This gene encodes a serine/threonine protein kinase related to the dual specific mitogen-activated protein kinase kinase (MAPKK) family. Evidence suggests that mitotic phosphorylation is required for its catalytic activity. The encoded protein may be involved in the activation of lymphoid cells and support testicular functions, with a suggested role in the process of spermatoge... See more...

Aliases for PBK Gene

Aliases for PBK Gene

  • PDZ Binding Kinase 2 3 5
  • T-LAK Cell-Originated Protein Kinase 2 3 4
  • Cancer/Testis Antigen 84 2 3 4
  • Lymphokine-Activated Killer T-Cell-Originated Protein Kinase 3 4
  • Spermatogenesis-Related Protein Kinase 3 4
  • MAPKK-Like Protein Kinase 3 4
  • Nori-3 3 4
  • CT84 3 4
  • TOPK 3 4
  • SPK 3 4
  • Serine/Threonine Protein Kinase 3
  • Epididymis Luminal Protein 164 3
  • PDZ-Binding Kinase 4
  • EC 2.7.12.2 4
  • HEL164 3

External Ids for PBK Gene

Previous GeneCards Identifiers for PBK Gene

  • GC08M027724
  • GC08M026212

Summaries for PBK Gene

Entrez Gene Summary for PBK Gene

  • This gene encodes a serine/threonine protein kinase related to the dual specific mitogen-activated protein kinase kinase (MAPKK) family. Evidence suggests that mitotic phosphorylation is required for its catalytic activity. The encoded protein may be involved in the activation of lymphoid cells and support testicular functions, with a suggested role in the process of spermatogenesis. Overexpression of this gene has been implicated in tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

CIViC Summary for PBK Gene

GeneCards Summary for PBK Gene

PBK (PDZ Binding Kinase) is a Protein Coding gene. Diseases associated with PBK include Plexiform Neurofibroma and Central Corneal Ulcer. Among its related pathways are DNA Damage and 4-hydroxytamoxifen, Dexamethasone, and Retinoic Acids Regulation of p27 Expression. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity.

UniProtKB/Swiss-Prot Summary for PBK Gene

  • 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.

Gene Wiki entry for PBK Gene

Additional gene information for PBK Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PBK Gene

Genomics for PBK Gene

GeneHancer (GH) Regulatory Elements for PBK Gene

Promoters and enhancers for PBK Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH08J027835 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 500.7 +0.6 628 3.3 ZNF217 EP300 ZSCAN5C SIN3A NRF1 TCF12 POLR2G SP1 NCOR1 GTF2E2 ENSG00000253176 LOC100130612 PBK lnc-ESCO2-3 piR-50443-355 CCDC25 ESCO2 RF00017-6909
GH08J027871 Enhancer 1.7 FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 12.5 -34.9 -34898 4 ZNF217 ZSCAN5C TCF12 ZNF639 ZNF10 ZIC2 POLR2A CLOCK TRIM28 CUX1 PBK ENSG00000253176 CCDC25 SCARA3 ELP3 HSALNG0064210 MIR4287 SCARA5
GH08J028004 Enhancer 1 Ensembl ENCODE 10.2 -167.6 -167559 4 ZSCAN5C USF1 ZNF10 ZIC2 ZNF423 CTBP1 MXI1 ZNF341 OSR2 ZNF266 INTS9 ENSG00000253176 PBK ZNF395 PTK2B CCDC25 SCARA5 piR-35002-106
GH08J027863 Enhancer 0.8 ENCODE dbSUPER 11.1 -25.9 -25894 0.2 CTCF TCF12 REST RAD21 TRIM22 SMC3 ZNF384 YY1 SIN3A ZNF513 SCARA5 PBK ENSG00000253176 HSALNG0064210 MIR4287
GH08J027973 Enhancer 0.3 ENCODE 10.5 -135.6 -135624 0.2 EZH2 FOS ENSG00000253176 PBK SCARA5 piR-52079-196
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PBK on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PBK

Top Transcription factor binding sites by QIAGEN in the PBK gene promoter:
  • AML1a
  • AP-1
  • ATF-2
  • c-Jun
  • CUTL1
  • PPAR-gamma1
  • PPAR-gamma2

Genomic Locations for PBK Gene

Genomic Locations for PBK Gene
chr8:27,809,621-27,838,095
(GRCh38/hg38)
Size:
28,475 bases
Orientation:
Minus strand
chr8:27,667,137-27,695,612
(GRCh37/hg19)
Size:
28,476 bases
Orientation:
Minus strand

Genomic View for PBK Gene

Genes around PBK on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PBK Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PBK Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PBK Gene

Proteins for PBK Gene

  • Protein details for PBK Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96KB5-TOPK_HUMAN
    Recommended name:
    Lymphokine-activated killer T-cell-originated protein kinase
    Protein Accession:
    Q96KB5
    Secondary Accessions:
    • B4DX68
    • D3DST2
    • Q9NPD9
    • Q9NYL7
    • Q9NZK6

    Protein attributes for PBK Gene

    Size:
    322 amino acids
    Molecular mass:
    36085 Da
    Quaternary structure:
    • Interacts with DLG1 and TP53.

