FAK1_MOUSE
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 03-AUG-2022, entry version 237.
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}; 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, Pancreas,
RC 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 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 [51]
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. 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.
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:7478517,
CC ECO:0000269|PubMed:7997267, 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=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: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, CASS4 and NEDD9. Interacts with
CC SORBS1. Interacts with ARHGEF28. Interacts with SHB. Part of a complex
CC composed of THSD1, PTK2/FAK1, TLN1 and VCL (By similarity). Interacts
CC with PXN and TLN1. Interacts with TGFB1I1. Interacts with PIK3R1 or
CC PIK3R2. Interacts with SRC, GRB2 and GRB7. Interacts with LPXN (via LD
CC motif 3). Interacts with CD36. Interacts with EMP2; regulates PTK2
CC activation and localization (By similarity). Interacts with DSCAM
CC (PubMed:22685302). Interacts with AMBRA1 (PubMed:28362576).
CC {ECO:0000250|UniProtKB:Q05397, ECO:0000269|PubMed:10896938,
CC ECO:0000269|PubMed:11278462, ECO:0000269|PubMed:11799401,
CC ECO:0000269|PubMed:12221124, ECO:0000269|PubMed:12464388,
CC ECO:0000269|PubMed:12674328, ECO:0000269|PubMed:12702722,
CC ECO:0000269|PubMed:14500712, ECO:0000269|PubMed:14676198,
CC ECO:0000269|PubMed:15494733, ECO:0000269|PubMed:15494734,
CC ECO:0000269|PubMed:17093062, ECO:0000269|PubMed:18206965,
CC ECO:0000269|PubMed:19473962, ECO:0000269|PubMed:22685302,
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. Cell membrane;
CC Peripheral membrane protein; Cytoplasmic side. Cytoplasm, perinuclear
CC region. Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome. Nucleus {ECO:0000250}. Cytoplasm,
CC cytoskeleton, cilium basal body {ECO:0000250|UniProtKB:Q05397}.
CC Note=Constituent of focal adhesions. Detected at microtubules.
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 is detected in neonate myocardium;
CC levels are low directly after birth, high five to fifteen days after
CC birth, and not detectable in adult (at protein level). Isoform 9 is
CC detected in neonate myocardium; levels are high directly after birth,
CC decrease during the first week of life and are low thereafter.
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 C-terminal region is the site of focal adhesion targeting
CC (FAT) sequence which 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};
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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_001123881.1; NM_001130409.1.
DR RefSeq; NP_032008.2; NM_007982.2. [P34152-3]
DR RefSeq; XP_006520496.1; XM_006520433.2.
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 PDBsum; 1K40; -.
DR PDBsum; 5F28; -.
DR PDBsum; 6BZ3; -.
DR AlphaFoldDB; P34152; -.
DR SMR; P34152; -.
DR BioGRID; 199587; 50.
DR CORUM; P34152; -.
DR DIP; DIP-31045N; -.
DR ELM; P34152; -.
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 MaxQB; P34152; -.
DR PaxDb; P34152; -.
DR PeptideAtlas; P34152; -.
DR PRIDE; 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 Antibodypedia; 725; 2912 antibodies from 48 providers.
DR DNASU; 14083; -.
DR Ensembl; ENSMUST00000110036; ENSMUSP00000105663; ENSMUSG00000022607. [P34152-3]
DR Ensembl; ENSMUST00000226988; ENSMUSP00000154242; ENSMUSG00000022607. [P34152-4]
DR Ensembl; ENSMUST00000228180; ENSMUSP00000155470; ENSMUSG00000022607. [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 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; ELECMFK; -.
DR OrthoDB; 43729at2759; -.
DR PhylomeDB; P34152; -.
DR TreeFam; TF316643; -.
DR BRENDA; 2.7.10.2; 3474.
DR Reactome; R-MMU-111465; Apoptotic cleavage of cellular proteins.
DR Reactome; R-MMU-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-MMU-354192; Integrin signaling.
DR Reactome; R-MMU-354194; GRB2:SOS provides linkage to MAPK signaling for Integrins.
DR Reactome; R-MMU-372708; p130Cas linkage to MAPK signaling for integrins.
DR Reactome; R-MMU-375165; NCAM signaling for neurite out-growth.
DR Reactome; R-MMU-3928662; EPHB-mediated forward signaling.
DR Reactome; R-MMU-418885; DCC mediated attractive signaling.
DR Reactome; R-MMU-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-MMU-5663213; RHO GTPases Activate WASPs and WAVEs.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-8874081; MET activates PTK2 signaling.
DR Reactome; R-MMU-9009391; Extra-nuclear estrogen signaling.
DR BioGRID-ORCS; 14083; 4 hits in 77 CRISPR screens.
DR ChiTaRS; Ptk2; mouse.
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 272 other tissues.
DR ExpressionAtlas; P34152; baseline and differential.
DR Genevisible; P34152; MM.
DR GO; GO:0016324; C:apical plasma membrane; IDA:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0036064; C:ciliary basal body; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0043197; C:dendritic spine; ISO:MGI.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0014704; C:intercalated disc; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0030027; C:lamellipodium; IDA:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0098794; C:postsynapse; ISO:MGI.
DR GO; GO:0042383; C:sarcolemma; ISO:MGI.
DR GO; GO:0001725; C:stress fiber; ISO:MGI.
DR GO; GO:0003779; F:actin binding; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005178; F:integrin binding; ISO:MGI.
DR GO; GO:0008432; F:JUN kinase binding; ISO:MGI.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IMP:UniProtKB.
DR GO; GO:0019902; F:phosphatase binding; ISO:MGI.
DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0042169; F:SH2 domain binding; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IMP:MGI.
DR GO; GO:0007409; P:axonogenesis; IMP:MGI.
DR GO; GO:0001568; P:blood vessel development; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; ISO:MGI.
DR GO; GO:0030644; P:cellular chloride ion homeostasis; ISO:MGI.
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:MGI.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0007254; P:JNK cascade; ISO:MGI.
DR GO; GO:0000165; P:MAPK cascade; ISO:MGI.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IDA:MGI.
DR GO; GO:2000811; P:negative regulation of anoikis; ISO:MGI.
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:0030336; P:negative regulation of cell migration; ISO:MGI.
DR GO; GO:0022408; P:negative regulation of cell-cell adhesion; ISO:MGI.
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:0035265; P:organ growth; IGI:MGI.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IDA:MGI.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IDA:MGI.
DR GO; GO:0045785; P:positive regulation of cell adhesion; ISO:MGI.
DR GO; GO:0030307; P:positive regulation of cell growth; ISO:MGI.
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:0010763; P:positive regulation of fibroblast migration; ISO:MGI.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; ISO:MGI.
DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; ISO:MGI.
DR GO; GO:0120041; P:positive regulation of macrophage proliferation; ISO:MGI.
DR GO; GO:0050766; P:positive regulation of phagocytosis; ISO:MGI.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISS:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; ISO:MGI.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0050806; P:positive regulation of synaptic transmission; ISO:MGI.
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:MGI.
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; ISS:UniProtKB.
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:MGI.
DR GO; GO:0051893; P:regulation of focal adhesion assembly; ISO:MGI.
DR GO; GO:0045667; P:regulation of osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0001932; P:regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:1900024; P:regulation of substrate adhesion-dependent cell spreading; ISO:MGI.
DR GO; GO:0007172; P:signal complex assembly; IEA:InterPro.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0001570; P:vasculogenesis; IMP:MGI.
DR GO; GO:0042311; P:vasodilation; ISO:MGI.
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"
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 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 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 885..921
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 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
