FAK1_HUMAN
ID FAK1_HUMAN Reviewed; 1052 AA.
AC Q05397; B4E2N6; F5H4S4; J3QT16; Q14291; Q8IYN9; Q9UD85;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 03-AUG-2022, entry version 249.
DE RecName: Full=Focal adhesion kinase 1 {ECO:0000305};
DE Short=FADK 1;
DE EC=2.7.10.2;
DE AltName: Full=Focal adhesion kinase-related nonkinase;
DE Short=FRNK;
DE AltName: Full=Protein phosphatase 1 regulatory subunit 71;
DE Short=PPP1R71;
DE AltName: Full=Protein-tyrosine kinase 2;
DE AltName: Full=p125FAK;
DE AltName: Full=pp125FAK;
GN Name=PTK2 {ECO:0000312|HGNC:HGNC:9611}; Synonyms=FAK, FAK1;
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), AND TISSUE SPECIFICITY.
RC TISSUE=T-cell;
RX PubMed=7692878; DOI=10.1089/dna.1993.12.823;
RA Whitney G.S., Chan P.Y., Blake J., Cosand W.L., Neubauer M.G., Aruffo A.,
RA Kanner S.B.;
RT "Human T and B lymphocytes express a structurally conserved focal adhesion
RT kinase, pp125FAK.";
RL DNA Cell Biol. 12:823-830(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=8422239; DOI=10.1006/bbrc.1993.1022;
RA Andre E., Becker-Andre M.;
RT "Expression of an N-terminally truncated form of human focal adhesion
RT kinase in brain.";
RL Biochem. Biophys. Res. Commun. 190:140-147(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7).
RC TISSUE=Placenta;
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 [6]
RP PROTEIN SEQUENCE OF 2-19; 192-199; 222-236; 243-252; 350-364; 414-419;
RP 468-476; 562-569; 674-690; 798-811; 832-838; 904-933; 963-981; 989-1000 AND
RP 1003-1042, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Osteosarcoma;
RA Bienvenut W.V., Glen H., Brunton V.G., Frame M.C.;
RL Submitted (JUL-2007) to UniProtKB.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 552-602, AND TISSUE SPECIFICITY.
RC TISSUE=Melanocyte;
RX PubMed=8247543;
RA Lee S.-T., Strunk K.M., Spritz R.A.;
RT "A survey of protein tyrosine kinase mRNAs expressed in normal human
RT melanocytes.";
RL Oncogene 8:3403-3410(1993).
RN [8]
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 [9]
RP INTERACTION WITH TGFB1I1, AND MUTAGENESIS OF VAL-928 AND LEU-1034.
RX PubMed=9756887; DOI=10.1074/jbc.273.41.26516;
RA Fujita H., Kamiguchi K., Cho D., Shibanuma M., Morimoto C., Tachibana K.;
RT "Interaction of Hic-5, A senescence-related protein, with focal adhesion
RT kinase.";
RL J. Biol. Chem. 273:26516-26521(1998).
RN [10]
RP FUNCTION IN PXN PHOSPHORYLATION; REGULATION OF CELL SHAPE AND MIGRATION,
RP INTERACTION WITH EPHA2, AUTOPHOSPHORYLATION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, DEPHOSPHORYLATION BY PTPN11, AND SUBCELLULAR LOCATION.
RX PubMed=10655584; DOI=10.1038/35000008;
RA Miao H., Burnett E., Kinch M., Simon E., Wang B.;
RT "Activation of EphA2 kinase suppresses integrin function and causes focal-
RT adhesion-kinase dephosphorylation.";
RL Nat. Cell Biol. 2:62-69(2000).
RN [11]
RP FUNCTION IN CELL MIGRATION AND ACTIVATION OF BMX, CATALYTIC ACTIVITY,
RP AUTOPHOSPHORYLATION, MUTAGENESIS OF TYR-397, AND INTERACTION WITH BMX.
RX PubMed=11331870; DOI=10.1038/35074500;
RA Chen R., Kim O., Li M., Xiong X., Guan J.L., Kung H.J., Chen H.,
RA Shimizu Y., Qiu Y.;
RT "Regulation of the PH-domain-containing tyrosine kinase Etk by focal
RT adhesion kinase through the FERM domain.";
RL Nat. Cell Biol. 3:439-444(2001).
RN [12]
RP FUNCTION IN PHOSPHORYLATION OF SHC1, AUTOPHOSPHORYLATION, INTERACTION WITH
RP SHC1 AND SRC, AND ROLE IN DISEASE.
RX PubMed=11980671;
RA Hecker T.P., Grammer J.R., Gillespie G.Y., Stewart J. Jr., Gladson C.L.;
RT "Focal adhesion kinase enhances signaling through the Shc/extracellular
RT signal-regulated kinase pathway in anaplastic astrocytoma tumor biopsy
RT samples.";
RL Cancer Res. 62:2699-2707(2002).
RN [13]
RP INTERACTION WITH RB1CC1.
RX PubMed=12221124; DOI=10.1091/mbc.e02-05-0295;
RA Abbi S., Ueda H., Zheng C., Cooper L.A., Zhao J., Christopher R.,
RA Guan J.L.;
RT "Regulation of focal adhesion kinase by a novel protein inhibitor FIP200.";
RL Mol. Biol. Cell 13:3178-3191(2002).
RN [14]
RP PHOSPHORYLATION AT TYR-397; TYR-407; TYR-577; TYR-861 AND TYR-925, AND
RP INTERACTION WITH FGR.
RX PubMed=12387730; DOI=10.1042/bj20020410;
RA Relou I.A.M., Bax L.A.B., Van Rijn H.J.M., Akkerman J.-W.N.;
RT "Site-specific phosphorylation of platelet focal adhesion kinase by low-
RT density lipoprotein.";
RL Biochem. J. 369:407-416(2003).
RN [15]
RP FUNCTION IN INTEGRIN SIGNALING; REGULATION OF APOPTOSIS; REGULATION OF CELL
RP SHAPE AND ACTIVATION OF PHOSPHATIDYLINOSITOL KINASE AND AKT1 SIGNALING
RP PATHWAY.
RX PubMed=15166238; DOI=10.1074/jbc.m313265200;
RA Xia H., Nho R.S., Kahm J., Kleidon J., Henke C.A.;
RT "Focal adhesion kinase is upstream of phosphatidylinositol 3-kinase/Akt in
RT regulating fibroblast survival in response to contraction of type I
RT collagen matrices via a beta 1 integrin viability signaling pathway.";
RL J. Biol. Chem. 279:33024-33034(2004).
RN [16]
RP FUNCTION IN REGULATION OF CELL MIGRATION, AND PHOSPHORYLATION AT TYR-407;
RP TYR-397 AND TYR-576.
RX PubMed=15561106; DOI=10.1016/j.yexcr.2004.09.005;
RA Continolo S., Baruzzi A., Majeed M., Caveggion E., Fumagalli L.,
RA Lowell C.A., Berton G.;
RT "The proto-oncogene Fgr regulates cell migration and this requires its
RT plasma membrane localization.";
RL Exp. Cell Res. 302:253-269(2005).
RN [17]
RP INTERACTION WITH P53/TP53, AND SUBCELLULAR LOCATION.
RX PubMed=15855171; DOI=10.1074/jbc.m414172200;
RA Golubovskaya V.M., Finch R., Cance W.G.;
RT "Direct interaction of the N-terminal domain of focal adhesion kinase with
RT the N-terminal transactivation domain of p53.";
RL J. Biol. Chem. 280:25008-25021(2005).
RN [18]
RP FUNCTION IN FOCAL ADHESION DISASSEMBLY.
RX PubMed=15895076; DOI=10.1038/ncb1262;
RA Ezratty E.J., Partridge M.A., Gundersen G.G.;
RT "Microtubule-induced focal adhesion disassembly is mediated by dynamin and
RT focal adhesion kinase.";
RL Nat. Cell Biol. 7:581-590(2005).
RN [19]
RP INTERACTION WITH FLT4.
RX PubMed=16452200; DOI=10.1158/0008-5472.can-05-1661;
RA Garces C.A., Kurenova E.V., Golubovskaya V.M., Cance W.G.;
RT "Vascular endothelial growth factor receptor-3 and focal adhesion kinase
RT bind and suppress apoptosis in breast cancer cells.";
RL Cancer Res. 66:1446-1454(2006).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [21]
RP ALTERNATIVE PROMOTER USAGE, IDENTIFICATION OF ISOFORM 6, AND DEVELOPMENTAL
RP STAGE (ISOFORM 6).
RX PubMed=16998626; DOI=10.1007/s00795-006-0325-8;
RA Nagoshi Y., Yamamoto G., Irie T., Tachikawa T.;
RT "Expression of FAK-related non-kinase (FRNK) coincides with morphological
RT change in the early stage of cell adhesion.";
RL Med. Mol. Morphol. 39:154-160(2006).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [23]
RP ACTIVITY REGULATION, ROLE IN DISEASE, AND PHOSPHORYLATION AT TYR-397 AND
RP TYR-861.
