ID   SPRE2_RAT               Reviewed;         410 AA.
AC   Q3C2P8;
DT   25-NOV-2008, integrated into UniProtKB/Swiss-Prot.
DT   22-NOV-2005, sequence version 1.
DT   24-JAN-2024, entry version 116.
DE   RecName: Full=Sprouty-related, EVH1 domain-containing protein 2;
DE            Short=Spred-2;
GN   Name=Spred2;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Saitoh A., Hirasawa N., Ohuchi K.;
RT   "Identification of cDNA encoding rat Spred-2.";
RL   Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   INTERACTION WITH TESK1.
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   [3]
RP   TISSUE SPECIFICITY.
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).
CC   -!- FUNCTION: Negatively regulates Ras signaling pathways and downstream
CC       activation of MAP kinases. Recruits and translocates NF1 to the cell
CC       membrane, thereby enabling NF1-dependent hydrolysis of active GTP-bound
CC       Ras to inactive GDP-bound Ras (By similarity). Inhibits fibroblast
CC       growth factor (FGF)-induced retinal lens fiber differentiation,
CC       probably by inhibiting FGF-mediated phosphorylation of ERK1/2 (By
CC       similarity). Inhibits TGFB-induced epithelial-to-mesenchymal transition
CC       in lens epithelial cells (By similarity).
CC       {ECO:0000250|UniProtKB:Q7Z698, ECO:0000250|UniProtKB:Q924S7}.
CC   -!- SUBUNIT: Homodimer and heterodimer (By similarity). Able to interact
CC       with SPRED1 to form heterodimers (By similarity). Interacts with RAS
CC       (By similarity). May interact with ZDHHC13 (via ANK repeats) and
CC       ZDHHC17 (via ANK repeats) (By similarity). Interacts with TESK1
CC       (PubMed:17974561). Interacts with NF1 (By similarity).
CC       {ECO:0000250|UniProtKB:Q7Z698, ECO:0000250|UniProtKB:Q924S7,
CC       ECO:0000269|PubMed:17974561}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q924S7};
CC       Peripheral membrane protein {ECO:0000250|UniProtKB:Q924S7}; Cytoplasmic
CC       side {ECO:0000250|UniProtKB:Q924S7}. Cytoplasmic vesicle, secretory
CC       vesicle membrane {ECO:0000250|UniProtKB:Q7Z698}; Peripheral membrane
CC       protein {ECO:0000250|UniProtKB:Q7Z698}; Cytoplasmic side
CC       {ECO:0000250|UniProtKB:Q7Z698}. Cytoplasm
CC       {ECO:0000250|UniProtKB:Q7Z698}. Note=Detected in the cytoplasm of the
CC       stratum spinosum cells, where it is associated with cytoplasmic
CC       vesicles that are supposed to be secretory granules.
CC       {ECO:0000250|UniProtKB:Q7Z698}.
CC   -!- TISSUE SPECIFICITY: Expressed in the eye, with higher expression in
CC       lens epithelium than in lens fiber cells at postnatal day 15.
CC       {ECO:0000269|PubMed:25576668}.
CC   -!- PTM: Phosphorylated on serine and threonine residues. Phosphorylated on
CC       tyrosine. Phosphorylation of Tyr-224 and Tyr-227 are required for
CC       ubiquitination. {ECO:0000250|UniProtKB:Q7Z698}.
CC   -!- PTM: Ubiquitinated; leading to degradation by the proteasome.
CC       {ECO:0000250|UniProtKB:Q7Z698}.
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DR   EMBL; AB125136; BAE46587.1; -; mRNA.
DR   RefSeq; NP_001040559.1; NM_001047094.1.
DR   AlphaFoldDB; Q3C2P8; -.
DR   BMRB; Q3C2P8; -.
DR   SMR; Q3C2P8; -.
DR   STRING; 10116.ENSRNOP00000071793; -.
DR   iPTMnet; Q3C2P8; -.
DR   PhosphoSitePlus; Q3C2P8; -.
DR   SwissPalm; Q3C2P8; -.
DR   PaxDb; 10116-ENSRNOP00000006573; -.
