ID SPY2_HUMAN Reviewed; 315 AA. AC O43597; B2R9J9; Q5T6Z7; DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1998, sequence version 1. DT 27-MAR-2024, entry version 198. DE RecName: Full=Protein sprouty homolog 2; DE Short=Spry-2; GN Name=SPRY2; 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]. RX PubMed=9458049; DOI=10.1016/s0092-8674(00)80919-8; RA Hacohen N., Kramer S., Sutherland D., Hiromi Y., Krasnow M.A.; RT "Sprouty encodes a novel antagonist of FGF signaling that patterns apical RT branching of the Drosophila airways."; RL Cell 92:253-263(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Substantia nigra; 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 [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057823; DOI=10.1038/nature02379; RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L., RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., RA Frankish A.G., Frankland J., French L., Garner P., Garnett J., RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., RA Rogers J., Ross M.T.; RT "The DNA sequence and analysis of human chromosome 13."; RL Nature 428:522-528(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Skin; 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 SUBCELLULAR LOCATION, AND DOMAIN. RX PubMed=10887178; DOI=10.1074/jbc.m002156200; RA Lim J., Wong E.S.M., Ong S.H., Yusoff P., Low B.C., Guy G.R.; RT "Sprouty proteins are targeted to membrane ruffles upon growth factor RT receptor tyrosine kinase activation. Identification of a novel RT translocation domain."; RL J. Biol. Chem. 275:32837-32845(2000). RN [7] RP INTERACTION WITH CAV1, AND MUTAGENESIS OF ARG-252. RX PubMed=16877379; DOI=10.1074/jbc.m603921200; RA Cabrita M.A., Jaeggi F., Widjaja S.P., Christofori G.; RT "A functional interaction between sprouty proteins and caveolin-1."; RL J. Biol. Chem. 281:29201-29212(2006). RN [8] RP INTERACTION WITH RAF1. RX PubMed=12717443; DOI=10.1038/ncb978; RA Sasaki A., Taketomi T., Kato R., Saeki K., Nonami A., Sasaki M., RA Kuriyama M., Saito N., Shibuya M., Yoshimura A.; RT "Mammalian Sprouty4 suppresses Ras-independent ERK activation by binding to RT Raf1."; RL Nat. Cell Biol. 5:427-432(2003). RN [9] RP FUNCTION, INTERACTION WITH TESK1; GRB2; CBL; PPP2R1A AND PPP2CA, AND RP MUTAGENESIS OF SER-115. RX PubMed=17974561; DOI=10.1074/jbc.m705457200; RA Chandramouli S., Yu C.Y., Yusoff P., Lao D.H., Leong H.F., Mizuno K., RA Guy G.R.; RT "Tesk1 interacts with Spry2 to abrogate its inhibition of ERK RT phosphorylation downstream of receptor tyrosine kinase signaling."; RL J. Biol. Chem. 283:1679-1691(2008). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [11] RP CLEAVAGE BY FAP, CLEAVAGE SITE, AND MUTAGENESIS OF PRO-144. RX PubMed=21288888; DOI=10.1093/jb/mvr017; RA Huang C.H., Suen C.S., Lin C.T., Chien C.H., Lee H.Y., Chung K.M., RA Tsai T.Y., Jiaang W.T., Hwang M.J., Chen X.; RT "Cleavage-site specificity of prolyl endopeptidase FAP investigated with a RT full-length protein substrate."; RL J. Biochem. 149:685-692(2011). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; 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 [13] RP INTERACTION WITH METTL13. RX PubMed=29408807; DOI=10.1172/jci97350; RA Yousaf R., Ahmed Z.M., Giese A.P., Morell R.J., Lagziel A., Dabdoub A., RA Wilcox E.R., Riazuddin S., Friedman T.B., Riazuddin S.; RT "Modifier variant of METTL13 suppresses human GAB1-associated profound RT deafness."; RL J. Clin. Invest. 128:1509-1522(2018). RN [14] RP VARIANT IGAN3 TRP-119, AND CHARACTERIZATION OF VARIANT IGAN3 TRP-119. RX PubMed=25782674; DOI=10.1038/ejhg.2015.52; RA Milillo A., La Carpia F., Costanzi S., D'Urbano V., Martini M., Lanuti P., RA Vischini G., Larocca L.M., Marchisio M., Miscia S., Amoroso A., RA Gurrieri F., Sangiorgi E.; RT "A SPRY2 mutation leading to MAPK/ERK pathway inhibition is associated with RT an autosomal dominant form of IgA nephropathy."; RL Eur. J. Hum. Genet. 23:1673-1678(2015). CC -!- FUNCTION: Antagonist of fibroblast growth factor (FGF) pathways via CC inhibition of FGF-mediated phosphorylation of ERK1/2 (By similarity). CC Thereby acts as an antagonist of FGF-induced retinal lens fiber CC differentiation, may inhibit limb bud outgrowth and may negatively CC modulate respiratory organogenesis (By similarity). Inhibits TGFB- CC induced epithelial-to-mesenchymal transition in retinal lens epithelial CC cells (By similarity). Inhibits CBL/C-CBL-mediated EGFR ubiquitination CC (PubMed:17974561). {ECO:0000250|UniProtKB:Q9QXV8, CC ECO:0000269|PubMed:17974561}. CC -!- SUBUNIT: Forms heterodimers with SPRY1 (By similarity). Forms a CC tripartite complex containing GAB1, METTL13 and SPRY2 CC (PubMed:29408807). Within the complex interacts with METTL13 CC (PubMed:29408807).Interacts with RAF1 (PubMed:12717443). Interacts (via CC C-terminus) with TESK1 (via C-terminus); the interaction disrupts SPRY2 CC interaction with GRB2, potentially via disruption of SPRY2 serine CC dephosphorylation (PubMed:17974561). Interacts with PPP2R1A/PP2A-A and CC PPP2CA/PP2A-C; the interaction with PPP2CA/PP2A-C is inhibited by CC interaction with TESK1, possibly by vesicular sequestration of SPRY2 CC (PubMed:17974561). Inhibition of the interaction with the CC serine/threonine-protein phosphatase 2A (PP2A) holoenzyme results in CC loss of PP2A-mediated dephosphorylation, resulting in the loss of SPRY2 CC interaction with GRB2 (PubMed:17974561). Interacts with GRB2 CC (PubMed:17974561). Interacts with CBL/C-CBL; the interaction inhibits CC CBL-mediated ubiquitination of EGFR (PubMed:17974561). Interacts (via CC C-terminus) with CAV1 (via C-terminus) (PubMed:16877379). CC {ECO:0000250|UniProtKB:Q9QXV8, ECO:0000269|PubMed:12717443, CC ECO:0000269|PubMed:16877379, ECO:0000269|PubMed:17974561, CC ECO:0000269|PubMed:29408807}. CC -!