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Protein

DNA endonuclease RBBP8

Gene

Rbbp8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.3 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Endonuclease, Hydrolase, Nuclease

Keywords - Biological processi

Cell cycle, Cell division, DNA damage, DNA repair, Meiosis, Mitosis

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiR-MMU-5685938. HDR through Single Strand Annealing (SSA).
R-MMU-5685939. HDR through MMEJ (alt-NHEJ).
R-MMU-5685942. HDR through Homologous Recombination (HRR).
R-MMU-5693554. Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA).
R-MMU-5693568. Resolution of D-loop Structures through Holliday Junction Intermediates.
R-MMU-5693579. Homologous DNA Pairing and Strand Exchange.
R-MMU-5693607. Processing of DNA double-strand break ends.
R-MMU-5693616. Presynaptic phase of homologous DNA pairing and strand exchange.
R-MMU-6804756. Regulation of TP53 Activity through Phosphorylation.
R-MMU-69473. G2/M DNA damage checkpoint.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA endonuclease RBBP8 (EC:3.1.-.-)
Alternative name(s):
CtBP-interacting protein
Short name:
CtIP
Retinoblastoma-binding protein 8
Short name:
RBBP-8
Retinoblastoma-interacting protein and myosin-like
Short name:
RIM
Sporulation in the absence of SPO11 protein 2 homolog
Short name:
SAE2
Gene namesi
Name:Rbbp8
Synonyms:Ctip
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:2442995. Rbbp8.

Subcellular locationi

  • Nucleus By similarity
  • Chromosome By similarity

  • Note: Associates with sites of DNA damage in S/G2 phase. Ubiquitinated RBBP8 binds to chromatin following DNA damage.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 893893DNA endonuclease RBBP8PRO_0000417036Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki193 – 193Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei233 – 2331PhosphoserineCombined sources
Modified residuei325 – 3251PhosphoserineBy similarity
Modified residuei326 – 3261PhosphoserineBy similarity
Modified residuei348 – 3481PhosphoserineBy similarity
Cross-linki377 – 377Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei431 – 4311N6-acetyllysineBy similarity
Modified residuei525 – 5251N6-acetyllysineBy similarity
Modified residuei602 – 6021N6-acetyllysine; alternateBy similarity
Cross-linki602 – 602Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Cross-linki611 – 611Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei662 – 6621Phosphoserine; by ATMBy similarity
Modified residuei677 – 6771PhosphoserineBy similarity
Modified residuei720 – 7201PhosphoserineCombined sources
Modified residuei742 – 7421Phosphoserine; by ATMBy similarity
Modified residuei843 – 8431Phosphothreonine; by CDK1By similarity
Cross-linki865 – 865Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity

Post-translational modificationi

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. Phosphorylated on 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).By similarity
Acetylated. Deacetylation by SIRT6 upon DNA damage promotes DNA end resection.By similarity
Ubiquitinated. 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. Ubiquitinated by RNF138 at its N-terminus.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ80YR6.
PaxDbiQ80YR6.
PRIDEiQ80YR6.

PTM databases

iPTMnetiQ80YR6.

Expressioni

Gene expression databases

BgeeiQ80YR6.
GenevisibleiQ80YR6. MM.

Interactioni

Subunit structurei

Homodimer; dimerizes via the coiled coil domain. Interacts (via the PXDLS motif) with CTBP1. Component of the BRCA1-RBBBP8 complex. Interacts (the Ser-326 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). Interacts with SIAH1. Interacts with RNF138. Interacts with EXD2 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi230366. 1 interaction.
STRINGi10090.ENSMUSP00000046255.

