Summary

Name RAPGEF2
Full Name Rap guanine nucleotide exchange factor 2
Synonyms Cyclic nucleotide ras GEF, CNrasGEF, Neural RAP guanine nucleotide exchange protein, nRap GEP, PDZ domain-containing guanine nucleotide exchange factor 1, PDZ-GEF1, RA-GEF-1, Ras/Rap1-associating GEF-1 | KIAA0313, NRAPGEP, PDZGEF1
Primary ID Q9Y4G8
Links - -
Type protein
Relations 8
Function 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.

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▶Modifications Tables

Relations

Regulator Mechanism target score ℹ
+ CDK5up-regulates activity img/direct-activation.png phosphorylation RAPGEF2
Publications: 1 Organism: Homo Sapiens
+ CSNK1A1down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation RAPGEF2 0.2
Publications: 2 Organism: Homo Sapiens
+ PRKCQup-regulates img/direct-activation.png phosphorylation RAPGEF2 0.2
Publications: 1 Organism: Homo Sapiens
+ NEDD4down-regulates quantity img/direct_inhibition.png ubiquitination RAPGEF2
Publications: 1 Organism: Homo Sapiens
+ SCF-betaTRCPdown-regulates quantity by destabilization img/direct_inhibition.png ubiquitination RAPGEF2 0.2
Publications: 2 Organism: Homo Sapiens
+ RAPGEF2up-regulates activity img/direct-activation.png guanine nucleotide exchange factor RAP1A 0.787
Publications: 1 Organism: Homo Sapiens