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MGP002595

UniProt Annotations

Entry Information
Gene Nameretinoblastoma binding protein 8
Protein EntryCOM1_HUMAN
UniProt IDQ99708
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; IsoId=Q99708-1; Sequence=Displayed; Name=2; IsoId=Q99708-2; Sequence=VSP_043220; Name=3; IsoId=Q99708-3; Sequence=VSP_045247, VSP_045248; Note=No experimental confirmation available. Ref.4 (BX648221) sequence is in conflict in position: 862:S->G. {ECO:0000305};
DiseaseJawad syndrome (JWDS) [MIM:251255]: A syndrome characterized by congenital microcephaly, moderately severe mental retardation, 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 mutations affecting the gene represented in this entry.
DiseaseNote=Genetic variability in RBBP8 is noted as a factor in BRCA1-associated breast cancer risk. Exhibits sensitivity to tamoxifen in certain breast cancer cell lines.
DiseaseSeckel 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 mental retardation. {ECO:0000269|PubMed:21998596}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainThe damage-recruitment motif is required for DNA binding and translocation to sites of DNA damage.
DomainThe PXDLS motif binds to a cleft in CtBP proteins.
FunctionEndonuclease that cooperates with the MRE11-RAD50-NBN (MRN) complex in processing meiotic and mitotic double-strand breaks (DSBs) by ensuring both resection and intrachromosomal association of the broken ends. 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. Component of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage. Promotes microhomology-mediated alternative end joining (A-NHEJ) during class-switch recombination and plays an essential role in chromosomal translocations. {ECO:0000269|PubMed:10764811, ECO:0000269|PubMed:10910365, 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:20829486}.
InductionLevels increase dramatically as dividing cells traverse the G1/S boubdary. Down-regulated in tamoxifen-resistant breast cancer cells.
InteractionP38398:BRCA1; NbExp=9; IntAct=EBI-745715, EBI-349905; Q9UQ84:EXO1; NbExp=3; IntAct=EBI-745715, EBI-944667;
PtmAcetylated. Deacetylation by SIRT6 upon DNA damage promotes DNA end resection. {ECO:0000269|PubMed:20829486}.
PtmHyperphosphorylation upon ionizing radiation results in dissociation from BRCA1. Phosphorylation at Thr-847 by CDK1 is essential for the recruitment to DNA and the DNA repair function. Phosphorylated on Ser-327 as cells enter G2 phase. This phosphorylation is required for binding BRCA1 and for the G2/M DNA damage transition checkpoint control. {ECO:0000269|PubMed:10910365, ECO:0000269|PubMed:15485915, ECO:0000269|PubMed:17965729, ECO:0000269|PubMed:19202191, ECO:0000269|PubMed:20068231}.
PtmUbiquitinated. Ubiquitination at multiple sites by BRCA1 (via its N-terminal RING domain) does not lead to its proteosomal degradation but instead the ubiquitinated RBBP8 binds to chromatin following DNA damage and may play a role in G2/M checkpoint control. {ECO:0000269|PubMed:14654780, ECO:0000269|PubMed:16818604}.
SimilarityBelongs to the COM1/SAE2/CtIP family. {ECO:0000305}.
Subcellular LocationNucleus {ECO:0000269|PubMed:10764811, ECO:0000269|PubMed:17965729}. Note=Associates with sites of DNA damage in S/G2 phase. Ubiquitinated RBBP8 binds to chromatin following DNA damage.
SubunitHomodimer; dimerizes via the coiled coil domain. Interacts (via the PXDLS motif) with CTBP1; the interaction is disrupted via binding of the adenovirus E1A to CTBP1. Component of the BRCA1-RBBBP8 complex. Interacts (the Ser-327 phosphorylated form) with BRCA1 (via the C-terminal BRCA1 domains): the interaction occurs in the G2 phase, ubiquitinates RBBP8 and involves RBBP8 in BRCA1-dependent G2/M checkpoint control on DNA damage. Interacts with RB1. Interacts with the MRN complex. Interacts directly with MRE11A; the interaction is required for efficient homologous recombination (HR) and regulation of the MRN complex. Interacts directly with RAD50. Interacts directly with NBN. Interacts with SIRT6; the interaction deacetylates RBBP8 upon DNA damage. Interacts with LM04 (via the LIM zinc-binding 1 domain). {ECO:0000269|PubMed:10764811, ECO:0000269|PubMed:11751867, ECO:0000269|PubMed:14654780, ECO:0000269|PubMed:15084581, ECO:0000269|PubMed:15485915, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:17965729, ECO:0000269|PubMed:19759395, ECO:0000269|PubMed:20829486, ECO:0000269|PubMed:9535825, ECO:0000269|PubMed:9721205}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/RBBP8ID42066ch18q11.html";
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