ID FAK2_HUMAN Reviewed; 1009 AA. AC Q14289; D3DST0; Q13475; Q14290; Q16709; Q6PID4; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 15-JUL-1998, sequence version 2. DT 27-MAR-2024, entry version 247. 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 Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION IN REGULATION OF POTASSIUM RP CHANNELS; PHOSPHORYLATION OF KCNA2 AND SHC1 AND ACTIVATION OF MAPK1/ERK2, RP INTERACTION WITH GRB2, AND TISSUE SPECIFICITY. RC TISSUE=Brain; 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 [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Hippocampus; RX PubMed=8838818; DOI=10.1006/geno.1996.0149; RA Herzog H., Nicholl J., Hort Y.J., Sutherland G.R., Shine J.; RT "Molecular cloning and assignment of FAK2, a novel human focal adhesion RT kinase, to 8p11.2-p22 by nonisotopic in situ hybridization."; RL Genomics 32:484-486(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Hippocampus; 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 [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). 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 [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PHOSPHORYLATION, AND TISSUE RP SPECIFICITY. RC TISSUE=Monocyte; RX PubMed=9545257; DOI=10.1074/jbc.273.16.9361; RA Li X., Hunter D., Morris J., Haskill J.S., Earp H.S.; RT "A calcium-dependent tyrosine kinase splice variant in human monocytes. RT Activation by a two-stage process involving adherence and a subsequent RT intracellular signal."; RL J. Biol. Chem. 273:9361-9364(1998). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., RA Platzer M., Shimizu N., Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lymph, and Testis; 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 [9] RP FUNCTION IN PHOSPHORYLATION OF SRC AND ACTIVATION OF THE MAP KINASE RP SIGNALING CASCADE, INTERACTION WITH SRC, AUTOPHOSPHORYLATION, AND RP MUTAGENESIS OF TYR-402. 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 [10] RP FUNCTION IN TNF SIGNALING AND ACTIVATION OF MAPK8/JNK1. RX PubMed=8670418; DOI=10.1126/science.273.5276.792; RA Tokiwa G., Dikic I., Lev S., Schlessinger J.; RT "Activation of Pyk2 by stress signals and coupling with JNK signaling RT pathway."; RL Science 273:792-794(1996). RN [11] 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 [12] RP INTERACTION WITH ASAP2, AND FUNCTION. RX PubMed=10022920; DOI=10.1128/mcb.19.3.2338; RA Andreev J., Simon J.-P., Sabatini D.D., Kam J., Plowman G., Randazzo P.A., RA Schlessinger J.; RT "Identification of a new Pyk2 target protein with Arf-GAP activity."; RL Mol. Cell. Biol. 19:2338-2350(1999). RN [13] RP INTERACTION WITH RB1CC1. RX PubMed=10769033; DOI=10.1083/jcb.149.2.423; RA Ueda H., Abbi S., Zheng C., Guan J.-L.; RT "Suppression of Pyk2 kinase and cellular activities by FIP200."; RL J. Cell Biol. 149:423-430(2000). RN [14] RP PHOSPHORYLATION AT TYR-402, MUTAGENESIS OF PRO-859, AND INTERACTION WITH RP 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 [15] RP FUNCTION IN ASAP1 PHOSPHORYLATION AND REGULATION OF ASAP1 ACTIVITY, AND RP INTERACTION WITH ASAP1. RX PubMed=12771146; DOI=10.1074/jbc.m302278200; RA Kruljac-Letunic A., Moelleken J., Kallin A., Wieland F., Blaukat A.; RT "The tyrosine kinase Pyk2 regulates Arf1 activity by phosphorylation and RT inhibition of the Arf-GTPase-activating protein ASAP1."; RL J. Biol. Chem. 278:29560-29570(2003). RN [16] RP INTERACTION WITH SKAP2, SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=12893833; DOI=10.1074/jbc.m213217200; RA Takahashi T., Yamashita H., Nagano Y., Nakamura T., Ohmori H., Avraham H., RA Avraham S., Yasuda M., Matsumoto M.; RT "Identification and characterization of a novel Pyk2/related adhesion focal RT tyrosine kinase-associated protein that inhibits alpha-synuclein RT phosphorylation."; RL J. Biol. Chem. 278:42225-42233(2003). RN [17] RP FUNCTION, INTERACTION WITH PDPK1, AND SUBCELLULAR LOCATION. RX PubMed=14585963; DOI=10.1128/mcb.23.22.8019-8029.2003; RA Taniyama Y., Weber D.S., Rocic P., Hilenski L., Akers M.L., Park J., RA Hemmings B.A., Alexander R.W., Griendling K.K.; RT "Pyk2- and Src-dependent tyrosine phosphorylation of PDK1 regulates focal RT adhesions."; RL Mol. Cell. Biol. 23:8019-8029(2003). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=12522270; DOI=10.1073/pnas.2436191100; RA Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T., Ericson C., RA Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C.; RT "Profiling of tyrosine phosphorylation pathways in human cells using mass RT spectrometry."; RL Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003). RN [19] RP FUNCTION IN INTEGRIN SIGNALING AND IN REGULATION OF CELL PROLIFERATION, RP CATALYTIC ACTIVITY, AND CHARACTERIZATION OF ISOFORM 2. RX PubMed=15050747; DOI=10.1016/j.exphem.2004.01.001; RA Dylla S.J., Deyle D.R., Theunissen K., Padurean A.M., Verfaillie C.M.; RT "Integrin engagement-induced inhibition of human myelopoiesis is mediated RT by proline-rich tyrosine kinase 2 gene products."; RL Exp. Hematol. 