Q80YR6 · CTIP_MOUSE
- ProteinDNA endonuclease RBBP8
- GeneRbbp8
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids893 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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 (By similarity).
HR is restricted to S and G2 phases of the cell cycle and preferentially repairs DSBs resulting from replication fork collapse (By similarity).
Key determinant of DSB repair pathway choice, as it commits cells to HR by preventing classical non-homologous end-joining (NHEJ) (By similarity).
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 (By similarity).
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 (By similarity).
Component of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage (By similarity).
During immunoglobulin heavy chain class-switch recombination, promotes microhomology-mediated alternative end joining (A-NHEJ) and plays an essential role in chromosomal translocations (PubMed:21131978, PubMed:21131982).
Binds preferentially to DNA Y-junctions and to DNA substrates with blocked ends and promotes intermolecular DNA bridging (By similarity).
HR is restricted to S and G2 phases of the cell cycle and preferentially repairs DSBs resulting from replication fork collapse (By similarity).
Key determinant of DSB repair pathway choice, as it commits cells to HR by preventing classical non-homologous end-joining (NHEJ) (By similarity).
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 (By similarity).
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 (By similarity).
Component of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage (By similarity).
During immunoglobulin heavy chain class-switch recombination, promotes microhomology-mediated alternative end joining (A-NHEJ) and plays an essential role in chromosomal translocations (PubMed:21131978, PubMed:21131982).
Binds preferentially to DNA Y-junctions and to DNA substrates with blocked ends and promotes intermolecular DNA bridging (By similarity).
Miscellaneous
Binds one Zn2+ atom per dimer. Zn2+-binding is not required for homotetramerization.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | BRCA1-C complex | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Cellular Component | site of double-strand break | |
Cellular Component | transcription repressor complex | |
Molecular Function | damaged DNA binding | |
Molecular Function | identical protein binding | |
Molecular Function | RNA polymerase II-specific DNA-binding transcription factor binding | |
Molecular Function | single-stranded DNA endodeoxyribonuclease activity | |
Molecular Function | transcription corepressor activity | |
Biological Process | blastocyst hatching | |
Biological Process | cell division | |
Biological Process | DNA double-strand break processing involved in repair via single-strand annealing | |
Biological Process | DNA strand resection involved in replication fork processing | |
Biological Process | double-strand break repair via homologous recombination | |
Biological Process | G1/S transition of mitotic cell cycle | |
Biological Process | homologous recombination | |
Biological Process | meiotic cell cycle | |
Biological Process | mitotic G2/M transition checkpoint |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDNA endonuclease RBBP8
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ80YR6
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Associates with sites of DNA damage in S/G2 phase. Recruited to DSBs by the MRE11-RAD50-NBN (MRN) complex following phosphorylation by CDK1, which promotes interaction with NBN. Ubiquitinated RBBP8 binds to chromatin following DNA damage.
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, cross-link, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000417036 | 1-893 | DNA endonuclease RBBP8 | |||
Sequence: MSISGSGCGSPNSADASNDFKELWTKLKEYHDKEVQGLQVKVTKLKKERILDAQRLEEFFTKNQQLRDQQKVLQETIKILEDRLRAGLCDRCAVTEEHMHKKQQEFENIRQQNLKLITELMNEKNTLQEENKKLSEQLQQKMENGQQDQVAELACEENIIPDSPVTSFSFSGINRLRKKENLHVRYVEQTHTKLERSLCTNELRKISKDSAPAPVNSEEHEILVADTCDQNHSPLSKICETSSYPTDKTSFNLDTVVAETLGLNGQEESEPQGPMSPLGSELYHCLKEDHKKHPFMESARSKEDSLRFSDSASKTPPQEFTTRASSPVFGATSTVKAHLGLNTSFSPSLLDIGKKNLLKTAPFSNIAVSRSEKVRSKSEDNALFTQHSLGSEVKVISQSFSSKQILTNKTVSDSVDEQCSADHMNTTVADKYLVPLKSLGGKASKRKRTEEESEHAVKCPQACFDKENALPFPMENQFSMNGDHVMDKPLDLSDRFAATQRQEKNHGNETSKNKLKQATIYEALKPIPKGSSSGRKALSGDCMPAKDSWETYCLQPRSLQSSSKFSPDQKTPLQIKEENPVFKTPPCSQESLETENLFGDVKGTGSLVPTKVKSRAVHGGCELASVLQLNPCRVAKTKALPSNQDTSFENIQWSVDPGADLSQYKMDVTVIDTKDSSHSRLGGETVDMDCTLVSETVLLKMKKQEQKERSPNGDIKMNDSLEDMFDRTTHEEYESCLADSFSQVPDEEELPDTTKKTNIPADKQDGVKQKAFVGPYFKDKERETSIQNFPHIEVVRKKEERRKLLGHTCKECEIYYADLPAEEREKKLASCSRHRFRYIPPNTPENFWEVGFPSTQTCLERGYIKEDLDLSPRPKRRQPYNAVFSPKGKEQRT | ||||||
Cross-link | 62 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 115 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 193 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 233 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 276 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 315 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 325 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 326 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 348 | Phosphoserine | ||||