RX PubMed=18006843; DOI=10.1158/0008-5472.can-07-2667;
RA Halder J., Lin Y.G., Merritt W.M., Spannuth W.A., Nick A.M., Honda T.,
RA Kamat A.A., Han L.Y., Kim T.J., Lu C., Tari A.M., Bornmann W.,
RA Fernandez A., Lopez-Berestein G., Sood A.K.;
RT "Therapeutic efficacy of a novel focal adhesion kinase inhibitor TAE226 in
RT ovarian carcinoma.";
RL Cancer Res. 67:10976-10983(2007).
RN [24]
RP FUNCTION, ACTIVITY REGULATION, ROLE IN DISEASE, AND PHOSPHORYLATION AT
RP TYR-397.
RX PubMed=17395594; DOI=10.1074/jbc.m606695200;
RA Slack-Davis J.K., Martin K.H., Tilghman R.W., Iwanicki M., Ung E.J.,
RA Autry C., Luzzio M.J., Cooper B., Kath J.C., Roberts W.G., Parsons J.T.;
RT "Cellular characterization of a novel focal adhesion kinase inhibitor.";
RL J. Biol. Chem. 282:14845-14852(2007).
RN [25]
RP FUNCTION IN OSTEOBLAST DIFFERENTIATION.
RX PubMed=16927379; DOI=10.1002/jcb.21074;
RA Salasznyk R.M., Klees R.F., Boskey A., Plopper G.E.;
RT "Activation of FAK is necessary for the osteogenic differentiation of human
RT mesenchymal stem cells on laminin-5.";
RL J. Cell. Biochem. 100:499-514(2007).
RN [26]
RP FUNCTION, ACTIVITY REGULATION, ROLE IN DISEASE, AND PHOSPHORYLATION AT
RP TYR-397.
RX PubMed=17431114; DOI=10.1158/1535-7163.mct-06-0476;
RA Liu T.J., LaFortune T., Honda T., Ohmori O., Hatakeyama S., Meyer T.,
RA Jackson D., de Groot J., Yung W.K.;
RT "Inhibition of both focal adhesion kinase and insulin-like growth factor-I
RT receptor kinase suppresses glioma proliferation in vitro and in vivo.";
RL Mol. Cancer Ther. 6:1357-1367(2007).
RN [27]
RP FUNCTION, AND INTERACTION WITH LPXN.
RX PubMed=18497331; DOI=10.1161/circresaha.107.170357;
RA Sundberg-Smith L.J., DiMichele L.A., Sayers R.L., Mack C.P., Taylor J.M.;
RT "The LIM protein leupaxin is enriched in smooth muscle and functions as an
RT serum response factor cofactor to induce smooth muscle cell gene
RT transcription.";
RL Circ. Res. 102:1502-1511(2008).
RN [28]
RP FUNCTION, AND INTERACTION WITH BMX.
RX PubMed=18292575; DOI=10.4049/jimmunol.180.5.3485;
RA Semaan N., Alsaleh G., Gottenberg J.E., Wachsmann D., Sibilia J.;
RT "Etk/BMX, a Btk family tyrosine kinase, and Mal contribute to the cross-
RT talk between MyD88 and FAK pathways.";
RL J. Immunol. 180:3485-3491(2008).
RN [29]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CASS4.
RX PubMed=18256281; DOI=10.1091/mbc.e07-09-0953;
RA Singh M.K., Dadke D., Nicolas E., Serebriiskii I.G., Apostolou S.,
RA Canutescu A., Egleston B.L., Golemis E.A.;
RT "A novel Cas family member, HEPL, regulates FAK and cell spreading.";
RL Mol. Biol. Cell 19:1627-1636(2008).
RN [30]
RP FUNCTION IN REGULATION OF P53/TP53 LEVELS; CELL PROLIFERATION AND CELL
RP SURVIVAL, AND SUBCELLULAR LOCATION.
RX PubMed=18206965; DOI=10.1016/j.molcel.2007.11.031;
RA Lim S.T., Chen X.L., Lim Y., Hanson D.A., Vo T.T., Howerton K.,
RA Larocque N., Fisher S.J., Schlaepfer D.D., Ilic D.;
RT "Nuclear FAK promotes cell proliferation and survival through FERM-enhanced
RT p53 degradation.";
RL Mol. Cell 29:9-22(2008).
RN [31]
RP INTERACTION WITH ESR1; PIK3R1 AND/OR PIK3R2 AND SRC.
RX PubMed=18657504; DOI=10.1016/j.molcel.2008.05.025;
RA Le Romancer M., Treilleux I., Leconte N., Robin-Lespinasse Y., Sentis S.,
RA Bouchekioua-Bouzaghou K., Goddard S., Gobert-Gosse S., Corbo L.;
RT "Regulation of estrogen rapid signaling through arginine methylation by
RT PRMT1.";
RL Mol. Cell 31:212-221(2008).
RN [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-13; SER-29; SER-887 AND
RP SER-910, 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 [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-910, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [34]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [35]
RP PHOSPHORYLATION AT TYR-397; TYR-576; TYR-577; SER-722; TYR-861 AND TYR-925,
RP AND IDENTIFICATION IN A COMPLEX WITH CTTN AND FER.
RX PubMed=19339212; DOI=10.1016/j.bbamcr.2009.01.015;
RA Oh M.A., Choi S., Lee M.J., Choi M.C., Lee S.A., Ko W., Cance W.G.,
RA Oh E.S., Buday L., Kim S.H., Lee J.W.;
RT "Specific tyrosine phosphorylation of focal adhesion kinase mediated by Fer
RT tyrosine kinase in suspended hepatocytes.";
RL Biochim. Biophys. Acta 1793:781-791(2009).
RN [36]
RP FUNCTION IN SRC-MEDIATED PHOSPHORYLATION OF PXN.
RX PubMed=19138410; DOI=10.1186/1471-2407-9-12;
RA Sachdev S., Bu Y., Gelman I.H.;
RT "Paxillin-Y118 phosphorylation contributes to the control of Src-induced
RT anchorage-independent growth by FAK and adhesion.";
RL BMC Cancer 9:12-12(2009).
RN [37]
RP INTERACTION WITH STEAP4.
RX PubMed=19787193; DOI=10.3892/ijmm_00000270;
RA Tamura T., Chiba J.;
RT "STEAP4 regulates focal adhesion kinase activation and CpG motifs within
RT STEAP4 promoter region are frequently methylated in DU145, human androgen-
RT independent prostate cancer cells.";
RL Int. J. Mol. Med. 24:599-604(2009).
RN [38]
RP INTERACTION WITH EMP2.
RX PubMed=19494199; DOI=10.1167/iovs.08-3315;
RA Morales S.A., Mareninov S., Coulam P., Wadehra M., Goodglick L., Braun J.,
RA Gordon L.K.;
RT "Functional consequences of interactions between FAK and epithelial
RT membrane protein 2 (EMP2).";
RL Invest. Ophthalmol. Vis. Sci. 50:4949-4956(2009).
RN [39]
RP FUNCTION IN SRC-MEDIATED PHOSPHORYLATION OF BCAR1, AND ROLE IN DISEASE.
RX PubMed=19147981; DOI=10.1172/jci37160;
RA Pylayeva Y., Gillen K.M., Gerald W., Beggs H.E., Reichardt L.F.,
RA Giancotti F.G.;
RT "Ras- and PI3K-dependent breast tumorigenesis in mice and humans requires
RT focal adhesion kinase signaling.";
RL J. Clin. Invest. 119:252-266(2009).
RN [40]
RP INTERACTION WITH EPHA1.
RX PubMed=19118217; DOI=10.1242/jcs.036467;
RA Yamazaki T., Masuda J., Omori T., Usui R., Akiyama H., Maru Y.;
RT "EphA1 interacts with integrin-linked kinase and regulates cell morphology
RT and motility.";
RL J. Cell Sci. 122:243-255(2009).
RN [41]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT TYR-5; THR-13; SER-29; TYR-397; TYR-570; SER-580 AND SER-910,
RP CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION
RP BY MASS 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 [42]
RP ROLE IN DISEASE, AND ACTIVITY REGULATION.
RX PubMed=20495381; DOI=10.4161/cbt.10.1.11993;
RA Sun H., Pisle S., Gardner E.R., Figg W.D.;
RT "Bioluminescent imaging study: FAK inhibitor, PF-562,271, preclinical study
RT in PC3M-luc-C6 local implant and metastasis xenograft models.";
RL Cancer Biol. Ther. 10:38-43(2010).
RN [43]
RP INTERACTION WITH LPXN.
RX PubMed=19917054; DOI=10.1111/j.1349-7006.2009.01398.x;
RA Tanaka T., Moriwaki K., Murata S., Miyasaka M.;
RT "LIM domain-containing adaptor, leupaxin, localizes in focal adhesion and
RT suppresses the integrin-induced tyrosine phosphorylation of paxillin.";
RL Cancer Sci. 101:363-368(2010).
RN [44]
RP FUNCTION (ISOFORM 6), AND TISSUE SPECIFICITY.
