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RAP GUANINE NUCLEOTIDE EXCHANGE FACTOR 6; RAPGEF6

RAP GUANINE NUCLEOTIDE EXCHANGE FACTOR 6; RAPGEF6

Alternative titles; symbolsRAS-ASSOCIATING GUANINE NUCLEOTIDE EXCHANGE FACTOR 2; RAGEF2PDZ DOMAIN-CONTAINING GUANINE NUCLEOTIDE EXCHANGE FACTOR 2; PDZGEF2HGNC Ap...

Alternative titles; symbols

  • RAS-ASSOCIATING GUANINE NUCLEOTIDE EXCHANGE FACTOR 2; RAGEF2
  • PDZ DOMAIN-CONTAINING GUANINE NUCLEOTIDE EXCHANGE FACTOR 2; PDZGEF2

HGNC Approved Gene Symbol: RAPGEF6

Cytogenetic location: 5q31.1 Genomic coordinates (GRCh38): 5:131,423,920-131,635,228 (from NCBI)

▼ Cloning and Expression
By searching for sequences similar to RAGEF1 (RAPGEF2; 609530), followed by screening a fetal brain cDNA library and 5-prime and 3-prime RACE, Gao et al. (2001) cloned RAPGEF6, which they called RAGEF2. The deduced 1,509-amino acid protein contains several of the domains present in RAPGEF2, including cNMP-binding, REM, PDZ, and RA domains as well as the GEF catalytic domain. Northern blot analysis detected a RAPGEF6 transcript of about 8 kb which was abundantly expressed in heart, brain, placenta, lung, and liver, but barely detectable in skeletal muscle, kidney, and pancreas.

Kuiperij et al. (2003) cloned 2 splice variants of RAPGEF6, which they called PDZGEF2A and PDZGEF2B, from human umbilical cord and Jurkat T-cell cDNA libraries. 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.

▼ Gene Function
Gao et al. (2001) found that human RAPGEF6 expressed in insect cells showed GEF activity toward RAP1A (179520) and RAP2A (179540), but not toward other RAS family members. RAPGEF6 colocalized with activated MRAS (608435) in the plasma membrane of cotransfected COS-7 cells, leading to an increase in the GTP-bound form of plasma membrane RAP1. Gao et al. (2001) concluded that RAPGEF6 acts as the GEF for RAP1 and RAP2 downstream of MRAS in the plasma membrane. Kuiperij et al. (2003) demonstrated that RAPGEF2 activated both RAP1 and RAP2.

▼ Mapping
By genomic sequence analysis, Gao et al. (2001) and Kuiperij et al. (2003) mapped the RAPGEF6 gene to chromosome 5.

Tags: 5q31.1