FAK2_HUMAN
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 03-AUG-2022, entry version 238.
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 -!- 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}.
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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 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 AlphaFoldDB; Q14289; -.
DR BMRB; Q14289; -.
DR SMR; Q14289; -.
DR BioGRID; 108480; 68.
DR CORUM; Q14289; -.
DR ELM; Q14289; -.
DR IntAct; Q14289; 43.
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; DB11817; Baricitinib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB01645; Genistein.
DR DrugBank; DB01097; Leflunomide.
DR DrugCentral; Q14289; -.
DR GuidetoPHARMACOLOGY; 2181; -.
DR iPTMnet; Q14289; -.
DR PhosphoSitePlus; Q14289; -.
DR SwissPalm; Q14289; -.
DR BioMuta; PTK2B; -.
DR DMDM; 3183003; -.
DR CPTAC; CPTAC-1791; -.
DR EPD; Q14289; -.
DR jPOST; Q14289; -.
DR MassIVE; Q14289; -.
DR MaxQB; Q14289; -.
DR PaxDb; Q14289; -.
DR PeptideAtlas; Q14289; -.
DR PRIDE; Q14289; -.
DR ProteomicsDB; 59955; -. [Q14289-1]
DR ProteomicsDB; 59956; -. [Q14289-2]
DR TopDownProteomics; Q14289-2; -. [Q14289-2]
DR Antibodypedia; 3551; 1056 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 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; IMELYSY; -.
DR OrthoDB; 43729at2759; -.
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; 19 hits in 1115 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 163 other tissues.
DR ExpressionAtlas; Q14289; baseline and differential.
DR Genevisible; Q14289; HS.
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:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; 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:0045121; C:membrane raft; IEA:Ensembl.
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: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:0008022; F:protein C-terminus binding; IMP:UniProtKB.
DR GO; GO:0043621; F:protein self-association; IPI:BHF-UCL.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR GO; GO:0090630; P:activation of GTPase activity; 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:0030154; P:cell differentiation; IBA:GO_Central.
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: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:0045087; P:innate immune response; IBA:GO_Central.
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:0043507; P:positive regulation of JUN kinase activity; IEA:Ensembl.
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:0051000; P:positive regulation of nitric-oxide synthase activity; IEA:Ensembl.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; ISS:UniProtKB.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; 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: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:2000249; P:regulation of actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0050848; P:regulation of calcium-mediated signaling; IEA:Ensembl.
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:0010752; P:regulation of cGMP-mediated signaling; IEA:Ensembl.
DR GO; GO:2000114; P:regulation of establishment of cell polarity; ISS:UniProtKB.
DR GO; GO:0032960; P:regulation of inositol trisphosphate biosynthetic process; ISS:UniProtKB.
DR GO; GO:0010758; P:regulation of macrophage chemotaxis; ISS:UniProtKB.
DR GO; GO:2000310; P:regulation of NMDA receptor activity; ISS:Alzheimers_University_of_Toronto.
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:0010226; P:response to lithium ion; 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:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
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 Gene3D; 1.20.80.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR041390; FADK_N.
DR InterPro; IPR041784; FAK1/PYK2_FERM_C.
DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_sf.
DR InterPro; IPR035963; FERM_2.
DR InterPro; IPR019748; FERM_central.
DR InterPro; IPR000299; FERM_domain.
DR InterPro; IPR036137; Focal_adhe_kin_target_dom_sf.
DR InterPro; IPR005189; Focal_adhesion_kin_target_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR030610; PTK2B.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR24418:SF94; PTHR24418:SF94; 1.
DR Pfam; PF00373; FERM_M; 1.
DR Pfam; PF18038; FERM_N_2; 1.
DR Pfam; PF03623; Focal_AT; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00295; B41; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF47031; SSF47031; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF68993; SSF68993; 1.
DR PROSITE; PS50057; FERM_3; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 1: Evidence at protein level;
KW 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
