SPR domain

Last updated
Sprouty
Identifiers
SymbolSPR
Pfam PF05210
InterPro IPR007875
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

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]

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:

Related Research Articles

A mitogen-activated protein kinase is a type of protein kinase that is specific to the amino acids serine and threonine. MAPKs are involved in directing cellular responses to a diverse array of stimuli, such as mitogens, osmotic stress, heat shock and proinflammatory cytokines. They regulate cell functions including proliferation, gene expression, differentiation, mitosis, cell survival, and apoptosis.

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<span class="mw-page-title-main">Platelet-derived growth factor receptor</span> Protein family

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<span class="mw-page-title-main">GRB2</span> Protein-coding gene in the species Homo sapiens

Growth factor receptor-bound protein 2, also known as Grb2, is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene.

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<span class="mw-page-title-main">MAPK14</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase 14, also called p38-α, is an enzyme that in humans is encoded by the MAPK14 gene.

<span class="mw-page-title-main">DUSP1</span> Protein-coding gene in the species Homo sapiens

Dual specificity protein phosphatase 1 is an enzyme that in humans is encoded by the DUSP1 gene.

<span class="mw-page-title-main">SPRY2</span> Protein-coding gene in the species Homo sapiens

Sprouty homolog 2 (Drosophila), also known as SPRY2, is a protein which in humans is encoded by the SPRY2 gene.

<span class="mw-page-title-main">FRS2</span> Protein-coding gene in humans

Fibroblast growth factor receptor substrate 2 is a protein that in humans is encoded by the FRS2 gene.

<span class="mw-page-title-main">TFG (gene)</span> Protein-coding gene in the species Homo sapiens

Protein TFG is a protein that in humans is encoded by the TFG gene.

<span class="mw-page-title-main">SPRED2</span> Protein-coding gene in the species Homo sapiens

Sprouty-related, EVH1 domain-containing protein 2 is a protein that in humans is encoded by the SPRED2 gene.

<span class="mw-page-title-main">SPRY1</span> Protein-coding gene in the species Homo sapiens

Protein sprouty homolog 1 is a protein that in humans is encoded by the SPRY1 gene.

Protein sprouty homolog 3 is a protein that in humans is encoded by the SPRY3 gene.

In molecular biology, the protein Sprouty is a developmental protein involved in cell signalling. It works by inhibiting the MAPK/ERK pathway.

<span class="mw-page-title-main">SPRED3</span> Protein-coding gene in the species Homo sapiens

Sprouty-related, EVH1 domain-containing protein 3 also known as Spread-3 is a protein that in humans is encoded by the SPRED3 gene.

<span class="mw-page-title-main">Tyrosine phosphorylation</span> Phosphorylation of peptidyl-tyrosine

Tyrosine phosphorylation is the addition of a phosphate (PO43−) group to the amino acid tyrosine on a protein. It is one of the main types of protein phosphorylation. This transfer is made possible through enzymes called tyrosine kinases. Tyrosine phosphorylation is a key step in signal transduction and the regulation of enzymatic activity.

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. 1 2 3 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. 1 2 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. 1 2 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