ID SPY3_HUMAN Reviewed; 288 AA. AC O43610; A8K0H8; DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot. DT 21-FEB-2001, sequence version 2. DT 24-JAN-2024, entry version 161. 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|HGNC:HGNC:11271}; DE AltName: Full=Sprouty3 {ECO:0000303|PubMed:30878395}; GN Name=SPRY3 {ECO:0000312|HGNC:HGNC:11271}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10655549; DOI=10.1093/hmg/9.3.395; RA Ciccodicola A., D'Esposito M., Esposito T., Gianfrancesco F., RA Migliaccio C., Miano M.G., Matarazzo M.R., Vacca M., Franze A., RA Cuccurese M., Cocchia M., Curci A., Terracciano A., Torino A., Cocchia S., RA Mercadante G., Pannone E., Archidiacono N., Rocchi M., Schlessinger D., RA D'Urso M.; RT "Differentially regulated and evolved genes in the fully sequenced Xq/Yq RT pseudoautosomal region."; RL Hum. Mol. Genet. 9:395-401(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Cerebellum; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 NUCLEOTIDE SEQUENCE [MRNA] OF 93-191, FUNCTION, AND INDUCTION BY FGF RP SIGNALING. RX PubMed=9458049; DOI=10.1016/s0092-8674(00)80919-8; RA Hacohen N., Kramer S., Sutherland D., Hiromi Y., Krasnow M.A.; RT "Sprouty encodes a novel antagonist of FGF signaling that patterns apical RT branching of the Drosophila airways."; RL Cell 92:253-263(1998). 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). RN [8] RP 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). RN [9] RP INTERACTION WITH USP11. RX PubMed=29293652; DOI=10.1371/journal.pone.0190513; RA Stockum A., Snijders A.P., Maertens G.N.; RT "USP11 deubiquitinates RAE1 and plays a key role in bipolar spindle RT formation."; RL PLoS ONE 13:e0190513-e0190513(2018). RN [10] RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION BY MICRORNA-143-3P. RX PubMed=30878395; DOI=10.1016/j.yjmcc.2019.03.005; RA Li C., Li J., Xue K., Zhang J., Wang C., Zhang Q., Chen X., Gao C., Yu X., RA Sun L.; RT "MicroRNA-143-3p promotes human cardiac fibrosis via targeting sprouty3 RT after myocardial infarction."; RL J. Mol. Cell. Cardiol. 129:281-292(2019). CC -!- FUNCTION: Inhibits neurite branching, arbor length and neurite CC complexity (By similarity). Inhibits EGF-mediated p42/44 ERK signaling CC (By similarity). Negatively regulates the MAPK cascade, resulting in a CC reduction of extracellular matrix protein accumulation CC (PubMed:30878395). May function as an antagonist of fibroblast growth CC factor (FGF) pathways and may negatively modulate respiratory CC organogenesis (PubMed:9458049). {ECO:0000250|UniProtKB:Q3UUD2, CC ECO:0000269|PubMed:30878395, ECO:0000269|PubMed:9458049}. CC -!- SUBUNIT: Interacts with TESK1 (PubMed:17974561). Interacts with USP11 CC (PubMed:29293652). Interacts with CAV1 (via C-terminus) (By CC similarity). {ECO:0000250|UniProtKB:Q3UUD2, CC ECO:0000269|PubMed:17974561, ECO:0000269|PubMed:29293652}. CC -!