ID FAK1_RAT Reviewed; 1055 AA. AC O35346; Q62900; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 24-JAN-2024, entry version 213. DE RecName: Full=Focal adhesion kinase 1 {ECO:0000305}; DE Short=FADK 1; DE EC=2.7.10.2; DE AltName: Full=Focal adhesion kinase-related nonkinase; DE Short=FRNK; DE AltName: Full=Protein-tyrosine kinase 2; DE AltName: Full=p125FAK; DE AltName: Full=pp125FAK; GN Name=Ptk2 {ECO:0000312|RGD:3443}; Synonyms=Fak, Fak1; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC STRAIN=Sprague-Dawley; TISSUE=Corpus striatum; RX PubMed=8738136; DOI=10.1016/0169-328x(95)00273-u; RA Burgaya F., Girault J.A.; RT "Cloning of focal adhesion kinase, pp125FAK, from rat brain reveals RT multiple transcripts with different patterns of expression."; RL Brain Res. Mol. Brain Res. 37:63-73(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 350-528 (ISOFORM 1). RC STRAIN=Wistar; RA Sasaki T., Nagura K., Sasaki H.; RL Submitted (DEC-1995) to the EMBL/GenBank/DDBJ databases. RN [3] RP INTERACTION WITH TGFB1I1. RX PubMed=9422762; DOI=10.1074/jbc.273.2.1003; RA Matsuya M., Sasaki H., Aoto H., Mitaka T., Nagura K., Ohba T., Ishino M., RA Takahashi S., Suzuki R., Sasaki T.; RT "Cell adhesion kinase beta forms a complex with a new member, Hic-5, of RT proteins localized at focal adhesions."; RL J. Biol. Chem. 273:1003-1014(1998). RN [4] RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-722 AND SER-913, AND RP CHARACTERIZATION OF ISOFORM 2. RX PubMed=12732587; DOI=10.1161/01.hyp.0000072772.74183.5f; RA Yi X.P., Wang X., Gerdes A.M., Li F.; RT "Subcellular redistribution of focal adhesion kinase and its related RT nonkinase in hypertrophic myocardium."; RL Hypertension 41:1317-1323(2003). RN [5] RP INTERACTION WITH ARHGEF28. RX PubMed=12702722; DOI=10.1074/jbc.m302381200; RA Zhai J., Lin H., Nie Z., Wu J., Canete-Soler R., Schlaepfer W.W., RA Schlaepfer D.D.; RT "Direct interaction of focal adhesion kinase with p190RhoGEF."; RL J. Biol. Chem. 278:24865-24873(2003). RN [6] RP SUMOYLATION AT LYS-152, MUTAGENESIS OF LYS-152, INTERACTION WITH PIAS1, RP AUTOPHOSPHORYLATION, PHOSPHORYLATION AT TYR-397, AND SUBCELLULAR LOCATION. RX PubMed=14500712; DOI=10.1074/jbc.m308562200; RA Kadare G., Toutant M., Formstecher E., Corvol J.C., Carnaud M., RA Boutterin M.C., Girault J.A.; RT "PIAS1-mediated sumoylation of focal adhesion kinase activates its RT autophosphorylation."; RL J. Biol. Chem. 278:47434-47440(2003). RN [7] RP FUNCTION, AND INTERACTION WITH DCC. RX PubMed=15494733; DOI=10.1038/nn1330; RA Ren X.R., Ming G.L., Xie Y., Hong Y., Sun D.M., Zhao Z.Q., Feng Z., RA Wang Q., Shim S., Chen Z.F., Song H.J., Mei L., Xiong W.C.; RT "Focal adhesion kinase in netrin-1 signaling."; RL Nat. Neurosci. 7:1204-1212(2004). RN [8] RP SUBCELLULAR LOCATION, PHOSPHORYLATION, AND CHARACTERIZATION OF ISOFORM 2. RX PubMed=16373587; DOI=10.1152/ajpheart.00659.2005; RA Yi X.P., Zhou J., Huber L., Qu J., Wang X., Gerdes A.M., Li F.; RT "Nuclear compartmentalization of FAK and FRNK in cardiac myocytes."; RL Am. J. Physiol. 290:H2509-H2515(2006). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-576; SER-913 AND TYR-928, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). CC -!