RX PubMed=20109444; DOI=10.1016/j.yexcr.2010.01.021;
RA Cai G.Q., Zheng A., Tang Q., White E.S., Chou C.F., Gladson C.L.,
RA Olman M.A., Ding Q.;
RT "Downregulation of FAK-related non-kinase mediates the migratory phenotype
RT of human fibrotic lung fibroblasts.";
RL Exp. Cell Res. 316:1600-1609(2010).
RN [45]
RP INTERACTION WITH ZFYVE21, AND DEPHOSPHORYLATION AT TYR-397.
RX PubMed=20439989; DOI=10.1074/jbc.m110.106443;
RA Nagano M., Hoshino D., Sakamoto T., Kawasaki N., Koshikawa N., Seiki M.;
RT "ZF21 protein regulates cell adhesion and motility.";
RL J. Biol. Chem. 285:21013-21022(2010).
RN [46]
RP INTERACTION WITH CD36.
RX PubMed=20037584; DOI=10.1038/ni.1836;
RA Stewart C.R., Stuart L.M., Wilkinson K., van Gils J.M., Deng J., Halle A.,
RA Rayner K.J., Boyer L., Zhong R., Frazier W.A., Lacy-Hulbert A.,
RA El Khoury J., Golenbock D.T., Moore K.J.;
RT "CD36 ligands promote sterile inflammation through assembly of a Toll-like
RT receptor 4 and 6 heterodimer.";
RL Nat. Immunol. 11:155-161(2010).
RN [47]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-910 AND THR-914, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [48]
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 [49]
RP INTERACTION WITH RET, FUNCTION IN RET PHOSPHORYLATION, AND PHOSPHORYLATION
RP AT TYR-576 AND TYR-577.
RX PubMed=21454698; DOI=10.1074/jbc.m110.168500;
RA Plaza-Menacho I., Morandi A., Mologni L., Boender P.,
RA Gambacorti-Passerini C., Magee A.I., Hofstra R.M.W., Knowles P.,
RA McDonald N.Q., Isacke C.M.;
RT "Focal adhesion kinase (FAK) binds RET kinase via its FERM domain, priming
RT a direct and reciprocal RET-FAK transactivation mechanism.";
RL J. Biol. Chem. 286:17292-17302(2011).
RN [50]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-13; SER-29; SER-843 AND
RP SER-910, AND 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 [51]
RP INTERACTION WITH CIB1 ISOFORM 2.
RC TISSUE=Brain;
RX PubMed=23503467; DOI=10.1038/onc.2013.43;
RA Armacki M., Joodi G., Nimmagadda S.C., de Kimpe L., Pusapati G.V.,
RA Vandoninck S., Van Lint J., Illing A., Seufferlein T.;
RT "A novel splice variant of calcium and integrin-binding protein 1 mediates
RT protein kinase D2-stimulated tumour growth by regulating angiogenesis.";
RL Oncogene 33:1167-1180(2014).
RN [52]
RP REVIEW ON SIGNALING AND ON DIRECT PTK2/FAK1 SUBSTRATES.
RX PubMed=10354709; DOI=10.1016/s0079-6107(98)00052-2;
RA Schlaepfer D.D., Hauck C.R., Sieg D.J.;
RT "Signaling through focal adhesion kinase.";
RL Prog. Biophys. Mol. Biol. 71:435-478(1999).
RN [53]
RP REVIEW ON FUNCTION IN NETRIN SIGNALING.
RX PubMed=15725728;
RA Nikolopoulos S.N., Giancotti F.G.;
RT "Netrin-integrin signaling in epithelial morphogenesis, axon guidance and
RT vascular patterning.";
RL Cell Cycle 4:E131-E135(2005).
RN [54]
RP REVIEW ON FUNCTION IN CELL MIGRATION; FOCAL ADHESION TURNOVER AND
RP ACTIVATION OF SIGNALING PATHWAYS, AND ROLE IN DISEASE.
RX PubMed=16919435; DOI=10.1016/j.ceb.2006.08.011;
RA Mitra S.K., Schlaepfer D.D.;
RT "Integrin-regulated FAK-Src signaling in normal and cancer cells.";
RL Curr. Opin. Cell Biol. 18:516-523(2006).
RN [55]
RP FUNCTION.
RX PubMed=17968709; DOI=10.1080/15216540701694245;
RA Vadali K., Cai X., Schaller M.D.;
RT "Focal adhesion kinase: an essential kinase in the regulation of
RT cardiovascular functions.";
RL IUBMB Life 59:709-716(2007).
RN [56]
RP REVIEW ON ROLE IN INTEGRIN SIGNALING AND IN REGULATION OF P53/TP53
RP ACTIVITIES, ROLE IN DISEASE, AND ACTIVITY REGULATION.
RX PubMed=18677107; DOI=10.4161/cc.6367;
RA Lim S.T., Mikolon D., Stupack D.G., Schlaepfer D.D.;
RT "FERM control of FAK function: implications for cancer therapy.";
RL Cell Cycle 7:2306-2314(2008).
RN [57]
RP REVIEW ON FUNCTION IN REGULATION OF RHO FAMILY GTPASE ACTIVITY.
RX PubMed=19525103; DOI=10.1016/j.ceb.2009.05.006;
RA Tomar A., Schlaepfer D.D.;
RT "Focal adhesion kinase: switching between GAPs and GEFs in the regulation
RT of cell motility.";
RL Curr. Opin. Cell Biol. 21:676-683(2009).
RN [58]
RP REVIEW ON EXPRESSION IN CANCER, AND ROLE IN DISEASE.
RX PubMed=19224453; DOI=10.14670/hh-24.503;
RA Golubovskaya V.M., Kweh F.A., Cance W.G.;
RT "Focal adhesion kinase and cancer.";
RL Histol. Histopathol. 24:503-510(2009).
RN [59]
RP REVIEW ON FUNCTION IN REGULATION OF P53/TP53.
RX PubMed=20515733; DOI=10.2741/3653;
RA Golubovskaya V.M., Cance W.;
RT "Focal adhesion kinase and p53 signal transduction pathways in cancer.";
RL Front. Biosci. 15:901-912(2010).
RN [60]
RP REVIEW ON ROLE IN DEVELOPMENT.
RX PubMed=20552554; DOI=10.14670/hh-25.1039;
RA Chatzizacharias N.A., Kouraklis G.P., Theocharis S.E.;
RT "The role of focal adhesion kinase in early development.";
RL Histol. Histopathol. 25:1039-1055(2010).
RN [61]
RP REVIEW ON FUNCTION IN INTEGRIN SIGNALING AND ACTIVATION OF DOWNSTREAM
RP SIGNALING PATHWAYS.
RX PubMed=20101634; DOI=10.1002/iub.303;
RA Guan J.L.;
RT "Integrin signaling through FAK in the regulation of mammary stem cells and
RT breast cancer.";
RL IUBMB Life 62:268-276(2010).
RN [62]
RP FUNCTION, AND SIGNALING.
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 [63]
RP REVIEW ON FUNCTION; SUBUNIT; PHOSPHORYLATION; ACTIVITY REGULATION AND ROLE
RP IN DISEASE.
RX PubMed=21482413; DOI=10.1016/b978-0-12-386041-5.00005-4;
RA Hall J.E., Fu W., Schaller M.D.;
RT "Focal adhesion kinase: exploring Fak structure to gain insight into
RT function.";
RL Int. Rev. Cell Mol. Biol. 288:185-225(2011).
RN [64]
RP INTERACTION WITH MISP.
RX PubMed=23509069; DOI=10.1083/jcb.201207050;
RA Zhu M., Settele F., Kotak S., Sanchez-Pulido L., Ehret L., Ponting C.P.,
RA Goenczy P., Hoffmann I.;
RT "MISP is a novel Plk1 substrate required for proper spindle orientation and
RT mitotic progression.";
RL J. Cell Biol. 200:773-787(2013).
RN [65]
RP SUBUNIT.
RX PubMed=29069646; DOI=10.1159/000484298;
RA Rui Y.N., Xu Z., Fang X., Menezes M.R., Balzeau J., Niu A., Hagan J.P.,
RA Kim D.H.;
RT "The Intracranial Aneurysm Gene THSD1 Connects Endosome Dynamics to Nascent
RT Focal Adhesion Assembly.";
RL Cell. Physiol. Biochem. 43:2200-2211(2017).
RN [66]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=31630787; DOI=10.1016/j.ajhg.2019.09.022;
RA Wallmeier J., Frank D., Shoemark A., Noethe-Menchen T., Cindric S.,
RA Olbrich H., Loges N.T., Aprea I., Dougherty G.W., Pennekamp P., Kaiser T.,
RA Mitchison H.M., Hogg C., Carr S.B., Zariwala M.A., Ferkol T., Leigh M.W.,
RA Davis S.D., Atkinson J., Dutcher S.K., Knowles M.R., Thiele H.,
RA Altmueller J., Krenz H., Woeste M., Brentrup A., Ahrens F., Vogelberg C.,
RA Morris-Rosendahl D.J., Omran H.;
RT "De Novo Mutations in FOXJ1 Result in a Motile Ciliopathy with
RT Hydrocephalus and Randomization of Left/Right Body Asymmetry.";
RL Am. J. Hum. Genet. 105:1030-1039(2019).
