FAK1_CHICK
ID FAK1_CHICK Reviewed; 1053 AA.
AC Q00944;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 2.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=Focal adhesion kinase 1;
DE Short=FADK 1;
DE EC=2.7.10.2;
DE AltName: Full=Focal adhesion kinase-related nonkinase;
DE Short=FRNK;
DE Short=p41/p43FRNK;
DE AltName: Full=Protein-tyrosine kinase 2;
DE AltName: Full=p125FAK;
DE AltName: Full=pp125FAK;
GN Name=PTK2; Synonyms=FAK, FAK1;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 26-1053 (ISOFORM 1).
RC TISSUE=Embryo;
RX PubMed=1594631; DOI=10.1073/pnas.89.11.5192;
RA Schaller M.D., Borgman C.A., Cobb B.S., Vines R.R., Reynolds A.B.,
RA Parsons J.T.;
RT "pp125FAK a structurally distinctive protein-tyrosine kinase associated
RT with focal adhesions.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:5192-5196(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-63 (ISOFORM 1).
RC TISSUE=Embryo;
RX PubMed=8439308; DOI=10.1006/bbrc.1993.1160;
RA Devor B.B., Zhang X., Patel S.K., Polte T.R., Hanks S.K.;
RT "Chicken and mouse focal adhesion kinases are similar in structure at their
RT amino termini.";
RL Biochem. Biophys. Res. Commun. 190:1084-1089(1993).
RN [3]
RP ALTERNATIVE PROMOTER USAGE, IDENTIFICATION OF ISOFORM 2, PHOSPHORYLATION,
RP AND SUBCELLULAR LOCATION.
RX PubMed=8423801; DOI=10.1128/mcb.13.2.785-791.1993;
RA Schaller M.D., Borgman C.A., Parsons J.T.;
RT "Autonomous expression of a noncatalytic domain of the focal adhesion-
RT associated protein tyrosine kinase pp125FAK.";
RL Mol. Cell. Biol. 13:785-791(1993).
RN [4]
RP INTERACTION WITH ARHGAP26.
RX PubMed=8649427; DOI=10.1128/mcb.16.6.3169;
RA Hildebrand J.D., Taylor J.M., Parsons J.T.;
RT "An SH3 domain-containing GTPase-activating protein for Rho and Cdc42
RT associates with focal adhesion kinase.";
RL Mol. Cell. Biol. 16:3169-3178(1996).
RN [5]
RP INTERACTION WITH PIK3R1 AND SRC, AND MUTAGENESIS OF ASP-395.
RX PubMed=10212207; DOI=10.1074/jbc.274.18.12361;
RA Reiske H.R., Kao S.C., Cary L.A., Guan J.L., Lai J.F., Chen H.C.;
RT "Requirement of phosphatidylinositol 3-kinase in focal adhesion kinase-
RT promoted cell migration.";
RL J. Biol. Chem. 274:12361-12366(1999).
RN [6]
RP INTERACTION WITH GRB7.
RX PubMed=12021278; DOI=10.1074/jbc.m203085200;
RA Shen T.L., Han D.C., Guan J.L.;
RT "Association of Grb7 with phosphoinositides and its role in the regulation
RT of cell migration.";
RL J. Biol. Chem. 277:29069-29077(2002).
RN [7]
RP PHOSPHORYLATION AT TYR-397; TYR-576 AND TYR-863.
RX PubMed=12370821; DOI=10.1038/sj.onc.1205904;
RA Leu T.H., Maa M.C.;
RT "Tyr-863 phosphorylation enhances focal adhesion kinase autophosphorylation
RT at Tyr-397.";
RL Oncogene 21:6992-7000(2002).
RN [8]
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 [9]
RP FUNCTION, AND INTERACTION WITH DCC.
RX PubMed=15494734; DOI=10.1038/nn1329;
RA Li W., Lee J., Vikis H.G., Lee S.H., Liu G., Aurandt J., Shen T.L.,
RA Fearon E.R., Guan J.L., Han M., Rao Y., Hong K., Guan K.L.;
RT "Activation of FAK and Src are receptor-proximal events required for netrin
RT signaling.";
RL Nat. Neurosci. 7:1213-1221(2004).
