SPRE1_MOUSE
ID SPRE1_MOUSE Reviewed; 444 AA.
AC Q924S8; Q3U2W6; Q6PET8;
DT 04-JAN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Sprouty-related, EVH1 domain-containing protein 1;
DE Short=Spred-1;
GN Name=Spred1;
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] (ISOFORM 1), SUBCELLULAR LOCATION, INTERACTION
RP WITH RAS, PHOSPHORYLATION, TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=11493923; DOI=10.1038/35088082;
RA Wakioka T., Sasaki A., Kato R., Shouda T., Matsumoto A., Miyoshi K.,
RA Tsuneoka M., Komiya S., Baron R., Yoshimura A.;
RT "Spred is a Sprouty-related suppressor of Ras signalling.";
RL Nature 412:647-651(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=NOD;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Brain, and Mammary gland;
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 [5]
RP TISSUE 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 [6]
RP TISSUE SPECIFICITY.
RX PubMed=15580519; DOI=10.1007/s00418-004-0725-6;
RA Engelhardt C.M., Bundschu K., Messerschmitt M., Renne T., Walter U.,
RA Reinhard M., Schuh K.;
RT "Expression and subcellular localization of Spred proteins in mouse and
RT human tissues.";
RL Histochem. Cell Biol. 122:527-538(2004).
RN [7]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15465815; DOI=10.1074/jbc.m405189200;
RA Nonami A., Kato R., Taniguchi K., Yoshiga D., Taketomi T., Fukuyama S.,
RA Harada M., Sasaki A., Yoshimura A.;
RT "Spred-1 negatively regulates interleukin-3-mediated ERK/mitogen-activated
RT protein (MAP) kinase activation in hematopoietic cells.";
RL J. Biol. Chem. 279:52543-52551(2004).
RN [8]
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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Lung, and Spleen;
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 [11]
RP INTERACTION WITH ZDHHC17, 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 [12]
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 [13]
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:11493923). Negatively
CC regulates hematopoiesis of bone marrow (PubMed:15465815). Inhibits
CC fibroblast growth factor (FGF)-induced retinal lens fiber
CC differentiation, probably by inhibiting FGF-mediated phosphorylation of
CC ERK1/2 (PubMed:29501879). Attenuates actin stress fiber formation via
CC inhibition of TESK1-mediated phosphorylation of cofilin (By
CC similarity). Inhibits TGFB-induced epithelial-to-mesenchymal transition
CC in lens epithelial cells (PubMed:25576668).
CC {ECO:0000250|UniProtKB:Q7Z699, ECO:0000269|PubMed:11493923,
CC ECO:0000269|PubMed:15465815, ECO:0000269|PubMed:25576668,
CC ECO:0000269|PubMed:29501879}.
CC -!- SUBUNIT: Homodimer and heterodimer (By similarity). Able to interact
CC with SPRED2 to form heterodimers (By similarity). Interacts (via C-
CC terminus) with TAOK1/MARKK (via C-terminus); the interaction does not
CC affect TAOK1 kinase activity (By similarity). Interacts (via C-
CC terminus) with TESK1 (via C-terminus); the interaction inhibits TESK1
CC kinase activity (PubMed:17974561). Interacts with CAV1 (By similarity).
CC Interacts with RAS (PubMed:11493923). Interacts with
CC palmitoyltransferase ZDHHC17/HIP14; the interaction leads to
CC palmitoylation of SPRED1 (PubMed:24705354).
CC {ECO:0000250|UniProtKB:Q7Z699, ECO:0000269|PubMed:11493923,
CC ECO:0000269|PubMed:17974561, ECO:0000269|PubMed:24705354}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11493923};
CC Peripheral membrane protein {ECO:0000269|PubMed:11493923}. Membrane,
CC caveola {ECO:0000269|PubMed:11493923}; Peripheral membrane protein
CC {ECO:0000269|PubMed:11493923}. Nucleus {ECO:0000269|PubMed:11493923}.
CC Note=Localized in cholesterol-rich membrane raft/caveola fractions.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q924S8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q924S8-2; Sequence=VSP_012412, VSP_012413;
CC -!- TISSUE SPECIFICITY: Expressed in brain. Weakly expressed in lung,
CC heart, liver, kidney, intestine, spleen, testis, thymus, colon and
CC ovary. Also expressed in embryonic tissues such as heart, lung, liver
CC and brain. Highly expressed in IL3-dependent hematopoietic cell lines
CC (Ba/F3 and MC/9) and bone marrow-derived mast cells (BMMC).
CC {ECO:0000269|PubMed:11493923, ECO:0000269|PubMed:12646235,
CC ECO:0000269|PubMed:15465815, ECO:0000269|PubMed:15580519}.
CC -!- PTM: Palmitoylated by ZDHHC17/HIP14. {ECO:0000269|PubMed:24705354}.
CC -!- PTM: Ubiquitinated. {ECO:0000250|UniProtKB:Q7Z699}.
CC -!- PTM: Phosphorylated on tyrosine. {ECO:0000269|PubMed:11493923}.
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DR EMBL; AB063495; BAB62848.1; -; mRNA.
DR EMBL; AK155065; BAE33024.1; -; mRNA.
DR EMBL; AL807741; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL928959; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC057874; AAH57874.1; -; mRNA.
DR EMBL; BC079606; AAH79606.1; -; mRNA.
DR CCDS; CCDS16570.1; -. [Q924S8-1]
DR CCDS; CCDS71115.1; -. [Q924S8-2]
DR RefSeq; NP_001264185.1; NM_001277256.1. [Q924S8-2]
DR RefSeq; NP_277059.1; NM_033524.3. [Q924S8-1]
DR AlphaFoldDB; Q924S8; -.
