SPY2_HUMAN
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 03-AUG-2022, entry version 189.
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 ith 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}.
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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; 150.
DR IntAct; O43597; 93.
DR MINT; O43597; -.
DR STRING; 9606.ENSP00000366306; -.
DR iPTMnet; O43597; -.
DR PhosphoSitePlus; O43597; -.
DR SwissPalm; O43597; -.
DR BioMuta; SPRY2; -.
DR EPD; O43597; -.
DR jPOST; O43597; -.
DR MassIVE; O43597; -.
DR PaxDb; O43597; -.
DR PeptideAtlas; O43597; -.
DR PRIDE; O43597; -.
DR ProteomicsDB; 49069; -.
DR Antibodypedia; 10392; 309 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 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; VCCKVPS; -.
DR OrthoDB; 1157681at2759; -.
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; 25 hits in 1085 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 193 other tissues.
DR Genevisible; O43597; HS.
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: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:0034260; P:negative regulation of GTPase activity; IEA:Ensembl.
DR GO; GO:1902747; P:negative regulation of lens fiber cell differentiation; ISS:UniProtKB.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IBA:GO_Central.
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: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 protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl.
DR IDEAL; IID00528; -.
DR InterPro; IPR007875; Sprouty.
DR InterPro; IPR030780; SPRY2.
DR PANTHER; PTHR12365:SF8; PTHR12365:SF8; 1.
DR Pfam; PF05210; Sprouty; 1.
DR PROSITE; PS51227; SPR; 1.
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