Sequence: S | ||||||
Cross-link | 359 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 377 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 378 | Phosphoserine | ||||
Sequence: S | ||||||
Cross-link | 394 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 403 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 409 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 437 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 525 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate | ||||
Sequence: K | ||||||
Cross-link | 529 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 570 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 576 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 602 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate | ||||
Sequence: K | ||||||
Cross-link | 611 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 636 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 638 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 662 | Phosphoserine; by ATM | ||||
Sequence: S | ||||||
Cross-link | 674 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 677 | Phosphoserine | ||||
Sequence: S | ||||||
Cross-link | 716 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 720 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 742 | Phosphoserine; by ATM | ||||
Sequence: S | ||||||
Cross-link | 778 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 843 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 855 | Phosphothreonine | ||||
Sequence: T | ||||||
Cross-link | 865 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K |
Post-translational modification
Hyperphosphorylation upon ionizing radiation results in dissociation from BRCA1. Phosphorylation at Thr-843 by CDK1 is essential for the recruitment to DNA and the DNA repair function. Phosphorylation at Thr-843 and Thr-855 promote interaction with NBN and recruitment to double-strand breaks (DSBs). Phosphorylated on Ser-326 as cells enter G2 phase. Phosphorylated at Ser-326 as cells enter G2 phase. This phosphorylation is required for binding BRCA1 and for the G2/M DNA damage transition checkpoint control (By similarity).
Phosphorylation at Thr-315 is required for PIN1-binding, while phosphorylation at Ser-276 serves as a PIN1 isomerization site. Phosphorylation at Thr-315 is cell-cycle dependent. It steadily increases during S phase, peaks at late S/G2 phase, and drops at G1 (By similarity).
Phosphorylation is not required for tetramerization (By similarity).
Binds to DNA more strongly when dephosphorylated (By similarity).
Phosphorylation at Thr-315 is required for PIN1-binding, while phosphorylation at Ser-276 serves as a PIN1 isomerization site. Phosphorylation at Thr-315 is cell-cycle dependent. It steadily increases during S phase, peaks at late S/G2 phase, and drops at G1 (By similarity).
Phosphorylation is not required for tetramerization (By similarity).
Binds to DNA more strongly when dephosphorylated (By similarity).
Ubiquitinated. 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. Ubiquitinated by RNF138 at its N-terminus. Ubiquitinated through 'Lys-48' by the E3 CUL3-KLHL15 complex; this modification leads to proteasomal degradation. Ubiquitinated by the E3 FZR1/APC/C complex; this modification leads to proteasomal degradation.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
Homotetramer; formed by antiparallel association of helical extensions protruding from the N-termini of two parallel coiled-coil dimers (By similarity).
Forms a dumbbell-shaped particle in which polar globular domains are held about 30 nm apart by a central rod (By similarity).
Homotetramerization is required for DNA-end resection and repair (By similarity).
Interacts (via the PXDLS motif) with CTBP1; the interaction is disrupted via binding of the adenovirus E1A to CTBP1. Component of the BRCA1-RBBP8 complex. Interacts (the Ser-326 phosphorylated form) with BRCA1 (via the C-terminal BRCT 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 MRE11; the interaction is required for efficient homologous recombination (HR) and regulation of the MRN complex. Interacts (when phosphorylated by CDK1) with NBN; promoting association with the MRN complex. Interacts with LMO4 (via the LIM zinc-binding 1 domain) (PubMed:23353824).
Interacts with SIAH1. Interacts with RNF138. Interacts with EXD2. Interacts with CUL3 and KLHL15; this interaction leads to RBBP8 proteasomal degradation. Directly interacts with PIN1; this interaction depends upon RBBP8 phosphorylation, predominantly at Thr-315. Interacts with FZR1; this interaction leads to APC/C-mediated RBBP8 proteasomal degradation. Interacts with AUNIP; leading to recruit RBBP8 to sites of DNA damage. Interacts with SAMHD1 (By similarity).
