Full text data of PBK
PBK
(TOPK)
[Confidence: low (only semi-automatic identification from reviews)]
Lymphokine-activated killer T-cell-originated protein kinase; 2.7.12.2 (Cancer/testis antigen 84; CT84; MAPKK-like protein kinase; Nori-3; PDZ-binding kinase; Spermatogenesis-related protein kinase; SPK; T-LAK cell-originated protein kinase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Lymphokine-activated killer T-cell-originated protein kinase; 2.7.12.2 (Cancer/testis antigen 84; CT84; MAPKK-like protein kinase; Nori-3; PDZ-binding kinase; Spermatogenesis-related protein kinase; SPK; T-LAK cell-originated protein kinase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q96KB5
ID TOPK_HUMAN Reviewed; 322 AA.
AC Q96KB5; D3DST2; Q9NPD9; Q9NYL7; Q9NZK6;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 06-DEC-2005, sequence version 3.
DT 22-JAN-2014, entry version 110.
DE RecName: Full=Lymphokine-activated killer T-cell-originated protein kinase;
DE EC=2.7.12.2;
DE AltName: Full=Cancer/testis antigen 84;
DE Short=CT84;
DE AltName: Full=MAPKK-like protein kinase;
DE AltName: Full=Nori-3;
DE AltName: Full=PDZ-binding kinase;
DE AltName: Full=Spermatogenesis-related protein kinase;
DE Short=SPK;
DE AltName: Full=T-LAK cell-originated protein kinase;
GN Name=PBK; Synonyms=TOPK;
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], FUNCTION, PHOSPHORYLATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Lymphoid tissue;
RX PubMed=10781613; DOI=10.1074/jbc.M909629199;
RA Abe Y., Matsumoto S., Kito K., Ueda N.;
RT "Cloning and expression of a novel MAPKK-like protein kinase,
RT lymphokine-activated killer T-cell-originated protein kinase,
RT specifically expressed in the testis and activated lymphoid cells.";
RL J. Biol. Chem. 275:21525-21531(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION, MUTAGENESIS OF
RP 64-LEU-LEU-65; THR-320 AND VAL-322, INTERACTION WITH DLG1, AND VARIANT
RP SER-107.
RX PubMed=10779557; DOI=10.1073/pnas.090102397;
RA Gaudet S., Branton D., Lue R.A.;
RT "Characterization of PDZ-binding kinase, a mitotic kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:5167-5172(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANT SER-107.
RC TISSUE=Fetal brain;
RX PubMed=11378444; DOI=10.1016/S1357-2725(01)00005-X;
RA Zhao S., Dai J., Zhao W., Xia F., Zhou Z., Wang W., Gu S., Ying K.,
RA Xie Y., Mao Y.;
RT "PDZ-binding kinase participates in spermatogenesis.";
RL Int. J. Biochem. Cell Biol. 33:631-636(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-107.
RC TISSUE=Embryo;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 FUNCTION, INTERACTION WITH TP53, AND MUTAGENESIS OF THR-9.
RX PubMed=17482142; DOI=10.1016/j.bbrc.2007.04.125;
RA Nandi A.K., Ford T., Fleksher D., Neuman B., Rapoport A.P.;
RT "Attenuation of DNA damage checkpoint by PBK, a novel mitotic kinase,
RT involves protein-protein interaction with tumor suppressor p53.";
RL Biochem. Biophys. Res. Commun. 358:181-188(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa
RT cells and high confident phosphopeptide identification by cross-
RT validation of MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-24; SER-32 AND SER-59,
RP AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT THR-9; SER-32 AND SER-59, AND MASS 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 [12]
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 [13]
RP VARIANTS [LARGE SCALE ANALYSIS] SER-107 AND LEU-241.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Phosphorylates MAP kinase p38. Seems to be active only
CC in mitosis. May also play a role in the activation of lymphoid
CC cells. When phosphorylated, forms a complex with TP53, leading to
CC TP53 destabilization and attenuation of G2/M checkpoint during
CC doxorubicin-induced DNA damage.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- ENZYME REGULATION: Activated by phosphorylation (By similarity).
CC -!- SUBUNIT: Interacts with DLG1 and TP53.
CC -!- INTERACTION:
CC P10398:ARAF; NbExp=3; IntAct=EBI-536853, EBI-365961;
CC P04637:TP53; NbExp=7; IntAct=EBI-536853, EBI-366083;
CC -!- TISSUE SPECIFICITY: Expressed in the testis and placenta. In the
CC testis, restrictedly expressed in outer cell layer of seminiferous
CC tubules.
