lmmol · Proteins

Protein-tyrosine kinase 2-beta

UniProt Q14289 Organism Homo sapiens Gene FAK2, PTK2B, PYK2, RAFTK EC 2.7.10.2

Also known as: FAK2, PTK2B, PYK2, RAFTK

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.

Classification

Family (Pfam)
PF21477 FERM_C_FAK1, PF00373 FERM_M, PF18038 FERM_N_2, PF03623 Focal_AT, PF07714 PK_Tyr_Ser-Thr
InterPro
Band_41_domain, FADK_N, FAK1-like_FERM_C, FAK1/PYK2_FERM_C, FERM/acyl-CoA-bd_prot_sf, FERM_2, FERM_central, FERM_domain, Focal_adhe_kin_target_dom_sf, Focal_adhesion_kin_target_dom, Kinase-like_dom_sf, PH-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS, Tyr_kinase_cat_dom, Ubiquitin-like_domsf
Functional cluster
Zinc-Finger & Chromatin Regulatory Proteins

Experimental structures · PDB · 26

A predicted model is available from AlphaFold.

Gene Ontology · 78

Drugs targeting this protein · 2

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 48 cited papers

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