Rap Guanine Nucleotide Exchange Factor 6 (RAPGEF6)

RAPGEF6 expressed in insect cells showed GEF activity toward RAP1A and RAP2A, but not toward other RAS family members.RAPGEF6 colocalized with activated MRAS in the plasma membrane of cotransfected COS-7 cells, leading to an increase in the GTP-bound form of plasma membrane RAP1. The deduced proteins contain 1,601 and 1,391 amino acids, respectively, and they differ after amino acid 1,249. Like RAPGEF2, PDZGEF2A contains a C-terminal proline-rich and a PDZ-binding motif, whereas PDZGEF2B lacks these motifs. Unlike RAPGEF2, both PDZGEF2 isoforms contain a second, less conserved, N-terminal RCBD (related cyclic nucleotide-binding domain) domain. Northern blot analysis detected ubiquitous expression of an approximately 9.0-kb RAPGEF6 transcript.