RN [10]
RP FUNCTION.
RX PubMed=15494732; DOI=10.1038/nn1331;
RA Liu G., Beggs H., Jurgensen C., Park H.T., Tang H., Gorski J., Jones K.R.,
RA Reichardt L.F., Wu J., Rao Y.;
RT "Netrin requires focal adhesion kinase and Src family kinases for axon
RT outgrowth and attraction.";
RL Nat. Neurosci. 7:1222-1232(2004).
RN [11]
RP INTERACTION WITH THE ARP2/3 COMPLEX.
RX PubMed=17721515; DOI=10.1038/ncb1626;
RA Serrels B., Serrels A., Brunton V.G., Holt M., McLean G.W., Gray C.H.,
RA Jones G.E., Frame M.C.;
RT "Focal adhesion kinase controls actin assembly via a FERM-mediated
RT interaction with the Arp2/3 complex.";
RL Nat. Cell Biol. 9:1046-1056(2007).
RN [12]
RP FUNCTION.
RX PubMed=20705914; DOI=10.1161/atvbaha.110.212761;
RA Koshman Y.E., Kim T., Chu M., Engman S.J., Iyengar R., Robia S.L.,
RA Samarel A.M.;
RT "FRNK inhibition of focal adhesion kinase-dependent signaling and migration
RT in vascular smooth muscle cells.";
RL Arterioscler. Thromb. Vasc. Biol. 30:2226-2233(2010).
RN [13]
RP FUNCTION.
RX PubMed=21852560; DOI=10.1161/atvbaha.111.235549;
RA Koshman Y.E., Chu M., Engman S.J., Kim T., Iyengar R., Robia S.L.,
RA Samarel A.M.;
RT "Focal adhesion kinase-related nonkinase inhibits vascular smooth muscle
RT cell invasion by focal adhesion targeting, tyrosine 168 phosphorylation,
RT and competition for p130Cas Binding.";
RL Arterioscler. Thromb. Vasc. Biol. 31:2432-2440(2011).
RN [14]
RP PHOSPHORYLATION AT SER-911, AND FUNCTION.
RX PubMed=21937583; DOI=10.1093/cvr/cvr247;
RA Chu M., Iyengar R., Koshman Y.E., Kim T., Russell B., Martin J.L.,
RA Heroux A.L., Robia S.L., Samarel A.M.;
RT "Serine-910 phosphorylation of focal adhesion kinase is critical for
RT sarcomere reorganization in cardiomyocyte hypertrophy.";
RL Cardiovasc. Res. 92:409-419(2011).
RN [15]
RP STRUCTURE BY NMR OF 916-1053.
RX PubMed=11909967; DOI=10.1128/mcb.22.8.2751-2760.2002;
RA Liu G., Guibao C.D., Zheng J.;
RT "Structural insight into the mechanisms of targeting and signaling of focal
RT adhesion kinase.";
RL Mol. Cell. Biol. 22:2751-2760(2002).
RN [16]
RP STRUCTURE BY NMR OF 920-1053 IN COMPLEX WITH PXN, AND INTERACTION WITH PXN.
RX PubMed=14662767; DOI=10.1074/jbc.m309808200;
RA Gao G., Prutzman K.C., King M.L., Scheswohl D.M., DeRose E.F., London R.E.,
RA Schaller M.D., Campbell S.L.;
RT "NMR solution structure of the focal adhesion targeting domain of focal
RT adhesion kinase in complex with a paxillin LD peptide: evidence for a two-
RT site binding model.";
RL J. Biol. Chem. 279:8441-8451(2004).
RN [17]
RP STRUCTURE BY NMR OF 920-1053.
RX PubMed=15130480; DOI=10.1016/j.str.2004.02.028;
RA Prutzman K.C., Gao G., King M.L., Iyer V.V., Mueller G.A., Schaller M.D.,
RA Campbell S.L.;
RT "The focal adhesion targeting domain of focal adhesion kinase contains a
RT hinge region that modulates tyrosine 926 phosphorylation.";
RL Structure 12:881-891(2004).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 31-405.
