniprot
proteins
mass_dalton
101942
uniprot
proteins
mutagenesis
MUTAGEN 27; /note="L->E: Can form homodimers but not homotetramers. Abolishes ability to promote homologous recombination and DNA resection. Defective binding to DNA. Defective in localizing to sites of DNA damage. Does not affect interaction with MRN complex components MRE11, NBN or RAD50."; /evidence="ECO:0000269|PubMed:25558984, ECO:0000269|PubMed:30601117"; MUTAGEN 31; /note="H->A: No effect on RPA focus formation on DNA damage."; /evidence="ECO:0000269|PubMed:19759395"; MUTAGEN 35; /note="V->A: No effect on RPA focus formation on DNA damage."; /evidence="ECO:0000269|PubMed:19759395"; MUTAGEN 41; /note="K->A: No effect on RPA focus formation on DNA damage."; /evidence="ECO:0000269|PubMed:19759395"; MUTAGEN 45; /note="L->A: No effect on RPA focus formation on DNA damage."; /evidence="ECO:0000269|PubMed:19759395"; MUTAGEN 62; /note="K->R: In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-78; R-115; R-132; R-133; R-404; R-572; R-578; R-640; R-759; R-760 and R-782. In K5R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-78; R-115; R-132 and R-133."; /evidence="ECO:0000269|PubMed:26502057"; MUTAGEN 78; /note="K->R: In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-115; R-132; R-133; R-404; R-572; R-578; R-640; R-759; R-760 and R-782. In K5R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-115; R-132 and R-133."; /evidence="ECO:0000269|PubMed:26502057"; MUTAGEN 89; /note="C->A: Reduces Zn(2+) content; when associated with A-92."; /evidence="ECO:0000269|PubMed:25558984"; MUTAGEN 92; /note="C->A: Reduces Zn(2+) content; when associated with A-89."; /evidence="ECO:0000269|PubMed:25558984"; MUTAGEN 115; /note="K->R: In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-132; R-133; R-404; R-572; R-578; R-640; R-759; R-760 and R-782. In K5R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-132 and R-133."; /evidence="ECO:0000269|PubMed:26502057"; MUTAGEN 132; /note="K->R: In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-133; R-404; R-572; R-578; R-640; R-759; R-760 and R-782. In K5R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115 and R-133."; /evidence="ECO:0000269|PubMed:26502057"; MUTAGEN 133; /note="K->R: In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-133; R-404; R-572; R-578; R-640; R-759; R-760 and R-782. In K5R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115 and R-132."; /evidence="ECO:0000269|PubMed:26502057"; MUTAGEN 179; /note="K->A: No effect on FZR1-binding."; /evidence="ECO:0000269|PubMed:25349192"; MUTAGEN 276; /note="S->A: No effect on PIN1-binding. Impaired PIN1-binding, partially decreased CUL3/KLHL15-mediated proteasomal degradation, no effect on BRCA1-, MRE11-, nor on KLHL15-binding; when associated with A-315."; /evidence="ECO:0000269|PubMed:23623683, ECO:0000269|PubMed:27561354"; MUTAGEN 315; /note="T->A: Decreased PIN1-binding. Impaired PIN1-binding, partially decreased CUL3/KLHL15-mediated proteasomal degradation, no effect on BRCA1-, MRE11-, nor on KLHL15-binding; when associated with A-276."; /evidence="ECO:0000269|PubMed:23623683, ECO:0000269|PubMed:27561354"; MUTAGEN 327; /note="S->A: Abolishes BRCA1 interaction and ubiquitination. No activation of CHEK1 after DNA damage."; /evidence="ECO:0000269|PubMed:15485915, ECO:0000269|PubMed:16818604"; MUTAGEN 404; /note="K->R: In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-132; R-133; R-572; R-578; R-640; R-759; R-760 and R-782."; /evidence="ECO:0000269|PubMed:26502057"; MUTAGEN 467; /note="K->A: Impaired FZR1-binding and APC/C-mediated polyubiquitination. Increased stability. No effect on MRE11-binding, nor on CUL3/KLHL15-mediated proteasomal degradation. No effect on DNA-en resection activity."; /evidence="ECO:0000269|PubMed:25349192, ECO:0000269|PubMed:27561354"; MUTAGEN 513; /note="K->A: Abolishes damage recruitment capability."; /evidence="ECO:0000269|PubMed:20064462"; MUTAGEN 515; /note="K->A: Abolishes damage recruitment