Q14289

Background

Protein Name
Protein-tyrosine kinase 2-beta
Gene Name
PTK2B
Organism
Homo sapiens

Annotations

Function
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.

Mapping Statistics

Site Maximum Consensus Site Population Minimum Consensus Site Population Median Consensus Site Population
MPP 26 2 10.0
AAS 9 9 9.0
MT3 7 2 7.0
ATP 17 3 8.5
DFG 4 2 3.0
EDI 3 3 3.0
PDIG 22 2 10.5
PIF 19 14 16.5

Mapping Results

PDB ID Maximum Consensus Site Population
MPP site AAS site MT3 site LBP site ATP site DEF site DFG site CMP site PMP site EDI site DRS site PDIG site PIF site
Total Druggable Structures per Site 3 0 0 0 2 0 0 0 0 0 0 4 1
3FZO 10 0 0 0 9 0 0 0 0 3 0 20 14
3FZS 11 0 7 0 8 0 0 0 0 0 0 8 0
3FZT 12 0 7 0 4 0 0 0 0 0 0 6 0
4H1J 15 0 0 0 3 0 0 0 0 0 0 12 0
3FZR 5 0 2 0 17 0 4 0 0 0 0 8 0
3FZP 14 0 0 0 11 0 0 0 0 0 0 20 0
3CC6 16 0 0 0 4 0 0 0 0 0 0 22 19
3ET7 5 0 0 0 17 0 2 0 0 0 0 2 0
4H1M 3 0 0 0 10 0 0 0 0 0 0 9 0
AFQ14289 26 0 0 0 0 0 0 0 0 0 0 0 0
3H3C 19 9 0 0 8 0 0 0 0 0 0 21 0