RN [67]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 891-1052, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=12005431; DOI=10.1016/s0969-2126(02)00717-7;
RA Arold S.T., Hoellerer M.K., Noble M.E.;
RT "The structural basis of localization and signaling by the focal adhesion
RT targeting domain.";
RL Structure 10:319-327(2002).
RN [68]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 411-686 IN COMPLEX WITH ATP.
RX PubMed=12467573; DOI=10.1016/s0969-2126(02)00907-3;
RA Nowakowski J., Cronin C.N., McRee D.E., Knuth M.W., Nelson C.G.,
RA Pavletich N.P., Rogers J., Sang B.C., Scheibe D.N., Swanson R.V.,
RA Thompson D.A.;
RT "Structures of the cancer-related Aurora-A, FAK, and EphA2 protein kinases
RT from nanovolume crystallography.";
RL Structure 10:1659-1667(2002).
RN [69]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 892-1052 IN COMPLEX WITH PXN, AND
RP INTERACTION WITH PXN.
RX PubMed=14527389; DOI=10.1016/j.str.2003.08.010;
RA Hoellerer M.K., Noble M.E., Labesse G., Campbell I.D., Werner J.M.,
RA Arold S.T.;
RT "Molecular recognition of paxillin LD motifs by the focal adhesion
RT targeting domain.";
RL Structure 11:1207-1217(2003).
RN [70]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 414-689 IN COMPLEX WITH
RP INHIBITOR, CATALYTIC ACTIVITY, AND AUTOPHOSPHORYLATION.
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 [71]
RP X-RAY CRYSTALLOGRAPHY (2.82 ANGSTROMS) OF 891-1052 IN COMPLEX WITH CD4,
RP SUBCELLULAR LOCATION, AND INTERACTION WITH CD4.
RX PubMed=18078954; DOI=10.1016/j.jmb.2007.11.040;
RA Garron M.L., Arthos J., Guichou J.F., McNally J., Cicala C., Arold S.T.;
RT "Structural basis for the interaction between focal adhesion kinase and
RT CD4.";
RL J. Mol. Biol. 375:1320-1328(2008).
RN [72]
RP VARIANTS [LARGE SCALE ANALYSIS] PRO-292; GLN-292; ALA-793; GLU-1030 AND
RP GLU-1044.
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 plays an essential
CC role in regulating cell migration, adhesion, spreading, reorganization
CC of the actin cytoskeleton, formation and disassembly of focal adhesions
CC and cell protrusions, cell cycle progression, cell proliferation and
CC apoptosis. Required for early embryonic development and placenta
CC development. Required for embryonic angiogenesis, normal cardiomyocyte
CC migration and proliferation, and normal heart development. Regulates
CC axon growth and neuronal cell migration, axon branching and synapse
CC formation; required for normal development of the nervous system. Plays
CC a role in osteogenesis and differentiation of osteoblasts. Functions in
CC integrin signal transduction, but also in signaling downstream of
CC numerous growth factor receptors, G-protein coupled receptors (GPCR),
CC EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling
CC complexes with SRC and SRC family members upon activation; this leads
CC to the phosphorylation of additional tyrosine residues, creating
CC binding sites for scaffold proteins, effectors and substrates.
CC Regulates numerous signaling pathways. Promotes activation of
CC phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes
CC activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling
CC cascade. Promotes localized and transient activation of guanine
CC nucleotide exchange factors (GEFs) and GTPase-activating proteins
CC (GAPs), and thereby modulates the activity of Rho family GTPases.
CC Signaling via CAS family members mediates activation of RAC1. Recruits
CC the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby
CC regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal
CC degradation. Phosphorylates SRC; this increases SRC kinase activity.
CC Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes
CC phosphorylation of PXN and STAT1; most likely PXN and STAT1 are
CC phosphorylated by a SRC family kinase that is recruited to
CC autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes
CC phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and
CC PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK)
CC does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation
CC and signaling. Its enhanced expression can attenuate the nuclear
CC accumulation of LPXN and limit its ability to enhance serum response
CC factor (SRF)-dependent gene transcription.
CC {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:11331870,
CC ECO:0000269|PubMed:11980671, ECO:0000269|PubMed:15166238,
CC ECO:0000269|PubMed:15561106, ECO:0000269|PubMed:15895076,
CC ECO:0000269|PubMed:16919435, ECO:0000269|PubMed:16927379,
CC ECO:0000269|PubMed:17395594, ECO:0000269|PubMed:17431114,
CC ECO:0000269|PubMed:17968709, ECO:0000269|PubMed:18006843,
CC ECO:0000269|PubMed:18206965, ECO:0000269|PubMed:18256281,
CC ECO:0000269|PubMed:18292575, ECO:0000269|PubMed:18497331,
CC ECO:0000269|PubMed:18677107, ECO:0000269|PubMed:19138410,
CC ECO:0000269|PubMed:19147981, ECO:0000269|PubMed:19224453,
CC ECO:0000269|PubMed:20332118, ECO:0000269|PubMed:20495381,
CC ECO:0000269|PubMed:21454698}.
CC -!- FUNCTION: [Isoform 6]: Isoform 6 (FRNK) does not contain a kinase
CC domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its
CC enhanced expression can attenuate the nuclear accumulation of LPXN and
CC limit its ability to enhance serum response factor (SRF)-dependent gene
CC transcription. {ECO:0000269|PubMed:20109444}.
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:10655584, ECO:0000269|PubMed:11331870,
CC ECO:0000269|PubMed:18339875};
CC -!- ACTIVITY REGULATION: Subject to autoinhibition, mediated by
CC interactions between the FERM domain and the kinase domain. Activated
CC by autophosphorylation at Tyr-397. This promotes interaction with SRC
CC and phosphorylation at Tyr-576 and Tyr-577 in the kinase activation
CC loop. Phosphorylation at Tyr-576 and Tyr-577 is required for maximal
CC kinase activity. Inhibited by TAC544, TAE226, PF-573,228 and PF-
CC 562,271. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:17395594,
CC ECO:0000269|PubMed:17431114, ECO:0000269|PubMed:18006843,
CC ECO:0000269|PubMed:18677107, ECO:0000269|PubMed:20495381}.
CC -!- SUBUNIT: Interacts (via first Pro-rich region) with CAS family members
CC (via SH3 domain), including BCAR1, BCAR3, CASS4 and NEDD9. Interacts
CC with GIT1. Interacts with SORBS1. Interacts with ARHGEF28. Interacts
CC with SHB. Part of a complex composed of THSD1, PTK2/FAK1, TLN1 and VCL
CC (PubMed:29069646). Interacts with PXN and TLN1. Interacts with STAT1.
CC Interacts with DCC. Interacts with WASL. Interacts with ARHGEF7.
CC Interacts with GRB2 and GRB7 (By similarity). Component of a complex
CC that contains at least FER, CTTN and PTK2/FAK1. Interacts with BMX.
CC Interacts with TGFB1I1. Interacts with STEAP4. Interacts with ZFYVE21.
CC Interacts with ESR1. Interacts with PIK3R1 or PIK3R2. Interacts with
CC SRC, FGR, FLT4 and RET. Interacts with EPHA2 in resting cells;
CC activation of EPHA2 recruits PTPN11, leading to dephosphorylation of
CC PTK2/FAK1 and dissociation of the complex. Interacts with EPHA1 (kinase
CC activity-dependent). Interacts with CD4; this interaction requires the
CC presence of HIV-1 gp120. Interacts with PIAS1. Interacts with ARHGAP26
CC and SHC1. Interacts with RB1CC1; this inhibits PTK2/FAK1 activity and
CC activation of downstream signaling pathways. Interacts with P53/TP53
CC and MDM2. Interacts with LPXN (via LD motif 3). Interacts with MISP.
CC Interacts with CIB1 isoform 2. Interacts with CD36. Interacts with
CC EMP2; regulates PTK2 activation and localization (PubMed:19494199).
CC Interacts with DSCAM (By similarity). Interacts with AMBRA1 (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:P34152,
CC ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:11331870,
CC ECO:0000269|PubMed:11980671, ECO:0000269|PubMed:12221124,
CC ECO:0000269|PubMed:12387730, ECO:0000269|PubMed:12467573,
CC ECO:0000269|PubMed:14527389, ECO:0000269|PubMed:15855171,
CC ECO:0000269|PubMed:16452200, ECO:0000269|PubMed:18078954,
CC ECO:0000269|PubMed:18256281, ECO:0000269|PubMed:18292575,
CC ECO:0000269|PubMed:18339875, ECO:0000269|PubMed:18497331,
CC ECO:0000269|PubMed:18657504, ECO:0000269|PubMed:19118217,
CC ECO:0000269|PubMed:19339212, ECO:0000269|PubMed:19494199,
CC ECO:0000269|PubMed:19787193, ECO:0000269|PubMed:19917054,
CC ECO:0000269|PubMed:20037584, ECO:0000269|PubMed:20439989,
CC ECO:0000269|PubMed:21454698, ECO:0000269|PubMed:23503467,
CC ECO:0000269|PubMed:23509069, ECO:0000269|PubMed:29069646,
CC ECO:0000269|PubMed:9422762, ECO:0000269|PubMed:9756887}.