RX PubMed=16221668; DOI=10.1074/jbc.m509188200;
RA Ceccarelli D.F., Song H.K., Poy F., Schaller M.D., Eck M.J.;
RT "Crystal structure of the FERM domain of focal adhesion kinase.";
RL J. Biol. Chem. 281:252-259(2006).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 411-686 IN COMPLEXES WITH
RP STAUROSPORINE AND ATP ANALOG, ACTIVITY REGULATION, AND PHOSPHORYLATION AT
RP TYR-576 AND TYR-577.
RX PubMed=17574028; DOI=10.1016/j.cell.2007.05.041;
RA Lietha D., Cai X., Ceccarelli D.F., Li Y., Schaller M.D., Eck M.J.;
RT "Structural basis for the autoinhibition of focal adhesion kinase.";
RL Cell 129:1177-1187(2007).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 411-686 IN COMPLEX WITH TAE226.
RX PubMed=19030106; DOI=10.1371/journal.pone.0003800;
RA Lietha D., Eck M.J.;
RT "Crystal structures of the FAK kinase in complex with TAE226 and related
RT bis-anilino pyrimidine inhibitors reveal a helical DFG conformation.";
RL PLoS ONE 3:E3800-E3800(2008).
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, embryonic
CC angiogenesis, normal cardiomyocyte migration and proliferation, and
CC normal heart development. Regulates axon growth and neuronal cell
CC migration, axon branching and synapse formation; required for normal
CC development of the nervous system. Plays a role in osteogenesis and
CC differentiation of osteoblasts. Functions in integrin signal
CC transduction, but also in signaling downstream of numerous growth
CC factor receptors, G-protein coupled receptors (GPCR), ephrin receptors,
CC 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. Regulates
CC P53/TP53 activity and stability. Phosphorylates SRC; this increases SRC
CC kinase activity. Isoform 2 (FRNK) does not contain a kinase domain and
CC inhibits PTK2/FAK1 phosphorylation and signaling.
CC {ECO:0000269|PubMed:15494732, ECO:0000269|PubMed:15494733,
CC ECO:0000269|PubMed:15494734, ECO:0000269|PubMed:20705914,
CC ECO:0000269|PubMed:21852560, ECO:0000269|PubMed:21937583}.
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. Phosphorylation at Tyr-576 and Tyr-577 is required for maximal
CC kinase activity. Inhibited by TAE226. {ECO:0000269|PubMed:17574028}.
CC -!- SUBUNIT: Interacts with ARHGAP26, GRB7, DCC, PIK3R1, PXN and SRC.
CC Interacts with the ARP2/3 complex. {ECO:0000269|PubMed:10212207,
CC ECO:0000269|PubMed:12021278, ECO:0000269|PubMed:14662767,
CC ECO:0000269|PubMed:15494733, ECO:0000269|PubMed:15494734,
CC ECO:0000269|PubMed:17721515, ECO:0000269|PubMed:19030106,
CC ECO:0000269|PubMed:8649427}.
CC -!- INTERACTION:
CC Q00944; Q00944: PTK2; NbExp=3; IntAct=EBI-2896409, EBI-2896409;
CC Q00944; P49024: PXN; NbExp=2; IntAct=EBI-2896409, EBI-2896280;
CC Q00944; P00523: SRC; NbExp=3; IntAct=EBI-2896409, EBI-848039;
CC Q00944; P61157: ACTR3; Xeno; NbExp=5; IntAct=EBI-2896409, EBI-351419;
CC Q00944; P08581: MET; Xeno; NbExp=5; IntAct=EBI-2896409, EBI-1039152;
CC -!- SUBCELLULAR LOCATION: Cell junction, focal adhesion
CC {ECO:0000269|PubMed:8423801}. Cell membrane
CC {ECO:0000269|PubMed:8423801}; Peripheral membrane protein
CC {ECO:0000269|PubMed:8423801}; Cytoplasmic side
CC {ECO:0000269|PubMed:8423801}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:8423801}. Cytoplasm, cytoskeleton {ECO:0000250}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000250}. Nucleus {ECO:0000269|PubMed:8423801}. Cytoplasm,
CC cytoskeleton, cilium basal body {ECO:0000250|UniProtKB:Q05397}.