Structurei

3D structure databases

ProteinModelPortaliQ80YR6.
SMRiQ80YR6. Positions 19-52, 639-675.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni22 – 4524Essential for binding to the MRN complex and for RPA focus formation on DNA damageBy similarityAdd
BLAST
Regioni489 – 4935PXDLS motif
Regioni508 – 55649Damage-recruitment motifBy similarityAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili54 – 14996Sequence analysisAdd
BLAST

Domaini

The damage-recruitment motif is required for DNA binding and translocation to sites of DNA damage.By similarity
The PXDLS motif binds to a cleft in CtBP proteins.By similarity

Sequence similaritiesi

Belongs to the COM1/SAE2/CtIP family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IJ39. Eukaryota.
ENOG410ZSBE. LUCA.
GeneTreeiENSGT00530000063835.
HOGENOMiHOG000293331.
HOVERGENiHBG057046.
InParanoidiQ80YR6.
OMAiETVDMDC.
OrthoDBiEOG771274.
PhylomeDBiQ80YR6.
TreeFamiTF106469.

Family and domain databases

InterProiIPR019518. CtIP_N.
IPR013882. Ctp1_C.
IPR033316. RBBP8-like.
[Graphical view]
PANTHERiPTHR15107. PTHR15107. 3 hits.
PfamiPF10482. CtIP_N. 1 hit.
PF08573. SAE2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q80YR6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSISGSGCGS PNSADASNDF KELWTKLKEY HDKEVQGLQV KVTKLKKERI
60 70 80 90 100
LDAQRLEEFF TKNQQLRDQQ KVLQETIKIL EDRLRAGLCD RCAVTEEHMH
110 120 130 140 150
KKQQEFENIR QQNLKLITEL MNEKNTLQEE NKKLSEQLQQ KMENGQQDQV
160 170 180 190 200
AELACEENII PDSPVTSFSF SGINRLRKKE NLHVRYVEQT HTKLERSLCT
210 220 230 240 250
NELRKISKDS APAPVNSEEH EILVADTCDQ NHSPLSKICE TSSYPTDKTS
260 270 280 290 300
FNLDTVVAET LGLNGQEESE PQGPMSPLGS ELYHCLKEDH KKHPFMESAR
310 320 330 340 350
SKEDSLRFSD SASKTPPQEF TTRASSPVFG ATSTVKAHLG LNTSFSPSLL
360 370 380 390 400
DIGKKNLLKT APFSNIAVSR SEKVRSKSED NALFTQHSLG SEVKVISQSF
410 420 430 440 450
SSKQILTNKT VSDSVDEQCS ADHMNTTVAD KYLVPLKSLG GKASKRKRTE
460 470 480 490 500
EESEHAVKCP QACFDKENAL PFPMENQFSM NGDHVMDKPL DLSDRFAATQ
510 520 530 540 550
RQEKNHGNET SKNKLKQATI YEALKPIPKG SSSGRKALSG DCMPAKDSWE
560 570 580 590 600
TYCLQPRSLQ SSSKFSPDQK TPLQIKEENP VFKTPPCSQE SLETENLFGD
610 620 630 640 650
VKGTGSLVPT KVKSRAVHGG CELASVLQLN PCRVAKTKAL PSNQDTSFEN
660 670 680 690 700
IQWSVDPGAD LSQYKMDVTV IDTKDSSHSR LGGETVDMDC TLVSETVLLK
710 720 730 740 750
MKKQEQKERS PNGDIKMNDS LEDMFDRTTH EEYESCLADS FSQVPDEEEL
760 770 780 790 800
PDTTKKTNIP ADKQDGVKQK AFVGPYFKDK ERETSIQNFP HIEVVRKKEE
810 820 830 840 850
RRKLLGHTCK ECEIYYADLP AEEREKKLAS CSRHRFRYIP PNTPENFWEV
860 870 880 890
GFPSTQTCLE RGYIKEDLDL SPRPKRRQPY NAVFSPKGKE QRT
Length:893
Mass (Da):100,831
Last modified:June 1, 2003 - v1
Checksum:i2F363F88D2190F13
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC090479 Genomic DNA. No translation available.
AC115894 Genomic DNA. No translation available.
BC050849 mRNA. Translation: AAH50849.1.
CCDSiCCDS37738.1.
RefSeqiNP_001074692.1. NM_001081223.2.
NP_001239424.1. NM_001252495.1.
XP_006525875.1. XM_006525812.2.
UniGeneiMm.154275.