CC -!- INTERACTION:
CC Q05397; P56945: BCAR1; NbExp=2; IntAct=EBI-702142, EBI-702093;
CC Q05397; P46108: CRK; NbExp=3; IntAct=EBI-702142, EBI-886;
CC Q05397; P00533: EGFR; NbExp=7; IntAct=EBI-702142, EBI-297353;
CC Q05397; P29317: EPHA2; NbExp=3; IntAct=EBI-702142, EBI-702104;
CC Q05397; P06241: FYN; NbExp=3; IntAct=EBI-702142, EBI-515315;
CC Q05397; P62993: GRB2; NbExp=4; IntAct=EBI-702142, EBI-401755;
CC Q05397; Q14451: GRB7; NbExp=3; IntAct=EBI-702142, EBI-970191;
CC Q05397; P08631-2: HCK; NbExp=2; IntAct=EBI-702142, EBI-9834454;
CC Q05397; P16144: ITGB4; NbExp=7; IntAct=EBI-702142, EBI-948678;
CC Q05397; Q92569: PIK3R3; NbExp=3; IntAct=EBI-702142, EBI-79893;
CC Q05397; P25105: PTAFR; NbExp=2; IntAct=EBI-702142, EBI-3906092;
CC Q05397; Q9H3S7: PTPN23; NbExp=4; IntAct=EBI-702142, EBI-724478;
CC Q05397; P29350-3: PTPN6; NbExp=3; IntAct=EBI-702142, EBI-7399369;
CC Q05397; Q9Y3E5: PTRH2; NbExp=2; IntAct=EBI-702142, EBI-1056751;
CC Q05397; P49023: PXN; NbExp=18; IntAct=EBI-702142, EBI-702209;
CC Q05397; Q9NP31: SH2D2A; NbExp=3; IntAct=EBI-702142, EBI-490630;
CC Q05397; P12931: SRC; NbExp=9; IntAct=EBI-702142, EBI-621482;
CC Q05397; Q96SB4: SRPK1; NbExp=2; IntAct=EBI-702142, EBI-539478;
CC Q05397; P42224: STAT1; NbExp=3; IntAct=EBI-702142, EBI-1057697;
CC Q05397; O43294: TGFB1I1; NbExp=4; IntAct=EBI-702142, EBI-1051449;
CC Q05397; Q68CZ2: TNS3; NbExp=3; IntAct=EBI-702142, EBI-1220488;
CC Q05397; P04637: TP53; NbExp=13; IntAct=EBI-702142, EBI-366083;
CC Q05397; P07947: YES1; NbExp=2; IntAct=EBI-702142, EBI-515331;
CC Q05397; Q824H6: CCA_00170; Xeno; NbExp=3; IntAct=EBI-702142, EBI-26494126;
CC Q05397; P05480: Src; Xeno; NbExp=5; IntAct=EBI-702142, EBI-298680;
CC Q05397; Q62219: Tgfb1i1; Xeno; NbExp=3; IntAct=EBI-702142, EBI-642844;
CC -!- SUBCELLULAR LOCATION: Cell junction, focal adhesion. Cell membrane;
CC Peripheral membrane protein; Cytoplasmic side. Cytoplasm, cell cortex.
CC Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250}. Nucleus. Cytoplasm,
CC cytoskeleton, cilium basal body {ECO:0000269|PubMed:31630787}.
CC Note=Constituent of focal adhesions. Detected at microtubules.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=7;
CC Name=1;
CC IsoId=Q05397-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q05397-2; Sequence=VSP_004967, VSP_004968, VSP_004969,
CC VSP_004970;
CC Name=3;
CC IsoId=Q05397-3; Sequence=VSP_004967, VSP_004968, VSP_004969,
CC VSP_004973, VSP_004974;
CC Name=4;
CC IsoId=Q05397-4; Sequence=VSP_004967, VSP_004968, VSP_004969,
CC VSP_004971, VSP_004972;
CC Name=5;
CC IsoId=Q05397-5; Sequence=VSP_042169, VSP_042170;
CC Name=6; Synonyms=FRNK;
CC IsoId=Q05397-6; Sequence=VSP_042168;
CC Name=7;
CC IsoId=Q05397-7; Sequence=VSP_057268;
CC -!- TISSUE SPECIFICITY: Detected in B and T-lymphocytes. Isoform 1 and
CC isoform 6 are detected in lung fibroblasts (at protein level).
CC Ubiquitous. Expressed in epithelial cells (at protein level)
CC (PubMed:31630787). {ECO:0000269|PubMed:20109444,
CC ECO:0000269|PubMed:31630787, ECO:0000269|PubMed:7692878,
CC ECO:0000269|PubMed:8247543, ECO:0000269|PubMed:8422239}.
CC -!- DEVELOPMENTAL STAGE: [Isoform 6]: Detected in cultured cells,
CC immediately after seeding and before formation of focal adhesions (at
CC protein level). {ECO:0000269|PubMed:20109444}.
CC -!- DOMAIN: The Pro-rich regions interact with the SH3 domain of CAS family
CC members, such as BCAR1 and NEDD9, and with the GTPase activating
CC protein ARHGAP26.
CC -!- DOMAIN: The carboxy-terminal region is the site of focal adhesion
CC targeting (FAT) sequence which mediates the localization of FAK1 to
CC focal adhesions.
CC -!- PTM: Phosphorylated on tyrosine residues upon activation, e.g. upon
CC integrin signaling. Tyr-397 is the major autophosphorylation site, but
CC other kinases can also phosphorylate this residue. Phosphorylation at
CC Tyr-397 promotes interaction with SRC and SRC family members, leading
CC to phosphorylation at Tyr-576, Tyr-577 and at additional tyrosine
CC residues. FGR promotes phosphorylation at Tyr-397 and Tyr-576. FER
CC promotes phosphorylation at Tyr-577, Tyr-861 and Tyr-925, even when
CC cells are not adherent. Tyr-397, Tyr-576 and Ser-722 are phosphorylated
CC only when cells are adherent. Phosphorylation at Tyr-397 is important
CC for interaction with BMX, PIK3R1 and SHC1. Phosphorylation at Tyr-925
CC is important for interaction with GRB2. Dephosphorylated by PTPN11;
CC PTPN11 is recruited to PTK2 via EPHA2 (tyrosine phosphorylated).
CC Microtubule-induced dephosphorylation at Tyr-397 is crucial for the
CC induction of focal adhesion disassembly; this dephosphorylation could
CC be catalyzed by PTPN11 and regulated by ZFYVE21. Phosphorylation on
CC tyrosine residues is enhanced by NTN1 (By similarity).
CC {ECO:0000250|UniProtKB:P34152, ECO:0000269|PubMed:12387730,
CC ECO:0000269|PubMed:15561106, ECO:0000269|PubMed:17395594,
CC ECO:0000269|PubMed:17431114, ECO:0000269|PubMed:18006843,
CC ECO:0000269|PubMed:19339212, ECO:0000269|PubMed:21454698}.
CC -!- PTM: Sumoylated; this enhances autophosphorylation. {ECO:0000250}.
CC -!- DISEASE: Note=Aberrant PTK2/FAK1 expression may play a role in cancer
CC cell proliferation, migration and invasion, in tumor formation and
CC metastasis. PTK2/FAK1 overexpression is seen in many types of cancer.
CC -!- MISCELLANEOUS: [Isoform 6]: Produced by alternative promoter usage.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. FAK subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PTK2ID41898ch8q24.html";
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DR EMBL; L13616; AAA58469.1; -; mRNA.
DR EMBL; L05186; AAA35819.1; -; mRNA.
DR EMBL; AK304356; BAG65198.1; -; mRNA.
DR EMBL; AC067931; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC100860; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC105009; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC105235; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF458878; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF458882; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC035404; AAH35404.1; -; mRNA.
DR CCDS; CCDS56557.1; -. [Q05397-5]
DR CCDS; CCDS6381.1; -. [Q05397-1]
DR PIR; I53012; I53012.
DR PIR; PC1225; PC1225.
DR RefSeq; NP_001186578.1; NM_001199649.1. [Q05397-5]
DR RefSeq; NP_722560.1; NM_153831.3. [Q05397-1]
DR RefSeq; XP_016869162.1; XM_017013673.1.
DR PDB; 1K04; X-ray; 1.95 A; A=891-1052.
DR PDB; 1K05; X-ray; 2.90 A; A/B/C=891-1052.
DR PDB; 1MP8; X-ray; 1.60 A; A=411-686.
DR PDB; 1OW6; X-ray; 2.35 A; A/B/C=892-1052.
DR PDB; 1OW7; X-ray; 2.60 A; A/B/C=892-1052.
DR PDB; 1OW8; X-ray; 2.85 A; A/B/C=892-1052.
DR PDB; 2ETM; X-ray; 2.30 A; A/B=411-689.
