ID FAK2_MOUSE Reviewed; 1009 AA.
AC Q9QVP9; B2RQ16; G3X8V1;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 27-MAR-2024, entry version 217.
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;
DE AltName: Full=Related adhesion focal tyrosine kinase;
DE Short=RAFTK;
GN Name=Ptk2b; Synonyms=Fak2, Pyk2, Raftk;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=7499242; DOI=10.1074/jbc.270.46.27742;
RA Avraham S., London R., Fu Y., Ota S., Hiregowdara D., Li J., Jiang S.,
RA Pasztor L.M., White R.A., Groopman J.E., Avraham H.;
RT "Identification and characterization of a novel related adhesion focal
RT tyrosine kinase (RAFTK) from megakaryocytes and brain.";
RL J. Biol. Chem. 270:27742-27751(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 PROTEIN SEQUENCE OF 469-479, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [6]
RP INTERACTION WITH PXN.
RX PubMed=8940124; DOI=10.1074/jbc.271.49.31222;
RA Salgia R., Avraham S., Pisick E., Li J.L., Raja S., Greenfield E.A.,
RA Sattler M., Avraham H., Griffin J.D.;
RT "The related adhesion focal tyrosine kinase forms a complex with paxillin
RT in hematopoietic cells.";
RL J. Biol. Chem. 271:31222-31226(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 INTERACTION WITH SIRPA.
RX PubMed=10469599; DOI=10.1016/s0960-9822(99)80401-1;
RA Timms J.F., Swanson K.D., Marie-Cardine A., Raab M., Rudd C.E.,
RA Schraven B., Neel B.G.;
RT "SHPS-1 is a scaffold for assembling distinct adhesion-regulated multi-
RT protein complexes in macrophages.";
RL Curr. Biol. 9:927-930(1999).
RN [9]
RP DISRUPTION PHENOTYPE, AND FUNCTION IN B-CELL DIFFERENTIATION; B-CELL
RP CHEMOTAXIS AND IMMUNE RESPONSE.
RX PubMed=10881171; DOI=10.1038/76882;
RA Guinamard R., Okigaki M., Schlessinger J., Ravetch J.V.;
RT "Absence of marginal zone B cells in Pyk-2-deficient mice defines their
RT role in the humoral response.";
RL Nat. Immunol. 1:31-36(2000).
RN [10]
RP INTERACTION WITH ARHGAP10, AND FUNCTION IN REGULATION OF ARHGAP10 ACTIVITY
RP AND ACTIVATION OF CDC42 AND RHOA.
RX PubMed=11238453; DOI=10.1083/jcb.152.5.971;
RA Ren X.-R., Du Q.-S., Huang Y.-Z., Ao S.-Z., Mei L., Xiong W.-C.;
RT "Regulation of CDC42 GTPase by proline-rich tyrosine kinase 2 interacting
RT with PSGAP, a novel pleckstrin homology and Src homology 3 domain
RT containing rhoGAP protein.";
RL J. Cell Biol. 152:971-984(2001).
RN [11]
RP PHOSPHORYLATION AT TYR-402; TYR-580 AND TYR-881.
RX PubMed=11420674; DOI=10.1038/sj.onc.1204359;
RA Nakamura K., Yano H., Schaefer E., Sabe H.;
RT "Different modes and qualities of tyrosine phosphorylation of Fak and Pyk2
RT during epithelial-mesenchymal transdifferentiation and cell migration:
RT analysis of specific phosphorylation events using site-directed
RT antibodies.";
RL Oncogene 20:2626-2635(2001).
RN [12]
RP PHOSPHORYLATION AT TYR-402, AND INTERACTION WITH NPHP1.
RX PubMed=11493697; DOI=10.1073/pnas.171269898;
RA Benzing T., Gerke P., Hoepker K., Hildebrandt F., Kim E., Walz G.;
RT "Nephrocystin interacts with Pyk2, p130(Cas), and tensin and triggers
RT phosphorylation of Pyk2.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:9784-9789(2001).