Interacts with HDGFL2 (By similarity).
Forms a dumbbell-shaped particle in which polar globular domains are held about 30 nm apart by a central rod (By similarity).
Homotetramerization is required for DNA-end resection and repair (By similarity).
Interacts (via the PXDLS motif) with CTBP1; the interaction is disrupted via binding of the adenovirus E1A to CTBP1. Component of the BRCA1-RBBP8 complex. Interacts (the Ser-326 phosphorylated form) with BRCA1 (via the C-terminal BRCT 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 MRE11; the interaction is required for efficient homologous recombination (HR) and regulation of the MRN complex. Interacts (when phosphorylated by CDK1) with NBN; promoting association with the MRN complex. Interacts with LMO4 (via the LIM zinc-binding 1 domain) (PubMed:23353824).
Interacts with SIAH1. Interacts with RNF138. Interacts with EXD2. Interacts with CUL3 and KLHL15; this interaction leads to RBBP8 proteasomal degradation. Directly interacts with PIN1; this interaction depends upon RBBP8 phosphorylation, predominantly at Thr-315. Interacts with FZR1; this interaction leads to APC/C-mediated RBBP8 proteasomal degradation. Interacts with AUNIP; leading to recruit RBBP8 to sites of DNA damage. Interacts with SAMHD1 (By similarity).
Interacts with HDGFL2 (By similarity).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, coiled coil, compositional bias, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 22-45 | Essential for binding to the MRN complex and for RPA focus formation on DNA damage | ||||
Sequence: ELWTKLKEYHDKEVQGLQVKVTKL | ||||||
Coiled coil | 35-84 | |||||
Sequence: VQGLQVKVTKLKKERILDAQRLEEFFTKNQQLRDQQKVLQETIKILEDRL | ||||||
Region | 45-160 | Required for interaction with LMO4, probably by stabilizing the interaction through RPPB8 dimerization | ||||
Sequence: LKKERILDAQRLEEFFTKNQQLRDQQKVLQETIKILEDRLRAGLCDRCAVTEEHMHKKQQEFENIRQQNLKLITELMNEKNTLQEENKKLSEQLQQKMENGQQDQVAELACEENII | ||||||
Coiled coil | 117-138 | |||||
Sequence: ITELMNEKNTLQEENKKLSEQL | ||||||
Region | 296-324 | Disordered | ||||
Sequence: MESARSKEDSLRFSDSASKTPPQEFTTRA | ||||||
Compositional bias | 310-324 | Polar residues | ||||
Sequence: DSASKTPPQEFTTRA | ||||||
Motif | 489-493 | PXDLS motif | ||||
Sequence: PLDLS | ||||||
Region | 508-556 | Damage-recruitment motif | ||||
Sequence: NETSKNKLKQATIYEALKPIPKGSSSGRKALSGDCMPAKDSWETYCLQP | ||||||
Region | 639-683 | Required for interaction with LMO4, probably by making physical contact with LMO4 | ||||
Sequence: ALPSNQDTSFENIQWSVDPGADLSQYKMDVTVIDTKDSSHSRLGG | ||||||
Motif | 836-838 | KLHL15-binding | ||||
Sequence: FRY | ||||||
Region | 869-893 | Disordered | ||||
Sequence: DLSPRPKRRQPYNAVFSPKGKEQRT |
Domain
The PXDLS motif binds to a cleft in CtBP proteins.
The damage-recruitment motif is required for DNA binding and translocation to sites of DNA damage.
Sequence similarities
Belongs to the COM1/SAE2/CtIP family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length893
- Mass (Da)100,831
- Last updated2003-06-01 v1
- Checksum2F363F88D2190F13
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A3Q4L2U0 | A0A3Q4L2U0_MOUSE | Rbbp8 | 118 | ||
A0A3Q4EBX2 | A0A3Q4EBX2_MOUSE | Rbbp8 | 26 | ||
A0A3Q4EGK0 | A0A3Q4EGK0_MOUSE | Rbbp8 | 612 | ||
A0A3Q4EGL1 | A0A3Q4EGL1_MOUSE | Rbbp8 | 247 |
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 310-324 | Polar residues | ||||
Sequence: DSASKTPPQEFTTRA |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AC090479 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC115894 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC050849 EMBL· GenBank· DDBJ | AAH50849.1 EMBL· GenBank· DDBJ | mRNA |