CC Note=Constituent of focal adhesions. Detected at microtubules (By
CC similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Name=1;
CC IsoId=Q00944-1; Sequence=Displayed;
CC Name=2; Synonyms=FRNK;
CC IsoId=Q00944-2; Sequence=VSP_042173;
CC -!- DOMAIN: The carboxy-terminal region is the site of focal adhesion
CC targeting (FAT) sequence which mediates the localization of FAK1 to
CC focal 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. Isoform 2 is phosphorylated on serine or threonine residues,
CC but apparently not on tyrosine residues. {ECO:0000269|PubMed:12370821,
CC ECO:0000269|PubMed:17574028, ECO:0000269|PubMed:21937583,
CC ECO:0000269|PubMed:8423801}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. FAK subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; M86656; AAA48765.1; -; mRNA.
DR EMBL; L08402; AAA48766.1; -; mRNA.
DR PIR; A45388; A45388.
DR PIR; PC1239; PC1239.
DR RefSeq; NP_990766.1; NM_205435.1. [Q00944-1]
DR PDB; 1KTM; NMR; -; A=916-1053.
DR PDB; 1PV3; NMR; -; A=920-1053.
DR PDB; 1QVX; NMR; -; A=920-1053.
DR PDB; 2AEH; X-ray; 2.53 A; A/B=31-399.
DR PDB; 2AL6; X-ray; 2.35 A; A/B=31-405.
DR PDB; 2J0J; X-ray; 2.80 A; A=31-686.
DR PDB; 2J0K; X-ray; 3.00 A; A/B=31-686.
DR PDB; 2J0L; X-ray; 2.30 A; A=411-686.
DR PDB; 2J0M; X-ray; 2.80 A; A=31-399, B=411-686.
DR PDB; 2JKK; X-ray; 2.00 A; A=411-686.
DR PDB; 2JKM; X-ray; 2.31 A; A=411-686.
DR PDB; 2JKO; X-ray; 1.65 A; A=411-686.
DR PDB; 2JKQ; X-ray; 2.60 A; A=411-686.
DR PDB; 2L6F; NMR; -; A=916-1053.
DR PDB; 2L6G; NMR; -; A=916-1053.
DR PDB; 2L6H; NMR; -; A=916-1053.
DR PDB; 3ZDT; X-ray; 3.15 A; A/B=31-405.
DR PDB; 4BRX; X-ray; 2.05 A; A=411-686.
DR PDB; 4C7T; X-ray; 2.05 A; A=411-686.
DR PDB; 4CYE; X-ray; 3.20 A; A/B=31-405.
DR PDB; 4D4R; X-ray; 1.55 A; A/B=411-686.
DR PDB; 4D4S; X-ray; 2.00 A; A/B=411-686.
DR PDB; 4D4V; X-ray; 2.10 A; A/B=411-686.
DR PDB; 4D4Y; X-ray; 1.80 A; A/B=411-686.
DR PDB; 4D55; X-ray; 2.30 A; A=411-686.
DR PDB; 4D58; X-ray; 1.95 A; A/B=411-686.
DR PDB; 4D5H; X-ray; 1.75 A; A/B=411-686.
DR PDB; 4D5K; X-ray; 1.75 A; A/B=411-686.
DR PDB; 6CB0; X-ray; 1.97 A; A/B=31-405.
DR PDB; 6GCR; X-ray; 2.30 A; A=411-686.
DR PDB; 6GCW; X-ray; 2.00 A; A/B=411-686.
DR PDB; 6GCX; X-ray; 1.55 A; A=411-686.
DR PDB; 6TY3; EM; 6.32 A; A/B=30-686.
DR PDB; 6TY4; EM; 5.96 A; A/B=30-686.
DR PDBsum; 1KTM; -.
DR PDBsum; 1PV3; -.
DR PDBsum; 1QVX; -.
DR PDBsum; 2AEH; -.
