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FLASH GENE
Symbol PTK2B contributors: mct - updated : 26-06-2017
HGNC name PTK2B protein tyrosine kinase 2 beta
HGNC id 9612
Location 8p21.2      Physical location : 27.168.998 - 27.316.903
Synonym name
  • proline-rich tyrosine kinase 2
  • cell adhesion kinase beta
  • calcium-dependent tyrosine kinase
  • focal adhesion kinase 2
    • Synonym symbol(s) CAKB, FAK2, PYK2, RAFTK, PKB, CADTK, PTK, FRNK
    EC.number 2.7.10.1, 2.7.10.2
    DNA
    TYPE functioning gene
    STRUCTURE 133.85 kb     31 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure 546 polymorphism in the PKCbeta promoter reduces promoter activity, which leads to a decreased expression of PKCbeta2 and subsequently is associated with decreased peripheral insulin-dependent glucose uptake
    MAPPING cloned Y linked   status confirmed
    RNA
    TRANSCRIPTS type messenger
    text variants 1, 2, and 3 encode the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    36 - 4555 115.7 1009 - 2002 12231407
    37 - 4715 115.7 1009 - 2002 12231407
    30 - 3936 111 967 - 2002 12231407
    31 - 4089 115.7 1009 - 2002 12231407
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain   highly Homo sapiens
    Reproductivemale systemtestis    Mus musculusFetal
    Urinarykidneytubule    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow    Homo sapiens
    Epithelialbarrier liningepidermisstratum granulosum 
    cells
    SystemCellPubmedSpeciesStageRna symbol
    ReproductiveSertoli cell Mus musculusFetal
    Skeletonosteoclast Mus musculus
    Skin/Tegumentkeratinocyte
    Urinaryepithelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a large proline rich domain in the C-terminal part, without Src homology SH2 and SH3 domains
  • a kinase-FAT linker and a FAT domain
  • C-terminal domain known as CRNK, functioning as a dominant-negative inhibitor of PTK2B-dependent signaling, presumably by displacing PTK2B from focal adhesions and costameres
    • HOMOLOGY
    Homologene
    FAMILY
  • AGC protein kinase family
  • focal adhesion kinase family
  • Tyr protein kinase family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • predominantly localized in the cytoplasm
    • basic FUNCTION
  • non receptor, protein tyrosine kinase, focal adhesion kinase, involved in Ca++ induced regulation of ion channel and MAP kinase functions
  • playing a role in role in regulation of keratinocyte differentiation
  • functions as an integrator of multiple signaling pathways involved in the regulation of fundamental cellular processes
  • inhibit insulin production in beta-cells and to support insulin action in skeletal muscle
  • Ca(2+)-dependent, nonreceptor protein tyrosine kinase that is involved in the induction of left ventricular hypertrophy (LVH) and its transition to heart failure
  • can regulate translation, potentially critical for the transforming capacity of AGC kinase family member
  • can directly phosphorylate eIF4B on serine 422 (ser422)
  • involved in mediating acute resposes in endothelium
  • PTK2 and PTK2B are downstream targets of the Rap GTPases that play a key role in regulating B cell morphology
  • like PTK2, PTK2B acts as an important scaffolding protein and transduces signals from G-protein-coupled receptors to downstream MAPK signaling pathways depending on which signaling kinase and/or adaptor protein binds to the phosphorylated enzyme
  • within FAC (focal adhesion complex), the focal adhesion kinase (PTK2) and PTK2B are believed to act as important scaffolding proteins
  • integrates receptor-mediated signals controlling actin cytoskeletal rearrangement, events needed for the activation and function of T cells
  • possible cell type- and stage-specific roles for PTK2B during early testis development
  • non-receptor tyrosine kinase that regulates cellular adhesion
  • critical function for NPHP4 and PTK2B in controlling NPHP1 and the NPH protein complex
  • protective role of PTK2B with respect to ventricular tachyarrhythmia during parasympathetic stimulation by regulation of gene expression related to Ca(2+) handling
  • novel role in mediating chloride secretion in airway epithelial cells
  • may be an important initiating factor in renal fibrosis
  • inhibits endothelial cell migration and shear-stimulated ERK activation
  • in the brain, it is involved in the induction of long term potentiation through regulation of N-methyl-d-aspartate receptor trafficking
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • part of a signaling complex with LPXN, CSK, and PTPN12 to regulate migration of prostate cancer cells
  • PTK2B/ARHGEF11 couples RHOA activation to Ca(2+)
  • PTK2B and actin play an important role in megakaryocytes-regulated signaling cascades that control osteoblast proliferation
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • PYK2 binding proteins NIR1, PITPN/NIR2, NIR3
  • GSK3B
  • paxilin
  • ARHGAP10
  • via interaction with MYD88, is involved in modulating cytokine stimulation of NF-kappaB activity and signaling, providing a mechanism underlying PTK2B regulation of an inflammatory response
  • PTPN12 controls PTK2B activity and is a positive regulator of secondary T cell activation
  • dephosphorylation by dynamin and PTPN12 may be critical for terminating outside-in integrin signaling, and for stabilizing cytoskeletal reorganization during osteoclast bone resorption
  • XIAP interacts with PTK2B, suggesting cross-talk between XIAP and PTK2B
  • XIAP plays a key role in vascular functions of PTK2B or PTK2B domain-mediated vascular functions of PTK2
  • substrate of striatal-enriched protein-tyrosine phosphatase (PTPN5)
  • is a critical regulator of EC inflammation by virtue of engaging IKK to promote the release and the transcriptional capacity of RELA, and, additionally, by its ability to facilitate the nuclear translocation of the released RELA
  • PTK2 contributes to cytokine signaling and bone resorption in osteoclasts and partially compensates for the absence of PTK2B to maintain proper adhesion structures in these cells
  • PTK2B was rapidly phosphorylated and activated in platelets adherent to fibrinogen through integrin ITGA2B/ITGB3
  • PTPN12 control phosphorylation of PTK2B and paxillin, thereby regulating cell polarization, migration, and spreading
  • upon the binding of CCL18 to PITPNM3, PTK2B translocates from the cytoplasm to the plasma membrane to form a stable complex with PITPNM3, subsequently activating SRC kinase
  • CBLB is a type of E3 ubiquitin ligase that interacted with PTK2B, reduced the expression of PTK2B, and promoted trypsin-induced degradation of PTK2B
  • PTK2B, but not PTK2, could directly phosphorylate PYCARD at Tyr146, and only the phosphorylated PYCARD could participate in speck formation and trigger IL1B secretion
  • PTK2B/STAP2 interaction is a novel mechanism to regulate CXCL12-dependent T-cell chemotaxis
  • role of IZUMO1R and CD9 in PTK2B activation and actin remodeling at the sperm binding site
    • cell & other
    REGULATION
    Other dephosphorylation by caicitonin and phosphorylation of focal adhesion kinase in osteoclasts
    PTPN5 binds to and dephosphorylates PTK2B at Tyr(402)
    hypophosphorylated and inactive PTK2B associates with paxillin at the microtubule organizing center in hematopoietic cells
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    in the human heart during heart failure may contribute to protection against arrhythmia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    osteoarticular  
    may be important for therapeutic interventions aimed at increasing bone formation in metabolic diseases of the skeleton
    miscelleaneousurinary 
    new therapeutic target for ameliorating renal fibrosis
    ANIMAL & CELL MODELS
  • mice lacking Pyk2 exhibit an increase in bone mass, in part due to impairment of osteoclast function