ID FAK1_MOUSE Reviewed; 1052 AA. AC P34152; O08578; Q5DTH7; Q8C513; Q8CFH7; Q8CHM2; Q8K2S0; Q9DAW3; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 13-FEB-2019, sequence version 4. DT 02-SEP-2026, entry version 256. 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-tyrosine kinase 2; DE AltName: Full=p125FAK; DE AltName: Full=pp125FAK; GN Name=Ptk2 {ECO:0000312|MGI:MGI:95481}; GN Synonyms=Fadk, Fak, Fak1, Kiaa4203; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), CATALYTIC ACTIVITY, SUBCELLULAR RP LOCATION, AND PHOSPHORYLATION. RC STRAIN=BALB/cJ; TISSUE=Embryo; RX PubMed=1528852; DOI=10.1073/pnas.89.18.8487; RA Hanks S.K., Calalb M.B., Harper M.C., Patel S.K.; RT "Focal adhesion protein-tyrosine kinase phosphorylated in response to cell RT attachment to fibronectin."; RL Proc. Natl. Acad. Sci. U.S.A. 89:8487-8491(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5 AND 7). RC STRAIN=BALB/cJ; TISSUE=Brain, and Embryo; RA Yamakawa N.; RT "Focal adhesion kinase."; RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 8). RC STRAIN=C57BL/6J; TISSUE=Placenta, and Thymus; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Fetal brain; RA Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O., RA Koga H.; RT "Prediction of the coding sequences of mouse homologues of KIAA gene. The RT complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by RT screening of terminal sequences of cDNA clones randomly sampled from size- RT fractionated libraries."; RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6). RC STRAIN=Czech II; TISSUE=Mammary tumor; 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; 39-57; 77-86; 92-121; 132-177; 179-204; 210-218; RP 222-259; 313-319; 350-381; 386-413; 427-454; 466-508; 551-578; 584-597; RP 628-665; 669-690; 697-724; 798-838; 847-933; 904-933; 942-955; 963-981 AND RP 1027-1082, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, RP PHOSPHORYLATION AT SER-910, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Embryonic fibroblast; RA Bienvenut W.V., Sandilands E., Serrels B., Brunton V.G., Sumpton D.P., RA Frame M.C.; RL Submitted (MAR-2008) to UniProtKB. RN [7] RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING RP (ISOFORM 2). RC STRAIN=ICR X Swiss Webster; RX PubMed=9353341; DOI=10.1074/jbc.272.45.28720; RA Burgaya F., Toutant M., Studler J.-M., Costa A., Le Bert M., Gelman M., RA Girault J.A.; RT "Alternatively spliced focal adhesion kinase in rat brain with increased RT autophosphorylation activity."; RL J. Biol. Chem. 272:28720-28725(1997). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 391-417. RC STRAIN=129/SvJ; RA Asano H., Komiyama H.K., Grant S.G.; RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases. RN [9] RP FUNCTION IN INTEGRIN SIGNALING AND ACTIVATION OF MAP KINASES, INTERACTION RP WITH GRB2; BCAR1; SHC1 AND SRC, PHOSPHORYLATION AT TYR-925, AND MUTAGENESIS RP OF TYR-925. RX PubMed=7997267; DOI=10.1038/372786a0; RA Schlaepfer D.D., Hanks S.K., Hunter T., van der Geer P.; RT "Integrin-mediated signal transduction linked to Ras pathway by GRB2 RT binding to focal adhesion kinase."; RL Nature 372:786-791(1994). RN [10] RP INTERACTION WITH TLN1. RX PubMed=7622520; DOI=10.1074/jbc.270.28.16995; RA Chen H.C., Appeddu P.A., Parsons J.T., Hildebrand J.D., Schaller M.D., RA Guan J.L.; RT "Interaction of focal adhesion kinase with cytoskeletal protein talin."; RL J. Biol. Chem. 270:16995-16999(1995). RN [11] RP PHOSPHORYLATION AT TYR-397; TYR-407; TYR-576 AND TYR-577, RP AUTOPHOSPHORYLATION, CATALYTIC ACTIVITY, MUTAGENESIS OF TYR-397 AND RP 576-TYR-TYR-577, AND ACTIVITY REGULATION. RX PubMed=7529876; DOI=10.1128/mcb.15.2.954; RA Calalb M.B., Polte T.R., Hanks S.K.; RT "Tyrosine phosphorylation of focal adhesion kinase at sites in the RT catalytic domain regulates kinase activity: a role for Src family RT kinases."; RL Mol. Cell. Biol. 15:954-963(1995). RN [12] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=7478517; RA Furuta Y., Ilic D., Kanazawa S., Takeda N., Yamamoto T., Aizawa S.; RT "Mesodermal defect in late phase of gastrulation by a targeted mutation of RT focal adhesion kinase, FAK."; RL Oncogene 11:1989-1995(1995). RN [13] RP INTERACTION WITH PIK3R1, MUTAGENESIS OF TYR-397, AND PHOSPHORYLATION AT RP TYR-397. RX PubMed=8824286; DOI=10.1074/jbc.271.42.26329; RA Chen H.C., Appeddu P.A., Isoda H., Guan J.L.; RT "Phosphorylation of tyrosine 397 in focal adhesion kinase is required for RT binding phosphatidylinositol 3-kinase."; RL J. Biol. Chem. 271:26329-26334(1996). RN [14] RP PHOSPHORYLATION AT TYR-925, MUTAGENESIS OF TYR-925, AND INTERACTION WITH RP GRB2. RX PubMed=8816475; DOI=10.1128/mcb.16.10.5623; RA Schlaepfer D.D., Hunter T.; RT "Evidence for in vivo phosphorylation of the Grb2 SH2-domain binding site RT on focal adhesion kinase by Src-family protein-tyrosine kinases."; RL Mol. Cell. Biol. 16:5623-5633(1996). RN [15] RP FUNCTION IN PHOSPHORYLATION OF SHC1 AND ACTIVATION OF MAPK1/ERK2, RP PHOSPHORYLATION AT TYR-925, AND INTERACTION WITH GRB2. RX PubMed=9148935; DOI=10.1074/jbc.272.20.13189; RA Schlaepfer D.D., Hunter T.; RT "Focal adhesion kinase overexpression enhances ras-dependent integrin RT signaling to ERK2/mitogen-activated protein kinase through interactions RT with and activation of c-Src."; RL J. Biol. Chem. 272:13189-13195(1997). RN [16] 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 [17] RP INTERACTION WITH SORBS1. RX PubMed=9461600; DOI=10.1074/jbc.273.7.4073; RA Ribon V., Herrera R., Kay B.K., Saltiel A.R.; RT "A role for CAP, a novel, multifunctional Src homology 3 domain-containing RT protein in formation of actin stress fibers and focal adhesions."; RL J. Biol. Chem. 273:4073-4080(1998). RN [18] RP INTERACTION WITH TGFB1I1. 