Q96KB5 (TOPK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	322 AA.
Sequence status	Complete.
Protein existence	Evidence 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 diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	mitosis Non-traceable author statement Ref.2. Source: UniProtKB
Molecular_function	ATP binding Non-traceable author statement. Source: UniProtKB protein serine/threonine kinase activity Traceable author statement Ref.2. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARAF	P10398	3	EBI-536853,EBI-365961
TP53	P04637	7	EBI-536853,EBI-366083

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 322	322	Lymphokine-activated killer T-cell-originated protein kinase		PRO_0000086763
Regions
	Domain	32 – 322	291	Protein kinase
	Nucleotide binding	38 – 46	9	ATP By similarity
	Region	320 – 322	3	PDZ-interaction
Sites
	Active site	167	1	Proton acceptor By similarity
	Binding site	64	1	ATP By similarity
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine Ref.10
	Modified residue	9	1	Phosphothreonine Ref.10
	Modified residue	24	1	Phosphothreonine Ref.9
	Modified residue	32	1	Phosphoserine Ref.9 Ref.10
	Modified residue	59	1	Phosphoserine Ref.9 Ref.10
Natural variations
	Natural variant	107	1	N → S. Ref.2 Ref.3 Ref.4 Ref.12 Corresponds to variant rs3779620 [ dbSNP | Ensembl ].		VAR_021162
	Natural variant	220	1	E → D. Corresponds to variant rs17057901 [ dbSNP | Ensembl ].		VAR_051676
	Natural variant	241	1	M → L. Ref.12 Corresponds to variant rs36086402 [ dbSNP | Ensembl ].		VAR_041234
Experimental info
	Mutagenesis	9	1	T → E: TP53-binding. Ref.7
	Mutagenesis	64 – 65	2	KK → AA: Loss of activity.
	Mutagenesis	320	1	T → A: Decrease in the binding to DLG1. Ref.2
	Mutagenesis	322	1	V → A: Decrease in the binding to DLG1. Ref.2
	Sequence conflict	34	1	F → I in AAF71521. Ref.3
	Sequence conflict	169	1	K → E in BAB55019. Ref.4
	Sequence conflict	254	1	D → N in BAB55019. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q96KB5 [UniParc]. Last modified December 6, 2005. Version 3. Checksum: 6BF55789BC204ABE	FASTA	322	36,085
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.
IPI	IPI00306708.
RefSeq	NP_060962.2. NM_018492.2.
UniGene	Hs.104741.
3D structure databases
ProteinModelPortal	Q96KB5.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96KB5. 8 interactions.
MINT	MINT-130347.
STRING	9606.ENSP00000301905.
PTM databases
PhosphoSite	Q96KB5.
Polymorphism databases
DMDM	83305809.
Proteomic databases
PaxDb	Q96KB5.
PeptideAtlas	Q96KB5.
PRIDE	Q96KB5.
Protocols and materials databases
DNASU	55872.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000301905; ENSP00000301905; ENSG00000168078.
GeneID	55872.
KEGG	hsa:55872.
UCSC	uc003xgi.3. human.
Organism-specific databases
CTD	55872.
GeneCards	GC08M027724.
HGNC	HGNC:18282. PBK.
HPA	HPA005753.
MIM	611210. gene.
neXtProt	NX_Q96KB5.
PharmGKB	PA134925802.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000294208.
HOVERGEN	HBG056011.
InParanoid	Q96KB5.
KO	K08865.
OrthoDB	EOG49ZXPN.
PhylomeDB	Q96KB5.
Gene expression databases
ArrayExpress	Q96KB5.
Bgee	Q96KB5.
CleanEx	HS_PBK.
Genevestigator	Q96KB5.
GermOnline	ENSG00000168078. Homo sapiens.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q96KB5.
ChEMBL	CHEMBL4896.
ChiTaRS	PBK. human.
GenomeRNAi	55872.
NextBio	61194.
SOURCE	Search...

Entry information

Entry name

TOPK_HUMAN

Accession

Primary (citable) accession number: Q96KB5
Secondary accession number(s): D3DST2 , 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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.