FAK1_RAT
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 03-AUG-2022, entry version 206.
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. Recruits
CC the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby
CC regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal
CC degradation. Phosphorylates SRC; this increases SRC kinase activity.
CC 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, CASS4 and NEDD9. Interacts
CC with TGFB1I1. Interacts with SRC, GRB2 and GRB7. Interacts with
CC ARHGEF28. Interacts with SHB. Part of a complex composed of THSD1,
CC PTK2/FAK1, TLN1 and VCL (By similarity). Interacts with PXN and TLN1.
CC Interacts with SORBS1. Interacts with STAT1. Interacts with WASL.
CC Interacts with ARHGAP26 and SHC1. Interacts with RB1CC1; this inhibits
CC PTK2/FAK1 activity and activation of downstream signaling pathways.
CC Interacts with ARHGEF7. Interacts with MDM2 (By similarity). Interacts
CC with PIAS1. Interacts with DCC. Interacts with LPXN (via LD motif 3)
CC (By similarity). Interacts with MISP (By similarity). Interacts with
CC EMP2; regulates PTK2 activation and localization (By similarity).
CC Interacts with DSCAM (By similarity). Interacts with AMBRA1 (By
CC similarity). {ECO:0000250|UniProtKB:P34152,
CC 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. Cell membrane;
CC Peripheral membrane protein; Cytoplasmic side. Cytoplasm, perinuclear
CC region. Cytoplasm, cytoskeleton {ECO:0000250}. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome {ECO:0000250}. Nucleus.
CC Cytoplasm, cytoskeleton, cilium basal body
CC {ECO:0000250|UniProtKB:Q05397}. Note=Constituent of focal adhesions.
CC Detected at microtubules (By similarity). {ECO:0000250}.
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 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. 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.ENSRNOP00000011219; -.
DR BindingDB; O35346; -.
DR ChEMBL; CHEMBL5773; -.
DR iPTMnet; O35346; -.
DR PhosphoSitePlus; O35346; -.
DR jPOST; O35346; -.
DR PaxDb; O35346; -.
DR PeptideAtlas; O35346; -.
DR PRIDE; O35346; -.
DR GeneID; 25614; -.
DR KEGG; rno:25614; -.
DR UCSC; RGD:3443; rat. [O35346-1]
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; 43729at2759; -.
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 tissues.
DR ExpressionAtlas; O35346; baseline and differential.
DR Genevisible; O35346; RN.
DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:RGD.
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:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
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:0005730; C:nucleolus; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA: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: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:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0042169; F:SH2 domain binding; ISO:RGD.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; ISO:RGD.
DR GO; GO:0001568; P:blood vessel development; ISO:RGD.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; ISO:RGD.
DR GO; GO:0030644; P:cellular chloride ion homeostasis; IMP: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:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IDA:SynGO.
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:0038083; P:peptidyl-tyrosine autophosphorylation; 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: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:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISS:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; 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:0006468; P:protein phosphorylation; IBA:GO_Central.
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: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:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
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 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 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
