Full text data of BCCIP
BCCIP
(TOK1)
[Confidence: low (only semi-automatic identification from reviews)]
BRCA2 and CDKN1A-interacting protein (P21- and CDK-associated protein 1; Protein TOK-1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
BRCA2 and CDKN1A-interacting protein (P21- and CDK-associated protein 1; Protein TOK-1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9P287
ID BCCIP_HUMAN Reviewed; 314 AA.
AC Q9P287; B3KP45; Q8ND15; Q96GC4; Q9P288;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-2000, sequence version 1.
DT 22-JAN-2014, entry version 98.
DE RecName: Full=BRCA2 and CDKN1A-interacting protein;
DE AltName: Full=P21- and CDK-associated protein 1;
DE AltName: Full=Protein TOK-1;
GN Name=BCCIP; Synonyms=TOK1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, INTERACTION
RP WITH CDKN1A, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC TISSUE=Brain;
RX PubMed=10878006; DOI=10.1074/jbc.M003031200;
RA Ono T., Kitaura H., Ugai H., Murata T., Yokoyama K.K.,
RA Iguchi-Ariga S.M.M., Ariga H.;
RT "TOK-1, a novel p21Cip1-binding protein that cooperatively enhances
RT p21-dependent inhibitory activity toward CDK2 kinase.";
RL J. Biol. Chem. 275:31145-31154(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2).
RX PubMed=12527204; DOI=10.1016/S0378-1119(02)01098-3;
RA Meng X., Liu J., Shen Z.;
RT "Genomic structure of the human BCCIP gene and its expression in
RT cancer.";
RL Gene 302:139-146(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH BRCA2, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11313963; DOI=10.1038/sj.onc.1204098;
RA Liu J., Yuan Y., Huan J., Shen Z.;
RT "Inhibition of breast and brain cancer cell growth by BCCIPalpha, an
RT evolutionarily conserved nuclear protein that interacts with BRCA2.";
RL Oncogene 20:336-345(2001).
RN [8]
RP FUNCTION, AND INTERACTION WITH CDKN1A.
RX PubMed=14726710;
RA Meng X., Liu J., Shen Z.;
RT "Inhibition of G1 to S cell cycle progression by BCCIP beta.";
RL Cell Cycle 3:343-348(2004).
RN [9]
RP FUNCTION.
RX PubMed=15539944;
RA Meng X., Lu H., Shen Z.;
RT "BCCIP functions through p53 to regulate the expression of
RT p21Waf1/Cip1.";
RL Cell Cycle 3:1457-1462(2004).
RN [10]
RP FUNCTION, INTERACTION WITH BRCA2, AND SUBCELLULAR LOCATION.
RX PubMed=15713648; DOI=10.1128/MCB.25.5.1949-1957.2005;
RA Lu H., Guo X., Meng X., Liu J., Allen C., Wray J., Nickoloff J.A.,
RA Shen Z.;
RT "The BRCA2-interacting protein BCCIP functions in RAD51 and BRCA2
RT focus formation and homologous recombinational repair.";
RL Mol. Cell. Biol. 25:1949-1957(2005).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [12]
RP FUNCTION.
RX PubMed=17947333; DOI=10.1093/nar/gkm732;
RA Lu H., Yue J., Meng X., Nickoloff J.A., Shen Z.;
RT "BCCIP regulates homologous recombination by distinct domains and
RT suppresses spontaneous DNA damage.";
RL Nucleic Acids Res. 35:7160-7170(2007).
RN [13]
RP INTERACTION WITH MTDH.
RX PubMed=18440304; DOI=10.1016/j.bbrc.2008.04.084;
RA Ash S.C., Yang D.Q., Britt D.E.;
RT "LYRIC/AEG-1 overexpression modulates BCCIPalpha protein levels in
RT prostate tumor cells.";
RL Biochem. Biophys. Res. Commun. 371:333-338(2008).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42 AND SER-115, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: May promote cell cycle arrest by enhancing the
CC inhibition of CDK2 activity by CDKN1A. May be required for repair
CC of DNA damage by homologous recombination in conjunction with
CC BRCA2. May not be involved in non-homologous end joining (NHEJ).
CC -!- SUBUNIT: Interacts with BRCA2, CDKN1A and MTDH/LYRIC.
