RAPGEF2 [The Human Chemical-Genetic Interaction Map Project]

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======= RAPGEF2 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: RAPGEF2
  * **<color #00a2e8>Official Name</color>**: Rap guanine nucleotide exchange factor 2
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=9693|9693]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q9Y4G8|Q9Y4G8]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=RAPGEF2&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20RAPGEF2|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/609530|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  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. {ECO:0000269|PubMed:10548487, ECO:0000269|PubMed:10608844, ECO:0000269|PubMed:10608883, ECO:0000269|PubMed:10801446, ECO:0000269|PubMed:10934204, ECO:0000269|PubMed:11359771, ECO:0000269|PubMed:12391161, ECO:0000269|PubMed:16272156, ECO:0000269|PubMed:17724123, ECO:0000269|PubMed:21840392, ECO:0000269|PubMed:23800469}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|RA|
|PDZ|
|RasGEF|
|cNMP binding|
|RasGEF N|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|positive regulation of dendritic cell apoptotic process|
|negative regulation of melanin biosynthetic process|
|negative regulation of secondary metabolite biosynthetic process|
|beta-1 adrenergic receptor binding|
|brain-derived neurotrophic factor receptor signaling pathway|
|Rap guanyl-nucleotide exchange factor activity|
|positive regulation of cAMP-dependent protein kinase activity|
|cellular response to cGMP|
|response to cGMP|
|regulation of dendritic cell apoptotic process|
|regulation of melanin biosynthetic process|
|positive regulation of vasculogenesis|
|regulation of secondary metabolite biosynthetic process|
|Rap protein signal transduction|
|nerve growth factor signaling pathway|
|diacylglycerol binding|
|regulation of secondary metabolic process|
|establishment of endothelial intestinal barrier|
|regulation of vasculogenesis|
|Ras guanyl-nucleotide exchange factor activity|
|negative regulation of dendrite morphogenesis|
|cGMP binding|
|positive regulation of neuron migration|
|regulation of cAMP-dependent protein kinase activity|
|microvillus assembly|
|microvillus organization|
|phosphatidic acid binding|
|adenylate cyclase-activating adrenergic receptor signaling pathway|
|adrenergic receptor signaling pathway|
|cAMP binding|
|positive regulation of cAMP-mediated signaling|
|ventricular system development|
|neurotrophin signaling pathway|
|positive regulation of leukocyte apoptotic process|
|negative regulation of dendrite development|
|forebrain neuron development|
|WW domain binding|
|establishment of endothelial barrier|
|regulation of neuron migration|
|cellular response to nerve growth factor stimulus|
|regulation of cAMP-mediated signaling|
|endothelial cell development|
|forebrain neuron differentiation|
|response to nerve growth factor|
|cellular response to cAMP|
|endocytic vesicle|
|forebrain generation of neurons|
|central nervous system neuron development|
|regulation of leukocyte apoptotic process|
|endothelial cell differentiation|
|PDZ domain binding|
|regulation of cell junction assembly|
|regulation of dendrite morphogenesis|
|positive regulation of protein binding|
|endothelium development|
|negative regulation of cell morphogenesis involved in differentiation|
|response to cAMP|
|neuropeptide signaling pathway|
|neuron migration|
|bicellular tight junction|
|late endosome|
|adenylate cyclase-activating G protein-coupled receptor signaling pathway|
|response to organophosphorus|
|cAMP-mediated signaling|
|regulation of dendrite development|
|response to purine-containing compound|
|negative regulation of neuron projection development|
|cell-cell junction|
|cyclic-nucleotide-mediated signaling|
|positive regulation of binding|
|central nervous system neuron differentiation|
|negative regulation of cell projection organization|
|positive regulation of vasculature development|
|protein localization to plasma membrane|
|regulation of synaptic plasticity|
|epithelial cell development|
|adenylate cyclase-modulating G protein-coupled receptor signaling pathway|
|positive regulation of ERK1 and ERK2 cascade|
|regulation of protein binding|
|negative regulation of neuron differentiation|
|protein localization to cell periphery|
|G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger|
|Ras protein signal transduction|
|synapse|
|positive regulation of neuron projection development|
|GTPase activator activity|
|negative regulation of neurogenesis|
|regulation of ERK1 and ERK2 cascade|
|regulation of cell morphogenesis involved in differentiation|
|negative regulation of nervous system development|
|apical plasma membrane|
|small GTPase mediated signal transduction|
|neuron projection|
|regulation of vasculature development|
|negative regulation of cell development|
|second-messenger-mediated signaling|
|positive regulation of protein serine/threonine kinase activity|
