| IED ID | IndEnz0002018467 |
| Enzyme Type ID | protease018467 |
| Protein Name |
Focal adhesion kinase 1 FADK 1 EC 2.7.10.2 Focal adhesion kinase-related nonkinase FRNK p41/p43FRNK Protein-tyrosine kinase 2 p125FAK pp125FAK |
| Gene Name | PTK2 FAK FAK1 |
| Organism | Gallus gallus (Chicken) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Sauropsida Sauria (diapsids) Archelosauria Archosauria Dinosauria Saurischia Theropoda Coelurosauria Aves Neognathae Galloanserae Galliformes Phasianidae (turkeys) Phasianinae Gallus Gallus gallus (Chicken) |
| Enzyme Sequence | MAAAYLDPNLNHTPSSSAKTHLGTGMERSPGAMERVLKVFHYFENSSEPTTWASIIRHGDATDVRGIIQKIVDCHKVKNVACYGLRLSHLQSEEVHWLHLDMGVSNVREKFELAHPPEEWKYELRIRYLPKGFLNQFTEDKPTLNFFYQQVKNDYMLEIADQVDQEIALKLGCLEIRRSYGEMRGNALEKKSNYEVLEKDVGLRRFFPKSLLDSVKAKTLRKLIQQTFRQFANLNREESILKFFEILSPVYRFDKECFKCALGSSWIISVELAIGPEEGISYLTDKGANPTHLADFNQVQTIQYSNSEDKDRKGMLQLKIAGAPEPLTVTAPSLTIAENMADLIDGYCRLVNGATQSFIIRPQKEGERALPSIPKLANNEKQGVRSHTVSVSETDDYAEIIDEEDTYTMPSTRDYEIQRERIELGRCIGEGQFGDVHQGIYMSPENPAMAVAIKTCKNCTSDSVREKFLQEALTMRQFDHPHIVKLIGVITENPVWIIMELCTLGELRSFLQVRKFSLDLASLILYAYQLSTALAYLESKRFVHRDIAARNVLVSATDCVKLGDFGLSRYMEDSTYYKASKGKLPIKWMAPESINFRRFTSASDVWMFGVCMWEILMHGVKPFQGVKNNDVIGRIENGERLPMPPNCPPTLYSLMTKCWAYDPSRRPRFTELKAQLSTILEEEKLQQEERMRMESRRQVTVSWDSGGSDEAPPKPSRPGYPSPRSSEGFYPSPQHMVQPNHYQVSGYSGSHGIPAMAGSIYPGQASLLDQTDSWNHRPQEVSAWQPNMEDSGTLDVRGMGQVLPTHLMEERLIRQQQEMEEDQRWLEKEERFLVMKPDVRLSRGSIEREDGGLQGPAGNQHIYQPVGKPDHAAPPKKPPRPGAPHLGSLASLNSPVDSYNEGVKIKPQEISPPPTANLDRSNDKVYENVTGLVKAVIEMSSKIQPAPPEEYVPMVKEVGLALRTLLATVDESLPVLPASTHREIEMAQKLLNSDLAELINKMKLAQQYVMTSLQQEYKKQMLTAAHALAVDAKNLLDVIDQARLKMISQSRPH |
| Enzyme Length | 1053 |
| Uniprot Accession Number | Q00944 |
| Absorption | |
| Active Site | ACT_SITE 546; /note="Proton acceptor"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-ProRule:PRU10028" |
| Activity Regulation | ACTIVITY 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 TAE226. {ECO:0000269|PubMed:17574028}. |
| Binding Site | BINDING 454; /note=ATP; /evidence=ECO:0000305 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028}; |
| DNA Binding | |
| EC Number | 2.7.10.2 |
| Enzyme 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, 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), ephrin receptors, 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. Regulates P53/TP53 activity and stability. Phosphorylates SRC; this increases SRC kinase activity. Isoform 2 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. {ECO:0000269|PubMed:15494732, ECO:0000269|PubMed:15494733, ECO:0000269|PubMed:15494734, ECO:0000269|PubMed:20705914, ECO:0000269|PubMed:21852560, ECO:0000269|PubMed:21937583}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 428..434; /note=ATP; /evidence=ECO:0000305; NP_BIND 500..502; /note=ATP; /evidence=ECO:0000305 |
| Features | Active site (1); Alternative sequence (1); Beta strand (27); Binding site (1); Chain (1); Compositional bias (2); Domain (2); Helix (38); Modified residue (7); Mutagenesis (1); Nucleotide binding (2); Region (3); Turn (12) |