- INTERACTION: CC O43597; P29972: AQP1; NbExp=3; IntAct=EBI-742487, EBI-745213; CC O43597; Q8WXE1: ATRIP; NbExp=3; IntAct=EBI-742487, EBI-747353; CC O43597; Q8NEC5: CATSPER1; NbExp=3; IntAct=EBI-742487, EBI-744545; CC O43597; P22681: CBL; NbExp=17; IntAct=EBI-742487, EBI-518228; CC O43597; Q9H2X0: CHRD; NbExp=3; IntAct=EBI-742487, EBI-947551; CC O43597; P07510-2: CHRNG; NbExp=3; IntAct=EBI-742487, EBI-11979451; CC O43597; Q02930-3: CREB5; NbExp=3; IntAct=EBI-742487, EBI-10192698; CC O43597; O60573: EIF4E2; NbExp=3; IntAct=EBI-742487, EBI-398610; CC O43597; Q9NVQ4: FAIM; NbExp=3; IntAct=EBI-742487, EBI-10314711; CC O43597; O43559: FRS3; NbExp=3; IntAct=EBI-742487, EBI-725515; CC O43597; Q9Y223: GNE; NbExp=3; IntAct=EBI-742487, EBI-4291090; CC O43597; P14770: GP9; NbExp=3; IntAct=EBI-742487, EBI-1754109; CC O43597; O75791: GRAP2; NbExp=3; IntAct=EBI-742487, EBI-740418; CC O43597; P62993: GRB2; NbExp=3; IntAct=EBI-742487, EBI-401755; CC O43597; P28799: GRN; NbExp=3; IntAct=EBI-742487, EBI-747754; CC O43597; Q96MH2: HEXIM2; NbExp=3; IntAct=EBI-742487, EBI-5460660; CC O43597; Q9H2F3: HSD3B7; NbExp=3; IntAct=EBI-742487, EBI-3918847; CC O43597; P60412: KRTAP10-11; NbExp=3; IntAct=EBI-742487, EBI-10217483; CC O43597; P60370: KRTAP10-5; NbExp=3; IntAct=EBI-742487, EBI-10172150; CC O43597; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-742487, EBI-10171774; CC O43597; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-742487, EBI-10172052; CC O43597; Q9BYQ6: KRTAP4-11; NbExp=3; IntAct=EBI-742487, EBI-10302392; CC O43597; Q9BQ66: KRTAP4-12; NbExp=4; IntAct=EBI-742487, EBI-739863; CC O43597; Q9BYR0: KRTAP4-7; NbExp=3; IntAct=EBI-742487, EBI-10302547; CC O43597; Q6L8G9: KRTAP5-6; NbExp=3; IntAct=EBI-742487, EBI-10250562; CC O43597; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-742487, EBI-3958099; CC O43597; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-742487, EBI-1044640; CC O43597; Q9BYQ2: KRTAP9-4; NbExp=3; IntAct=EBI-742487, EBI-10185730; CC O43597; Q14847: LASP1; NbExp=3; IntAct=EBI-742487, EBI-742828; CC O43597; Q5T7P3: LCE1B; NbExp=5; IntAct=EBI-742487, EBI-10245913; CC O43597; Q5TA82: LCE2D; NbExp=3; IntAct=EBI-742487, EBI-10246750; CC O43597; Q5T5A8: LCE3C; NbExp=3; IntAct=EBI-742487, EBI-10245291; CC O43597; Q5T5B0: LCE3E; NbExp=3; IntAct=EBI-742487, EBI-10245456; CC O43597; Q5TA78: LCE4A; NbExp=3; IntAct=EBI-742487, EBI-10246358; CC O43597; Q17RB8: LONRF1; NbExp=3; IntAct=EBI-742487, EBI-2341787; CC O43597; O60336: MAPKBP1; NbExp=3; IntAct=EBI-742487, EBI-947402; CC O43597; Q99750: MDFI; NbExp=3; IntAct=EBI-742487, EBI-724076; CC O43597; P50222: MEOX2; NbExp=3; IntAct=EBI-742487, EBI-748397; CC O43597; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-742487, EBI-10172526; CC O43597; Q6P2C6: MLLT6; NbExp=3; IntAct=EBI-742487, EBI-5773143; CC O43597; O43639: NCK2; NbExp=3; IntAct=EBI-742487, EBI-713635; CC O43597; P32242: OTX1; NbExp=4; IntAct=EBI-742487, EBI-740446; CC O43597; Q9UKS6: PACSIN3; NbExp=3; IntAct=EBI-742487, EBI-77926; CC O43597; O43741: PRKAB2; NbExp=4; IntAct=EBI-742487, EBI-1053424; CC O43597; P43115-12: PTGER3; NbExp=3; IntAct=EBI-742487, EBI-10234038; CC O43597; Q06455-4: RUNX1T1; NbExp=3; IntAct=EBI-742487, EBI-10224192; CC O43597; Q96B97: SH3KBP1; NbExp=2; IntAct=EBI-742487, EBI-346595; CC O43597; Q9NUL5: SHFL; NbExp=3; IntAct=EBI-742487, EBI-10313866; CC O43597; O43609: SPRY1; NbExp=3; IntAct=EBI-742487, EBI-3866665; CC O43597; O75716: STK16; NbExp=3; IntAct=EBI-742487, EBI-749295; CC O43597; Q9Y4C2: TCAF1; NbExp=3; IntAct=EBI-742487, EBI-750484; CC O43597; Q86UY0: TXNDC5; NbExp=3; IntAct=EBI-742487, EBI-2825190; CC O43597; P57075: UBASH3A; NbExp=4; IntAct=EBI-742487, EBI-2105393; CC O43597; Q8TF42: UBASH3B; NbExp=3; IntAct=EBI-742487, EBI-1380492; CC O43597; Q9Y2K6: USP20; NbExp=3; IntAct=EBI-742487, EBI-2511991; CC O43597; Q8IUH5: ZDHHC17; NbExp=3; IntAct=EBI-742487, EBI-524753; CC O43597; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-742487, EBI-740727; CC O43597; Q96SQ5: ZNF587; NbExp=3; IntAct=EBI-742487, EBI-6427977; CC O43597; Q5JPT6; NbExp=3; IntAct=EBI-742487, EBI-10244213; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton CC {ECO:0000269|PubMed:10887178}. Cell projection, ruffle membrane CC {ECO:0000269|PubMed:10887178}. Note=Associated with microtubules in CC unstimulated cells but is translocated to the membrane ruffles in cells CC stimulated with EGF (epidermal growth factor). CC {ECO:0000269|PubMed:10887178}. CC -!- DOMAIN: The Cys-rich domain is responsible for the localization of the CC protein to the membrane ruffles. {ECO:0000269|PubMed:10887178}. CC -!- PTM: Cleaved at Pro-144 by the prolyl endopeptidase FAP (seprase) CC activity (in vitro). {ECO:0000269|PubMed:21288888}. CC -!- DISEASE: IgA nephropathy 3 (IGAN3) [MIM:616818]: A form of IgA CC nephropathy, a common primary glomerulonephritis characterized by CC glomerular sclerosis, interstitial fibrosis, and mesangial glomerular CC deposits of immunoglobulin A and immunoglobulin G visible on renal CC biopsies. IgA nephropathy is associated with renal insufficiency that CC can progress to end-stage renal disease. Proteinuria and hematuria are CC characteristic clinical presentations. {ECO:0000269|PubMed:25782674}. CC Note=Disease susceptibility is associated with variants affecting the CC gene represented in this entry. CC -!- SIMILARITY: Belongs to the sprouty family. {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; AF039843; AAC04258.1; -; mRNA. DR EMBL; AL713749; CAD28524.1; -; mRNA. DR EMBL; AK313810; BAG36546.1; -; mRNA. DR EMBL; AL354668; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC015745; AAH15745.1; -; mRNA. DR CCDS; CCDS9463.1; -. DR RefSeq; NP_001305465.1; NM_001318536.1. DR RefSeq; NP_001305466.1; NM_001318537.1. DR RefSeq; NP_001305467.1; NM_001318538.1. DR RefSeq; NP_005833.1; NM_005842.3. DR PDB; 3BUM; X-ray; 2.00 A; A=49-61. DR PDB; 3OB1; X-ray; 2.20 A; A=49-60. DR PDB; 5HKY; X-ray; 1.80 A; B=36-60. DR PDB; 5HKZ; X-ray; 1.80 A; B=36-60. DR PDB; 5HL0; X-ray; 2.20 A; B=54-60. DR PDBsum; 3BUM; -. DR PDBsum; 3OB1; -. DR PDBsum; 5HKY; -. DR PDBsum; 5HKZ; -. DR PDBsum; 5HL0; -. DR AlphaFoldDB; O43597; -. DR SMR; O43597; -. DR BioGRID; 115547; 152. DR IntAct; O43597; 95. DR MINT; O43597; -. DR STRING; 9606.ENSP00000366306; -. DR GlyGen; O43597; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O43597; -. DR PhosphoSitePlus; O43597; -. DR SwissPalm; O43597; -. DR BioMuta; SPRY2; -. DR EPD; O43597; -. DR jPOST; O43597; -. DR MassIVE; O43597; -. DR PaxDb; 9606-ENSP00000366306; -. DR PeptideAtlas; O43597; -. DR ProteomicsDB; 49069; -. DR Antibodypedia; 10392; 344 antibodies from 36 providers. DR DNASU; 10253; -. DR Ensembl; ENST00000377102.5; ENSP00000366306.1; ENSG00000136158.12. DR