Reviewed, UniProtKB/Swiss-Prot Q9P287 (BCCIP_HUMAN)

Names and origin

Protein names

Recommended name:
    BRCA2 and CDKN1A-interacting protein
Alternative name(s):
    Protein TOK-1
    P21- and CDK-associated protein 1

Gene names

Name:	BCCIP
Synonyms:	TOK1

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	314 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	May promote cell cycle arrest by enhancing the inhibition of CDK2 activity by CDKN1A. May be required for repair of DNA damage by homologous recombination in conjunction with BRCA2. May not be involved in non-homologous end joining (NHEJ). Ref.1 Ref.7 Ref.8 Ref.9 Ref.12
Subunit structure	Interacts with BRCA2, CDKN1A and MTDH/LYRIC. Ref.1 Ref.7 Ref.9 Ref.6 Ref.13
Subcellular location	Nucleus. Note: Colocalizes with BRCA2 in discrete nuclear foci. Ref.1 Ref.9 Ref.6
Tissue specificity	Expressed at high levels in testis and skeletal muscle and at lower levels in brain, heart, kidney, liver, lung, ovary, pancreas, placenta, and spleen. Ref.1 Ref.6
Developmental stage	Isoform 1 is expressed throughout the cell cycle while isoform 2 is expressed following mitosis and peaks in the G1/S phase of the cell cycle. Ref.1
Miscellaneous	HT1080 cells that constitutively express low levels of BCCIP display increased levels of spontaneous single-stranded DNA and double-strand breaks.
Sequence similarities	Belongs to the BCP1 family.

Ontologies

Keywords
Biological process	Cell cycle DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	DNA repair Inferred from electronic annotation. Source: UniProtKB-KW cell cycle Inferred from electronic annotation. Source: UniProtKB-KW regulation of cyclin-dependent protein kinase activity Ref.1 Traceable author statement. Source: ProtInc
Cellular component	nucleus Ref.1 Traceable author statement. Source: ProtInc
Molecular function	protein binding Ref.13 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EIF6	P56537	1	EBI-711154,EBI-372243

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9P287-1)

Also known as: Beta;

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: Q9P287-2)

Also known as: Alpha;

The sequence of this isoform differs from the canonical sequence as follows:
     259-314: KAILKFNYSV...MDKLKEYLSV → EQGKPEVLGG...TFMTVGIALS

Isoform 3 (identifier: Q9P287-3)

The sequence of this isoform differs from the canonical sequence as follows:
     285-314: VPMTPLRTVMLIPGDKMNEIMDKLKEYLSV → WSVPPVLE