DR PDBsum; 2AL6; -.
DR PDBsum; 2J0J; -.
DR PDBsum; 2J0K; -.
DR PDBsum; 2J0L; -.
DR PDBsum; 2J0M; -.
DR PDBsum; 2JKK; -.
DR PDBsum; 2JKM; -.
DR PDBsum; 2JKO; -.
DR PDBsum; 2JKQ; -.
DR PDBsum; 2L6F; -.
DR PDBsum; 2L6G; -.
DR PDBsum; 2L6H; -.
DR PDBsum; 3ZDT; -.
DR PDBsum; 4BRX; -.
DR PDBsum; 4C7T; -.
DR PDBsum; 4CYE; -.
DR PDBsum; 4D4R; -.
DR PDBsum; 4D4S; -.
DR PDBsum; 4D4V; -.
DR PDBsum; 4D4Y; -.
DR PDBsum; 4D55; -.
DR PDBsum; 4D58; -.
DR PDBsum; 4D5H; -.
DR PDBsum; 4D5K; -.
DR PDBsum; 6CB0; -.
DR PDBsum; 6GCR; -.
DR PDBsum; 6GCW; -.
DR PDBsum; 6GCX; -.
DR PDBsum; 6TY3; -.
DR PDBsum; 6TY4; -.
DR AlphaFoldDB; Q00944; -.
DR BMRB; Q00944; -.
DR SMR; Q00944; -.
DR BioGRID; 676665; 2.
DR ELM; Q00944; -.
DR IntAct; Q00944; 11.
DR STRING; 9031.ENSGALP00000026014; -.
DR iPTMnet; Q00944; -.
DR PaxDb; Q00944; -.
DR PRIDE; Q00944; -.
DR Ensembl; ENSGALT00000072414; ENSGALP00000044406; ENSGALG00000031741. [Q00944-1]
DR GeneID; 396416; -.
DR KEGG; gga:396416; -.
DR CTD; 5747; -.
DR VEuPathDB; HostDB:geneid_396416; -.
DR eggNOG; KOG4257; Eukaryota.
DR GeneTree; ENSGT00940000155113; -.
DR HOGENOM; CLU_002646_0_0_1; -.
DR InParanoid; Q00944; -.
DR OMA; ELECMFK; -.
DR OrthoDB; 43729at2759; -.
DR PhylomeDB; Q00944; -.
DR BRENDA; 2.7.10.2; 1306.
DR Reactome; R-GGA-111465; Apoptotic cleavage of cellular proteins.
DR Reactome; R-GGA-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-GGA-354192; Integrin signaling.
DR Reactome; R-GGA-354194; GRB2:SOS provides linkage to MAPK signaling for Integrins.
DR Reactome; R-GGA-372708; p130Cas linkage to MAPK signaling for integrins.
DR Reactome; R-GGA-3928662; EPHB-mediated forward signaling.
DR Reactome; R-GGA-418885; DCC mediated attractive signaling.
DR Reactome; R-GGA-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-GGA-5663213; RHO GTPases Activate WASPs and WAVEs.
DR Reactome; R-GGA-8874081; MET activates PTK2 signaling.
DR Reactome; R-GGA-9009391; Extra-nuclear estrogen signaling.
DR EvolutionaryTrace; Q00944; -.
DR PRO; PR:Q00944; -.
DR Proteomes; UP000000539; Chromosome 2.
DR Bgee; ENSGALG00000031741; Expressed in ovary and 12 other tissues.
DR ExpressionAtlas; Q00944; baseline and differential.
DR GO; GO:0036064; C:ciliary basal body; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:AgBase.
DR GO; GO:0043197; C:dendritic spine; IBA:GO_Central.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005925; C:focal adhesion; IDA:AgBase.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0042383; C:sarcolemma; IDA:AgBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; IMP:AgBase.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005178; F:integrin binding; IPI:AgBase.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0002020; F:protease binding; IPI:AgBase.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:AgBase.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0007015; P:actin filament organization; IMP:AgBase.
DR GO; GO:0001525; P:angiogenesis; IBA:GO_Central.
