Protein: Focal adhesion kinase 1 (FADK 1) (EC 2.7.10.2) (Focal adhesion kinase-related nonkinase) (FRNK) (Protein-tyrosine kinase 2) (p125FAK) (pp125FAK) (P34152)
Organism: Mus musculus (Mouse)
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.
Subcellular location: Cell junction, focal adhesion {ECO:0000269|PubMed:1528852}. Cell membrane {ECO:0000250|UniProtKB:Q00944}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q00944}; Cytoplasmic side {ECO:0000250|UniProtKB:Q00944}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:12941275}. Cytoplasm, cell cortex. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:O35346}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Nucleus {ECO:0000269|PubMed:18206965}. Cytoplasm, cytoskeleton, cilium basal body {ECO:0000250|UniProtKB:Q05397}. Cytoplasm {ECO:0000269|PubMed:18206965}. Note=Constituent of focal adhesions. Detected at microtubules. {ECO:0000269|PubMed:12941275}.
Sequence: MAAAYLDPNLNHTPSSSTKTHLGTGMERSPGAMERVLKVFHYFESSSEPTTWASIIRHGDATDVRGIIQKIVDSHKVKHVACYGFRLSHLRSEEVHWLHVDMGVSSVREKYELAHPPEEWKYELRIRYLPKGFLNQFTEDKPTLNFFYQQVKSDYMQEIADQVDQEIALKLGCLEIRRSYWEMRGNALEKKSNYEVLEKDVGLKRFFPKSLLDSVKAKTLRKLIQQTFRQFANLNREESILKFFEILSPVYRFDKECFKCALGSSWIISVELAIGPEEGISYLTDKGCNPTHLADFNQVQTIQYSNSEDKDRKGMLQLKIAGAPEPLTVTAPSLTIAENMADLIDGYCRLVNGATQSFIIRPQKEGERALPSIPKLANSEKQGMRTHAVSVSETDDYAEIIDEEDTYTMPSTRDYEIQRERIELGRCIGEGQFGDVHQGVYLSPENPALAVAIKTCKNCTSDSVREKFLQEALTMRQFDHPHIVKLIGVITENPVWIIMELCTLGELRSFLQVRKYSLDLASLILYAYQLSTALAYLESKRFVHRDIAARNVLVSSNDCVKLGDFGLSRYMEDSTYYKASKGKLPIKWMAPESINFRRFTSASDVWMFGVCMWEILMHGVKPFQGVKNNDVIGRIENGERLPMPPNCPPTLYSLMTKCWAYDPSRRPRFTELKAQLSTILEEEKVQQEERMRMESRRQATVSWDSGGSDEAPPKPSRPGYPSPRSSEGFYPSPQHMVQTNHYQVSGYPGSHGIPAMAGSIYQGQASLLDQTELWNHRPQEMSMWQPSVEDSAALDLRGMGQVLPPHLMEERLIRQQQEMEEDQRWLEKEERFLKPDVRLSRGSIDREDGSFQGPTGNQHIYQPVGKPDPAAPPKKPPRPGAPGHLSNLSSISSPADSYNEGVKLQPQEISPPPTANLDRSNDKVYENVTGLVKAVIEMSSKIQPAPPEEYVPMVKEVGLALRTLLATVDETIPALPASTHREIEMAQKLLNSDLGELISKMKLAQQYVMTSLQQEYKKQMLTAAHALAVDAKNLLDVIDQARLKMLGQTRPH
InterPro domains: - IPR011009: Protein kinase-like domain superfamily (homologous_superfamily) [409-696]
- IPR035963: FERM superfamily, second domain (homologous_superfamily) [132-253]
- IPR029071: Ubiquitin-like domain superfamily (homologous_superfamily) [31-130]
- IPR005189: Focal adhesion kinase, targeting (FAT) domain (domain) [914-1045]
- IPR041784: FAK1/PYK2, FERM domain C-lobe (domain) [254-364]
- IPR041390: Focal adhesion kinase, N-terminal (domain) [35-130]
- IPR000299: FERM domain (domain) [35-355]
- IPR019748: FERM central domain (domain) [136-249]
- IPR019749: Band 4.1 domain (domain) [31-258]
- IPR014352: FERM/acyl-CoA-binding protein superfamily (homologous_superfamily) [128-252]
- IPR049385: FAK1-like, FERM domain C-lobe (domain) [260-357]
- IPR001245: Serine-threonine/tyrosine-protein kinase, catalytic domain (domain) [422-676]
- IPR017441: Protein kinase, ATP binding site (binding_site) [428-454]
- IPR000719: Protein kinase domain (domain) [422-680]
- IPR008266: Tyrosine-protein kinase, active site (active_site) [542-554]
- IPR020635: Tyrosine-protein kinase, catalytic domain (domain) [422-676]
- IPR036137: Focal adhesion kinase, targeting (FAT) domain superfamily (homologous_superfamily) [908-1046]
- IPR011993: PH-like domain superfamily (homologous_superfamily) [253-371]
Interaction partners: - Breast cancer anti-estrogen resistance protein 1
- Paxillin
- Growth factor receptor-bound protein 2
- Proto-oncogene tyrosine-protein kinase Src
- Integrin beta-1
- Epidermal growth factor receptor
- Talin-1
- Vinculin
- Tyrosine-protein kinase Fyn