    Three dimensional structures from OCA and Proteopedia for PBK Gene

    Alternative splice isoforms for PBK Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PBK Gene

Post-translational modifications for PBK Gene

  • Phosphorylated; in a cell-cycle dependent manner at mitosis.
  • Ubiquitination at Lys8, Lys90, and Lys132
  • Modification sites at PhosphoSitePlus

Other Protein References for PBK Gene

No data available for DME Specific Peptides for PBK Gene

Domains & Families for PBK Gene

Gene Families for PBK Gene

IUPHAR :
Human Protein Atlas (HPA):
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for PBK Gene

Suggested Antigen Peptide Sequences for PBK Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ58333, highly similar to T-lymphokine-activated killer cell-originated protein kinase (EC 2.7.12.2) (B4DX68_HUMAN)
  • T-LAK cell-originated protein kinase (TOPK_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q96KB5

UniProtKB/Swiss-Prot:

TOPK_HUMAN :
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.
Family:
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.
genes like me logo Genes that share domains with PBK: view

Function for PBK Gene

Molecular function for PBK Gene

UniProtKB/Swiss-Prot 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.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.12.2;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.12.2;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.12.2;.
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated by phosphorylation.

Enzyme Numbers (IUBMB) for PBK Gene

Phenotypes From GWAS Catalog for PBK Gene

Gene Ontology (GO) - Molecular Function for PBK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity IEA --
GO:0004674 protein serine/threonine kinase activity IEA,TAS 10779557
GO:0005515 protein binding IPI 10779557
GO:0005524 ATP binding IEA --
GO:0016301 kinase activity IEA --
genes like me logo Genes that share ontologies with PBK: view
genes like me logo Genes that share phenotypes with PBK: view

Animal Models for PBK Gene

MGI Knock Outs for PBK:
  • Pbk Pbk<tm1Zgdo>

Animal Model Products

  • Taconic Biosciences Mouse Models for PBK

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PBK

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for PBK Gene

Localization for PBK Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PBK gene
Compartment Confidence
nucleus 5
cytosol 4
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 2
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for PBK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 25575812
genes like me logo Genes that share ontologies with PBK: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for PBK Gene

Pathways & Interactions for PBK Gene

genes like me logo Genes that share pathways with PBK: view

Pathways by source for PBK Gene

1 Cell Signaling Technology pathway for PBK Gene

SIGNOR curated interactions for PBK Gene

Activates:
Other effect:

Gene Ontology (GO) - Biological Process for PBK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000278 mitotic cell cycle NAS,IEA 10779557
GO:0001933 negative regulation of protein phosphorylation IEA --
GO:0006468 protein phosphorylation IEA --
GO:0016310 phosphorylation IEA --
GO:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic process IEA --
genes like me logo Genes that share ontologies with PBK: view

Drugs & Compounds for PBK Gene

(3) Drugs for PBK Gene - From: ApexBio, DGIdb, and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
ATP Investigational Nutra Agonist, Activator, Full agonist, Antagonist, Pore Blocker, Potentiation 0
OTS964 Pharma TOPK inhibitor,potent and selective 0
OTS514 Pharma TOPK inhibitor,highly potent 0

(1) Additional Compounds for PBK Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
Full agonist, Agonist, Partial agonist, Antagonist, Gating inhibitor 58-64-0

(2) ApexBio Compounds for PBK Gene

Compound Action Cas Number
OTS514 TOPK inhibitor,highly potent 1338540-55-8
OTS964 TOPK inhibitor,potent and selective 1338545-07-5
genes like me logo Genes that share compounds with PBK: view

Drug Products

Transcripts for PBK Gene

mRNA/cDNA for PBK Gene

3 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PBK

Alternative Splicing Database (ASD) splice patterns (SP) for PBK Gene

No ASD Table

Relevant External Links for PBK Gene

GeneLoc Exon Structure for
PBK

Expression for PBK Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PBK Gene

mRNA differential expression in normal tissues according to GTEx for PBK Gene

This gene is overexpressed in Testis (x17.4).

