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SPRY3_MOUSE
ID   SPRY3_MOUSE             Reviewed;         288 AA.
AC   Q3UUD2;
DT   10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT   11-OCT-2005, sequence version 1.
DT   03-AUG-2022, entry version 119.
DE   RecName: Full=Protein sprouty homolog 3 {ECO:0000305};
DE            Short=Spry-3 {ECO:0000305};
DE   AltName: Full=Sprouty RTK signaling antagonist 3 {ECO:0000312|MGI:MGI:1345188};
DE   AltName: Full=Sprouty3 {ECO:0000250|UniProtKB:O43610};
GN   Name=Spry3 {ECO:0000312|MGI:MGI:1345188};
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 {ECO:0000312|EMBL:BAE23695.1};
RN   [1] {ECO:0000312|EMBL:BAE23695.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE23695.1};
RC   TISSUE=Spinal cord {ECO:0000312|EMBL:BAE23695.1};
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   [2] {ECO:0000312|EMBL:AAI32136.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain {ECO:0000312|EMBL:AAI32136.1};
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   [3] {ECO:0000305}
RP   FUNCTION, INTERACTION WITH CAV1, AND MUTAGENESIS OF ARG-221.
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   [4] {ECO:0000305}
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=26089202; DOI=10.1093/hmg/ddv231;
RA   Ning Z., McLellan A.S., Ball M., Wynne F., O'Neill C., Mills W.,
RA   Quinn J.P., Kleinjan D.A., Anney R.J., Carmody R.J., O'Keeffe G., Moore T.;
RT   "Regulation of SPRY3 by X chromosome and PAR2-linked promoters in an autism
RT   susceptibility region.";
RL   Hum. Mol. Genet. 24:5126-5141(2015).
CC   -!- FUNCTION: Inhibits neurite branching, arbor length and neurite
CC       complexity (PubMed:26089202). Inhibits EGF-mediated p42/44 ERK
CC       signaling (PubMed:16877379). Negatively regulates the MAPK cascade,
CC       resulting in a reduction of extracellular matrix protein accumulation
CC       (By similarity). May function as an antagonist of fibroblast growth
CC       factor (FGF) pathways and may negatively modulate respiratory
CC       organogenesis (By similarity). {ECO:0000250|UniProtKB:O43610,
CC       ECO:0000269|PubMed:16877379, ECO:0000269|PubMed:26089202}.
CC   -!- SUBUNIT: Interacts with TESK1 (By similarity). Interacts with USP11 (By
CC       similarity). Interacts with CAV1 (via C-terminus) (PubMed:16877379).
CC       {ECO:0000250|UniProtKB:O43610, ECO:0000269|PubMed:16877379}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O43610}.
CC   -!- TISSUE SPECIFICITY: Expressed in the brain with expression the highest
CC       in Purkinje cell bodies and projections in the cerebellum (at protein
CC       level) (PubMed:26089202). Also expressed in central and peripheral
CC       nervous system ganglion cells, superior cervical ganglion and dorsal
CC       root ganglion (at protein level) (PubMed:26089202). Expressed in the
CC       retinal ganglion cell layer and the inner nuclear layer (at protein
CC       level) (PubMed:26089202). {ECO:0000269|PubMed:26089202}.
CC   -!- INDUCTION: By FGF signaling. {ECO:0000250|UniProtKB:O43610}.
CC   -!- SIMILARITY: Belongs to the sprouty family. {ECO:0000305}.
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DR   EMBL; BC132135; AAI32136.1; -; mRNA.
DR   EMBL; BC132137; AAI32138.1; -; mRNA.
DR   EMBL; AK138539; BAE23695.1; -; mRNA.
DR   RefSeq; NP_001025464.1; NM_001030293.2.
DR   AlphaFoldDB; Q3UUD2; -.
DR   PhosphoSitePlus; Q3UUD2; -.
DR   MaxQB; Q3UUD2; -.
DR   DNASU; 236576; -.
DR   GeneID; 236576; -.
DR   KEGG; mmu:236576; -.
DR   UCSC; uc009uyn.1; mouse.
DR   CTD; 10251; -.
DR   MGI; MGI:1345188; Spry3.
DR   VEuPathDB; HostDB:ENSMUSG00000061654; -.
DR   HOGENOM; CLU_077696_1_0_1; -.
DR   OrthoDB; 1157681at2759; -.
DR   PhylomeDB; Q3UUD2; -.
DR   BioGRID-ORCS; 236576; 0 hits in 13 CRISPR screens.
DR   Proteomes; UP000000589; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:InterPro.
DR   GO; GO:0061564; P:axon development; IEA:InterPro.
DR   GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR   GO; GO:0043409; P:negative regulation of MAPK cascade; ISS:UniProtKB.
DR   GO; GO:0150013; P:negative regulation of neuron projection arborization; IMP:UniProtKB.
DR   InterPro; IPR007875; Sprouty.
DR   InterPro; IPR030786; SPRY3.
DR   PANTHER; PTHR12365:SF9; PTHR12365:SF9; 1.
DR   Pfam; PF05210; Sprouty; 1.
DR   PROSITE; PS51227; SPR; 1.
PE   1: Evidence at protein level;
KW   Cytoplasm; Neurogenesis; Reference proteome.
FT   CHAIN           1..288
FT                   /note="Protein sprouty homolog 3"
FT                   /id="PRO_0000452086"
FT   DOMAIN          154..267
FT                   /note="SPR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00572"
FT   MUTAGEN         221
FT                   /note="R->D: Abolishes inhibition of EGF-mediated p42/44
FT                   ERK signaling."
FT                   /evidence="ECO:0000269|PubMed:16877379"
SQ   SEQUENCE   288 AA;  31363 MW;  19A3F311D5F8351E CRC64;
     MDATVIDELQ QILPIEQLRS THASNDYVER PPAPCKQALS SPSLIVQTHK SDWSLATMPT
     ALPRSISQCH QLQPLPQHLS QSSISSSMSQ STTASDQRLL ASITPSPSGQ SIIRTQPGAG
     AHPKVDGALK GEAEQSVGHS SDHLFICEEC GRCKCVPCTA VRPLPSCWMC NQRCLCSAES
     LLDYGTCLCC VKGLFYHCST DDEDNCADEP CSCGPSSCFI RWAAMSLISL FLPCLCCYLP
     TRGCLHMCQQ GYDSLRRPGC RCKRHTNTVC RKISSSSSPF PKAQEKSV
 
 
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