SPY4_MOUSE
ID SPY4_MOUSE Reviewed; 300 AA.
AC Q9WTP2; Q543R1; Q9QXV7;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Protein sprouty homolog 4;
DE Short=Spry-4;
GN Name=Spry4;
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], AND DEVELOPMENTAL STAGE.
RX PubMed=10330503; DOI=10.1016/s0925-4773(98)00241-x;
RA de Maximy A.A., Nakatake Y., Moncada S., Itoh N., Thiery J.P., Bellusci S.;
RT "Cloning and expression pattern of a mouse homologue of Drosophila sprouty
RT in the mouse embryo.";
RL Mech. Dev. 81:213-216(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10498682; DOI=10.1242/dev.126.20.4465;
RA Minowada G., Jarvis L.A., Chi C.L., Neubueser A., Sun X., Hacohen N.,
RA Krasnow M.A., Martin G.R.;
RT "Vertebrate sprouty genes are induced by FGF signaling and can cause
RT chondrodysplasia when overexpressed.";
RL Development 126:4465-4475(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head, and Skin;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
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 [6]
RP INTERACTION WITH CAV1.
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 [7]
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).
CC -!- FUNCTION: Suppresses the insulin receptor and EGFR-transduced MAPK
CC signaling pathway, but does not inhibit MAPK activation by a
CC constitutively active mutant Ras. Probably impairs the formation of
CC GTP-Ras (By similarity). Inhibits Ras-independent, but not Ras-
CC dependent, activation of RAF1 (By similarity). Represses integrin-
CC mediated cell spreading via inhibition of TESK1-mediated
CC phosphorylation of cofilin (By similarity).
CC {ECO:0000250|UniProtKB:Q9C004}.
CC -!- SUBUNIT: Interacts (via C-terminus) with TESK1 (via both C- and N-
CC termini); the interaction inhibits TESK1 kinase activity
CC (PubMed:17974561). Interacts with RAF1 (By similarity). Interacts with
CC CAV1 (via C-terminus) (PubMed:16877379). {ECO:0000250|UniProtKB:Q9C004,
CC ECO:0000269|PubMed:16877379, ECO:0000269|PubMed:17974561}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9C004}. Cell
CC projection, ruffle membrane {ECO:0000305}; Peripheral membrane protein
CC {ECO:0000305}. Note=Found in the cytoplasm in unstimulated cells but is
CC translocated to the membrane ruffles in cells stimulated with EGF
CC (epidermal growth factor). Colocalizes with TESK1 in vesicular spots in
CC the cytoplasm (By similarity). {ECO:0000250|UniProtKB:Q9C004}.
CC -!- TISSUE SPECIFICITY: Expressed in the embryo and adult tissues including
CC heart, brain, lung, kidney, and skeletal muscle.
CC -!- DEVELOPMENTAL STAGE: At 8 dpc expressed in the lateral plate mesoderm
CC of the primitive streak. At 9.5 and 10.5 dpc expressed in the nasal
CC placodes, maxillary and mandibular processes, posterior part of the
CC hyoid arch and the progress zone of the limb buds and the presomitic
CC mesoderm. At 11.5 dpc expressed in the dorso-lateral region of the
CC somites (mostly in the myotome) and in the otic vesicle. At 11.5 and
CC 12.5 dpc expressed in the distal lung mesenchyme, with a strong
CC expression in the accessory lobe of the lung.
CC {ECO:0000269|PubMed:10330503}.
CC -!- INDUCTION: By FGF signaling.
CC -!- DOMAIN: The Cys-rich domain is responsible for the localization of the
CC protein to the membrane ruffles.
CC -!- SIMILARITY: Belongs to the sprouty family. {ECO:0000305}.
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DR EMBL; AB019280; BAA77689.1; -; mRNA.
DR EMBL; AF176906; AAD56007.1; -; mRNA.
DR EMBL; AK037180; BAC29739.1; -; mRNA.
DR EMBL; AK048122; BAC33249.1; -; mRNA.