CC -!- PTM: Phosphorylated; in a cell-cycle dependent manner at mitosis.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. MAP kinase kinase subfamily.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
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DR EMBL; AB027249; BAA99576.1; -; mRNA.
DR EMBL; AB027250; BAA99577.1; -; mRNA.
DR EMBL; AF189722; AAF69107.1; -; mRNA.
DR EMBL; AF237709; AAF71521.1; -; mRNA.
DR EMBL; AK027291; BAB55019.1; -; mRNA.
DR EMBL; CH471080; EAW63536.1; -; Genomic_DNA.
DR EMBL; CH471080; EAW63537.1; -; Genomic_DNA.
DR EMBL; BC015191; AAH15191.1; -; mRNA.
DR RefSeq; NP_001265874.1; NM_001278945.1.
DR RefSeq; NP_060962.2; NM_018492.3.
DR UniGene; Hs.104741; -.
DR ProteinModelPortal; Q96KB5; -.
DR SMR; Q96KB5; 34-319.
DR IntAct; Q96KB5; 10.
DR MINT; MINT-130347; -.
DR STRING; 9606.ENSP00000301905; -.
DR BindingDB; Q96KB5; -.
DR ChEMBL; CHEMBL4896; -.
DR GuidetoPHARMACOLOGY; 2140; -.
DR PhosphoSite; Q96KB5; -.
DR DMDM; 83305809; -.
DR PaxDb; Q96KB5; -.
DR PeptideAtlas; Q96KB5; -.
DR PRIDE; Q96KB5; -.
DR DNASU; 55872; -.
DR Ensembl; ENST00000301905; ENSP00000301905; ENSG00000168078.
DR GeneID; 55872; -.
DR KEGG; hsa:55872; -.
DR UCSC; uc003xgi.3; human.
DR CTD; 55872; -.
DR GeneCards; GC08M027724; -.
DR HGNC; HGNC:18282; PBK.
DR HPA; HPA005753; -.
DR MIM; 611210; gene.
DR neXtProt; NX_Q96KB5; -.
DR PharmGKB; PA134925802; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000294208; -.
DR HOVERGEN; HBG056011; -.
DR InParanoid; Q96KB5; -.
DR KO; K08865; -.
DR OrthoDB; EOG7S4X6F; -.
DR PhylomeDB; Q96KB5; -.
DR SignaLink; Q96KB5; -.
DR ChiTaRS; PBK; human.
DR GeneWiki; PBK_(gene); -.
DR GenomeRNAi; 55872; -.
DR NextBio; 61194; -.
DR PRO; PR:Q96KB5; -.
DR ArrayExpress; Q96KB5; -.
DR Bgee; Q96KB5; -.
DR CleanEx; HS_PBK; -.
DR Genevestigator; Q96KB5; -.
DR GO; GO:0005524; F:ATP binding; NAS:UniProtKB.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; TAS:UniProtKB.
DR GO; GO:0007067; P:mitosis; NAS:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; FALSE_NEG.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Complete proteome; Kinase;
KW Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1 322 Lymphokine-activated killer T-cell-
FT originated protein kinase.
FT /FTId=PRO_0000086763.
FT DOMAIN 32 322 Protein kinase.
FT NP_BIND 38 46 ATP (By similarity).
FT REGION 320 322 PDZ-interaction.
FT ACT_SITE 167 167 Proton acceptor (By similarity).
FT BINDING 64 64 ATP (By similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 9 9 Phosphothreonine.
FT MOD_RES 24 24 Phosphothreonine.
FT MOD_RES 32 32 Phosphoserine.
FT MOD_RES 59 59 Phosphoserine.
FT VARIANT 107 107 N -> S (in dbSNP:rs3779620).
FT /FTId=VAR_021162.
FT VARIANT 220 220 E -> D (in dbSNP:rs17057901).
FT /FTId=VAR_051676.
FT VARIANT 241 241 M -> L (in dbSNP:rs36086402).
FT /FTId=VAR_041234.
FT MUTAGEN 9 9 T->E: TP53-binding.
FT MUTAGEN 64 65 KK->AA: Loss of activity.
FT MUTAGEN 320 320 T->A: Decrease in the binding to DLG1.
FT MUTAGEN 322 322 V->A: Decrease in the binding to DLG1.
FT CONFLICT 34 34 F -> I (in Ref. 3; AAF71521).
FT CONFLICT 169 169 K -> E (in Ref. 4; BAB55019).
FT CONFLICT 254 254 D -> N (in Ref. 4; BAB55019).
