PROSITE documentation PDOC51227Sprouty (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 <PDOC50229>) (located in the N-terminal part of the proteins) in the Spred proteins.
We developed a profile that spans the entire SPR domain.
Note:The SPR domain is also named Spry translocation domain (SpryTD).
Last update:July 2006 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | 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. |
| Title | Distinct requirements for the Sprouty domain for functional activity of Spred proteins. | |
| Source | Biochem. J. 388:445-454(2005). | |
| PubMed ID | 15683364 | |
| DOI | 10.1042/BJ20041284 |
| 2 | Authors | Lim J. Yusoff P. Wong E.S.M. Chandramouli S. Lao D.-H. Fong C.W. Guy G.R. |
| Title | The cysteine-rich sprouty translocation domain targets mitogen-activated protein kinase inhibitory proteins to phosphatidylinositol 4,5-bisphosphate in plasma membranes. | |
| Source | Mol. Cell. Biol. 22:7953-7966(2002). | |
| PubMed ID | 12391162 |
| 3 | Authors | Lim J. Wong E.S.M. Ong S.H. Yusoff P. Low B.C. Guy G.R. |
| Title | Sprouty proteins are targeted to membrane ruffles upon growth factor receptor tyrosine kinase activation. Identification of a novel translocation domain. | |
| Source | J. Biol. Chem. 275:32837-32845(2000). | |
| PubMed ID | 10887178 | |
| DOI | 10.1074/jbc.M002156200 |
| 4 | Authors | Wakioka T. Sasaki A. Kato R. Shouda T. Matsumoto A. Miyoshi K. Tsuneoka M. Komiya S. Baron R. Yoshimura A. |
| Title | Spred is a Sprouty-related suppressor of Ras signalling. | |
| Source | Nature 412:647-651(2001). | |
| PubMed ID | 11493923 | |
| DOI | 10.1038/35088082 |
| 5 | Authors | Hanafusa H. Torii S. Yasunaga T. Nishida E. |
| Title | Sprouty1 and Sprouty2 provide a control mechanism for the Ras/MAPK signalling pathway. | |
| Source | Nat. Cell Biol. 4:850-858(2002). | |
| PubMed ID | 12402043 | |
| DOI | 10.1038/ncb867 |
| 6 | Authors | Lim J. Yusoff P. Wong E.S.M. Chandramouli S. Lao D.-H. Fong C.W. Guy G.R. |
| Title | The cysteine-rich sprouty translocation domain targets mitogen-activated protein kinase inhibitory proteins to phosphatidylinositol 4,5-bisphosphate in plasma membranes. | |
| Source | Mol. Cell. Biol. 22:7953-7966(2002). | |
| PubMed ID | 12391162 |
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