RAPGEF2 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 or not. 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. Belongs to the RAPGEF2 family. Expressed in primary neuronal and endocrine cells (at protein level). Highest expression levels in brain. Lower expression levels in heart, kidney, lung, placenta and blood leukocytes. Note: This description may include information from UniProtKB.
Protein type: GEF; GEF, Ras; Motility/polarity/chemotaxis
Chromosomal Location of human Ortholog: 4q32.1
Cellular Component:  apical plasma membrane; bicellular tight junction; cell-cell junction; cytoplasm; cytosol; endocytic vesicle; late endosome; membrane; neuron projection; neuronal cell body; perinuclear region of cytoplasm; plasma membrane; protein-containing complex; synapse
Molecular Function:  beta-1 adrenergic receptor binding; calcium ion binding; cAMP binding; cGMP binding; diacylglycerol binding; GTPase activator activity; guanyl-nucleotide exchange factor activity; PDZ domain binding; phosphatidic acid binding; protein binding; WW domain binding
Biological Process:  adenylate cyclase-activating adrenergic receptor signaling pathway; blood vessel development; brain-derived neurotrophic factor receptor signaling pathway; cAMP-mediated signaling; cellular response to cAMP; cellular response to cGMP; cellular response to nerve growth factor stimulus; establishment of endothelial barrier; establishment of endothelial intestinal barrier; forebrain neuron development; G protein-coupled receptor signaling pathway; intracellular signal transduction; MAPK cascade; microvillus assembly; negative regulation of cell population proliferation; negative regulation of dendrite morphogenesis; negative regulation of melanin biosynthetic process; nerve growth factor signaling pathway; neuron migration; neuron projection development; neuropeptide signaling pathway; positive regulation of cAMP-dependent protein kinase activity; positive regulation of cAMP-mediated signaling; positive regulation of dendritic cell apoptotic process; positive regulation of ERK1 and ERK2 cascade; positive regulation of GTPase activity; positive regulation of neuron migration; positive regulation of neuron projection development; positive regulation of protein binding; positive regulation of protein kinase activity; positive regulation of vasculogenesis; protein localization to plasma membrane; proteolysis; Rap protein signal transduction; Ras protein signal transduction; regulation of cell junction assembly; regulation of synaptic plasticity; small GTPase mediated signal transduction; ventricular system development
Disease: Epilepsy, Familial Adult Myoclonic, 7
Reference #:  Q9Y4G8 (UniProtKB)
Alt. Names/Synonyms: CNrasGEF; Cyclic nucleotide ras GEF; KIAA0313; Neural RAP guanine nucleotide exchange protein; nRap GEP; NRAPGEP; PDZ domain containing guanine nucleotide exchange factor (GEF) 1; PDZ domain-containing guanine nucleotide exchange factor 1; PDZ-GEF1; PDZGEF1; RA(Ras/Rap1A-associating)-GEF; RA-GEF; RA-GEF-1; RAGEF; Rap guanine nucleotide exchange factor (GEF) 2; Rap guanine nucleotide exchange factor 2; Rap-GEP; RAPGEF2; Ras/Rap1-associating GEF-1; RPGF2
Gene Symbols: RAPGEF2
Molecular weight: 167,417 Da
Basal Isoelectric point: 6.21  Predict pI for various phosphorylation states
Select Structure to View Below


Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  cBioPortal  |  CCLE  |  Wikipedia  |  neXtProt  |  Protein Atlas  |  BioGPS  |  Pfam  |  RCSB PDB  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  Ensembl Protein