DR SMR; Q924S8; -.
DR IntAct; Q924S8; 3.
DR MINT; Q924S8; -.
DR STRING; 10090.ENSMUSP00000028829; -.
DR iPTMnet; Q924S8; -.
DR PhosphoSitePlus; Q924S8; -.
DR SwissPalm; Q924S8; -.
DR EPD; Q924S8; -.
DR MaxQB; Q924S8; -.
DR PaxDb; Q924S8; -.
DR PeptideAtlas; Q924S8; -.
DR PRIDE; Q924S8; -.
DR ProteomicsDB; 263325; -. [Q924S8-1]
DR ProteomicsDB; 263326; -. [Q924S8-2]
DR Antibodypedia; 22853; 384 antibodies from 32 providers.
DR DNASU; 114715; -.
DR Ensembl; ENSMUST00000028829; ENSMUSP00000028829; ENSMUSG00000027351. [Q924S8-1]
DR Ensembl; ENSMUST00000110901; ENSMUSP00000106526; ENSMUSG00000027351. [Q924S8-2]
DR GeneID; 114715; -.
DR KEGG; mmu:114715; -.
DR UCSC; uc008lrh.2; mouse. [Q924S8-2]
DR UCSC; uc008lri.2; mouse. [Q924S8-1]
DR CTD; 161742; -.
DR MGI; MGI:2150016; Spred1.
DR VEuPathDB; HostDB:ENSMUSG00000027351; -.
DR eggNOG; KOG4590; Eukaryota.
DR GeneTree; ENSGT00940000159180; -.
DR HOGENOM; CLU_038867_1_1_1; -.
DR InParanoid; Q924S8; -.
DR OMA; NNDNSYA; -.
DR OrthoDB; 759156at2759; -.
DR PhylomeDB; Q924S8; -.
DR TreeFam; TF321411; -.
DR Reactome; R-MMU-5658442; Regulation of RAS by GAPs.
DR Reactome; R-MMU-5658623; FGFRL1 modulation of FGFR1 signaling.
DR BioGRID-ORCS; 114715; 3 hits in 76 CRISPR screens.
DR ChiTaRS; Spred1; mouse.
DR PRO; PR:Q924S8; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q924S8; protein.
DR Bgee; ENSMUSG00000027351; Expressed in condyle and 246 other tissues.
DR Genevisible; Q924S8; MM.
DR GO; GO:0005901; C:caveola; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0019902; F:phosphatase binding; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL.
DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; IDA:BHF-UCL.
DR GO; GO:0005173; F:stem cell factor receptor binding; IPI:MGI.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:BHF-UCL.
DR GO; GO:0090051; P:negative regulation of cell migration involved in sprouting angiogenesis; IDA:BHF-UCL.
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:0010801; P:negative regulation of peptidyl-threonine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; ISO:MGI.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0043517; P:positive regulation of DNA damage response, signal transduction by p53 class mediator; IDA:BHF-UCL.
DR GO; GO:0090311; P:regulation of protein deacetylation; IDA:BHF-UCL.
DR GO; GO:0060979; P:vasculogenesis involved in coronary vascular morphogenesis; ISO:MGI.
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 Acetylation; Alternative splicing; Cell membrane; Lipoprotein; Membrane;
KW Methylation; Nucleus; Palmitate; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q7Z699"
FT CHAIN 2..444
FT /note="Sprouty-related, EVH1 domain-containing protein 1"
FT /id="PRO_0000076908"
FT DOMAIN 6..123
FT /note="WH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00410"
FT DOMAIN 234..286
FT /note="KBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00821"
FT DOMAIN 334..442
FT /note="SPR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00572"
FT REGION 268..287
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 333..444
FT /note="Required for interaction with TESK1"
FT /evidence="ECO:0000269|PubMed:17974561"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z699"
FT MOD_RES 225
FT /note="N6-methyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z699"
FT MOD_RES 239
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 309
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z699"
FT VAR_SEQ 196..229
FT /note="IPFSQQGLDIQSRSMEYVQRQISKECGSLKSQTR -> VRRRILFPCIAYIE
FT KLGVLQNTKALRSFPCYETI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_012412"
FT VAR_SEQ 230..444
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_012413"
FT CONFLICT 144
FT /note="T -> I (in Ref. 2; AAH57874)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 444 AA; 50664 MW; B716DCB4AEA9F171 CRC64;
MSEETATSDN DNSYARVRAV VMTRDDSSGG WLPLGGSGLS SVTVFRVPHQ EENGCADFFI
RGERLRDKMV VLECMLKKDL IYNKVTPTFH HWKIDDKKFG LTFQSPADAR AFDRGIRRAI
EDISLGCPAS KTEAEGGDDD LQTTEEDTSR SLVKDHFFQQ ETVVTSEPYR SSDIRPLPFE
DLNARRVYLQ SQVSQIPFSQ QGLDIQSRSM EYVQRQISKE CGSLKSQTRV PLKSIRHVSF
QDEDEIVRIN PRDILIRRYA DYRHPDMWKN DLERDDTDSS VPFSKQDSKK SDYLYHCGDE
TKLSSLKDSV VFKTQPPSLK FKSKRRKEDG ERSRCVYCQE RFNHEENARG KCQDAPDPVK
RCIYQVSCML CAESMLYHCM SDSEGDFSDP CSCDTSDDKF CLRWLALVAL SFIVPCMCCY
VPLRMCHRCG EACGCCGGKH KAAG
