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Q99708 (COM1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:RBBP8
Synonyms:CTIP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length897 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8 Ref.9 Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.19 Ref.20 Ref.23

Subunit structure

Homodimer; dimerizes via the coiled coil domain. Interacts (via the PXDLS motif) with CTBP1; the interaction is disrupted via binding of the adenovirus E1A to CTBP1. Component of the BRCA1-RBBBP8 complex. Interacts (the Ser-327 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). Ref.1 Ref.2 Ref.8 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16 Ref.19 Ref.23

Subcellular location

Nucleus. Note: Associates with sites of DNA damage in S/G2 phase. Ubiquitinated RBBP8 binds to chromatin following DNA damage. Ref.8 Ref.16

Induction

Levels increase dramatically as dividing cells traverse the G1/S boubdary. Down-regulated in tamoxifen-resistant breast cancer cells.

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.

Post-translational modification

Acetylated. Deacetylation by SIRT6 upon DNA damage promotes DNA end resection. Ref.23

Hyperphosphorylation upon ionizing radiation results in dissociation from BRCA1. Phosphorylation at Thr-847 by CDK1 is essential for the recruitment to DNA and the DNA repair function. Phosphorylated on Ser-327 as cells enter G2 phase. This phosphorylation is required for binding BRCA1 and for the G2/M DNA damage transition checkpoint control. Ref.9 Ref.13 Ref.16 Ref.18

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. Ref.11 Ref.14

Involvement in disease

Seckel syndrome 2 (SCKL2) [MIM:606744]: A rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and mental retardation.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.25

Jawad syndrome (JWDS) [MIM:251255]: A syndrome characterized by congenital microcephaly, moderately severe mental retardation, and symmetrical digital anomalies. Digital malformations of variable degree include hallux valgus, syndactyly of toes 4 and 5, short fifth fingers, single flexion crease of fifth fingers, polydactyly and synpolydactyly.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.25

Genetic variability in RBBP8 is noted as a factor in BRCA1-associated breast cancer risk. Exhibits sensitivity to tamoxifen in certain breast cancer cell lines.

Sequence similarities

Belongs to the COM1/SAE2/CtIP family.

Ontologies

Keywords
   Biological processCell cycle
Cell division
DNA damage
DNA repair
Meiosis
Mitosis
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDwarfism
Mental retardation
   DomainCoiled coil
   LigandDNA-binding
   Molecular functionEndonuclease
Hydrolase
Nuclease
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA catabolic process, endonucleolytic

Inferred from mutant phenotype PubMed 18716619PubMed 19702191. Source: GOC

DNA double-strand break processing involved in repair via single-strand annealing

Inferred from mutant phenotype PubMed 18716619PubMed 19702191. Source: UniProtKB

DNA repair

Traceable author statement Ref.8. Source: ProtInc

G1/S transition of mitotic cell cycle

Inferred from electronic annotation. Source: Ensembl

G2 DNA damage checkpoint

Inferred from direct assay Ref.13. Source: UniProtKB

blastocyst hatching

Inferred from electronic annotation. Source: Ensembl

cell cycle checkpoint

Traceable author statement Ref.8. Source: ProtInc

double-strand break repair via homologous recombination

Inferred from direct assay Ref.23. Source: UniProtKB

meiotic nuclear division

Inferred from electronic annotation. Source: UniProtKB-KW

mitosis

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 16287852. Source: GOC

regulation of transcription from RNA polymerase II promoter

Traceable author statement Ref.8. Source: ProtInc

   Cellular_componentnucleolus

Inferred from direct assay. Source: HPA

nucleus

Inferred from direct assay. Source: HPA

transcriptional repressor complex

Inferred from direct assay PubMed 16287852. Source: BHF-UCL

   Molecular_functionRNA polymerase II repressing transcription factor binding

Inferred from physical interaction PubMed 16287852. Source: BHF-UCL

RNA polymerase II transcription corepressor activity

Inferred from direct assay PubMed 16287852. Source: BHF-UCL

damaged DNA binding

Inferred from direct assay PubMed 18716619. Source: UniProtKB

single-stranded DNA endodeoxyribonuclease activity

Inferred from mutant phenotype PubMed 18716619PubMed 19702191. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

