Q99708 (COM1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	RBBP8
Synonyms:	CTIP

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	897 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Cell cycle Cell division DNA damage DNA repair Meiosis Mitosis
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Dwarfism Mental retardation
Domain	Coiled coil
Ligand	DNA-binding
Molecular function	Endonuclease Hydrolase Nuclease
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA 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_component	nucleolus 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_function	RNA 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
BRCA1	P38398	9	EBI-745715,EBI-349905
EXO1	Q9UQ84	3	EBI-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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 897

897

DNA endonuclease RBBP8

PRO_0000097179

Regions

Region

22 – 45

24

Essential for binding to the MRN complex and for RPA focus formation on DNA damage

Region

509 – 557

49

Damage-recruitment motif

Coiled coil

28 – 157

130

Potential

Motif

490 – 494

5

PXDLS motif

Compositional bias

750 – 753

4

Poly-Glu

Amino acid modifications

Modified residue

326

1

Phosphoserine

Modified residue

327

1

Phosphoserine Ref.13

Modified residue

349

1

Phosphoserine

Modified residue

432

1

N6-acetyllysine Ref.23

Modified residue

526

1

N6-acetyllysine Ref.23

Modified residue

604

1

N6-acetyllysine Ref.23

Modified residue

664

1

Phosphoserine; by ATM Ref.9

Modified residue

679

1

Phosphoserine

Modified residue

723

1

Phosphoserine Ref.22

Modified residue

745

1

Phosphoserine; by ATM Ref.9

Modified residue

847

1

Phosphothreonine; by CDK1 Ref.18

Natural variations

Alternative sequence

714

1

S → SMLFYI in isoform 2.

VSP_043220

Alternative sequence

786 – 867

82

RETSL…MERGY → SIMQICQQKKEKRNWLPAQD TDSATFHPTHQRIFGKLVFL PLRLVWKEVILRKILILVLV QKDVSLTTQYFLQKARSRRH RR in isoform 3.

VSP_045247

Alternative sequence

868 – 897

30

Missing in isoform 3.

VSP_045248

Natural variant

357

1

K → N.
Corresponds to variant rs34678569 [ dbSNP | Ensembl ].

VAR_051308

Natural variant

387

1

H → Y.
Corresponds to variant rs1804732 [ dbSNP | Ensembl ].

VAR_028308

Experimental info

Mutagenesis

31

1

H → A: No effect on RPA focus formation on DNA damage. Ref.19

Mutagenesis

35

1

V → A: No effect on RPA focus formation on DNA damage. Ref.19

Mutagenesis

41

1

K → A: No effect on RPA focus formation on DNA damage. Ref.19

Mutagenesis

45

1

L → A: No effect on RPA focus formation on DNA damage. Ref.19

Mutagenesis

327

1

S → A: Abolishes BRCA1 interaction and ubiquitination. No activation of CHEK1 after DNA damage. Ref.13 Ref.14

Mutagenesis

432

1

K → R: Greatly reduced acetylation. Alleviates resection defects caused by depletion of SIRT6; when associated with R-526 and R-604. Ref.23

Mutagenesis

513

1

K → A: Abolishes damage recruitment capability. Ref.20

Mutagenesis

515

1

K → A: Abolishes damage recruitment capability. Ref.20

Mutagenesis

526

1

K → R: Greatly reduced acetylation. Alleviates resection defects caused by depletion of SIRT6; when associated with R-432 and R-604. Ref.23

Mutagenesis

604

1

K → R: Greatly reduced acetylation. Alleviates resection defects caused by depletion of SIRT6; when associated with R-432 and R-526. Ref.23

Mutagenesis

664

1

S → A: Abrogates dissociation of BRCA1. Ref.9

Mutagenesis

745

1

S → A: Abrogates dissociation of BRCA1. Ref.9

Mutagenesis

847

1

T → A: Impairs DNA resection. Ref.18

Mutagenesis

847

1

T → E: Mimics constitutive phosphorylation. Ref.18

Sequence conflict

4

1

S → L in AAC14371. Ref.1

Sequence conflict

74

1

H → Q in BX648221. Ref.4

Sequence conflict

92

1

C → Y in BAF85170. Ref.3

Sequence conflict

123

1

E → G in BAF85170. Ref.3

Sequence conflict

341

1

D → G in BX648221. Ref.4

Sequence conflict

515

1

K → R in BX648221. Ref.4

Sequence conflict

521

1

L → P in BAF85170. Ref.3

Sequence conflict

642

1

L → P in BX648221. Ref.4

Isoform 3:

Sequence conflict

862

1

S → G in BX648221. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

897

Helix Strand Turn

Details...