|positive regulation of neuron differentiation|
|neuronal cell body|
|MAPK cascade|
|regulation of binding|
|positive regulation of cell projection organization|
|forebrain development|
|signal transduction by protein phosphorylation|
|positive regulation of GTPase activity|
|modulation of chemical synaptic transmission|
|regulation of trans-synaptic signaling|
|plasma membrane bounded cell projection assembly|
|cell projection assembly|
|positive regulation of neurogenesis|
|protein localization to membrane|
|regulation of GTPase activity|
|blood vessel development|
|regulation of cell morphogenesis|
|regulation of neuron projection development|
|positive regulation of cell migration|
|cellular response to growth factor stimulus|
|vasculature development|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|regulation of protein serine/threonine kinase activity|
|cardiovascular system development|
|positive regulation of cell motility|
|response to growth factor|
|positive regulation of protein kinase activity|
|positive regulation of nervous system development|
|positive regulation of cellular component movement|
|positive regulation of cell development|
|cellular response to organic cyclic compound|
|positive regulation of MAPK cascade|
|positive regulation of locomotion|
|positive regulation of kinase activity|
|protein-containing complex|
|cellular response to organonitrogen compound|
|positive regulation of apoptotic process|
|positive regulation of programmed cell death|
|positive regulation of transferase activity|
|regulation of neuron differentiation|
|cellular response to nitrogen compound|
|neuron projection development|
|negative regulation of cell population proliferation|
|epithelial cell differentiation|
|regulation of plasma membrane bounded cell projection organization|
|positive regulation of cell death|
|perinuclear region of cytoplasm|
|negative regulation of cellular component organization|
|regulation of cell projection organization|
|negative regulation of cell differentiation|
|enzyme linked receptor protein signaling pathway|
|calcium ion binding|
|brain development|
|regulation of MAPK cascade|
|positive regulation of hydrolase activity|
|head development|
|regulation of protein kinase activity|
|neuron development|
|regulation of neurogenesis|
|regulation of cell migration|
|circulatory system development|
|regulation of kinase activity|
|regulation of cell motility|
|response to organic cyclic compound|
|regulation of nervous system development|
|regulation of cell development|
|negative regulation of developmental process|
|regulation of cellular component biogenesis|
|cell migration|
|positive regulation of cell differentiation|
|protein phosphorylation|
|regulation of transferase activity|
|central nervous system development|
|regulation of locomotion|
|regulation of cellular component movement|
|response to organonitrogen compound|
|neuron differentiation|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|regulation of anatomical structure morphogenesis|
|cell motility|
|localization of cell|
|response to nitrogen compound|
|epithelium development|
|plasma membrane bounded cell projection organization|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|cell projection organization|
|negative regulation of multicellular organismal process|
|positive regulation of cellular component organization|
|cellular response to endogenous stimulus|
|positive regulation of protein modification process|
|regulation of hydrolase activity|
|phosphorylation|
|locomotion|
|G protein-coupled receptor signaling pathway|
|positive regulation of developmental process|
|integral component of plasma membrane|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|response to endogenous stimulus|
|negative regulation of cellular biosynthetic process|
|generation of neurons|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|movement of cell or subcellular component|
|response to oxygen-containing compound|
|regulation of programmed cell death|
|cellular protein localization|
|regulation of phosphorylation|
|cellular macromolecule localization|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|neurogenesis|
|cell development|
|positive regulation of signal transduction|
|regulation of cell death|
|intracellular signal transduction|
|positive regulation of protein metabolic process|
|positive regulation of multicellular organismal process|
|tissue development|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|membrane|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp134|MS023 2μM R03 exp134]]|-2.16|
|[[:results:exp484|GSK-J5 1.5μM R08 exp484]]|-2.03|
|[[:results:exp474|CR131-b 0.005μM R08 exp474]]|-2.02|
|[[:results:exp128|GSK591 2.6μM R03 exp128]]|-1.82|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 18904
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.82 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='RAPGEF2 Expression in NALM6 Cells: 6.82'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>