DR PDB; 2IJM; X-ray; 2.19 A; A/B=411-689.
DR PDB; 3B71; X-ray; 2.82 A; A/B/C=891-1052.
DR PDB; 3BZ3; X-ray; 2.20 A; A=414-689.
DR PDB; 3PXK; X-ray; 1.79 A; A/B=411-689.
DR PDB; 3S9O; X-ray; 2.60 A; A/B/C=891-1052.
DR PDB; 4EBV; X-ray; 1.67 A; A=411-686.
DR PDB; 4EBW; X-ray; 2.65 A; A=411-686.
DR PDB; 4GU6; X-ray; 1.95 A; A/B=411-689.
DR PDB; 4GU9; X-ray; 2.40 A; A/B=410-686.
DR PDB; 4I4E; X-ray; 1.55 A; A=411-686.
DR PDB; 4I4F; X-ray; 1.75 A; A=411-686.
DR PDB; 4K8A; X-ray; 2.91 A; A/B=410-686.
DR PDB; 4K9Y; X-ray; 2.00 A; A=410-686.
DR PDB; 4KAB; X-ray; 2.71 A; A/B=410-686.
DR PDB; 4KAO; X-ray; 2.39 A; A/B=410-689.
DR PDB; 4NY0; X-ray; 2.80 A; A/B/C/D=31-405.
DR PDB; 4Q9S; X-ray; 2.07 A; A=411-686.
DR PDB; 6I8Z; X-ray; 1.99 A; A=411-689.
DR PDB; 6LES; X-ray; 2.00 A; A/B/X/Y=805-832.
DR PDB; 6PW8; X-ray; 1.95 A; A=922-1047.
DR PDB; 6YOJ; X-ray; 1.36 A; A=411-689.
DR PDB; 6YQ1; X-ray; 1.78 A; A/B/C/D=411-689.
DR PDB; 6YR9; X-ray; 1.93 A; A/B/C/D=411-689.
DR PDB; 6YT6; X-ray; 1.54 A; A/B=411-689.
DR PDB; 6YVS; X-ray; 1.81 A; A/B/C/D=411-689.
DR PDB; 6YVY; X-ray; 1.92 A; A/B/C/D=411-689.
DR PDB; 6YXV; X-ray; 2.30 A; A/B/C/D=411-689.
DR PDB; 7PI4; X-ray; 2.24 A; DDD=415-687.
DR PDBsum; 1K04; -.
DR PDBsum; 1K05; -.
DR PDBsum; 1MP8; -.
DR PDBsum; 1OW6; -.
DR PDBsum; 1OW7; -.
DR PDBsum; 1OW8; -.
DR PDBsum; 2ETM; -.
DR PDBsum; 2IJM; -.
DR PDBsum; 3B71; -.
DR PDBsum; 3BZ3; -.
DR PDBsum; 3PXK; -.
DR PDBsum; 3S9O; -.
DR PDBsum; 4EBV; -.
DR PDBsum; 4EBW; -.
DR PDBsum; 4GU6; -.
DR PDBsum; 4GU9; -.
DR PDBsum; 4I4E; -.
DR PDBsum; 4I4F; -.
DR PDBsum; 4K8A; -.
DR PDBsum; 4K9Y; -.
DR PDBsum; 4KAB; -.
DR PDBsum; 4KAO; -.
DR PDBsum; 4NY0; -.
DR PDBsum; 4Q9S; -.
DR PDBsum; 6I8Z; -.
DR PDBsum; 6LES; -.
DR PDBsum; 6PW8; -.
DR PDBsum; 6YOJ; -.
DR PDBsum; 6YQ1; -.
DR PDBsum; 6YR9; -.
DR PDBsum; 6YT6; -.
DR PDBsum; 6YVS; -.
DR PDBsum; 6YVY; -.
DR PDBsum; 6YXV; -.
DR PDBsum; 7PI4; -.
DR AlphaFoldDB; Q05397; -.
DR SMR; Q05397; -.
DR BioGRID; 111719; 219.
DR CORUM; Q05397; -.
DR ELM; Q05397; -.
DR IntAct; Q05397; 137.
DR MINT; Q05397; -.
DR STRING; 9606.ENSP00000341189; -.
DR BindingDB; Q05397; -.
DR ChEMBL; CHEMBL2695; -.
DR DrugBank; DB07460; 2-({5-CHLORO-2-[(2-METHOXY-4-MORPHOLIN-4-YLPHENYL)AMINO]PYRIMIDIN-4-YL}AMINO)-N-METHYLBENZAMIDE.
DR DrugBank; DB07248; 7-PYRIDIN-2-YL-N-(3,4,5-TRIMETHOXYPHENYL)-7H-PYRROLO[2,3-D]PYRIMIDIN-2-AMINE.
DR DrugBank; DB06423; Endostatin.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q05397; -.
DR GuidetoPHARMACOLOGY; 2180; -.
DR CarbonylDB; Q05397; -.
DR GlyGen; Q05397; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q05397; -.
DR PhosphoSitePlus; Q05397; -.
DR BioMuta; PTK2; -.
DR DMDM; 3183518; -.
DR CPTAC; CPTAC-1785; -.
DR EPD; Q05397; -.
DR jPOST; Q05397; -.
DR MassIVE; Q05397; -.
DR MaxQB; Q05397; -.
DR PaxDb; Q05397; -.
DR PeptideAtlas; Q05397; -.
DR PRIDE; Q05397; -.
DR ProteomicsDB; 58320; -. [Q05397-1]
DR ProteomicsDB; 58321; -. [Q05397-2]
DR ProteomicsDB; 58322; -. [Q05397-3]
DR ProteomicsDB; 58323; -. [Q05397-4]
DR ProteomicsDB; 58324; -. [Q05397-5]
DR ProteomicsDB; 58325; -. [Q05397-6]
DR ProteomicsDB; 71210; -.
DR Antibodypedia; 725; 2912 antibodies from 48 providers.
DR DNASU; 5747; -.
DR Ensembl; ENST00000340930.7; ENSP00000341189.3; ENSG00000169398.19. [Q05397-5]
DR Ensembl; ENST00000395218.3; ENSP00000378644.3; ENSG00000169398.19. [Q05397-7]
DR Ensembl; ENST00000521059.5; ENSP00000429474.1; ENSG00000169398.19. [Q05397-1]
DR Ensembl; ENST00000522684.5; ENSP00000429911.1; ENSG00000169398.19. [Q05397-1]
DR GeneID; 5747; -.
DR KEGG; hsa:5747; -.
DR UCSC; uc003yvu.4; human. [Q05397-1]
DR CTD; 5747; -.
DR DisGeNET; 5747; -.
DR GeneCards; PTK2; -.
DR HGNC; HGNC:9611; PTK2.
DR HPA; ENSG00000169398; Low tissue specificity.
DR MIM; 600758; gene.
DR neXtProt; NX_Q05397; -.
DR OpenTargets; ENSG00000169398; -.
DR PharmGKB; PA33955; -.
DR VEuPathDB; HostDB:ENSG00000169398; -.
DR eggNOG; KOG4257; Eukaryota.
DR GeneTree; ENSGT00940000155113; -.
DR HOGENOM; CLU_002646_0_0_1; -.
DR InParanoid; Q05397; -.
DR OMA; ELECMFK; -.
DR OrthoDB; 43729at2759; -.
DR PhylomeDB; Q05397; -.
DR TreeFam; TF316643; -.
DR BRENDA; 2.7.10.2; 2681.
DR PathwayCommons; Q05397; -.
DR Reactome; R-HSA-111465; Apoptotic cleavage of cellular proteins.
DR Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-HSA-354192; Integrin signaling.
DR Reactome; R-HSA-354194; GRB2:SOS provides linkage to MAPK signaling for Integrins.
DR Reactome; R-HSA-372708; p130Cas linkage to MAPK signaling for integrins.
DR Reactome; R-HSA-375165; NCAM signaling for neurite out-growth.
DR Reactome; R-HSA-391160; Signal regulatory protein family interactions.
DR Reactome; R-HSA-3928662; EPHB-mediated forward signaling.
DR Reactome; R-HSA-418885; DCC mediated attractive signaling.
DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-HSA-5663213; RHO GTPases Activate WASPs and WAVEs.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-8874081; MET activates PTK2 signaling.
DR Reactome; R-HSA-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-HSA-9634638; Estrogen-dependent nuclear events downstream of ESR-membrane signaling.
DR Reactome; R-HSA-9664422; FCGR3A-mediated phagocytosis.
DR SignaLink; Q05397; -.
DR SIGNOR; Q05397; -.
DR BioGRID-ORCS; 5747; 398 hits in 1128 CRISPR screens.
DR ChiTaRS; PTK2; human.
DR EvolutionaryTrace; Q05397; -.
DR GeneWiki; PTK2; -.
DR GenomeRNAi; 5747; -.
DR Pharos; Q05397; Tclin.
DR PRO; PR:Q05397; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q05397; protein.
DR Bgee; ENSG00000169398; Expressed in corpus callosum and 208 other tissues.