- FUNCTION: Non-receptor protein-tyrosine kinase that plays an essential CC role in regulating cell migration, adhesion, spreading, reorganization CC of the actin cytoskeleton, formation and disassembly of focal adhesions CC and cell protrusions, cell cycle progression, cell proliferation and CC apoptosis. Required for early embryonic development and placenta CC development. Required for embryonic angiogenesis, normal cardiomyocyte CC migration and proliferation, and normal heart development. Regulates CC axon growth and neuronal cell migration, axon branching and synapse CC formation; required for normal development of the nervous system. Plays CC a role in osteogenesis and differentiation of osteoblasts. Functions in CC integrin signal transduction, but also in signaling downstream of CC numerous growth factor receptors, G-protein coupled receptors (GPCR), CC EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling CC complexes with SRC and SRC family members upon activation; this leads CC to the phosphorylation of additional tyrosine residues, creating CC binding sites for scaffold proteins, effectors and substrates. CC Regulates numerous signaling pathways. Promotes activation of CC phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes CC activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling CC cascade. Promotes localized and transient activation of guanine CC nucleotide exchange factors (GEFs) and GTPase-activating proteins CC (GAPs), and thereby modulates the activity of Rho family GTPases. CC Signaling via CAS family members mediates activation of RAC1. CC Phosphorylates NEDD9 following integrin stimulation (By similarity). CC Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and CC thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and CC proteasomal degradation. Phosphorylates SRC; this increases SRC kinase CC activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes CC phosphorylation of PXN and STAT1; most likely PXN and STAT1 are CC phosphorylated by a SRC family kinase that is recruited to CC autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes CC phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and CC PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. CC {ECO:0000250|UniProtKB:P34152, ECO:0000250|UniProtKB:Q05397, CC ECO:0000269|PubMed:15494733}. CC -!- FUNCTION: [Isoform 2]: Does not contain a kinase domain and inhibits CC PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can CC attenuate the nuclear accumulation of LPXN and limit its ability to CC enhance serum response factor (SRF)-dependent gene transcription (By CC similarity). {ECO:0000250|UniProtKB:Q05397}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028}; CC -!- ACTIVITY REGULATION: Subject to autoinhibition, mediated by CC interactions between the FERM domain and the kinase domain. Activated CC by autophosphorylation at Tyr-397. This promotes interaction with SRC CC and phosphorylation at Tyr-576 and Tyr-577 in the kinase activation CC loop by SRC. Phosphorylation at Tyr-397, Tyr-576 and Tyr-577 is CC required for maximal kinase activity. CC -!- SUBUNIT: Interacts with GIT1. Component of a complex that contains at CC least FER, CTTN and PTK2/FAK1. Interacts with BMX. Interacts with CC STEAP4. Interacts with ZFYVE21. Interacts with ESR1. Interacts with CC PIK3R1 or PIK3R2. Interacts with FGR, FLT4 and RET. Interacts with CC EPHA2 in resting cells; activation of EPHA2 recruits PTPN11, leading to CC dephosphorylation of PTK2/FAK1 and dissociation of the complex. CC Interacts with EPHA1 (kinase activity-dependent). Interacts with CC P53/TP53. Interacts (via first Pro-rich region) with CAS family members CC (via SH3 domain), including BCAR1, BCAR3, and CASS4. Interacts with CC NEDD9 (via SH3 domain) (By similarity). Interacts with TGFB1I1. CC Interacts with SRC, GRB2 and