Names & Taxonomy

Uniprot ID:
Q05397
Entry Name:
FAK1_HUMAN
Status:
reviewed
Protein Names:
Focal adhesion kinase 1 (FADK 1) (EC 2.7.10.2) (Focal adhesion kinase-related nonkinase) (FRNK) (Protein phosphatase 1 regulatory subunit 71) (PPP1R71) (Protein-tyrosine kinase 2) (p125FAK) (pp125FAK)
Gene Names:
PTK2 FAK FAK1
Gene Names Primary:
PTK2
Organism:
Homo sapiens (Human)

Structure

Length:
1052
Sequence:
MAAAYLDPNLNHTPNSSTKTHLGTGMERSPGAMERVLKVFHYFESNSEPTTWASIIRHGDATDVRGIIQKIVDSHKVKHVACYGFRLSHLRSEEVHWLHVDMGVSSVREKYELAHPPEEWKYELRIRYLPKGFLNQFTEDKPTLNFFYQQVKSDYMLEIADQVDQEIALKLGCLEIRRSYWEMRGNALEKKSNYEVLEKDVGLKRFFPKSLLDSVKAKTLRKLIQQTFRQFANLNREESILKFFEILSPVYRFDKECFKCALGSSWIISVELAIGPEEGISYLTDKGCNPTHLADFTQVQTIQYSNSEDKDRKGMLQLKIAGAPEPLTVTAPSLTIAENMADLIDGYCRLVNGTSQSFIIRPQKEGERALPSIPKLANSEKQGMRTHAVSVSETDDYAEIIDEEDTYTMPSTRDYEIQRERIELGRCIGEGQFGDVHQGIYMSPENPALAVAIKTCKNCTSDSVREKFLQEALTMRQFDHPHIVKLIGVITENPVWIIMELCTLGELRSFLQVRKYSLDLASLILYAYQLSTALAYLESKRFVHRDIAARNVLVSSNDCVKLGDFGLSRYMEDSTYYKASKGKLPIKWMAPESINFRRFTSASDVWMFGVCMWEILMHGVKPFQGVKNNDVIGRIENGERLPMPPNCPPTLYSLMTKCWAYDPSRRPRFTELKAQLSTILEEEKAQQEERMRMESRRQATVSWDSGGSDEAPPKPSRPGYPSPRSSEGFYPSPQHMVQTNHYQVSGYPGSHGITAMAGSIYPGQASLLDQTDSWNHRPQEIAMWQPNVEDSTVLDLRGIGQVLPTHLMEERLIRQQQEMEEDQRWLEKEERFLKPDVRLSRGSIDREDGSLQGPIGNQHIYQPVGKPDPAAPPKKPPRPGAPGHLGSLASLSSPADSYNEGVKLQPQEISPPPTANLDRSNDKVYENVTGLVKAVIEMSSKIQPAPPEEYVPMVKEVGLALRTLLATVDETIPLLPASTHREIEMAQKLLNSDLGELINKMKLAQQYVMTSLQQEYKKQMLTAAHALAVDAKNLLDVIDQARLKMLGQTRPH
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cell junction, focal adhesion. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasm, cell cortex. Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome

Function

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. 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.
Catalytic Activity:
ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
Enzyme Regulation:
ENZYME REGULATION: Subject to autoinhibition, mediated by interactions between the FERM domain and the kinase domain. Activated by autophosphorylation at Tyr-397. This promotes interaction with SRC and phosphorylation at Tyr-576 and Tyr-577 in the kinase activation loop. Phosphorylation at Tyr-576 and Tyr-577 is required for maximal kinase activity. Inhibited by TAC544, TAE226, PF-573,228 and PF-562,271.
Active Site:
ACT_SITE 546 546 Proton acceptor.
Gene Ontology Go:
apical plasma membrane
cell cortex
cytoplasm
cytoskeleton
cytosol
extrinsic component of cytoplasmic side of plasma membrane
focal adhesion
lamellipodium
microtubule organizing center
nucleus
plasma membrane
stress fiber
actin binding
ATP binding
JUN kinase binding
non-membrane spanning protein tyrosine kinase activity
protein kinase activity
protein kinase binding
protein tyrosine kinase activity
receptor binding
SH2 domain binding
signal transducer activity
activation of MAPKK activity
angiogenesis
apoptotic process
axon guidance
blood coagulation
cell adhesion
cell motility
cellular component disassembly involved in execution phase of apoptosis
central nervous system neuron axonogenesis
cytoskeleton organization
embryo development
endothelial cell migration
ephrin receptor signaling pathway
epidermal growth factor receptor signaling pathway
establishment of cell polarity
establishment of nucleus localization
extracellular matrix organization
Fc-epsilon receptor signaling pathway
Fc-gamma receptor signaling pathway involved in phagocytosis
fibroblast growth factor receptor signaling pathway
growth hormone receptor signaling pathway
heart morphogenesis
innate immune response
insulin receptor signaling pathway
integrin-mediated signaling pathway
MAPK cascade
microtubule cytoskeleton organization
negative regulation of anoikis
negative regulation of apoptotic process
negative regulation of axonogenesis
negative regulation of cell-cell adhesion
negative regulation of organ growth
negative regulation of synapse assembly
netrin-activated signaling pathway
neuron migration
neurotrophin TRK receptor signaling pathway
peptidyl-tyrosine autophosphorylation
peptidyl-tyrosine phosphorylation
placenta development
platelet activation
positive regulation of cell migration
positive regulation of cell proliferation
positive regulation of phosphatidylinositol 3-kinase activity
positive regulation of phosphatidylinositol 3-kinase signaling
positive regulation of protein kinase activity
positive regulation of protein kinase B signaling
positive regulation of protein phosphorylation
positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
programmed cell death
protein autophosphorylation
Ras protein signal transduction
regulation of cell adhesion mediated by integrin
regulation of cell proliferation
regulation of cell shape
regulation of cytoskeleton organization
regulation of endothelial cell migration
regulation of epithelial cell migration
regulation of focal adhesion assembly
regulation of GTPase activity
regulation of osteoblast differentiation
regulation of protein phosphorylation
regulation of substrate adhesion-dependent cell spreading
signal complex assembly
small GTPase mediated signal transduction
transforming growth factor beta receptor signaling pathway
vascular endothelial growth factor receptor signaling pathway
vasculogenesis
Gene Ontology Biological Process:
activation of MAPKK activity
angiogenesis
apoptotic process
axon guidance
blood coagulation
cell adhesion
cell motility
cellular component disassembly involved in execution phase of apoptosis
central nervous system neuron axonogenesis
cytoskeleton organization
embryo development
endothelial cell migration
ephrin receptor signaling pathway
epidermal growth factor receptor signaling pathway
establishment of cell polarity
establishment of nucleus localization
extracellular matrix organization
Fc-epsilon receptor signaling pathway
Fc-gamma receptor signaling pathway involved in phagocytosis
fibroblast growth factor receptor signaling pathway
growth hormone receptor signaling pathway
heart morphogenesis
innate immune response
insulin receptor signaling pathway
integrin-mediated signaling pathway
MAPK cascade
microtubule cytoskeleton organization
negative regulation of anoikis
negative regulation of apoptotic process
negative regulation of axonogenesis
negative regulation of cell-cell adhesion
negative regulation of organ growth
negative regulation of synapse assembly
netrin-activated signaling pathway
neuron migration
neurotrophin TRK receptor signaling pathway
peptidyl-tyrosine autophosphorylation
peptidyl-tyrosine phosphorylation
placenta development
platelet activation
positive regulation of cell migration
positive regulation of cell proliferation
positive regulation of phosphatidylinositol 3-kinase activity
positive regulation of phosphatidylinositol 3-kinase signaling
positive regulation of protein kinase activity
positive regulation of protein kinase B signaling
positive regulation of protein phosphorylation
positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
programmed cell death
protein autophosphorylation
Ras protein signal transduction
regulation of cell adhesion mediated by integrin
regulation of cell proliferation
regulation of cell shape
regulation of cytoskeleton organization
regulation of endothelial cell migration
regulation of epithelial cell migration
regulation of focal adhesion assembly
regulation of GTPase activity
regulation of osteoblast differentiation
regulation of protein phosphorylation
regulation of substrate adhesion-dependent cell spreading
signal complex assembly
small GTPase mediated signal transduction
transforming growth factor beta receptor signaling pathway
vascular endothelial growth factor receptor signaling pathway
vasculogenesis
Gene Ontology Molecular Function:
actin binding
ATP binding
JUN kinase binding
non-membrane spanning protein tyrosine kinase activity
protein kinase activity
protein kinase binding
protein tyrosine kinase activity
receptor binding
SH2 domain binding
signal transducer activity
Gene Ontology Cellular Component:
apical plasma membrane
cell cortex
cytoplasm
cytoskeleton
cytosol
extrinsic component of cytoplasmic side of plasma membrane
focal adhesion
lamellipodium
microtubule organizing center
nucleus
plasma membrane
stress fiber
Keywords:
3D-structure
ATP-binding
Acetylation
Alternative promoter usage
Alternative splicing
Angiogenesis
Cell junction
Cell membrane
Complete proteome
Cytoplasm
Cytoskeleton
Developmental protein
Direct protein sequencing
Isopeptide bond
Kinase
Membrane
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Transferase
Tyrosine-protein kinase
Ubl conjugation
Interacts With:
P56945; P46108; P46109; P00533; P29317; P04626; P17948; Q14451; P08631-2; Q92569; Q9H3S7; P29350-3; Q9Y3E5; P49023; Q9NP31; P12931; P05480; O43294; Q62219; Q68CZ2; P04637

Publication

PubMed ID:
7692878 8422239 14702039 16421571 15489334 8247543 9422762 9756887 10655584 11331870 11980671 12221124 12387730 15166238 15561106 15855171 15895076 16452200 17081983 16998626 16964243 18006843 17395594 16927379 17431114 18497331 18292575 18256281 18206965 18657504 18691976 18669648 19413330 19339212 19138410 19787193 19494199 19147981 19118217 19369195 20495381 19917054 20109444 20439989 20037584 20068231 21269460 21454698 23503467 10354709 15725728 16919435 17968709 18677107 19525103 19224453 20515733 20552554 20101634 20332118 21482413 23509069 12005431 12467573 14527389 18339875 18078954 17344846