DR GO; GO:0060055; P:angiogenesis involved in wound healing; IMP:AgBase.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:2000811; P:negative regulation of anoikis; IMP:AgBase.
DR GO; GO:0010812; P:negative regulation of cell-substrate adhesion; IMP:AgBase.
DR GO; GO:0031953; P:negative regulation of protein autophosphorylation; IMP:AgBase.
DR GO; GO:0030335; P:positive regulation of cell migration; IBA:GO_Central.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:AgBase.
DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; IMP:AgBase.
DR GO; GO:0032092; P:positive regulation of protein binding; IMP:AgBase.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; IMP:AgBase.
DR GO; GO:1904237; P:positive regulation of substrate-dependent cell migration, cell attachment to substrate; IMP:AgBase.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:AgBase.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0140650; P:radial glia-guided pyramidal neuron migration; IMP:GO_Central.
DR GO; GO:0030155; P:regulation of cell adhesion; IBA:GO_Central.
DR GO; GO:0035994; P:response to muscle stretch; IDA:AgBase.
DR GO; GO:0009268; P:response to pH; IMP:AgBase.
DR GO; GO:0007172; P:signal complex assembly; IEA:InterPro.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0044319; P:wound healing, spreading of cells; IMP:AgBase.
DR CDD; cd14473; FERM_B-lobe; 1.
DR CDD; cd13190; FERM_C_FAK1; 1.
DR DisProt; DP02120; -.
DR Gene3D; 1.20.80.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR041390; FADK_N.
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 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; SSF47031; SSF47031; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF68993; SSF68993; 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.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative promoter usage; Angiogenesis; ATP-binding;
KW Cell junction; Cell membrane; Cell projection; Cytoplasm; Cytoskeleton;
KW Developmental protein; Kinase; Membrane; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Transferase; Tyrosine-protein kinase.
FT CHAIN 1..1053
FT /note="Focal adhesion kinase 1"
FT /id="PRO_0000088076"
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..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 686..741
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 843..892
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 9..23
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 727..741
FT /note="Polar 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:0000305"
FT BINDING 454
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT BINDING 500..502
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT MOD_RES 397
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:12370821"
FT MOD_RES 407
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250"
FT MOD_RES 576
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000269|PubMed:12370821,