Protein differential expression in normal tissues from HIPED for PBK Gene

This gene is overexpressed in Monocytes (44.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for PBK Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PBK

SOURCE GeneReport for Unigene cluster for PBK Gene:

Hs.104741

mRNA Expression by UniProt/SwissProt for PBK Gene:

Q96KB5-TOPK_HUMAN
Tissue specificity: Expressed in the testis and placenta. In the testis, restrictedly expressed in outer cell layer of seminiferous tubules.

Evidence on tissue expression from TISSUES for PBK Gene

  • Nervous system(4.6)
  • Liver(2)
genes like me logo Genes that share expression patterns with PBK: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for PBK Gene

Orthologs for PBK Gene

This gene was present in the common ancestor of animals.

Orthologs for PBK Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PBK 31 30
  • 99.38 (n)
OneToOne
dog
(Canis familiaris)
Mammalia -- 31
  • 94 (a)
OneToMany
PBK 30
  • 92.96 (n)
-- 31
  • 86 (a)
OneToMany
cow
(Bos Taurus)
Mammalia PBK 31 30
  • 91.3 (n)
OneToMany
-- 31
  • 81 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Pbk 30
  • 88.16 (n)
mouse
(Mus musculus)
Mammalia Pbk 17 31 30
  • 87.19 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia PBK 31
  • 83 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 82 (a)
OneToMany
-- 31
  • 79 (a)
OneToMany
chicken
(Gallus gallus)
Aves PBK 31 30
  • 71.37 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia -- 31
  • 69 (a)
OneToMany
-- 31
  • 56 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia pbk 30
  • 66.67 (n)
Str.5851 30
zebrafish
(Danio rerio)
Actinopterygii pbk 31 30
  • 66.03 (n)
OneToOne
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.11180 30
fruit fly
(Drosophila melanogaster)
Insecta CG8173 31 30
  • 52.14 (n)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea CSA.54 31
  • 45 (a)
OneToOne
Species where no ortholog for PBK was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for PBK Gene

ENSEMBL:
Gene Tree for PBK (if available)
TreeFam:
Gene Tree for PBK (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PBK: view image

Paralogs for PBK Gene

No data available for Paralogs for PBK Gene

Variants for PBK Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PBK Gene

SNP ID Clinical significance and condition Chr 08 pos Variation AA Info Type
776305 Benign: not provided 27,811,070(-) C/G MISSENSE_VARIANT
776306 Benign: not provided 27,828,125(-) T/C SYNONYMOUS_VARIANT
rs17057901 - p.Glu220Asp
rs36086402 - p.Met241Leu
rs3779620 - p.Asn107Ser

Additional dbSNP identifiers (rs#s) for PBK Gene

Structural Variations from Database of Genomic Variants (DGV) for PBK Gene

Variant ID Type Subtype PubMed ID
dgv7153n100 CNV loss 25217958
dgv7154n100 CNV loss 25217958
esv23502 CNV loss 19812545
esv2668206 CNV deletion 23128226
esv2736800 CNV deletion 23290073
esv2736801 CNV deletion 23290073
esv2736802 CNV deletion 23290073
esv3543270 CNV deletion 23714750
esv4741 CNV loss 18987735
nsv1017032 CNV loss 25217958
nsv1030500 CNV loss 25217958
nsv398258 CNV deletion 16902084
nsv519636 CNV gain 19592680
nsv524133 CNV loss 19592680
nsv824582 CNV loss 20364138
nsv956049 CNV deletion 24416366

Variation tolerance for PBK Gene

Residual Variation Intolerance Score: 45.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.42; 77.17% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PBK Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
PBK

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PBK Gene

Disorders for PBK Gene

MalaCards: The human disease database

(8) MalaCards diseases for PBK Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
plexiform neurofibroma
  • neurofibroma plexiform
central corneal ulcer
perforated corneal ulcer
corneal edema
  • corneal oedema
neurofibroma
  • nerve sheath tumors
- elite association - COSMIC cancer census association via MalaCards
Search PBK in MalaCards View complete list of genes associated with diseases

Additional Disease Information for PBK

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with PBK: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PBK Gene

Publications for PBK Gene

  1. Characterization of PDZ-binding kinase, a mitotic kinase. (PMID: 10779557) Gaudet S … Lue RA (Proceedings of the National Academy of Sciences of the United States of America 2000) 2 3 4 23 54
  2. 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. (PMID: 10781613) Abe Y … Ueda N (The Journal of biological chemistry 2000) 2 3 4 23 54
  3. PDZ-binding kinase participates in spermatogenesis. (PMID: 11378444) Zhao S … Mao Y (The international journal of biochemistry & cell biology 2001) 3 4 23 54
  4. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41 54
  5. Critical roles of T-LAK cell-originated protein kinase in cytokinesis. (PMID: 19900192) Park JH … Katagiri T (Cancer science 2010) 3 23 54

Products for PBK Gene

Sources for PBK Gene