SPR domain

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
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

The SPR domain can occur in association with the WH1 domain (see InterPro: IPR000697) (located in the N-terminus) in the Spred proteins.

Examples

Human genes encoding protein containing the SPR domain include:

• SPRED1, SPRED2, SPRED3, SPRY1, SPRY2, SPRY3, SPRY4

References

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.

This article incorporates text from the public domain Pfam and InterPro: IPR007875