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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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 MRN complex in processing meiotic and mitotic double-strand breaks by ensuring both resection and intrachromosomal association of the broken ends. Promotes ATR and RPA recruitment to DSBs in S/G2 phase and facilitates the generation of ssDNA. May modulate the functions ascribed to BRCA1 in transcriptional regulation, DNA repair, and/or cell cycle checkpoint control. Ref.7 Ref.10
Subunit structure	Interacts with CTBP, with the C-terminal (BRCT) domains of BRCA1, and with the retinoblastoma protein. Interacts with MRN complex subunits MRE11 and RAD50. Ref.6 Ref.7
Subcellular location	Nucleus. Note: Associates with sites of DNA damage in S/G2 phase. Ref.3 Ref.7
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Hyperphosphorylation upon ionizing radiation results in dissociation from BRCA1. Phosphorylated at Thr-847 by CDK1, which is essential for the recruitment to DNA and DNA repair function. Ref.4 Ref.5 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ubiquitinated; mediated by SIAH1 and leading to its subsequent proteasomal degradation Probable. Ref.6
Sequence similarities	Belongs to the COM1/SAE2/CtIP family.

Ontologies

Keywords
Biological process	DNA damage DNA repair Meiosis
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Domain	Coiled coil
Ligand	DNA-binding
Molecular function	Endonuclease Hydrolase Nuclease
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA double-strand break processing involved in repair via single-strand annealing Inferred from mutant phenotype. Source: UniProtKB cell cycle checkpoint Traceable author statement. Source: ProtInc meiosis Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription from RNA polymerase II promoter Traceable author statement. Source: ProtInc
Cellular component	nucleus Traceable author statement. Source: ProtInc
Molecular function	damaged DNA binding Inferred from direct assay. Source: UniProtKB protein binding Inferred from physical interaction. Source: UniProtKB single-stranded DNA specific endodeoxyribonuclease activity Inferred from mutant phenotype. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BRCA1	P38398	9	EBI-1263531,EBI-349905

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	490 – 494	5	CTBP-binding motif
	Coiled coil	28 – 157	130	Potential
	Compositional bias	750 – 753	4	Poly-Glu
Amino acid modifications
	Modified residue	326	1	Phosphoserine Ref.9
	Modified residue	327	1	Phosphoserine Ref.5 Ref.9
	Modified residue	349	1	Phosphoserine Ref.11
	Modified residue	664	1	Phosphoserine; by ATM Ref.4
	Modified residue	679	1	Phosphoserine Ref.8
	Modified residue	745	1	Phosphoserine; by ATM Ref.4
	Modified residue	847	1	Phosphothreonine; by CDK1 Ref.10
Natural variations
	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	664	1	S → A: Abrogates dissociation of BRCA1. Ref.4
	Mutagenesis	745	1	S → A: Abrogates dissociation of BRCA1. Ref.4
	Mutagenesis	847	1	T → A: Impairs DNA resection. Ref.10
	Mutagenesis	847	1	T → E: Mimics constitutive phosphorylation. Ref.10
	Sequence conflict	4	1	S → L in AAC14371. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q99708 [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

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: 9535825] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Molecular cloning and characterization of a novel retinoblastoma-binding protein." Fusco C., Reymond A., Zervos A.S. Genomics 51:351-358(1998) [PubMed: 9721205] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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: 10764811] [Abstract] Cited for: SUBCELLULAR LOCATION.
[4]	"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: 10910365] [Abstract] Cited for: PHOSPHORYLATION AT SER-664 AND SER-745, MUTAGENESIS OF SER-664 AND SER-745.
[5]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-327, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[6]	"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: 14654780] [Abstract] Cited for: INTERACTION WITH SIAH1, DEGRADATION.
[7]	"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: 17965729] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION, INTERACTION WITH BRCA1; MRE11 AND RAD50.
[8]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-679, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[9]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-326 AND SER-327, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[10]	"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: 19202191] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT THR-847, MUTAGENESIS OF THR-847.
[11]	"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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-349, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U72066 mRNA. Translation: AAC14371.1.
AF043431 mRNA. Translation: AAC34368.1.

IPI

IPI00480111.

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.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-24244N.

IntAct

Q99708. 13 interactions.

MINT

MINT-102295.

STRING

Q99708.

PTM databases

PhosphoSite

Q99708.

Polymorphism databases

DMDM

116242745.

Proteomic databases

PRIDE

Q99708.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000327155; ENSP00000323050; ENSG00000101773.
ENST00000399722; ENSP00000382628; ENSG00000101773.

GeneID

5932.

KEGG

hsa:5932.

UCSC

uc002ktw.1. human.

Organism-specific databases

CTD

5932.

GeneCards

GC18P020513.

H-InvDB

HIX0014362.

HGNC

HGNC:9891. RBBP8.

HPA

HPA039890.

MIM

604124. gene.

neXtProt

NX_Q99708.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04650.

GeneTree

ENSGT00530000063835.

HOVERGEN

HBG057046.

OrthoDB

EOG49078H.

Enzyme and pathway databases

Pathway_Interaction_DB

bard1pathway. BARD1 signaling events.

Reactome

REACT_111183. Meiosis.

Gene expression databases

ArrayExpress

Q99708.

Bgee

Q99708.

CleanEx

HS_RBBP8.

Genevestigator

Q99708.

GermOnline

ENSG00000101773. Homo sapiens.

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

NextBio

23118.

SOURCE

Search...

Entry information

Entry name

COM1_HUMAN

Accession

Primary (citable) accession number: Q99708
Secondary accession number(s): O75371

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	October 17, 2006
Last modified:	January 25, 2012
This is version 104 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.