ID FRS2_MOUSE Reviewed; 508 AA. AC Q8C180; DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 24-JAN-2024, entry version 158. DE RecName: Full=Fibroblast growth factor receptor substrate 2; DE Short=FGFR substrate 2; DE AltName: Full=FGFR-signaling adaptor SNT; DE AltName: Full=FRS2-alpha; DE AltName: Full=Suc1-associated neurotrophic factor target 1; DE Short=SNT-1; GN Name=Frs2; Synonyms=Frs2a; 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 [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Skin; 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Brain; 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 [3] RP PROTEIN SEQUENCE OF 251-260; 305-320; 344-361 AND 468-480, FUNCTION, RP INTERACTION WITH GRB2, IDENTIFICATION IN A COMPLEX WITH GRB2 AND SOS1, RP MYRISTOYLATION AT GLY-2, MUTAGENESIS OF GLY-2; TYR-196; TYR-306; TYR-349 RP AND TYR-392, PHOSPHORYLATION AT TYR-196; TYR-306; TYR-349 AND TYR-392, AND RP TISSUE SPECIFICITY. RX PubMed=9182757; DOI=10.1016/s0092-8674(00)80252-4; RA Kouhara H., Hadari Y.R., Spivak-Kroizman T., Schilling J., Bar-Sagi D., RA Lax I., Schlessinger J.; RT "A lipid-anchored Grb2-binding protein that links FGF-receptor activation RT to the Ras/MAPK signaling pathway."; RL Cell 89:693-702(1997). RN [4] RP INTERACTION WITH SUC1 AND GRB2, PHOSPHORYLATION AT TYROSINE RESIDUES, AND RP SUBCELLULAR LOCATION. RX PubMed=8780727; DOI=10.1006/bbrc.1996.1288; RA Ong S.-H., Goh K.C., Lim Y.P., Low B.C., Klint P., Claesson-Welsh L., RA Cao X., Tan Y.H., Guy G.R.; RT "Suc1-associated neurotrophic factor target (SNT) protein is a major FGF- RT stimulated tyrosine phosphorylated 90-kDa protein which binds to the SH2 RT domain of GRB2."; RL Biochem. Biophys. Res. Commun. 225:1021-1026(1996). RN [5] RP INTERACTION WITH PTPN11, FUNCTION, PHOSPHORYLATION AT TYR-196; TYR-306; RP TYR-349; TYR-392 AND TYR-436, AND MUTAGENESIS OF TYR-436. RX PubMed=9632781; DOI=10.1128/mcb.18.7.3966; RA Hadari Y.R., Kouhara H., Lax I., Schlessinger J.; RT "Binding of Shp2 tyrosine phosphatase to FRS2 is essential for fibroblast RT growth factor-induced PC12 cell differentiation."; RL Mol. Cell. Biol. 18:3966-3973(1998). RN [6] RP PHOSPHORYLATION IN RESPONSE TO FRFR2 AND FGFR3 ACTIVATION. RX PubMed=10851026; DOI=10.1083/jcb.149.6.1297; RA Mansukhani A., Bellosta P., Sahni M., Basilico C.; RT "Signaling by fibroblast growth factors (FGF) and fibroblast growth factor RT receptor 2 (FGFR2)-activating mutations blocks mineralization and induces RT apoptosis in osteoblasts."; RL J. Cell Biol. 149:1297-1308(2000). RN [7] RP INTERACTION WITH FGFR1 AND NTRK1. RX PubMed=10629055; DOI=10.1128/mcb.20.3.979-989.2000; RA Ong S.-H., Guy G.R., Hadari Y.R., Laks S., Gotoh N., Schlessinger J., RA Lax I.; RT "FRS2 proteins recruit intracellular signaling pathways by binding to RT diverse targets on fibroblast growth factor and nerve growth factor RT receptors."; RL Mol. Cell. Biol. 20:979-989(2000). RN [8] RP FUNCTION, INTERACTION WITH RET, AND PHOSPHORYLATION AT TYROSINE RESIDUES. RX PubMed=11390647; DOI=10.1128/mcb.21.13.4177-4187.2001; RA Melillo R.M., Santoro M., Ong S.-H., Billaud M., Fusco A., Hadari Y.R., RA Schlessinger J., Lax I.; RT "Docking protein FRS2 links the protein tyrosine kinase RET and its RT oncogenic forms with the mitogen-activated protein kinase signaling RT cascade."; RL Mol. Cell. Biol. 21:4177-4187(2001). RN [9] RP IDENTIFICATION IN A COMPLEX WITH NCAM1; CDH2; PLCG1; FRS2; SRC; SHC1; GAP43 RP AND CTTN. RX PubMed=11433297; DOI=10.1038/35083041; RA Cavallaro U., Niedermeyer J., Fuxa M., Christofori G.; RT "N-CAM modulates tumour-cell adhesion to matrix by inducing FGF-receptor RT signalling."; RL Nat. Cell Biol. 3:650-657(2001). RN [10] RP FUNCTION, INTERACTION WITH GRB2 AND GAB1, AND PHOSPHORYLATION AT TYR-196; RP TYR-306; TYR-349; TYR-392; TYR-436 AND TYR-471. RX PubMed=11353842; DOI=10.1073/pnas.111114298; RA Ong S.H., Hadari Y.R., Gotoh N., Guy G.R., Schlessinger J., Lax I.; RT "Stimulation of phosphatidylinositol 3-kinase by fibroblast growth factor RT receptors is mediated by coordinated recruitment of multiple docking RT proteins."; RL Proc. Natl. Acad. Sci. U.S.A. 98:6074-6079(2001). RN [11] RP FUNCTION IN ACTIVATION OF SIGNALING VIA RAS AND MAP KINASES, INTERACTION RP WITH PTPN11, AND PHOSPHORYLATION. RX PubMed=12181353; DOI=10.1091/mbc.e02-02-0103; RA Cross M.J., Lu L., Magnusson P., Nyqvist D., Holmqvist K., Welsh M., RA Claesson-Welsh L.; RT "The Shb adaptor protein binds to tyrosine 766 in the FGFR-1 and regulates RT the Ras/MEK/MAPK pathway via FRS2 phosphorylation in endothelial cells."; RL Mol. Biol. Cell 13:2881-2893(2002). RN [12] RP IDENTIFICATION IN A COMPLEX WITH GRB2 AND CBL, AND UBIQUITINATION. RX PubMed=11997436; DOI=10.1073/pnas.052138899; RA Wong A., Lamothe B., Lee A., Schlessinger J., Lax I.; RT "FRS2 alpha attenuates FGF receptor signaling by Grb2-mediated recruitment RT of the ubiquitin ligase Cbl."; RL Proc. Natl. Acad. Sci. U.S.A. 99:6684-6689(2002). RN [13] RP PHOSPHORYLATION BY ULK2. RX PubMed=16887332; DOI=10.1016/j.cellsig.2006.06.003; RA Avery A.W., Figueroa C., Vojtek A.B.; RT "UNC-51-like kinase regulation of fibroblast growth factor receptor RT substrate 2/3."; RL Cell. Signal. 19:177-184(2007). RN [14] 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 [15] RP REVIEW ON FUNCTION; SUBUNIT AND PHOSPHORYLATION. RX PubMed=18452557; DOI=10.1111/j.1349-7006.2008.00840.x; RA Gotoh N.; RT "Regulation of growth factor signaling by FRS2 family docking/scaffold RT adaptor proteins."; RL Cancer Sci. 99:1319-1325(2008). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-211, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006; RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M., RA Thibault P.; RT "The phagosomal proteome in interferon-gamma-activated macrophages."; RL Immunity 30:143-154(2009). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-349, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200; RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.; RT "Large scale localization of protein phosphorylation by use of electron RT capture dissociation mass spectrometry."; RL Mol. Cell. Proteomics 8:904-912(2009). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Heart, Kidney, Lung, and Spleen; 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 [19] RP REVIEW ON FUNCTION IN FGF SIGNALING. RX PubMed=20094046; DOI=10.1038/nrc2780; RA Turner N., Grose R.; RT "Fibroblast growth factor signalling: from development to cancer."; RL Nat. Rev. Cancer 10:116-129(2010). CC -!- FUNCTION: Adapter protein that links activated FGR and NGF receptors to CC downstream signaling pathways. Plays an important role in the CC activation of MAP kinases and in the phosphorylation of PIK3R1, the CC regulatory subunit of phosphatidylinositol 3-kinase, in response to CC ligand-mediated activation of FGFR1. Modulates signaling via SHC1 by CC competing for a common binding site on NTRK1. CC {ECO:0000269|PubMed:11353842, ECO:0000269|PubMed:11390647, CC ECO:0000269|PubMed:12181353, ECO:0000269|PubMed:9182757, CC ECO:0000269|PubMed:9632781}. CC -!- SUBUNIT: Part of a complex containing FRS2, GRB2, GAB1, PIK3R1 and CC SOS1. Part of a complex containing GRB2 and CBL. Binds ALK, CKS2, CC FGFR1, RET, MAPK1/ERK2, MAPK3/ERK1 and SRC. The tyrosine-phosphorylated CC protein binds the SH2 domains of GRB2 and PTPN11. Interacts with NTRK1, CC NTRK2 and NTRK3 (phosphorylated upon ligand-binding) (By similarity). CC Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, CC SRC, SHC1, GAP43 and CTTN. {ECO:0000250, ECO:0000269|PubMed:10629055, CC ECO:0000269|PubMed:11353842, ECO:0000269|PubMed:11390647, CC ECO:0000269|PubMed:11433297, ECO:0000269|PubMed:11997436, CC ECO:0000269|PubMed:12181353, ECO:0000269|PubMed:8780727, CC ECO:0000269|PubMed:9182757, ECO:0000269|PubMed:9632781}. CC -!- INTERACTION: CC Q8C180; Q60631: Grb2; NbExp=5; IntAct=EBI-6880000, EBI-1688; CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:8780727}; Lipid- CC anchor {ECO:0000269|PubMed:8780727}. CC -!- TISSUE SPECIFICITY: Ubiquitous. Expression is highest in brain, kidney, CC lung and testis. {ECO:0000269|PubMed:9182757}. CC -!- PTM: Phosphorylated on tyrosine residues upon stimulation by FGF2 or CC NGFB. Phosphorylated by ULK2 (in vitro). Phosphorylated on tyrosine CC residues by activated ALK and FGFR1. Phosphorylated on tyrosine CC residues upon activation of FGFR2 and FGFR3. Phosphorylated on CC threonine residues by MAP kinases; this inhibits tyrosine CC phosphorylation, and thereby down-regulates FRS2-mediated activation of CC MAP kinases. CC -!- PTM: Ubiquitinated when tyrosine phosphorylated and in a complex with CC GRB2. The unphosphorylated form is not subject to ubiquitination. CC {ECO:0000269|PubMed:11997436}. 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; AK028813; BAC26132.1; -; mRNA. DR EMBL; BC043109; AAH43109.1; -; mRNA. DR EMBL; BC055334; AAH55334.1; -; mRNA. DR CCDS; CCDS24190.1; -. DR RefSeq; NP_808466.1; NM_177798.3. DR AlphaFoldDB; Q8C180; -. DR BMRB; Q8C180; -. DR SMR; Q8C180; -. DR BioGRID; 236497; 7. DR CORUM; Q8C180; -. DR IntAct; Q8C180; 2. DR MINT; Q8C180; -. DR STRING; 10090.ENSMUSP00000020381; -. DR GlyGen; Q8C180; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; Q8C180; -. DR PhosphoSitePlus; Q8C180; -. DR SwissPalm; Q8C180; -. DR EPD; Q8C180; -. DR jPOST; Q8C180; -. DR MaxQB; Q8C180; -. DR PaxDb; 10090-ENSMUSP00000020381; -. DR PeptideAtlas; Q8C180; -. DR ProteomicsDB; 267526; -. DR Pumba; Q8C180; -. DR Antibodypedia; 4156; 588 antibodies from 39 providers. DR DNASU; 327826; -. DR Ensembl; ENSMUST00000020381.5; ENSMUSP00000020381.4; ENSMUSG00000020170.5. DR GeneID; 327826; -. DR KEGG; mmu:327826; -. DR UCSC; uc007hct.1; mouse. DR AGR; MGI:1100860; -. DR CTD; 10818; -. DR MGI; MGI:1100860; Frs2. DR VEuPathDB; HostDB:ENSMUSG00000020170; -. DR eggNOG; KOG4047; Eukaryota. DR GeneTree; ENSGT00940000157033; -. DR HOGENOM; CLU_022374_0_0_1; -. DR InParanoid; Q8C180; -. DR OMA; SAHKIDY; -. DR OrthoDB; 2996885at2759; -. DR PhylomeDB; Q8C180; -. DR TreeFam; TF324994; -. DR Reactome; R-MMU-109704; PI3K Cascade. DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling. DR Reactome; R-MMU-170968; Frs2-mediated activation. DR Reactome; R-MMU-5654689; PI-3K cascade:FGFR1. DR Reactome; R-MMU-5654693; FRS-mediated FGFR1 signaling. DR Reactome; R-MMU-5654695; PI-3K cascade:FGFR2. DR Reactome; R-MMU-5654700; FRS-mediated FGFR2 signaling. DR Reactome; R-MMU-5654706; FRS-mediated FGFR3 signaling. DR Reactome; R-MMU-5654710; PI-3K cascade:FGFR3. DR Reactome; R-MMU-5654712; FRS-mediated FGFR4 signaling. DR Reactome; R-MMU-5654720; PI-3K cascade:FGFR4. DR Reactome; R-MMU-5654726; Negative regulation of FGFR1 signaling. DR Reactome; R-MMU-5654727; Negative regulation of FGFR2 signaling. DR Reactome; R-MMU-5654732; Negative regulation of FGFR3 signaling. DR Reactome; R-MMU-5654733; Negative regulation of FGFR4 signaling. DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade. DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR Reactome; R-MMU-8853659; RET signaling. DR Reactome; R-MMU-9028731; Activated NTRK2 signals through FRS2 and FRS3. DR Reactome; R-MMU-9696270; RND2 GTPase cycle. DR Reactome; R-MMU-9696273; RND1 GTPase cycle. DR BioGRID-ORCS; 327826; 4 hits in 77 CRISPR screens. DR ChiTaRS; Frs2; mouse. DR PRO; PR:Q8C180; -. DR Proteomes; UP000000589; Chromosome 10. DR RNAct; Q8C180; Protein. DR Bgee; ENSMUSG00000020170; Expressed in manus and 243 other cell types or tissues. DR GO; GO:0005912; C:adherens junction; ISO:MGI. DR GO; GO:0005911; C:cell-cell junction; IDA:MGI. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; IDA:MGI. DR GO; GO:0005104; F:fibroblast growth factor receptor binding; ISO:MGI. DR GO; GO:0005168; F:neurotrophin TRKA receptor binding; ISO:MGI. DR GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; IDA:MGI. DR GO; GO:0008595; P:anterior/posterior axis specification, embryo; IMP:MGI. DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; ISO:MGI. DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IMP:MGI. DR GO; GO:0030900; P:forebrain development; IMP:MGI. DR GO; GO:0001702; P:gastrulation with mouth forming second; IMP:MGI. DR GO; GO:0002088; P:lens development in camera-type eye; IMP:MGI. DR GO; GO:0070307; P:lens fiber cell development; IMP:MGI. DR GO; GO:0046619; P:lens placode formation involved in camera-type eye formation; IMP:MGI. DR GO; GO:2000726; P:negative regulation of cardiac muscle cell differentiation; ISO:MGI. DR GO; GO:0007405; P:neuroblast proliferation; IMP:MGI. DR GO; GO:0001759; P:organ induction; IMP:MGI. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:MGI. DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; ISO:MGI. DR GO; GO:0060527; P:prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis; IMP:MGI. DR GO; GO:0042981; P:regulation of apoptotic process; IMP:MGI. DR GO; GO:0050678; P:regulation of epithelial cell proliferation; IMP:MGI. DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; IMP:MGI. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IDA:MGI. DR GO; GO:0003281; P:ventricular septum development; IMP:MGI. DR CDD; cd01202; PTB_FRS2; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR InterPro; IPR038742; FRS2_PTB. DR InterPro; IPR002404; IRS_PTB. DR InterPro; IPR011993; PH-like_dom_sf. DR PANTHER; PTHR21258; DOCKING PROTEIN RELATED; 1. DR PANTHER; PTHR21258:SF40; FIBROBLAST GROWTH FACTOR RECEPTOR SUBSTRATE 2; 1. DR Pfam; PF02174; IRS; 1. DR SMART; SM01244; IRS; 1. DR SMART; SM00310; PTBI; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR PROSITE; PS51064; IRS_PTB; 1. DR Genevisible; Q8C180; MM. PE 1: Evidence at protein level; KW Direct protein sequencing; Lipoprotein; Membrane; Myristate; KW Phosphoprotein; Reference proteome; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000255" FT CHAIN 2..508 FT /note="Fibroblast growth factor receptor substrate 2" FT /id="PRO_0000087345" FT DOMAIN 13..115 FT /note="IRS-type PTB" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00389" FT REGION 116..180 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 201..243 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 268..298 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 315..345 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 441..467 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 483..508 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 128..144 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 177 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8WU20" FT MOD_RES 196 FT /note="Phosphotyrosine; by FGFR1" FT /evidence="ECO:0000269|PubMed:11353842, FT ECO:0000269|PubMed:9182757, ECO:0000269|PubMed:9632781" FT MOD_RES 211 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19144319" FT MOD_RES 221 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8WU20" FT MOD_RES 306 FT /note="Phosphotyrosine; by FGFR1" FT /evidence="ECO:0000269|PubMed:11353842, FT ECO:0000269|PubMed:9182757, ECO:0000269|PubMed:9632781" FT MOD_RES 349 FT /note="Phosphotyrosine; by FGFR1" FT /evidence="ECO:0000269|PubMed:11353842, FT ECO:0000269|PubMed:9182757, ECO:0000269|PubMed:9632781, FT ECO:0007744|PubMed:19131326" FT MOD_RES 365 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8WU20" FT MOD_RES 392 FT /note="Phosphotyrosine; by FGFR1" FT /evidence="ECO:0000269|PubMed:11353842, FT ECO:0000269|PubMed:9182757, ECO:0000269|PubMed:9632781" FT MOD_RES 436 FT /note="Phosphotyrosine; by FGFR1" FT /evidence="ECO:0000269|PubMed:11353842, FT ECO:0000269|PubMed:9632781" FT MOD_RES 471 FT /note="Phosphotyrosine; by FGFR1" FT /evidence="ECO:0000269|PubMed:11353842" FT LIPID 2 FT /note="N-myristoyl glycine" FT /evidence="ECO:0000269|PubMed:9182757" FT MUTAGEN 2 FT /note="G->A: Abolishes myristoylation and membrane FT association." FT /evidence="ECO:0000269|PubMed:9182757" FT MUTAGEN 196 FT /note="Y->F: Abolishes tyrosine phosphorylation and FT interactions with GRB2 and PTPN11; when associated with FT F-306; F-349; F-392 and F-436." FT /evidence="ECO:0000269|PubMed:9182757" FT MUTAGEN 306 FT /note="Y->F: Abolishes tyrosine phosphorylation and FT interactions with GRB2 and PTPN11; when associated with FT F-196; F-349; F-392 and F-436." FT /evidence="ECO:0000269|PubMed:9182757" FT MUTAGEN 349 FT /note="Y->F: Abolishes tyrosine phosphorylation and FT interactions with GRB2 and PTPN11; when associated with FT F-196; F-306; F-392 and F-436." FT /evidence="ECO:0000269|PubMed:9182757" FT MUTAGEN 392 FT /note="Y->F: Abolishes tyrosine phosphorylation and FT interactions with GRB2 and PTPN11; when associated with FT F-196; F-306; F-349 and F-436." FT /evidence="ECO:0000269|PubMed:9182757" FT MUTAGEN 436 FT /note="Y->F: Abolishes tyrosine phosphorylation and FT interactions with GRB2 and PTPN11; when associated with FT F-196; F-306; F-349 and F-392." FT /evidence="ECO:0000269|PubMed:9632781" SQ SEQUENCE 508 AA; 56794 MW; DFFE8A818BFF8631 CRC64; MGSCCSCPDK DTVPDNHRNK FKVINVDDDG NELGSGVMEL TDTELILYTR KRDSVKWHYL CLRRYGYDSN LFSFESGRRC QTGQGIFAFK CARAEELFNM LQEIMQNNSI NVVEEPVVER SSHQTELEVP RTPRTPTTPG LGAQNLPNGY PRYPSFGDAS SHPSSRHPSV GSARLPSVGE ESTHPLLVAE EQVHTYVNTT GVQEERKNRA SVHVPPEARV SNAESNTPKE EPSNPEDRDP QVLLKPEGVR FVLGPTPVQK QLMEKEKLEQ LGKDPVSGSG AGNTEWDTGY DSDERRDVPP VNKLVYENIN GLSIPSASGV RRGRLTSTST SDTQNINNSA QRRPALLNYE NLPSLPPVWE ARKLSRDEDD NLGPKTPSLN GYHNNLDPMH NYVNTENVTV PASAHKIDYS KRRDCTPTVF NFDIRRPSLE HRQLNYIQVD LEGGSDSDNP QTPKTPTTPL PQTPTRRTEL YAVIDIERTA AMSNLQKALP RDDGTSRKTR HNSTDLPM //