GRB7. Interacts with ARHGEF28. Interacts CC with SHB. Part of a complex composed of THSD1, PTK2/FAK1, TLN1 and VCL CC (By similarity). Interacts with PXN and TLN1. Interacts with SORBS1. CC Interacts with STAT1. Interacts with WASL. Interacts with ARHGAP26 and CC SHC1. Interacts with RB1CC1; this inhibits PTK2/FAK1 activity and CC activation of downstream signaling pathways. Interacts with ARHGEF7. CC Interacts with MDM2 (By similarity). Interacts with PIAS1. Interacts CC with DCC. Interacts with LPXN (via LD motif 3) (By similarity). CC Interacts with MISP (By similarity). Interacts with EMP2; regulates CC PTK2 activation and localization (By similarity). Interacts with DSCAM CC (By similarity). Interacts with AMBRA1 (By similarity). Interacts (when CC tyrosine-phosphorylated) with tensin TNS1; the interaction is increased CC by phosphorylation of TNS1 (By similarity). CC {ECO:0000250|UniProtKB:P34152, ECO:0000250|UniProtKB:Q05397}. CC -!- INTERACTION: CC O35346; Q6P6T5: Ocln; NbExp=2; IntAct=EBI-6252940, EBI-15348891; CC O35346; O35346: Ptk2; NbExp=12; IntAct=EBI-6252940, EBI-6252940; CC O35346; Q5XI86: Ptrh2; NbExp=3; IntAct=EBI-6252940, EBI-6252926; CC -!- SUBCELLULAR LOCATION: Cell junction, focal adhesion CC {ECO:0000250|UniProtKB:Q00944}. Cell membrane CC {ECO:0000250|UniProtKB:Q00944}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:Q00944}; Cytoplasmic side CC {ECO:0000250|UniProtKB:Q00944}. Cytoplasm, perinuclear region CC {ECO:0000250|UniProtKB:Q00944}. Cytoplasm, cell cortex. Cytoplasm, CC cytoskeleton {ECO:0000269|PubMed:12732587}. Cytoplasm, cytoskeleton, CC microtubule organizing center, centrosome {ECO:0000250}. Nucleus CC {ECO:0000269|PubMed:12732587, ECO:0000269|PubMed:14500712, CC ECO:0000269|PubMed:16373587}. Cytoplasm, cytoskeleton, cilium basal CC body {ECO:0000250|UniProtKB:Q05397}. Cytoplasm CC {ECO:0000269|PubMed:16373587}. Note=Constituent of focal adhesions. CC Detected at microtubules. {ECO:0000250|UniProtKB:P34152}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage; Named isoforms=2; CC Name=1; CC IsoId=O35346-1; Sequence=Displayed; CC Name=2; Synonyms=FRNK; CC IsoId=O35346-2; Sequence=VSP_042172; CC -!- DOMAIN: The first Pro-rich domain interacts with the SH3 domain of CAS CC family members, such as BCAR1 and NEDD9. {ECO:0000250}. CC -!- DOMAIN: The C-terminal region is the site of focal adhesion targeting CC (FAT) sequence which mediates the localization of FAK1 to focal CC adhesions. CC -!- PTM: Phosphorylated on tyrosine residues upon activation, e.g. upon CC integrin signaling. Tyr-397 is the major autophosphorylation site, but CC other kinases can also phosphorylate this residue. Phosphorylation at CC Tyr-397 promotes interaction with SRC and SRC family members, leading CC to phosphorylation at Tyr-576, Tyr-577 and at additional tyrosine CC residues. FGR promotes phosphorylation at Tyr-397 and Tyr-576. FER CC promotes phosphorylation at Tyr-577, Tyr-861 and Tyr-928, even when CC cells are not adherent. Tyr-397, Tyr-576 and Ser-722 are phosphorylated CC only when cells are adherent. Phosphorylation at Tyr-397 is important CC for interaction with BMX, PIK3R1 and SHC1. Phosphorylation at Tyr-928 CC is important for interaction with GRB2. Dephosphorylated by PTPN11; CC PTPN11 is recruited to PTK2 via EPHA2 (tyrosine phosphorylated). CC Microtubule-induced dephosphorylation at Tyr-397 is crucial for the CC induction of focal adhesion disassembly; this dephosphorylation could CC be catalyzed by PTPN11 and regulated by ZFYVE21 (By similarity). CC Phosphorylation on tyrosine residues is enhanced by NTN1 (By CC similarity). {ECO:0000250|UniProtKB:P34152}. CC -!