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RIC8 GUANINE NUCLEOTIDE EXCHANGE FACTOR B; RIC8B

RIC8 GUANINE NUCLEOTIDE EXCHANGE FACTOR B; RIC8B

Alternative titles; symbolsRIC8, C. ELEGANS, HOMOLOG OF, BSYNEMBRYN, C. ELEGANS, HOMOLOG OF, BHGNC Approved Gene Symbol: RIC8BCytogenetic location: 12q23.3 G...

Alternative titles; symbols

  • RIC8, C. ELEGANS, HOMOLOG OF, B
  • SYNEMBRYN, C. ELEGANS, HOMOLOG OF, B

HGNC Approved Gene Symbol: RIC8B

Cytogenetic location: 12q23.3 Genomic coordinates (GRCh38): 12:106,774,620-106,889,315 (from NCBI)

▼ Cloning and Expression
Using G-alpha proteins (see GNAS; 139320) as bait in a yeast 2-hybrid screen of a rat brain cDNA library, Tall et al. (2003) cloned Ric8b, a homolog of C. elegans Ric8/synembryn. By database analysis, they identified human RIC8B. The deduced 520-amino acid rat protein shares 86% identity with the deduced 536-amino acid human protein over the first 483 amino acids; their C termini are completely divergent. RIC8B shares 40% amino acid identity with mouse synembryn (RIC8A; 609146).

Using GTPase-deficient GNAS as bait in a yeast 2-hybrid screen of a human brain cDNA library, followed by database analysis, Klattenhoff et al. (2003) cloned 2 splice variants of RIC8B, which they called synembryn (SYN) because it belongs to the synembryn family. The deduced 536- and 535-amino acid proteins differ only in the last 11 C-terminal amino acids.

▼ Gene Function
By yeast 2-hybrid analysis, Tall et al. (2003) determined that rat Ric8b interacted strongly with GNAQ (139313) and weakly with GNAS. It interacted preferentially with wildtype GNAS compared with GTPase-deficient GNAS.

By yeast 2-hybrid analysis, Klattenhoff et al. (2003) confirmed direct binding between RIC8B and GNAS. In vitro binding assays showed constitutively activated forms of GNAS and GNAQ interacted with RIC8B, but GNAI3 (139370) did not. Carbachol, a cholinergic agonist, induced the reversible translocation of fluorescence-tagged RIC8B from the cytosol to the plasma membrane of human neuroblastoma cells. In rat pheochromocytoma cells and human neuroblastoma cells, treatment with carbachol led to the colocalization of RIC8B with plasma membrane GNAQ, and treatment with isoproterenol, a beta-adrenergic agonist, led to the colocalization of RIC8B with plasma membrane GNAS. Klattenhoff et al. (2003) concluded that RIC8B does not interact with inactive heterotrimeric forms of GNAS or GNAQ at the membrane, but the generation of active GTP-bound G proteins by ligand-activated G protein-coupled receptors promotes the translocation of RIC8B to the plasma membrane.

Afshar et al. (2004) determined that C. elegans Ric8 is required for proper asymmetric division of 1-cell-stage embryos. Spindle severing experiments demonstrated that Ric8 was required for the generation of substantial pulling forces on astral microtubules. Ric8 physically interacted with 2 nematode G-alpha subunits that act in a partially redundant manner in 1-cell-stage embryos. Ric8 behaved as a guanine nucleotide exchange factor for the G-alpha protein Goa1.

Von Dannecker et al. (2006) found that Ric8b promoted functional olfactory receptor expression in a heterologous expression system and amplified olfactory receptor signaling through G-alpha-olf (GNAL; 139312).

▼ Gene Structure
Klattenhoff et al. (2003) determined that the RIC8B gene contains 10 exons.

▼ Mapping
Gross (2015) mapped the RIC8B gene to chromosome 12q23.3 based on an alignment of the RIC8B sequence (GenBank BC132689) with the genomic sequence (GRCh38).

Tags: 12q23.3