RN [13]
RP INTERACTION WITH SH2D3C.
RX PubMed=12486027; DOI=10.1074/jbc.m207942200;
RA Sakakibara A., Hattori S., Nakamura S., Katagiri T.;
RT "A novel hematopoietic adaptor protein, Chat-H, positively regulates T cell
RT receptor-mediated interleukin-2 production by Jurkat cells.";
RL J. Biol. Chem. 278:6012-6017(2003).
RN [14]
RP INTERACTION WITH LPXN AMD PTPN12.
RX PubMed=12674328; DOI=10.1359/jbmr.2003.18.4.669;
RA Gupta A., Lee B.S., Khadeer M.A., Tang Z., Chellaiah M., Abu-Amer Y.,
RA Goldknopf J., Hruska K.A.;
RT "Leupaxin is a critical adaptor protein in the adhesion zone of the
RT osteoclast.";
RL J. Bone Miner. Res. 18:669-685(2003).
RN [15]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=12960403; DOI=10.1073/pnas.1834348100;
RA Okigaki M., Davis C., Falasca M., Harroch S., Felsenfeld D.P., Sheetz M.P.,
RA Schlessinger J.;
RT "Pyk2 regulates multiple signaling events crucial for macrophage morphology
RT and migration.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:10740-10745(2003).
RN [16]
RP FUNCTION IN BONE RESORPTION, INTERACTION WITH SRC, PHOSPHORYLATION AT
RP TYR-402, AND MUTAGENESIS OF TYR-402.
RX PubMed=14739300; DOI=10.1074/jbc.m311032200;
RA Miyazaki T., Sanjay A., Neff L., Tanaka S., Horne W.C., Baron R.;
RT "Src kinase activity is essential for osteoclast function.";
RL J. Biol. Chem. 279:17660-17666(2004).
RN [17]
RP PHOSPHORYLATION IN RESPONSE TO FGR.
RX PubMed=15561106; DOI=10.1016/j.yexcr.2004.09.005;
RA Continolo S., Baruzzi A., Majeed M., Caveggion E., Fumagalli L.,
RA Lowell C.A., Berton G.;
RT "The proto-oncogene Fgr regulates cell migration and this requires its
RT plasma membrane localization.";
RL Exp. Cell Res. 302:253-269(2005).
RN [18]
RP FUNCTION IN VEGFA SIGNALING; REGULATION OF INTRACELLULAR CALCIUM LEVELS;
RP ACTIVATION OF AKT1 AND RAC1; PHOSPHORYLATION OF SRC; REORGANIZATION OF
RP ACTIN CYTOSKELETON; CELL MIGRATION AND ANGIOGENESIS, AND INTERACTION WITH
RP SRC.
RX PubMed=17698736; DOI=10.1161/circulationaha.106.645416;
RA Matsui A., Okigaki M., Amano K., Adachi Y., Jin D., Takai S., Yamashita T.,
RA Kawashima S., Kurihara T., Miyazaki M., Tateishi K., Matsunaga S.,
RA Katsume A., Honshou S., Takahashi T., Matoba S., Kusaba T., Tatsumi T.,
RA Matsubara H.;
RT "Central role of calcium-dependent tyrosine kinase PYK2 in endothelial
RT nitric oxide synthase-mediated angiogenic response and vascular function.";
RL Circulation 116:1041-1051(2007).
RN [19]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=17846174; DOI=10.1083/jcb.200701148;
RA Gil-Henn H., Destaing O., Sims N.A., Aoki K., Alles N., Neff L., Sanjay A.,
RA Bruzzaniti A., De Camilli P., Baron R., Schlessinger J.;
RT "Defective microtubule-dependent podosome organization in osteoclasts leads
RT to increased bone density in Pyk2(-/-) mice.";
RL J. Cell Biol. 178:1053-1064(2007).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-402; TYR-579 AND TYR-580, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [21]
RP DISRUPTION PHENOTYPE, FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY
RP REGULATION.
