FAK2_RAT
ID FAK2_RAT Reviewed; 1009 AA.
AC P70600; O88489; Q3T1H4; Q63201;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Protein-tyrosine kinase 2-beta;
DE EC=2.7.10.2;
DE AltName: Full=Calcium-dependent tyrosine kinase;
DE Short=CADTK;
DE AltName: Full=Calcium-regulated non-receptor proline-rich tyrosine kinase;
DE AltName: Full=Cell adhesion kinase beta;
DE Short=CAK-beta;
DE Short=CAKB;
DE AltName: Full=Focal adhesion kinase 2;
DE Short=FADK 2;
DE AltName: Full=Proline-rich tyrosine kinase 2;
GN Name=Ptk2b; Synonyms=Fak2, Pyk2;
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), AND PROTEIN SEQUENCE OF 310-334;
RP 553-572; 672-687 AND 989-998.
RC TISSUE=Liver epithelium;
RX PubMed=8939945; DOI=10.1074/jbc.271.47.29993;
RA Yu H., Li X., Marchetto G.S., Dy R., Hunter D., Calvo B., Dawson T.L.,
RA Wilm M., Anderegg R.J., Graves L.M., Earp H.S.;
RT "Activation of a novel calcium-dependent protein-tyrosine kinase.
RT Correlation with c-Jun N-terminal kinase but not mitogen-activated protein
RT kinase activation.";
RL J. Biol. Chem. 271:29993-29998(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=7673154; DOI=10.1074/jbc.270.36.21206;
RA Sasaki H., Nagura K., Ishino M., Tobioka H., Kotani K., Sasaki T.;
RT "Cloning and characterization of cell adhesion kinase beta, a novel
RT protein-tyrosine kinase of the focal adhesion kinase subfamily.";
RL J. Biol. Chem. 270:21206-21219(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), SUBCELLULAR LOCATION, AND
RP DOMAIN FAT.
RC TISSUE=Hippocampus;
RX PubMed=9645946; DOI=10.1242/jcs.111.14.1981;
RA Xiong W.-C., Macklem M., Parsons J.T.;
RT "Expression and characterization of splice variants of PYK2, a focal
RT adhesion kinase-related protein.";
RL J. Cell Sci. 111:1981-1991(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, AND PHOSPHORYLATION.
RX PubMed=7544443; DOI=10.1038/376737a0;
RA Lev S., Moreno H., Martinez R., Canoll P., Peles E., Musacchio J.M.,
RA Plowman G.D., Rudy B., Schlessinger J.;
RT "Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion
RT channel and MAP kinase functions.";
RL Nature 376:737-745(1995).
RN [6]
RP FUNCTION IN G-PROTEIN COUPLED RECEPTOR SIGNALING AND PHOSPHORYLATION OF
RP SRC, INTERACTION WITH SRC, AND PHOSPHORYLATION.
RX PubMed=8849729; DOI=10.1038/383547a0;
RA Dikic I., Tokiwa G., Lev S., Courtneidge S.A., Schlessinger J.;
RT "A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP
RT kinase activation.";
RL Nature 383:547-550(1996).
RN [7]
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 [8]
RP FUNCTION IN ANGIOGENESIS; CELL MIGRATION; CELL SPREADING AND REORGANIZATION
RP OF THE ACTIN CYTOSKELETON, AND TISSUE SPECIFICITY.
RX PubMed=11739395; DOI=10.1074/jbc.m110673200;
RA Tang H., Hao Q., Fitzgerald T., Sasaki T., Landon E.J., Inagami T.;
RT "Pyk2/CAKbeta tyrosine kinase activity-mediated angiogenesis of pulmonary
RT vascular endothelial cells.";
RL J. Biol. Chem. 277:5441-5447(2002).
RN [9]
RP INTERACTION WITH KCNA2.
RX PubMed=11739373; DOI=10.1074/jbc.m104726200;
RA Byron K.L., Lucchesi P.A.;
RT "Signal transduction of physiological concentrations of vasopressin in A7r5
RT vascular smooth muscle cells. A role for PYK2 and tyrosine phosphorylation
RT of K+ channels in the stimulation of Ca2+ spiking.";
RL J. Biol. Chem. 277:7298-7307(2002).
RN [10]
RP FUNCTION IN SRC-MEDIATED PHOSPHORYLATION OF NMDA RECEPTORS AND REGULATION
RP OF NMDA RECEPTOR CHANNEL ACTIVITY.