- PTM: Sumoylated; this enhances autophosphorylation. CC {ECO:0000269|PubMed:12732587, ECO:0000269|PubMed:14500712, CC ECO:0000269|PubMed:16373587}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. FAK subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF020777; AAB72203.1; -; mRNA. DR EMBL; U43942; AAA86280.1; -; mRNA. DR RefSeq; NP_037213.1; NM_013081.2. [O35346-1] DR AlphaFoldDB; O35346; -. DR SMR; O35346; -. DR BioGRID; 247643; 7. DR CORUM; O35346; -. DR DIP; DIP-41330N; -. DR IntAct; O35346; 6. DR MINT; O35346; -. DR STRING; 10116.ENSRNOP00000075518; -. DR BindingDB; O35346; -. DR ChEMBL; CHEMBL5773; -. DR iPTMnet; O35346; -. DR PhosphoSitePlus; O35346; -. DR jPOST; O35346; -. DR PaxDb; 10116-ENSRNOP00000011219; -. DR PeptideAtlas; O35346; -. DR GeneID; 25614; -. DR KEGG; rno:25614; -. DR UCSC; RGD:3443; rat. [O35346-1] DR AGR; RGD:3443; -. DR CTD; 5747; -. DR RGD; 3443; Ptk2. DR VEuPathDB; HostDB:ENSRNOG00000007916; -. DR eggNOG; KOG4257; Eukaryota. DR HOGENOM; CLU_002646_0_0_1; -. DR InParanoid; O35346; -. DR OrthoDB; 1614410at2759; -. DR PhylomeDB; O35346; -. DR BRENDA; 2.7.10.2; 5301. DR Reactome; R-RNO-111465; Apoptotic cleavage of cellular proteins. DR Reactome; R-RNO-2029482; Regulation of actin dynamics for phagocytic cup formation. DR Reactome; R-RNO-354192; Integrin signaling. DR Reactome; R-RNO-354194; GRB2:SOS provides linkage to MAPK signaling for Integrins. DR Reactome; R-RNO-372708; p130Cas linkage to MAPK signaling for integrins. DR Reactome; R-RNO-375165; NCAM signaling for neurite out-growth. DR Reactome; R-RNO-3928662; EPHB-mediated forward signaling. DR Reactome; R-RNO-418885; DCC mediated attractive signaling. DR Reactome; R-RNO-4420097; VEGFA-VEGFR2 Pathway. DR Reactome; R-RNO-5663213; RHO GTPases Activate WASPs and WAVEs. DR Reactome; R-RNO-5673001; RAF/MAP kinase cascade. DR Reactome; R-RNO-8874081; MET activates PTK2 signaling. DR Reactome; R-RNO-9009391; Extra-nuclear estrogen signaling. DR PRO; PR:O35346; -. DR Proteomes; UP000002494; Chromosome 7. DR Bgee; ENSRNOG00000007916; Expressed in lung and 19 other cell types or tissues. DR ExpressionAtlas; O35346; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD. DR GO; GO:0016323; C:basolateral plasma membrane; IDA:RGD. DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell. DR GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell. DR GO; GO:0036064; C:ciliary basal body; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0043197; C:dendritic spine; IDA:SynGO. DR GO; GO:0005925; C:focal adhesion; IDA:RGD. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0014704; C:intercalated disc; IDA:RGD. DR GO; GO:0030027; C:lamellipodium; ISO:RGD. DR GO; GO:0016604; C:nuclear body; IDA:RGD. DR GO; GO:0005634; C:nucleus; ISO:RGD. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; ISO:RGD. DR GO; GO:0098794; C:postsynapse; IDA:SynGO. DR GO; GO:0042383; C:sarcolemma; IDA:RGD. DR GO; GO:0001725; C:stress fiber; ISO:RGD. DR GO; GO:0003779; F:actin binding; ISO:RGD. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0005178; F:integrin binding; IPI:RGD. DR GO; GO:0008432; F:JUN kinase binding; ISO:RGD. DR GO; GO:0140677; F:molecular function activator activity; ISO:RGD. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; ISS:UniProtKB. DR GO; GO:0019902; F:phosphatase binding; IDA:RGD. DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IPI:RGD. DR GO; GO:0019901; F:protein kinase binding; ISO:RGD. DR GO; GO:0019903; F:protein phosphatase binding; ISO:RGD. DR GO; GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB. DR GO; GO:0004725; F:protein tyrosine phosphatase activity; ISO:RGD. DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD. DR GO; GO:0042169; F:SH2 domain binding; ISO:RGD. DR GO; GO:0001525; P:angiogenesis; ISO:RGD. DR GO; GO:0007409; P:axonogenesis; ISO:RGD. DR GO; GO:0001568; P:blood vessel development; ISO:RGD. DR GO; GO:0016477; P:cell migration; ISO:RGD. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISO:RGD. DR GO; GO:0021955; P:central nervous system neuron axonogenesis; ISO:RGD. DR GO; GO:0043542; P:endothelial cell migration; ISO:RGD. DR GO; GO:0048013; P:ephrin receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IBA:GO_Central. DR GO; GO:0030198; P:extracellular matrix organization; ISO:RGD. DR GO; GO:0045444; P:fat cell differentiation; IEP:RGD. DR GO; GO:0060396; P:growth hormone receptor signaling pathway; ISO:RGD. DR GO; GO:0007229; P:integrin-mediated signaling pathway; IDA:SynGO. DR GO; GO:0030644; P:intracellular chloride ion homeostasis; IMP:RGD. DR GO; GO:0007254; P:JNK cascade; IMP:RGD. DR GO; GO:0000165; P:MAPK cascade; IMP:RGD. DR GO; GO:0000226; P:microtubule cytoskeleton organization; ISO:RGD. DR GO; GO:2000811; P:negative regulation of anoikis; ISO:RGD. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD. DR GO; GO:0010507; P:negative regulation of autophagy; ISO:RGD. DR GO; GO:0050771; P:negative regulation of axonogenesis; ISO:RGD. DR GO; GO:0030336; P:negative regulation of cell migration; IMP:RGD. DR GO; GO:0022408; P:negative regulation of cell-cell adhesion; ISO:RGD. DR GO; GO:0046621; P:negative regulation of organ growth; ISO:RGD. DR GO; GO:0051964; P:negative regulation of synapse assembly; ISO:RGD. DR GO; GO:0001764; P:neuron migration; ISO:RGD. DR GO; GO:0007097; P:nuclear migration; ISO:RGD. DR GO; GO:0035265; P:organ growth; ISO:RGD. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB. DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; ISO:RGD. DR GO; GO:0045785; P:positive regulation of cell adhesion; IMP:RGD. DR GO; GO:0030307; P:positive regulation of cell growth; IMP:RGD. DR GO; GO:0030335; P:positive regulation of cell migration; IMP:RGD. DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB. DR GO; GO:0010634; P:positive regulation of epithelial cell migration; ISO:RGD. DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISO:RGD. DR GO; GO:0010763; P:positive regulation of fibroblast migration; ISO:RGD. DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IMP:RGD. DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; ISO:RGD. DR GO; GO:0120041; P:positive regulation of macrophage proliferation; ISO:RGD. DR GO; GO:0050766; P:positive regulation of phagocytosis; IMP:RGD. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISS:UniProtKB. DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISS:UniProtKB. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB. DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IMP:RGD. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:RGD. DR GO; GO:0050806; P:positive regulation of synaptic transmission; IMP:RGD. DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; ISS:UniProtKB. DR GO; GO:0090303; P:positive regulation of wound healing; ISO:RGD. DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB. DR GO; GO:0030155; P:regulation of cell adhesion; IBA:GO_Central. DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; ISS:UniProtKB. DR GO; GO:0042127; P:regulation of cell population proliferation; ISS:UniProtKB. DR GO; GO:0008360; P:regulation of cell shape; ISS:UniProtKB. DR GO; GO:0010632; P:regulation of epithelial cell migration; ISO:RGD. DR GO; GO:0051893; P:regulation of focal adhesion assembly; ISO:RGD. DR GO; GO:1905274; P:regulation of modification of postsynaptic actin cytoskeleton; ISO:RGD. DR GO; GO:0045667; P:regulation of osteoblast differentiation; ISS:UniProtKB. DR GO; GO:0001932; P:regulation of protein phosphorylation; ISO:RGD. DR GO; GO:1900024; P:regulation of substrate adhesion-dependent cell spreading; ISO:RGD. DR GO; GO:0046685; P:response to arsenic-containing substance; IEP:RGD. DR GO; GO:0032355; P:response to estradiol; IEP:RGD. DR GO; GO:0009749; P:response to glucose; IEP:RGD. DR GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD. DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD. DR GO; GO:0010033; P:response to organic substance; IEP:RGD. DR GO; GO:0010243; P:response to organonitrogen compound; IEP:RGD. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD. DR GO; GO:0007172; P:signal complex assembly; IEA:InterPro. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:RGD. DR GO; GO:0001570; P:vasculogenesis; ISO:RGD. DR GO; GO:0042311; P:vasodilation; IMP:RGD. DR CDD; cd14473; FERM_B-lobe; 1. DR CDD; cd13190; FERM_C_FAK1; 1. DR CDD; cd05056; PTKc_FAK; 1. DR Gene3D; 1.20.80.10; -; 1. DR Gene3D; 1.20.120.330; Nucleotidyltransferases domain 2; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 1.20.5.540; Single helix bin; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR019749; Band_41_domain. DR InterPro; IPR041390; FADK_N. DR InterPro; IPR049385; FAK1-like_FERM_C. DR InterPro; IPR041784; FAK1/PYK2_FERM_C. DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_sf. DR InterPro; IPR035963; FERM_2. DR InterPro; IPR019748; FERM_central. DR InterPro; IPR000299; FERM_domain. DR InterPro; IPR036137; Focal_adhe_kin_target_dom_sf. DR InterPro; IPR005189; Focal_adhesion_kin_target_dom. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR InterPro; IPR029071; Ubiquitin-like_domsf. DR PANTHER; PTHR46221; FERM AND PDZ DOMAIN-CONTAINING PROTEIN FAMILY MEMBER; 1. DR PANTHER; PTHR46221:SF8; NON-SPECIFIC PROTEIN-TYROSINE KINASE; 1. DR Pfam; PF21477; FERM_C_FAK1; 1. DR Pfam; PF00373; FERM_M; 1. DR Pfam; PF18038; FERM_N_2; 1. DR Pfam; PF03623; Focal_AT; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00295; B41; 1. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF68993; FAT domain of focal adhesion kinase; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF47031; Second domain of FERM; 1. DR SUPFAM; SSF54236; Ubiquitin-like; 1. DR PROSITE; PS00661; FERM_2; 1. DR PROSITE; PS50057; FERM_3; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR Genevisible; O35346; RN. PE 1: Evidence at protein level; KW Acetylation; Alternative promoter usage; Angiogenesis; ATP-binding; KW Cell junction; Cell membrane; Cell projection; Cytoplasm; Cytoskeleton; KW Developmental protein; Isopeptide bond; Kinase; Membrane; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; KW Transferase; Tyrosine-protein kinase; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:Q05397" FT CHAIN 2..1055 FT /note="Focal adhesion kinase 1" FT /id="PRO_0000088079" FT DOMAIN 35..355 FT /note="FERM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084" FT DOMAIN 422..680 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 1..29 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 