DR ExpressionAtlas; Q05397; baseline and differential.
DR Genevisible; Q05397; HS.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
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:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0001725; C:stress fiber; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; IDA:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005178; F:integrin binding; IPI:ARUK-UCL.
DR GO; GO:0008432; F:JUN kinase binding; IDA:BHF-UCL.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:BHF-UCL.
DR GO; GO:0004713; F:protein tyrosine kinase activity; EXP:Reactome.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IMP:UniProtKB.
DR GO; GO:0042169; F:SH2 domain binding; IPI:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IBA:GO_Central.
DR GO; GO:0007411; P:axon guidance; TAS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; IMP:BHF-UCL.
DR GO; GO:0048870; P:cell motility; TAS:UniProtKB.
DR GO; GO:0035995; P:detection of muscle stretch; TAS:BHF-UCL.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0030010; P:establishment of cell polarity; TAS:UniProtKB.
DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR GO; GO:0060396; P:growth hormone receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0003007; P:heart morphogenesis; TAS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:2000811; P:negative regulation of anoikis; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0022408; P:negative regulation of cell-cell adhesion; IDA:BHF-UCL.
DR GO; GO:0038007; P:netrin-activated signaling pathway; TAS:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0001890; P:placenta development; TAS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0010763; P:positive regulation of fibroblast migration; IDA:ARUK-UCL.
DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; IGI:ARUK-UCL.
DR GO; GO:0120041; P:positive regulation of macrophage proliferation; IGI:ARUK-UCL.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; TAS:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IMP:UniProtKB.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IMP:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:UniProtKB.
DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0090303; P:positive regulation of wound healing; IDA:ARUK-UCL.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0030155; P:regulation of cell adhesion; IBA:GO_Central.
DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; IDA:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IMP:UniProtKB.
DR GO; GO:0051493; P:regulation of cytoskeleton organization; TAS:UniProtKB.
DR GO; GO:0010594; P:regulation of endothelial cell migration; TAS:UniProtKB.
DR GO; GO:0010632; P:regulation of epithelial cell migration; IGI:UniProtKB.
DR GO; GO:0051893; P:regulation of focal adhesion assembly; IGI:UniProtKB.
DR GO; GO:0043087; P:regulation of GTPase activity; TAS:UniProtKB.
DR GO; GO:0045667; P:regulation of osteoblast differentiation; IMP:UniProtKB.
DR GO; GO:0001932; P:regulation of protein phosphorylation; IGI:UniProtKB.
DR GO; GO:1900024; P:regulation of substrate adhesion-dependent cell spreading; IGI:UniProtKB.
DR GO; GO:0007172; P:signal complex assembly; IEA:InterPro.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; TAS:Reactome.
DR CDD; cd14473; FERM_B-lobe; 1.
DR CDD; cd13190; FERM_C_FAK1; 1.
DR Gene3D; 1.20.80.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR041390; FADK_N.
DR InterPro; IPR041784; FAK1/PYK2_FERM_C.
DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_sf.
DR InterPro; IPR035963; FERM_2.
DR InterPro; IPR019748; FERM_central.
DR InterPro; IPR000299; FERM_domain.
DR InterPro; IPR036137; Focal_adhe_kin_target_dom_sf.
DR InterPro; IPR005189; Focal_adhesion_kin_target_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR Pfam; PF00373; FERM_M; 1.
DR Pfam; PF18038; FERM_N_2; 1.
DR Pfam; PF03623; Focal_AT; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00295; B41; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF47031; SSF47031; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF68993; SSF68993; 1.
DR PROSITE; PS00661; FERM_2; 1.
DR PROSITE; PS50057; FERM_3; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative promoter usage;
KW Alternative splicing; Angiogenesis; ATP-binding; Cell junction;
KW Cell membrane; Cell projection; Cytoplasm; Cytoskeleton;
KW Developmental protein; Direct protein sequencing; Isopeptide bond; Kinase;
KW Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Transferase; Tyrosine-protein kinase; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:19413330"
FT CHAIN 2..1052
FT /note="Focal adhesion kinase 1"
FT /id="PRO_0000088077"
FT DOMAIN 35..355
FT /note="FERM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084"
FT DOMAIN 422..680
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 684..734
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 707..1052
FT /note="Interaction with TGFB1I1"
FT REGION 839..922
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 912..1052
FT /note="Interaction with ARHGEF28"
FT /evidence="ECO:0000250"
FT COMPBIAS 9..24
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 866..880
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 890..922
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 546
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 428..434
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:12467573"
FT BINDING 454
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:12467573"
FT BINDING 500..502
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:12467573"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:19413330"
FT MOD_RES 5
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 13
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT MOD_RES 29
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT MOD_RES 54
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P34152"
FT MOD_RES 397
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:12387730,
FT ECO:0000269|PubMed:15561106, ECO:0000269|PubMed:17395594,
FT ECO:0000269|PubMed:17431114, ECO:0000269|PubMed:18006843,
FT ECO:0000269|PubMed:19339212, ECO:0007744|PubMed:19369195"
FT MOD_RES 407
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:12387730,
FT ECO:0000269|PubMed:15561106"
FT MOD_RES 570
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 576
FT /note="Phosphotyrosine; by RET and SRC"
FT /evidence="ECO:0000269|PubMed:15561106,
FT ECO:0000269|PubMed:19339212, ECO:0000269|PubMed:21454698"
FT MOD_RES 577
FT /note="Phosphotyrosine; by RET and SRC"
FT /evidence="ECO:0000269|PubMed:12387730,
FT ECO:0000269|PubMed:19339212, ECO:0000269|PubMed:21454698"
FT MOD_RES 580
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 722
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19339212"
FT MOD_RES 732
FT /note="Phosphoserine; by CDK5"
FT /evidence="ECO:0000250|UniProtKB:P34152"
FT MOD_RES 843
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 861
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:12387730,
FT ECO:0000269|PubMed:18006843, ECO:0000269|PubMed:19339212"
FT MOD_RES 887
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 910
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 914
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 925
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:12387730,
FT ECO:0000269|PubMed:19339212"
FT CROSSLNK 152
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..692
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_042168"
FT VAR_SEQ 1..181
FT /note="Missing (in isoform 2, isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:8422239"
FT /id="VSP_004967"
FT VAR_SEQ 182..189
FT /note="EMRGNALE -> MSDYWVVG (in isoform 2, isoform 3 and
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:8422239"
FT /id="VSP_004968"
FT VAR_SEQ 472
FT /note="A -> ACHYTSLHWNWCRYISDPNVDACPDPRNAE (in isoform 2,
FT isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:8422239"
FT /id="VSP_004969"
FT VAR_SEQ 579..583
FT /note="ASKGK -> GKKSG (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:8422239"
FT /id="VSP_004971"
FT VAR_SEQ 584..1052
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:8422239"
FT /id="VSP_004972"
FT VAR_SEQ 677..706
FT /note="STILEEEKAQQEERMRMESRRQATVSWDSG -> FQNPAQMLPASGRLPNQP
FT CPERENYSFATF (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:8422239"
FT /id="VSP_004973"
FT VAR_SEQ 707..1052
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:8422239"
FT /id="VSP_004974"
FT VAR_SEQ 744..789
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_057268"
FT VAR_SEQ 834..854
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8422239"
FT /id="VSP_004970"
FT VAR_SEQ 868
FT /note="D -> GKEEKNWAERN (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042169"
FT VAR_SEQ 903
FT /note="K -> KPWR (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042170"
FT VARIANT 292
FT /note="H -> P"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041682"
FT VARIANT 292
FT /note="H -> Q"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041683"
FT VARIANT 793
FT /note="V -> A (in a glioblastoma multiforme sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041684"
FT VARIANT 1030
FT /note="D -> E"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041685"
FT VARIANT 1044
FT /note="K -> E (in a metastatic melanoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041686"
FT MUTAGEN 397
FT /note="Y->F: Abolishes autophosphorylation. Abolishes
FT interaction with SRC and activation of BMX."
FT /evidence="ECO:0000269|PubMed:11331870"
FT MUTAGEN 928
FT /note="V->G: Loss of interaction with TGFB1I1."
FT /evidence="ECO:0000269|PubMed:9756887"
FT MUTAGEN 1034
FT /note="L->S: Loss of interaction with TGFB1I1."