BRCA1P383989EBI-745715,EBI-349905
EXO1Q9UQ843EBI-745715,EBI-944667

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q99708-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q99708-2)

The sequence of this isoform differs from the canonical sequence as follows:
     714-714: S → SMLFYI
Isoform 3 (identifier: Q99708-3)

The sequence of this isoform differs from the canonical sequence as follows:
     786-867: RETSLQNFPH...STQTCMERGY → SIMQICQQKK...QKARSRRHRR
     868-897: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 897897DNA endonuclease RBBP8
PRO_0000097179

Regions

Region22 – 4524Essential for binding to the MRN complex and for RPA focus formation on DNA damage
Region509 – 55749Damage-recruitment motif
Coiled coil28 – 157130 Potential
Motif490 – 4945PXDLS motif
Compositional bias750 – 7534Poly-Glu

Amino acid modifications

Modified residue3261Phosphoserine
Modified residue3271Phosphoserine Ref.13
Modified residue3491Phosphoserine
Modified residue4321N6-acetyllysine Ref.23
Modified residue5261N6-acetyllysine Ref.23
Modified residue6041N6-acetyllysine Ref.23
Modified residue6641Phosphoserine; by ATM Ref.9
Modified residue6791Phosphoserine
Modified residue7231Phosphoserine Ref.22
Modified residue7451Phosphoserine; by ATM Ref.9
Modified residue8471Phosphothreonine; by CDK1 Ref.18

Natural variations

Alternative sequence7141S → SMLFYI in isoform 2.
VSP_043220
Alternative sequence786 – 86782RETSL…MERGY → SIMQICQQKKEKRNWLPAQD TDSATFHPTHQRIFGKLVFL PLRLVWKEVILRKILILVLV QKDVSLTTQYFLQKARSRRH RR in isoform 3.
VSP_045247
Alternative sequence868 – 89730Missing in isoform 3.
VSP_045248
Natural variant3571K → N.
Corresponds to variant rs34678569 [ dbSNP | Ensembl ].
VAR_051308
Natural variant3871H → Y.
Corresponds to variant rs1804732 [ dbSNP | Ensembl ].
VAR_028308

Experimental info

Mutagenesis311H → A: No effect on RPA focus formation on DNA damage. Ref.19
Mutagenesis351V → A: No effect on RPA focus formation on DNA damage. Ref.19
Mutagenesis411K → A: No effect on RPA focus formation on DNA damage. Ref.19
Mutagenesis451L → A: No effect on RPA focus formation on DNA damage. Ref.19
Mutagenesis3271S → A: Abolishes BRCA1 interaction and ubiquitination. No activation of CHEK1 after DNA damage. Ref.13 Ref.14
Mutagenesis4321K → R: Greatly reduced acetylation. Alleviates resection defects caused by depletion of SIRT6; when associated with R-526 and R-604. Ref.23
Mutagenesis5131K → A: Abolishes damage recruitment capability. Ref.20
Mutagenesis5151K → A: Abolishes damage recruitment capability. Ref.20
Mutagenesis5261K → R: Greatly reduced acetylation. Alleviates resection defects caused by depletion of SIRT6; when associated with R-432 and R-604. Ref.23
Mutagenesis6041K → R: Greatly reduced acetylation. Alleviates resection defects caused by depletion of SIRT6; when associated with R-432 and R-526. Ref.23
Mutagenesis6641S → A: Abrogates dissociation of BRCA1. Ref.9
Mutagenesis7451S → A: Abrogates dissociation of BRCA1. Ref.9
Mutagenesis8471T → A: Impairs DNA resection. Ref.18
Mutagenesis8471T → E: Mimics constitutive phosphorylation. Ref.18
Sequence conflict41S → L in AAC14371. Ref.1
Sequence conflict741H → Q in BX648221. Ref.4
Sequence conflict921C → Y in BAF85170. Ref.3
Sequence conflict1231E → G in BAF85170. Ref.3
Sequence conflict3411D → G in BX648221. Ref.4
Sequence conflict5151K → R in BX648221. Ref.4
Sequence conflict5211L → P in BAF85170. Ref.3
Sequence conflict6421L → P in BX648221. Ref.4
Isoform 3:
Sequence conflict8621S → G in BX648221. Ref.4