CC -!- SUBCELLULAR LOCATION: Nucleus. Note=Colocalizes with BRCA2 in
CC discrete nuclear foci.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Beta;
CC IsoId=Q9P287-1; Sequence=Displayed;
CC Name=2; Synonyms=Alpha;
CC IsoId=Q9P287-2; Sequence=VSP_020540;
CC Name=3;
CC IsoId=Q9P287-3; Sequence=VSP_020541;
CC Name=4;
CC IsoId=Q9P287-4; Sequence=VSP_042023;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed at high levels in testis and
CC skeletal muscle and at lower levels in brain, heart, kidney,
CC liver, lung, ovary, pancreas, placenta, and spleen.
CC -!- DEVELOPMENTAL STAGE: Isoform 1 is expressed throughout the cell
CC cycle. Isoform 2 is expressed following mitosis and peaks in the
CC G1/S phase of the cell cycle.
CC -!- MISCELLANEOUS: HT1080 cells that constitutively express low levels
CC of BCCIP display increased levels of spontaneous single-stranded
CC DNA and double-strand breaks.
CC -!- SIMILARITY: Belongs to the BCP1 family.
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DR EMBL; AB040450; BAA92927.1; -; mRNA.
DR EMBL; AB040451; BAA92928.1; -; mRNA.
DR EMBL; AY064247; AAL55436.1; -; Genomic_DNA.
DR EMBL; AY064247; AAL55438.1; -; Genomic_DNA.
DR EMBL; AY064248; AAL55439.1; -; mRNA.
DR EMBL; AY064249; AAL55440.1; -; mRNA.
DR EMBL; AK055691; BAG51557.1; -; mRNA.
DR EMBL; AL834458; CAD39118.1; -; mRNA.
DR EMBL; AL360176; CAI12091.1; -; Genomic_DNA.
DR EMBL; AL360176; CAI12092.1; -; Genomic_DNA.
DR EMBL; AL360176; CAI12093.1; -; Genomic_DNA.
DR EMBL; BC009771; AAH09771.1; -; mRNA.
DR RefSeq; NP_057651.1; NM_016567.3.
DR RefSeq; NP_510868.1; NM_078468.2.
DR RefSeq; NP_510869.1; NM_078469.2.
DR UniGene; Hs.370292; -.
DR UniGene; Hs.715543; -.
DR ProteinModelPortal; Q9P287; -.
DR IntAct; Q9P287; 9.
DR MINT; MINT-3275575; -.
DR STRING; 9606.ENSP00000357748; -.
DR PhosphoSite; Q9P287; -.
DR DMDM; 74753124; -.
DR PaxDb; Q9P287; -.
DR PRIDE; Q9P287; -.
DR DNASU; 56647; -.
DR Ensembl; ENST00000278100; ENSP00000278100; ENSG00000107949.
DR Ensembl; ENST00000299130; ENSP00000299130; ENSG00000107949.
DR Ensembl; ENST00000368759; ENSP00000357748; ENSG00000107949.
DR GeneID; 56647; -.
DR KEGG; hsa:56647; -.
DR UCSC; uc001ljb.4; human.
DR CTD; 56647; -.
DR GeneCards; GC10P127502; -.
DR HGNC; HGNC:978; BCCIP.
DR MIM; 611883; gene.
DR neXtProt; NX_Q9P287; -.
DR PharmGKB; PA25290; -.
DR eggNOG; NOG310413; -.
DR HOGENOM; HOG000047210; -.
DR HOVERGEN; HBG054955; -.
DR KO; K15262; -.
DR OMA; MISKTCK; -.
DR OrthoDB; EOG7992RJ; -.
DR GeneWiki; BCCIP; -.
DR GenomeRNAi; 56647; -.
DR NextBio; 62077; -.
DR PRO; PR:Q9P287; -.
DR ArrayExpress; Q9P287; -.
DR Bgee; Q9P287; -.
DR CleanEx; HS_BCCIP; -.
DR Genevestigator; Q9P287; -.
DR GO; GO:0019908; C:nuclear cyclin-dependent protein kinase holoenzyme complex; IDA:MGI.
DR GO; GO:0019207; F:kinase regulator activity; IDA:MGI.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0061101; P:neuroendocrine cell differentiation; IDA:UniProtKB.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:MGI.
DR InterPro; IPR025602; BCP1_family.