RX PubMed=12097497; DOI=10.1523/jneurosci.22-13-05452.2002;
RA Heidinger V., Manzerra P., Wang X.Q., Strasser U., Yu S.P., Choi D.W.,
RA Behrens M.M.;
RT "Metabotropic glutamate receptor 1-induced upregulation of NMDA receptor
RT current: mediation through the Pyk2/Src-family kinase pathway in cortical
RT neurons.";
RL J. Neurosci. 22:5452-5461(2002).
RN [11]
RP FUNCTION, PHOSPHORYLATION AT TYR-402 AND TYR-580, AND CATALYTIC ACTIVITY.
RX PubMed=16574377; DOI=10.1016/j.cellsig.2006.02.013;
RA Wu S.S., Jacamo R.O., Vong S.K., Rozengurt E.;
RT "Differential regulation of Pyk2 phosphorylation at Tyr-402 and Tyr-580 in
RT intestinal epithelial cells: roles of calcium, Src, Rho kinase, and the
RT cytoskeleton.";
RL Cell. Signal. 18:1932-1940(2006).
RN [12]
RP AUTOPHOSPHORYLATION, AND INTERACTION WITH DLG4.
RX PubMed=20071509; DOI=10.1523/jneurosci.4992-08.2010;
RA Bartos J.A., Ulrich J.D., Li H., Beazely M.A., Chen Y., Macdonald J.F.,
RA Hell J.W.;
RT "Postsynaptic clustering and activation of Pyk2 by PSD-95.";
RL J. Neurosci. 30:449-463(2010).
RN [13]
RP FUNCTION.
RX PubMed=21451101; DOI=10.1152/ajpcell.00315.2010;
RA Perez J., Torres R.A., Rocic P., Cismowski M.J., Weber D.S.,
RA Darley-Usmar V.M., Lucchesi P.A.;
RT "PYK2 signaling is required for PDGF-dependent vascular smooth muscle cell
RT proliferation.";
RL Am. J. Physiol. 301:C242-C251(2011).
RN [14]
RP PHOSPHORYLATION AT TYR-402; TYR-579 AND TYR-580, AND SUBUNIT.
RX PubMed=20849950; DOI=10.1016/j.cellsig.2010.09.015;
RA Riggs D., Yang Z., Kloss J., Loftus J.C.;
RT "The Pyk2 FERM regulates Pyk2 complex formation and phosphorylation.";
RL Cell. Signal. 23:288-296(2011).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-375, AND IDENTIFICATION BY
RP 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 regulates
CC reorganization of the actin cytoskeleton, cell polarization, cell
CC migration, adhesion, spreading and bone remodeling. Plays a role in the
CC regulation of the humoral immune response, and is required for normal
CC levels of marginal B-cells in the spleen and normal migration of
CC splenic B-cells. Required for normal macrophage polarization and
CC migration towards sites of inflammation. Regulates cytoskeleton
CC rearrangement and cell spreading in T-cells, and contributes to the
CC regulation of T-cell responses. Promotes osteoclastic bone resorption;
CC this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and
CC activity of osteoprogenitor cells. Functions in signaling downstream of
CC integrin and collagen receptors, immune receptors, G-protein coupled
CC receptors (GPCR), cytokine, chemokine and growth factor receptors, and
CC mediates responses to cellular stress. 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 of the AKT1 signaling cascade.
CC Promotes activation of NOS3. Regulates production of the cellular
CC messenger cGMP. Promotes activation of the MAP kinase signaling
CC cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1.
CC Promotes activation of Rho family GTPases, such as RHOA and RAC1.
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. Acts as a scaffold, binding to both PDPK1 and
CC SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373',
CC and 'Tyr-376' (By similarity). Promotes phosphorylation of NMDA
CC receptors by SRC family members, and thereby contributes to the
CC regulation of NMDA receptor ion channel activity and intracellular
CC Ca(2+) levels. May also regulate potassium ion transport by
CC phosphorylation of potassium channel subunits. Phosphorylates SRC; this
CC increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and
CC SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires
CC both SRC and PTK2/PYK2 (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:7544443}.
