In molecular biology the SPR ___domain is a protein ___domain found in the Sprouty (Spry) and Spred (Sprouty related EVH1 ___domain) proteins. These 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.[2][3][4][5] 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.[2][6] It also mediates homodimer formation of these proteins.[3][6]
| Sprouty | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | SPR | ||||||||
| Pfam | PF05210 | ||||||||
| InterPro | IPR007875 | ||||||||
| |||||||||
The SPR ___domain can occur in association with the WH1 ___domain (see InterPro: IPR000697) (located in the N-terminus) in the Spred proteins.
Examples
editHuman genes encoding protein containing the SPR ___domain include:
References
edit- ^ Zhang S, Lin Y, Itäranta P, Yagi A, Vainio S (December 2001). "Expression of Sprouty genes 1, 2 and 4 during mouse organogenesis". Mechanisms of Development. 109 (2): 367–70. doi:10.1016/S0925-4773(01)00526-3. PMID 11731251. S2CID 17189370.
- ^ a b c Lim J, Yusoff P, Wong ES, Chandramouli S, Lao DH, Fong CW, Guy GR (November 2002). "The cysteine-rich sprouty translocation ___domain targets mitogen-activated protein kinase inhibitory proteins to phosphatidylinositol 4,5-bisphosphate in plasma membranes". Molecular and Cellular Biology. 22 (22): 7953–66. doi:10.1128/MCB.22.22.7953-7966.2002. PMC 134720. PMID 12391162.
- ^ a b King JA, Straffon AF, D'Abaco GM, Poon CL, I ST, Smith CM, Buchert M, Corcoran NM, Hall NE, Callus BA, Sarcevic B, Martin D, Lock P, Hovens CM (June 2005). "Distinct requirements for the Sprouty ___domain for functional activity of Spred proteins". The Biochemical Journal. 388 (Pt 2): 445–54. doi:10.1042/BJ20041284. PMC 1138951. PMID 15683364.
- ^ Lim J, Wong ES, Ong SH, Yusoff P, Low BC, Guy GR (October 2000). "Sprouty proteins are targeted to membrane ruffles upon growth factor receptor tyrosine kinase activation. Identification of a novel translocation ___domain". The Journal of Biological Chemistry. 275 (42): 32837–45. doi:10.1074/jbc.M002156200. PMID 10887178.
- ^ Wakioka T, Sasaki A, Kato R, Shouda T, Matsumoto A, Miyoshi K, Tsuneoka M, Komiya S, Baron R, Yoshimura A (August 2001). "Spred is a Sprouty-related suppressor of Ras signalling". Nature. 412 (6847): 647–51. Bibcode:2001Natur.412..647W. doi:10.1038/35088082. PMID 11493923. S2CID 4345140.
- ^ a b Hanafusa H, Torii S, Yasunaga T, Nishida E (November 2002). "Sprouty1 and Sprouty2 provide a control mechanism for the Ras/MAPK signalling pathway". Nature Cell Biology. 4 (11): 850–8. doi:10.1038/ncb867. PMID 12402043. S2CID 31064800.