SQ SEQUENCE 322 AA; 36085 MW; 6BF55789BC204ABE CRC64;
MEGISNFKTP SKLSEKKKSV LCSTPTINIP ASPFMQKLGF GTGVNVYLMK RSPRGLSHSP
WAVKKINPIC NDHYRSVYQK RLMDEAKILK SLHHPNIVGY RAFTEANDGS LCLAMEYGGE
KSLNDLIEER YKASQDPFPA AIILKVALNM ARGLKYLHQE KKLLHGDIKS SNVVIKGDFE
TIKICDVGVS LPLDENMTVT DPEACYIGTE PWKPKEAVEE NGVITDKADI FAFGLTLWEM
MTLSIPHINL SNDDDDEDKT FDESDFDDEA YYAALGTRPP INMEELDESY QKVIELFSVC
TNEDPKDRPS AAHIVEALET DV
//
ID TOPK_HUMAN Reviewed; 322 AA.
AC Q96KB5; D3DST2; Q9NPD9; Q9NYL7; Q9NZK6;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 06-DEC-2005, sequence version 3.
DT 22-JAN-2014, entry version 110.
DE RecName: Full=Lymphokine-activated killer T-cell-originated protein kinase;
DE EC=2.7.12.2;
DE AltName: Full=Cancer/testis antigen 84;
DE Short=CT84;
DE AltName: Full=MAPKK-like protein kinase;
DE AltName: Full=Nori-3;
DE AltName: Full=PDZ-binding kinase;
DE AltName: Full=Spermatogenesis-related protein kinase;
DE Short=SPK;
DE AltName: Full=T-LAK cell-originated protein kinase;
GN Name=PBK; Synonyms=TOPK;
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], FUNCTION, PHOSPHORYLATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Lymphoid tissue;
RX PubMed=10781613; DOI=10.1074/jbc.M909629199;
RA Abe Y., Matsumoto S., Kito K., Ueda N.;
RT "Cloning and expression of a novel MAPKK-like protein kinase,
RT lymphokine-activated killer T-cell-originated protein kinase,
RT specifically expressed in the testis and activated lymphoid cells.";
RL J. Biol. Chem. 275:21525-21531(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION, MUTAGENESIS OF
RP 64-LEU-LEU-65; THR-320 AND VAL-322, INTERACTION WITH DLG1, AND VARIANT
RP SER-107.
RX PubMed=10779557; DOI=10.1073/pnas.090102397;
RA Gaudet S., Branton D., Lue R.A.;
RT "Characterization of PDZ-binding kinase, a mitotic kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:5167-5172(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANT SER-107.
RC TISSUE=Fetal brain;
RX PubMed=11378444; DOI=10.1016/S1357-2725(01)00005-X;
RA Zhao S., Dai J., Zhao W., Xia F., Zhou Z., Wang W., Gu S., Ying K.,
RA Xie Y., Mao Y.;
RT "PDZ-binding kinase participates in spermatogenesis.";
RL Int. J. Biochem. Cell Biol. 33:631-636(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-107.
RC TISSUE=Embryo;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 FUNCTION, INTERACTION WITH TP53, AND MUTAGENESIS OF THR-9.
RX PubMed=17482142; DOI=10.1016/j.bbrc.2007.04.125;
RA Nandi A.K., Ford T., Fleksher D., Neuman B., Rapoport A.P.;
RT "Attenuation of DNA damage checkpoint by PBK, a novel mitotic kinase,
RT involves protein-protein interaction with tumor suppressor p53.";
RL Biochem. Biophys. Res. Commun. 358:181-188(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa
RT cells and high confident phosphopeptide identification by cross-
RT validation of MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-24; SER-32 AND SER-59,
RP AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT THR-9; SER-32 AND SER-59, AND MASS 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 [12]
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 [13]
RP VARIANTS [LARGE SCALE ANALYSIS] SER-107 AND LEU-241.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Phosphorylates MAP kinase p38. Seems to be active only
CC in mitosis. May also play a role in the activation of lymphoid
CC cells. When phosphorylated, forms a complex with TP53, leading to
CC TP53 destabilization and attenuation of G2/M checkpoint during
CC doxorubicin-induced DNA damage.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- ENZYME REGULATION: Activated by phosphorylation (By similarity).
CC -!- SUBUNIT: Interacts with DLG1 and TP53.
