SPRE2_RAT
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 03-AUG-2022, entry version 110.
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 (By similarity). Inhibits fibroblast growth
CC factor (FGF)-induced retinal lens fiber differentiation, probably by
CC inhibiting FGF-mediated phosphorylation of ERK1/2 (By similarity).
CC Inhibits TGFB-induced epithelial-to-mesenchymal transition in lens
CC epithelial cells (By similarity). {ECO:0000250|UniProtKB:Q7Z698,
CC 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). {ECO:0000250|UniProtKB:Q7Z698,
CC ECO:0000250|UniProtKB:Q924S7, 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.ENSRNOP00000006573; -.
DR iPTMnet; Q3C2P8; -.
DR PhosphoSitePlus; Q3C2P8; -.
DR SwissPalm; Q3C2P8; -.
DR PaxDb; Q3C2P8; -.
DR Ensembl; ENSRNOT00000079874; ENSRNOP00000071793; ENSRNOG00000004888.
DR GeneID; 305539; -.
DR KEGG; rno:305539; -.
DR UCSC; RGD:1309304; rat.
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 OrthoDB; 759156at2759; -.
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 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; -; 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 Pfam; PF05210; Sprouty; 1.
DR Pfam; PF00568; WH1; 1.
DR SMART; SM00461; WH1; 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