32:365-374(2004). RN [20] RP PHOSPHORYLATION AT TYR-402, CATALYTIC ACTIVITY, FUNCTION IN SRC-MEDIATED RP PHOSPHORYLATION OF PXN, AND MUTAGENESIS OF LYS-457. RX PubMed=15166227; DOI=10.1074/jbc.m313527200; RA Park S.Y., Avraham H.K., Avraham S.; RT "RAFTK/Pyk2 activation is mediated by trans-acting autophosphorylation in a RT Src-independent manner."; RL J. Biol. Chem. 279:33315-33322(2004). RN [21] RP INTERACTION WITH LPXN AND PTPN12, PHOSPHORYLATION AT TYR-402, AND RP DEPHOSPHORYLATION BY PTPN12. RX PubMed=17329398; DOI=10.1152/ajpcell.00503.2006; RA Sahu S.N., Nunez S., Bai G., Gupta A.; RT "Interaction of Pyk2 and PTP-PEST with leupaxin in prostate cancer cells."; RL Am. J. Physiol. 292:C2288-C2296(2007). RN [22] RP FUNCTION IN MIGRATION OF T-LYMPHOCYTES, AND INTERACTION WITH EPHA1; LCK AND RP PI3-KINASE. RX PubMed=17634955; DOI=10.1002/eji.200737111; RA Hjorthaug H.S., Aasheim H.C.; RT "Ephrin-A1 stimulates migration of CD8+CCR7+ T lymphocytes."; RL Eur. J. Immunol. 37:2326-2336(2007). RN [23] RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND ROLE IN DISEASE. RX PubMed=18339875; DOI=10.1158/0008-5472.can-07-5155; RA Roberts W.G., Ung E., Whalen P., Cooper B., Hulford C., Autry C., RA Richter D., Emerson E., Lin J., Kath J., Coleman K., Yao L., RA Martinez-Alsina L., Lorenzen M., Berliner M., Luzzio M., Patel N., RA Schmitt E., LaGreca S., Jani J., Wessel M., Marr E., Griffor M., Vajdos F.; RT "Antitumor activity and pharmacology of a selective focal adhesion kinase RT inhibitor, PF-562,271."; RL Cancer Res. 68:1935-1944(2008). RN [24] RP FUNCTION IN CELL ADHESION; MIGRATION; PROLIFERATION; REGULATION OF ACTIN RP FIBER POLYMERIZATION AND IN ACTIVATION OF SRC; MAPK1/ERK2 AND MAPK3/ERK1, RP INTERACTION WITH SRC, SUBCELLULAR LOCATION, AND ROLE IN DISEASE. RX PubMed=18765415; DOI=10.1093/carcin/bgn203; RA Sun C.K., Man K., Ng K.T., Ho J.W., Lim Z.X., Cheng Q., Lo C.M., Poon R.T., RA Fan S.T.; RT "Proline-rich tyrosine kinase 2 (Pyk2) promotes proliferation and RT invasiveness of hepatocellular carcinoma cells through c-Src/ERK RT activation."; RL Carcinogenesis 29:2096-2105(2008). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-375, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-375; THR-765; SER-839 AND RP THR-842, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [27] RP INTERACTION WITH RHOU, AND FUNCTION IN REORGANIZATION OF ACTIN CYTOSKELETON RP AND SRC-MEDIATED RHOU PHOSPHORYLATION. RX PubMed=18086875; DOI=10.1128/mcb.00201-07; RA Ruusala A., Aspenstrom P.; RT "The atypical Rho GTPase Wrch1 collaborates with the nonreceptor tyrosine RT kinases Pyk2 and Src in regulating cytoskeletal dynamics."; RL Mol. Cell. Biol. 28:1802-1814(2008). RN [28] 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 [29] RP FUNCTION IN REGULATION OF ACTIN CYTOSKELETON REORGANIZATION AND ACTIVATION RP OF RHO FAMILY GTPASES, PHOSPHORYLATION AT TYR-402, SUBCELLULAR LOCATION, RP AND INTERACTION WITH VAV1. RX PubMed=19207108; DOI=10.1042/bj20090037; RA Gao C., Blystone S.D.; RT "A Pyk2-Vav1 complex is recruited to beta3-adhesion sites to initiate Rho RT activation."; RL Biochem. J. 420:49-56(2009). RN [30] RP ROLE IN DISEASE, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=19648005; DOI=10.1016/j.bmcl.2009.07.084; RA Allen J.G., Lee M.R., Han C.Y., Scherrer J., Flynn S., Boucher C., Zhao H., RA O'Connor A.B., Roveto P., Bauer D., Graceffa R., Richards W.G., Babij P.; RT "Identification of small molecule inhibitors of proline-rich tyrosine RT kinase 2 (Pyk2) with osteogenic activity in osteoblast cells."; RL Bioorg. Med. Chem. Lett. 19:4924-4928(2009). RN [31] RP FUNCTION IN CELL ADHESION AND SPREADING, AUTOPHOSPHORYLATION, AND RP INTERACTION WITH BCAR1. RX PubMed=19086031; DOI=10.1002/jcp.21649; RA Rufanova V.A., Alexanian A., Wakatsuki T., Lerner A., Sorokin A.; RT "Pyk2 mediates endothelin-1 signaling via p130Cas/BCAR3 cascade and RT regulates human glomerular mesangial cell adhesion and spreading."; RL J. Cell. Physiol. 219:45-56(2009). RN [32] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-361; SER-375; SER-399; RP TYR-722; SER-762; TYR-819; TYR-834; SER-839; THR-842; TYR-849 AND SER-866, RP VARIANT [LARGE SCALE ANALYSIS] THR-838, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [33] RP FUNCTION IN IGF1 SIGNALING AND ACTIVATION OF MAPK1/ERK2 AND MAPK3/ERK1, RP INTERACTION WITH SRC AND GRB2, PHOSPHORYLATION AT TYR-402 AND TYR-881, AND RP MUTAGENESIS OF TYR-881. RX PubMed=20521079; DOI=10.1007/s00018-010-0411-x; RA Shen X., Xi G., Radhakrishnan Y., Clemmons D.R.; RT "Recruitment of Pyk2 to SHPS-1 signaling complex is required for IGF-I- RT dependent mitogenic signaling in vascular smooth muscle cells."; RL Cell. Mol. Life Sci. 67:3893-3903(2010). RN [34] 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 [35] RP PHOSPHORYLATION AT TYR-402 AND TYR-580 BY FYN AND LCK. RX PubMed=20028775; DOI=10.1189/jlb.0409227; RA Collins M., Tremblay M., Chapman N., Curtiss M., Rothman P.B., RA Houtman J.C.; RT "The T cell receptor-mediated phosphorylation of Pyk2 tyrosines 402 and 580 RT occurs via a distinct mechanism than other receptor systems."; RL J. Leukoc. Biol. 87:691-701(2010). RN [36] RP FUNCTION IN T-CELL RECEPTOR-MEDIATED SIGNALING, AND PHOSPHORYLATION AT RP TYR-402 AND TYR-580. RX PubMed=20381867; DOI=10.1016/j.molimm.2010.03.009; RA Collins M., Bartelt R.R., Houtman J.C.; RT "T cell receptor activation leads to two distinct phases of Pyk2 activation RT and actin cytoskeletal rearrangement in human T cells."; RL Mol. Immunol. 