FT /evidence="ECO:0000269|PubMed:9756887"
FT CONFLICT 184
FT /note="R -> L (in Ref. 3; BAG65198)"
FT /evidence="ECO:0000305"
FT CONFLICT 211
FT /note="L -> I (in Ref. 3; BAG65198)"
FT /evidence="ECO:0000305"
FT CONFLICT 778
FT /note="P -> S (in Ref. 2; AAA35819)"
FT /evidence="ECO:0000305"
FT STRAND 35..40
FT /evidence="ECO:0007829|PDB:4NY0"
FT HELIX 49..51
FT /evidence="ECO:0007829|PDB:4NY0"
FT STRAND 53..58
FT /evidence="ECO:0007829|PDB:4NY0"
FT HELIX 64..73
FT /evidence="ECO:0007829|PDB:4NY0"
FT TURN 74..76
FT /evidence="ECO:0007829|PDB:4NY0"
FT HELIX 80..82
FT /evidence="ECO:0007829|PDB:4NY0"
FT STRAND 83..89
FT /evidence="ECO:0007829|PDB:4NY0"
FT STRAND 95..98
FT /evidence="ECO:0007829|PDB:4NY0"
FT HELIX 104..114
FT /evidence="ECO:0007829|PDB:4NY0"
FT HELIX 117..119
FT /evidence="ECO:0007829|PDB:4NY0"
FT STRAND 120..126
FT /evidence="ECO:0007829|PDB:4NY0"
FT HELIX 133..137
FT /evidence="ECO:0007829|PDB:4NY0"
FT HELIX 141..158
FT /evidence="ECO:0007829|PDB:4NY0"
FT HELIX 165..179
FT /evidence="ECO:0007829|PDB:4NY0"
FT HELIX 185..187
FT /evidence="ECO:0007829|PDB:4NY0"
FT STRAND 188..190
FT /evidence="ECO:0007829|PDB:4NY0"
FT HELIX 191..194
FT /evidence="ECO:0007829|PDB:4NY0"
FT HELIX 197..201
FT /evidence="ECO:0007829|PDB:4NY0"
FT TURN 204..206
FT /evidence="ECO:0007829|PDB:4NY0"
FT HELIX 209..214
FT /evidence="ECO:0007829|PDB:4NY0"
FT TURN 217..219
FT /evidence="ECO:0007829|PDB:4NY0"
FT HELIX 220..228
FT /evidence="ECO:0007829|PDB:4NY0"
FT HELIX 229..231
FT /evidence="ECO:0007829|PDB:4NY0"
FT HELIX 236..247
FT /evidence="ECO:0007829|PDB:4NY0"
FT HELIX 248..250
FT /evidence="ECO:0007829|PDB:4NY0"
FT STRAND 256..262
FT /evidence="ECO:0007829|PDB:4NY0"
FT STRAND 264..266
FT /evidence="ECO:0007829|PDB:4NY0"
FT STRAND 268..275
FT /evidence="ECO:0007829|PDB:4NY0"
FT TURN 276..278
FT /evidence="ECO:0007829|PDB:4NY0"
FT STRAND 279..283
FT /evidence="ECO:0007829|PDB:4NY0"
FT STRAND 290..294
FT /evidence="ECO:0007829|PDB:4NY0"
FT HELIX 296..298
FT /evidence="ECO:0007829|PDB:4NY0"
FT STRAND 299..306
FT /evidence="ECO:0007829|PDB:4NY0"
FT STRAND 308..311
FT /evidence="ECO:0007829|PDB:4NY0"
FT STRAND 314..320
FT /evidence="ECO:0007829|PDB:4NY0"
FT STRAND 327..333
FT /evidence="ECO:0007829|PDB:4NY0"
FT HELIX 334..351
FT /evidence="ECO:0007829|PDB:4NY0"
FT HELIX 413..415
FT /evidence="ECO:0007829|PDB:4EBV"
FT HELIX 419..421
FT /evidence="ECO:0007829|PDB:6YOJ"
FT STRAND 422..431
FT /evidence="ECO:0007829|PDB:6YOJ"
FT STRAND 434..441
FT /evidence="ECO:0007829|PDB:6YOJ"
FT STRAND 444..446
FT /evidence="ECO:0007829|PDB:6YVY"
FT STRAND 449..455
FT /evidence="ECO:0007829|PDB:6YOJ"
FT TURN 457..460
FT /evidence="ECO:0007829|PDB:6YOJ"
FT HELIX 462..476
FT /evidence="ECO:0007829|PDB:6YOJ"
FT STRAND 486..490
FT /evidence="ECO:0007829|PDB:6YOJ"
FT STRAND 492..494
FT /evidence="ECO:0007829|PDB:6YOJ"
FT STRAND 496..500
FT /evidence="ECO:0007829|PDB:6YOJ"
FT HELIX 507..513
FT /evidence="ECO:0007829|PDB:6YOJ"
FT TURN 514..517
FT /evidence="ECO:0007829|PDB:6YOJ"
FT HELIX 520..539
FT /evidence="ECO:0007829|PDB:6YOJ"
FT HELIX 549..551
FT /evidence="ECO:0007829|PDB:6YOJ"
FT STRAND 552..556
FT /evidence="ECO:0007829|PDB:6YOJ"
FT STRAND 559..562
FT /evidence="ECO:0007829|PDB:6YOJ"
FT HELIX 565..568
FT /evidence="ECO:0007829|PDB:6YOJ"
FT HELIX 570..573
FT /evidence="ECO:0007829|PDB:4GU6"
FT HELIX 574..576
FT /evidence="ECO:0007829|PDB:4GU6"
FT HELIX 586..588
FT /evidence="ECO:0007829|PDB:6YOJ"
FT HELIX 591..596
FT /evidence="ECO:0007829|PDB:6YOJ"
FT HELIX 601..616
FT /evidence="ECO:0007829|PDB:6YOJ"
FT TURN 617..619
FT /evidence="ECO:0007829|PDB:4EBV"
FT TURN 622..625
FT /evidence="ECO:0007829|PDB:6YOJ"
FT HELIX 628..636
FT /evidence="ECO:0007829|PDB:6YOJ"
FT HELIX 649..658
FT /evidence="ECO:0007829|PDB:6YOJ"
FT HELIX 663..665
FT /evidence="ECO:0007829|PDB:6YOJ"
FT HELIX 669..685
FT /evidence="ECO:0007829|PDB:6YOJ"
FT STRAND 915..917
FT /evidence="ECO:0007829|PDB:1K04"
FT HELIX 923..942
FT /evidence="ECO:0007829|PDB:1K04"
FT HELIX 947..949
FT /evidence="ECO:0007829|PDB:1K04"
FT HELIX 950..971
FT /evidence="ECO:0007829|PDB:1K04"
FT HELIX 972..974
FT /evidence="ECO:0007829|PDB:1K04"
FT HELIX 977..979
FT /evidence="ECO:0007829|PDB:1K04"
FT HELIX 980..1006
FT /evidence="ECO:0007829|PDB:1K04"
FT TURN 1007..1009
FT /evidence="ECO:0007829|PDB:1K04"
FT STRAND 1010..1012
FT /evidence="ECO:0007829|PDB:1K04"
FT HELIX 1013..1045
FT /evidence="ECO:0007829|PDB:1K04"
SQ SEQUENCE 1052 AA; 119233 MW; D8A4C15138AB0243 CRC64;
MAAAYLDPNL NHTPNSSTKT HLGTGMERSP GAMERVLKVF HYFESNSEPT TWASIIRHGD
ATDVRGIIQK IVDSHKVKHV ACYGFRLSHL RSEEVHWLHV DMGVSSVREK YELAHPPEEW
KYELRIRYLP KGFLNQFTED KPTLNFFYQQ VKSDYMLEIA DQVDQEIALK LGCLEIRRSY
WEMRGNALEK KSNYEVLEKD VGLKRFFPKS LLDSVKAKTL RKLIQQTFRQ FANLNREESI
LKFFEILSPV YRFDKECFKC ALGSSWIISV ELAIGPEEGI SYLTDKGCNP THLADFTQVQ
TIQYSNSEDK DRKGMLQLKI AGAPEPLTVT APSLTIAENM ADLIDGYCRL VNGTSQSFII
RPQKEGERAL PSIPKLANSE KQGMRTHAVS VSETDDYAEI IDEEDTYTMP STRDYEIQRE
RIELGRCIGE GQFGDVHQGI YMSPENPALA VAIKTCKNCT SDSVREKFLQ EALTMRQFDH
PHIVKLIGVI TENPVWIIME LCTLGELRSF LQVRKYSLDL ASLILYAYQL STALAYLESK
RFVHRDIAAR NVLVSSNDCV KLGDFGLSRY MEDSTYYKAS KGKLPIKWMA PESINFRRFT
SASDVWMFGV CMWEILMHGV KPFQGVKNND VIGRIENGER LPMPPNCPPT LYSLMTKCWA
YDPSRRPRFT ELKAQLSTIL EEEKAQQEER MRMESRRQAT VSWDSGGSDE APPKPSRPGY
PSPRSSEGFY PSPQHMVQTN HYQVSGYPGS HGITAMAGSI YPGQASLLDQ TDSWNHRPQE
IAMWQPNVED STVLDLRGIG QVLPTHLMEE RLIRQQQEME EDQRWLEKEE RFLKPDVRLS
RGSIDREDGS LQGPIGNQHI YQPVGKPDPA APPKKPPRPG APGHLGSLAS LSSPADSYNE
GVKLQPQEIS PPPTANLDRS NDKVYENVTG LVKAVIEMSS KIQPAPPEEY VPMVKEVGLA
LRTLLATVDE TIPLLPASTH REIEMAQKLL NSDLGELINK MKLAQQYVMT SLQQEYKKQM
LTAAHALAVD AKNLLDVIDQ ARLKMLGQTR PH
