Contents

Search

dbl/MCF2 proto-oncogene protein (MCF2, DBL)

Function: - guanine nucleotide exchange factor (GEF) - catalyzes exchange of GTP for GDP in rho proteins - specifically acts on rhoG [6] & perhaps on others - isoform 1 exhibits no activity toward RHOA, RAC1 or CDC42 - isoform 2 exhibits decreased GEF activity toward CDC42 - isoform 3 exhibits a weak but significant activity toward RAC1 & CDC42 - isoform 4 exhibits significant activity toward RHOA & CDC42 - the truncated DBL oncoprotein is active toward RHOA, RAC1 & CDC42 - interacts with an array of inositol phospholipids including a) phosphatidylinositol 3-phosphate (PI3P) b) phosphatidylinositol 4-phosphate (PI4P) c) phosphatidylinositol 5-phosphate (PI5P) - may interact with CCPG1 Structure: - the CRAL-TRIO domain is involved in interaction with inositol phospholipids - the DH domain is essential for transforming activity & directly catalyzes GDP-GTP exchange activity; it may interact with CCPG1 - belongs to the MCF2 family - contains 1 CRAL-TRIO domain - contains 1 DH (DBL-homology) domain - contains 1 PH domain - contains 1 spectrin repeat Compartment: - cytoplasm - isoform 1: membrane - isoform 3: membrane; colocalizes with CDC42 to plasma membrane Alternative splicing: named isoforms=4 Expression: - isoform 1 is expressed only in brain - isoform 3 is expressed in heart, kidney, spleen, liver & testis - isoform 4 is expressed in brain, heart, kidney, testis, placenta, stomach & peripheral blood - the protein is detectable in brain, heart, kidney, intestine, muscle, lung & testis Pathology: - MCF2 & DBL represent two activated versions of the same proto-oncogene

Related

dbl/MCF2 proto-oncogene

General

cytoskeletal protein guanine nucleotide exchange factor (GDP/GTP dissociation stimulator, guanine nucleotide-releasing factor/protein, GNEF, GNDS, GDS) proto oncogene protein

Properties

SIZE: entity length = 925 aa MW = 108 kD COMPARTMENT: cytoplasm MOTIF: CRAL-TRIO lipid binding domain {1-88} Spectrin {221-322} Dbl homology domain {495-675} PH domain {687-809}

Database Correlations

OMIM 311030 UniProt P10911 PFAM correlations Entrez Gene 4168 Kegg hsa:4168

References

  1. UniProt :accession P10911
  2. Hunter T. Cooperation between oncogenes. Cell. 1991 Jan 25;64(2):249-70. Review. PMID: 1988147
  3. OMIM :accession 310970
  4. Marx J. New genes may shed light on cell growth control. Science. 1992 Jul 24;257(5069):484-5. PMID: 1636083
  5. Musacchio A, Gibson T, Rice P, Thompson J, Saraste M. The PH domain: a common piece in the structural patchwork of signalling proteins. Trends Biochem Sci. 1993 Sep;18(9):343-8. Review. PMID: 8236453
  6. Boguski MS & McCormick F Proteins regulating Ras and its relative. Nature 366:643 1993 PMID: 8259209