CTIP_BOVIN
ID CTIP_BOVIN Reviewed; 757 AA.
AC A6QNQ6; E1BLK8;
DT 16-MAY-2012, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2012, sequence version 2.
DT 03-AUG-2022, entry version 99.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Hereford;
RX PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42;
RA Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C., Puiu D.,
RA Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G.,
RA Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.;
RT "A whole-genome assembly of the domestic cow, Bos taurus.";
RL Genome Biol. 10:R42.01-R42.10(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Ascending colon;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
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-321 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, predominantly at Thr-309. Interacts with
CC FZR1; this interaction leads to APC/C-mediated RBBP8 proteasomal
CC degradation. Interacts with AUNIP; leading to recruit RBBP8 to sites of
CC DNA damage. Interacts with SAMHD1 (By similarity). Interacts with
CC HDGFL2 (By similarity). {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}.
CC -!- PTM: Hyperphosphorylation upon ionizing radiation results in
CC dissociation from BRCA1. Phosphorylation by CDK1 is essential for the
CC recruitment to DNA and the DNA repair function. Phosphorylated on Ser-
CC 321 as cells enter G2 phase. This phosphorylation is required for
CC binding BRCA1 and for the G2/M DNA damage transition checkpoint control
CC (By similarity). Phosphorylation at Thr-309, probably catalyzed by
CC CDK2, is required for PIN1-binding, while phosphorylation at Ser-272
CC serves as a PIN1 isomerization site. Phosphorylation at Thr-309 is
CC cell-cycle dependent. It steadily increases during S phase, peaks at
CC late S/G2 phase, and drops at G1 (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}.
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DR EMBL; DAAA02056622; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; DAAA02056623; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC148953; AAI48954.1; -; mRNA.
DR RefSeq; NP_001095436.1; NM_001101966.1.
DR AlphaFoldDB; A6QNQ6; -.
DR SMR; A6QNQ6; -.
DR STRING; 9913.ENSBTAP00000008875; -.
DR PaxDb; A6QNQ6; -.
DR PRIDE; A6QNQ6; -.
DR GeneID; 512977; -.
DR KEGG; bta:512977; -.
DR CTD; 5932; -.
DR eggNOG; ENOG502QTV5; Eukaryota.
DR HOGENOM; CLU_019262_0_0_1; -.
DR InParanoid; A6QNQ6; -.
DR OrthoDB; 962036at2759; -.
DR TreeFam; TF106469; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0035861; C:site of double-strand break; IBA:GO_Central.
DR GO; GO:0003684; F:damaged DNA binding; IBA:GO_Central.
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:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0070336; F:flap-structured DNA binding; IBA:GO_Central.
DR GO; GO:0003697; F:single-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0000403; F:Y-form DNA binding; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IBA:GO_Central.
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 InterPro; IPR019518; CtIP_N.
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.
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..757
FT /note="DNA endonuclease RBBP8"
FT /id="PRO_0000417035"
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 348..375
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 407..430
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 484..488
FT /note="PXDLS motif"
FT REGION 503..551
FT /note="Damage-recruitment motif"
FT /evidence="ECO:0000250"
FT REGION 524..544
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 696..757
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 61..146
FT /evidence="ECO:0000255"
FT COMPBIAS 348..367
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 696..729
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 272
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT MOD_RES 309
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT MOD_RES 320
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT MOD_RES 321
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT MOD_RES 343
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT MOD_RES 373
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT MOD_RES 656
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT MOD_RES 671
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT MOD_RES 715
FT /note="Phosphoserine"
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 115
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 354
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 372
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 390
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 399
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 405
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 433
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 443
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 520
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 564
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 570
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 596
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 605
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 630
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 632
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 668
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CROSSLNK 711
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99708"
FT CONFLICT 35
FT /note="T -> V (in Ref. 2; AAI48954)"
FT /evidence="ECO:0000305"
FT CONFLICT 753..755
FT /note="PNI -> TKH (in Ref. 2; AAI48954)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 757 AA; 85265 MW; F9DE5EDFCAA0F078 CRC64;
MNLSGSSCGS PSSADVSNDF KDLWTKLKEY HDKETQGLQV KVTKLKKERI LDAQRLEEFF
TKNQQLREQQ KVLHETIKVL EDRLRAGLCD RCAVTEEHMR KKQQEFENIR QQNLKLITEL
MNEKNTLQEE NKKLSEQLQQ KIENDQPHKA TDLESEEDVI PDSPITTFSF SGTNRLRRKE
NLRVRYIEQT HAKLEHSGCA HELRTVPKSS AHPQHKPKES EILVADTCDQ SQAPVAKPHG
KSSYTPDNLA TVVAETLGLC VQEESESRGP QSPLGDELYH CLEGDHKKQA FEECRRNSED
NLRFSDSKTP FQEELTTRVS SPVFGAPSNV KSSLGLNTSL SPSLLETGKK THLKTVPLSN
TSAPGPEKPR SKSEDGTLIT HHHLGTEVNK IPSQSSSNKQ MLINKNTSEP ISEQGNIGHS
KDTDRDKHVV PLKSLGGRTK RKKIEEESED EVICPQASFD KENAFPFPLD SHSSMNGDYV
MDKPLDLSDR FSAIQRQEKS QGCENSKIRF RQVTLYEALK PIPRDSSSSR KALSGSCGLT
KDSPEEPCLQ ESLFQSLSKS PDNKTLLQIK EENPVFKIPL RPRESFETEN LFDDTKGAGS
HEPIKIKTRS VRGACEVASV LQLNPCRIAK TKSLQNNQDV SFENIQWSID PGADLSQYKM
GVTVDDTKDG SQSRLAGETV DMDCTLVSET MLLKLKKQEQ KGEESPNGER KMNDSLEDMF
DRTTHEEYES CLAESFPQVA DEEKELSTTT KKPNISW