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 [19] RP FUNCTION IN CELL SPREADING; MIGRATION AND PHOSPHORYLATION OF BCAR1, RP CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, MUTAGENESIS OF TYR-397 AND RP 576-TYR-TYR-577, AND PHOSPHORYLATION AT TYR-397; TYR-576 AND TYR-577. RX PubMed=10373530; DOI=10.1128/mcb.19.7.4806; RA Owen J.D., Ruest P.J., Fry D.W., Hanks S.K.; RT "Induced focal adhesion kinase (FAK) expression in FAK-null cells enhances RT cell spreading and migration requiring both auto- and activation loop RT phosphorylation sites and inhibits adhesion-dependent tyrosine RT phosphorylation of Pyk2."; RL Mol. Cell. Biol. 19:4806-4818(1999). RN [20] RP INTERACTION WITH BCAR3. RX PubMed=10896938; DOI=10.1074/jbc.m003074200; RA Gotoh T., Cai D., Tian X., Feig L.A., Lerner A.; RT "p130Cas regulates the activity of AND-34, a novel Ral, Rap1, and R-Ras RT guanine nucleotide exchange factor."; RL J. Biol. Chem. 275:30118-30123(2000). RN [21] RP FUNCTION, AND PHOSPHORYLATION AT TYR-397. RX PubMed=10806474; DOI=10.1038/35010517; RA Sieg D.J., Hauck C.R., Ilic D., Klingbeil C.K., Schaefer E., Damsky C.H., RA Schlaepfer D.D.; RT "FAK integrates growth-factor and integrin signals to promote cell RT migration."; RL Nat. Cell Biol. 2:249-256(2000). RN [22] RP INTERACTION WITH STAT1, AND FUNCTION IN STAT1 PHOSPHORYLATION. RX PubMed=11278462; DOI=10.1074/jbc.m009063200; RA Xie B., Zhao J., Kitagawa M., Durbin J., Madri J.A., Guan J.L., Fu X.Y.; RT "Focal adhesion kinase activates Stat1 in integrin-mediated cell migration RT and adhesion."; RL J. Biol. Chem. 276:19512-19523(2001). RN [23] RP FUNCTION IN PHOSPHORYLATION OF ACTN1. RX PubMed=11369769; DOI=10.1074/jbc.m101678200; RA Izaguirre G., Aguirre L., Hu Y.P., Lee H.Y., Schlaepfer D.D., RA Aneskievich B.J., Haimovich B.; RT "The cytoskeletal/non-muscle isoform of alpha-actinin is phosphorylated on RT its actin-binding domain by the focal adhesion kinase."; RL J. Biol. Chem. 276:28676-28685(2001). RN [24] RP PHOSPHORYLATION AT TYR-397; TYR-407; TYR-576; TYR-577; TYR-861 AND TYR-925. RX PubMed=11420674; DOI=10.1038/sj.onc.1204359; RA Nakamura K., Yano H., Schaefer E., Sabe H.; RT "Different modes and qualities of tyrosine phosphorylation of Fak and Pyk2 RT during epithelial-mesenchymal transdifferentiation and cell migration: RT analysis of specific phosphorylation events using site-directed RT antibodies."; RL Oncogene 20:2626-2635(2001). RN [25] 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 [26] RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-732. RX PubMed=12941275; DOI=10.1016/s0092-8674(03)00605-6; RA Xie Z., Sanada K., Samuels B.A., Shih H., Tsai L.H.; RT "Serine 732 phosphorylation of FAK by Cdk5 is important for microtubule RT organization, nuclear movement, and neuronal migration."; RL Cell 114:469-482(2003). RN [27] RP INTERACTION WITH SHB. RX PubMed=12464388; DOI=10.1016/s0898-6568(02)00076-1; RA Holmqvist K., Cross M.J., Riley D., Welsh M.; RT "The Shb adaptor protein causes Src-dependent cell spreading and activation RT of focal adhesion kinase in murine brain endothelial cells."; RL Cell. Signal. 15:171-179(2003). RN [28] RP FUNCTION, INTERACTION WITH ARHGEF28, AND MUTAGENESIS OF LEU-1034. RX PubMed=12702722; DOI=10.1074/jbc.m302381200; RA Zhai J., Lin H., Nie Z., Wu J., Canete-Soler R., Schlaepfer W.W., RA Schlaepfer D.D.; RT "Direct interaction of focal adhesion kinase with p190RhoGEF."; RL J. Biol. Chem. 278:24865-24873(2003). RN [29] RP INTERACTION WITH PIAS1. RX PubMed=14500712; DOI=10.1074/jbc.m308562200; RA Kadare G., Toutant M., Formstecher E., Corvol J.C., Carnaud M., RA Boutterin M.C., Girault J.A.; RT "PIAS1-mediated sumoylation of focal adhesion kinase activates its RT autophosphorylation."; RL J. Biol. Chem. 278:47434-47440(2003). RN [30] RP INTERACTION WITH LPXN. RX PubMed=12674328; DOI=10.1359/jbmr.2003.18.4.669; RA Gupta A., Lee B.S., Khadeer M.A., Tang Z., Chellaiah M., Abu-Amer Y., RA Goldknopf J., Hruska K.A.; RT "Leupaxin is a critical adaptor protein in the adhesion zone of the RT osteoclast."; RL J. Bone Miner. Res. 18:669-685(2003). RN [31] RP INTERACTION WITH WASL, AND PHOSPHORYLATION OF WASL. RX PubMed=14676198; DOI=10.1074/jbc.m310739200; RA Wu X., Suetsugu S., Cooper L.A., Takenawa T., Guan J.L.; RT "Focal adhesion kinase regulation of N-WASP subcellular localization and RT function."; RL J. Biol. Chem. 279:9565-9576(2004). RN [32] RP INTERACTION WITH DCC. RX PubMed=15494733; DOI=10.1038/nn1330; RA Ren X.R., Ming G.L., Xie Y., Hong Y., Sun D.M., Zhao Z.Q., Feng Z., RA Wang Q., Shim S., Chen Z.F., Song H.J., Mei L., Xiong W.C.; RT "Focal adhesion kinase in netrin-1 signaling."; RL Nat. Neurosci. 7:1204-1212(2004). RN [33] RP INTERACTION WITH DCC. RX PubMed=15494734; DOI=10.1038/nn1329; RA Li W., Lee J., Vikis H.G., Lee S.H., Liu G., Aurandt J., Shen T.L., RA Fearon E.R., Guan J.L., Han M., Rao Y., Hong K., Guan K.L.; RT "Activation of FAK and Src are receptor-proximal events required for netrin RT signaling."; RL Nat. Neurosci. 