RX PubMed=17537919; DOI=10.1073/pnas.0701421104;
RA Buckbinder L., Crawford D.T., Qi H., Ke H.Z., Olson L.M., Long K.R.,
RA Bonnette P.C., Baumann A.P., Hambor J.E., Grasser W.A. III, Pan L.C.,
RA Owen T.A., Luzzio M.J., Hulford C.A., Gebhard D.F., Paralkar V.M.,
RA Simmons H.A., Kath J.C., Roberts W.G., Smock S.L., Guzman-Perez A.,
RA Brown T.A., Li M.;
RT "Proline-rich tyrosine kinase 2 regulates osteoprogenitor cells and bone
RT formation, and offers an anabolic treatment approach for osteoporosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:10619-10624(2007).
RN [22]
RP FUNCTION DURING LUNG INJURY, PHOSPHORYLATION BY MYLK, AND INTERACTION WITH
RP MYLK.
RX PubMed=18587400; DOI=10.1038/ni.1628;
RA Xu J., Gao X.-P., Ramchandran R., Zhao Y.-Y., Vogel S.M., Malik A.B.;
RT "Nonmuscle myosin light-chain kinase mediates neutrophil transmigration in
RT sepsis-induced lung inflammation by activating beta2 integrins.";
RL Nat. Immunol. 9:880-886(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-375, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [24]
RP FUNCTION.
RX PubMed=19561089; DOI=10.1074/jbc.m109.013169;
RA Tse K.W., Dang-Lawson M., Lee R.L., Vong D., Bulic A., Buckbinder L.,
RA Gold M.R.;
RT "B cell receptor-induced phosphorylation of Pyk2 and focal adhesion kinase
RT involves integrins and the Rap GTPases and is required for B cell
RT spreading.";
RL J. Biol. Chem. 284:22865-22877(2009).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-375, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [26]
RP FUNCTION IN CELL PROLIFERATION AND REGULATION OF P53/TP53 UBIQUITINATION,
RP AND SUBCELLULAR LOCATION.
RX PubMed=19880522; DOI=10.1074/jbc.m109.064212;
RA Lim S.T., Miller N.L., Nam J.O., Chen X.L., Lim Y., Schlaepfer D.D.;
RT "Pyk2 inhibition of p53 as an adaptive and intrinsic mechanism facilitating
RT cell proliferation and survival.";
RL J. Biol. Chem. 285:1743-1753(2010).
RN [27]
RP FUNCTION, PHOSPHORYLATION AT TYR-402 AND TYR-579, AND ACTIVITY REGULATION.
RX PubMed=20688918; DOI=10.1074/jbc.m110.118265;
RA Lysechko T.L., Cheung S.M., Ostergaard H.L.;
RT "Regulation of the tyrosine kinase Pyk2 by calcium is through production of
RT reactive oxygen species in cytotoxic T lymphocytes.";
RL J. Biol. Chem. 285:31174-31184(2010).
RN [28]
RP INTERACTION WITH PXN, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT TYR-402;
RP TYR-580 AND TYR-881.
RX PubMed=21195757; DOI=10.1016/j.cellsig.2010.12.006;
RA St-Pierre J., Lysechko T.L., Ostergaard H.L.;
RT "Hypophosphorylated and inactive Pyk2 associates with paxillin at the
RT microtubule organizing center in hematopoietic cells.";
RL Cell. Signal. 23:718-730(2011).
RN [29]
RP FUNCTION IN SPROUTING ANGIOGENESIS.
RX PubMed=21640103; DOI=10.1016/j.yexcr.2011.05.006;
RA Shen C.J., Raghavan S., Xu Z., Baranski J.D., Yu X., Wozniak M.A.,
RA Miller J.S., Gupta M., Buckbinder L., Chen C.S.;
RT "Decreased cell adhesion promotes angiogenesis in a Pyk2-dependent
RT manner.";
RL Exp. Cell Res. 317:1860-1871(2011).