DR PANTHER; PTHR13261; PTHR13261; 1.
DR Pfam; PF13862; BCIP; 1.
DR PIRSF; PIRSF028983; BCP1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Complete proteome; DNA damage;
KW DNA repair; Nucleus; Phosphoprotein; Polymorphism; Reference proteome.
FT CHAIN 1 314 BRCA2 and CDKN1A-interacting protein.
FT /FTId=PRO_0000249687.
FT REGION 59 167 Interaction with BRCA2.
FT REGION 161 259 Interaction with CDKN1A.
FT MOD_RES 42 42 Phosphoserine.
FT MOD_RES 115 115 Phosphoserine.
FT VAR_SEQ 259 314 KAILKFNYSVQEESDTCLGGKWSFDDVPMTPLRTVMLIPGD
FT KMNEIMDKLKEYLSV -> EQGKPEVLGGPDTRRGLEPVPI
FT QHNGGSRGQVTALVSLKAGLIQSRSTLSDFQGTFMTVGIAL
FT S (in isoform 2).
FT /FTId=VSP_020540.
FT VAR_SEQ 259 314 KAILKFNYSVQEESDTCLGGKWSFDDVPMTPLRTVMLIPGD
FT KMNEIMDKLKEYLSV -> EQGKPEVLGGPDTRRGLEPVPI
FT QHNGWSVPPVLE (in isoform 4).
FT /FTId=VSP_042023.
FT VAR_SEQ 285 314 VPMTPLRTVMLIPGDKMNEIMDKLKEYLSV -> WSVPPVL
FT E (in isoform 3).
FT /FTId=VSP_020541.
FT VARIANT 254 254 E -> Q (in dbSNP:rs17153610).
FT /FTId=VAR_046642.
FT CONFLICT 75 75 K -> R (in Ref. 3; BAG51557).
FT CONFLICT 230 230 G -> E (in Ref. 6; AAH09771).
SQ SEQUENCE 314 AA; 35979 MW; 203CA32F7BE0A806 CRC64;
MASRSKRRAV ESGVPQPPDP PVQRDEEEEK EVENEDEDDD DSDKEKDEED EVIDEEVNIE
FEAYSLSDND YDGIKKLLQQ LFLKAPVNTA ELTDLLIQQN HIGSVIKQTD VSEDSNDDMD
EDEVFGFISL LNLTERKGTQ CVEQIQELVL RFCEKNCEKS MVEQLDKFLN DTTKPVGLLL
SERFINVPPQ IALPMYQQLQ KELAGAHRTN KPCGKCYFYL LISKTFVEAG KNNSKKKPSN
KKKAALMFAN AEEEFFYEKA ILKFNYSVQE ESDTCLGGKW SFDDVPMTPL RTVMLIPGDK
MNEIMDKLKE YLSV
//
ID BCCIP_HUMAN Reviewed; 314 AA.
AC Q9P287; B3KP45; Q8ND15; Q96GC4; Q9P288;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-2000, sequence version 1.
DT 22-JAN-2014, entry version 98.
DE RecName: Full=BRCA2 and CDKN1A-interacting protein;
DE AltName: Full=P21- and CDK-associated protein 1;
DE AltName: Full=Protein TOK-1;
GN Name=BCCIP; Synonyms=TOK1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, INTERACTION
RP WITH CDKN1A, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC TISSUE=Brain;
RX PubMed=10878006; DOI=10.1074/jbc.M003031200;
RA Ono T., Kitaura H., Ugai H., Murata T., Yokoyama K.K.,
RA Iguchi-Ariga S.M.M., Ariga H.;
RT "TOK-1, a novel p21Cip1-binding protein that cooperatively enhances
RT p21-dependent inhibitory activity toward CDK2 kinase.";
RL J. Biol. Chem. 275:31145-31154(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2).
RX PubMed=12527204; DOI=10.1016/S0378-1119(02)01098-3;
RA Meng X., Liu J., Shen Z.;
RT "Genomic structure of the human BCCIP gene and its expression in
RT cancer.";
RL Gene 302:139-146(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH BRCA2, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11313963; DOI=10.1038/sj.onc.1204098;
RA Liu J., Yuan Y., Huan J., Shen Z.;
RT "Inhibition of breast and brain cancer cell growth by BCCIPalpha, an
RT evolutionarily conserved nuclear protein that interacts with BRCA2.";
RL Oncogene 20:336-345(2001).
