ID   SPRE3_MOUSE             Reviewed;         408 AA.
AC   Q6P6N5; Q7TNJ8;
DT   04-JAN-2005, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   24-JAN-2024, entry version 128.
DE   RecName: Full=Sprouty-related, EVH1 domain-containing protein 3;
DE            Short=Spred-3;
GN   Name=Spred3;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=12646235; DOI=10.1016/s0006-291x(03)00259-6;
RA   Kato R., Nonami A., Taketomi T., Wakioka T., Kuroiwa A., Matsuda Y.,
RA   Yoshimura A.;
RT   "Molecular cloning of mammalian Spred-3 which suppresses tyrosine kinase-
RT   mediated Erk activation.";
RL   Biochem. Biophys. Res. Commun. 302:767-772(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [4]
RP   INTERACTION WITH ZDHHC17, SUBCELLULAR LOCATION, AND PALMITOYLATION.
RX   PubMed=24705354; DOI=10.1093/hmg/ddu137;
RA   Butland S.L., Sanders S.S., Schmidt M.E., Riechers S.P., Lin D.T.,
RA   Martin D.D., Vaid K., Graham R.K., Singaraja R.R., Wanker E.E.,
RA   Conibear E., Hayden M.R.;
RT   "The palmitoyl acyltransferase HIP14 shares a high proportion of
RT   interactors with huntingtin: implications for a role in the pathogenesis of
RT   Huntington's disease.";
RL   Hum. Mol. Genet. 23:4142-4160(2014).
RN   [5]
RP   METHYLATION [LARGE SCALE ANALYSIS] AT ARG-238 AND ARG-246, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, and Embryo;
RX   PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA   Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA   Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA   Bedford M.T., Comb M.J.;
RT   "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT   methylation.";
RL   Mol. Cell. Proteomics 13:372-387(2014).
RN   [6]
RP   FUNCTION.
RX   PubMed=25576668; DOI=10.1016/j.exer.2015.01.001;
RA   Zhao G., Wojciechowski M.C., Jee S., Boros J., McAvoy J.W., Lovicu F.J.;
RT   "Negative regulation of TGFbeta-induced lens epithelial to mesenchymal
RT   transition (EMT) by RTK antagonists.";
RL   Exp. Eye Res. 132:9-16(2015).
RN   [7]
RP   FUNCTION.
RX   PubMed=29501879; DOI=10.1016/j.exer.2018.02.025;
RA   Zhao G., Bailey C.G., Feng Y., Rasko J., Lovicu F.J.;
RT   "Negative regulation of lens fiber cell differentiation by RTK antagonists
RT   Spry and Spred.";
RL   Exp. Eye Res. 170:148-159(2018).
CC   -!- FUNCTION: Tyrosine kinase substrate that inhibits growth-factor-
CC       mediated activation of MAP kinase (PubMed:12646235). Inhibits
CC       fibroblast growth factor (FGF)-induced retinal lens fiber
CC       differentiation, probably by inhibiting FGF-mediated phosphorylation of
CC       ERK1/2 (PubMed:29501879). Inhibits TGFB-induced epithelial-to-
CC       mesenchymal transition in lens epithelial cells (PubMed:25576668).
CC       {ECO:0000269|PubMed:12646235, ECO:0000269|PubMed:25576668,
CC       ECO:0000269|PubMed:29501879}.
CC   -!- SUBUNIT: Interacts with palmitoyltransferase ZDHHC17/HIP14; the
CC       interaction leads to palmitoylation of SPRED3.
CC       {ECO:0000269|PubMed:24705354}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12646235,
CC       ECO:0000269|PubMed:24705354}; Peripheral membrane protein
CC       {ECO:0000269|PubMed:12646235}.
CC   -!- TISSUE SPECIFICITY: Brain specific. {ECO:0000269|PubMed:12646235}.
CC   -!- PTM: Phosphorylated on tyrosine. {ECO:0000250|UniProtKB:Q2MJR0}.
CC   -!- PTM: Palmitoylated by ZDHHC17/HIP14. {ECO:0000269|PubMed:24705354}.
CC   -!- PTM: Ubiquitinated. {ECO:0000250|UniProtKB:Q2MJR0}.
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DR   EMBL; AB115762; BAC80222.1; -; mRNA.
DR   EMBL; BC062119; AAH62119.1; -; mRNA.
DR   CCDS; CCDS21065.1; -.
DR   RefSeq; NP_891557.3; NM_182927.3.
DR   RefSeq; XP_006539516.1; XM_006539453.2.
DR   RefSeq; XP_006539517.1; XM_006539454.3.
DR   RefSeq; XP_006539518.1; XM_006539455.3.
DR   RefSeq; XP_006539519.1; XM_006539456.2.
DR   AlphaFoldDB; Q6P6N5; -.
DR   SMR; Q6P6N5; -.
