CTIP_RAT
ID CTIP_RAT Reviewed; 893 AA.
AC B1WC58;
DT 16-MAY-2012, integrated into UniProtKB/Swiss-Prot.
DT 20-MAY-2008, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=DNA endonuclease RBBP8;
DE EC=3.1.-.-;
DE AltName: Full=CtBP-interacting protein;
DE Short=CtIP;
DE AltName: Full=Retinoblastoma-binding protein 8;
DE Short=RBBP-8;
DE AltName: Full=Retinoblastoma-interacting protein and myosin-like;
DE Short=RIM;
DE AltName: Full=Sporulation in the absence of SPO11 protein 2 homolog;
DE Short=SAE2;
GN Name=Rbbp8; Synonyms=Ctip;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Endonuclease that cooperates with the MRE11-RAD50-NBN (MRN)
CC complex in DNA-end resection, the first step of double-strand break
CC (DSB) repair through the homologous recombination (HR) pathway. HR is
CC restricted to S and G2 phases of the cell cycle and preferentially
CC repairs DSBs resulting from replication fork collapse. Key determinant
CC of DSB repair pathway choice, as it commits cells to HR by preventing
CC classical non-homologous end-joining (NHEJ). Functions downstream of
CC the MRN complex and ATM, promotes ATR activation and its recruitment to
CC DSBs in the S/G2 phase facilitating the generation of ssDNA. Component
CC of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls
CC cell cycle G2/M checkpoints on DNA damage (By similarity). During
CC immunoglobulin heavy chain class-switch recombination, promotes
CC microhomology-mediated alternative end joining (A-NHEJ) and plays an
CC essential role in chromosomal translocations (By similarity).
CC {ECO:0000250|UniProtKB:Q80YR6, ECO:0000250|UniProtKB:Q99708}.
CC -!- SUBUNIT: Homodimer; dimerizes via the coiled coil domain. Interacts
CC (via the PXDLS motif) with CTBP1; the interaction is disrupted via
CC binding of the adenovirus E1A to CTBP1. Component of the BRCA1-RBBP8
CC complex. Interacts (the Ser-326 phosphorylated form) with BRCA1 (via
CC the C-terminal BRCA1 domains): the interaction occurs in the G2 phase,
CC ubiquitinates RBBP8 and involves RBBP8 in BRCA1-dependent G2/M
CC checkpoint control on DNA damage. Interacts with RB1. Interacts with
CC the MRN complex. Interacts directly with MRE11; the interaction is
CC required for efficient homologous recombination (HR) and regulation of
CC the MRN complex. Interacts directly with RAD50. Interacts directly with
CC NBN. Interacts with LM04 (via the LIM zinc-binding 1 domain). Interacts
CC with SIAH1. Interacts with RNF138. Interacts with EXD2. Interacts with
CC CUL3 and KLHL15; this interaction leads to RBBP8 proteasomal
CC degradation. Directly interacts with PIN1; this interaction depends
CC upon RBBP8 phosphorylation. Interacts with FZR1; this interaction leads
CC to APC/C-mediated RBBP8 proteasomal degradation. Interacts with AUNIP;
CC leading to recruit RBBP8 to sites of DNA damage. Interacts with SAMHD1
CC (By similarity). Interacts with HDGFL2 (By similarity).
CC {ECO:0000250|UniProtKB:Q99708}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q99708}.
CC Chromosome {ECO:0000250|UniProtKB:Q99708}. Note=Associates with sites
CC of DNA damage in S/G2 phase. Ubiquitinated RBBP8 binds to chromatin
CC following DNA damage. {ECO:0000250|UniProtKB:Q99708}.
CC -!- DOMAIN: The damage-recruitment motif is required for DNA binding and
CC translocation to sites of DNA damage. {ECO:0000250}.
CC -!- DOMAIN: The PXDLS motif binds to a cleft in CtBP proteins.
CC {ECO:0000250|UniProtKB:Q99708}.
CC -!- PTM: Hyperphosphorylation upon ionizing radiation results in
CC dissociation from BRCA1. Phosphorylation at Thr-843 by CDK1 is
CC essential for the recruitment to DNA and the DNA repair function.