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:10881171, ECO:0000269|PubMed:11238453,
CC ECO:0000269|PubMed:12960403, ECO:0000269|PubMed:14739300,
CC ECO:0000269|PubMed:17537919, ECO:0000269|PubMed:17698736,
CC ECO:0000269|PubMed:17846174, ECO:0000269|PubMed:18587400,
CC ECO:0000269|PubMed:19561089, ECO:0000269|PubMed:19880522,
CC ECO:0000269|PubMed:20688918, ECO:0000269|PubMed:21640103}.
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:17537919};
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 {ECO:0000269|PubMed:17537919, ECO:0000269|PubMed:20688918}.
CC -!- SUBUNIT: Homodimer, or homooligomer. Interacts with KCNA2 (By
CC similarity). Interacts with NPHP1, ASAP1, ASAP2, ARHGAP26, SKAP2 and
CC TGFB1I1. The Tyr-402 phosphorylated form interacts with SRC (via SH2
CC domain) and SRC family members. Forms a signaling complex with EPHA1,
CC LCK and phosphatidylinositol 3-kinase; upon activation by EFNA1.
CC Interacts with GRB2 (via SH2 domain). Interacts with P53/TP53 and MDM2.
CC Interacts with MYLK. Interacts with BCAR1. Interacts with RB1CC1.
CC Interacts with RHOU. Interacts with VAV1. Interacts with PDPK1.
CC Interacts with DLG4. Interacts with LPXN and PTPN12. Interacts with
CC SIRPA and SH2D3C. Interacts (hypophosphorylated) with PXN. Interacts
CC with ARHGAP10. {ECO:0000250|UniProtKB:P70600,
CC ECO:0000269|PubMed:10469599, ECO:0000269|PubMed:11238453,
CC ECO:0000269|PubMed:11493697, ECO:0000269|PubMed:12486027,
CC ECO:0000269|PubMed:12674328, ECO:0000269|PubMed:14739300,
CC ECO:0000269|PubMed:17698736, ECO:0000269|PubMed:18587400,
CC ECO:0000269|PubMed:21195757, ECO:0000269|PubMed:8940124,
CC ECO:0000269|PubMed:9422762}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, perinuclear region
CC {ECO:0000250}. Cell membrane; Peripheral membrane protein; Cytoplasmic
CC side. Cell junction, focal adhesion. Cell projection, lamellipodium
CC {ECO:0000250}. Cytoplasm, cell cortex {ECO:0000250}. Nucleus
CC {ECO:0000250}. Note=Colocalizes with integrins at the cell periphery
CC (By similarity). Interaction with NPHP1 induces the membrane-
CC association of the kinase. Colocalizes with PXN at the microtubule-
CC organizing center. The tyrosine phosphorylated form is detected at
CC cell-cell contacts. {ECO:0000250}.
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 -!- DISRUPTION PHENOTYPE: Mice are born at the expected Mendelian rate,
CC appear normal and are fertile. Mice display increased bone formation
CC and high bone mass, due to defects in osteoclastic bone resorption.
CC Osteoclasts display defects in actin cytoskeleton reorganization, plus
CC altered Rho activity, microtubule stabilization and podosome
CC organization. Mice also display increased differentiation and activity
CC of osteoprogenitor cells. Macrophages from mutant mice display defects
CC in their responses to chemokines, including defects in cell
CC polarization, actin cytoskeleton reorganization, directed migration
CC towards sites of inflammation, but also defects in the regulation of
CC intracellular Ca(2+) levels, phosphatidylinositol 3-kinase activity and
CC inositol 1,4,5-trisphosphate production. Mutant mice have normal B-cell
CC polulations in bone marrow, lymph nodes and blood, but lack marginal
CC zone B-cells in the spleen. {ECO:0000269|PubMed:10881171,
CC ECO:0000269|PubMed:12960403, ECO:0000269|PubMed:17537919,
CC ECO:0000269|PubMed:17846174}.