47:1665-1674(2010). RN [37] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [38] RP INTERACTION WITH NPHP1, AND FUNCTION IN PHOSPHORYLATION OF NPHP1. RX PubMed=21357692; DOI=10.1074/jbc.m110.165464; RA Liebau M.C., Hopker K., Muller R.U., Schmedding I., Zank S., Schairer B., RA Fabretti F., Hohne M., Bartram M.P., Dafinger C., Hackl M., Burst V., RA Habbig S., Zentgraf H., Blaukat A., Walz G., Benzing T., Schermer B.; RT "Nephrocystin-4 regulates Pyk2-induced tyrosine phosphorylation of RT nephrocystin-1 to control targeting to monocilia."; RL J. Biol. Chem. 286:14237-14245(2011). RN [39] RP FUNCTION IN REORGANIZATION OF CYTOSKELETON; FORMATION OF MEMBRANE RUFFLES RP AND CELL MIGRATION, AND ROLE IN DISEASE. RX PubMed=21533080; DOI=10.1371/journal.pone.0018878; RA Sun C.K., Ng K.T., Lim Z.X., Cheng Q., Lo C.M., Poon R.T., Man K., Wong N., RA Fan S.T.; RT "Proline-rich tyrosine kinase 2 (Pyk2) promotes cell motility of RT hepatocellular carcinoma through induction of epithelial to mesenchymal RT transition."; RL PLoS ONE 6:E18878-E18878(2011). RN [40] RP REVIEW ON ROLE IN IMMUNITY. RX PubMed=15888917; DOI=10.1385/ir:31:3:267; RA Ostergaard H.L., Lysechko T.L.; RT "Focal adhesion kinase-related protein tyrosine kinase Pyk2 in T-cell RT activation and function."; RL Immunol. Res. 31:267-282(2005). RN [41] RP REVIEW ON FUNCTION; SIGNALING; INTERACTION PARTNERS; ACTIVITY REGULATION; RP PHOSPHORYLATION, AND ROLE IN DISEASE. RX PubMed=20001213; DOI=10.1517/14728220903473194; RA Lipinski C.A., Loftus J.C.; RT "Targeting Pyk2 for therapeutic intervention."; RL Expert Opin. Ther. Targets 14:95-108(2010). RN [42] RP REVIEW. RX PubMed=20332118; DOI=10.1242/jcs.045112; RA Schaller M.D.; RT "Cellular functions of FAK kinases: insight into molecular mechanisms and RT novel functions."; RL J. Cell Sci. 123:1007-1013(2010). RN [43] RP REVIEW ON ROLE IN DISEASE. RX PubMed=21196189; DOI=10.2741/3706; RA Felty Q.; RT "Redox sensitive Pyk2 as a target for therapeutics in breast cancer."; RL Front. Biosci. 16:568-577(2011). RN [44] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-375 AND THR-842, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [45] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 416-692 IN COMPLEX WITH RP PF-2318841, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=18951788; DOI=10.1016/j.bmcl.2008.10.030; RA Walker D.P., Bi F.C., Kalgutkar A.S., Bauman J.N., Zhao S.X., Soglia J.R., RA Aspnes G.E., Kung D.W., Klug-McLeod J., Zawistoski M.P., McGlynn M.A., RA Oliver R., Dunn M., Li J.C., Richter D.T., Cooper B.A., Kath J.C., RA Hulford C.A., Autry C.L., Luzzio M.J., Ung E.J., Roberts W.G., RA Bonnette P.C., Buckbinder L., Mistry A., Griffor M.C., Han S., RA Guzman-Perez A.; RT "Trifluoromethylpyrimidine-based inhibitors of proline-rich tyrosine kinase RT 2 (PYK2): structure-activity relationships and strategies for the RT elimination of reactive metabolite formation."; RL Bioorg. Med. Chem. Lett. 18:6071-6077(2008). RN [46] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 861-1009 IN COMPLEX WITH PXN, AND RP INTERACTION WITH PXN. RX PubMed=19358827; DOI=10.1016/j.bbrc.2009.04.011; RA Lulo J., Yuzawa S., Schlessinger J.; RT "Crystal structures of free and ligand-bound focal adhesion targeting RT domain of Pyk2."; RL Biochem. Biophys. Res. Commun. 383:347-352(2009). RN [47] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 416-692 IN COMPLEX WITH INHIBITOR RP P1E, ROLE IN DISEASE, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=19428251; DOI=10.1016/j.bmcl.2009.04.093; RA Walker D.P., Zawistoski M.P., McGlynn M.A., Li J.C., Kung D.W., RA Bonnette P.C., Baumann A., Buckbinder L., Houser J.A., Boer J., Mistry A., RA Han S., Xing L., Guzman-Perez A.; RT "Sulfoximine-substituted trifluoromethylpyrimidine analogs as inhibitors of RT proline-rich tyrosine kinase 2 (PYK2) show reduced hERG activity."; RL Bioorg. Med. Chem. Lett. 19:3253-3258(2009). RN [48] RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 416-692 IN COMPLEXES WITH ATP RP ANALOG; PF-431396; BIRB796 AND PF-4618433, AND ROLE IN DISEASE. RX PubMed=19244237; DOI=10.1074/jbc.m809038200; RA Han S., Mistry A., Chang J.S., Cunningham D., Griffor M., Bonnette P.C., RA Wang H., Chrunyk B.A., Aspnes G.E., Walker D.P., Brosius A.D., RA Buckbinder L.; RT "Structural characterization of proline-rich tyrosine kinase 2 (PYK2) RT reveals a unique (DFG-out) conformation and enables inhibitor design."; RL J. Biol. Chem. 284:13193-13201(2009). RN [49] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 414-692. RG Structural genomics consortium (SGC); RT "Structure of protein tyrosine kinase 2 beta (PTK2B) kinase domain."; RL Submitted (JUL-2011) to the PDB data bank. RN [50] RP VARIANTS [LARGE SCALE ANALYSIS] GLU-359; HIS-698; PRO-808; THR-838 AND RP LYS-970. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). 