CC Phosphorylated on Ser-326 as cells enter G2 phase. This phosphorylation
CC is required for binding BRCA1 and for the G2/M DNA damage transition
CC checkpoint control (By similarity). Phosphorylation at Ser-276 may
CC serve as a PIN1 isomerization site (By similarity).
CC {ECO:0000250|UniProtKB:Q99708}.
CC -!- PTM: Ubiquitinated. Ubiquitination at multiple sites by BRCA1 (via its
CC N-terminal RING domain) does not lead to its proteosomal degradation
CC but instead the ubiquitinated RBBP8 binds to chromatin following DNA
CC damage and may play a role in G2/M checkpoint control. Ubiquitinated by
CC RNF138 at its N-terminus. Ubiquitinated through 'Lys-48' by the E3
CC CUL3-KLHL15 complex; this modification leads to proteasomal degradation
CC (By similarity). Ubiquitinated by the E3 FZR1/APC/C complex; this
CC modification leads to proteasomal degradation (By similarity).
CC {ECO:0000250|UniProtKB:Q99708}.
CC -!- SIMILARITY: Belongs to the COM1/SAE2/CtIP family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC162012; AAI62012.1; -; mRNA.
DR RefSeq; NP_001127889.1; NM_001134417.1.
DR RefSeq; XP_008770161.2; XM_008771939.2.
DR AlphaFoldDB; B1WC58; -.
DR SMR; B1WC58; -.
DR STRING; 10116.ENSRNOP00000017291; -.
DR jPOST; B1WC58; -.
DR PaxDb; B1WC58; -.
DR Ensembl; ENSRNOT00000017291; ENSRNOP00000017291; ENSRNOG00000012899.
DR GeneID; 291787; -.
DR KEGG; rno:291787; -.
DR UCSC; RGD:1308872; rat.
DR CTD; 5932; -.
DR RGD; 1308872; Rbbp8.
DR eggNOG; ENOG502QTV5; Eukaryota.
DR GeneTree; ENSGT00530000063835; -.
DR HOGENOM; CLU_019262_0_0_1; -.
DR InParanoid; B1WC58; -.
DR OMA; FKIPLCP; -.
DR OrthoDB; 962036at2759; -.
DR PhylomeDB; B1WC58; -.
DR TreeFam; TF106469; -.
DR Reactome; R-RNO-5685938; HDR through Single Strand Annealing (SSA).
DR Reactome; R-RNO-5685939; HDR through MMEJ (alt-NHEJ).
DR Reactome; R-RNO-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-RNO-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR Reactome; R-RNO-5693579; Homologous DNA Pairing and Strand Exchange.
DR Reactome; R-RNO-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-RNO-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR Reactome; R-RNO-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-RNO-69473; G2/M DNA damage checkpoint.
DR PRO; PR:B1WC58; -.
DR Proteomes; UP000002494; Chromosome 18.
DR Bgee; ENSRNOG00000012899; Expressed in lung and 19 other tissues.
DR ExpressionAtlas; B1WC58; baseline and differential.
DR Genevisible; B1WC58; RN.
DR GO; GO:0070533; C:BRCA1-C complex; ISO:RGD.
DR GO; GO:0035861; C:site of double-strand break; IBA:GO_Central.
DR GO; GO:0017053; C:transcription repressor complex; ISO:RGD.
DR GO; GO:0003684; F:damaged DNA binding; ISO:RGD.
DR GO; GO:0000406; F:double-strand/single-strand DNA junction binding; IBA:GO_Central.
DR GO; GO:0003690; F:double-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0070336; F:flap-structured DNA binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0003697; F:single-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0000014; F:single-stranded DNA endodeoxyribonuclease activity; ISO:RGD.
DR GO; GO:0003714; F:transcription corepressor activity; ISO:RGD.
DR GO; GO:0000403; F:Y-form DNA binding; IBA:GO_Central.
DR GO; GO:0001835; P:blastocyst hatching; ISO:RGD.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0010792; P:DNA double-strand break processing involved in repair via single-strand annealing; ISO:RGD.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IBA:GO_Central.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISO:RGD.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:1905168; P:positive regulation of double-strand break repair via homologous recombination; ISS:UniProtKB.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR InterPro; IPR019518; CtIP_N.