capability."; /evidence="ECO:0000269|PubMed:20064462"; MUTAGEN 572; /note="K->R: In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-132; R-133; R-404; R-578; R-640; R-759; R-760 and R-782."; /evidence="ECO:0000269|PubMed:26502057"; MUTAGEN 578; /note="K->R: In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-132; R-133; R-404; R-572; R-640; R-759; R-760 and R-782."; /evidence="ECO:0000269|PubMed:26502057"; MUTAGEN 640; /note="K->R: In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-132; R-133; R-404; R-572; R-578; R-759; R-760 and R-782."; /evidence="ECO:0000269|PubMed:26502057"; MUTAGEN 664; /note="S->A: Abrogates dissociation of BRCA1."; /evidence="ECO:0000269|PubMed:10910365"; MUTAGEN 745; /note="S->A: Abrogates dissociation of BRCA1."; /evidence="ECO:0000269|PubMed:10910365"; MUTAGEN 759; /note="K->R: In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-132; R-133; R-404; R-572; R-578; R-640; R-760 and R-782."; /evidence="ECO:0000269|PubMed:26502057"; MUTAGEN 760; /note="K->R: In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-132; R-133; R-404; R-572; R-578; R-640; R-759 and R-782."; /evidence="ECO:0000269|PubMed:26502057"; MUTAGEN 782; /note="K->R: In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-132; R-133; R-404; R-572; R-578; R-640; R-759 and R-760."; /evidence="ECO:0000269|PubMed:26502057"; MUTAGEN 839; /note="R->A: Defective binding to DNA. No effect on CUL3/KLHL15-mediated proteasomal degradation. Does not affect tetramerization."; /evidence="ECO:0000269|PubMed:27561354, ECO:0000269|PubMed:30601117"; MUTAGEN 840; /note="F->A: Decreased CUL3/KLHL15-mediated proteasomal degradation."; /evidence="ECO:0000269|PubMed:27561354"; MUTAGEN 842; /note="Y->A: Decreased interaction with KLHL15, decreased polyubiquitination and CUL3/KLHL15-mediated proteasomal degradation. No effect on DNA-end resection activity."; /evidence="ECO:0000269|PubMed:27561354, ECO:0000269|PubMed:35219381"; MUTAGEN 842; /note="Y->F: No effect on KLHL15-binding, nor on CUL3/KLHL15-mediated proteasomal degradation."; /evidence="ECO:0000269|PubMed:27561354"; MUTAGEN 847; /note="T->A: Impairs DNA resection. Impaired ability to promote the endonuclease activity of MRE11. Impaired ability to promote the endonuclease activity of MRE11; when associated with A-859."; /evidence="ECO:0000269|PubMed:19202191, ECO:0000269|PubMed:27814491, ECO:0000269|PubMed:27889449"; MUTAGEN 847; /note="T->E: Mimics constitutive phosphorylation. Increased ability to promote the endonuclease activity of MRE11; when associated with E-859."; /evidence="ECO:0000269|PubMed:19202191, ECO:0000269|PubMed:27814491"; MUTAGEN 859; /note="T->A: Decreased phosphorylation by ATR. Impaired ability to promote the endonuclease activity of MRE11; when associated with A-847."; /evidence="ECO:0000269|PubMed:23273981, ECO:0000269|PubMed:27814491"; MUTAGEN 859; /note="T->E: Mimics constitutive phosphorylation. Increased ability to promote the endonuclease activity of MRE11; when associated with E-847."; /evidence="ECO:0000269|PubMed:27814491
uniprot
proteins
post_translational_modification
PTM: Hyperphosphorylation upon ionizing radiation results in dissociation from BRCA1 (PubMed:10910365, PubMed:17965729). Phosphorylation at Thr-847 by CDK1 is essential for the recruitment to DNA and the DNA repair function (PubMed:19202191, PubMed:27814491, PubMed:27889449). Phosphorylation at Thr-847 and Thr-859 promote interaction with NBN and recruitment to double-strand breaks (DSBs) (PubMed:23273981, PubMed:27814491, PubMed:27889449, PubMed:33836577). Phosphorylated on Ser-327 as cells enter G2 phase (PubMed:15485915). This phosphorylation is required for binding BRCA1 and for the G2/M DNA damage transition checkpoint control (PubMed:15485915). Phosphorylation at Thr-315, probably catalyzed by CDK2, is required for PIN1-binding, while phosphorylation at Ser-276 serves as a PIN1 isomerization site (PubMed:23623683). Phosphorylation at Thr-315 is cell-cycle dependent (PubMed:23623683). It steadily increases during S phase, peaks at late S/G2 phase, and drops at G1 (PubMed:23623683). Phosphorylation is not required for tetramerization (PubMed:30601117). Binds to DNA more strongly when dephosphorylated (PubMed:30601117). {ECO:0000269|PubMed:10910365, ECO:0000269|PubMed:15485915, ECO:0000269|PubMed:17965729, ECO:0000269|PubMed:19202191, ECO:0000269|PubMed:23273981, ECO:0000269|PubMed:23623683, ECO:0000269|PubMed:27814491, ECO:0000269|PubMed:27889449, ECO:0000269|PubMed:30601117, ECO:0000269|PubMed:33836577}.; PTM: Ubiquitinated (PubMed:14654780, PubMed:16818604, PubMed:27561354). Ubiquitination at multiple sites by BRCA1 (via its N-terminal RING domain) does not lead to its proteasomal degradation but instead the ubiquitinated RBBP8 binds to chromatin following DNA damage and may play a role in G2/M checkpoint control (PubMed:16818604). Ubiquitinated by RNF138 at its N-terminus (PubMed:26502057). Ubiquitinated through 'Lys-48' by the E3 CUL3-KLHL15 complex; this modification leads to proteasomal degradation (PubMed:27561354, PubMed:35219381). Ubiquitinated by the E3 FZR1/APC/C complex; this modification leads to proteasomal degradation (PubMed:25349192). {ECO:0000269|PubMed:14654780, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:25349192, ECO:0000269|PubMed:26502057, ECO:0000269|PubMed:27561354, ECO:0000269|PubMed:35219381}.
uniprot
proteins
protein_family
COM1/SAE2/CtIP family
uniprot
proteins
pubmed
10764811
uniprot
proteins
pubmed
10910365
uniprot
proteins
pubmed
11751867
uniprot
proteins
pubmed
14654780
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15084581
uniprot
proteins
pubmed
15485915
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16101277
uniprot
proteins
pubmed
16177791
uniprot
proteins
pubmed
16581787
uniprot
proteins
pubmed
16818604
uniprot
proteins
pubmed
17965729
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18171986
uniprot
proteins
pubmed
19202191
uniprot
proteins
pubmed
19270026
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19759395
uniprot
proteins
pubmed
20064462
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20829486
uniprot
proteins
pubmed
21799032
uniprot
proteins
pubmed
21998596
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23273981
uniprot
proteins
pubmed
23353824
uniprot
proteins
pubmed
23623683
uniprot
proteins
pubmed
24389050
uniprot
proteins
pubmed
25218447
uniprot
proteins
pubmed
25349192
uniprot
proteins
pubmed
25558984
uniprot
proteins
pubmed
25755297
uniprot
proteins
pubmed
26502057
uniprot
proteins
pubmed
26721387
uniprot
proteins
pubmed
26807646
uniprot
proteins
pubmed
27561354
uniprot
proteins
pubmed
27814491
uniprot
proteins
pubmed
27889449
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
28834754
uniprot
proteins
pubmed
29042561
uniprot
proteins
pubmed
30601117
uniprot
proteins
pubmed
30787182
uniprot
proteins
pubmed
30975768
uniprot
proteins
pubmed
31802118
uniprot
proteins
pubmed
33836577
uniprot
proteins
pubmed
34129781
uniprot
proteins
pubmed
35219381
uniprot
proteins
pubmed
9535825
uniprot
proteins
pubmed
9721205
uniprot
proteins
sequence_length
897
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10764811, ECO:0000269|PubMed:17965729, ECO:0000269|PubMed:23623683}. Chromosome {ECO:0000269|PubMed:10764811, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:27814491, ECO:0000269|PubMed:27889449, ECO:0000269|PubMed:29042561, ECO:0000269|PubMed:33836577}. Note=Associates with sites of DNA damage in S/G2 phase (PubMed:10764811, PubMed:25349192). Recruited to DSBs by the MRE11-RAD50-NBN (MRN) complex following phosphorylation by CDK1, which promotes interaction with NBN (PubMed:27814491, PubMed:27889449, PubMed:33836577). Ubiquitinated RBBP8 binds to chromatin following DNA damage (PubMed:16818604). {ECO:0000269|PubMed:10764811, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:25349192, ECO:0000269|PubMed:27814491, ECO:0000269|PubMed:27889449, ECO:0000269|PubMed:33836577}.
uniprot
proteins