Reviewed, UniProtKB/Swiss-Prot Q99708 (RBBP8_HUMAN)

Names and origin

Protein names

Recommended name:
    Retinoblastoma-binding protein 8
      Short name=RBBP-8
Alternative name(s):
    CtBP-interacting protein
      Short name=CtIP
    Retinoblastoma-interacting protein and myosin-like
      Short name=RIM

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.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	May modulate the functions ascribed to BRCA1 in transcriptional regulation, DNA repair, and/or cell cycle checkpoint control.
Subunit structure	Interacts with CTBP, with the C-terminal (BRCT) domains of BRCA1, and with the retinoblastoma protein. Ref.6
Subcellular location	Nucleus. Note: Predominantly nuclear. Ref.3
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Hyperphosphorylation upon ionizing radiation results in dissociation from BRCA1. Ref.4 Ref.5 Ref.7 Ubiquitinated; mediated by SIAH1 and leading to its subsequent proteasomal degradation Probable.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Domain	Coiled coil
PTM	Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	DNA repair Ref.3 Traceable author statement. Source: ProtInc cell cycle checkpoint Ref.3 Traceable author statement. Source: ProtInc regulation of transcription from RNA polymerase II promoter Ref.3 Traceable author statement. Source: ProtInc
Cellular component	nucleus Ref.3 Traceable author statement. Source: ProtInc
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BRCA1	P38398	5	EBI-1263531,EBI-349905
FAM175A	Q6UWZ7	1	EBI-1263531,EBI-1263451

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 897	897	Retinoblastoma-binding protein 8		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	327	1	Phosphoserine Ref.5
	Modified residue	664	1	Phosphoserine; by ATM Ref.4
	Modified residue	679	1	Phosphoserine Ref.7
	Modified residue	745	1	Phosphoserine; by ATM Ref.4
Natural variations
	Natural variant	357	1	K → N: dbSNP rs34678569.		VAR_051308
	Natural variant	387	1	H → Y: dbSNP rs1804732.		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
	Sequence conflict	4	1	S → L in AAC14371. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q99708-1 [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

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: Epithelium.
[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]	"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.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBLGenBankDDBJ	U72066 mRNA. Translation: AAC14371.1. AF043431 mRNA. Translation: AAC34368.1.
IPI	IPI00480111.
RefSeq	NP_002885.1. NP_976036.1. NP_976037.1.
UniGene	Hs.546282
3D structure databases
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:24244N.
IntAct	Q99708. 3 interactions.
PTM databases
PhosphoSite	Q99708.
Proteomic databases
PRIDE	Q99708.
Genome annotation databases
Ensembl	ENSG00000101773. Homo sapiens. [Contig view]
GeneID	5932.
KEGG	hsa:5932.
Organism-specific databases
GeneCards	GC18P018767.
H-InvDB	HIX0014362.
HGNC	HGNC:9891. RBBP8.
MIM	604124. gene.
PharmGKB	PA34255.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q99708.
Enzyme and pathway databases
Pathway_Interaction_DB	bard1pathway. BARD1 signaling events.
Gene expression databases
ArrayExpress	Q99708.
Bgee	Q99708.
CleanEx	HS_RBBP8.
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 Resources
NextBio	23118.
SOURCE	Search...

Entry information

Entry name

RBBP8_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:	June 16, 2009
This is version 81 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)