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'. Promotes phosphorylation of NMDA receptors by SRC family CC members, and thereby contributes to the regulation of NMDA receptor ion CC channel activity and intracellular Ca(2+) levels. May also regulate CC potassium ion transport by phosphorylation of potassium channel CC subunits. Phosphorylates SRC; this increases SRC kinase activity. CC Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation CC of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2. CC {ECO:0000269|PubMed:10022920, ECO:0000269|PubMed:12771146, CC ECO:0000269|PubMed:12893833, ECO:0000269|PubMed:14585963, CC ECO:0000269|PubMed:15050747, ECO:0000269|PubMed:15166227, CC ECO:0000269|PubMed:17634955, ECO:0000269|PubMed:18086875, CC ECO:0000269|PubMed:18339875, ECO:0000269|PubMed:18587400, CC ECO:0000269|PubMed:18765415, ECO:0000269|PubMed:19086031, CC ECO:0000269|PubMed:19207108, ECO:0000269|PubMed:19244237, CC ECO:0000269|PubMed:19428251, ECO:0000269|PubMed:19648005, CC ECO:0000269|PubMed:19880522, ECO:0000269|PubMed:20001213, CC ECO:0000269|PubMed:20381867, ECO:0000269|PubMed:20521079, CC ECO:0000269|PubMed:21357692, ECO:0000269|PubMed:21533080, CC ECO:0000269|PubMed:7544443, ECO:0000269|PubMed:8670418, CC ECO:0000269|PubMed:8849729}. 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:15050747, ECO:0000269|PubMed:15166227, CC ECO:0000269|PubMed:18339875, ECO:0000269|PubMed:18951788, CC ECO:0000269|PubMed:19428251, ECO:0000269|PubMed:19648005}; 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 Inhibited by PF-562,271, BIRB796, PF-4618433 and by PF-431396, PF- CC 2318841 and their derivatives. Inhibited by sulfoximine-substituted CC trifluoromethylpyrimidines. Inhibited by 4-amino and 5-aryl substituted CC pyridinone compounds. {ECO:0000269|PubMed:18339875, CC ECO:0000269|PubMed:18951788, ECO:0000269|PubMed:19428251, CC ECO:0000269|PubMed:19648005}. CC -!- SUBUNIT: Homodimer, or homooligomer. Interacts with SIRPA and SH2D3C. CC Interacts with ARHGAP10. Interacts with DLG4 (By similarity). Interacts CC with KCNA2 (By similarity). Interacts with NPHP1, ASAP1, ASAP2, CC ARHGAP26, SKAP2 and TGFB1I1. The Tyr-402 phosphorylated form interacts CC with SRC (via SH2 domain) and SRC family members. Forms a signaling CC complex with EPHA1, LCK and phosphatidylinositol 3-kinase; upon CC activation by EFNA1. Interacts with GRB2 (via SH2 domain). Interacts CC with P53/TP53 and MDM2. Interacts with MYLK. Interacts with BCAR1. CC Interacts with PDPK1. Interacts (hypophosphorylated) with PXN. CC Interacts with RB1CC1. Interacts with RHOU. Interacts with VAV1. CC Interacts with LPXN and PTPN12. {ECO:0000250|UniProtKB:P70600, CC ECO:0000250|UniProtKB:Q9QVP9, ECO:0000269|PubMed:10022920, CC ECO:0000269|PubMed:10769033, ECO:0000269|PubMed:11493697, CC ECO:0000269|PubMed:12771146, ECO:0000269|PubMed:12893833, CC ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:17329398, CC ECO:0000269|PubMed:17634955, ECO:0000269|PubMed:18086875, CC ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:18765415, CC ECO:0000269|PubMed:18951788, ECO:0000269|PubMed:19086031, CC ECO:0000269|PubMed:19207108, ECO:0000269|PubMed:19358827, CC ECO:0000269|PubMed:19428251, ECO:0000269|PubMed:20521079, CC ECO:0000269|PubMed:21357692, ECO:0000269|PubMed:7544443, CC ECO:0000269|PubMed:8849729, ECO:0000269|PubMed:9422762}. CC -!- INTERACTION: CC Q14289; P05067: APP; NbExp=3; IntAct=EBI-298640, EBI-77613; CC Q14289; P06241: FYN; NbExp=5; IntAct=EBI-298640, EBI-515315; CC Q14289; O15259: NPHP1; NbExp=2; IntAct=EBI-298640, EBI-953828; CC Q14289; O75161: NPHP4; NbExp=2; IntAct=EBI-298640, EBI-4281852; CC Q14289; Q7L0Q8: RHOU; NbExp=4; IntAct=EBI-298640, EBI-1638043; CC Q14289; P12931: SRC; NbExp=3; IntAct=EBI-298640, EBI-621482; CC Q14289; P62258: YWHAE; NbExp=2; IntAct=EBI-298640, EBI-356498; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, perinuclear region. Cell CC membrane; Peripheral membrane protein; Cytoplasmic side. Cell junction, CC focal adhesion. Cell projection, lamellipodium. Cytoplasm, cell cortex. CC Nucleus. Note=Interaction with NPHP1 induces the membrane-association CC of the kinase. Colocalizes with integrins at the cell periphery. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q14289-1; Sequence=Displayed; CC Name=2; Synonyms=PYK2H; CC IsoId=Q14289-2; Sequence=VSP_004981; CC -!- TISSUE SPECIFICITY: Most abundant in the brain, with highest levels in CC amygdala and hippocampus. Low levels in kidney (at protein level). Also CC expressed in spleen and lymphocytes. {ECO:0000269|PubMed:7544443, CC ECO:0000269|PubMed:9545257}. 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. CC {ECO:0000269|PubMed:11493697, ECO:0000269|PubMed:15166227, CC ECO:0000269|PubMed:17329398, ECO:0000269|PubMed:18587400, CC ECO:0000269|PubMed:19207108, ECO:0000269|PubMed:20028775, CC ECO:0000269|PubMed:20381867, ECO:0000269|PubMed:20521079, CC ECO:0000269|PubMed:9545257}. CC -!- DISEASE: Note=Aberrant PTK2B/PYK2 expression may play a role in cancer CC cell proliferation, migration and invasion, in tumor formation and CC metastasis. Elevated PTK2B/PYK2 expression is seen in gliomas, CC hepatocellular carcinoma, lung cancer and breast cancer. CC -!