Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

PTK2B (Q14289) - Overview - Molecular Target Synopsis

Protein


PTK2B, Protein-tyrosine kinase 2-beta
Enzyme Classification 2.7.10.2
UniProt Q14289

Also Known as FAK2_HUMAN, PTK2B, FAK2, PYK2, RAFTK

Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T-cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Promotes activation of NOS3. Regulates production of the cellular messenger cGMP. Promotes activation of the MAP kinase signaling cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. Promotes activation of Rho family GTPases, such as RHOA and RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Acts as a scaffold, binding to both PDPK1 and SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373', and 'Tyr-376'. Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca(2+) levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2. Homodimer, or homooligomer. Interacts with SIRPA and SH2D3C. Interacts with ARHGAP10. Interacts with DLG4 (By similarity). Interacts with KCNA2 (By similarity). Interacts with NPHP1, ASAP1, ASAP2, ARHGAP26, SKAP2 and TGFB1I1. The Tyr-402 phosphorylated form interacts with SRC (via SH2 domain) and SRC family members. Forms a signaling complex with EPHA1, LCK and phosphatidylinositol 3-kinase; upon activation by EFNA1. Interacts with GRB2 (via SH2 domain). Interacts with P53/TP53 and MDM2. Interacts with MYLK. Interacts with BCAR1. Interacts with PDPK1. Interacts (hypophosphorylated) with PXN. Interacts with RB1CC1. Interacts with RHOU. Interacts with VAV1. Interacts with LPXN and PTPN12.

5TOB
SELECTIVITY SWITCH BETWEEN FAK AND PYK2: MACROCYCLIZATION OF FAK INHIBITORS IMPROVES PYK2 POTENCY
RCSB/PDB
Inspect Structure
See all 3D Structures for PTK2B

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: PTK2B is active in the following subcellular-locations: cell cortex, cell junction, cell membrane, cell projection, cytoplasm, focal adhesion, lamellipodium, nucleus, perinuclear region.
GO terms: PTK2B is active in the following subcellular-locations: apical dendrite, cell body, cell cortex, cytoplasm, cytoskeleton, cytosol, dendrite, dendritic spine, extrinsic component of cytoplasmic side of plasma membrane, focal adhesion, glutamatergic synapse, growth cone, lamellipodium, membrane raft, neuronal cell body, NMDA selective glutamate receptor complex, nucleus, perinuclear region of cytoplasm, postsynaptic density.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PTK2B has gain in 0 cell-lines, loss in 10 cell-lines and no signal in 994 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: K_562, HL_60, RPMI_8226

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: CCRF-SB, UKE-1, NCI-H929

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: K562, CD20-positive B cell, GM12878

(see details)

RNA Interference


PTK2B was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: SUM44, JIMT1. (see details)

3D Structures


For PTK2B there are:
22 structures (28 chains) solved
10 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PTK2B has been screened with 884 compounds (1520 bioactivities), 73 compounds have bioactivities that show binding affinity of <= 500nM (101 bioactivities). (see details)