Beta strand

648 – 650

3

Helix

651 – 653

3

Turn

662 – 666

5

Beta strand

677 – 679

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: E028DE56DE55C0F2	FASTA	897	101,942
	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
	Isoform 2 [UniParc]. Checksum: 43DEA11A0349322B	FASTA	902	102,610
	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 EKSSMLFYIN 730 740 750 760 770 780 EERKMNDSLE DMFDRTTHEE YESCLADSFS QAADEEEELS TATKKLHTHG DKQDKVKQKA 790 800 810 820 830 840 FVEPYFKGDE RETSLQNFPH IEVVRKKEER RKLLGHTCKE CEIYYADMPA EEREKKLASC 850 860 870 880 890 900 SRHRFRYIPP NTPENFWEVG FPSTQTCMER GYIKEDLDPC PRPKRRQPYN AIFSPKGKEQ KT
	Isoform 3 [UniParc]. Checksum: A8CFDB72587619E3	FASTA	867	98,434
	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 FKGDESIMQI CQQKKEKRNW LPAQDTDSAT FHPTHQRIFG KLVFLPLRLV WKEVILRKIL 850 860 ILVLVQKDVS LTTQYFLQKA RSRRHRR

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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. , 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

RefSeq

NP_002885.1. NM_002894.2.
NP_976036.1. NM_203291.1.
NP_976037.1. NM_203292.1.

UniGene

Hs.546282.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2L4Z	NMR	-	A	641-685	[»]

ProteinModelPortal

Q99708.

SMR

Q99708. Positions 641-677.

ModBase

Search...

MobiDB

Search...

Protein-protein interaction databases

BioGrid

111867. 38 interactions.

DIP

DIP-24244N.

IntAct

Q99708. 24 interactions.

MINT

MINT-102295.

STRING

9606.ENSP00000323050.

PTM databases

PhosphoSite

Q99708.

Polymorphism databases

DMDM

116242745.

Proteomic databases

PaxDb

Q99708.

PRIDE

Q99708.

Protocols and materials databases

DNASU

5932.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000327155; ENSP00000323050; ENSG00000101773. [Q99708-1]
ENST00000399722; ENSP00000382628; ENSG00000101773. [Q99708-1]
ENST00000399725; ENSP00000382630; ENSG00000101773. [Q99708-3]

GeneID

5932.

KEGG

hsa:5932.

UCSC

uc002ktw.3. human. [Q99708-1]

Organism-specific databases

CTD

5932.

GeneCards

GC18P020402.

HGNC

HGNC:9891. RBBP8.

HPA

HPA039890.
HPA052946.

MIM

251255. phenotype.
604124. gene.
606744. phenotype.

neXtProt

NX_Q99708.

Orphanet

313795. Jawad syndrome.
808. Seckel syndrome.

PharmGKB

PA34255.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG145529.

HOGENOM

HOG000293331.

HOVERGEN

HBG057046.

OrthoDB

EOG771274.

PhylomeDB

Q99708.

TreeFam

TF106469.

Enzyme and pathway databases

Reactome

REACT_111183. Meiosis.

Gene expression databases

ArrayExpress

Q99708.

Bgee

Q99708.

CleanEx

HS_RBBP8.

Genevestigator

Q99708.

Family and domain databases

InterPro

IPR019518. CtIP_N.
IPR013882. DNA-repair_Sae2/CtIP.
[Graphical view]

Pfam

PF10482. CtIP_N. 1 hit.
PF08573. SAE2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

RBBP8. human.

EvolutionaryTrace

Q99708.

GeneWiki

RBBP8.

GenomeRNAi

5932.

NextBio

23118.

PRO

Q99708.

SOURCE

Search...

Entry information

Entry name

COM1_HUMAN

Accession

Primary (citable) accession number: Q99708
Secondary accession number(s): A6NKN2 , 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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.