FRS2_HUMAN
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 03-AUG-2022, entry version 176.
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; 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; 89.
DR ELM; Q8WU20; -.
DR IntAct; Q8WU20; 12.
DR MINT; Q8WU20; -.
DR STRING; 9606.ENSP00000447241; -.
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; Q8WU20; -.
DR PeptideAtlas; Q8WU20; -.
DR PRIDE; Q8WU20; -.
DR ProteomicsDB; 74624; -.
DR Antibodypedia; 4156; 525 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 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; LMHNYVN; -.
DR OrthoDB; 473504at2759; -.
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; 21 hits in 1080 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 175 other tissues.
DR ExpressionAtlas; Q8WU20; baseline and differential.
DR Genevisible; Q8WU20; HS.
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:0005887; C:integral component of plasma membrane; TAS:UniProtKB.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
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:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
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; -; 1.
DR IDEAL; IID00675; -.
DR InterPro; IPR038742; FRS2_PTB.
DR InterPro; IPR002404; IRS_PTB.
DR InterPro; IPR011993; PH-like_dom_sf.
DR Pfam; PF02174; IRS; 1.
DR SMART; SM00310; PTBI; 1.
DR PROSITE; PS51064; IRS_PTB; 1.
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