7:1213-1221(2004). RN [34] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=15967814; DOI=10.1083/jcb.200411155; RA Shen T.L., Park A.Y., Alcaraz A., Peng X., Jang I., Koni P., Flavell R.A., RA Gu H., Guan J.L.; RT "Conditional knockout of focal adhesion kinase in endothelial cells reveals RT its role in angiogenesis and vascular development in late embryogenesis."; RL J. Cell Biol. 169:941-952(2005). RN [35] RP FUNCTION. RX PubMed=16000375; DOI=10.1091/mbc.e05-02-0131; RA Brown M.C., Cary L.A., Jamieson J.S., Cooper J.A., Turner C.E.; RT "Src and FAK kinases cooperate to phosphorylate paxillin kinase linker, RT stimulate its focal adhesion localization, and regulate cell spreading and RT protrusiveness."; RL Mol. Biol. Cell 16:4316-4328(2005). RN [36] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-397, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [37] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=16391003; DOI=10.1083/jcb.200506184; RA Braren R., Hu H., Kim Y.H., Beggs H.E., Reichardt L.F., Wang R.; RT "Endothelial FAK is essential for vascular network stability, cell RT survival, and lamellipodial formation."; RL J. Cell Biol. 172:151-162(2006). RN [38] RP FUNCTION IN CELL SPREADING; PHOSPHORYLATION OF ARHGEF7; RAC1 TARGETING TO RP FOCAL ADHESIONS AND RAC1 ACTIVATION, AND INTERACTION WITH ARHGEF7. RX PubMed=17093062; DOI=10.1091/mbc.e06-03-0207; RA Chang F., Lemmon C.A., Park D., Romer L.H.; RT "FAK potentiates Rac1 activation and localization to matrix adhesion sites: RT a role for betaPIX."; RL Mol. Biol. Cell 18:253-264(2007). RN [39] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-576 AND TYR-577, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [40] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-576; TYR-577 AND TYR-925, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; RX PubMed=18034455; DOI=10.1021/pr0701254; RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.; RT "Large-scale identification and evolution indexing of tyrosine RT phosphorylation sites from murine brain."; RL J. Proteome Res. 7:311-318(2008). RN [41] RP DISRUPTION PHENOTYPE, FUNCTION IN REGULATION OF P53/TP53 LEVELS; CELL RP PROLIFERATION AND CELL SURVIVAL, INTERACTION WITH MDM2, AND SUBCELLULAR RP 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 [42] RP DEVELOPMENTAL STAGE (ISOFORM 9). RX PubMed=19372463; DOI=10.1161/circresaha.109.195941; RA DiMichele L.A., Hakim Z.S., Sayers R.L., Rojas M., Schwartz R.J., RA Mack C.P., Taylor J.M.; RT "Transient expression of FRNK reveals stage-specific requirement for focal RT adhesion kinase activity in cardiac growth."; RL Circ. Res. 104:1201-1208(2009). RN [43] RP FUNCTION IN PHOSPHORYLATION OF GRB7, AND INTERACTION WITH GRB7. RX PubMed=19473962; DOI=10.1074/jbc.m109.018259; RA Chu P.Y., Huang L.Y., Hsu C.H., Liang C.C., Guan J.L., Hung T.H., RA Shen T.L.; RT "Tyrosine phosphorylation of growth factor receptor-bound protein-7 by RT focal adhesion kinase in the regulation of cell migration, proliferation, RT and tumorigenesis."; RL J. Biol. Chem. 284:20215-20226(2009). RN [44] 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 [45] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54; TYR-576 AND TYR-577, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [46] RP FUNCTION. RX PubMed=22056317; DOI=10.1016/j.yjmcc.2011.10.015; RA Clemente C.F., Xavier-Neto J., Dalla Costa A.P., Consonni S.R., RA Antunes J.E., Rocco S.A., Pereira M.B., Judice C.C., Strauss B., RA Joazeiro P.P., Matos-Souza J.R., Franchini K.G.; RT "Focal adhesion kinase governs cardiac concentric hypertrophic growth by RT activating the AKT and mTOR pathways."; RL J. Mol. Cell. Cardiol. 52:493-501(2012). RN [47] RP INTERACTION WITH DSCAM, AND PHOSPHORYLATION. RX PubMed=22685302; DOI=10.1074/jbc.m112.340174; RA Purohit A.A., Li W., Qu C., Dwyer T., Shao Q., Guan K.L., Liu G.; RT "Down syndrome cell adhesion molecule (DSCAM) associates with RT uncoordinated-5C (UNC5C) in netrin-1-mediated growth cone collapse."; RL J. Biol. Chem. 287:27126-27138(2012). RN [48] 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 [49] RP REVIEW ON FUNCTION; SUBUNIT; PHOSPHORYLATION AND ACTIVITY REGULATION. 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 [50] RP FUNCTION, AND INTERACTION WITH NEDD9. RX PubMed=25059660; DOI=10.1074/jbc.m113.544106; RA Bradbury P., Bach C.T., Paul A., O'Neill G.M.; RT "Src kinase determines the dynamic exchange of the docking protein NEDD9 RT (neural precursor cell expressed developmentally down-regulated gene 9) at RT focal adhesions."; RL J. Biol. Chem. 289:24792-24800(2014). RN [51] RP INTERACTION WITH AMBRA1. RX PubMed=28362576; DOI=10.7554/elife.23172; RA Schoenherr C., Byron A., Sandilands E., Paliashvili K., Baillie G.S., RA Garcia-Munoz A., Valacca C., Cecconi F., Serrels B., Frame M.C.; RT "Ambra1 spatially regulates Src activity and Src/FAK-mediated cancer cell RT invasion via trafficking networks."; RL Elife 6:0-0(2017). RN [52] RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 921-1046, AND INTERACTION WITH RP PXN. RX PubMed=11799401; DOI=10.1038/nsb755; RA Hayashi I., Vuori K., Liddington R.C.; RT "The focal adhesion targeting (FAT) region of focal adhesion kinase is a RT four-helix bundle that binds paxillin."; RL Nat. Struct. Biol. 9:101-106(2002). 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. CC Phosphorylates NEDD9 following integrin stimulation (PubMed:25059660). 