InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: RBBP8

Summary

InnateDB Protein

IDBP-1498.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

RBBP8

Protein Name

retinoblastoma binding protein 8

Synonyms

COM1; CTIP; JWDS; RIM; SAE2; SCKL2;

Species

Homo sapiens

Ensembl Protein

ENSP00000323050

InnateDB Gene

IDBG-1496 (RBBP8)

Protein Structure

UniProt Annotation

Function

Endonuclease 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:0000269PubMed:10764811, ECO:0000269PubMed:10910365, ECO:0000269PubMed:15485915, ECO:0000269PubMed:16581787, ECO:0000269PubMed:16818604, ECO:0000269PubMed:17965729, ECO:0000269PubMed:19202191, ECO:0000269PubMed:19759395, ECO:0000269PubMed:20064462, ECO:0000269PubMed:20829486}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:10764811, ECO:0000269PubMed:17965729}. Note=Associates with sites of DNA damage in S/G2 phase. Ubiquitinated RBBP8 binds to chromatin following DNA damage.

Disease Associations

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 mental retardation. {ECO:0000269PubMed:21998596}. Note=The disease is caused by mutations affecting the gene represented in this entry.Jawad 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:0000269PubMed:21998596}. Note=The disease is caused by mutations affecting the gene represented in this entry.Note=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.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 65 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	65 [view]
Protein-Protein	62 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000014	single-stranded DNA endodeoxyribonuclease activity
GO:0001103	RNA polymerase II repressing transcription factor binding
GO:0001106	RNA polymerase II transcription corepressor activity
GO:0003684	damaged DNA binding
GO:0005515	protein binding

Biological Process

GO:0000075	cell cycle checkpoint
GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0000724	double-strand break repair via homologous recombination
GO:0000737	DNA catabolic process, endonucleolytic
GO:0006281	DNA repair
GO:0006357	regulation of transcription from RNA polymerase II promoter
GO:0007067	mitotic nuclear division
GO:0007126	meiotic nuclear division
GO:0010792	DNA double-strand break processing involved in repair via single-strand annealing
GO:0031572	G2 DNA damage checkpoint