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 ECO:0000269|PubMed:16574377};
CC -!- ACTIVITY REGULATION: Activated in response to stimuli that lead to
CC increased intracellular Ca(2+) levels; this activation is indirect and
CC may be mediated by calcium-mediated production of reactive oxygen
CC species (ROS). Activated by autophosphorylation at Tyr-402; this
CC creates a binding site for SRC family kinases and leads to
CC phosphorylation at additional tyrosine residues. Phosphorylation at
CC Tyr-402, Tyr-579 and Tyr-580 is required for optimal kinase activity
CC (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer, or homooligomer. Interacts with NPHP1, ASAP1,
CC ASAP2, ARHGAP26, SKAP2 and TGFB1I1. The Tyr-402 phosphorylated form
CC interacts with SRC (via SH2 domain) and SRC family members. Forms a
CC signaling complex with EPHA1, LCK and phosphatidylinositol 3-kinase;
CC upon activation by EFNA1. Interacts with GRB2 (via SH2 domain).
CC Interacts with P53/TP53 and MDM2. Interacts with MYLK. Interacts with
CC BCAR1. Interacts with RB1CC1. Interacts with RHOU. Interacts with VAV1.
CC Interacts with PDPK1. Interacts with LPXN and PTPN12 (By similarity).
CC Interacts with SIRPA and SH2D3C. Interacts (hypophosphorylated) with
CC PXN. Interacts with ARHGAP10. Interacts with KCNA2 (PubMed:11739373).
CC {ECO:0000250, ECO:0000269|PubMed:11739373, ECO:0000269|PubMed:20071509,
CC ECO:0000269|PubMed:20849950, ECO:0000269|PubMed:8849729,
CC ECO:0000269|PubMed:9422762}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9645946}.
CC Cytoplasm, perinuclear region {ECO:0000250}. Cell membrane
CC {ECO:0000269|PubMed:9645946}; Peripheral membrane protein
CC {ECO:0000269|PubMed:9645946}; Cytoplasmic side
CC {ECO:0000269|PubMed:9645946}. Cell projection, lamellipodium
CC {ECO:0000250}. Cytoplasm, cell cortex {ECO:0000250}. Nucleus
CC {ECO:0000250}. Note=Colocalizes with integrins at the cell periphery.
CC Interaction with NPHP1 induces the membrane-association of the kinase.
CC Colocalizes with PXN at the microtubule-organizing center. The tyrosine
CC phosphorylated form is detected at cell-cell contacts (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell junction, focal adhesion.
CC Note=Localizes to focal adhesions, but not isoform 1 and isoform 3.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P70600-1; Sequence=Displayed;
CC Name=2; Synonyms=PRNK;
CC IsoId=P70600-2; Sequence=VSP_004982, VSP_004983;
CC Name=3; Synonyms=PYK2s;
CC IsoId=P70600-3; Sequence=VSP_004984;
CC -!- TISSUE SPECIFICITY: Highly expressed in pulmonary vein endothelial
CC cells, lung and brain (at protein level). Isoform 1 is expressed at
CC high levels in the brain (hippocampus, cerebral cortex and olfactory
CC bulb) and poorly in the spleen and other tissues, whereas isoforms 2
CC and 3 are expressed in the spleen and brain (highest in cerebellum).
CC {ECO:0000269|PubMed:11739395}.
CC -!- PTM: Phosphorylated on tyrosine residues in response to various stimuli
CC that elevate the intracellular calcium concentration; this activation
CC is indirect and may be mediated by production of reactive oxygen
CC species (ROS). Tyr-402 is the major autophosphorylation site, but other
CC kinases can also phosphorylate Tyr-402. Autophosphorylation occurs in
CC trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine
CC residues on the other subunit. Phosphorylation at Tyr-402 promotes
CC interaction with SRC and SRC family members, leading to phosphorylation
CC at Tyr-579; Tyr-580 and Tyr-881. Phosphorylation at Tyr-881 is
CC important for interaction with GRB2. Phosphorylated on tyrosine
CC residues upon activation of FGR and PKC. Recruitment by NPHP1 to cell
CC matrix adhesions initiates Tyr-402 phosphorylation. In monocytes,
CC adherence to substrata is required for tyrosine phosphorylation and
CC kinase activation. Angiotensin II, thapsigargin and L-alpha-
CC lysophosphatidic acid (LPA) also induce autophosphorylation and
CC increase kinase activity. Phosphorylation by MYLK promotes ITGB2
CC activation and is thus essential to trigger neutrophil transmigration
CC during lung injury. Dephosphorylated by PTPN12 (By similarity).
CC {ECO:0000250}.
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; U69109; AAC52895.1; -; mRNA.
DR EMBL; D45854; BAA08290.1; -; mRNA.