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. Phosphorylates SRC; this increases SRC kinase CC activity. 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. CC {ECO:0000250|UniProtKB:Q05397, ECO:0000269|PubMed:10373530, CC ECO:0000269|PubMed:10806474, ECO:0000269|PubMed:11278462, CC ECO:0000269|PubMed:11369769, ECO:0000269|PubMed:12702722, CC ECO:0000269|PubMed:12941275, ECO:0000269|PubMed:15967814, CC ECO:0000269|PubMed:16000375, ECO:0000269|PubMed:16391003, CC ECO:0000269|PubMed:17093062, ECO:0000269|PubMed:18206965, CC ECO:0000269|PubMed:19147981, ECO:0000269|PubMed:19473962, CC ECO:0000269|PubMed:22056317, ECO:0000269|PubMed:25059660, CC ECO:0000269|PubMed:7478517, ECO:0000269|PubMed:7997267, CC ECO:0000269|PubMed:9148935}. CC -!- FUNCTION: [Isoform 9]: Does not contain a kinase domain and inhibits CC PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can CC attenuate the nuclear accumulation of LPXN and limit its ability to CC enhance serum response factor (SRF)-dependent gene transcription (By CC similarity). {ECO:0000250|UniProtKB:Q05397}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:20101, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:61978, ChEBI:CHEBI:456216; EC=2.7.10.2; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028, CC ECO:0000269|PubMed:10373530, ECO:0000269|PubMed:1528852, CC ECO:0000269|PubMed:7529876}; 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 by SRC. Phosphorylation at Tyr-397, Tyr-576 and Tyr-577 is CC required for maximal kinase activity. {ECO:0000269|PubMed:7529876}. CC -!- SUBUNIT: Interacts with GIT1. Component of a complex that contains at CC least FER, CTTN and PTK2/FAK1. Interacts with BMX. Interacts with CC STEAP4. Interacts with ZFYVE21. Interacts with ESR1. Interacts with CC FGR, FLT4 and RET. Interacts with EPHA2 in resting cells; activation of CC EPHA2 recruits PTPN11, leading to dephosphorylation of PTK2/FAK1 and CC dissociation of the complex. Interacts with EPHA1 (kinase activity- CC dependent) (By similarity). Interacts with MISP (By similarity). CC Interacts with PIAS1. Interacts with ARHGAP26 and SHC1. Interacts with CC RB1CC1; this inhibits PTK2/FAK1 activity and activation of downstream CC signaling pathways. Interacts with P53/TP53. Interacts with STAT1. CC Interacts with WASL. Interacts with ARHGEF7. Interacts with DCC. CC Interacts (via first Pro-rich region) with CAS family members (via SH3 CC domain), including BCAR1, BCAR3 and CASS4. Interacts with NEDD9 (via C- CC terminus) (PubMed:25059660). Interacts with SORBS1. Interacts with CC ARHGEF28. Interacts with SHB. Part of a complex composed of THSD1, CC PTK2/FAK1, TLN1 and VCL (By similarity). Interacts with PXN and TLN1. CC Interacts with TGFB1I1. Interacts with PIK3R1 or PIK3R2. Interacts with CC SRC, GRB2 and GRB7. Interacts with LPXN (via LD motif 3). Interacts CC with CD36. Interacts with EMP2; regulates PTK2 activation and CC localization (By similarity). Interacts with DSCAM (PubMed:22685302). CC Interacts with AMBRA1 (PubMed:28362576). Interacts (when tyrosine- CC phosphorylated) with tensin TNS1; the interaction is increased by CC phosphorylation of TNS1 (By similarity). {ECO:0000250|UniProtKB:Q05397, CC ECO:0000269|PubMed:10896938, ECO:0000269|PubMed:11278462, CC ECO:0000269|PubMed:11799401, ECO:0000269|PubMed:12221124, CC ECO:0000269|PubMed:12464388, ECO:0000269|PubMed:12674328, CC ECO:0000269|PubMed:12702722, ECO:0000269|PubMed:14500712, CC ECO:0000269|PubMed:14676198, ECO:0000269|PubMed:15494733, CC ECO:0000269|PubMed:15494734, ECO:0000269|PubMed:17093062, CC ECO:0000269|PubMed:18206965, ECO:0000269|PubMed:19473962, CC ECO:0000269|PubMed:22685302, ECO:0000269|PubMed:25059660, CC ECO:0000269|PubMed:28362576, ECO:0000269|PubMed:7622520, CC ECO:0000269|PubMed:7997267, ECO:0000269|PubMed:8816475, CC ECO:0000269|PubMed:8824286, ECO:0000269|PubMed:9148935, CC ECO:0000269|PubMed:9422762, ECO:0000269|PubMed:9461600, CC ECO:0000269|PubMed:9756887}. CC -!- INTERACTION: CC P34152; Q61140: Bcar1; NbExp=3; IntAct=EBI-77070, EBI-77088; CC P34152; P54763: Ephb2; NbExp=3; IntAct=EBI-77070, EBI-537711; CC P34152; P11627: L1cam; NbExp=4; IntAct=EBI-77070, EBI-397964; CC P34152; P97333: Nrp1; NbExp=2; IntAct=EBI-77070, EBI-1555129; CC P34152; Q8VI36: Pxn; NbExp=5; IntAct=EBI-77070, EBI-983394; CC P34152; P62993: GRB2; Xeno; NbExp=3; IntAct=EBI-77070, EBI-401755; CC P34152; P18031: PTPN1; Xeno; NbExp=2; IntAct=EBI-77070, EBI-968788; CC P34152; P12931: SRC; Xeno; NbExp=2; IntAct=EBI-77070, EBI-621482; CC -!- SUBCELLULAR LOCATION: Cell junction, focal adhesion CC {ECO:0000269|PubMed:1528852}. Cell membrane CC {ECO:0000250|UniProtKB:Q00944}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:Q00944}; Cytoplasmic side CC {ECO:0000250|UniProtKB:Q00944}. Cytoplasm, perinuclear region CC {ECO:0000269|PubMed:12941275}. Cytoplasm, cell cortex. Cytoplasm, CC cytoskeleton {ECO:0000250|UniProtKB:O35346}. Cytoplasm, cytoskeleton, CC microtubule organizing center, centrosome. Nucleus CC {ECO:0000269|PubMed:18206965}. Cytoplasm, cytoskeleton, cilium basal CC body {ECO:0000250|UniProtKB:Q05397}. Cytoplasm CC {ECO:0000269|PubMed:18206965}. Note=Constituent of focal adhesions. CC Detected at microtubules. {ECO:0000269|PubMed:12941275}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=8; CC Name=3; CC IsoId=P34152-3; Sequence=Displayed; CC Name=2; CC IsoId=P34152-2; Sequence=VSP_060036; CC Name=4; CC IsoId=P34152-4; Sequence=VSP_060042; CC Name=5; CC IsoId=P34152-5; Sequence=VSP_060037, VSP_060039, VSP_060043, CC VSP_060044; CC Name=6; CC IsoId=P34152-6; Sequence=VSP_060043, VSP_060044; CC Name=7; CC IsoId=P34152-7; Sequence=VSP_060038, VSP_060039, VSP_060040, CC VSP_060041; CC Name=8; CC IsoId=P34152-8; Sequence=VSP_060035; CC Name=9; Synonyms=FRNK; CC IsoId=P34152-9; Sequence=VSP_060034; CC -!