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   27-MAR-2024, entry version 146.
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; 10090-ENSMUSP00000025295; -.
DR   PeptideAtlas; Q9WTP2; -.
DR   ProteomicsDB; 261646; -.
DR   Antibodypedia; 3761; 322 antibodies from 32 providers.
DR   DNASU; 24066; -.
DR   Ensembl; ENSMUST00000025295.8; ENSMUSP00000025295.7; ENSMUSG00000024427.8.
DR   GeneID; 24066; -.
DR   KEGG; mmu:24066; -.
DR   UCSC; uc008esl.1; mouse.
DR   AGR; MGI:1345144; -.
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; 4219076at2759; -.
DR   PhylomeDB; Q9WTP2; -.
DR   TreeFam; TF325070; -.
DR   BioGRID-ORCS; 24066; 2 hits in 80 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 240 other cell types or tissues.
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:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; IBA:GO_Central.
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   PANTHER; PTHR12365:SF6; PROTEIN SPROUTY HOMOLOG 4; 1.
DR   PANTHER; PTHR12365; SPROUTY; 1.
DR   Pfam; PF05210; Sprouty; 1.
DR   PROSITE; PS51227; SPR; 1.
DR   Genevisible; Q9WTP2; MM.
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
//