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IID00897
UniprotQ9Y4G8
ProteinRap guanine nucleotide exchange factor 2
GeneRAPGEF2
OrganismHomo sapiens
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS
Network xml rdf
Structure
Experiment
  :order   disorder   conflict   PDB cluster   ProS   Pfam Domain   SEG
1499
 order/disorder by at least rule
     disorder by at least rule
     order by at least rule
 order/disorder by majority rule
Seq 747-757 Hetero dimer : IID00301Complex
 Evidence X-RAY 6qdt B Reference
       Region 6qdt B 747-748 disorder
       Region 6qdt B 749-754 order
       Region 6qdt B 755-757 disorder
Seqphosphorylation
    1159-1159 Phosphoserine
    501-501 Phosphoserine
    644-644 Phosphothreonine; by PLK2
    1176-1176 Phosphoserine; by PLK2
    806-806 Phosphoserine; by PLK2
    1120-1120 Phosphoserine
    1116-1116 Phosphoserine
    1095-1095 Phosphoserine
    1089-1089 Phosphoserine
    1080-1080 Phosphoserine
    1022-1022 Phosphoserine
    933-933 Phosphoserine; by PLK2
    930-930 Phosphoserine
 
Prediction
NeProc
Disorder 1-96,478-590,924-964,993-1386,1436-1499
Order 97-477,591-923,965-992,1387-1435
ProS 1-17,22-86,91-96,485-494,499-524,537-557,586-590,924-937,993-1003,1073-1086,1211-1215,1227-1252,1258-1282,1287-1291,1305-1312,1324-1347,1372-1379,1436-1440,1476-1488,1494-1499
AlphaFold
Disorder 1-104,138-138,238-238,240-240,259-266,346-346,479-606,749-753,860-860,918-962,1004-1499
Order 105-137,139-237,239-239,241-258,267-345,347-478,607-748,754-859,861-917,963-1003
Pfam Hmmer
PF00027 154-240 7.2e-05
PF00618 270-357 3.4e-23
PF00595 387-464 2.4e-11
PF00788 606-692 1e-19
PF00617 714-899 1.8e-55
SEG 38-62 ,84-95 ,352-364 ,1031-1046 ,1111-1125 ,1141-1162 ,1355-1369 ,1393-1412
Function
Function in SwissProt
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.