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RASGEF DOMAIN FAMILY, MEMBER 1A; RASGEF1A

RASGEF DOMAIN FAMILY, MEMBER 1A; RASGEF1A

HGNC Approved Gene Symbol: RASGEF1ACytogenetic location: 10q11.21 Genomic coordinates (GRCh38): 10:43,194,534-43,267,064 (from NCBI)▼ DescriptionRAS proteins...

HGNC Approved Gene Symbol: RASGEF1A

Cytogenetic location: 10q11.21 Genomic coordinates (GRCh38): 10:43,194,534-43,267,064 (from NCBI)

▼ Description
RAS proteins (see HRAS; 190020) are small GTPases that are interconvertible between an active GTP-bound form and an inactive GDP-bound form. Guanine nucleotide exchange factors (GEFs), such as RASGEF1A, induce release of GDP, permitting reloading of GTP onto RAS and activation of cell signaling (Ura et al., 2006).

▼ Cloning and Expression
Using microarray analysis to identify genes upregulated in intrahepatic cholangiocarcinoma, Ura et al. (2006) identified RASGEF1A. The deduced protein contains a RASGEF domain and a RAS exchange motif, and it shares 30% and 29% identity with PDZGEF2 (RAPGEF6; 610499) and PDZGEF1 (RAPGEF2; 609530), respectively. Northern blot analysis detected a transcript of about 3.3 kb that was moderately expressed in brain and spinal cord and weakly expressed in lymph node and adrenal gland, but not in any of 19 other tissues examined.

▼ Gene Function
Ura et al. (2006) found that recombinant RASGEF1A stimulated radiolabeled GDP dissociation from KRAS (190070), HRAS, and NRAS (164790). In transfected COS-7 cells, exogenous RASGEF1A activated Ras, which increased its affinity for Raf1 (164760). Overexpression of RASGEF1A in COS-7 cells increased cell migration, but it had no effect on colony-forming ability. Knockdown of RASGEF1A via small interfering RNA reduced cell growth of COS-7 and intrahepatic cholangiocarcinoma cells.

Yaman et al. (2009) presented evidence that RASGEF1A and RASGEF1B (614532) function as specific GEFs for RAP2 (RAP2A; 179540), but not for RAP1 (RAP1A; 179520) or other members of the RAS family.

▼ Mapping
Hartz (2012) mapped the RASGEF1A gene to chromosome 10q11.21 based on an alignment of the RASGEF1A sequence (GenBank AK095136) with the genomic sequence (GRCh37).

Tags: 10q11.21

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