- Adapter molecule crk
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0016740 (transferase activity), GO:0140096 (catalytic activity, acting on a protein), GO:0005515 (protein binding), GO:0016772 (transferase activity, transferring phosphorus-containing groups), GO:0004672 (protein kinase activity), GO:0016301 (kinase activity), GO:0016773 (phosphotransferase activity, alcohol group as acceptor), GO:0004713 (protein tyrosine kinase activity), GO:0004715 (non-membrane spanning protein tyrosine kinase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0023052 (signaling), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0008152 (metabolic process), GO:0042592 (homeostatic process), GO:0002376 (immune system process), GO:0048519 (negative regulation of biological process), GO:0048856 (anatomical structure development), GO:0009653 (anatomical structure morphogenesis), GO:0042221 (response to chemical), GO:0045321 (leukocyte activation), GO:0006955 (immune response), GO:0051240 (positive regulation of multicellular organismal process), GO:0002684 (positive regulation of immune system process), GO:0006807 (nitrogen compound metabolic process), GO:0051241 (negative regulation of multicellular organismal process), GO:0051239 (regulation of multicellular organismal process), GO:0048871 (multicellular organismal-level homeostasis), GO:0048646 (anatomical structure formation involved in morphogenesis), GO:0050793 (regulation of developmental process), GO:0002683 (negative regulation of immune system process), GO:0040017 (positive regulation of locomotion), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0051093 (negative regulation of developmental process), GO:0048523 (negative regulation of cellular process), GO:0007165 (signal transduction), GO:0040012 (regulation of locomotion), GO:0048869 (cellular developmental process), GO:0001775 (cell activation), GO:0007275 (multicellular organism development), GO:0048584 (positive regulation of response to stimulus), GO:0019222 (regulation of metabolic process), GO:0032879 (regulation of localization), GO:0048771 (tissue remodeling), GO:0002682 (regulation of immune system process), GO:0071704 (organic substance metabolic process), GO:0044237 (cellular metabolic process), GO:0009893 (positive regulation of metabolic process), GO:0002252 (immune effector process), GO:0065009 (regulation of molecular function), GO:0044238 (primary metabolic process), GO:0006950 (response to stress), GO:0051094 (positive regulation of developmental process), GO:0007154 (cell communication), GO:0048522 (positive regulation of cellular process), GO:0032103 (positive regulation of response to external stimulus), GO:2000145 (regulation of cell motility), GO:0060548 (negative regulation of cell death), GO:0002685 (regulation of leukocyte migration), GO:0002366 (leukocyte activation involved in immune response), GO:0034405 (response to fluid shear stress), GO:0048468 (cell development), GO:0030154 (cell differentiation), GO:0051282 (regulation of sequestering of calcium ion), GO:0048731 (system development), GO:0009966 (regulation of signal transduction), GO:0060255 (regulation of macromolecule metabolic process), GO:0032101 (regulation of response to external stimulus), GO:0050803 (regulation of synapse structure or activity), GO:0030279 (negative regulation of ossification), GO:0032970 (regulation of actin filament-based process), GO:0046649 (lymphocyte activation), GO:0044087 (regulation of cellular component biogenesis), GO:0006793 (phosphorus metabolic process), GO:0035295 (tube development), GO:0009894 (regulation of catabolic process), GO:0010632 (regulation of epithelial cell migration), GO:1904018 (positive regulation of vasculature development), GO:0022603 (regulation of anatomical structure morphogenesis), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0032878 (regulation of establishment or maintenance of cell polarity), GO:0007166 (cell surface receptor signaling pathway), GO:0051128 (regulation of cellular component organization), GO:0030278 (regulation of ossification), GO:0070168 (negative regulation of biomineral tissue development), GO:0008284 (positive regulation of cell population proliferation), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0035239 (tube morphogenesis), GO:0050790 (regulation of catalytic activity), GO:0044093 (positive regulation of molecular function), GO:0051049 (regulation of transport), GO:1901564 (organonitrogen compound metabolic process), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0001568 (blood vessel development), GO:0050920 (regulation of chemotaxis), GO:0019538 (protein metabolic process), GO:0034762 (regulation of transmembrane transport), GO:0043170 (macromolecule metabolic process), GO:0010033 (response to organic substance), GO:2000147 (positive regulation of cell motility), GO:0060249 (anatomical structure homeostasis), GO:0002687 (positive regulation of leukocyte migration), GO:0001525 (angiogenesis), GO:2000026 (regulation of multicellular organismal development), GO:0042127 (regulation of cell population proliferation), GO:0010941 (regulation of cell death), GO:0010646 (regulation of cell communication), GO:0031325 (positive regulation of cellular metabolic process), GO:0070887 (cellular response to chemical stimulus), GO:0033554 (cellular response to stress), GO:0046849 (bone remodeling), GO:0002263 (cell activation involved in immune response), GO:0009889 (regulation of biosynthetic process), GO:0062012 (regulation of small molecule metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0001894 (tissue homeostasis), GO:0080090 (regulation of primary metabolic process), GO:0045834 (positive regulation of lipid metabolic process), GO:0050921 (positive regulation of chemotaxis), GO:0009896 (positive regulation of catabolic process), GO:0051341 (regulation of oxidoreductase activity), GO:0050807 (regulation of synapse organization), GO:0051246 (regulation of protein metabolic process), GO:0043069 (negative regulation of programmed cell death), GO:0043067 (regulation of programmed cell death), GO:0001944 (vasculature development), GO:0010675 (regulation of cellular carbohydrate metabolic process), GO:0032956 (regulation of actin cytoskeleton organization), GO:0045453 (bone resorption), GO:0030334 (regulation of cell migration), GO:0030098 (lymphocyte differentiation), GO:0043412 (macromolecule modification), GO:0010594 (regulation of endothelial cell migration), GO:0072359 (circulatory system development), GO:0071677 (positive regulation of mononuclear cell migration), GO:0090218 (positive regulation of lipid kinase activity), GO:0030335 (positive regulation of cell migration), GO:0071498 (cellular response to fluid shear stress), GO:0002688 (regulation of leukocyte chemotaxis), GO:0071675 (regulation of mononuclear cell migration), GO:0043085 (positive regulation of catalytic activity), GO:0002040 (sprouting angiogenesis), GO:0019221 (cytokine-mediated signaling pathway), GO:0042113 (B cell activation), GO:0030097 (hemopoiesis), GO:0034097 (response to cytokine), GO:0022604 (regulation of cell morphogenesis), GO:0043255 (regulation of carbohydrate biosynthetic