- DEVELOPMENTAL STAGE: [Isoform 9]: Detected in neonate myocardium; CC levels are low directly after birth but high five to fifteen days after CC birth, and not detectable in adults. {ECO:0000269|PubMed:19372463}. CC -!- DOMAIN: The first Pro-rich domain interacts with the SH3 domain of CAS CC family members, such as BCAR1 and NEDD9. CC -!- DOMAIN: The focal AT domain mediates the localization of FAK1 to focal CC 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 (PubMed:22685302). CC {ECO:0000269|PubMed:10373530, ECO:0000269|PubMed:10806474, CC ECO:0000269|PubMed:11420674, ECO:0000269|PubMed:12941275, CC ECO:0000269|PubMed:14676198, ECO:0000269|PubMed:1528852, CC ECO:0000269|PubMed:22685302, ECO:0000269|PubMed:7529876, CC ECO:0000269|PubMed:7997267, ECO:0000269|PubMed:8816475, CC ECO:0000269|PubMed:8824286, ECO:0000269|PubMed:9148935, CC ECO:0000269|Ref.6}. CC -!- PTM: Sumoylated; this enhances autophosphorylation. {ECO:0000250}. CC -!- DISRUPTION PHENOTYPE: Embryonically lethal. Embryos die at about 8.5 CC dpc, despite normal implantation. Embryos do not develop a normal head CC fold, neural tube or heart tube. Endothelial-specific gene disruption CC is lethal at about 11 dpc, due to defects in embryonic angiogenesis. CC {ECO:0000269|PubMed:15967814, ECO:0000269|PubMed:16391003, CC ECO:0000269|PubMed:18206965, ECO:0000269|PubMed:7478517}. CC -!- MISCELLANEOUS: [Isoform 9]: 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 -!- SEQUENCE CAUTION: CC Sequence=BAC37757.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAD90317.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- SEQUENCE CAUTION: [Isoform 6]: CC Sequence=BC030180; Type=Miscellaneous discrepancy; Note=a stop codon in position 912 which was translated as Trp to extend the sequence.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M95408; AAA37592.1; -; mRNA. DR EMBL; AB030035; BAC53924.1; -; mRNA. DR EMBL; AB011499; BAC53890.1; -; mRNA. DR EMBL; AK005468; BAB24058.1; -; mRNA. DR EMBL; AK079821; BAC37757.1; ALT_INIT; mRNA. DR EMBL; AK220543; BAD90317.1; ALT_INIT; mRNA. DR EMBL; BC030180; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AH005806; AAB95262.1; -; Genomic_DNA. DR EMBL; AH005806; AAB95263.1; -; Genomic_DNA. DR EMBL; U77074; AAB51229.1; -; Genomic_DNA. DR CCDS; CCDS37099.1; -. [P34152-3] DR PIR; A46166; A46166. DR RefSeq; NP_032008.2; NM_007982.2. [P34152-3] DR RefSeq; XP_030104191.1; XM_030248331.1. [P34152-4] DR RefSeq; XP_030104192.1; XM_030248332.2. [P34152-4] DR RefSeq; XP_036015042.1; XM_036159149.1. [P34152-4] DR PDB; 1K40; X-ray; 2.25 A; A=921-1046. DR PDB; 5F28; X-ray; 2.90 A; E/F/G=904-1052. DR PDB; 6BZ3; X-ray; 2.50 A; A/C=921-1046. DR AlphaFoldDB; P34152; -. DR MDposit; P34152; -. DR SMR; P34152; -. DR BioGRID; 199587; 53. DR CORUM; P34152; -. DR DIP; DIP-31045N; -. DR ELM; P34152; -. DR FunCoup; P34152; 3176. DR IntAct; P34152; 24. DR MINT; P34152; -. DR STRING; 10090.ENSMUSP00000105663; -. DR BindingDB; P34152; -. DR ChEMBL; CHEMBL1075288; -. DR iPTMnet; P34152; -. DR PhosphoSitePlus; P34152; -. DR SwissPalm; P34152; -. DR jPOST; P34152; -. DR PaxDb; 10090-ENSMUSP00000105663; -. DR PeptideAtlas; P34152; -. DR ProteomicsDB; 275852; -. [P34152-3] DR ProteomicsDB; 275853; -. [P34152-2] DR ProteomicsDB; 275854; -. [P34152-3] DR ProteomicsDB; 275855; -. [P34152-4] DR ProteomicsDB; 275856; -. [P34152-5] DR ProteomicsDB; 275857; -. [P34152-6] DR ProteomicsDB; 275858; -. [P34152-7] DR ProteomicsDB; 275859; -. [P34152-8] DR ProteomicsDB; 275860; -. [P34152-9] DR Pumba; P34152; -. DR Antibodypedia; 725; 2934 antibodies from 53 providers. DR DNASU; 14083; -. DR Ensembl; ENSMUST00000110036.11; ENSMUSP00000105663.3; ENSMUSG00000022607.19. [P34152-3] DR Ensembl; ENSMUST00000226988.3; ENSMUSP00000154242.2; ENSMUSG00000022607.19. [P34152-4] DR Ensembl; ENSMUST00000228180.3; ENSMUSP00000155470.2; ENSMUSG00000022607.19. [P34152-8] DR GeneID; 14083; -. DR KEGG; mmu:14083; -. DR UCSC; uc007wbw.2; mouse. [P34152-4] DR UCSC; uc007wbx.2; mouse. [P34152-3] DR UCSC; uc007wby.2; mouse. [P34152-5] DR UCSC; uc007wbz.2; mouse. [P34152-6] DR UCSC; uc007wca.1; mouse. [P34152-8] DR AGR; MGI:95481; -. DR CTD; 5747; -. DR MGI; MGI:95481; Ptk2. DR VEuPathDB; HostDB:ENSMUSG00000022607; -. DR eggNOG; KOG4257; Eukaryota. DR GeneTree; ENSGT00940000155113; -. DR HOGENOM; CLU_002646_0_0_1; -. DR InParanoid; P34152; -. DR OMA; HCTNTAE; -. DR PhylomeDB; P34152; -. DR BRENDA; 2.7.10.2; 3474. DR Reactome; R-MMU-111465; Apoptotic cleavage of cellular proteins. [P34152-4] DR Reactome; R-MMU-2029482; Regulation of actin dynamics for phagocytic cup formation. [P34152-4] DR Reactome; R-MMU-354192; Integrin signaling. [P34152-4] DR Reactome; R-MMU-354194; GRB2:SOS provides linkage to MAPK signaling for Integrins. [P34152-4] DR Reactome; R-MMU-372708; p130Cas linkage to MAPK signaling for integrins. [P34152-4] DR Reactome; R-MMU-375165; NCAM signaling for neurite out-growth. [P34152-4] DR