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; AC126272; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC140329; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466535; EDL36001.1; -; Genomic_DNA.
DR EMBL; BC137704; AAI37705.1; -; mRNA.
DR EMBL; BC144849; AAI44850.1; -; mRNA.
DR CCDS; CCDS49526.1; -.
DR RefSeq; NP_001155838.1; NM_001162366.1.
DR RefSeq; XP_006518789.1; XM_006518726.3.
DR RefSeq; XP_011243296.1; XM_011244994.2.
DR AlphaFoldDB; Q9QVP9; -.
DR SMR; Q9QVP9; -.
DR BioGRID; 202467; 36.
DR CORUM; Q9QVP9; -.
DR IntAct; Q9QVP9; 6.
DR MINT; Q9QVP9; -.
DR STRING; 10090.ENSMUSP00000022622; -.
DR BindingDB; Q9QVP9; -.
DR ChEMBL; CHEMBL1075289; -.
DR GlyGen; Q9QVP9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9QVP9; -.
DR PhosphoSitePlus; Q9QVP9; -.
DR SwissPalm; Q9QVP9; -.
DR CPTAC; non-CPTAC-3644; -.
DR EPD; Q9QVP9; -.
DR jPOST; Q9QVP9; -.
DR MaxQB; Q9QVP9; -.
DR PaxDb; 10090-ENSMUSP00000106750; -.
DR ProteomicsDB; 271727; -.
DR Antibodypedia; 3551; 1182 antibodies from 44 providers.
DR DNASU; 19229; -.
DR Ensembl; ENSMUST00000022622.14; ENSMUSP00000022622.8; ENSMUSG00000059456.14.
DR Ensembl; ENSMUST00000178730.8; ENSMUSP00000137008.2; ENSMUSG00000059456.14.
DR GeneID; 19229; -.
DR KEGG; mmu:19229; -.
DR UCSC; uc011znr.1; mouse.
DR AGR; MGI:104908; -.
DR CTD; 2185; -.
DR MGI; MGI:104908; Ptk2b.
DR VEuPathDB; HostDB:ENSMUSG00000059456; -.
DR eggNOG; KOG4257; Eukaryota.
DR GeneTree; ENSGT00940000157269; -.
DR InParanoid; Q9QVP9; -.
DR OMA; EIMSYGQ; -.
DR OrthoDB; 1614410at2759; -.
DR PhylomeDB; Q9QVP9; -.
DR BRENDA; 2.7.10.2; 3474.
DR Reactome; R-MMU-391160; Signal regulatory protein family interactions.
DR Reactome; R-MMU-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-MMU-9013420; RHOU GTPase cycle.
DR Reactome; R-MMU-9020558; Interleukin-2 signaling.
DR BioGRID-ORCS; 19229; 2 hits in 81 CRISPR screens.
DR ChiTaRS; Ptk2b; mouse.
DR PRO; PR:Q9QVP9; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q9QVP9; Protein.
DR Bgee; ENSMUSG00000059456; Expressed in dentate gyrus of hippocampal formation granule cell and 187 other cell types or tissues.
DR ExpressionAtlas; Q9QVP9; baseline and differential.
DR Genevisible; Q9QVP9; MM.
DR GO; GO:0097440; C:apical dendrite; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0044297; C:cell body; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0005938; C:cell cortex; ISO:MGI.
DR GO; GO:0042995; C:cell projection; ISO:MGI.
DR GO; GO:0005856; C:cytoskeleton; IEA:InterPro.
DR GO; GO:0030425; C:dendrite; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0043197; C:dendritic spine; ISO:MGI.
DR GO; GO:0005925; C:focal adhesion; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0030426; C:growth cone; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0017146; C:NMDA selective glutamate receptor complex; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:MGI.
