{PDOC51227} {PS51227; SPR} {BEGIN} ******************************** * Sprouty (SPR) domain profile * ******************************** Sprouty (Spry) and Spred (Sprouty related EVH1 domain) proteins have been identified as inhibitors of the Ras/mitogen-activated protein kinase (MAPK) cascade, a pathway crucial for developmental processes initiated by activation of various receptor tyrosine kinases [1,2]. These proteins share a conserved, C-terminal cysteine-rich region, the SPR domain. This domain has been defined as a novel cytosol to membrane translocation domain [1,2,3,4]. It has been found to be a PtdIns(4,5)P2-binding domain that targets the proteins to a cellular localization that maximizes their inhibitory potential [5,6]. It also mediates homodimer formation of these proteins [1,5]. The SPR domain can occur in association with the WH1 domain (see ) (located in the N-terminal part of the proteins) in the Spred proteins. We developed a profile that spans the entire SPR domain. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Note: The SPR domain is also named Spry translocation domain (SpryTD). -Last update: July 2006 / First entry. [ 1] King J.A.J., Straffon A.F.L., D'Abaco G.M., Poon C.L.C., I S.T.T., Smith C.M., Buchert M., Corcoran N.M., Hall N.E., Callus B.A., Sarcevic B., Martin D., Lock P., Hovens C.M. "Distinct requirements for the Sprouty domain for functional activity of Spred proteins." Biochem. J. 388:445-454(2005). PubMed=15683364; DOI=10.1042/BJ20041284 [ 2] Lim J., Yusoff P., Wong E.S.M., Chandramouli S., Lao D.-H., Fong C.W., Guy G.R. "The cysteine-rich sprouty translocation domain targets mitogen-activated protein kinase inhibitory proteins to phosphatidylinositol 4,5-bisphosphate in plasma membranes." Mol. Cell. Biol. 22:7953-7966(2002). PubMed=12391162 [ 3] Lim J., Wong E.S.M., Ong S.H., Yusoff P., Low B.C., Guy G.R. "Sprouty proteins are targeted to membrane ruffles upon growth factor receptor tyrosine kinase activation. Identification of a novel translocation domain." J. Biol. Chem. 275:32837-32845(2000). PubMed=10887178; DOI=10.1074/jbc.M002156200 [ 4] Wakioka T., Sasaki A., Kato R., Shouda T., Matsumoto A., Miyoshi K., Tsuneoka M., Komiya S., Baron R., Yoshimura A. "Spred is a Sprouty-related suppressor of Ras signalling." Nature 412:647-651(2001). PubMed=11493923; DOI=10.1038/35088082 [ 5] Hanafusa H., Torii S., Yasunaga T., Nishida E. "Sprouty1 and Sprouty2 provide a control mechanism for the Ras/MAPK signalling pathway." Nat. Cell Biol. 4:850-858(2002). PubMed=12402043; DOI=10.1038/ncb867 [ 6] Lim J., Yusoff P., Wong E.S.M., Chandramouli S., Lao D.-H., Fong C.W., Guy G.R. "The cysteine-rich sprouty translocation domain targets mitogen-activated protein kinase inhibitory proteins to phosphatidylinositol 4,5-bisphosphate in plasma membranes." Mol. Cell. Biol. 22:7953-7966(2002). PubMed=12391162 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}