DR EMBL; CH466528; EDL10072.1; -; Genomic_DNA.
DR EMBL; BC050944; AAH50944.1; -; mRNA.
DR EMBL; BC057005; AAH57005.1; -; mRNA.
DR CCDS; CCDS29202.1; -.
DR RefSeq; NP_036028.2; NM_011898.2.
DR AlphaFoldDB; Q9WTP2; -.
DR BioGRID; 204878; 7.
DR STRING; 10090.ENSMUSP00000025295; -.
DR iPTMnet; Q9WTP2; -.
DR PhosphoSitePlus; Q9WTP2; -.
DR SwissPalm; Q9WTP2; -.
DR MaxQB; Q9WTP2; -.
DR PaxDb; Q9WTP2; -.
DR PeptideAtlas; Q9WTP2; -.
DR PRIDE; Q9WTP2; -.
DR ProteomicsDB; 261646; -.
DR Antibodypedia; 3761; 297 antibodies from 32 providers.
DR DNASU; 24066; -.
DR Ensembl; ENSMUST00000025295; ENSMUSP00000025295; ENSMUSG00000024427.
DR GeneID; 24066; -.
DR KEGG; mmu:24066; -.
DR UCSC; uc008esl.1; mouse.
DR CTD; 81848; -.
DR MGI; MGI:1345144; Spry4.
DR VEuPathDB; HostDB:ENSMUSG00000024427; -.
DR eggNOG; ENOG502QQ4V; Eukaryota.
DR GeneTree; ENSGT00950000183055; -.
DR HOGENOM; CLU_077696_0_0_1; -.
DR InParanoid; Q9WTP2; -.
DR OMA; MCLVQGV; -.
DR OrthoDB; 1157681at2759; -.
DR PhylomeDB; Q9WTP2; -.
DR TreeFam; TF325070; -.
DR BioGRID-ORCS; 24066; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Spry4; mouse.
DR PRO; PR:Q9WTP2; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q9WTP2; protein.
DR Bgee; ENSMUSG00000024427; Expressed in secondary oocyte and 237 other tissues.
DR Genevisible; Q9WTP2; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004860; F:protein kinase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0048513; P:animal organ development; IBA:GO_Central.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IEA:InterPro.
DR GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IDA:MGI.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; IBA:GO_Central.
DR GO; GO:1900025; P:negative regulation of substrate adhesion-dependent cell spreading; ISS:UniProtKB.
DR InterPro; IPR007875; Sprouty.
DR InterPro; IPR030790; SPRY4.
DR PANTHER; PTHR12365:SF6; PTHR12365:SF6; 1.
DR Pfam; PF05210; Sprouty; 1.
DR PROSITE; PS51227; SPR; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cell membrane; Cell projection; Cytoplasm;
KW Developmental protein; Membrane; Phosphoprotein; Reference proteome.
FT CHAIN 1..300
FT /note="Protein sprouty homolog 4"
FT /id="PRO_0000076906"
FT DOMAIN 167..274
FT /note="SPR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00572"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 52..114
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 91..112
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q9C004"
FT MOD_RES 126
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9C004"
FT CONFLICT 10
FT /note="V -> F (in Ref. 2; AAD56007)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 300 AA; 32523 MW; DA963036EFC0E73F CRC64;
MEPPVPQSSV PVNPSSVMVQ PLLDSRAPHS RLQHPLTILP IDQMKTSHVE NDYIDNPSLA
PATGPKRPRG GPPELAPTPA RCDQDITHHW ISFSGRPSSV SSSSSTSSDQ RLLDHMAPPP
VAEQASPRAV RLQPKVVHCK PLDLKGPTAP PELDKHFLLC EACGKCKCKE CASPRTLPSC
WVCNQECLCS AQTLVNYGTC MCLVQGIFYH CTNEDDEGSC ADHPCSCSGS NCCARWSFMG
ALSVVLPCLL CYLPATGCVK LAQRGYDRLR RPGCRCKHTN SVICKAASGD TKTSRSDKPF