RN [8]
RP FUNCTION, AND INTERACTION WITH CDKN1A.
RX PubMed=14726710;
RA Meng X., Liu J., Shen Z.;
RT "Inhibition of G1 to S cell cycle progression by BCCIP beta.";
RL Cell Cycle 3:343-348(2004).
RN [9]
RP FUNCTION.
RX PubMed=15539944;
RA Meng X., Lu H., Shen Z.;
RT "BCCIP functions through p53 to regulate the expression of
RT p21Waf1/Cip1.";
RL Cell Cycle 3:1457-1462(2004).
RN [10]
RP FUNCTION, INTERACTION WITH BRCA2, AND SUBCELLULAR LOCATION.
RX PubMed=15713648; DOI=10.1128/MCB.25.5.1949-1957.2005;
RA Lu H., Guo X., Meng X., Liu J., Allen C., Wray J., Nickoloff J.A.,
RA Shen Z.;
RT "The BRCA2-interacting protein BCCIP functions in RAD51 and BRCA2
RT focus formation and homologous recombinational repair.";
RL Mol. Cell. Biol. 25:1949-1957(2005).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [12]
RP FUNCTION.
RX PubMed=17947333; DOI=10.1093/nar/gkm732;
RA Lu H., Yue J., Meng X., Nickoloff J.A., Shen Z.;
RT "BCCIP regulates homologous recombination by distinct domains and
RT suppresses spontaneous DNA damage.";
RL Nucleic Acids Res. 35:7160-7170(2007).
RN [13]
RP INTERACTION WITH MTDH.
RX PubMed=18440304; DOI=10.1016/j.bbrc.2008.04.084;
RA Ash S.C., Yang D.Q., Britt D.E.;
RT "LYRIC/AEG-1 overexpression modulates BCCIPalpha protein levels in
RT prostate tumor cells.";
RL Biochem. Biophys. Res. Commun. 371:333-338(2008).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42 AND SER-115, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: May promote cell cycle arrest by enhancing the
CC inhibition of CDK2 activity by CDKN1A. May be required for repair
CC of DNA damage by homologous recombination in conjunction with
CC BRCA2. May not be involved in non-homologous end joining (NHEJ).
CC -!- SUBUNIT: Interacts with BRCA2, CDKN1A and MTDH/LYRIC.
CC -!- SUBCELLULAR LOCATION: Nucleus. Note=Colocalizes with BRCA2 in
CC discrete nuclear foci.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Beta;
CC IsoId=Q9P287-1; Sequence=Displayed;
CC Name=2; Synonyms=Alpha;
CC IsoId=Q9P287-2; Sequence=VSP_020540;
CC Name=3;
CC IsoId=Q9P287-3; Sequence=VSP_020541;
CC Name=4;
CC IsoId=Q9P287-4; Sequence=VSP_042023;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed at high levels in testis and
CC skeletal muscle and at lower levels in brain, heart, kidney,
CC liver, lung, ovary, pancreas, placenta, and spleen.
CC -!- DEVELOPMENTAL STAGE: Isoform 1 is expressed throughout the cell
CC cycle. Isoform 2 is expressed following mitosis and peaks in the
CC G1/S phase of the cell cycle.
CC -!- MISCELLANEOUS: HT1080 cells that constitutively express low levels
CC of BCCIP display increased levels of spontaneous single-stranded
CC DNA and double-strand breaks.
CC -!- SIMILARITY: Belongs to the BCP1 family.
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; AB040450; BAA92927.1; -; mRNA.
DR EMBL; AB040451; BAA92928.1; -; mRNA.
DR EMBL; AY064247; AAL55436.1; -; Genomic_DNA.
DR EMBL; AY064247; AAL55438.1; -; Genomic_DNA.
DR EMBL; AY064248; AAL55439.1; -; mRNA.
DR EMBL; AY064249; AAL55440.1; -; mRNA.
DR EMBL; AK055691; BAG51557.1; -; mRNA.
DR EMBL; AL834458; CAD39118.1; -; mRNA.
DR EMBL; AL360176; CAI12091.1; -; Genomic_DNA.
DR EMBL; AL360176; CAI12092.1; -; Genomic_DNA.