- MISCELLANEOUS: Promotes bone resorption, and thus PTK2B/PYK2 inhibitors CC might be used to treat osteoporosis. 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; U33284; AAC50203.1; -; mRNA. DR EMBL; L49207; AAB47217.1; -; mRNA. DR EMBL; D45853; BAA08289.1; -; mRNA. DR EMBL; U43522; AAC05330.1; -; mRNA. DR EMBL; S80542; AAB35701.1; -; mRNA. DR EMBL; AF311103; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471080; EAW63553.1; -; Genomic_DNA. DR EMBL; CH471080; EAW63555.1; -; Genomic_DNA. DR EMBL; CH471080; EAW63556.1; -; Genomic_DNA. DR EMBL; BC036651; AAH36651.1; -; mRNA. DR EMBL; BC042599; AAH42599.1; -; mRNA. DR CCDS; CCDS6057.1; -. [Q14289-1] DR CCDS; CCDS6058.1; -. [Q14289-2] DR PIR; S60248; S60248. DR RefSeq; NP_004094.3; NM_004103.4. [Q14289-1] DR RefSeq; NP_775266.1; NM_173174.2. [Q14289-1] DR RefSeq; NP_775267.1; NM_173175.2. [Q14289-2] DR RefSeq; NP_775268.1; NM_173176.2. [Q14289-1] DR RefSeq; XP_005273504.1; XM_005273447.4. [Q14289-1] DR RefSeq; XP_011542743.1; XM_011544441.2. [Q14289-1] DR RefSeq; XP_016868703.1; XM_017013214.1. [Q14289-1] DR PDB; 2LK4; NMR; -; A=871-1005. DR PDB; 3CC6; X-ray; 1.60 A; A=414-692. DR PDB; 3ET7; X-ray; 2.70 A; A=416-692. DR PDB; 3FZO; X-ray; 2.20 A; A=416-692. DR PDB; 3FZP; X-ray; 2.10 A; A=416-692. DR PDB; 3FZR; X-ray; 2.70 A; A=416-692. DR PDB; 3FZS; X-ray; 1.75 A; A=416-692. DR PDB; 3FZT; X-ray; 1.95 A; A=416-692. DR PDB; 3GM1; X-ray; 2.95 A; A/B=861-1009. DR PDB; 3GM2; X-ray; 2.71 A; A=861-1009. DR PDB; 3GM3; X-ray; 2.60 A; A=861-1009. DR PDB; 3H3C; X-ray; 2.00 A; A=416-692. DR PDB; 3U3F; X-ray; 3.10 A; A/B/C/D=871-1005. DR PDB; 4EKU; X-ray; 3.25 A; A=21-409. DR PDB; 4H1J; X-ray; 2.00 A; A=416-692. DR PDB; 4H1M; X-ray; 1.99 A; A=416-692. DR PDB; 4R32; X-ray; 3.50 A; A=871-1005. DR PDB; 4XEF; X-ray; 2.50 A; A/D=871-1005. DR PDB; 4XEK; X-ray; 1.79 A; A=871-1005. DR PDB; 4XEV; X-ray; 2.01 A; A/D=871-1005. DR PDB; 5TO8; X-ray; 1.98 A; A=414-692. DR PDB; 5TOB; X-ray; 2.12 A; A=414-692. DR PDB; 6LF3; X-ray; 3.20 A; A/B/C/D/E/F=790-839. DR PDB; 7PLL; NMR; -; B=708-726. DR PDBsum; 2LK4; -. DR PDBsum; 3CC6; -. DR PDBsum; 3ET7; -. DR PDBsum; 3FZO; -. DR PDBsum; 3FZP; -. DR PDBsum; 3FZR; -. DR PDBsum; 3FZS; -. DR PDBsum; 3FZT; -. DR PDBsum; 3GM1; -. DR PDBsum; 3GM2; -. DR PDBsum; 3GM3; -. DR PDBsum; 3H3C; -. DR PDBsum; 3U3F; -. DR PDBsum; 4EKU; -. DR PDBsum; 4H1J; -. DR PDBsum; 4H1M; -. DR PDBsum; 4R32; -. DR PDBsum; 4XEF; -. DR PDBsum; 4XEK; -. DR PDBsum; 4XEV; -. DR PDBsum; 5TO8; -. DR PDBsum; 5TOB; -. DR PDBsum; 6LF3; -. DR PDBsum; 7PLL; -. DR AlphaFoldDB; Q14289; -. DR BMRB; Q14289; -. DR SMR; Q14289; -. DR BioGRID; 108480; 78. DR CORUM; Q14289; -. DR ELM; Q14289; -. DR IntAct; Q14289; 46. DR MINT; Q14289; -. DR STRING; 9606.ENSP00000380638; -. DR BindingDB; Q14289; -. DR ChEMBL; CHEMBL5469; -. DR DrugBank; DB08341; 4-{[4-{[(1R,2R)-2-(dimethylamino)cyclopentyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-N-methylbenzenesulfonamide. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB01645; Genistein. DR DrugBank; DB01097; Leflunomide. DR DrugCentral; Q14289; -. DR GuidetoPHARMACOLOGY; 2181; -. DR GlyGen; Q14289; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q14289; -. DR PhosphoSitePlus; Q14289; -. DR SwissPalm; Q14289; -. DR BioMuta; PTK2B; -. DR DMDM; 3183003; -. DR CPTAC; CPTAC-1791; -. DR CPTAC; CPTAC-2886; -. DR CPTAC; CPTAC-2887; -. DR EPD; Q14289; -. DR jPOST; Q14289; -. DR MassIVE; Q14289; -. DR MaxQB; Q14289; -. DR PaxDb; 9606-ENSP00000380638; -. DR PeptideAtlas; Q14289; -. DR ProteomicsDB; 59955; -. [Q14289-1] DR ProteomicsDB; 59956; -. [Q14289-2] DR Pumba; Q14289; -. DR TopDownProteomics; Q14289-2; -. [Q14289-2] DR Antibodypedia; 3551; 1182 antibodies from 44 providers. DR DNASU; 2185; -. DR Ensembl; ENST00000346049.10; ENSP00000332816.6; ENSG00000120899.18. [Q14289-1] DR Ensembl; ENST00000397501.5; ENSP00000380638.1; ENSG00000120899.18. [Q14289-1] DR Ensembl; ENST00000420218.3; ENSP00000391995.2; ENSG00000120899.18. [Q14289-2] DR Ensembl; ENST00000517339.5; ENSP00000427931.1; ENSG00000120899.18. [Q14289-2] DR GeneID; 2185; -. DR KEGG; hsa:2185; -. DR MANE-Select; ENST00000346049.10; ENSP00000332816.6; NM_173176.3; NP_775268.1. DR UCSC; uc003xfn.3; human. [Q14289-1] DR AGR; HGNC:9612; -. DR CTD; 2185; -. DR DisGeNET; 2185; -. DR GeneCards; PTK2B; -. DR HGNC; HGNC:9612; PTK2B. DR HPA; ENSG00000120899; Tissue enhanced (bone marrow, brain). DR MIM; 601212; gene. DR neXtProt; NX_Q14289; -. DR NIAGADS; ENSG00000120899; -. DR OpenTargets; ENSG00000120899; -. DR PharmGKB; PA33956; -. DR VEuPathDB; HostDB:ENSG00000120899; -. DR eggNOG; KOG4257; Eukaryota. DR GeneTree; ENSGT00940000157269; -. DR HOGENOM; CLU_002646_0_1_1; -. DR InParanoid; Q14289; -. DR OMA; EIMSYGQ; -. DR OrthoDB; 1614410at2759; -. DR PhylomeDB; Q14289; -. DR TreeFam; TF316643; -. DR BRENDA; 2.7.10.2; 2681. DR PathwayCommons; Q14289; -. DR Reactome; R-HSA-391160; Signal regulatory protein family interactions. DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway. DR Reactome; R-HSA-9013420; RHOU GTPase cycle. DR Reactome; R-HSA-9020558; Interleukin-2 signaling. DR SignaLink; Q14289; -. DR SIGNOR; Q14289; -. DR BioGRID-ORCS; 2185; 20 hits in 1194 CRISPR screens. DR ChiTaRS; PTK2B; human. DR EvolutionaryTrace; Q14289; -. DR GeneWiki; PTK2B; -. DR GenomeRNAi; 2185; -. DR Pharos; Q14289; Tclin. DR PRO; PR:Q14289; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q14289; Protein. DR Bgee; ENSG00000120899; Expressed in right hemisphere of cerebellum and 165 other cell types or tissues. DR ExpressionAtlas; Q14289; baseline and differential. DR GO; GO:0097440; C:apical dendrite; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0044297; C:cell body; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc. DR GO; GO:0005856; C:cytoskeleton; IEA:InterPro. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0030425; C:dendrite; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0043197; C:dendritic spine; IBA:GO_Central. DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0030426; C:growth cone; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0030027; C:lamellipodium; IDA: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:UniProtKB. DR GO; GO:0014069; C:postsynaptic density; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0099092; C:postsynaptic density, intracellular component; IEA:Ensembl. DR GO; GO:0098793; C:presynapse; IEA:Ensembl. DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl. DR GO; GO:0043423; F:3-phosphoinositide-dependent protein kinase binding; IEA:Ensembl. 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: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:0043621; F:protein self-association; IPI:BHF-UCL. DR GO; GO:0004713; F:protein tyrosine kinase activity; TAS:ProtInc. DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl. DR GO; GO:0042976; P:activation of Janus kinase activity; IMP:UniProtKB. DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW. DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc. DR GO; GO:0043534; P:blood vessel endothelial cell migration; IEA:Ensembl. DR GO; GO:0045453; P:bone resorption; ISS:UniProtKB. DR GO; GO:0007166; P:cell surface receptor signaling pathway; IMP: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; IEA:Ensembl. DR GO; GO:0071300; P:cellular response to retinoic acid; IMP:BHF-UCL. DR GO; GO:0070098; P:chemokine-mediated signaling pathway; ISS:UniProtKB. DR GO; GO:0030865; P:cortical cytoskeleton organization; ISS:UniProtKB. DR GO; GO:0086100; P:endothelin receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IBA:GO_Central. DR GO; GO:0048041; P:focal adhesion assembly; IEA:Ensembl. DR GO; GO:0014009; P:glial cell proliferation; IEA:Ensembl. DR GO; GO:0007229; P:integrin-mediated signaling pathway; IMP: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; IEA:Ensembl. DR GO; GO:0060291; P:long-term synaptic potentiation; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0000165; P:MAPK cascade; IEA:Ensembl. DR GO; GO:0002315; P:marginal zone B cell differentiation; ISS:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0030502; P:negative regulation of bone mineralization; ISS:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:UniProtKB. DR GO; GO:0010656; P:negative regulation of muscle cell apoptotic process; IEA:Ensembl. DR GO; GO:0045638; P:negative regulation of myeloid cell differentiation; IMP:UniProtKB. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0043267; P:negative regulation of potassium ion transport; IDA:UniProtKB. DR GO; GO:0031175; P:neuron projection development; IEA:Ensembl. DR GO; GO:0001556; P:oocyte maturation; IEA:Ensembl. DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IDA:CACAO. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB. DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IMP:UniProtKB. DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl. DR GO; GO:2000538; P:positive regulation of B cell chemotaxis; ISS:UniProtKB. DR GO; GO:0030307; P:positive regulation of cell growth; IEA:Ensembl. DR GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB. DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; IMP:UniProtKB. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl. DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; IEA:Ensembl. DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IDA:BHF-UCL. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP: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; IMP:UniProtKB. DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:BHF-UCL. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IEA:Ensembl. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:BHF-UCL. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISS:UniProtKB. DR GO; GO:0045860; P:positive regulation of protein kinase activity; IMP:UniProtKB. DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IEA:Ensembl. 