DR InterPro; IPR013882; Ctp1_C.
DR InterPro; IPR033594; RBBP8.
DR InterPro; IPR033316; RBBP8-like.
DR PANTHER; PTHR15107; PTHR15107; 1.
DR PANTHER; PTHR15107:SF4; PTHR15107:SF4; 1.
DR Pfam; PF10482; CtIP_N; 1.
DR Pfam; PF08573; SAE2; 1.
PE 2: Evidence at transcript level;
KW Cell cycle; Cell division; Chromosome; Coiled coil; DNA damage; DNA repair;
KW DNA-binding; Endonuclease; Hydrolase; Isopeptide bond; Meiosis; Mitosis;
KW Nuclease; Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..893
FT /note="DNA endonuclease RBBP8"
FT /id="PRO_0000417037"
FT REGION 22..45
FT /note="Essential for binding to the MRN complex and for RPA
FT focus formation on DNA damage"
FT /evidence="ECO:0000250"
FT REGION 306..333
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 489..493
FT /note="PXDLS motif"
FT REGION 508..556
FT /note="Damage-recruitment motif"
FT /evidence="ECO:0000250"
FT REGION 744..763
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 870..893
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 54..147
FT /evidence="ECO:0000255"
FT MOTIF 836..838
FT /note="KLHL15-binding"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT COMPBIAS 315..333
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 748..763
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 233
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT MOD_RES 276
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT MOD_RES 325
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT MOD_RES 326
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT MOD_RES 348
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT MOD_RES 378
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT MOD_RES 662
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT MOD_RES 677
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT MOD_RES 720
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT MOD_RES 742
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT MOD_RES 843
FT /note="Phosphothreonine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 62
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 193
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 377
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 394
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 403
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 409
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 437
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 525
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 529
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 576
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 602
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 611
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 636
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 638
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 674
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 716
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 778
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 865
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
SQ SEQUENCE 893 AA; 100705 MW; 57A4189635AA5F9B CRC64;
MSISGSSCGS PNSTDISSDF KELWTKLKEY HDKEVQGLQI KVTKLKKERI LDAQRLEEFF
TKNQQLRDQQ KVLQETIKIL EDRLRAGLCD RCAVTEEHMH KKQQEFENIR QQNLRLITEL
MNEKSALQEE NKKLSEQLQQ KMESGQQDQV AELECEENII PDSPITSFSF SGINRLRRKE
NLHVRYVEQT HTKLEHSACT SELRKFSKGS TPAPVNSEEH EILVADTCDQ SHSPLSKICG
TSSYPADKLS SNLDAVVAET LGLDGQEESE PQGPVSPLGN ELYHCLKEDH KKQPFMESAI
RNEDNVRFSD SASKAPPREL TTRGSSPVFG PTSTVKTHLG LKTSFSPSLL DSGKKNLLST
APFSSISVSR SEKVRSKSED NALFTQQSAG SEVKVISQSF PSKQILTSKN VSDSVDEQGG
ADHMKDAVSD KHLVPLKSLG GKASKRKRTE EEGEHAVHCP QTCFDKENAL PFPMENQFPV
NGDHVMDKPL DLSDRFAANQ RQEKNHGDET CKHKLKQVTI YEALKPVPKG SSSGRKALSG
ACTLAQDSAE TYCLQQRTLQ CSSKFSPDHN TQLQIKEENP VFKTPPRSQE SLETENLFGD
VKGIGSLVPI KVKGRSAHGG CELASVLQLN PCRVAKTKSL PSNHDMSFEN IQWSVDPGAD
LSQYKMDVTV IDTKDSSHSR LGGETVDMDC TLVSETMLLK MKKQEQREKS PNGDIKMNDS
LEDMFDRTTH EEYESCLADN FSQVPDEEEL SDTTKKPNIH GDKQDGIKQK AFVEPYFKDK
ERETSIQNFP HIEVVRKKEE RRKLLGHTCK ECEIYYADLP AEEREKKLAS CSRHRFRYIP
TNTPENFWEV GFPSTQTCLE RGYIKEDLDP CPRPKRRQPY NAVFSPKGKE QRT