CC -!- INTERACTION:
CC P10398:ARAF; NbExp=3; IntAct=EBI-536853, EBI-365961;
CC P04637:TP53; NbExp=7; IntAct=EBI-536853, EBI-366083;
CC -!- TISSUE SPECIFICITY: Expressed in the testis and placenta. In the
CC testis, restrictedly expressed in outer cell layer of seminiferous
CC tubules.
CC -!- PTM: Phosphorylated; in a cell-cycle dependent manner at mitosis.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. MAP kinase kinase subfamily.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -----------------------------------------------------------------------
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DR EMBL; AB027249; BAA99576.1; -; mRNA.
DR EMBL; AB027250; BAA99577.1; -; mRNA.
DR EMBL; AF189722; AAF69107.1; -; mRNA.
DR EMBL; AF237709; AAF71521.1; -; mRNA.
DR EMBL; AK027291; BAB55019.1; -; mRNA.
DR EMBL; CH471080; EAW63536.1; -; Genomic_DNA.
DR EMBL; CH471080; EAW63537.1; -; Genomic_DNA.
DR EMBL; BC015191; AAH15191.1; -; mRNA.
DR RefSeq; NP_001265874.1; NM_001278945.1.
DR RefSeq; NP_060962.2; NM_018492.3.
DR UniGene; Hs.104741; -.
DR ProteinModelPortal; Q96KB5; -.
DR SMR; Q96KB5; 34-319.
DR IntAct; Q96KB5; 10.
DR MINT; MINT-130347; -.
DR STRING; 9606.ENSP00000301905; -.
DR BindingDB; Q96KB5; -.
DR ChEMBL; CHEMBL4896; -.
DR GuidetoPHARMACOLOGY; 2140; -.
DR PhosphoSite; Q96KB5; -.
DR DMDM; 83305809; -.
DR PaxDb; Q96KB5; -.
DR PeptideAtlas; Q96KB5; -.
DR PRIDE; Q96KB5; -.
DR DNASU; 55872; -.
DR Ensembl; ENST00000301905; ENSP00000301905; ENSG00000168078.
DR GeneID; 55872; -.
DR KEGG; hsa:55872; -.
DR UCSC; uc003xgi.3; human.
DR CTD; 55872; -.
DR GeneCards; GC08M027724; -.
DR HGNC; HGNC:18282; PBK.
DR HPA; HPA005753; -.
DR MIM; 611210; gene.
DR neXtProt; NX_Q96KB5; -.
DR PharmGKB; PA134925802; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000294208; -.
DR HOVERGEN; HBG056011; -.
DR InParanoid; Q96KB5; -.
DR KO; K08865; -.
DR OrthoDB; EOG7S4X6F; -.
DR PhylomeDB; Q96KB5; -.
DR SignaLink; Q96KB5; -.
DR ChiTaRS; PBK; human.
DR GeneWiki; PBK_(gene); -.
DR GenomeRNAi; 55872; -.
DR NextBio; 61194; -.
DR PRO; PR:Q96KB5; -.
DR ArrayExpress; Q96KB5; -.
DR Bgee; Q96KB5; -.
DR CleanEx; HS_PBK; -.
DR Genevestigator; Q96KB5; -.
DR GO; GO:0005524; F:ATP binding; NAS:UniProtKB.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; TAS:UniProtKB.
DR GO; GO:0007067; P:mitosis; NAS:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; FALSE_NEG.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Complete proteome; Kinase;
KW Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1 322 Lymphokine-activated killer T-cell-
FT originated protein kinase.
FT /FTId=PRO_0000086763.
FT DOMAIN 32 322 Protein kinase.
FT NP_BIND 38 46 ATP (By similarity).
FT REGION 320 322 PDZ-interaction.
FT ACT_SITE 167 167 Proton acceptor (By similarity).
FT BINDING 64 64 ATP (By similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 9 9 Phosphothreonine.
FT MOD_RES 24 24 Phosphothreonine.
FT MOD_RES 32 32 Phosphoserine.
FT MOD_RES 59 59 Phosphoserine.
FT VARIANT 107 107 N -> S (in dbSNP:rs3779620).
FT /FTId=VAR_021162.
FT VARIANT 220 220 E -> D (in dbSNP:rs17057901).
FT /FTId=VAR_051676.
FT VARIANT 241 241 M -> L (in dbSNP:rs36086402).
FT /FTId=VAR_041234.
FT MUTAGEN 9 9 T->E: TP53-binding.
FT MUTAGEN 64 65 KK->AA: Loss of activity.
FT MUTAGEN 320 320 T->A: Decrease in the binding to DLG1.
FT MUTAGEN 322 322 V->A: Decrease in the binding to DLG1.