DR EMBL; AF063890; AAC28340.1; -; mRNA.
DR EMBL; BC101921; AAI01922.1; -; mRNA.
DR PIR; A57434; A57434.
DR RefSeq; NP_059014.2; NM_017318.2. [P70600-1]
DR RefSeq; XP_006252205.1; XM_006252143.3. [P70600-1]
DR RefSeq; XP_006252206.1; XM_006252144.3. [P70600-1]
DR RefSeq; XP_006252207.1; XM_006252145.3. [P70600-3]
DR RefSeq; XP_008768995.1; XM_008770773.2. [P70600-1]
DR RefSeq; XP_008768996.1; XM_008770774.2. [P70600-1]
DR AlphaFoldDB; P70600; -.
DR SMR; P70600; -.
DR BioGRID; 248405; 9.
DR CORUM; P70600; -.
DR IntAct; P70600; 1.
DR MINT; P70600; -.
DR STRING; 10116.ENSRNOP00000031615; -.
DR ChEMBL; CHEMBL1075222; -.
DR iPTMnet; P70600; -.
DR PhosphoSitePlus; P70600; -.
DR jPOST; P70600; -.
DR PaxDb; P70600; -.
DR PRIDE; P70600; -.
DR Ensembl; ENSRNOT00000030007; ENSRNOP00000031615; ENSRNOG00000027839. [P70600-1]
DR Ensembl; ENSRNOT00000030036; ENSRNOP00000036813; ENSRNOG00000027839. [P70600-3]
DR GeneID; 50646; -.
DR KEGG; rno:50646; -.
DR UCSC; RGD:628758; rat. [P70600-1]
DR CTD; 2185; -.
DR RGD; 628758; Ptk2b.
DR eggNOG; KOG4257; Eukaryota.
DR GeneTree; ENSGT00940000157269; -.
DR HOGENOM; CLU_002646_0_1_1; -.
DR InParanoid; P70600; -.
DR OMA; IMELYSY; -.
DR OrthoDB; 43729at2759; -.
DR PhylomeDB; P70600; -.
DR TreeFam; TF316643; -.
DR BRENDA; 2.7.10.2; 5301.
DR Reactome; R-RNO-391160; Signal regulatory protein family interactions.
DR Reactome; R-RNO-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-RNO-9013420; RHOU GTPase cycle.
DR Reactome; R-RNO-9020558; Interleukin-2 signaling.
DR PRO; PR:P70600; -.
DR Proteomes; UP000002494; Chromosome 15.
DR Bgee; ENSRNOG00000027839; Expressed in frontal cortex and 19 other tissues.
DR Genevisible; P70600; RN.
DR GO; GO:0097440; C:apical dendrite; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0044297; C:cell body; IDA:UniProtKB.
DR GO; GO:0005938; C:cell cortex; IDA:RGD.
DR GO; GO:0042995; C:cell projection; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:InterPro.
DR GO; GO:0030425; C:dendrite; IDA:Alzheimers_University_of_Toronto.
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:0030426; C:growth cone; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0017146; C:NMDA selective glutamate receptor complex; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0098794; C:postsynapse; IDA:SynGO.
DR GO; GO:0014069; C:postsynaptic density; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0043423; F:3-phosphoinositide-dependent protein kinase binding; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0019899; F:enzyme binding; IPI:RGD.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:RGD.
DR GO; GO:0004672; F:protein kinase activity; ISO:RGD.
DR GO; GO:0043621; F:protein self-association; ISO:RGD.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:RGD.
DR GO; GO:0007015; P:actin filament organization; IMP:RGD.
DR GO; GO:0090630; P:activation of GTPase activity; IMP:RGD.
DR GO; GO:0042976; P:activation of Janus kinase activity; IMP:RGD.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0001525; P:angiogenesis; IMP:RGD.
DR GO; GO:0043534; P:blood vessel endothelial cell migration; IMP:RGD.
DR GO; GO:0045453; P:bone resorption; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IMP:RGD.
DR GO; GO:0030154; P:cell differentiation; IEP:RGD.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0006968; P:cellular defense response; IMP:Alzheimers_University_of_Toronto.
DR GO; GO:0071498; P:cellular response to fluid shear stress; ISO:RGD.
DR GO; GO:0071300; P:cellular response to retinoic acid; ISO:RGD.
DR GO; GO:0070098; P:chemokine-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0086100; P:endothelin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IMP:RGD.