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 314	314	BRCA2 and CDKN1A-interacting protein		PRO_0000249687
Regions
	Region	59 – 167	109	Interaction with BRCA2
	Region	161 – 259	99	Interaction with CDKN1A
Amino acid modifications
	Modified residue	12	1	Phosphoserine Ref.11
	Modified residue	42	1	Phosphoserine Ref.10
	Modified residue	112	1	Phosphoserine Ref.10
	Modified residue	115	1	Phosphoserine Ref.10
Natural variations
	Alternative sequence	259 – 314	56	KAILK…EYLSV → EQGKPEVLGGPDTRRGLEPV PIQHNGGSRGQVTALVSLKA GLIQSRSTLSDFQGTFMTVG IALS in isoform 2.		VSP_020540
	Alternative sequence	285 – 314	30	VPMTP…EYLSV → WSVPPVLE in isoform 3.		VSP_020541
	Natural variant	254	1	E → Q: dbSNP rs17153610.		VAR_046642
Experimental info
	Sequence conflict	230	1	G → E in AAH09771. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Beta) [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 203CA32F7BE0A806	FASTA	314	35,979
	10 20 30 40 50 60 MASRSKRRAV ESGVPQPPDP PVQRDEEEEK EVENEDEDDD DSDKEKDEED EVIDEEVNIE 70 80 90 100 110 120 FEAYSLSDND YDGIKKLLQQ LFLKAPVNTA ELTDLLIQQN HIGSVIKQTD VSEDSNDDMD 130 140 150 160 170 180 EDEVFGFISL LNLTERKGTQ CVEQIQELVL RFCEKNCEKS MVEQLDKFLN DTTKPVGLLL 190 200 210 220 230 240 SERFINVPPQ IALPMYQQLQ KELAGAHRTN KPCGKCYFYL LISKTFVEAG KNNSKKKPSN 250 260 270 280 290 300 KKKAALMFAN AEEEFFYEKA ILKFNYSVQE ESDTCLGGKW SFDDVPMTPL RTVMLIPGDK 310 MNEIMDKLKE YLSV
	Isoform 2 (Alpha). Checksum: 09B96B373DE27F56	FASTA	322	36,215
	10 20 30 40 50 60 MASRSKRRAV ESGVPQPPDP PVQRDEEEEK EVENEDEDDD DSDKEKDEED EVIDEEVNIE 70 80 90 100 110 120 FEAYSLSDND YDGIKKLLQQ LFLKAPVNTA ELTDLLIQQN HIGSVIKQTD VSEDSNDDMD 130 140 150 160 170 180 EDEVFGFISL LNLTERKGTQ CVEQIQELVL RFCEKNCEKS MVEQLDKFLN DTTKPVGLLL 190 200 210 220 230 240 SERFINVPPQ IALPMYQQLQ KELAGAHRTN KPCGKCYFYL LISKTFVEAG KNNSKKKPSN 250 260 270 280 290 300 KKKAALMFAN AEEEFFYEEQ GKPEVLGGPD TRRGLEPVPI QHNGGSRGQV TALVSLKAGL 310 320 IQSRSTLSDF QGTFMTVGIA LS
	Isoform 3. Checksum: D6EB060145DCEE1C	FASTA	292	33,442
	10 20 30 40 50 60 MASRSKRRAV ESGVPQPPDP PVQRDEEEEK EVENEDEDDD DSDKEKDEED EVIDEEVNIE 70 80 90 100 110 120 FEAYSLSDND YDGIKKLLQQ LFLKAPVNTA ELTDLLIQQN HIGSVIKQTD VSEDSNDDMD 130 140 150 160 170 180 EDEVFGFISL LNLTERKGTQ CVEQIQELVL RFCEKNCEKS MVEQLDKFLN DTTKPVGLLL 190 200 210 220 230 240 SERFINVPPQ IALPMYQQLQ KELAGAHRTN KPCGKCYFYL LISKTFVEAG KNNSKKKPSN 250 260 270 280 290 KKKAALMFAN AEEEFFYEKA ILKFNYSVQE ESDTCLGGKW SFDDWSVPPV LE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"TOK-1, a novel p21Cip1-binding protein that cooperatively enhances p21-dependent inhibitory activity toward CDK2 kinase." Ono T., Kitaura H., Ugai H., Murata T., Yokoyama K.K., Iguchi-Ariga S.M.M., Ariga H. J. Biol. Chem. 275:31145-31154(2000) [PubMed: 10878006] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, INTERACTION WITH CDKN1A, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. Tissue: Brain.
[2]	"Genomic structure of the human BCCIP gene and its expression in cancer." Meng X., Liu J., Shen Z. Gene 302:139-146(2003) [PubMed: 12527204] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2).
[3]	"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., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Brain.
[4]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[6]	"Inhibition of breast and brain cancer cell growth by BCCIPalpha, an evolutionarily conserved nuclear protein that interacts with BRCA2." Liu J., Yuan Y., Huan J., Shen Z. Oncogene 20:336-345(2001) [PubMed: 11313963] [Abstract] Cited for: INTERACTION WITH BRCA2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[7]	"Inhibition of G1 to S cell cycle progression by BCCIP beta." Meng X., Liu J., Shen Z. Cell Cycle 3:343-348(2004) [PubMed: 14726710] [Abstract] Cited for: FUNCTION, INTERACTION WITH CDKN1A.
[8]	"BCCIP functions through p53 to regulate the expression of p21Waf1/Cip1." Meng X., Lu H., Shen Z. Cell Cycle 3:1457-1462(2004) [PubMed: 15539944] [Abstract] Cited for: FUNCTION.
[9]	"The BRCA2-interacting protein BCCIP functions in RAD51 and BRCA2 focus formation and homologous recombinational repair." Lu H., Guo X., Meng X., Liu J., Allen C., Wray J., Nickoloff J.A., Shen Z. Mol. Cell. Biol. 25:1949-1957(2005) [PubMed: 15713648] [Abstract] Cited for: FUNCTION, INTERACTION WITH BRCA2, SUBCELLULAR LOCATION.
[10]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42; SER-112 AND SER-115, MASS SPECTROMETRY. Tissue: Epithelium.
[11]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12, MASS SPECTROMETRY.
[12]	"BCCIP regulates homologous recombination by distinct domains and suppresses spontaneous DNA damage." Lu H., Yue J., Meng X., Nickoloff J.A., Shen Z. Nucleic Acids Res. 35:7160-7170(2007) [PubMed: 17947333] [Abstract] Cited for: FUNCTION.
[13]	"LYRIC/AEG-1 overexpression modulates BCCIPalpha protein levels in prostate tumor cells." Ash S.C., Yang D.Q., Britt D.E. Biochem. Biophys. Res. Commun. 371:333-338(2008) [PubMed: 18440304] [Abstract] Cited for: INTERACTION WITH MTDH.
[14]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB040450 mRNA. Translation: BAA92927.1. AB040451 mRNA. Translation: BAA92928.1. AY064247 Genomic DNA. Translation: AAL55436.1. AY064247 Genomic DNA. Translation: AAL55438.1. AY064248 mRNA. Translation: AAL55439.1. AY064249 mRNA. Translation: AAL55440.1. AL834458 mRNA. Translation: CAD39118.1. AL360176 Genomic DNA. Translation: CAI12091.1. AL360176 Genomic DNA. Translation: CAI12092.1. AL360176 Genomic DNA. Translation: CAI12093.1. BC009771 mRNA. Translation: AAH09771.1.
IPI	IPI00002203. IPI00220152. IPI00786906.
RefSeq	NP_057651.1. NP_510868.1. NP_510869.1.
UniGene	Hs.370292 Hs.501379
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9P287. 7 interactions.
PTM databases
PhosphoSite	Q9P287.
Proteomic databases
PRIDE	Q9P287.
Genome annotation databases
Ensembl	ENSG00000107949. Homo sapiens. [Contig view]
GeneID	56647.
KEGG	hsa:56647.
Organism-specific databases
GeneCards	GC10P127502.
HGNC	HGNC:978. BCCIP.
MIM	611883. gene.
PharmGKB	PA25290.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q9P287.
OMA	Q9P287. LGGRWSF.
Gene expression databases
ArrayExpress	Q9P287.
Bgee	Q9P287.
CleanEx	HS_BCCIP.
GermOnline	ENSG00000107949. Homo sapiens.
Family and domain databases
ProtoNet	Search...
Other Resources
NextBio	62077.
SOURCE	Search...

Entry information

Entry name

BCCIP_HUMAN

Accession

Primary (citable) accession number: Q9P287
Secondary accession number(s): Q8ND15, Q96GC4, Q9P288

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2006
Last sequence update:	October 1, 2000
Last modified:	June 16, 2009
This is version 53 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)