FT CONFLICT 34 34 F -> I (in Ref. 3; AAF71521).
FT CONFLICT 169 169 K -> E (in Ref. 4; BAB55019).
FT CONFLICT 254 254 D -> N (in Ref. 4; BAB55019).
SQ SEQUENCE 322 AA; 36085 MW; 6BF55789BC204ABE CRC64;
MEGISNFKTP SKLSEKKKSV LCSTPTINIP ASPFMQKLGF GTGVNVYLMK RSPRGLSHSP
WAVKKINPIC NDHYRSVYQK RLMDEAKILK SLHHPNIVGY RAFTEANDGS LCLAMEYGGE
KSLNDLIEER YKASQDPFPA AIILKVALNM ARGLKYLHQE KKLLHGDIKS SNVVIKGDFE
TIKICDVGVS LPLDENMTVT DPEACYIGTE PWKPKEAVEE NGVITDKADI FAFGLTLWEM
MTLSIPHINL SNDDDDEDKT FDESDFDDEA YYAALGTRPP INMEELDESY QKVIELFSVC
TNEDPKDRPS AAHIVEALET DV
//
MIM
611210
*RECORD*
*FIELD* NO
611210
*FIELD* TI
*611210 PDZ-BINDING KINASE; PBK
;;LYMPHOKINE-ACTIVATED KILLER T CELL-ORIGINATED PROTEIN KINASE; TOPK
read more*FIELD* TX
CLONING
By screening for genes upregulated during activation of
lymphokine-activated killer T (T-LAK) cells, Abe et al. (2000) cloned 2
variants of PBK, which they called TOPK. The variants differ at their
5-prime ends and encode the same protein, a deduced 322-amino acid
serine/threonine kinase with a calculated molecular mass of 37.4 kD.
Northern blot analysis of 12 human tissues detected transcripts of 1.9
and 2 kb in testis only. RT-PCR detected TOPK in activated, but not
deactivated, T-LAK cells.
Using DLG (DLG1; 601014) as bait in a yeast 2-hybrid screen, followed by
PCR of a HeLa cell cDNA library, Gaudet et al. (2000) cloned PBK. The
PBK protein has active-site sequences conserved in serine/threonine or
dual-specificity kinases, as well as a C-terminal PDZ domain-binding
ETDV motif. Northern blot analysis detected highest expression of PBK in
placenta, with lower expression in heart and pancreas and very low
expression in skeletal muscle, kidney, liver, and lung; no expression
was detected in adult brain.
Using Northern blot analysis, Simons-Evelyn et al. (2001) found that PBK
was expressed in fetal kidney, lung, brain, spleen, and testis, but not
in adult kidney and lung. By Northern blot analysis, Park et al. (2006)
found highest PBK expression in testis, weaker levels in thymus, and no
expression in other normal tissues.
GENE FUNCTION
Abe et al. (2000) found that transfection of TOPK into COS-7 cells
upregulated phosphorylation of p38 MAPK (MAPK14; 600289), but not ERK1
(MAPK3; 601795)/ERK2 (MAPK1; 176948) or JNK (MAPK8; 601158). Gel
precipitation analysis showed that TOPK associated with p38 in vitro.
Using an in vitro protein binding assay, Gaudet et al. (2000) showed
that the C-terminal PDZ-binding motif of PBK bound the second PDZ domain
of DLG. PBK mutants in which thr320 or val322 were mutated to ala showed
reduced binding to DLG. In vitro, PBK phosphorylated itself and histone
on threonines, and it phosphorylated MBP (159430) on both threonines and
serines. PBK bearing mutations at lys64 and lys65 showed no activity.
Both PBK and DLG were phosphorylated at mitosis in HeLa cells, and
phosphorylation of PBK was required for its kinase activity. In vitro,
CDC2 (116940)/cyclin B (123836) phosphorylated PBK on a conserved
N-terminal motif, but this phosphorylation alone was insufficient for
activation of PBK.
Using Northern blot analysis, Simons-Evelyn et al. (2001) found that PBK
expression was upregulated in several human tumor cell lines, including
Burkitt lymphoma, but PBK was not expressed in normal peripheral blood
cells.
Using synchronized HeLa cells, Matsumoto et al. (2004) found that TOPK
was expressed in the cytosol and nucleus during interphase. During
mitosis, thr9 of TOPK was phosphorylated by CDK1/cyclin B, and TOPK
associated with mitotic spindles. Knockdown of TOPK expression altered
spindle midzone formation and disturbed cytokinesis.