FT ECO:0000269|PubMed:17574028"
FT MOD_RES 577
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250"
FT MOD_RES 863
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:12370821"
FT MOD_RES 911
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21937583"
FT MOD_RES 926
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..692
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_042173"
FT MUTAGEN 395
FT /note="D->A: Abolishes interaction with PIK3R1."
FT /evidence="ECO:0000269|PubMed:10212207"
FT STRAND 36..40
FT /evidence="ECO:0007829|PDB:6CB0"
FT HELIX 49..51
FT /evidence="ECO:0007829|PDB:6CB0"
FT STRAND 53..58
FT /evidence="ECO:0007829|PDB:6CB0"
FT HELIX 64..74
FT /evidence="ECO:0007829|PDB:6CB0"
FT HELIX 80..82
FT /evidence="ECO:0007829|PDB:6CB0"
FT STRAND 83..89
FT /evidence="ECO:0007829|PDB:6CB0"
FT STRAND 95..98
FT /evidence="ECO:0007829|PDB:6CB0"
FT STRAND 100..103
FT /evidence="ECO:0007829|PDB:2J0M"
FT HELIX 104..114
FT /evidence="ECO:0007829|PDB:6CB0"
FT HELIX 117..119
FT /evidence="ECO:0007829|PDB:6CB0"
FT STRAND 120..126
FT /evidence="ECO:0007829|PDB:6CB0"
FT HELIX 133..138
FT /evidence="ECO:0007829|PDB:6CB0"
FT HELIX 141..158
FT /evidence="ECO:0007829|PDB:6CB0"
FT TURN 159..162
FT /evidence="ECO:0007829|PDB:6CB0"
FT HELIX 165..179
FT /evidence="ECO:0007829|PDB:6CB0"
FT TURN 180..182
FT /evidence="ECO:0007829|PDB:6CB0"
FT HELIX 187..189
FT /evidence="ECO:0007829|PDB:6CB0"
FT HELIX 191..199
FT /evidence="ECO:0007829|PDB:6CB0"
FT TURN 200..202
FT /evidence="ECO:0007829|PDB:2J0J"
FT HELIX 203..205
FT /evidence="ECO:0007829|PDB:6CB0"
FT HELIX 209..213
FT /evidence="ECO:0007829|PDB:6CB0"
FT HELIX 217..229
FT /evidence="ECO:0007829|PDB:6CB0"
FT TURN 230..233
FT /evidence="ECO:0007829|PDB:6CB0"
FT HELIX 236..247
FT /evidence="ECO:0007829|PDB:6CB0"
FT HELIX 248..250
FT /evidence="ECO:0007829|PDB:6CB0"
FT STRAND 256..262
FT /evidence="ECO:0007829|PDB:6CB0"
FT STRAND 264..266
FT /evidence="ECO:0007829|PDB:6CB0"
FT STRAND 268..275
FT /evidence="ECO:0007829|PDB:6CB0"
FT TURN 276..278
FT /evidence="ECO:0007829|PDB:6CB0"
FT STRAND 279..282
FT /evidence="ECO:0007829|PDB:6CB0"
FT STRAND 285..288
FT /evidence="ECO:0007829|PDB:2AEH"
FT STRAND 291..294
FT /evidence="ECO:0007829|PDB:6CB0"
FT HELIX 296..298
FT /evidence="ECO:0007829|PDB:6CB0"
FT STRAND 299..306
FT /evidence="ECO:0007829|PDB:6CB0"
FT STRAND 309..311
FT /evidence="ECO:0007829|PDB:6CB0"
FT STRAND 314..320
FT /evidence="ECO:0007829|PDB:6CB0"
FT STRAND 327..333
FT /evidence="ECO:0007829|PDB:6CB0"
FT HELIX 334..352
FT /evidence="ECO:0007829|PDB:6CB0"
FT STRAND 398..400
FT /evidence="ECO:0007829|PDB:6CB0"
FT HELIX 412..414
FT /evidence="ECO:0007829|PDB:2J0J"
FT HELIX 419..421
FT /evidence="ECO:0007829|PDB:4D4R"
FT STRAND 422..431
FT /evidence="ECO:0007829|PDB:4D4R"
FT STRAND 434..441
FT /evidence="ECO:0007829|PDB:4D4R"
FT STRAND 444..446
FT /evidence="ECO:0007829|PDB:6GCX"
FT STRAND 449..455
FT /evidence="ECO:0007829|PDB:4D4R"
