RAPGEF2 - Rap guanine nucleotide exchange factor 2 - human protein (Function)
 
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RAPGEF2 »  Rap guanine nucleotide exchange factor 2
 
Protein also known as:  PDZ domain-containing guanine nucleotide exchange factor 1 (PDZ-GEF1).
Gene name:  RAPGEF2
Family name: RAPGEF2
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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 (PubMed23800469, PubMed10801446) or not (PubMed:10608844, PubMed10548487, PubMed11359771). 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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  • CuratedUniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathway:
MAPK signaling pathway  hsa04010+9693  
 

Keywords

Biological process 
Differentiation  definition   [KW-0221]
Neurogenesis  definition   [KW-0524]
Molecular function 
Developmental protein  definition   [KW-0217]
GTPase activation  definition   [KW-0343]
Guanine-nucleotide releasing factor  definition   [KW-0344]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: RAPGEF2
GenomeRNAi: 9693
PRO: PR:Q9Y4G8