685..734 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 707..1055 FT /note="Interaction with TGFB1I1" FT /evidence="ECO:0000250" FT REGION 837..923 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 915..1055 FT /note="Interaction with ARHGEF28" FT /evidence="ECO:0000250" FT COMPBIAS 9..25 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 866..880 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 546 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 428..434 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 454 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 500..502 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000250|UniProtKB:Q05397" FT MOD_RES 5 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q05397" FT MOD_RES 13 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q05397" FT MOD_RES 29 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q05397" FT MOD_RES 54 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P34152" FT MOD_RES 397 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:14500712" FT MOD_RES 407 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q05397" FT MOD_RES 570 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q05397" FT MOD_RES 576 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 577 FT /note="Phosphotyrosine; by RET and SRC" FT /evidence="ECO:0000250|UniProtKB:Q05397" FT MOD_RES 580 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q05397" FT MOD_RES 722 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:12732587" FT MOD_RES 732 FT /note="Phosphoserine; by CDK5" FT /evidence="ECO:0000250|UniProtKB:P34152" FT MOD_RES 843 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q05397" FT MOD_RES 861 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q05397" FT MOD_RES 913 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:12732587, FT ECO:0007744|PubMed:22673903" FT MOD_RES 917 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q05397" FT MOD_RES 928 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:22673903" FT CROSSLNK 152 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:14500712" FT VAR_SEQ 1..692 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_042172" FT MUTAGEN 152 FT /note="K->R: Abolishes sumoylation." FT /evidence="ECO:0000269|PubMed:14500712" SQ SEQUENCE 1055 AA; 119717 MW; 3AFB4ED682D14A33 CRC64; MAAAYLDPNL NHTPSSSTKT HLGTGTERSP GAMERVLKVF HYFESSNEPT TWASIIRHGD ATDVRGIIQK IVDSHKVKHV ACYGFRLSHL RSEEVHWLHV DMGVSSVREK YELAHPPEEW KYELRIRYLP KGFLNQFTED KPTLNFFYQQ VKSDYMLEIA DQVDQDIALK LGCLEIRRSY WEMRGNALEK KSNYEVLEKD VGLKRFFPKS LLDSVKAKTL RKLIQQTFRQ FANLNREESI LKFFEILSPV YRFDKECFKC ALGSSWIISV ELAIGPEEGI SYLTDKGCNP THLADFNQVQ TIQYSNSEDK DRKGMLQLKI AGAPEPLTVT APSLTIAENM ADLIDGYCRL VNGATQSFII RPQKEGERAL PSIPKLANNE KQGMRTHAVS VSETDDYAEI IDEEDTYTMP STRDYEIQRE RIELGRCIGE GQFGDVHQGV YLSPENPALA VAIKTCKNCT SDSVREKFLQ EALTMRQFDH PHIVKLIGVI TENPVWIIME LCTLGELRSF LQVRKYSLDL ASLILYAYQL STALAYLESK RFVHRDIAAR NVLVSSNDCV KLGDFGLSRY MEDSTYYKAS KGKLPIKWMA PESINFRRFT SASDVWMFGV CMWEILMHGV KPFQGVKNND VIGRIENGER LPMPPNCPPT LYSLMTKCWA YDPSRRPRFT ELKAQLSTIL EEEKVQQEER MRMESRRQAT VSWDSGGSDE APPKPSRPGY PSPRSSEGFY PSPQHMVQTN HYQISGYPGS HGIPAMAGSI YPGQASLLDQ TELWNHRPQE MSMWQPSVED SAALDLRGMG QVLPPHLMEE RLIRQQQEME EDQRWLEKEE RFLKPDVRLS RGSIDREDGS FQGPTGNQHI YQPVGKPDPA APPKKPPRPG APGHLSNLSS ISSPAESYNE GVKPWRLQPQ EISPPPTANL DRSNDKVYEN VTGLVKAVIE MSSKIQPAPP EEYVPMVKEV GLALRTLLAT VDETIPILPA STHREIEMAQ KLLNSDLGEL ISKMKLAQQY VMTSLQQEYK KQMLTAAHAL AVDAKNLLDV IDQARLKMLG QTRPH //