lmmol · Proteins

Focal adhesion kinase 1

UniProt Q05397 Organism Homo sapiens Gene FAK, FAK1, PTK2 EC 2.7.10.2

Also known as: FAK, FAK1, PTK2

Function

Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G protein-coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. 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 the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Phosphorylates NEDD9 following integrin stimulation. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription.

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
Protein Serine/Threonine Kinases

Experimental structures · PDB · 40

A predicted model is available from AlphaFold.

Gene Ontology · 63

Drugs targeting this protein · 7

Neighborhood · nearest proteins

FAKFakFAKFadkFKHL13C20orf32Lpxn
Nearest neighbours of Focal adhesion kinase 1: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 73 cited papers

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