DR GO; GO:0048041; P:focal adhesion assembly; IMP:RGD.
DR GO; GO:0014009; P:glial cell proliferation; IEP:RGD.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0035235; P:ionotropic glutamate receptor signaling pathway; IMP:Alzheimers_University_of_Toronto.
DR GO; GO:0060292; P:long-term synaptic depression; IMP:RGD.
DR GO; GO:0060291; P:long-term synaptic potentiation; IMP:Alzheimers_University_of_Toronto.
DR GO; GO:0000165; P:MAPK cascade; IMP:RGD.
DR GO; GO:0002315; P:marginal zone B cell differentiation; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0030502; P:negative regulation of bone mineralization; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0010656; P:negative regulation of muscle cell apoptotic process; IMP:RGD.
DR GO; GO:0045638; P:negative regulation of myeloid cell differentiation; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:Alzheimers_University_of_Toronto.
DR GO; GO:0030279; P:negative regulation of ossification; IMP:RGD.
DR GO; GO:0043267; P:negative regulation of potassium ion transport; ISO:RGD.
DR GO; GO:0031175; P:neuron projection development; IMP:RGD.
DR GO; GO:0001556; P:oocyte maturation; IMP:RGD.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:RGD.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; ISS:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:RGD.
DR GO; GO:2000538; P:positive regulation of B cell chemotaxis; ISS:UniProtKB.
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; IEP:RGD.
DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; ISS:UniProtKB.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IMP:RGD.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; IMP:RGD.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; IMP:Alzheimers_University_of_Toronto.
DR GO; GO:0046330; P:positive regulation of JNK cascade; ISS:UniProtKB.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; IMP:RGD.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:RGD.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IMP:RGD.
DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; IMP:RGD.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; ISS:UniProtKB.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISS:UniProtKB.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IMP:RGD.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IMP:Alzheimers_University_of_Toronto.
DR GO; GO:0045727; P:positive regulation of translation; IMP:RGD.
DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
DR GO; GO:2000249; P:regulation of actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0050848; P:regulation of calcium-mediated signaling; ISO:RGD.
DR GO; GO:0030155; P:regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; ISS:UniProtKB.
DR GO; GO:0010752; P:regulation of cGMP-mediated signaling; ISO:RGD.
DR GO; GO:2000114; P:regulation of establishment of cell polarity; ISS:UniProtKB.
DR GO; GO:0032960; P:regulation of inositol trisphosphate biosynthetic process; ISS:UniProtKB.
DR GO; GO:0010758; P:regulation of macrophage chemotaxis; ISS:UniProtKB.
DR GO; GO:0045428; P:regulation of nitric oxide biosynthetic process; ISO:RGD.
DR GO; GO:2000310; P:regulation of NMDA receptor activity; IMP:Alzheimers_University_of_Toronto.
DR GO; GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; ISS:UniProtKB.
DR GO; GO:2000058; P:regulation of ubiquitin-dependent protein catabolic process; ISO:RGD.
DR GO; GO:0051592; P:response to calcium ion; IEP:RGD.
DR GO; GO:0051591; P:response to cAMP; IEP:RGD.
DR GO; GO:0043157; P:response to cation stress; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0042220; P:response to cocaine; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0009749; P:response to glucose; IEP:RGD.
DR GO; GO:0009725; P:response to hormone; IEP:RGD.
DR GO; GO:0042542; P:response to hydrogen peroxide; IPI:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0035902; P:response to immobilization stress; IEP:RGD.
DR GO; GO:0002931; P:response to ischemia; IMP:Alzheimers_University_of_Toronto.
DR GO; GO:0010226; P:response to lithium ion; IEP:RGD.
DR GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD.
DR GO; GO:0010243; P:response to organonitrogen compound; IEP:RGD.
DR GO; GO:0006970; P:response to osmotic stress; IEP:RGD.
DR GO; GO:0000302; P:response to reactive oxygen species; 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:0002040; P:sprouting angiogenesis; ISS:UniProtKB.
DR GO; GO:0043149; P:stress fiber assembly; IMP:RGD.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; ISO:RGD.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; ISO: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; IPR030610; PTK2B.
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; PTHR24418:SF94; PTHR24418:SF94; 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; SSF47031; SSF47031; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF68993; SSF68993; 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 Adaptive immunity; Alternative splicing; Angiogenesis; ATP-binding;
KW Cell junction; Cell membrane; Cell projection; Cytoplasm;
KW Direct protein sequencing; Immunity; Kinase; Membrane; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Transferase;
KW Tyrosine-protein kinase.
