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Q96KB5 (TOPK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Lymphokine-activated killer T-cell-originated protein kinase

EC=2.7.12.2
Alternative name(s):
Cancer/testis antigen 84
Short name=CT84
MAPKK-like protein kinase
Nori-3
PDZ-binding kinase
Spermatogenesis-related protein kinase
Short name=SPK
T-LAK cell-originated protein kinase
Gene names
Name:PBK
Synonyms:TOPK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length322 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Phosphorylates MAP kinase p38. Seems to be active only in mitosis. May also play a role in the activation of lymphoid cells. When phosphorylated, forms a complex with TP53, leading to TP53 destabilization and attenuation of G2/M checkpoint during doxorubicin-induced DNA damage. Ref.1 Ref.7

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Activated by phosphorylation By similarity.

Subunit structure

Interacts with DLG1 and TP53. Ref.2 Ref.7

Tissue specificity

Expressed in the testis and placenta. In the testis, restrictedly expressed in outer cell layer of seminiferous tubules. Ref.1 Ref.3

Post-translational modification

Phosphorylated; in a cell-cycle dependent manner at mitosis. Ref.1 Ref.2

Sequence similarities

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Coding sequence diversityPolymorphism
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processmitosis

Non-traceable author statement Ref.2. Source: UniProtKB

   Molecular_functionATP binding

Non-traceable author statement. Source: UniProtKB

protein serine/threonine kinase activity

Traceable author statement Ref.2. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 322322Lymphokine-activated killer T-cell-originated protein kinase
PRO_0000086763

Regions

Domain32 – 322291Protein kinase
Nucleotide binding38 – 469ATP By similarity
Region320 – 3223PDZ-interaction

Sites

Active site1671Proton acceptor By similarity
Binding site641ATP By similarity

Amino acid modifications

Modified residue11N-acetylmethionine Ref.10
Modified residue91Phosphothreonine Ref.10
Modified residue241Phosphothreonine Ref.9
Modified residue321Phosphoserine Ref.9 Ref.10
Modified residue591Phosphoserine Ref.9 Ref.10

Natural variations

Natural variant1071N → S. Ref.2 Ref.3 Ref.4 Ref.12
Corresponds to variant rs3779620 [ dbSNP | Ensembl ].
VAR_021162
Natural variant2201E → D.
Corresponds to variant rs17057901 [ dbSNP | Ensembl ].
VAR_051676
Natural variant2411M → L. Ref.12
Corresponds to variant rs36086402 [ dbSNP | Ensembl ].
VAR_041234

Experimental info

Mutagenesis91T → E: TP53-binding. Ref.7
Mutagenesis64 – 652KK → AA: Loss of activity.
Mutagenesis3201T → A: Decrease in the binding to DLG1. Ref.2
Mutagenesis3221V → A: Decrease in the binding to DLG1. Ref.2
Sequence conflict341F → I in AAF71521. Ref.3
Sequence conflict1691K → E in BAB55019. Ref.4
Sequence conflict2541D → N in BAB55019. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Q96KB5 [UniParc].

Last modified December 6, 2005. Version 3.
Checksum: 6BF55789BC204ABE

FASTA32236,085
        10         20         30         40         50         60 
MEGISNFKTP SKLSEKKKSV LCSTPTINIP ASPFMQKLGF GTGVNVYLMK RSPRGLSHSP 

        70         80         90        100        110        120 
WAVKKINPIC NDHYRSVYQK RLMDEAKILK SLHHPNIVGY RAFTEANDGS LCLAMEYGGE 

       130        140        150        160        170        180 
KSLNDLIEER YKASQDPFPA AIILKVALNM ARGLKYLHQE KKLLHGDIKS SNVVIKGDFE 

       190        200        210        220        230        240 
TIKICDVGVS LPLDENMTVT DPEACYIGTE PWKPKEAVEE NGVITDKADI FAFGLTLWEM 

       250        260        270        280        290        300 
MTLSIPHINL SNDDDDEDKT FDESDFDDEA YYAALGTRPP INMEELDESY QKVIELFSVC 