Ensembl; ENST00000377104.4; ENSP00000366308.3; ENSG00000136158.12. DR GeneID; 10253; -. DR KEGG; hsa:10253; -. DR MANE-Select; ENST00000377104.4; ENSP00000366308.3; NM_005842.4; NP_005833.1. DR UCSC; uc001vli.4; human. DR AGR; HGNC:11270; -. DR CTD; 10253; -. DR DisGeNET; 10253; -. DR GeneCards; SPRY2; -. DR HGNC; HGNC:11270; SPRY2. DR HPA; ENSG00000136158; Low tissue specificity. DR MalaCards; SPRY2; -. DR MIM; 602466; gene. DR MIM; 616818; phenotype. DR neXtProt; NX_O43597; -. DR OpenTargets; ENSG00000136158; -. DR PharmGKB; PA36099; -. DR VEuPathDB; HostDB:ENSG00000136158; -. DR eggNOG; ENOG502QTG8; Eukaryota. DR GeneTree; ENSGT00950000183055; -. DR HOGENOM; CLU_077696_0_0_1; -. DR InParanoid; O43597; -. DR OMA; MHAYRCE; -. DR OrthoDB; 4219076at2759; -. DR PhylomeDB; O43597; -. DR TreeFam; TF325070; -. DR PathwayCommons; O43597; -. DR Reactome; R-HSA-1295596; Spry regulation of FGF signaling. DR Reactome; R-HSA-182971; EGFR downregulation. DR SignaLink; O43597; -. DR SIGNOR; O43597; -. DR BioGRID-ORCS; 10253; 30 hits in 1162 CRISPR screens. DR ChiTaRS; SPRY2; human. DR EvolutionaryTrace; O43597; -. DR GeneWiki; SPRY2; -. DR GenomeRNAi; 10253; -. DR Pharos; O43597; Tbio. DR PRO; PR:O43597; -. DR Proteomes; UP000005640; Chromosome 13. DR RNAct; O43597; Protein. DR Bgee; ENSG00000136158; Expressed in cartilage tissue and 195 other cell types or tissues. DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA. DR GO; GO:0005856; C:cytoskeleton; ISS:BHF-UCL. DR GO; GO:0005829; C:cytosol; ISS:BHF-UCL. DR GO; GO:0016020; C:membrane; ISS:BHF-UCL. DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA. DR GO; GO:1990752; C:microtubule end; IDA:HPA. DR GO; GO:0005634; C:nucleus; ISS:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL. DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IMP:UniProtKB. DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; IC:BHF-UCL. DR GO; GO:0055105; F:ubiquitin-protein transferase inhibitor activity; IEA:Ensembl. DR GO; GO:0048513; P:animal organ development; IBA:GO_Central. DR GO; GO:0060449; P:bud elongation involved in lung branching; IEA:Ensembl. DR GO; GO:0045165; P:cell fate commitment; IEA:Ensembl. DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl. DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IDA:BHF-UCL. DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IEA:Ensembl. DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IEA:Ensembl. DR GO; GO:0042472; P:inner ear morphogenesis; IEA:Ensembl. DR GO; GO:0060437; P:lung growth; IEA:Ensembl. DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:BHF-UCL. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl. DR GO; GO:0031345; P:negative regulation of cell projection organization; ISS:BHF-UCL. DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; ISS:UniProtKB. DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IDA:BHF-UCL. DR GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; IBA:GO_Central. DR GO; GO:1902747; P:negative regulation of lens fiber cell differentiation; ISS:UniProtKB. DR GO; GO:0051387; P:negative regulation of neurotrophin