Secondary structure

........ 897
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 17, 2006. Version 2.
Checksum: E028DE56DE55C0F2

FASTA897101,942
        10         20         30         40         50         60 
MNISGSSCGS PNSADTSSDF KDLWTKLKEC HDREVQGLQV KVTKLKQERI LDAQRLEEFF 

        70         80         90        100        110        120 
TKNQQLREQQ KVLHETIKVL EDRLRAGLCD RCAVTEEHMR KKQQEFENIR QQNLKLITEL 

       130        140        150        160        170        180 
MNERNTLQEE NKKLSEQLQQ KIENDQQHQA AELECEEDVI PDSPITAFSF SGVNRLRRKE 

       190        200        210        220        230        240 
NPHVRYIEQT HTKLEHSVCA NEMRKVSKSS THPQHNPNEN EILVADTYDQ SQSPMAKAHG 

       250        260        270        280        290        300 
TSSYTPDKSS FNLATVVAET LGLGVQEESE TQGPMSPLGD ELYHCLEGNH KKQPFEESTR 

       310        320        330        340        350        360 
NTEDSLRFSD STSKTPPQEE LPTRVSSPVF GATSSIKSGL DLNTSLSPSL LQPGKKKHLK 

       370        380        390        400        410        420 
TLPFSNTCIS RLEKTRSKSE DSALFTHHSL GSEVNKIIIQ SSNKQILINK NISESLGEQN 

       430        440        450        460        470        480 
RTEYGKDSNT DKHLEPLKSL GGRTSKRKKT EEESEHEVSC PQASFDKENA FPFPMDNQFS 

       490        500        510        520        530        540 
MNGDCVMDKP LDLSDRFSAI QRQEKSQGSE TSKNKFRQVT LYEALKTIPK GFSSSRKASD 

       550        560        570        580        590        600 
GNCTLPKDSP GEPCSQECII LQPLNKCSPD NKPSLQIKEE NAVFKIPLRP RESLETENVL 

       610        620        630        640        650        660 
DDIKSAGSHE PIKIQTRSDH GGCELASVLQ LNPCRTGKIK SLQNNQDVSF ENIQWSIDPG 

       670        680        690        700        710        720 
ADLSQYKMDV TVIDTKDGSQ SKLGGETVDM DCTLVSETVL LKMKKQEQKG EKSSNEERKM 

       730        740        750        760        770        780 
NDSLEDMFDR TTHEEYESCL ADSFSQAADE EEELSTATKK LHTHGDKQDK VKQKAFVEPY 

       790        800        810        820        830        840 
FKGDERETSL QNFPHIEVVR KKEERRKLLG HTCKECEIYY ADMPAEEREK KLASCSRHRF 

       850        860        870        880        890 
RYIPPNTPEN FWEVGFPSTQ TCMERGYIKE DLDPCPRPKR RQPYNAIFSP KGKEQKT 

« Hide

Isoform 2 [UniParc].

Checksum: 43DEA11A0349322B
Show »

FASTA902102,610
Isoform 3 [UniParc].

Checksum: A8CFDB72587619E3
Show »