Genome annotation databases

EnsembliENSMUST00000047322; ENSMUSP00000046255; ENSMUSG00000041238.
ENSMUST00000115861; ENSMUSP00000111527; ENSMUSG00000041238.
GeneIDi225182.
KEGGimmu:225182.
UCSCiuc008ebl.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC090479 Genomic DNA. No translation available.
AC115894 Genomic DNA. No translation available.
BC050849 mRNA. Translation: AAH50849.1.
CCDSiCCDS37738.1.
RefSeqiNP_001074692.1. NM_001081223.2.
NP_001239424.1. NM_001252495.1.
XP_006525875.1. XM_006525812.2.
UniGeneiMm.154275.

3D structure databases

ProteinModelPortaliQ80YR6.
SMRiQ80YR6. Positions 19-52, 639-675.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi230366. 1 interaction.
STRINGi10090.ENSMUSP00000046255.

PTM databases

iPTMnetiQ80YR6.

Proteomic databases

EPDiQ80YR6.
PaxDbiQ80YR6.
PRIDEiQ80YR6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000047322; ENSMUSP00000046255; ENSMUSG00000041238.
ENSMUST00000115861; ENSMUSP00000111527; ENSMUSG00000041238.
GeneIDi225182.
KEGGimmu:225182.
UCSCiuc008ebl.1. mouse.

Organism-specific databases

CTDi5932.
MGIiMGI:2442995. Rbbp8.

Phylogenomic databases

eggNOGiENOG410IJ39. Eukaryota.
ENOG410ZSBE. LUCA.
GeneTreeiENSGT00530000063835.
HOGENOMiHOG000293331.
HOVERGENiHBG057046.
InParanoidiQ80YR6.
OMAiETVDMDC.
OrthoDBiEOG771274.
PhylomeDBiQ80YR6.
TreeFamiTF106469.

Enzyme and pathway databases

ReactomeiR-MMU-5685938. HDR through Single Strand Annealing (SSA).
R-MMU-5685939. HDR through MMEJ (alt-NHEJ).
R-MMU-5685942. HDR through Homologous Recombination (HRR).
R-MMU-5693554. Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA).
R-MMU-5693568. Resolution of D-loop Structures through Holliday Junction Intermediates.
R-MMU-5693579. Homologous DNA Pairing and Strand Exchange.
R-MMU-5693607. Processing of DNA double-strand break ends.
R-MMU-5693616. Presynaptic phase of homologous DNA pairing and strand exchange.
R-MMU-6804756. Regulation of TP53 Activity through Phosphorylation.
R-MMU-69473. G2/M DNA damage checkpoint.

Miscellaneous databases

PROiQ80YR6.
SOURCEiSearch...

Gene expression databases

BgeeiQ80YR6.
GenevisibleiQ80YR6. MM.

Family and domain databases

InterProiIPR019518. CtIP_N.
IPR013882. Ctp1_C.
IPR033316. RBBP8-like.
[Graphical view]
PANTHERiPTHR15107. PTHR15107. 3 hits.
PfamiPF10482. CtIP_N. 1 hit.
PF08573. SAE2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Limb.
  3. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-233 AND SER-720, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Spleen and Testis.
  4. "Human SIRT6 promotes DNA end resection through CtIP deacetylation."
    Kaidi A., Weinert B.T., Choudhary C., Jackson S.P.
    Science 329:1348-1353(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  5. "An essential role for CtIP in chromosomal translocation formation through an alternative end-joining pathway."
    Zhang Y., Jasin M.
    Nat. Struct. Mol. Biol. 18:80-84(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "CtIP promotes microhomology-mediated alternative end joining during class-switch recombination."
    Lee-Theilen M., Matthews A.J., Kelly D., Zheng S., Chaudhuri J.
    Nat. Struct. Mol. Biol. 18:75-79(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, DNA-BINDING.

Entry informationi

Entry nameiCOM1_MOUSE
AccessioniPrimary (citable) accession number: Q80YR6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 16, 2012
Last sequence update: June 1, 2003
Last modified: June 8, 2016
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.