- INTERACTION: CC O43610; P29972: AQP1; NbExp=3; IntAct=EBI-12290641, EBI-745213; CC O43610; Q9BXY8: BEX2; NbExp=3; IntAct=EBI-12290641, EBI-745073; CC O43610; Q8NEC5: CATSPER1; NbExp=3; IntAct=EBI-12290641, EBI-744545; CC O43610; Q9H2X0: CHRD; NbExp=3; IntAct=EBI-12290641, EBI-947551; CC O43610; Q02930-3: CREB5; NbExp=3; IntAct=EBI-12290641, EBI-10192698; CC O43610; Q9Y223-2: GNE; NbExp=3; IntAct=EBI-12290641, EBI-11975289; CC O43610; Q9Y4H4: GPSM3; NbExp=3; IntAct=EBI-12290641, EBI-347538; CC O43610; P49639: HOXA1; NbExp=3; IntAct=EBI-12290641, EBI-740785; CC O43610; O43593: HR; NbExp=3; IntAct=EBI-12290641, EBI-2880706; CC O43610; Q5T749: KPRP; NbExp=3; IntAct=EBI-12290641, EBI-10981970; CC O43610; O76011: KRT34; NbExp=3; IntAct=EBI-12290641, EBI-1047093; CC O43610; Q5T7P2: LCE1A; NbExp=3; IntAct=EBI-12290641, EBI-11962058; CC O43610; Q5T7P3: LCE1B; NbExp=3; IntAct=EBI-12290641, EBI-10245913; CC O43610; Q5T754: LCE1F; NbExp=3; IntAct=EBI-12290641, EBI-11958008; CC O43610; O14633: LCE2B; NbExp=3; IntAct=EBI-12290641, EBI-11478468; CC O43610; Q5TA76: LCE3A; NbExp=3; IntAct=EBI-12290641, EBI-9394625; CC O43610; Q9BYE3: LCE3D; NbExp=3; IntAct=EBI-12290641, EBI-6658837; CC O43610; Q5T5B0: LCE3E; NbExp=3; IntAct=EBI-12290641, EBI-10245456; CC O43610; O60336: MAPKBP1; NbExp=3; IntAct=EBI-12290641, EBI-947402; CC O43610; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12290641, EBI-16439278; CC O43610; Q9HC98-4: NEK6; NbExp=3; IntAct=EBI-12290641, EBI-11750983; CC O43610; Q9Y2K5: R3HDM2; NbExp=3; IntAct=EBI-12290641, EBI-948428; CC O43610; Q92504: SLC39A7; NbExp=3; IntAct=EBI-12290641, EBI-1051105; CC O43610; P62760: VSNL1; NbExp=3; IntAct=EBI-12290641, EBI-740943; CC O43610; Q8IUH5: ZDHHC17; NbExp=3; IntAct=EBI-12290641, EBI-524753; CC O43610; Q96SQ5: ZNF587; NbExp=3; IntAct=EBI-12290641, EBI-6427977; CC O43610; Q8N720: ZNF655; NbExp=3; IntAct=EBI-12290641, EBI-625509; CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- TISSUE SPECIFICITY: Widely expressed; particularly in the fetal CC tissues. Expressed in the brain with expression the highest in Purkinje CC cells in the cerebellum (at protein level) (PubMed:26089202). Expressed CC in the myocardium of the heart (PubMed:30878395). CC {ECO:0000269|PubMed:26089202, ECO:0000269|PubMed:30878395}. CC -!- INDUCTION: By FGF signaling (PubMed:9458049). Repressed by microRNA- CC 143-3P, which results in activation of MAPK signaling and promotion of CC excess accumulation of extracellular matrix. May thereby play a role in CC myocardial fibrosis (PubMed:30878395). {ECO:0000269|PubMed:30878395, CC ECO:0000269|PubMed:9458049}. CC -!- MISCELLANEOUS: The gene coding for this protein is located in the CC pseudoautosomal region 2 (PAR2) of X and Y chromosomes. CC -!- SIMILARITY: Belongs to the sprouty family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC39567.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ271735; CAB96768.1; -; Genomic_DNA. DR EMBL; AK289543; BAF82232.1; -; mRNA. DR EMBL; CH471247; EAW55876.1; -; Genomic_DNA. DR EMBL; BC069609; AAH69609.1; -; mRNA. DR EMBL; BC074972; AAH74972.1; -; mRNA. DR EMBL; BC074973; AAH74973.1; -; mRNA. DR EMBL; AF041038; AAC39567.1; ALT_FRAME; mRNA. DR CCDS; CCDS14769.4; -. DR RefSeq; NP_001291919.1; NM_001304990.1. DR RefSeq; NP_005831.1; NM_005840.2. DR AlphaFoldDB; O43610; -. DR BioGRID; 115545; 29. DR IntAct; O43610; 27. DR STRING; 9606.ENSP00000302978; -. DR iPTMnet; O43610; -. DR PhosphoSitePlus; O43610; -. DR