DR   BioGRID; 221733; 1.
DR   IntAct; Q6P6N5; 3.
DR   MINT; Q6P6N5; -.
DR   STRING; 10090.ENSMUSP00000046216; -.
DR   GlyGen; Q6P6N5; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; Q6P6N5; -.
DR   PhosphoSitePlus; Q6P6N5; -.
DR   SwissPalm; Q6P6N5; -.
DR   MaxQB; Q6P6N5; -.
DR   PaxDb; 10090-ENSMUSP00000046216; -.
DR   ProteomicsDB; 261630; -.
DR   DNASU; 101809; -.
DR   GeneID; 101809; -.
DR   KEGG; mmu:101809; -.
DR   UCSC; uc009gax.1; mouse.
DR   AGR; MGI:2142186; -.
DR   CTD; 399473; -.
DR   MGI; MGI:2142186; Spred3.
DR   eggNOG; KOG4590; Eukaryota.
DR   InParanoid; Q6P6N5; -.
DR   OrthoDB; 3031266at2759; -.
DR   PhylomeDB; Q6P6N5; -.
DR   TreeFam; TF321411; -.
DR   Reactome; R-MMU-5658442; Regulation of RAS by GAPs.
DR   BioGRID-ORCS; 101809; 1 hit in 78 CRISPR screens.
DR   PRO; PR:Q6P6N5; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q6P6N5; Protein.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR   GO; GO:0019901; F:protein kinase binding; IBA:GO_Central.
DR   GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; IDA:UniProtKB.
DR   GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR   GO; GO:1902747; P:negative regulation of lens fiber cell differentiation; IDA:UniProtKB.
DR   GO; GO:0043409; P:negative regulation of MAPK cascade; IMP:MGI.
DR   GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
DR   CDD; cd10574; EVH1_SPRED-like; 1.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR   InterPro; IPR023337; KBD.
DR   InterPro; IPR011993; PH-like_dom_sf.
DR   InterPro; IPR041937; SPRE_EVH1.
DR   InterPro; IPR007875; Sprouty.
DR   InterPro; IPR000697; WH1/EVH1_dom.
DR   PANTHER; PTHR11202:SF19; SPROUTY-RELATED, EVH1 DOMAIN-CONTAINING PROTEIN 3; 1.
DR   PANTHER; PTHR11202; SPROUTY-RELATED, EVH1 DOMAIN-CONTAINING PROTEIN FAMILY MEMBER; 1.
DR   Pfam; PF05210; Sprouty; 1.
DR   Pfam; PF00568; WH1; 1.
DR   SMART; SM00461; WH1; 1.
DR   SUPFAM; SSF50729; PH domain-like; 1.
DR   PROSITE; PS51488; KBD; 1.
DR   PROSITE; PS51227; SPR; 1.
DR   PROSITE; PS50229; WH1; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Lipoprotein; Membrane; Methylation; Palmitate;
KW   Phosphoprotein; Reference proteome; Ubl conjugation.
FT   CHAIN           1..408
FT                   /note="Sprouty-related, EVH1 domain-containing protein 3"
FT                   /id="PRO_0000076914"
FT   DOMAIN          1..113
FT                   /note="WH1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00410"
FT   DOMAIN          192..242
FT                   /note="KBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00821"
FT   DOMAIN          294..405
FT                   /note="SPR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00572"
FT   REGION          118..226
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          256..286
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        118..162
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        258..283
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         238
FT                   /note="Asymmetric dimethylarginine"
FT                   /evidence="ECO:0007744|PubMed:24129315"
FT   MOD_RES         246
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0007744|PubMed:24129315"
FT   CONFLICT        177
FT                   /note="R -> P (in Ref. 1; BAC80222)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   408 AA;  42794 MW;  2EFCD3BAF01325B6 CRC64;
     MVRVRAVVMA RDDSSGGWLP VGGGGLSQVS VCRVRGARPE GGARQGHYVI HGERLRDQKT
     TLECTLRPGL VYNKVNPIFH HWSLGDCKFG LTFQSPAEAD EFQKSLLAAL AALSRGSLTP
     SSSSSSSSPS QDTAETPCPL TSHVDSDSSS SHSRQETPPT APIATVESAA AFPLATRPQR
     RRSSAQSYPP LLPFTGIPEP SESLAGAGSQ GWGSRGYEDY RRSGPPPPPL ALSTCVVRFA
     KTGALRGAAL GPPVSLPAPL TEAAPPAPPA RPPPGPGPTP APAKASPEAE EAARCVHCRA
     LFRRRADGRG GRCAEAPDPG RLLVRRLSCL WCAESLLYHC LSDAEGDFSD PCACEPGHPR
     PAARWAALAA LSLAVPCLCC YAPLRACHWV AARCGCAGCG GRHEEAAR
//