| Keywords | 3D-structure;ATP-binding;Alternative promoter usage;Angiogenesis;Cell junction;Cell membrane;Cell projection;Cytoplasm;Cytoskeleton;Developmental protein;Kinase;Membrane;Nucleotide-binding;Nucleus;Phosphoprotein;Reference proteome;Transferase;Tyrosine-protein kinase |
| Interact With | Itself; P49024; P00523; P61157; P08581 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell junction, focal adhesion {ECO:0000269|PubMed:8423801}. Cell membrane {ECO:0000269|PubMed:8423801}; Peripheral membrane protein {ECO:0000269|PubMed:8423801}; Cytoplasmic side {ECO:0000269|PubMed:8423801}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:8423801}. Cytoplasm, cytoskeleton {ECO:0000250}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250}. Nucleus {ECO:0000269|PubMed:8423801}. Cytoplasm, cytoskeleton, cilium basal body {ECO:0000250|UniProtKB:Q05397}. Note=Constituent of focal adhesions. Detected at microtubules (By similarity). {ECO:0000250}. |
| Modified Residue | MOD_RES 397; /note="Phosphotyrosine; by autocatalysis"; /evidence="ECO:0000269|PubMed:12370821"; MOD_RES 407; /note="Phosphotyrosine"; /evidence="ECO:0000250"; MOD_RES 576; /note="Phosphotyrosine; by SRC"; /evidence="ECO:0000269|PubMed:12370821, ECO:0000269|PubMed:17574028"; MOD_RES 577; /note="Phosphotyrosine; by SRC"; /evidence="ECO:0000250"; MOD_RES 863; /note="Phosphotyrosine"; /evidence="ECO:0000269|PubMed:12370821"; MOD_RES 911; /note="Phosphoserine"; /evidence="ECO:0000269|PubMed:21937583"; MOD_RES 926; /note="Phosphotyrosine"; /evidence="ECO:0000250" |
| Post Translational Modification | PTM: Phosphorylated on tyrosine residues upon activation, e.g. upon integrin signaling. Tyr-397 is the major autophosphorylation site, but other kinases can also phosphorylate this residue. Phosphorylation at Tyr-397 promotes interaction with SRC and SRC family members, leading to phosphorylation at Tyr-576, Tyr-577 and at additional tyrosine residues. Isoform 2 is phosphorylated on serine or threonine residues, but apparently not on tyrosine residues. {ECO:0000269|PubMed:12370821, ECO:0000269|PubMed:17574028, ECO:0000269|PubMed:21937583, ECO:0000269|PubMed:8423801}. |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (6); Electron microscopy (2); X-ray crystallography (26) |
| Cross Reference PDB | 1KTM; 1PV3; 1QVX; 2AEH; 2AL6; 2J0J; 2J0K; 2J0L; 2J0M; 2JKK; 2JKM; 2JKO; 2JKQ; 2L6F; 2L6G; 2L6H; 3ZDT; 4BRX; 4C7T; 4CYE; 4D4R; 4D4S; 4D4V; 4D4Y; 4D55; 4D58; 4D5H; 4D5K; 6CB0; 6GCR; 6GCW; 6GCX; 6TY3; 6TY4; |
| Mapped Pubmed ID | 10512882; 12242282; 15340073; 17604018; 18171471; 19590089; 20802513; 22101605; 23845217; 24657306; 25049397; 25650936; 26645346; 27895123; 29897729; 30877242; 31109284; 32779739; 8922390; 9425168; |
| Motif | |
| Gene Encoded By | |
| Mass | 119,207 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:10596 |
| Cross Reference Brenda | 2.7.10.2; |