By microarray analysis, Dougherty et al. (2005) found that Pbk
expression was enriched in mouse neural stem cell cultures. Both Pbk and
p38 were activated in a cell cycle-dependent manner in progenitor cells
in vitro, and inhibition of this pathway disrupted progenitor
proliferation and self renewal. Pbk was expressed in rapidly
proliferating cells in the adult subependymal zone and early postnatal
cerebellar external granular layer. Pbk-positive cells in the
subependymal zone arose from Gfap (137780)-positive neural stem cells
during adult neurogenesis, and ablation of the adult stem cell
population led to concomitant loss of Pbk-positive cells in the
subependymal zone.
Park et al. (2006) showed that PBK was highly expressed in breast cancer
cell lines but not in normal mammary gland. Immunohistochemical analysis
localized PBK mainly around chromosomal surfaces in mitotic breast
cancer cells, particularly at prophase and metaphase. Using cDNA
microarray analysis of 81 breast cancer cases, the authors found that
PBK was among dozens of genes highly and commonly upregulated in breast
cancer. Reduction of PBK expression by small interfering RNA (siRNA)
significantly suppressed cell growth in human breast cancer cell lines.
In vitro and in vivo, PBK phosphorylated histone H3 (see H3F2; 142780)
at ser10. Park et al. (2006) concluded that PBK mediates cell growth
through histone H3 modification.
Ayllon and O'Connor (2007) found that siRNA-mediated knockdown of PBK in
human and other mammalian cell lines did not prevent progression through
the cell cycle, but it slowed cell growth and motility, impaired p38
activation by growth factors, and impaired cellular responses to DNA
damage.
Nandi et al. (2007) stated that expression of PBK is regulated by cell
cycle-specific transcription factors E2F (E2F1; 189971) and CREB
(123810). Using coimmunoprecipitation and yeast 2-hybrid analyses, they
showed that PBK interacted directly with p53 (TP53; 191170). PBK formed
a complex with p53 when ectopically expressed in fibrosarcoma cells,
leading to destabilization of p53 and attenuation of G2/M checkpoint
during doxorubicin-induced DNA damage.
MAPPING
Hartz (2007) mapped the PBK gene to chromosome 8p21.1 based on an
alignment of the PBK sequence (GenBank GENBANK AB027249) with the
genomic sequence (build 36.1).
*FIELD* RF
1. Abe, Y.; Matsumoto, S.; Kito, K.; Ueda, N.: Cloning and expression
of a novel MAPKK-like protein kinase, lymphokine-activated killer
T-cell-originated protein kinase, specifically expressed in the testis
and activated lymphoid cells. J. Biol. Chem. 275: 21525-21531, 2000.
2. Ayllon, V.; O'Connor, R.: PBK/TOPK promotes tumour cell proliferation
through p38 MAPK activity and regulation of the DNA damage response. Oncogene 26:
3451-3461, 2007.
3. Dougherty, J. D.; Garcia, A. D. R.; Nakano, I.; Livingstone, M.;
Norris, B.; Polakiewicz, R.; Wexler, E. M.; Sofroniew, M. V.; Kornblum,
H. I.; Geschwind, D. H.: PBK/TOPK, a proliferating neural progenitor-specific
mitogen-activated protein kinase kinase. J. Neurosci. 25: 10773-10785,
2005.
4. Gaudet, S.; Branton, D.; Lue, R. A.: Characterization of PDZ-binding
kinase, a mitotic kinase. Proc. Nat. Acad. Sci. 97: 5167-5172, 2000.
5. Hartz, P. A.: Personal Communication. Baltimore, Md. 7/16/2007.
6. Matsumoto, S.; Abe, Y.; Fujibuchi, T.; Takeuchi, T.; Kito, K.;
Ueda, N.; Shigemoto, K.; Gyo, K.: Characterization of a MAPKK-like
protein kinase TOPK. Biochem. Biophys. Res. Commun. 325: 997-1004,
2004.
7. Nandi, A. K.; Ford, T.; Fleksher, D.; Neuman, B.; Rapoport, A.
P.: Attenuation of DNA damage checkpoint by PBK, a novel mitotic
kinase, involves protein-protein interaction with tumor suppressor
p53. Biochem. Biophys. Res. Commun. 358: 181-188, 2007.
8. Park, J.-H.; Lin, M.-L.; Nishidate, T.; Nakamura, Y.; Katagiri,
T.: PDZ-binding kinase/T-LAK cell-originated protein kinase, a putative
cancer/testis antigen with an oncogenic activity in breast cancer. Cancer
Res. 66: 9186-9195, 2006.