FASTA86798,434

References

« Hide 'large scale' references
[1]"Molecular cloning and characterization of a novel retinoblastoma-binding protein."
Fusco C., Reymond A., Zervos A.S.
Genomics 51:351-358(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH RB1.
[2]"Interaction between a cellular protein that binds to the C-terminal region of adenovirus E1A (CtBP) and a novel cellular protein is disrupted by E1A through a conserved PLDLS motif."
Schaeper U., Subramanian T., Lim L., Boyd J.M., Chinnadurai G.
J. Biol. Chem. 273:8549-8552(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH CTBP1.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Testis.
[4]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Endometrial cancer.
[5]"DNA sequence and analysis of human chromosome 18."
Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. expand/collapse author list , Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.
Nature 437:551-555(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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] (ISOFORM 2).
Tissue: Testis.
[8]"Nuclear localization and cell cycle-specific expression of CtIP, a protein that associates with the BRCA1 tumor suppressor."
Yu X., Baer R.
J. Biol. Chem. 275:18541-18549(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH BRCA1.
[9]"Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response."
Li S., Ting N.S.Y., Zheng L., Chen P.-L., Ziv Y., Shiloh Y., Lee E.Y.-H.P., Lee W.-H.
Nature 406:210-215(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT SER-664 AND SER-745, MUTAGENESIS OF SER-664 AND SER-745.
[10]"The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity."
Sum E.Y., Peng B., Yu X., Chen J., Byrne J., Lindeman G.J., Visvader J.E.
J. Biol. Chem. 277:7849-7856(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LMO4.
[11]"SIAH-1 interacts with CtIP and promotes its degradation by the proteasome pathway."
Germani A., Prabel A., Mourah S., Podgorniak M.-P., Di Carlo A., Ehrlich R., Gisselbrecht S., Varin-Blank N., Calvo F., Bruzzoni-Giovanelli H.
Oncogene 22:8845-8851(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SIAH1, UBIQUITINATION.
[12]"Dimerization of CtIP, a BRCA1- and CtBP-interacting protein, is mediated by an N-terminal coiled-coil motif."
Dubin M.J., Stokes P.H., Sum E.Y., Williams R.S., Valova V.A., Robinson P.J., Lindeman G.J., Glover J.N., Visvader J.E., Matthews J.M.
J. Biol. Chem. 279:26932-26938(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, IDENTIFICATION BY MASS SPECTROMETRY.
[13]"DNA damage-induced cell cycle checkpoint control requires CtIP, a phosphorylation-dependent binding partner of BRCA1 C-terminal domains."
Yu X., Chen J.
Mol. Cell. Biol. 24:9478-9486(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT SER-327, INTERACTION WITH BRCA1, MUTAGENESIS OF SER-327.
[14]"BRCA1 ubiquitinates its phosphorylation-dependent binding partner CtIP."
Yu X., Fu S., Lai M., Baer R., Chen J.
Genes Dev. 20:1721-1726(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BRCA1, FUNCTION, UBIQUITINATION, MUTAGENESIS OF SER-327.
[15]"CtIP activates its own and cyclin D1 promoters via the E2F/RB pathway during G1/S progression."
Liu F., Lee W.H.
Mol. Cell. Biol. 26:3124-3134(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[16]"Human CtIP promotes DNA end resection."
Sartori A.A., Lukas C., Coates J., Mistrik M., Fu S., Bartek J., Baer R., Lukas J., Jackson S.P.
Nature 450:509-514(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION, INTERACTION WITH BRCA1; MRE11A AND RAD50.
[17]"Functional complementation studies identify candidate genes and common genetic variants associated with ovarian cancer survival."
Quaye L., Dafou D., Ramus S.J., Song H., Gentry-Maharaj A., Notaridou M., Hogdall E., Kjaer S.K., Christensen L., Hogdall C., Easton D.F., Jacobs I., Menon U., Pharoah P.D., Gayther S.A.
Hum. Mol. Genet. 18:1869-1878(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION WITH OVARIAN CANCER SURVIVAL.
[18]"Human CtIP mediates cell cycle control of DNA end resection and double strand break repair."
Huertas P., Jackson S.P.
J. Biol. Chem. 284:9558-9565(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DNA-BINDING, PHOSPHORYLATION AT THR-847, MUTAGENESIS OF THR-847.
[19]"N terminus of CtIP is critical for homologous recombination-mediated double-strand break repair."
Yuan J., Chen J.
J. Biol. Chem. 284:31746-31752(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MRE11A; RAD50 AND NBN, MUTAGENESIS OF HIS-31; VAL-35; LYS-41 AND LEU-45.
[20]"CtIP links DNA double-strand break sensing to resection."
You Z., Shi L.Z., Zhu Q., Wu P., Zhang Y.W., Basilio A., Tonnu N., Verma I.M., Berns M.W., Hunter T.
Mol. Cell 36:954-969(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF LYS-513 AND LYS-515.
[21]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[22]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-723, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[23]"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, ACETYLATION AT LYS-432; LYS-526 AND LYS-604, INTERACTION WITH SIRT6, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF LYS-432; LYS-526 AND LYS-604.
[24]"Modification of BRCA1-associated breast and ovarian cancer risk by BRCA1-interacting genes."
Rebbeck T.R., Mitra N., Domchek S.M., Wan F., Friebel T.M., Tran T.V., Singer C.F., Tea M.K., Blum J.L., Tung N., Olopade O.I., Weitzel J.N., Lynch H.T., Snyder C.L., Garber J.E., Antoniou A.C., Peock S., Evans D.G. expand/collapse author list , Paterson J., Kennedy M.J., Donaldson A., Dorkins H., Easton D.F., Rubinstein W.S., Daly M.B., Isaacs C., Nevanlinna H., Couch F.J., Andrulis I.L., Freidman E., Laitman Y., Ganz P.A., Tomlinson G.E., Neuhausen S.L., Narod S.A., Phelan C.M., Greenberg R., Nathanson K.L.
Cancer Res. 71:5792-5805(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION WITH BREAST CANCER.
[25]"CtIP mutations cause Seckel and Jawad syndromes."
Jackson S.P., Borglum A.D.
PLoS Genet. 7:E1002310-E1002310(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN JWDS, INVOLVEMENT IN SCKL2.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF043431 mRNA. Translation: AAC34368.1.
U72066 mRNA. Translation: AAC14371.1.
AK292481 mRNA. Translation: BAF85170.1.
BX648221 mRNA. No translation available.
AC091147 Genomic DNA. No translation available.
AC106033 Genomic DNA. No translation available.
CH471088 Genomic DNA. Translation: EAX01144.1.
BC030590 mRNA. Translation: AAH30590.1.
RefSeqNP_002885.1. NM_002894.2.
NP_976036.1. NM_203291.1.
NP_976037.1. NM_203292.1.
UniGeneHs.546282.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2L4ZNMR-A641-685[»]
ProteinModelPortalQ99708.
SMRQ99708. Positions 641-677.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111867. 38 interactions.
DIPDIP-24244N.
IntActQ99708. 24 interactions.
MINTMINT-102295.
STRING9606.ENSP00000323050.