DR EMBL; AL360176; CAI12093.1; -; Genomic_DNA.
DR EMBL; BC009771; AAH09771.1; -; mRNA.
DR RefSeq; NP_057651.1; NM_016567.3.
DR RefSeq; NP_510868.1; NM_078468.2.
DR RefSeq; NP_510869.1; NM_078469.2.
DR UniGene; Hs.370292; -.
DR UniGene; Hs.715543; -.
DR ProteinModelPortal; Q9P287; -.
DR IntAct; Q9P287; 9.
DR MINT; MINT-3275575; -.
DR STRING; 9606.ENSP00000357748; -.
DR PhosphoSite; Q9P287; -.
DR DMDM; 74753124; -.
DR PaxDb; Q9P287; -.
DR PRIDE; Q9P287; -.
DR DNASU; 56647; -.
DR Ensembl; ENST00000278100; ENSP00000278100; ENSG00000107949.
DR Ensembl; ENST00000299130; ENSP00000299130; ENSG00000107949.
DR Ensembl; ENST00000368759; ENSP00000357748; ENSG00000107949.
DR GeneID; 56647; -.
DR KEGG; hsa:56647; -.
DR UCSC; uc001ljb.4; human.
DR CTD; 56647; -.
DR GeneCards; GC10P127502; -.
DR HGNC; HGNC:978; BCCIP.
DR MIM; 611883; gene.
DR neXtProt; NX_Q9P287; -.
DR PharmGKB; PA25290; -.
DR eggNOG; NOG310413; -.
DR HOGENOM; HOG000047210; -.
DR HOVERGEN; HBG054955; -.
DR KO; K15262; -.
DR OMA; MISKTCK; -.
DR OrthoDB; EOG7992RJ; -.
DR GeneWiki; BCCIP; -.
DR GenomeRNAi; 56647; -.
DR NextBio; 62077; -.
DR PRO; PR:Q9P287; -.
DR ArrayExpress; Q9P287; -.
DR Bgee; Q9P287; -.
DR CleanEx; HS_BCCIP; -.
DR Genevestigator; Q9P287; -.
DR GO; GO:0019908; C:nuclear cyclin-dependent protein kinase holoenzyme complex; IDA:MGI.
DR GO; GO:0019207; F:kinase regulator activity; IDA:MGI.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0061101; P:neuroendocrine cell differentiation; IDA:UniProtKB.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:MGI.
DR InterPro; IPR025602; BCP1_family.
DR PANTHER; PTHR13261; PTHR13261; 1.
DR Pfam; PF13862; BCIP; 1.
DR PIRSF; PIRSF028983; BCP1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Complete proteome; DNA damage;
KW DNA repair; Nucleus; Phosphoprotein; Polymorphism; Reference proteome.
FT CHAIN 1 314 BRCA2 and CDKN1A-interacting protein.
FT /FTId=PRO_0000249687.
FT REGION 59 167 Interaction with BRCA2.
FT REGION 161 259 Interaction with CDKN1A.
FT MOD_RES 42 42 Phosphoserine.
FT MOD_RES 115 115 Phosphoserine.
FT VAR_SEQ 259 314 KAILKFNYSVQEESDTCLGGKWSFDDVPMTPLRTVMLIPGD
FT KMNEIMDKLKEYLSV -> EQGKPEVLGGPDTRRGLEPVPI
FT QHNGGSRGQVTALVSLKAGLIQSRSTLSDFQGTFMTVGIAL
FT S (in isoform 2).
FT /FTId=VSP_020540.
FT VAR_SEQ 259 314 KAILKFNYSVQEESDTCLGGKWSFDDVPMTPLRTVMLIPGD
FT KMNEIMDKLKEYLSV -> EQGKPEVLGGPDTRRGLEPVPI
FT QHNGWSVPPVLE (in isoform 4).
FT /FTId=VSP_042023.
FT VAR_SEQ 285 314 VPMTPLRTVMLIPGDKMNEIMDKLKEYLSV -> WSVPPVL
FT E (in isoform 3).
FT /FTId=VSP_020541.
FT VARIANT 254 254 E -> Q (in dbSNP:rs17153610).
FT /FTId=VAR_046642.
FT CONFLICT 75 75 K -> R (in Ref. 3; BAG51557).
FT CONFLICT 230 230 G -> E (in Ref. 6; AAH09771).
