Disease relevance of RAP2A

• Isoprenylation of rap2 proteins in platelets and human erythroleukemia cells [1].
• Rap2 belongs to the Ras superfamily of GTPases, whose role in breast cancer remains unknown [2].
• A severe decrease in the expression of the rap1A gene was shown in the fibrosarcomas and the adenocarcinoma of the salivary gland studied, as compared to their normal counterparts, whereas no rap2 expression was found in the polyadenylated RNA of sarcoma samples [3].

Psychiatry related information on RAP2A

• Prenyl group identification of rap2 proteins: a ras superfamily member other than ras that is farnesylated [4].

High impact information on RAP2A

• The accelerated cell migration was suppressed by the expression of active Rap1, Rap2 and R-Ras [5].
• RAP2B is 90% identical to RAP2 at the amino acid level with the most variability at the carboxyl terminus of the protein [6].
• Nitric Oxide Produced in Response to Engagement of beta2 Integrins on Human Neutrophils Activates the Monomeric GTPases Rap1 and Rap2 and Promotes Adhesion [7].
• Surprisingly, the beta2 integrin-induced activation of Rap2 was not regulated by any of the signaling pathways mentioned above [7].
• Among our observations, TNIK interacted with Rap2 through its CNH domain but did not interact with Rap1 or Ras [8].

Biological context of RAP2A

• To elucidate Rap2 function, we searched for potential effectors by screening a mouse brain cDNA library in a yeast two-hybrid system using as a bait a Rap2A protein bearing a mutation of Gly to Val at position 12 [9].
• Using transient transfections of HIT-T15 cells it was possible to demonstrate that [Val12]Rap2 and wild-type Rap2 could be immunoprecipitated with RPIP8 [9].
• DNA sequence analysis of one clone revealed that it encoded a partial amino acid sequence of a protein closely related to RAP2, which we have named RAP2B [6].
• RAP3 has homology with RAP2, and the genes are encoded on chromosome 5 in a head-to-tail fashion [10].
• Naturally occurring antibody responses to Plasmodium falciparum rhoptry-associated proteins 1 and 2 (RAP-1 and RAP-2) were measured with recombinant and parasite-derived forms of the antigens [11].

Anatomical context of RAP2A

• When co-expressed in cultured cells, TNIK colocalized with Rap2, while a mutant TNIK lacking the CNH domain did not [8].
• To identify the specific isoprenoid attached to each protein, the cDNAs were transcribed in vitro and the rap2 specific RNA was translated in a rabbit reticulocyte lysate system in the presence of [3H]mevalonolactone [4].
• Rap2, but not Rap1 GTPase is expressed in human red blood cells and is involved in vesiculation [12].
• By immunoblot analysis, we observed that rap2p is predominantly located in specific granules, whereas rap1p is detected both in specific granules and a fraction enriched in plasma membranes [13].
• Neither rap1p nor rap2p was found in the cytosol or in azurophil granules [13].

Associations of RAP2A with chemical compounds

• RA-GEF-2 stimulates guanine nucleotide exchange of both Rap1 and Rap2, but not Ha-Ras [14].
• Tuberin did not stimulate the GTPase activity of Rap2, Ha-Ras, Rac, or Rho [15].
• This anti-rap2 antiserum was used for two-dimensional immunoblotting analysis and immunoprecipitation of mevalonate-labeled rap2 from platelets and HEL cells [1].
• During its maturation, the Rap2 protein is modified by the attachment of both palmitate and polyisoprenoid groups, as is also the case for H- and N-Ras proteins [16].
• Subcellular fractionation by sucrose density centrifugation as well as indirect immunofluorescence experiments show that the Rap2 protein is localized in a low-density compartment that morphologically overlaps with the endoplasmic reticulum, whereas Ras proteins are associated with the plasma membrane [16].

Regulatory relationships of RAP2A

• Rap2 suppressed this in vivo action of PARG1 but not that of the mutant PARG1 [17].

Other interactions of RAP2A

• Rap2 potently enhanced the inhibitory function of TNIK against cell spreading, but this was not observed for the mutant TNIK lacking the CNH domain [8].
• Little is known about the specific signaling roles of Rap2, a Ras family small GTP-binding protein [18].
• The rap1 and rap2 genes encode proteins of 184 and 183 amino acid respectively with molecular weights of 20.9 kd and 20.7 kd [19].
• The human rap2 gene encodes a 183 amino acid protein that shares 46% identity with the K-ras p21 [20].
• These properties of the normal and mutant rap2 proteins are compared with those of ras p21 carrying similar substitutions and are discussed in relation to the structural models proposed for ras p21 [20].

Analytical, diagnostic and therapeutic context of RAP2A

• The product of the rap2 gene, member of the ras superfamily. Biochemical characterization and site-directed mutagenesis [20].
• Epac2 and Rap2 were detected in hamster spermatozoa using immunoblotting [21].
• Western blot analysis indicated that the protein level of Ras and RalB in both the cytosolic and membranous fractions and that of Rap2 in the cytosolic fraction was significantly decreased, while that of Rab8 in the membranous fraction was significantly increased in AD brains compared with controls [22].

References