9. Simons-Evelyn, M.; Bailey-Dell, K.; Toretsky, J. A.; Ross, D. D.;
Fenton, R.; Kalvakolanu, D.; Rapoport, A. P.: PBK/TOPK is a novel
mitotic kinase which is upregulated in Burkitt's lymphoma and other
highly proliferative malignant cells. Blood Cells Molec. Dis. 27:
825-829, 2001.
*FIELD* CD
Patricia A. Hartz: 7/16/2007
*FIELD* ED
carol: 12/05/2011
wwang: 10/4/2007
mgross: 7/16/2007
*RECORD*
*FIELD* NO
611210
*FIELD* TI
*611210 PDZ-BINDING KINASE; PBK
;;LYMPHOKINE-ACTIVATED KILLER T CELL-ORIGINATED PROTEIN KINASE; TOPK
read more*FIELD* TX
CLONING
By screening for genes upregulated during activation of
lymphokine-activated killer T (T-LAK) cells, Abe et al. (2000) cloned 2
variants of PBK, which they called TOPK. The variants differ at their
5-prime ends and encode the same protein, a deduced 322-amino acid
serine/threonine kinase with a calculated molecular mass of 37.4 kD.
Northern blot analysis of 12 human tissues detected transcripts of 1.9
and 2 kb in testis only. RT-PCR detected TOPK in activated, but not
deactivated, T-LAK cells.
Using DLG (DLG1; 601014) as bait in a yeast 2-hybrid screen, followed by
PCR of a HeLa cell cDNA library, Gaudet et al. (2000) cloned PBK. The
PBK protein has active-site sequences conserved in serine/threonine or
dual-specificity kinases, as well as a C-terminal PDZ domain-binding
ETDV motif. Northern blot analysis detected highest expression of PBK in
placenta, with lower expression in heart and pancreas and very low
expression in skeletal muscle, kidney, liver, and lung; no expression
was detected in adult brain.
Using Northern blot analysis, Simons-Evelyn et al. (2001) found that PBK
was expressed in fetal kidney, lung, brain, spleen, and testis, but not
in adult kidney and lung. By Northern blot analysis, Park et al. (2006)
found highest PBK expression in testis, weaker levels in thymus, and no
expression in other normal tissues.
GENE FUNCTION
Abe et al. (2000) found that transfection of TOPK into COS-7 cells
upregulated phosphorylation of p38 MAPK (MAPK14; 600289), but not ERK1
(MAPK3; 601795)/ERK2 (MAPK1; 176948) or JNK (MAPK8; 601158). Gel
precipitation analysis showed that TOPK associated with p38 in vitro.
Using an in vitro protein binding assay, Gaudet et al. (2000) showed
that the C-terminal PDZ-binding motif of PBK bound the second PDZ domain
of DLG. PBK mutants in which thr320 or val322 were mutated to ala showed
reduced binding to DLG. In vitro, PBK phosphorylated itself and histone
on threonines, and it phosphorylated MBP (159430) on both threonines and
serines. PBK bearing mutations at lys64 and lys65 showed no activity.
Both PBK and DLG were phosphorylated at mitosis in HeLa cells, and
phosphorylation of PBK was required for its kinase activity. In vitro,
CDC2 (116940)/cyclin B (123836) phosphorylated PBK on a conserved
N-terminal motif, but this phosphorylation alone was insufficient for
activation of PBK.
Using Northern blot analysis, Simons-Evelyn et al. (2001) found that PBK
expression was upregulated in several human tumor cell lines, including
Burkitt lymphoma, but PBK was not expressed in normal peripheral blood
cells.
Using synchronized HeLa cells, Matsumoto et al. (2004) found that TOPK
was expressed in the cytosol and nucleus during interphase. During
mitosis, thr9 of TOPK was phosphorylated by CDK1/cyclin B, and TOPK
associated with mitotic spindles. Knockdown of TOPK expression altered
spindle midzone formation and disturbed cytokinesis.
By microarray analysis, Dougherty et al. (2005) found that Pbk
expression was enriched in mouse neural stem cell cultures. Both Pbk and
p38 were activated in a cell cycle-dependent manner in progenitor cells
in vitro, and inhibition of this pathway disrupted progenitor
proliferation and self renewal. Pbk was expressed in rapidly
proliferating cells in the adult subependymal zone and early postnatal
cerebellar external granular layer. Pbk-positive cells in the
subependymal zone arose from Gfap (137780)-positive neural stem cells
during adult neurogenesis, and ablation of the adult stem cell
population led to concomitant loss of Pbk-positive cells in the
subependymal zone.
