Tbio RAPGEF2 Rap guanine nucleotide exchange factor 2

Protein Summary

Description

Functions as a guanine nucleotide exchange factor (GEF), which activates Rap and Ras family of small GTPases by exchanging bound GDP for free GTP in a cAMP-dependent manner. Serves as a link between cell surface receptors and Rap/Ras GTPases in intracellular signaling cascades. Acts also as an effector for Rap1 by direct association with Rap1-GTP thereby leading to the amplification of Rap1-mediated signaling. Shows weak activity on HRAS. It is controversial whether RAPGEF2 binds cAMP and cGMP (PubMed:23800469, PubMed:10801446) or not (PubMed:10608844, PubMed:10548487, PubMed:11359771). Its binding to ligand-activated beta-1 adrenergic receptor ADRB1 leads to the Ras activation through the G(s)-alpha signaling pathway. Involved in the cAMP-induced Ras and Erk1/2 signaling pathway that leads to sustained inhibition of long term melanogenesis by reducing dendrite extension and melanin synthesis. Provides also inhibitory signals for cell proliferation of melanoma cells and promotes their apoptosis in a cAMP-independent nanner. Regulates cAMP-induced neuritogenesis by mediating the Rap1/B-Raf/ERK signaling through a pathway that is independent on both PKA and RAPGEF3/RAPGEF4. Involved in neuron migration and in the formation of the major forebrain fiber connections forming the corpus callosum, the anterior commissure and the hippocampal commissure during brain development. Involved in neuronal growth factor (NGF)-induced sustained activation of Rap1 at late endosomes and in brain-derived neurotrophic factor (BDNF)-induced axon outgrowth of hippocampal neurons. Plays a role in the regulation of embryonic blood vessel formation and in the establishment of basal junction integrity and endothelial barrier function. May be involved in the regulation of the vascular endothelial growth factor receptor KDR and cadherin CDH5 expression at allantois endothelial cell-cell junctions. Members of the RAS (see HRAS; MIM 190020) subfamily of GTPases function in signal transduction as GTP/GDP-regulated switches that cycle between inactive GDP- and active GTP-bound states. Guanine nucleotide exchange factors (GEFs), such as RAPGEF2, serve as RAS activators by promoting acquisition of GTP to maintain the active GTP-bound state and are the key link between cell surface receptors and RAS activation (Rebhun et al., 2000 [PubMed 10934204]).[supplied by OMIM, Mar 2008]

Uniprot Accession IDs

• Q9Y4G8
• D3DP27

Gene Name

• RAPGEF2

Ensembl ID

• ENST00000264431
• ENSP00000264431
• ENSG00000109756

Symbol

• KIAA0313
• NRAPGEP
• PDZGEF1
• RAGEF
• RA-GEF
• NRAPGEP
• PDZGEF1
• Rap-GEP
• CNrasGEF
• PDZ-GEF1
• RA-GEF-1
• nRap GEP

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
molecular function	1
protein domain	0.99
transcription factor perturbation	0.84
cellular component	0.82

Protein Classes

PANTHER Classes

Protein / Enzyme Modulator / G-protein Modulator / Guanyl-nucleotide Exchange Factor / Rap Guanine Nucleotide Exchange Factor 2

DTO Classes

Protein / Enzyme Modulator / G-protein Modulator / Guanyl-nucleotide Exchange Factor / Rap Guanine Nucleotide Exchange Factor 2

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 36.2   (req: < 5)

Gene RIFs: 14   (req: <= 3)

Antibodies: 115   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 36.2   (req: >= 5)

Gene RIFs: 14   (req: > 3)

Antibodies: 115   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 47

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0