FT CHAIN 1..1009
FT /note="Protein-tyrosine kinase 2-beta"
FT /id="PRO_0000088083"
FT DOMAIN 39..359
FT /note="FERM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084"
FT DOMAIN 425..683
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 702..725
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 801..1009
FT /note="Interaction with TGFB1I1"
FT /evidence="ECO:0000269|PubMed:9422762"
FT REGION 868..1009
FT /note="Focal adhesion targeting (FAT)"
FT COMPBIAS 707..722
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 549
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 431..439
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 457
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 503..509
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 361
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14289"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 399
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14289"
FT MOD_RES 402
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:16574377,
FT ECO:0000269|PubMed:20849950"
FT MOD_RES 579
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:20849950"
FT MOD_RES 580
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:16574377,
FT ECO:0000269|PubMed:20849950"
FT MOD_RES 722
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q14289"
FT MOD_RES 762
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14289"
FT MOD_RES 765
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14289"
FT MOD_RES 834
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q14289"
FT MOD_RES 839
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14289"
FT MOD_RES 842
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14289"
FT MOD_RES 849
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q14289"
FT MOD_RES 866
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14289"
FT MOD_RES 881
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q14289"
FT VAR_SEQ 1..771
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9645946"
FT /id="VSP_004982"
FT VAR_SEQ 739..780
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:9645946"
FT /id="VSP_004984"
FT VAR_SEQ 772..780
FT /note="NVFKRHSMR -> MGLIVLSSQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9645946"
FT /id="VSP_004983"
FT CONFLICT 205
FT /note="E -> A (in Ref. 2; BAA08290)"
FT /evidence="ECO:0000305"
FT CONFLICT 807
FT /note="V -> F (in Ref. 3; AAC28340)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1009 AA; 115784 MW; D435A475BCA49E9B CRC64;
MSGVSEPLSR VKVGTLRPPE GPPEPMVVVP VDVEKEDVRI LKVCFYSNSF NPGKNFKLVK
CTVQTEIQEI ITSILLSGRI GPNIQLAECY GLRLKHMKSD EIHWLHPQMT VGEVQDKYEC
LHVEAEWRYD LQIRYLPEDF MESLKEDRTT LLYFYQQLRN DYMQRYASKV SEGMALQLGC
LELRRFFKDM PHNALDKKSN FELLEKEVGL DLFFPKQMQE NLKPKQFRKM IQQTFQQYAS
LREEECVMKF FNTLAGFANI DQETYRCELI QGWNITVDLV IGPKGIRQLT SQDTKPTCLA
EFKQIRSIRC LPLEETQAVL QLGIEGAPQS LSIKTSSLAE AENMADLIDG YCRLQGEHKG
SLIIHAKKDG EKRNSLPQIP TLNLESRRSH LSESCSIESD IYAEIPDETL RRPGGPQYGV
AREDVVLNRI LGEGFFGEVY EGVYTNHKGE KINVAVKTCK KDCTLDNKEK FMSEAVIMKN
LDHPHIVKLI GIIEEEPTWI VMELYPYGEL GHYLERNKNS LKVPTLVLYA LQICKAMAYL
ESINCVHRDI AVRNILVASP ECVKLGDFGL SRYIEDEDYY KASVTRLPIK WMSPESINFR
RFTTASDVWM FAVCMWEILS FGKQPFFWLE NKDVIGVLEK GDRLPKPELC PPVLYTLMTR
CWDYDPSDRP RFTELVCSLS DIYQMERDIA IEQERNARYR PPKILEPTAF QEPPPKPSRP
KYKHPPQTNL LAPKLQFQVP EGLCASSPTL TSPMEYPSPV NSLHTPPLHR HNVFKRHSMR
EEDFIRPSSR EEAQQLWEAE KIKMRQVLDR QQKQMVEDSQ WLRREERCLD PMVYMNDKSP
LTPEKEAGYT EFTGPPQKPP RLGAQSIQPT ANLDRTDDLV YHNVMTLVEA VLELKNKLSQ
LPPEEYVVVV KNVGLNLRKL IGSVDDLLPS LPASSRTEIE GTQKLLNKDL AELINKMRLA
QQNAVTSLSE DCKRQMLTAS HTLAVDAKNL LDAVDQAKVV ANLAHPPAE
