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Protein

DNA endonuclease RBBP8

Gene

Rbbp8

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

Functioni

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. HR is restricted to S and G2 phases of the cell cycle and preferentially repairs DSBs resulting from replication fork collapse. Key determinant of DSB repair pathway choice, as it commits cells to HR by preventing classical non-homologous end-joining (NHEJ). 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. During immunoglobulin heavy chain class-switch recombination, promotes microhomology-mediated alternative end joining (A-NHEJ) and plays an essential role in chromosomal translocations.3 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, Endonuclease, Hydrolase, Nuclease
Biological processCell cycle, Cell division, DNA damage, DNA repair, Meiosis, Mitosis

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-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:2442995 Rbbp8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004170361 – 893DNA endonuclease RBBP8Add BLAST893

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki62Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki115Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki193Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei233PhosphoserineCombined sources1
Modified residuei276PhosphoserineBy similarity1
Modified residuei315PhosphothreonineBy similarity1
Modified residuei325PhosphoserineBy similarity1
Modified residuei326PhosphoserineBy similarity1
Modified residuei348PhosphoserineBy similarity1
Cross-linki359Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki377Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei378PhosphoserineBy similarity1
Cross-linki394Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki403Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki409Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei431N6-acetyllysineBy similarity1
Cross-linki437Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei525N6-acetyllysine; alternateBy similarity1
Cross-linki525Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Cross-linki529Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki570Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki576Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei602N6-acetyllysine; alternateBy similarity1
Cross-linki602Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Cross-linki611Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki636Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki638Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei662Phosphoserine; by ATMBy similarity1
Cross-linki674Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei677PhosphoserineBy similarity1
Cross-linki716Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei720PhosphoserineCombined sources1
Modified residuei742Phosphoserine; by ATMBy similarity1
Cross-linki778Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei843PhosphothreonineBy similarity1
Cross-linki865Glycyl 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 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).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. 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.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ80YR6
PaxDbiQ80YR6
PRIDEiQ80YR6

PTM databases

iPTMnetiQ80YR6
PhosphoSitePlusiQ80YR6

Expressioni

Gene expression databases

BgeeiENSMUSG00000041238
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 MRE11; 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). Interacts with CUL3 and KLHL15; this interaction leads to RBBP8 proteasomal degradation (By similarity). Directly interacts with PIN1; this interaction depends upon RBBP8 phosphorylation, predominantly at Thr-315 (By similarity). Interacts with FZR1; this interaction leads to APC/C-mediated RBBP8 proteasomal degradation (By similarity). Interacts with AUNIP; leading to recruit RBBP8 to sites of DNA damage (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi230366, 1 interactor
IntActiQ80YR6, 1 interactor
STRINGi10090.ENSMUSP00000046255

Structurei

3D structure databases

ProteinModelPortaliQ80YR6
SMRiQ80YR6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni22 – 45Essential for binding to the MRN complex and for RPA focus formation on DNA damageBy similarityAdd BLAST24
Regioni489 – 493PXDLS motif5
Regioni508 – 556Damage-recruitment motifBy similarityAdd BLAST49

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili54 – 149Sequence analysisAdd BLAST96

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi836 – 838KLHL15-bindingBy similarity3

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
KOiK20773
OMAiETVDMDC
OrthoDBiEOG091G0QP3
PhylomeDBiQ80YR6
TreeFamiTF106469

Family and domain databases

InterProiView protein in InterPro
IPR019518 CtIP_N
IPR013882 Ctp1_C
IPR033594 RBBP8
IPR033316 RBBP8-like
PANTHERiPTHR15107 PTHR15107, 1 hit
PTHR15107:SF4 PTHR15107:SF4, 1 hit
PfamiView protein in Pfam
PF10482 CtIP_N, 1 hit
PF08573 SAE2, 1 hit

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_006525812.3
UniGeneiMm.154275

Genome annotation databases

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

Similar proteinsi

Entry informationi

Entry nameiCTIP_MOUSE
AccessioniPrimary (citable) accession number: Q80YR6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 16, 2012
Last sequence update: June 1, 2003
Last modified: May 23, 2018
This is version 121 of the entry and version 1 of the sequence. See 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

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