PTM databases

PhosphoSiteQ99708.

Polymorphism databases

DMDM116242745.

Proteomic databases

PaxDbQ99708.
PRIDEQ99708.

Protocols and materials databases

DNASU5932.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000327155; ENSP00000323050; ENSG00000101773. [Q99708-1]
ENST00000399722; ENSP00000382628; ENSG00000101773. [Q99708-1]
ENST00000399725; ENSP00000382630; ENSG00000101773. [Q99708-3]
GeneID5932.
KEGGhsa:5932.
UCSCuc002ktw.3. human. [Q99708-1]

Organism-specific databases

CTD5932.
GeneCardsGC18P020402.
HGNCHGNC:9891. RBBP8.
HPAHPA039890.
HPA052946.
MIM251255. phenotype.
604124. gene.
606744. phenotype.
neXtProtNX_Q99708.
Orphanet313795. Jawad syndrome.
808. Seckel syndrome.
PharmGKBPA34255.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG145529.
HOGENOMHOG000293331.
HOVERGENHBG057046.
OrthoDBEOG771274.
PhylomeDBQ99708.
TreeFamTF106469.

Enzyme and pathway databases

ReactomeREACT_111183. Meiosis.

Gene expression databases

ArrayExpressQ99708.
BgeeQ99708.
CleanExHS_RBBP8.
GenevestigatorQ99708.

Family and domain databases

InterProIPR019518. CtIP_N.
IPR013882. DNA-repair_Sae2/CtIP.
[Graphical view]
PfamPF10482. CtIP_N. 1 hit.
PF08573. SAE2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSRBBP8. human.
EvolutionaryTraceQ99708.
GeneWikiRBBP8.
GenomeRNAi5932.
NextBio23118.
PROQ99708.
SOURCESearch...

Entry information

Entry nameCOM1_HUMAN
AccessionPrimary (citable) accession number: Q99708
Secondary accession number(s): A6NKN2 expand/collapse secondary AC list , A8K8W6, E7ETY1, O75371, Q8NHQ3
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: October 17, 2006
Last modified: April 16, 2014
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM