ID FRS2_HUMAN Reviewed; 508 AA. AC Q8WU20; B0LPF2; B2R684; O43558; Q7LDQ6; DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot. DT 14-OCT-2008, sequence version 4. DT 24-JAN-2024, entry version 184. DE RecName: Full=Fibroblast growth factor receptor substrate 2; DE Short=FGFR substrate 2; DE AltName: Full=FGFR-signaling adaptor SNT; DE AltName: Full=Suc1-associated neurotrophic factor target 1; DE Short=SNT-1; GN Name=FRS2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH FGFR1, MYRISTOYLATION AT RP GLY-2, AND PHOSPHORYLATION AT TYROSINE RESIDUES. RC TISSUE=Placenta; RX PubMed=9660748; DOI=10.1074/jbc.273.29.17987; RA Xu H., Lee K.W., Goldfarb M.P.; RT "Novel recognition motif on fibroblast growth factor receptor mediates RT direct association and activation of SNT adapter proteins."; RL J. Biol. Chem. 273:17987-17990(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Hippocampus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NHLBI resequencing and genotyping service (RS&G); RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Uterus; 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 [7] RP INTERACTION WITH CKS2; GRB2; PTPN11; SRC; NTRK1; NTRK2 AND NTRK3, RP MYRISTOYLATION AT GLY-2, PHOSPHORYLATION AT TYROSINE RESIDUES, AND TISSUE RP SPECIFICITY. RX PubMed=10092678; DOI=10.1074/jbc.274.14.9861; RA Meakin S.O., MacDonald J.I.S., Gryz E.A., Kubu C.J., Verdi J.M.; RT "The signaling adapter FRS-2 competes with Shc for binding to the nerve RT growth factor receptor TrkA. A model for discriminating proliferation and RT differentiation."; RL J. Biol. Chem. 274:9861-9870(1999). RN [8] RP PHOSPHORYLATION BY MAPK1/ERK2 AND MAPK3/ERK1, INTERACTION WITH MAPK1/ERK2 RP AND MAPK3/ERK1, AND FUNCTION. RX PubMed=12974390; DOI=10.1515/bc.2003.134; RA Wu Y., Chen Z., Ullrich A.; RT "EGFR and FGFR signaling through FRS2 is subject to negative feedback RT control by ERK1/2."; RL Biol. Chem. 384:1215-1226(2003). RN [9] RP INTERACTION WITH NTRK1. RX PubMed=15488758; DOI=10.1016/j.ccr.2004.09.011; RA Tacconelli A., Farina A.R., Cappabianca L., Desantis G., Tessitore A., RA Vetuschi A., Sferra R., Rucci N., Argenti B., Screpanti I., Gulino A., RA Mackay A.R.; RT "TrkA alternative splicing: a regulated tumor-promoting switch in human RT neuroblastoma."; RL Cancer Cell 6:347-360(2004). RN [10] RP INTERACTION WITH ALK, AND PHOSPHORYLATION. RX PubMed=17274988; DOI=10.1016/j.febslet.2007.01.039; RA Degoutin J., Vigny M., Gouzi J.Y.; RT "ALK activation induces Shc and FRS2 recruitment: Signaling and phenotypic RT outcomes in PC12 cells differentiation."; RL FEBS Lett. 581:727-734(2007). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-221, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [12] RP FUNCTION IN ACTIVATION OF AKT1; PLCG1; MAPK1/ERK2, MAPK3/ERK1 AND MAP RP KINASE SIGNALING, INTERACTION WITH FGFR1, AND PHOSPHORYLATION. RX PubMed=21765395; DOI=10.1038/emboj.2011.234; RA Persaud A., Alberts P., Hayes M., Guettler S., Clarke I., Sicheri F., RA Dirks P., Ciruna B., Rotin D.; RT "Nedd4-1 binds and ubiquitylates activated FGFR1 to control its endocytosis RT and function."; RL EMBO J. 30:3259-3273(2011). RN [13] 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 [14] 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). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-211 AND SER-365, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-177, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [17] RP STRUCTURE BY NMR OF 11-136 IN COMPLEX WITH FGFR1. RX PubMed=11090629; DOI=10.1016/s1097-2765(05)00087-0; RA Dhalluin C., Yan K.S., Plotnikova O., Lee K.W., Zeng L., Kuti M., RA Mujtaba S., Goldfarb M.P., Zhou M.-M.; RT "Structural basis of SNT PTB domain interactions with distinct neurotrophic RT receptors."; RL Mol. Cell 6:921-929(2000). 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:12974390, ECO:0000269|PubMed:21765395}. CC -!- SUBUNIT: Part of a complex containing FRS2, GRB2, GAB1, PIK3R1 and CC SOS1. Part of a complex containing GRB2 and CBL. Identified in a CC complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 CC and CTTN. Binds RET (By similarity). Binds ALK, FGFR1, CKS2, CC MAPK1/ERK2, MAPK3/ERK1 and SRC. The tyrosine-phosphorylated protein CC binds the SH2 domains of GRB2 and PTPN11. Interacts with NTRK1, NTRK2 CC and NTRK3 (phosphorylated upon ligand-binding). {ECO:0000250, CC ECO:0000269|PubMed:10092678, ECO:0000269|PubMed:11090629, CC ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:15488758, CC ECO:0000269|PubMed:17274988, ECO:0000269|PubMed:21765395, CC ECO:0000269|PubMed:9660748}. CC -!- INTERACTION: CC Q8WU20; P11362: FGFR1; NbExp=3; IntAct=EBI-1104330, EBI-1028277; CC Q8WU20; Q06124: PTPN11; NbExp=4; IntAct=EBI-1104330, EBI-297779; CC -!- SUBCELLULAR LOCATION: Endomembrane system. Note=Cytoplasmic, membrane- CC bound. CC -!- TISSUE SPECIFICITY: Highly expressed in heart, brain, spleen, lung, CC liver, skeletal muscle, kidney and testis. CC {ECO:0000269|PubMed:10092678}. CC -!- PTM: Phosphorylated by ULK2 in vitro (By similarity). Phosphorylated on CC tyrosine residues upon stimulation by NGF or FGF2. Phosphorylated on CC tyrosine residues by activated ALK and FGFR1. Phosphorylated on CC tyrosine 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. {ECO:0000250, ECO:0000269|PubMed:10092678, CC ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:17274988, CC ECO:0000269|PubMed:21765395, ECO:0000269|PubMed:9660748}. CC -!- PTM: Ubiquitinated when tyrosine phosphorylated and in a complex with CC GRB2. The unphosphorylated form is not subject to ubiquitination (By CC similarity). {ECO:0000250}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH21562.1; Type=Erroneous termination; Note=Extended C-terminus.; Evidence={ECO:0000305}; CC Sequence=BAG35381.1; Type=Erroneous termination; Note=Extended C-terminus.; 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; AF036717; AAB92554.1; -; mRNA. DR EMBL; AK312477; BAG35381.1; ALT_SEQ; mRNA. DR EMBL; EU332842; ABY87531.1; -; Genomic_DNA. DR EMBL; AC018921; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471054; EAW97225.1; -; Genomic_DNA. DR EMBL; BC021562; AAH21562.1; ALT_SEQ; mRNA. DR CCDS; CCDS41809.1; -. DR RefSeq; NP_001036020.1; NM_001042555.2. DR RefSeq; NP_001265280.1; NM_001278351.1. DR RefSeq; NP_001265282.1; NM_001278353.1. DR RefSeq; NP_001265283.1; NM_001278354.1. DR RefSeq; NP_001265284.1; NM_001278355.1. DR RefSeq; NP_001265285.1; NM_001278356.1. DR RefSeq; NP_001265286.1; NM_001278357.1. DR RefSeq; NP_006645.3; NM_006654.4. DR RefSeq; XP_016874206.1; XM_017018717.1. DR RefSeq; XP_016874207.1; XM_017018718.1. DR RefSeq; XP_016874208.1; XM_017018719.1. DR PDB; 1XR0; NMR; -; B=11-136. DR PDB; 2MFQ; NMR; -; A=11-122. DR PDBsum; 1XR0; -. DR PDBsum; 2MFQ; -. DR AlphaFoldDB; Q8WU20; -. DR BMRB; Q8WU20; -. DR SMR; Q8WU20; -. DR BioGRID; 116031; 97. DR ELM; Q8WU20; -. DR IntAct; Q8WU20; 24. DR MINT; Q8WU20; -. DR STRING; 9606.ENSP00000447241; -. DR GlyGen; Q8WU20; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q8WU20; -. DR PhosphoSitePlus; Q8WU20; -. DR SwissPalm; Q8WU20; -. DR BioMuta; FRS2; -. DR DMDM; 209572769; -. DR EPD; Q8WU20; -. DR jPOST; Q8WU20; -. DR MassIVE; Q8WU20; -. DR MaxQB; Q8WU20; -. DR PaxDb; 9606-ENSP00000447241; -. DR PeptideAtlas; Q8WU20; -. DR ProteomicsDB; 74624; -. DR Pumba; Q8WU20; -. DR Antibodypedia; 4156; 588 antibodies from 39 providers. DR DNASU; 10818; -. DR Ensembl; ENST00000397997.6; ENSP00000381083.2; ENSG00000166225.9. DR Ensembl; ENST00000549921.6; ENSP00000450048.1; ENSG00000166225.9. DR Ensembl; ENST00000550389.5; ENSP00000447241.1; ENSG00000166225.9. DR GeneID; 10818; -. DR KEGG; hsa:10818; -. DR MANE-Select; ENST00000549921.6; ENSP00000450048.1; NM_001278356.2; NP_001265285.1. DR UCSC; uc009zrj.5; human. DR AGR; HGNC:16971; -. DR CTD; 10818; -. DR DisGeNET; 10818; -. DR GeneCards; FRS2; -. DR HGNC; HGNC:16971; FRS2. DR HPA; ENSG00000166225; Low tissue specificity. DR MIM; 607743; gene. DR neXtProt; NX_Q8WU20; -. DR OpenTargets; ENSG00000166225; -. DR PharmGKB; PA134850063; -. DR VEuPathDB; HostDB:ENSG00000166225; -. DR eggNOG; KOG4047; Eukaryota. DR GeneTree; ENSGT00940000157033; -. DR HOGENOM; CLU_022374_0_0_1; -. DR InParanoid; Q8WU20; -. DR OMA; SAHKIDY; -. DR OrthoDB; 2996885at2759; -. DR PhylomeDB; Q8WU20; -. DR TreeFam; TF324994; -. DR PathwayCommons; Q8WU20; -. DR Reactome; R-HSA-109704; PI3K Cascade. DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. DR Reactome; R-HSA-170968; Frs2-mediated activation. DR Reactome; R-HSA-201556; Signaling by ALK. DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. DR Reactome; R-HSA-5654689; PI-3K cascade:FGFR1. DR Reactome; R-HSA-5654693; FRS-mediated FGFR1 signaling. DR Reactome; R-HSA-5654695; PI-3K cascade:FGFR2. DR Reactome; R-HSA-5654700; FRS-mediated FGFR2 signaling. DR Reactome; R-HSA-5654706; FRS-mediated FGFR3 signaling. DR Reactome; R-HSA-5654710; PI-3K cascade:FGFR3. DR Reactome; R-HSA-5654712; FRS-mediated FGFR4 signaling. DR Reactome; R-HSA-5654720; PI-3K cascade:FGFR4. DR Reactome; R-HSA-5654726; Negative regulation of FGFR1 signaling. DR Reactome; R-HSA-5654727; Negative regulation of FGFR2 signaling. DR Reactome; R-HSA-5654732; Negative regulation of FGFR3 signaling. DR Reactome; R-HSA-5654733; Negative regulation of FGFR4 signaling. DR Reactome; R-HSA-5655253; Signaling by FGFR2 in disease. DR Reactome; R-HSA-5655291; Signaling by FGFR4 in disease. DR Reactome; R-HSA-5655302; Signaling by FGFR1 in disease. DR Reactome; R-HSA-5655332; Signaling by FGFR3 in disease. DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR Reactome; R-HSA-8853659; RET signaling. DR Reactome; R-HSA-9028731; Activated NTRK2 signals through FRS2 and FRS3. DR Reactome; R-HSA-9696270; RND2 GTPase cycle. DR Reactome; R-HSA-9696273; RND1 GTPase cycle. DR Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants. DR SignaLink; Q8WU20; -. DR SIGNOR; Q8WU20; -. DR BioGRID-ORCS; 10818; 27 hits in 1158 CRISPR screens. DR ChiTaRS; FRS2; human. DR EvolutionaryTrace; Q8WU20; -. DR GeneWiki; FRS2; -. DR GenomeRNAi; 10818; -. DR Pharos; Q8WU20; Tbio. DR PRO; PR:Q8WU20; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q8WU20; Protein. DR Bgee; ENSG00000166225; Expressed in calcaneal tendon and 177 other cell types or tissues. DR ExpressionAtlas; Q8WU20; baseline and differential. DR GO; GO:0005912; C:adherens junction; IDA:BHF-UCL. DR GO; GO:0005911; C:cell-cell junction; IBA:GO_Central. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; TAS:UniProtKB. DR GO; GO:0005104; F:fibroblast growth factor receptor binding; IPI:MGI. DR GO; GO:0005168; F:neurotrophin TRKA receptor binding; IPI:UniProtKB. DR GO; GO:0019211; F:phosphatase activator activity; TAS:UniProtKB. DR GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; IBA:GO_Central. DR GO; GO:0008595; P:anterior/posterior axis specification, embryo; IEA:Ensembl. DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IGI:MGI. DR GO; GO:0030900; P:forebrain development; IEA:Ensembl. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:UniProtKB. DR GO; GO:0001702; P:gastrulation with mouth forming second; IEA:Ensembl. DR GO; GO:0070307; P:lens fiber cell development; IEA:Ensembl. DR GO; GO:0046619; P:lens placode formation involved in camera-type eye formation; IEA:Ensembl. DR GO; GO:2000726; P:negative regulation of cardiac muscle cell differentiation; IGI:BHF-UCL. DR GO; GO:0007405; P:neuroblast proliferation; IEA:Ensembl. DR GO; GO:0001759; P:organ induction; IEA:Ensembl. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl. DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IEA:Ensembl. DR GO; GO:0060527; P:prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis; IEA:Ensembl. DR GO; GO:0042981; P:regulation of apoptotic process; IEA:Ensembl. DR GO; GO:0050678; P:regulation of epithelial cell proliferation; IEA:Ensembl. DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:0007185; P:transmembrane receptor protein tyrosine phosphatase signaling pathway; TAS:UniProtKB. DR GO; GO:0003281; P:ventricular septum development; IEA:Ensembl. DR CDD; cd01202; PTB_FRS2; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR IDEAL; IID00675; -. 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; Q8WU20; HS. PE 1: Evidence at protein level; KW 3D-structure; Lipoprotein; Membrane; Myristate; Phosphoprotein; KW Reference proteome; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT CHAIN 2..508 FT /note="Fibroblast growth factor receptor substrate 2" FT /id="PRO_0000087344" FT DOMAIN 13..115 FT /note="IRS-type PTB" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00389" FT REGION 122..180 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 200..243 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 270..297 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 315..338 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 366..385 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:0007744|PubMed:24275569" FT MOD_RES 196 FT /note="Phosphotyrosine; by FGFR1" FT /evidence="ECO:0000250|UniProtKB:Q8C180" FT MOD_RES 211 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 221 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 306 FT /note="Phosphotyrosine; by FGFR1" FT /evidence="ECO:0000250|UniProtKB:Q8C180" FT MOD_RES 349 FT /note="Phosphotyrosine; by FGFR1" FT /evidence="ECO:0000250|UniProtKB:Q8C180" FT MOD_RES 365 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 392 FT /note="Phosphotyrosine; by FGFR1" FT /evidence="ECO:0000250|UniProtKB:Q8C180" FT MOD_RES 436 FT /note="Phosphotyrosine; by FGFR1" FT /evidence="ECO:0000250|UniProtKB:Q8C180" FT MOD_RES 471 FT /note="Phosphotyrosine; by FGFR1" FT /evidence="ECO:0000250|UniProtKB:Q8C180" FT LIPID 2 FT /note="N-myristoyl glycine" FT /evidence="ECO:0000269|PubMed:10092678, FT ECO:0000269|PubMed:9660748" FT VARIANT 303 FT /note="K -> N (in dbSNP:rs12580717)" FT /id="VAR_046966" FT VARIANT 449 FT /note="N -> D (in dbSNP:rs35232109)" FT /id="VAR_046967" FT TURN 15..18 FT /evidence="ECO:0007829|PDB:2MFQ" FT STRAND 20..26 FT /evidence="ECO:0007829|PDB:1XR0" FT STRAND 32..34 FT /evidence="ECO:0007829|PDB:2MFQ" FT STRAND 36..40 FT /evidence="ECO:0007829|PDB:1XR0" FT STRAND 45..49 FT /evidence="ECO:0007829|PDB:1XR0" FT TURN 50..52 FT /evidence="ECO:0007829|PDB:1XR0" FT STRAND 53..57 FT /evidence="ECO:0007829|PDB:1XR0" FT TURN 59..61 FT /evidence="ECO:0007829|PDB:2MFQ" FT STRAND 62..67 FT /evidence="ECO:0007829|PDB:1XR0" FT STRAND 69..76 FT /evidence="ECO:0007829|PDB:1XR0" FT STRAND 84..90 FT /evidence="ECO:0007829|PDB:1XR0" FT HELIX 94..107 FT /evidence="ECO:0007829|PDB:1XR0" SQ SEQUENCE 508 AA; 57029 MW; 833714EE12097C75 CRC64; MGSCCSCPDK DTVPDNHRNK FKVINVDDDG NELGSGIMEL TDTELILYTR KRDSVKWHYL CLRRYGYDSN LFSFESGRRC QTGQGIFAFK CARAEELFNM LQEIMQNNSI NVVEEPVVER NNHQTELEVP RTPRTPTTPG FAAQNLPNGY PRYPSFGDAS SHPSSRHPSV GSARLPSVGE ESTHPLLVAE EQVHTYVNTT GVQEERKNRT SVHVPLEARV SNAESSTPKE EPSSIEDRDP QILLEPEGVK FVLGPTPVQK QLMEKEKLEQ LGRDQVSGSG ANNTEWDTGY DSDERRDAPS VNKLVYENIN GLSIPSASGV RRGRLTSTST SDTQNINNSA QRRTALLNYE NLPSLPPVWE ARKLSRDEDD NLGPKTPSLN GYHNNLDPMH NYVNTENVTV PASAHKIEYS RRRDCTPTVF NFDIRRPSLE HRQLNYIQVD LEGGSDSDNP QTPKTPTTPL PQTPTRRTEL YAVIDIERTA AMSNLQKALP RDDGTSRKTR HNSTDLPM //