SQ SEQUENCE 314 AA; 35979 MW; 203CA32F7BE0A806 CRC64;
MASRSKRRAV ESGVPQPPDP PVQRDEEEEK EVENEDEDDD DSDKEKDEED EVIDEEVNIE
FEAYSLSDND YDGIKKLLQQ LFLKAPVNTA ELTDLLIQQN HIGSVIKQTD VSEDSNDDMD
EDEVFGFISL LNLTERKGTQ CVEQIQELVL RFCEKNCEKS MVEQLDKFLN DTTKPVGLLL
SERFINVPPQ IALPMYQQLQ KELAGAHRTN KPCGKCYFYL LISKTFVEAG KNNSKKKPSN
KKKAALMFAN AEEEFFYEKA ILKFNYSVQE ESDTCLGGKW SFDDVPMTPL RTVMLIPGDK
MNEIMDKLKE YLSV
//
MIM
611883
*RECORD*
*FIELD* NO
611883
*FIELD* TI
*611883 BRCA2- AND CDKN1A-INTERACTING PROTEIN; BCCIP
;;p21- AND CDK-ASSOCIATED PROTEIN 1; TOK1
read more*FIELD* TX
CLONING
Using the C-terminal half of p21 (CDK1A; 116899) as bait in a yeast
2-hybrid screen of a brain cDNA library, Ono et al. (2000) cloned BCCIP,
which they called TOK1. EST database analysis and PCR of a brain cDNA
library revealed 2 TOK1 variants, TOK1-alpha and -beta. The deduced
proteins contain 322 and 314 amino acids, respectively, and are
identical for the first 259 amino acids. Northern blot analysis using a
probe common to both TOK1 variants detected a major 1.5-kb transcript
and a minor 3-kb transcript. Specific probes detected both TOK1 variants
as 1.5-kb transcripts. TOK1-alpha was highly expressed in skeletal
muscle, with little to no expression in other tissues examined.
TOK1-beta was highly expressed in skeletal muscle and heart, moderately
expressed in placenta and pancreas, and weakly expressed in brain,
kidney, and liver. Western blot analysis detected TOK1-alpha and
TOK1-beta as 50- and 45-kD proteins, respectively. In synchronized HeLa
cells, expression of TOK1-alpha began after G2/M phase and peaked before
S phase. TOK1-beta was expressed throughout the cell cycle, but like
TOK1-alpha, its expression increased before S phase.
Using an internal conserved region of BRCA2 (600185) as bait in a yeast
2-hybrid screen, followed by database analysis, Liu et al. (2001) cloned
BCCIP-alpha and -beta, which correspond to TOK1-alpha and -beta,
respectively. Both BCCIP isoforms have an N-terminal acidic domain and
an evolutionarily conserved internal domain, followed by the C-terminal
variable domain. The internal domain contains a putative calcium-binding
domain. Western blot analysis detected both BCCIP proteins in all
tissues examined. Immunohistochemical analysis of several human cell
lines showed nuclear expression of endogenous BCCIP.
GENE FUNCTION
Using mutation analysis, Ono et al. (2000) found that TOK1-alpha bound
to the C-terminal proximal region of p21. However, TOK1-beta did not
bind p21. TOK1-alpha formed a ternary complex with p21 and an active
form of CDK2 (116953) in human embryonic kidney cells via its
interaction with p21. TOK1-alpha enhanced the inhibitory activity of p21
toward the histone H1 (see 142709) kinase activity of CDK2.
By coimmunoprecipitation analysis of transfected human embryonic kidney
cells, Liu et al. (2001) confirmed that BCCIP-alpha interacted with
endogenous BRCA2. Expression of BCCIP-beta protein was relatively
consistent among various tumor cell lines examined. In contrast,
expression of BCCIP-alpha protein was reduced in some brain, breast, and
endometrial tumor cell lines and increased in some endometrial tumor
cell lines, with relatively consistent expression among lung cancer cell
lines. BCCIP-alpha expression inhibited growth of some breast and brain
tumor cells, but it had no effect on other types of cancer cells.
