dbl/MCF2 proto-oncogene protein (MCF2, DBL)
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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
- 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
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/P10911.html
- ↑ Hunter T. Cooperation between oncogenes. Cell. 1991 Jan 25;64(2):249-70. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1988147
- ↑ OMIM https://mirror.omim.org/entry/310970
- ↑ Marx J. New genes may shed light on cell growth control. Science. 1992 Jul 24;257(5069):484-5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1636083
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/8236453
- ↑ 6.0 6.1 Boguski MS & McCormick F Proteins regulating Ras and its relative. Nature 366:643 1993 PMID: https://www.ncbi.nlm.nih.gov/pubmed/8259209