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; IEA:Ensembl. DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; IEA:Ensembl. DR GO; GO:0099170; P:postsynaptic modulation of chemical synaptic transmission; IEA:Ensembl. DR GO; GO:0046777; P:protein autophosphorylation; TAS:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc. DR GO; GO:0065003; P:protein-containing complex assembly; TAS:ProtInc. DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISS:UniProtKB. DR GO; GO:0030155; P:regulation of cell adhesion; IMP:UniProtKB. DR GO; GO:0008360; P:regulation of cell shape; IMP:UniProtKB. DR GO; GO:0010758; P:regulation of macrophage chemotaxis; ISS: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; IEA:Ensembl. DR GO; GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; ISS:UniProtKB. DR GO; GO:0048167; P:regulation of synaptic plasticity; TAS:ARUK-UCL. DR GO; GO:2000058; P:regulation of ubiquitin-dependent protein catabolic process; IDA:UniProtKB. 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; IEA:Ensembl. 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; IEA:Ensembl. 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; IEA:Ensembl. 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; TAS:ProtInc. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0002040; P:sprouting angiogenesis; ISS:UniProtKB. DR GO; GO:0043149; P:stress fiber assembly; IEA:Ensembl. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IMP:UniProtKB. DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IMP:BHF-UCL. 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. DR Genevisible; Q14289; HS. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; Alternative splicing; Angiogenesis; KW ATP-binding; Cell junction; Cell membrane; Cell projection; Cytoplasm; KW Immunity; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; KW Reference proteome; Transferase; Tyrosine-protein kinase. FT CHAIN 1..1009 FT /note="Protein-tyrosine kinase 2-beta" FT /id="PRO_0000088081" 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 701..725 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 708..725 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:0000269|PubMed:19244237, FT ECO:0007744|PDB:3FZP" FT BINDING 457 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:19244237, FT ECO:0007744|PDB:3FZP" FT BINDING 503..509 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:19244237, FT ECO:0007744|PDB:3FZP" FT MOD_RES 361 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 375 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18088087, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:23186163" FT MOD_RES 399 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 402 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:11493697, FT ECO:0000269|PubMed:15166227, ECO:0000269|PubMed:17329398, FT ECO:0000269|PubMed:19207108, ECO:0000269|PubMed:20028775, FT ECO:0000269|PubMed:20381867, ECO:0000269|PubMed:20521079" FT MOD_RES 579 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q9QVP9" FT MOD_RES 580 FT /note="Phosphotyrosine; by SRC, FYN and LCK" FT /evidence="ECO:0000269|PubMed:20028775, FT ECO:0000269|PubMed:20381867" FT MOD_RES 722 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 762 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 765 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18691976" FT MOD_RES 819 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 834 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 839 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195" FT MOD_RES 842 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163" FT MOD_RES 849 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 866 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 881 FT /note="Phosphotyrosine; by SRC" FT /evidence="ECO:0000269|PubMed:20521079" FT VAR_SEQ 739..780 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9545257" FT /id="VSP_004981" FT VARIANT 359 FT /note="Q -> E (in dbSNP:rs56175011)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041687" FT VARIANT 698 FT /note="R -> H (in dbSNP:rs35174236)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041688" FT VARIANT 808 FT /note="L -> P (in dbSNP:rs55747955)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041689" FT VARIANT 838 FT /note="K -> T (in dbSNP:rs751019)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0007744|PubMed:19369195" FT /id="VAR_020284" FT VARIANT 970 FT /note="E -> K (in dbSNP:rs56263944)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041690" FT MUTAGEN 402 FT /note="Y->F: Abolishes autophosphorylation. Abolishes FT interaction with SRC." FT /evidence="ECO:0000269|PubMed:8849729" FT MUTAGEN 457 FT /note="K->A: Abolishes kinase activity." FT /evidence="ECO:0000269|PubMed:15166227" FT MUTAGEN 859 FT /note="P->A: Loss of interaction with NPHP1." FT /evidence="ECO:0000269|PubMed:11493697" FT MUTAGEN 881 FT /note="Y->F: Loss of phosphorylation site. Strongly reduced FT interaction with GRB2." FT /evidence="ECO:0000269|PubMed:20521079" FT CONFLICT 23 FT /note="A -> G (in Ref. 3; BAA08289/AAC05330)" FT /evidence="ECO:0000305" FT CONFLICT 256 FT /note="G -> P (in Ref. 2; AAB47217)" FT /evidence="ECO:0000305" FT CONFLICT 435 FT /note="F -> L (in Ref. 3; AAC05330)" FT /evidence="ECO:0000305" FT CONFLICT 780 FT /note="R -> G (in Ref. 2; AAB47217)" FT /evidence="ECO:0000305" FT CONFLICT 985 FT /note="V -> M (in Ref. 