       310        320 
TNEDPKDRPS AAHIVEALET DV 

« Hide

References

« Hide 'large scale' references
[1]"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."
Abe Y., Matsumoto S., Kito K., Ueda N.
J. Biol. Chem. 275:21525-21531(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, PHOSPHORYLATION, TISSUE SPECIFICITY.
Tissue: Lymphoid tissue.
[2]"Characterization of PDZ-binding kinase, a mitotic kinase."
Gaudet S., Branton D., Lue R.A.
Proc. Natl. Acad. Sci. U.S.A. 97:5167-5172(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION, MUTAGENESIS OF 64-LEU-LEU-65; THR-320 AND VAL-322, INTERACTION WITH DLG1, VARIANT SER-107.
[3]"PDZ-binding kinase participates in spermatogenesis."
Zhao S., Dai J., Zhao W., Xia F., Zhou Z., Wang W., Gu S., Ying K., Xie Y., Mao Y.
Int. J. Biochem. Cell Biol. 33:631-636(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANT SER-107.
Tissue: Fetal brain.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-107.
Tissue: Embryo.
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[7]"Attenuation of DNA damage checkpoint by PBK, a novel mitotic kinase, involves protein-protein interaction with tumor suppressor p53."
Nandi A.K., Ford T., Fleksher D., Neuman B., Rapoport A.P.
Biochem. Biophys. Res. Commun. 358:181-188(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TP53, MUTAGENESIS OF THR-9.
[8]"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra."
Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.
J. Proteome Res. 6:4150-4162(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-24; SER-32 AND SER-59, MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[10]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-9; SER-32 AND SER-59, MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[11]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-107 AND LEU-241.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB027249 mRNA. Translation: BAA99576.1.
AB027250 mRNA. Translation: BAA99577.1.
AF189722 mRNA. Translation: AAF69107.1.
AF237709 mRNA. Translation: AAF71521.1.
AK027291 mRNA. Translation: BAB55019.1.
CH471080 Genomic DNA. Translation: EAW63536.1.
CH471080 Genomic DNA. Translation: EAW63537.1.
BC015191 mRNA. Translation: AAH15191.1.
IPIIPI00306708.
RefSeqNP_060962.2. NM_018492.2.
UniGeneHs.104741.

3D structure databases

ProteinModelPortalQ96KB5.
ModBaseSearch...

Protein-protein interaction databases

IntActQ96KB5. 8 interactions.
MINTMINT-130347.
STRING9606.ENSP00000301905.

PTM databases

PhosphoSiteQ96KB5.

Polymorphism databases

DMDM83305809.

Proteomic databases

PaxDbQ96KB5.
PeptideAtlasQ96KB5.
PRIDEQ96KB5.

Protocols and materials databases

DNASU55872.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000301905; ENSP00000301905; ENSG00000168078.
GeneID55872.
KEGGhsa:55872.
UCSCuc003xgi.3. human.

Organism-specific databases

CTD55872.
GeneCardsGC08M027724.
HGNCHGNC:18282. PBK.
HPAHPA005753.
MIM611210. gene.
neXtProtNX_Q96KB5.
PharmGKBPA134925802.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000294208.
HOVERGENHBG056011.
InParanoidQ96KB5.
KOK08865.
OrthoDBEOG49ZXPN.
PhylomeDBQ96KB5.

Gene expression databases

ArrayExpressQ96KB5.
BgeeQ96KB5.
CleanExHS_PBK.
GenevestigatorQ96KB5.
GermOnlineENSG00000168078. Homo sapiens.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMSSF56112. Kinase_like. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. False negative.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

BindingDBQ96KB5.
ChEMBLCHEMBL4896.
ChiTaRSPBK. human.
GenomeRNAi55872.
NextBio61194.
SOURCESearch...

Entry information

Entry nameTOPK_HUMAN
AccessionPrimary (citable) accession number: Q96KB5
Secondary accession number(s): D3DST2 expand/collapse secondary AC list , Q9NPD9, Q9NYL7, Q9NZK6
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 2005
Last sequence update: December 6, 2005
Last modified: May 1, 2013
This is version 103 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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Human and mouse protein kinases: classification and index

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM

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List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families