FT TURN 457..460
FT /evidence="ECO:0007829|PDB:4D4R"
FT HELIX 462..475
FT /evidence="ECO:0007829|PDB:4D4R"
FT STRAND 486..490
FT /evidence="ECO:0007829|PDB:4D4R"
FT STRAND 492..494
FT /evidence="ECO:0007829|PDB:4D4R"
FT STRAND 496..500
FT /evidence="ECO:0007829|PDB:4D4R"
FT HELIX 507..514
FT /evidence="ECO:0007829|PDB:4D4R"
FT TURN 515..517
FT /evidence="ECO:0007829|PDB:4D4R"
FT HELIX 520..539
FT /evidence="ECO:0007829|PDB:4D4R"
FT HELIX 549..551
FT /evidence="ECO:0007829|PDB:4D4R"
FT STRAND 552..556
FT /evidence="ECO:0007829|PDB:4D4R"
FT STRAND 559..562
FT /evidence="ECO:0007829|PDB:4D4R"
FT HELIX 565..568
FT /evidence="ECO:0007829|PDB:6GCX"
FT HELIX 572..575
FT /evidence="ECO:0007829|PDB:4D4R"
FT HELIX 577..579
FT /evidence="ECO:0007829|PDB:4D4R"
FT HELIX 586..588
FT /evidence="ECO:0007829|PDB:4D4R"
FT HELIX 591..596
FT /evidence="ECO:0007829|PDB:4D4R"
FT HELIX 601..616
FT /evidence="ECO:0007829|PDB:4D4R"
FT TURN 617..619
FT /evidence="ECO:0007829|PDB:4D4R"
FT TURN 622..625
FT /evidence="ECO:0007829|PDB:4D4R"
FT HELIX 628..630
FT /evidence="ECO:0007829|PDB:4D4R"
FT HELIX 631..636
FT /evidence="ECO:0007829|PDB:4D4R"
FT HELIX 649..658
FT /evidence="ECO:0007829|PDB:4D4R"
FT HELIX 663..665
FT /evidence="ECO:0007829|PDB:4D4R"
FT HELIX 669..684
FT /evidence="ECO:0007829|PDB:4D4R"
FT TURN 919..921
FT /evidence="ECO:0007829|PDB:1KTM"
FT HELIX 922..941
FT /evidence="ECO:0007829|PDB:1KTM"
FT TURN 942..945
FT /evidence="ECO:0007829|PDB:1KTM"
FT HELIX 948..975
FT /evidence="ECO:0007829|PDB:1KTM"
FT TURN 978..980
FT /evidence="ECO:0007829|PDB:1PV3"
FT HELIX 982..1005
FT /evidence="ECO:0007829|PDB:1KTM"
FT STRAND 1008..1012
FT /evidence="ECO:0007829|PDB:1KTM"
FT HELIX 1014..1047
FT /evidence="ECO:0007829|PDB:1KTM"
SQ SEQUENCE 1053 AA; 119207 MW; 8051154219B953B9 CRC64;
MAAAYLDPNL NHTPSSSAKT HLGTGMERSP GAMERVLKVF HYFENSSEPT TWASIIRHGD
ATDVRGIIQK IVDCHKVKNV ACYGLRLSHL QSEEVHWLHL DMGVSNVREK FELAHPPEEW
KYELRIRYLP KGFLNQFTED KPTLNFFYQQ VKNDYMLEIA DQVDQEIALK LGCLEIRRSY
GEMRGNALEK KSNYEVLEKD VGLRRFFPKS LLDSVKAKTL RKLIQQTFRQ FANLNREESI
LKFFEILSPV YRFDKECFKC ALGSSWIISV ELAIGPEEGI SYLTDKGANP THLADFNQVQ
TIQYSNSEDK DRKGMLQLKI AGAPEPLTVT APSLTIAENM ADLIDGYCRL VNGATQSFII
RPQKEGERAL PSIPKLANNE KQGVRSHTVS VSETDDYAEI IDEEDTYTMP STRDYEIQRE
RIELGRCIGE GQFGDVHQGI YMSPENPAMA VAIKTCKNCT SDSVREKFLQ EALTMRQFDH
PHIVKLIGVI TENPVWIIME LCTLGELRSF LQVRKFSLDL ASLILYAYQL STALAYLESK
RFVHRDIAAR NVLVSATDCV KLGDFGLSRY MEDSTYYKAS KGKLPIKWMA PESINFRRFT
SASDVWMFGV CMWEILMHGV KPFQGVKNND VIGRIENGER LPMPPNCPPT LYSLMTKCWA
YDPSRRPRFT ELKAQLSTIL EEEKLQQEER MRMESRRQVT VSWDSGGSDE APPKPSRPGY
PSPRSSEGFY PSPQHMVQPN HYQVSGYSGS HGIPAMAGSI YPGQASLLDQ TDSWNHRPQE
VSAWQPNMED SGTLDVRGMG QVLPTHLMEE RLIRQQQEME EDQRWLEKEE RFLVMKPDVR
LSRGSIERED GGLQGPAGNQ HIYQPVGKPD HAAPPKKPPR PGAPHLGSLA SLNSPVDSYN
EGVKIKPQEI SPPPTANLDR SNDKVYENVT GLVKAVIEMS SKIQPAPPEE YVPMVKEVGL
ALRTLLATVD ESLPVLPAST HREIEMAQKL LNSDLAELIN KMKLAQQYVM TSLQQEYKKQ
MLTAAHALAV DAKNLLDVID QARLKMISQS RPH