TRK receptor signaling pathway; IEA:Ensembl. DR GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; IDA:BHF-UCL. DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IDA:UniProtKB. DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; IBA:GO_Central. DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISS:UniProtKB. DR GO; GO:1900747; P:negative regulation of vascular endothelial growth factor signaling pathway; IDA:BHF-UCL. DR GO; GO:0030335; P:positive regulation of cell migration; IMP:BHF-UCL. DR GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; IEA:Ensembl. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IMP:UniProtKB. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:UniProtKB. DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl. DR IDEAL; IID00528; -. DR InterPro; IPR007875; Sprouty. DR PANTHER; PTHR12365:SF8; PROTEIN SPROUTY HOMOLOG 2; 1. DR PANTHER; PTHR12365; SPROUTY; 1. DR Pfam; PF05210; Sprouty; 1. DR PROSITE; PS51227; SPR; 1. DR Genevisible; O43597; HS. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Cell projection; Cytoplasm; Cytoskeleton; KW Developmental protein; Disease variant; Membrane; Microtubule; KW Reference proteome. FT CHAIN 1..315 FT /note="Protein sprouty homolog 2" FT /id="PRO_0000076901" FT DOMAIN 177..291 FT /note="SPR" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00572" FT REGION 1..39 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 51..140 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 118..315 FT /note="Required for interaction with CAV1" FT /evidence="ECO:0000250|UniProtKB:Q9QXV8" FT REGION 178..315 FT /note="Required for interaction with TESK1" FT /evidence="ECO:0000269|PubMed:17974561" FT COMPBIAS 1..18 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 73..94 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 95..140 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 144..145 FT /note="Cleavage; by FAP" FT /evidence="ECO:0000269|PubMed:21288888" FT VARIANT 106 FT /note="P -> S (in dbSNP:rs504122)" FT /id="VAR_024647" FT VARIANT 119 FT /note="R -> W (in IGAN3; no effect on protein expression; FT negatively regulates ERK1 and ERK2 cascade; FT dbSNP:rs869025336)" FT /evidence="ECO:0000269|PubMed:25782674" FT /id="VAR_076288" FT MUTAGEN 115 FT /note="S->A: Abolishes interaction with GRB2." FT /evidence="ECO:0000269|PubMed:17974561" FT MUTAGEN 144 FT /note="P->L: Inhibits cleavage by the prolyl endopeptidase FT FAP." FT /evidence="ECO:0000269|PubMed:21288888" FT MUTAGEN 252 FT /note="R->D: Abolishes interaction with CAV1." FT /evidence="ECO:0000269|PubMed:16877379" FT CONFLICT 48 FT /note="A -> V (in Ref. 2; BAG36546)" FT /evidence="ECO:0000305" FT TURN 43..45 FT /evidence="ECO:0007829|PDB:5HKY" SQ SEQUENCE 315 AA; 34688 MW; 8CC6256929D91A7E CRC64; MEARAQSGNG SQPLLQTPRD GGRQRGEPDP RDALTQQVHV LSLDQIRAIR NTNEYTEGPT VVPRPGLKPA PRPSTQHKHE RLHGLPEHRQ PPRLQHSQVH SSARAPLSRS ISTVSSGSRS STRTSTSSSS SEQRLLGSSF SSGPVADGII RVQPKSELKP GELKPLSKED LGLHAYRCED CGKCKCKECT YPRPLPSDWI CDKQCLCSAQ NVIDYGTCVC CVKGLFYHCS NDDEDNCADN PCSCSQSHCC TRWSAMGVMS LFLPCLWCYL PAKGCLKLCQ GCYDRVNRPG CRCKNSNTVC CKVPTVPPRN FEKPT //