process), GO:0030500 (regulation of bone mineralization), GO:0010562 (positive regulation of phosphorus metabolic process), GO:0007167 (enzyme-linked receptor protein signaling pathway), GO:0002521 (leukocyte differentiation), GO:1905521 (regulation of macrophage migration), GO:0071310 (cellular response to organic substance), GO:1901888 (regulation of cell junction assembly), GO:0034765 (regulation of monoatomic ion transmembrane transport), GO:1901342 (regulation of vasculature development), GO:0045766 (positive regulation of angiogenesis), GO:1902930 (regulation of alcohol biosynthetic process), GO:0006796 (phosphate-containing compound metabolic process), GO:0006109 (regulation of carbohydrate metabolic process), GO:0002690 (positive regulation of leukocyte chemotaxis), GO:2000114 (regulation of establishment of cell polarity), GO:1902115 (regulation of organelle assembly), GO:0036211 (protein modification process), GO:0070167 (regulation of biomineral tissue development), GO:0080164 (regulation of nitric oxide metabolic process), GO:0048514 (blood vessel morphogenesis), GO:0031326 (regulation of cellular biosynthetic process), GO:0010634 (positive regulation of epithelial cell migration), GO:0051247 (positive regulation of protein metabolic process), GO:0033043 (regulation of organelle organization), GO:0031331 (positive regulation of cellular catabolic process), GO:0045765 (regulation of angiogenesis), GO:0051338 (regulation of transferase activity), GO:0043269 (regulation of monoatomic ion transport), GO:0019216 (regulation of lipid metabolic process), GO:0031329 (regulation of cellular catabolic process), GO:1902531 (regulation of intracellular signal transduction), GO:0051174 (regulation of phosphorus metabolic process), GO:0051279 (regulation of release of sequestered calcium ion into cytosol), GO:0002285 (lymphocyte activation involved in immune response), GO:0099150 (regulation of postsynaptic specialization assembly), GO:0051353 (positive regulation of oxidoreductase activity), GO:0042981 (regulation of apoptotic process), GO:0051493 (regulation of cytoskeleton organization), GO:0030162 (regulation of proteolysis), GO:2000249 (regulation of actin cytoskeleton reorganization), GO:0045937 (positive regulation of phosphate metabolic process), GO:0010959 (regulation of metal ion transport), GO:0018193 (peptidyl-amino acid modification), GO:0071345 (cellular response to cytokine stimulus), GO:2000403 (positive regulation of lymphocyte migration), GO:0016310 (phosphorylation), GO:0051963 (regulation of synapse assembly), GO:0043549 (regulation of kinase activity), GO:0050848 (regulation of calcium-mediated signaling), GO:1903131 (mononuclear cell differentiation), GO:1901623 (regulation of lymphocyte chemotaxis), GO:0010752 (regulation of cGMP-mediated signaling), GO:1990868 (response to chemokine)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0030054 (cell junction), GO:0098794 (postsynapse), GO:0005829 (cytosol), GO:0005737 (cytoplasm), GO:0043229 (intracellular organelle), GO:0045202 (synapse), GO:0043227 (membrane-bounded organelle), GO:0099572 (postsynaptic specialization), GO:0043228 (non-membrane-bounded organelle), GO:0098984 (neuron to neuron synapse), GO:0043231 (intracellular membrane-bounded organelle), GO:0099091 (postsynaptic specialization, intracellular component), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0014069 (postsynaptic density), GO:0098978 (glutamatergic synapse), GO:0099092 (postsynaptic density, intracellular component), GO:0032279 (asymmetric synapse), GO:0005634 (nucleus)