Reactome; R-MMU-3928662; EPHB-mediated forward signaling. [P34152-4] DR Reactome; R-MMU-418885; DCC mediated attractive signaling. [P34152-4] DR Reactome; R-MMU-4420097; VEGFA-VEGFR2 Pathway. [P34152-4] DR Reactome; R-MMU-5663213; RHO GTPases Activate WASPs and WAVEs. [P34152-4] DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade. [P34152-4] DR Reactome; R-MMU-8874081; MET activates PTK2 signaling. [P34152-4] DR Reactome; R-MMU-9009391; Extra-nuclear estrogen signaling. [P34152-4] DR Reactome; R-MMU-9860927; Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells. [P34152-4] DR BioGRID-ORCS; 14083; 4 hits in 82 CRISPR screens. DR EvolutionaryTrace; P34152; -. DR PRO; PR:P34152; -. DR Proteomes; UP000000589; Chromosome 15. DR RNAct; P34152; protein. DR Bgee; ENSMUSG00000022607; Expressed in metanephric ureteric bud and 275 other cell types or tissues. DR ExpressionAtlas; P34152; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IDA:MGI. DR GO; GO:0016323; C:basolateral plasma membrane; ISO:GO_Central. DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell. DR GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell. DR GO; GO:0036064; C:ciliary basal body; ISS:UniProtKB. DR GO; GO:0097542; C:ciliary tip; ISO:GO_Central. DR GO; GO:0005929; C:cilium; ISO:GO_Central. DR GO; GO:0005737; C:cytoplasm; EXP:UniProtKB. DR GO; GO:0005829; C:cytosol; ISO:GO_Central. DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0014704; C:intercalated disc; ISO:GO_Central. DR GO; GO:0030027; C:lamellipodium; IDA:MGI. DR GO; GO:0016604; C:nuclear body; ISO:GO_Central. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0098794; C:postsynapse; ISO:GO_Central. DR GO; GO:0042383; C:sarcolemma; ISO:GO_Central. DR GO; GO:0001725; C:stress fiber; ISO:GO_Central. DR GO; GO:0003779; F:actin binding; ISO:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0042802; F:identical protein binding; ISO:GO_Central. DR GO; GO:0005178; F:integrin binding; ISO:GO_Central. DR GO; GO:0008432; F:JUN kinase binding; ISO:GO_Central. DR GO; GO:0140677; F:molecular function activator activity; ISO:GO_Central. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IMP:UniProtKB. DR GO; GO:0019902; F:phosphatase binding; ISO:GO_Central. DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; ISO:GO_Central. DR GO; GO:0019901; F:protein kinase binding; ISO:GO_Central. DR GO; GO:0019903; F:protein phosphatase binding; ISO:GO_Central. DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:0004725; F:protein tyrosine phosphatase activity; ISO:GO_Central. DR GO; GO:0044877; F:protein-containing complex binding; ISO:GO_Central. DR GO; GO:0042169; F:SH2 domain binding; ISO:GO_Central. DR GO; GO:0001525; P:angiogenesis; IMP:MGI. DR GO; GO:0001568; P:blood vessel development; IMP:MGI. DR GO; GO:0016477; P:cell migration; ISO:GO_Central. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:MGI. DR GO; GO:0021955; P:central nervous system neuron axonogenesis; IMP:MGI. DR GO; GO:0043542; P:endothelial cell migration; IMP:MGI. DR GO; GO:0048013; P:ephrin receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IBA:GO_Central. DR GO; GO:0030198; P:extracellular matrix organization; IMP:MGI. DR GO; GO:0060396; P:growth hormone receptor signaling pathway; ISO:GO_Central. DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISS:UniProtKB. DR GO; GO:0030644; P:intracellular chloride ion homeostasis; ISO:GO_Central. DR GO; GO:0007254; P:JNK cascade; ISO:GO_Central. DR GO; GO:0000165; P:MAPK cascade; ISO:GO_Central. DR GO; GO:0000226; P:microtubule cytoskeleton organization; IDA:MGI. DR GO; GO:2000811; P:negative regulation of anoikis; ISO:GO_Central. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:0010507; P:negative regulation of autophagy; IDA:MGI. DR GO; GO:0050771; P:negative regulation of axonogenesis; IMP:MGI. DR GO; GO:0033629; P:negative regulation of cell adhesion mediated by integrin; ISS:UniProtKB. DR GO; GO:0030336; P:negative regulation of cell migration; ISO:GO_Central. DR GO; GO:0022408; P:negative regulation of cell-cell adhesion; ISO:GO_Central. DR GO; GO:0046621; P:negative regulation of organ growth; IGI:MGI. DR GO; GO:0051964; P:negative regulation of synapse assembly; IMP:MGI. DR GO; GO:0001764; P:neuron migration; IDA:MGI. DR GO; GO:0007097; P:nuclear migration; IDA:MGI. DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IDA:MGI. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:MGI. DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IDA:MGI. DR GO; GO:0045785; P:positive regulation of cell adhesion; ISO:GO_Central. DR GO; GO:0030307; P:positive regulation of cell growth; ISO:GO_Central. DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB. DR GO; GO:0033634; P:positive regulation of cell-cell adhesion mediated by integrin; ISO:GO_Central. DR GO; GO:0010634; P:positive regulation of epithelial cell migration; ISO:GO_Central. DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISO:GO_Central. DR GO; GO:0010763; P:positive regulation of fibroblast migration; ISO:GO_Central. DR GO; GO:0060252; P:positive regulation of glial cell proliferation; ISO:GO_Central. DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; ISO:GO_Central. DR GO; GO:0120041; P:positive regulation of macrophage proliferation; ISO:GO_Central. DR GO; GO:0050766; P:positive regulation of phagocytosis; ISO:GO_Central. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISS:UniProtKB. DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; ISO:GO_Central. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:GO_Central. DR GO; GO:0050806; P:positive regulation of synaptic transmission; ISO:GO_Central. DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR GO; GO:0090303; P:positive regulation of wound healing; ISO:GO_Central. DR GO; GO:0046777; P:protein autophosphorylation; IMP:MGI. DR GO; GO:0030155; P:regulation of cell adhesion; IBA:GO_Central. DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; ISO:GO_Central. DR GO; GO:0042127; P:regulation of cell population proliferation; ISS:UniProtKB. DR GO; GO:0008360; P:regulation of cell shape; ISS:UniProtKB. DR GO; GO:0010632; P:regulation of epithelial cell migration; ISO:GO_Central. DR GO; GO:0051893; P:regulation of focal adhesion assembly; ISO:GO_Central. DR GO; GO:1905274; P:regulation of modification of postsynaptic actin cytoskeleton; IDA:SynGO. DR GO; GO:0045667; P:regulation of osteoblast differentiation; ISS:UniProtKB. DR GO; GO:1900024; P:regulation of substrate adhesion-dependent cell spreading; ISO:GO_Central. DR GO; GO:0007172; P:signal complex assembly; IEA:InterPro. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:GO_Central. DR GO; GO:0001570; P:vasculogenesis; IMP:MGI. DR GO; GO:0042311; P:vasodilation; ISO:GO_Central. DR CDD; cd14473; FERM_B-lobe; 1. DR CDD; cd13190; FERM_C_FAK1; 1. DR CDD; cd05056; PTKc_FAK; 1. DR FunFam; 1.20.120.330:FF:000001; focal adhesion kinase 1 isoform X1; 1. DR FunFam; 2.30.29.30:FF:000058; focal adhesion kinase 1 isoform X1; 1. DR FunFam; 3.10.20.90:FF:000021; focal adhesion kinase 1 isoform X1; 1. DR FunFam; 3.30.200.20:FF:000047; focal adhesion kinase 1 isoform X2; 1. DR FunFam; 1.10.510.10:FF:000039; Focal adhesion kinase, isoform D; 1. DR FunFam; 1.20.80.10:FF:000004; Protein-tyrosine kinase 2-beta isoform 1; 1. DR Gene3D; 1.20.80.10; -; 1. DR Gene3D; 1.20.120.330; Nucleotidyltransferases domain 2; 1. DR Gene3D; 3.10.20.90; Phosphatidylinositol 3-kinase Catalytic Subunit, Chain A, domain 1; 1. DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 1.20.5.540; Single helix bin; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR019749; Band_41_domain. DR InterPro; IPR041390; FADK_N. DR InterPro; IPR049385; FAK1-like_FERM_C. DR InterPro; IPR041784; FAK1/PYK2_FERM_C. DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_sf. DR InterPro; IPR035963; FERM_2. DR InterPro; IPR019748; FERM_central. DR InterPro; IPR000299; FERM_domain. DR InterPro; IPR036137; Focal_adhe_kin_target_dom_sf. DR InterPro; IPR005189; Focal_adhesion_kin_target_dom. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR InterPro; IPR029071; Ubiquitin-like_domsf. DR PANTHER; PTHR46221; FERM AND PDZ DOMAIN-CONTAINING PROTEIN FAMILY MEMBER; 1. DR PANTHER; PTHR46221:SF12; NON-SPECIFIC PROTEIN-TYROSINE KINASE; 1. DR Pfam; PF21477; FERM_C_FAK1; 1. DR Pfam; PF00373; FERM_M; 1. DR Pfam; PF18038; FERM_N_2; 1. DR Pfam; PF03623; Focal_AT; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00295; B41; 1. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF68993; FAT domain of focal adhesion kinase; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF47031; Second domain of FERM; 1. DR SUPFAM; SSF54236; Ubiquitin-like; 1. DR PROSITE; 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. DR PDBsum; 1K40; -. DR PDBsum; 5F28; -. DR PDBsum; 6BZ3; -. 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" FT CHAIN 2..1052 FT /note="Focal adhesion kinase 1" FT /id="PRO_0000088078" FT DOMAIN 35..355 FT /note="FERM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084" FT DOMAIN 431..680 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 914..1045 FT /note="Focal AT" FT /evidence="ECO:0000255" FT REGION 1..27 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 685..734 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 707..1052 FT /note="Interaction with TGFB1I1" FT /evidence="ECO:0000250" FT REGION 837..921 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 912..1052 FT /note="Interaction with ARHGEF28" FT /evidence="ECO:0000269|PubMed:12702722" FT COMPBIAS 10..21 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 685..697 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 837..849 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 869..880 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 886..896 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 BINDING 454 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 500..502 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|Ref.6" FT MOD_RES 5 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q05397" FT MOD_RES 13 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q05397" FT MOD_RES 29 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q05397" FT MOD_RES 54 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 397 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:10373530, FT ECO:0000269|PubMed:10806474, ECO:0000269|PubMed:11420674, FT ECO:0000269|PubMed:7529876, ECO:0000269|PubMed:8824286, FT ECO:0007744|PubMed:15592455" FT MOD_RES 407 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:11420674, FT ECO:0000269|PubMed:7529876" FT MOD_RES 570 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q05397" FT MOD_RES 576 FT /note="Phosphotyrosine; by RET and SRC" FT /evidence="ECO:0000269|PubMed:10373530, FT