Lu et al. (2007) stated that BCCIP regulates BRCA2 and RAD51 (179617)
nuclear focus formation, DNA double-strand break-induced homologous
recombination, and cell cycle progression. They transfected full-length
and truncated fragments of BCCIP into a human fibrosarcoma cell line and
found that BCCIP fragments that interacted with either BRCA2 or p21
inhibited homologous recombination similarly. Transient downregulation
of BCCIP in human cells did not affect nonspecific integration of
transfected DNA, but it significantly inhibited homology-directed gene
targeting. Cells with constitutive downregulation of BCCIP showed
increased levels of spontaneous single-stranded DNA and double-strand
breaks. Lu et al. (2007) concluded that multiple domains of BCCIP are
involved in homologous recombination and that BCCIP plays a critical
role in resolving spontaneous DNA damage.
Using a matched normal/tumor cDNA array, Meng et al. (2003) found
reduced expression of both BCCIP-alpha and -beta in kidney tumors.
GENE STRUCTURE
Meng et al. (2003) determined that the BCCIP gene contains 9 exons and
spans about 30 kb. The 5-prime end of the BCCIP gene abuts the UROS gene
(606938) on the opposite strand in a head-to-head manner. BCCIP and UROS
share a functional intergenic bidirectional promoter that contains
binding sites for various transcription factors. The last 3 exons of
BCCIP overlap with seven 3-prime exons of the DHX32 gene (607960) on the
opposite strand.
MAPPING
By FISH and genomic sequence analysis, Liu et al. (2001) mapped the
BCCIP gene to chromosome 10q25.3-q26.2.
*FIELD* RF
1. Liu, J.; Yuan, Y.; Huan, J.; Shen, Z.: Inhibition of breast and
brain cancer cell growth by BCCIP-alpha, an evolutionarily conserved
nuclear protein that interacts with BRCA2. Oncogene 20: 336-345,
2001.
2. Lu, H.; Yue, J.; Meng, X.; Nickoloff, J. A.; Shen, Z.: BCCIP regulates
homologous recombination by distinct domains and suppresses spontaneous
DNA damage. Nucleic Acids Res. 35: 7160-7170, 2007.
3. Meng, X.; Liu, J.; Shen, Z.: Genomic structure of the human BCCIP
gene and its expression in cancer. Gene 302: 139-146, 2003.
4. Ono, T.; Kitaura, H.; Ugai, H.; Murata, T.; Yokoyama, K. K.; Iguchi-Ariga,
S. M. M.; Ariga, H.: TOK-1, a novel p21(Cip1)-binding protein that
cooperatively enhances p21-dependent inhibitory activity toward CDK2
kinase. J. Biol. Chem. 275: 31145-31154, 2000.
*FIELD* CD
Patricia A. Hartz: 3/7/2008
*FIELD* ED
wwang: 03/31/2010
mgross: 3/7/2008
*RECORD*
*FIELD* NO
611883
*FIELD* TI
*611883 BRCA2- AND CDKN1A-INTERACTING PROTEIN; BCCIP
;;p21- AND CDK-ASSOCIATED PROTEIN 1; TOK1
read more*FIELD* TX
CLONING
Using the C-terminal half of p21 (CDK1A; 116899) as bait in a yeast
2-hybrid screen of a brain cDNA library, Ono et al. (2000) cloned BCCIP,
which they called TOK1. EST database analysis and PCR of a brain cDNA
library revealed 2 TOK1 variants, TOK1-alpha and -beta. The deduced
proteins contain 322 and 314 amino acids, respectively, and are
identical for the first 259 amino acids. Northern blot analysis using a
probe common to both TOK1 variants detected a major 1.5-kb transcript
and a minor 3-kb transcript. Specific probes detected both TOK1 variants
as 1.5-kb transcripts. TOK1-alpha was highly expressed in skeletal
muscle, with little to no expression in other tissues examined.
TOK1-beta was highly expressed in skeletal muscle and heart, moderately
expressed in placenta and pancreas, and weakly expressed in brain,
kidney, and liver. Western blot analysis detected TOK1-alpha and
TOK1-beta as 50- and 45-kD proteins, respectively. In synchronized HeLa
cells, expression of TOK1-alpha began after G2/M phase and peaked before
S phase. TOK1-beta was expressed throughout the cell cycle, but like
TOK1-alpha, its expression increased before S phase.