DR   Ensembl; ENSRNOT00000079874.2; ENSRNOP00000071793.2; ENSRNOG00000004888.8.
DR   Ensembl; ENSRNOT00055012847; ENSRNOP00055010239; ENSRNOG00055007678.
DR   Ensembl; ENSRNOT00060024913; ENSRNOP00060019846; ENSRNOG00060014566.
DR   Ensembl; ENSRNOT00065009168; ENSRNOP00065006557; ENSRNOG00065006055.
DR   GeneID; 305539; -.
DR   KEGG; rno:305539; -.
DR   UCSC; RGD:1309304; rat.
DR   AGR; RGD:1309304; -.
DR   CTD; 200734; -.
DR   RGD; 1309304; Spred2.
DR   eggNOG; KOG4590; Eukaryota.
DR   GeneTree; ENSGT00940000156841; -.
DR   HOGENOM; CLU_038867_1_1_1; -.
DR   InParanoid; Q3C2P8; -.
DR   OMA; CEYAPDT; -.
DR   OrthoDB; 3031266at2759; -.
DR   Reactome; R-RNO-5658442; Regulation of RAS by GAPs.
DR   Reactome; R-RNO-5658623; FGFRL1 modulation of FGFR1 signaling.
DR   PRO; PR:Q3C2P8; -.
DR   Proteomes; UP000002494; Chromosome 14.
DR   Bgee; ENSRNOG00000004888; Expressed in frontal cortex and 18 other cell types or tissues.
DR   ExpressionAtlas; Q3C2P8; baseline and differential.
DR   GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR   GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR   GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR   GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; ISO:RGD.
DR   GO; GO:0005173; F:stem cell factor receptor binding; ISO:RGD.
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; ISS:UniProtKB.
DR   GO; GO:1902747; P:negative regulation of lens fiber cell differentiation; ISS:UniProtKB.
DR   GO; GO:0043409; P:negative regulation of MAPK cascade; ISO:RGD.
DR   GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; ISO:RGD.
DR   GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:0043517; P:positive regulation of DNA damage response, signal transduction by p53 class mediator; ISO:RGD.
DR   GO; GO:0090311; P:regulation of protein deacetylation; ISO:RGD.
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:SF11; SPROUTY-RELATED, EVH1 DOMAIN-CONTAINING PROTEIN 2; 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; Cytoplasm; Cytoplasmic vesicle; Membrane; Phosphoprotein;
KW   Reference proteome; Ubl conjugation.
FT   CHAIN           1..410
FT                   /note="Sprouty-related, EVH1 domain-containing protein 2"
FT                   /id="PRO_0000354679"
FT   DOMAIN          5..122
FT                   /note="WH1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00410"
FT   DOMAIN          197..252
FT                   /note="KBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00821"
FT   DOMAIN          300..408
FT                   /note="SPR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00572"
FT   REGION          127..171
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          274..294
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        145..171
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         224
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q7Z698"
FT   MOD_RES         227
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q7Z698"
SQ   SEQUENCE   410 AA;  46805 MW;  18F2F3FBB616BCBB CRC64;
     MTEETHPDDD SYIVRVKAVV MTRDDSSGGW FPQEGGGISR VGVCKVMHPE GNGRSGFLIH
     GERQKDKLVV LECYVRKDLV YTKANPTFHH WKVDNRKFGL TFQSPADARA FDRGVRKAIE
     DLIEGSTTSS STIHNEAELG DDDVFTTATD SSSNSSQKRE PNTRTISSPT SCEHRRIYTL
     DPYPMDLYHP DQRLPRSYPQ VTFPEDDEEI VRINPREKIW MTGYEDYRHA PVRGKYLDST
     EDADSYVRFA KGEVPKHEYT YPYVDSSDFG FGEDPKGNVI KTQPPRAKSR RRKENGERSR
     CVYCRDMFNH EENRRGHCQD APDAVRTCIR RVSCMWCADS MLYHCMSDPE GDYTDPCSCD
     TSDEKFCLRW MALIALSFLA PCMCCYLPLR ACHHCGVMCR CCGGKHKAAA
//