8; AAH36651)" FT /evidence="ECO:0000305" FT HELIX 35..37 FT /evidence="ECO:0007829|PDB:4EKU" FT STRAND 38..45 FT /evidence="ECO:0007829|PDB:4EKU" FT STRAND 48..50 FT /evidence="ECO:0007829|PDB:4EKU" FT HELIX 52..54 FT /evidence="ECO:0007829|PDB:4EKU" FT STRAND 55..62 FT /evidence="ECO:0007829|PDB:4EKU" FT HELIX 67..76 FT /evidence="ECO:0007829|PDB:4EKU" FT TURN 77..80 FT /evidence="ECO:0007829|PDB:4EKU" FT HELIX 87..89 FT /evidence="ECO:0007829|PDB:4EKU" FT STRAND 90..99 FT /evidence="ECO:0007829|PDB:4EKU" FT STRAND 102..105 FT /evidence="ECO:0007829|PDB:4EKU" FT HELIX 111..117 FT /evidence="ECO:0007829|PDB:4EKU" FT TURN 119..121 FT /evidence="ECO:0007829|PDB:4EKU" FT HELIX 124..126 FT /evidence="ECO:0007829|PDB:4EKU" FT STRAND 127..133 FT /evidence="ECO:0007829|PDB:4EKU" FT TURN 138..140 FT /evidence="ECO:0007829|PDB:4EKU" FT HELIX 141..144 FT /evidence="ECO:0007829|PDB:4EKU" FT HELIX 148..165 FT /evidence="ECO:0007829|PDB:4EKU" FT TURN 166..169 FT /evidence="ECO:0007829|PDB:4EKU" FT HELIX 172..186 FT /evidence="ECO:0007829|PDB:4EKU" FT TURN 187..189 FT /evidence="ECO:0007829|PDB:4EKU" FT HELIX 194..196 FT /evidence="ECO:0007829|PDB:4EKU" FT HELIX 198..207 FT /evidence="ECO:0007829|PDB:4EKU" FT HELIX 210..212 FT /evidence="ECO:0007829|PDB:4EKU" FT HELIX 216..221 FT /evidence="ECO:0007829|PDB:4EKU" FT HELIX 224..238 FT /evidence="ECO:0007829|PDB:4EKU" FT HELIX 243..254 FT /evidence="ECO:0007829|PDB:4EKU" FT STRAND 263..273 FT /evidence="ECO:0007829|PDB:4EKU" FT STRAND 277..282 FT /evidence="ECO:0007829|PDB:4EKU" FT STRAND 285..289 FT /evidence="ECO:0007829|PDB:4EKU" FT STRAND 297..300 FT /evidence="ECO:0007829|PDB:4EKU" FT HELIX 302..304 FT /evidence="ECO:0007829|PDB:4EKU" FT STRAND 310..313 FT /evidence="ECO:0007829|PDB:4EKU" FT TURN 314..316 FT /evidence="ECO:0007829|PDB:4EKU" FT STRAND 317..322 FT /evidence="ECO:0007829|PDB:4EKU" FT STRAND 331..336 FT /evidence="ECO:0007829|PDB:4EKU" FT HELIX 338..355 FT /evidence="ECO:0007829|PDB:4EKU" FT STRAND 356..360 FT /evidence="ECO:0007829|PDB:4EKU" FT HELIX 422..424 FT /evidence="ECO:0007829|PDB:3CC6" FT STRAND 425..433 FT /evidence="ECO:0007829|PDB:3CC6" FT STRAND 435..445 FT /evidence="ECO:0007829|PDB:3CC6" FT STRAND 447..449 FT /evidence="ECO:0007829|PDB:3FZR" FT STRAND 451..458 FT /evidence="ECO:0007829|PDB:3CC6" FT STRAND 461..463 FT /evidence="ECO:0007829|PDB:3FZO" FT HELIX 465..481 FT /evidence="ECO:0007829|PDB:3CC6" FT STRAND 489..493 FT /evidence="ECO:0007829|PDB:3CC6" FT STRAND 495..497 FT /evidence="ECO:0007829|PDB:3CC6" FT STRAND 499..503 FT /evidence="ECO:0007829|PDB:3CC6" FT HELIX 510..517 FT /evidence="ECO:0007829|PDB:3CC6" FT TURN 518..520 FT /evidence="ECO:0007829|PDB:3CC6" FT HELIX 523..542 FT /evidence="ECO:0007829|PDB:3CC6" FT STRAND 546..548 FT /evidence="ECO:0007829|PDB:5TO8" FT HELIX 552..554 FT /evidence="ECO:0007829|PDB:3CC6" FT STRAND 555..559 FT /evidence="ECO:0007829|PDB:3CC6" FT STRAND 562..565 FT /evidence="ECO:0007829|PDB:3CC6" FT HELIX 570..572 FT /evidence="ECO:0007829|PDB:3CC6" FT HELIX 589..591 FT /evidence="ECO:0007829|PDB:3CC6" FT HELIX 594..599 FT /evidence="ECO:0007829|PDB:3CC6" FT HELIX 604..619 FT /evidence="ECO:0007829|PDB:3CC6" FT TURN 620..622 FT /evidence="ECO:0007829|PDB:3CC6" FT TURN 625..628 FT /evidence="ECO:0007829|PDB:3CC6" FT HELIX 631..633 FT /evidence="ECO:0007829|PDB:3CC6" FT HELIX 634..640 FT /evidence="ECO:0007829|PDB:3CC6" FT HELIX 652..661 FT /evidence="ECO:0007829|PDB:3CC6" FT HELIX 666..668 FT /evidence="ECO:0007829|PDB:3CC6" FT HELIX 672..691 FT /evidence="ECO:0007829|PDB:3CC6" FT HELIX 879..897 FT /evidence="ECO:0007829|PDB:4XEK" FT HELIX 898..900 FT /evidence="ECO:0007829|PDB:3GM3" FT HELIX 903..905 FT /evidence="ECO:0007829|PDB:4XEK" FT HELIX 906..927 FT /evidence="ECO:0007829|PDB:4XEK" FT HELIX 928..930 FT /evidence="ECO:0007829|PDB:4XEK" FT HELIX 933..962 FT /evidence="ECO:0007829|PDB:4XEK" FT TURN 963..965 FT /evidence="ECO:0007829|PDB:4XEK" FT HELIX 969..1004 FT /evidence="ECO:0007829|PDB:4XEK" SQ SEQUENCE 1009 AA; 115875 MW; 420B21046274E7C2 CRC64; MSGVSEPLSR VKLGTLRRPE GPAEPMVVVP VDVEKEDVRI LKVCFYSNSF NPGKNFKLVK CTVQTEIREI ITSILLSGRI GPNIRLAECY GLRLKHMKSD EIHWLHPQMT VGEVQDKYEC LHVEAEWRYD LQIRYLPEDF MESLKEDRTT LLYFYQQLRN DYMQRYASKV SEGMALQLGC LELRRFFKDM PHNALDKKSN FELLEKEVGL DLFFPKQMQE NLKPKQFRKM IQQTFQQYAS LREEECVMKF FNTLAGFANI DQETYRCELI QGWNITVDLV IGPKGIRQLT SQDAKPTCLA EFKQIRSIRC LPLEEGQAVL QLGIEGAPQA LSIKTSSLAE AENMADLIDG YCRLQGEHQG SLIIHPRKDG EKRNSLPQIP MLNLEARRSH LSESCSIESD IYAEIPDETL RRPGGPQYGI AREDVVLNRI LGEGFFGEVY EGVYTNHKGE KINVAVKTCK KDCTLDNKEK FMSEAVIMKN LDHPHIVKLI GIIEEEPTWI IMELYPYGEL GHYLERNKNS LKVLTLVLYS LQICKAMAYL ESINCVHRDI AVRNILVASP ECVKLGDFGL SRYIEDEDYY KASVTRLPIK WMSPESINFR RFTTASDVWM FAVCMWEILS FGKQPFFWLE NKDVIGVLEK GDRLPKPDLC PPVLYTLMTR CWDYDPSDRP RFTELVCSLS DVYQMEKDIA MEQERNARYR TPKILEPTAF QEPPPKPSRP KYRPPPQTNL LAPKLQFQVP EGLCASSPTL TSPMEYPSPV NSLHTPPLHR HNVFKRHSMR EEDFIQPSSR EEAQQLWEAE KVKMRQILDK QQKQMVEDYQ WLRQEEKSLD PMVYMNDKSP LTPEKEVGYL EFTGPPQKPP RLGAQSIQPT ANLDRTDDLV YLNVMELVRA VLELKNELCQ LPPEGYVVVV KNVGLTLRKL IGSVDDLLPS LPSSSRTEIE GTQKLLNKDL AELINKMRLA QQNAVTSLSE ECKRQMLTAS HTLAVDAKNL LDAVDQAKVL ANLAHPPAE //