Park et al. (2006) showed that PBK was highly expressed in breast cancer
cell lines but not in normal mammary gland. Immunohistochemical analysis
localized PBK mainly around chromosomal surfaces in mitotic breast
cancer cells, particularly at prophase and metaphase. Using cDNA
microarray analysis of 81 breast cancer cases, the authors found that
PBK was among dozens of genes highly and commonly upregulated in breast
cancer. Reduction of PBK expression by small interfering RNA (siRNA)
significantly suppressed cell growth in human breast cancer cell lines.
In vitro and in vivo, PBK phosphorylated histone H3 (see H3F2; 142780)
at ser10. Park et al. (2006) concluded that PBK mediates cell growth
through histone H3 modification.
Ayllon and O'Connor (2007) found that siRNA-mediated knockdown of PBK in
human and other mammalian cell lines did not prevent progression through
the cell cycle, but it slowed cell growth and motility, impaired p38
activation by growth factors, and impaired cellular responses to DNA
damage.
Nandi et al. (2007) stated that expression of PBK is regulated by cell
cycle-specific transcription factors E2F (E2F1; 189971) and CREB
(123810). Using coimmunoprecipitation and yeast 2-hybrid analyses, they
showed that PBK interacted directly with p53 (TP53; 191170). PBK formed
a complex with p53 when ectopically expressed in fibrosarcoma cells,
leading to destabilization of p53 and attenuation of G2/M checkpoint
during doxorubicin-induced DNA damage.
MAPPING
Hartz (2007) mapped the PBK gene to chromosome 8p21.1 based on an
alignment of the PBK sequence (GenBank GENBANK AB027249) with the
genomic sequence (build 36.1).
*FIELD* RF
1. Abe, Y.; Matsumoto, S.; Kito, K.; Ueda, N.: Cloning and expression
of a novel MAPKK-like protein kinase, lymphokine-activated killer
T-cell-originated protein kinase, specifically expressed in the testis
and activated lymphoid cells. J. Biol. Chem. 275: 21525-21531, 2000.
2. Ayllon, V.; O'Connor, R.: PBK/TOPK promotes tumour cell proliferation
through p38 MAPK activity and regulation of the DNA damage response. Oncogene 26:
3451-3461, 2007.
3. Dougherty, J. D.; Garcia, A. D. R.; Nakano, I.; Livingstone, M.;
Norris, B.; Polakiewicz, R.; Wexler, E. M.; Sofroniew, M. V.; Kornblum,
H. I.; Geschwind, D. H.: PBK/TOPK, a proliferating neural progenitor-specific
mitogen-activated protein kinase kinase. J. Neurosci. 25: 10773-10785,
2005.
4. Gaudet, S.; Branton, D.; Lue, R. A.: Characterization of PDZ-binding
kinase, a mitotic kinase. Proc. Nat. Acad. Sci. 97: 5167-5172, 2000.
5. Hartz, P. A.: Personal Communication. Baltimore, Md. 7/16/2007.
6. Matsumoto, S.; Abe, Y.; Fujibuchi, T.; Takeuchi, T.; Kito, K.;
Ueda, N.; Shigemoto, K.; Gyo, K.: Characterization of a MAPKK-like
protein kinase TOPK. Biochem. Biophys. Res. Commun. 325: 997-1004,
2004.
7. Nandi, A. K.; Ford, T.; Fleksher, D.; Neuman, B.; Rapoport, A.
P.: Attenuation of DNA damage checkpoint by PBK, a novel mitotic
kinase, involves protein-protein interaction with tumor suppressor
p53. Biochem. Biophys. Res. Commun. 358: 181-188, 2007.
8. Park, J.-H.; Lin, M.-L.; Nishidate, T.; Nakamura, Y.; Katagiri,
T.: PDZ-binding kinase/T-LAK cell-originated protein kinase, a putative
cancer/testis antigen with an oncogenic activity in breast cancer. Cancer
Res. 66: 9186-9195, 2006.
9. Simons-Evelyn, M.; Bailey-Dell, K.; Toretsky, J. A.; Ross, D. D.;
Fenton, R.; Kalvakolanu, D.; Rapoport, A. P.: PBK/TOPK is a novel
mitotic kinase which is upregulated in Burkitt's lymphoma and other
highly proliferative malignant cells. Blood Cells Molec. Dis. 27:
825-829, 2001.
*FIELD* CD
Patricia A. Hartz: 7/16/2007
*FIELD* ED
carol: 12/05/2011
wwang: 10/4/2007
mgross: 7/16/2007