Using an internal conserved region of BRCA2 (600185) as bait in a yeast
2-hybrid screen, followed by database analysis, Liu et al. (2001) cloned
BCCIP-alpha and -beta, which correspond to TOK1-alpha and -beta,
respectively. Both BCCIP isoforms have an N-terminal acidic domain and
an evolutionarily conserved internal domain, followed by the C-terminal
variable domain. The internal domain contains a putative calcium-binding
domain. Western blot analysis detected both BCCIP proteins in all
tissues examined. Immunohistochemical analysis of several human cell
lines showed nuclear expression of endogenous BCCIP.
GENE FUNCTION
Using mutation analysis, Ono et al. (2000) found that TOK1-alpha bound
to the C-terminal proximal region of p21. However, TOK1-beta did not
bind p21. TOK1-alpha formed a ternary complex with p21 and an active
form of CDK2 (116953) in human embryonic kidney cells via its
interaction with p21. TOK1-alpha enhanced the inhibitory activity of p21
toward the histone H1 (see 142709) kinase activity of CDK2.
By coimmunoprecipitation analysis of transfected human embryonic kidney
cells, Liu et al. (2001) confirmed that BCCIP-alpha interacted with
endogenous BRCA2. Expression of BCCIP-beta protein was relatively
consistent among various tumor cell lines examined. In contrast,
expression of BCCIP-alpha protein was reduced in some brain, breast, and
endometrial tumor cell lines and increased in some endometrial tumor
cell lines, with relatively consistent expression among lung cancer cell
lines. BCCIP-alpha expression inhibited growth of some breast and brain
tumor cells, but it had no effect on other types of cancer cells.
Lu et al. (2007) stated that BCCIP regulates BRCA2 and RAD51 (179617)
nuclear focus formation, DNA double-strand break-induced homologous
recombination, and cell cycle progression. They transfected full-length
and truncated fragments of BCCIP into a human fibrosarcoma cell line and
found that BCCIP fragments that interacted with either BRCA2 or p21
inhibited homologous recombination similarly. Transient downregulation
of BCCIP in human cells did not affect nonspecific integration of
transfected DNA, but it significantly inhibited homology-directed gene
targeting. Cells with constitutive downregulation of BCCIP showed
increased levels of spontaneous single-stranded DNA and double-strand
breaks. Lu et al. (2007) concluded that multiple domains of BCCIP are
involved in homologous recombination and that BCCIP plays a critical
role in resolving spontaneous DNA damage.
Using a matched normal/tumor cDNA array, Meng et al. (2003) found
reduced expression of both BCCIP-alpha and -beta in kidney tumors.
GENE STRUCTURE
Meng et al. (2003) determined that the BCCIP gene contains 9 exons and
spans about 30 kb. The 5-prime end of the BCCIP gene abuts the UROS gene
(606938) on the opposite strand in a head-to-head manner. BCCIP and UROS
share a functional intergenic bidirectional promoter that contains
binding sites for various transcription factors. The last 3 exons of
BCCIP overlap with seven 3-prime exons of the DHX32 gene (607960) on the
opposite strand.
MAPPING
By FISH and genomic sequence analysis, Liu et al. (2001) mapped the
BCCIP gene to chromosome 10q25.3-q26.2.
*FIELD* RF
1. Liu, J.; Yuan, Y.; Huan, J.; Shen, Z.: Inhibition of breast and
brain cancer cell growth by BCCIP-alpha, an evolutionarily conserved
nuclear protein that interacts with BRCA2. Oncogene 20: 336-345,
2001.
2. Lu, H.; Yue, J.; Meng, X.; Nickoloff, J. A.; Shen, Z.: BCCIP regulates
homologous recombination by distinct domains and suppresses spontaneous
DNA damage. Nucleic Acids Res. 35: 7160-7170, 2007.
3. Meng, X.; Liu, J.; Shen, Z.: Genomic structure of the human BCCIP
gene and its expression in cancer. Gene 302: 139-146, 2003.
4. Ono, T.; Kitaura, H.; Ugai, H.; Murata, T.; Yokoyama, K. K.; Iguchi-Ariga,
S. M. M.; Ariga, H.: TOK-1, a novel p21(Cip1)-binding protein that
cooperatively enhances p21-dependent inhibitory activity toward CDK2
kinase. J. Biol. Chem. 275: 31145-31154, 2000.
*FIELD* CD
Patricia A. Hartz: 3/7/2008
*FIELD* ED
wwang: 03/31/2010
mgross: 3/7/2008