ECO:0000269|PubMed:11420674, ECO:0000269|PubMed:7529876, FT ECO:0007744|PubMed:17242355, ECO:0007744|PubMed:18034455, FT ECO:0007744|PubMed:21183079" FT MOD_RES 577 FT /note="Phosphotyrosine; by RET and SRC" FT /evidence="ECO:0000269|PubMed:10373530, FT ECO:0000269|PubMed:11420674, ECO:0000269|PubMed:7529876, FT ECO:0007744|PubMed:17242355, ECO:0007744|PubMed:18034455, FT ECO:0007744|PubMed:21183079" FT MOD_RES 580 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q05397" FT MOD_RES 722 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q05397" FT MOD_RES 732 FT /note="Phosphoserine; by CDK5" FT /evidence="ECO:0000269|PubMed:12941275" FT MOD_RES 843 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q05397" FT MOD_RES 861 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:11420674" FT MOD_RES 910 FT /note="Phosphoserine" FT /evidence="ECO:0000269|Ref.6" FT MOD_RES 914 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q05397" FT MOD_RES 925 FT /note="Phosphotyrosine; by SRC" FT /evidence="ECO:0000269|PubMed:11420674, FT ECO:0000269|PubMed:7997267, ECO:0000269|PubMed:8816475, FT ECO:0000269|PubMed:9148935, ECO:0007744|PubMed:18034455" 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 9)" FT /id="VSP_060034" FT VAR_SEQ 199..1052 FT /note="Missing (in isoform 8)" FT /id="VSP_060035" FT VAR_SEQ 392 FT /note="S -> SHCQHKVKKARRFLPLVFCSLEPPPTDEISGD (in isoform FT 2)" FT /id="VSP_060036" FT VAR_SEQ 392 FT /note="S -> SGVSHCQHKVKKARRFLPLVFCSLEPPPTDEISGD (in isoform FT 5)" FT /id="VSP_060037" FT VAR_SEQ 392 FT /note="S -> SDEISGD (in isoform 7)" FT /id="VSP_060038" FT VAR_SEQ 412 FT /note="T -> KSYGIDEA (in isoform 5 and isoform 7)" FT /id="VSP_060039" FT VAR_SEQ 473..496 FT /note="LTMRQFDHPHIVKLIGVITENPVW -> SEVIFASKKIQLGPGIFDIICLSA FT (in isoform 7)" FT /id="VSP_060040" FT VAR_SEQ 497..1052 FT /note="Missing (in isoform 7)" FT /id="VSP_060041" FT VAR_SEQ 903 FT /note="K -> KPWR (in isoform 4)" FT /id="VSP_060042" FT VAR_SEQ 904..916 FT /note="LQPQEISPPPTAN -> VGICACAMWSVPC (in isoform 5 and FT isoform 6)" FT /id="VSP_060043" FT VAR_SEQ 917..1052 FT /note="Missing (in isoform 5 and isoform 6)" FT /id="VSP_060044" FT MUTAGEN 397 FT /note="Y->F: Strongly reduced enzyme activity; when FT associated with 576-F-F-577. Abolishes activation of FT MAPK1/ERK2 in response to integrin signaling. Abolishes FT activation of SRC. Abolishes interaction with PIK3R1." FT /evidence="ECO:0000269|PubMed:10373530, FT ECO:0000269|PubMed:7529876, ECO:0000269|PubMed:8824286" FT MUTAGEN 576..577 FT /note="YY->FF: Strongly reduced enzyme activity; when FT associated with F-397." FT /evidence="ECO:0000269|PubMed:10373530, FT ECO:0000269|PubMed:7529876" FT MUTAGEN 925 FT /note="Y->F: Abolishes interaction with GRB2." FT /evidence="ECO:0000269|PubMed:7997267, FT ECO:0000269|PubMed:8816475" FT MUTAGEN 1034 FT /note="L->S: Loss of interaction with ARHGEF28." FT /evidence="ECO:0000269|PubMed:12702722" FT CONFLICT 32 FT /note="A -> T (in Ref. 5; BC030180)" FT /evidence="ECO:0000305" FT CONFLICT 42 FT /note="Y -> H (in Ref. 1; AAA37592)" FT /evidence="ECO:0000305" FT CONFLICT 87 FT /note="L -> V (in Ref. 3; BAB24058)" FT /evidence="ECO:0000305" FT CONFLICT 128 FT /note="Y -> D (in Ref. 3; BAB24058)" FT /evidence="ECO:0000305" FT CONFLICT 146 FT /note="F -> V (in Ref. 3; BAB24058)" FT /evidence="ECO:0000305" FT CONFLICT 157 FT /note="Q -> L (in Ref. 5; BC030180)" FT /evidence="ECO:0000305" FT CONFLICT 225 FT /note="Q -> H (in Ref. 3; BAC37757)" FT /evidence="ECO:0000305" FT CONFLICT 250 FT /note="V -> M (in Ref. 3; BAC37757)" FT /evidence="ECO:0000305" FT CONFLICT 762 FT /note="Q -> P (in Ref. 5; BC030180)" FT /evidence="ECO:0000305" FT HELIX 922..942 FT /evidence="ECO:0007829|PDB:1K40" FT HELIX 944..946 FT /evidence="ECO:0007829|PDB:6BZ3" FT HELIX 947..949 FT /evidence="ECO:0007829|PDB:1K40" FT HELIX 951..971 FT /evidence="ECO:0007829|PDB:1K40" FT HELIX 972..974 FT /evidence="ECO:0007829|PDB:1K40" FT HELIX 977..979 FT /evidence="ECO:0007829|PDB:6BZ3" FT HELIX 980..1006 FT /evidence="ECO:0007829|PDB:1K40" FT HELIX 1010..1043 FT /evidence="ECO:0007829|PDB:1K40" FT MOD_RES P34152-4:397 FT /note="Phosphotyrosine" FT /evidence="ECO:0000305" SQ SEQUENCE 1052 AA; 119243 MW; 4B7453C5D81F0F63 CRC64; MAAAYLDPNL NHTPSSSTKT HLGTGMERSP GAMERVLKVF HYFESSSEPT TWASIIRHGD ATDVRGIIQK IVDSHKVKHV ACYGFRLSHL RSEEVHWLHV DMGVSSVREK YELAHPPEEW KYELRIRYLP KGFLNQFTED KPTLNFFYQQ VKSDYMQEIA DQVDQEIALK LGCLEIRRSY WEMRGNALEK KSNYEVLEKD VGLKRFFPKS LLDSVKAKTL RKLIQQTFRQ FANLNREESI LKFFEILSPV YRFDKECFKC ALGSSWIISV ELAIGPEEGI SYLTDKGCNP THLADFNQVQ TIQYSNSEDK DRKGMLQLKI AGAPEPLTVT APSLTIAENM ADLIDGYCRL VNGATQSFII RPQKEGERAL PSIPKLANSE KQGMRTHAVS VSETDDYAEI IDEEDTYTMP STRDYEIQRE RIELGRCIGE GQFGDVHQGV YLSPENPALA VAIKTCKNCT SDSVREKFLQ EALTMRQFDH PHIVKLIGVI TENPVWIIME LCTLGELRSF LQVRKYSLDL ASLILYAYQL STALAYLESK RFVHRDIAAR NVLVSSNDCV KLGDFGLSRY MEDSTYYKAS KGKLPIKWMA PESINFRRFT SASDVWMFGV CMWEILMHGV KPFQGVKNND VIGRIENGER LPMPPNCPPT LYSLMTKCWA YDPSRRPRFT ELKAQLSTIL EEEKVQQEER MRMESRRQAT VSWDSGGSDE APPKPSRPGY PSPRSSEGFY PSPQHMVQTN HYQVSGYPGS HGIPAMAGSI YQGQASLLDQ TELWNHRPQE MSMWQPSVED SAALDLRGMG QVLPPHLMEE RLIRQQQEME EDQRWLEKEE RFLKPDVRLS RGSIDREDGS FQGPTGNQHI YQPVGKPDPA APPKKPPRPG APGHLSNLSS ISSPADSYNE GVKLQPQEIS PPPTANLDRS NDKVYENVTG LVKAVIEMSS KIQPAPPEEY VPMVKEVGLA LRTLLATVDE TIPALPASTH REIEMAQKLL NSDLGELISK MKLAQQYVMT SLQQEYKKQM LTAAHALAVD AKNLLDVIDQ ARLKMLGQTR PH //