DR GO; GO:0098794; C:postsynapse; ISO:MGI.
DR GO; GO:0014069; C:postsynaptic density; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0099092; C:postsynaptic density, intracellular component; IDA:SynGO.
DR GO; GO:0098793; C:presynapse; IDA:SynGO.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; ISO:MGI.
DR GO; GO:0043423; F:3-phosphoinositide-dependent protein kinase binding; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0004972; F:NMDA glutamate receptor activity; IEA:Ensembl.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0043621; F:protein self-association; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0007015; P:actin filament organization; ISO:MGI.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0001525; P:angiogenesis; ISO:MGI.
DR GO; GO:0043534; P:blood vessel endothelial cell migration; ISO:MGI.
DR GO; GO:0045453; P:bone resorption; IMP:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; ISO:MGI.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0006968; P:cellular defense response; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0071498; P:cellular response to fluid shear stress; IMP:MGI.
DR GO; GO:0071300; P:cellular response to retinoic acid; ISO:MGI.
DR GO; GO:0070098; P:chemokine-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0030865; P:cortical cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0086100; P:endothelin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; ISO:MGI.
DR GO; GO:0048041; P:focal adhesion assembly; ISO:MGI.
DR GO; GO:0014009; P:glial cell proliferation; IEA:Ensembl.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0035235; P:ionotropic glutamate receptor signaling pathway; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0060292; P:long-term synaptic depression; ISO:MGI.
DR GO; GO:0060291; P:long-term synaptic potentiation; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0000165; P:MAPK cascade; ISO:MGI.
DR GO; GO:0002315; P:marginal zone B cell differentiation; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0030502; P:negative regulation of bone mineralization; IMP: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; ISO:MGI.
DR GO; GO:0045638; P:negative regulation of myeloid cell differentiation; ISO:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0030279; P:negative regulation of ossification; ISO:MGI.
DR GO; GO:0043267; P:negative regulation of potassium ion transport; ISO:MGI.
DR GO; GO:0031175; P:neuron projection development; ISO:MGI.
DR GO; GO:0001556; P:oocyte maturation; ISO:MGI.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; ISS:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:UniProtKB.
DR GO; GO:2000538; P:positive regulation of B cell chemotaxis; IMP:UniProtKB.
DR GO; GO:0030307; P:positive regulation of cell growth; ISO:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
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; ISO:MGI.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; ISO:MGI.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IMP:UniProtKB.
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; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0046330; P:positive regulation of JNK cascade; ISS:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISO:MGI.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:MGI.
DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:UniProtKB.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISS:UniProtKB.
DR GO; GO:0051247; P:positive regulation of protein metabolic process; ISO:MGI.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; ISO:MGI.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0045727; P:positive regulation of translation; ISO:MGI.
DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0099170; P:postsynaptic modulation of chemical synaptic transmission; ISO:MGI.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0030155; P:regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; ISO:MGI.
DR GO; GO:0010758; P:regulation of macrophage chemotaxis; IMP:UniProtKB.
DR GO; GO:2000310; P:regulation of NMDA receptor activity; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0099151; P:regulation of postsynaptic density assembly; IDA:SynGO.
DR GO; GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; IMP:UniProtKB.
DR GO; GO:2000058; P:regulation of ubiquitin-dependent protein catabolic process; ISO:MGI.
DR GO; GO:0051592; P:response to calcium ion; IEA:Ensembl.
DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl.
DR GO; GO:0043157; P:response to cation stress; ISO:MGI.
DR GO; GO:0042220; P:response to cocaine; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0009749; P:response to glucose; IEA:Ensembl.
DR GO; GO:0009725; P:response to hormone; IEA:Ensembl.
DR GO; GO:0042542; P:response to hydrogen peroxide; ISO:MGI.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0035902; P:response to immobilization stress; IEA:Ensembl.
DR GO; GO:0002931; P:response to ischemia; ISO:MGI.
DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007172; P:signal complex assembly; IEA:InterPro.
DR GO; GO:0002040; P:sprouting angiogenesis; IMP:UniProtKB.
DR GO; GO:0043149; P:stress fiber assembly; ISO:MGI.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; ISO:MGI.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IMP:UniProtKB.
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; 1.10.510.10; 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:SF7; 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; 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; Angiogenesis; ATP-binding; Cell junction; Cell membrane;
KW Cell projection; Cytoplasm; Direct protein sequencing; Immunity; Kinase;
KW Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Transferase; Tyrosine-protein kinase.
FT CHAIN 1..1009
FT /note="Protein-tyrosine kinase 2-beta"
FT /id="PRO_0000088082"
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 696..728
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 801..1009
FT /note="Interaction with TGFB1I1"
FT /evidence="ECO:0000250"
FT REGION 868..1009
FT /note="Focal adhesion targeting (FAT)"
FT COMPBIAS 707..727
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:19144319,
FT ECO:0007744|PubMed:21183079"
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:11420674,
FT ECO:0000269|PubMed:11493697, ECO:0000269|PubMed:14739300,
FT ECO:0000269|PubMed:20688918, ECO:0000269|PubMed:21195757,
FT ECO:0007744|PubMed:17947660"
FT MOD_RES 579
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:20688918,
FT ECO:0007744|PubMed:17947660"
FT MOD_RES 580
FT /note="Phosphotyrosine; by SRC, FYN and LCK"
FT /evidence="ECO:0000269|PubMed:11420674,
FT ECO:0000269|PubMed:21195757, ECO:0007744|PubMed:17947660"
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:0000269|PubMed:11420674,
FT ECO:0000269|PubMed:21195757"
FT MUTAGEN 402
FT /note="Y->A: Loss of phosphorylation and interaction with
FT SRC, and inhibition of bone resorption."
FT /evidence="ECO:0000269|PubMed:14739300"
FT CONFLICT 306
FT /note="K -> R (in Ref. 4; AAI37705/AAI44850)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1009 AA; 115794 MW; A17C858ECC9990E9 CRC64;
MSGVSEPLSR VKVGTLRRPE 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
EFKQIKSIRC LPLEETQAVL QLGIEGAPQS LSIKTSSLAE AENMADLIDG YCRLQGEHKG
SLIMHAKKDG EKRNSLPQIP TLNLEARRSH LSESCSIESD IYAEIPDETL RRPGGPQYGV
AREEVVLNRI LGEGFFGEVY EGVYTNHKGE KINVAVKTCK KDCTQDNKEK FMSEAVIMKN
LDHPHIVKLI GIIEEEPTWI IMELYPYGEL GHYLERNKNS LKVPTLVLYT LQICKAMAYL
ESINCVHRDI AVRNILVASP ECVKLGDFGL SRYIEDEDYY KASVTRLPIK WMSPESINFR
RFTTASDVWM FAVCMWEILS FGKQPFFWLE NKDVIGVLEK GDRLPKPELC PPVLYTLMTR
CWDYDPSDRP RFTELVCSLS DIYQMEKDIA IEQERNARYR PPKILEPTTF QEPPPKPSRP
KYRPPPQTNL LAPKLQFQVP EGLCASSPTL TSPMEYPSPV NSLHTPPLHR HNVFKRHSMR
EEDFIRPSSR EEAQQLWEAE KIKMKQVLER QQKQMVEDSQ WLRREERCLD PMVYMNDKSP
LTPEKEAGYT EFTGPPQKPP RLGAQSIQPT ANLDRTDDLV YHNVMTLVEA VLELKNKLGQ
LPPEDYVVVV KNVGLNLRKL IGSVDDLLPS LPASSRTEIE GTQKLLNKDL AELINKMKLA
QQNAVTSLSE DCKRQMLTAS HTLAVDAKNL LDAVDQAKVV ANLAHPPAE
//