BioMuta; SPRY3; -. DR jPOST; O43610; -. DR MassIVE; O43610; -. DR MaxQB; O43610; -. DR PaxDb; 9606-ENSP00000302978; -. DR PeptideAtlas; O43610; -. DR ProteomicsDB; 49079; -. DR Antibodypedia; 31439; 118 antibodies from 21 providers. DR DNASU; 10251; -. DR Ensembl; ENST00000302805.7; ENSP00000302978.2; ENSG00000168939.13. DR Ensembl; ENST00000675360.1; ENSP00000502489.1; ENSG00000168939.13. DR Ensembl; ENST00000695325.1; ENSP00000511806.1; ENSG00000168939.13. DR GeneID; 10251; -. DR KEGG; hsa:10251; -. DR MANE-Select; ENST00000695325.1; ENSP00000511806.1; NM_001304990.2; NP_001291919.1. DR UCSC; uc004fnq.2; human. DR AGR; HGNC:11271; -. DR CTD; 10251; -. DR DisGeNET; 10251; -. DR GeneCards; SPRY3; -. DR HGNC; HGNC:11271; SPRY3. DR HPA; ENSG00000168939; Low tissue specificity. DR MIM; 300531; gene. DR neXtProt; NX_O43610; -. DR OpenTargets; ENSG00000168939; -. DR PharmGKB; PA36100; -. DR VEuPathDB; HostDB:ENSG00000168939; -. DR eggNOG; ENOG502R5TY; Eukaryota. DR GeneTree; ENSGT00950000183055; -. DR HOGENOM; CLU_077696_1_0_1; -. DR InParanoid; O43610; -. DR OMA; PHKQEWS; -. DR OrthoDB; 4219076at2759; -. DR PhylomeDB; O43610; -. DR TreeFam; TF325070; -. DR PathwayCommons; O43610; -. DR SignaLink; O43610; -. DR BioGRID-ORCS; 10251; 9 hits in 604 CRISPR screens. DR ChiTaRS; SPRY3; human. DR GeneWiki; SPRY3; -. DR GenomeRNAi; 10251; -. DR Pharos; O43610; Tbio. DR PRO; PR:O43610; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; O43610; Protein. DR Bgee; ENSG00000168939; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 98 other cell types or tissues. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0016020; C:membrane; IEA:InterPro. DR GO; GO:0048513; P:animal organ development; IBA:GO_Central. DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISS:UniProtKB. DR GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; IBA:GO_Central. DR GO; GO:0043409; P:negative regulation of MAPK cascade; IMP:UniProtKB. DR GO; GO:0150013; P:negative regulation of neuron projection arborization; ISS:UniProtKB. DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; IBA:GO_Central. DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW. DR InterPro; IPR007875; Sprouty. DR PANTHER; PTHR12365:SF9; PROTEIN SPROUTY HOMOLOG 3; 1. DR PANTHER; PTHR12365; SPROUTY; 1. DR Pfam; PF05210; Sprouty; 1. DR PROSITE; PS51227; SPR; 1. DR Genevisible; O43610; HS. PE 1: Evidence at protein level; KW Cytoplasm; Neurogenesis; Reference proteome. FT CHAIN 1..288 FT /note="Protein sprouty homolog 3" FT /id="PRO_0000076904" FT DOMAIN 154..260 FT /note="SPR" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00572" FT VARIANT 161 FT /note="A -> T (in dbSNP:rs35474915)" FT /id="VAR_034519" FT CONFLICT 93 FT /note="T -> P (in Ref. 6; AAC39567)" FT /evidence="ECO:0000305|PubMed:9458049" SQ SEQUENCE 288 AA; 31222 MW; 62C59F5E897D99B8 CRC64; MDAAVTDDFQ QILPIEQLRS THASNDYVER PPAPCKQALS SPSLIVQTHK SDWSLATMPT SLPRSLSQCH QLQPLPQHLS QSSIASSMSH STTASDQRLL ASITPSPSGQ SIIRTQPGAG VHPKADGALK GEAEQSAGHP SEHLFICEEC GRCKCVPCTA ARPLPSCWLC NQRCLCSAES LLDYGTCLCC VKGLFYHCST DDEDNCADEP CSCGPSSCFV RWAAMSLISL FLPCLCCYLP TRGCLHLCQQ GYDSLRRPGC RCKRHTNTVC RKISSGSAPF PKAQEKSV //