The reference OMIM entry for this protein is 179530

Ras-related protein rap1b; rap1b

DESCRIPTION

RAP1B and RAP1A (179520) belong to a superfamily of RAS (see 190020)-like small GTP-binding proteins involved in cell signaling.

CLONING

Pizon et al. (1988) cloned human RAP1B. The deduced 184-amino acid protein is 95% identical to RAP1A. RAP1B shares several properties with the RAS protein, suggesting that it may bind GTP/GDP and have a membrane location. Matsui et al. (1990) reported the amino acid sequence of RAP1B, which they called SMG p21B, purified from bovine brain and human platelets. The bovine and human proteins are identical.

GENE FUNCTION

Hoshijima et al. (1988) and Kawata et al. (1989) reported that RAP1B is phosphorylated by cAMP-dependent protein kinase (see 601639) on ser179. Kawata et al., 1990 found that phosphorylation enhanced GDP/GTP exchange. Kawata et al. (1990) determined that purified human platelet RAP1B is posttranslationally modified by the geranylgeranylation of cys181. Further modifications cause proteolytic removal of the last 3 C-terminal amino acids, followed by partial methylation of the remaining terminal cysteinyl carboxyl group. Kawata et al. (1990) suggested that geranylgeranylation and methylation of RAP1B are important, because they found that C-terminal modification was required for the binding of RAP1B to membranes. Lova et al. (2003) noted that, in resting cells, RAP1B is mainly located at the membrane, but translocates to the cytosol upon activation. In activated platelets, RAP1B interacts with the reorganized actin-based cytoskeleton. RAP1B is activated by phosphorylation, increased intracellular Ca(2+), and by agonist-induced stimulation of Gi (139310), which results in the rapid binding of GTP to RAP1B. Lova et al. (2003) found that stimulation of Gi-dependent signaling could activate human platelet RAP1B through phosphatidylinositol(3,4,5)-trisphosphate (PtdIns(3,4,5)P3), but not PtdIns(3,4)P2. They concluded that the PI3 kinase (see 601232) pathway of RAP1B activation may contribute to potentiation of platelet aggregation. Schwamborn and Puschel (2004) found that localization of Rap1b to the tip of a single neurite in rat hippocampal neurons was a decisive step in determining which neurite became the axon.

MAPPING

By in situ hybridization, Rousseau-Merck et al. (1990) mapped the RAP1B gene to chromosome 12q14.

BIOCHEMICAL FEATURES

- Crystal Structure Rehmann et al. (2008) determined the structure of EPAC2 (606058) in complex with a cAMP analog (Sp-cAMPS) and RAP1B by x-ray crystallography and single-particle electron microscopy. The structure represents the cAMP-activated state of the EPAC2 protein with the RAP1B protein trapped in the course of the exchange reaction. Comparison with the inactive conformation revealed that cAMP binding causes conformational changes that allow the cyclic nucleotide binding domain to swing from a position blocking the Rap binding site toward a docking site at the Ras exchange motif domain.

ANIMAL MODEL

Chrzanowska-Wodnicka et al. (2005) generated Rap1b -/- mice and observed a bleeding defect due to defective platelet function. Aggregation of Rap1b-null platelets was reduced in response to stimulation with both G protein-coupled receptor (GPCR; see 600239)-linked and GPCR-independent agonists and was found to be due to decreased agonist-induced activation of integrin alpha-IIb-beta-3 (see 607759, 173470) and signaling downstream. In vivo, Rap1b-null mice were protected from arteri ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 179530 was added.