RAPGEF2
entrez
9693
canonical
uniprot
Q9Y4G8
canonical
ensembl
ENSG00000109756
resolver
ensp
ENSP00000264431
resolver
ensp
ENSP00000495298
resolver
ensp
ENSP00000495906
resolver
ensp
ENSP00000510694
resolver
ensp
ENSP00000516108
resolver
enst
ENST00000505026
resolver
genesymbol
RAPGEF2
resolver
genesymbol_syn
KIAA0313
resolver
genesymbol_syn
NRAPGEP
resolver
genesymbol_syn
PDZGEF1
resolver
hgnc
HGNC:16854
resolver
uniprot
A0A8I5KZ40
resolver
uniprot
A0A994J7S7
resolver
uniprot
D3DP27
resolver
uniprot_entry
A0A994J7S7_HUMAN
resolver
uniprot_entry
RPGF2_HUMAN
resolver
uniprot_sec
A0A8I5KZ40
resolver
uniprot_sec
D3DP27
resolver
amino_acid_sequence
MKPLAIPANHGVMGQQEKHSLPADFTKLHLTDSLHPQVTHVSSSHSGCSITSDSGSSSLSDIYQATESEAGDMDLSGLPETAVDSEDDDDEEDIERASDPLMSRDIVRDCLEKDPIDRTDDDIEQLLEFMHQLPAFANMTMSVRRELCAVMVFAVVERAGTIVLNDGEELDSWSVILNGSVEVTYPDGKAEILCMGNSFGVSPTMDKEYMKGVMRTKVDDCQFVCIAQQDYCRILNQVEKNMQKVEEEGEIVMVKEHRELDRTGTRKGHIVIKGTSERLTMHLVEEHSVVDPTFIEDFLLTYRTFLSSPMEVGKKLLEWFNDPSLRDKVTRVVLLWVNNHFNDFEGDPAMTRFLEEFENNLEREKMGGHLRLLNIACAAKAKRRLMTLTKPSREAPLPFILLGGSEKGFGIFVDSVDSGSKATEAGLKRGDQILEVNGQNFENIQLSKAMEILRNNTHLSITVKTNLFVFKELLTRLSEEKRNGAPHLPKIGDIKKASRYSIPDLAVDVEQVIGLEKVNKKSKANTVGGRNKLKKILDKTRISILPQKPYNDIGIGQSQDDSIVGLRQTKHIPTALPVSGTLSSSNPDLLQSHHRILDFSATPDLPDQVLRVFKADQQSRYIMISKDTTAKEVVIQAIREFAVTATPDQYSLCEVSVTPEGVIKQRRLPDQLSKLADRIQLSGRYYLKNNMETETLCSDEDAQELLRESQISLLQLSTVEVATQLSMRNFELFRNIEPTEYIDDLFKLRSKTSCANLKRFEEVINQETFWVASEILRETNQLKRMKIIKHFIKIALHCRECKNFNSMFAIISGLNLAPVARLRTTWEKLPNKYEKLFQDLQDLFDPSRNMAKYRNVLNSQNLQPPIIPLFPVIKKDLTFLHEGNDSKVDGLVNFEKLRMIAKEIRHVGRMASVNMDPALMFRTRKKKWRSLGSLSQGSTNATVLDVAQTGGHKKRVRRSSFLNAKKLYEDAQMARKVKQYLSNLELEMDEESLQTLSLQCEPATNTLPKNPGDKKPVKSETSPVAPRAGSQQKAQSLPQPQQQPPPAHKINQGLQVPAVSLYPSRKKVPVKDLPPFGINSPQALKKILSLSEEGSLERHKKQAEDTISNASSQLSSPPTSPQSSPRKGYTLAPSGTVDNFSDSGHSEISSRSSIVSNSSFDSVPVSLHDERRQRHSVSIVETNLGMGRMERRTMIEPDQYSLGSYAPMSEGRGLYATATVISSPSTEELSQDQGDRASLDAADSGRGSWTSCSSGSHDNIQTIQHQRSWETLPFGHTHFDYSGDPAGLWASSSHMDQIMFSDHSTKYNRQNQSRESLEQAQSRASWASSTGYWGEDSEGDTGTIKRRGGKDVSIEAESSSLTSVTTEETKPVPMPAHIAVASSTTKGLIARKEGRYREPPPTPPGYIGIPITDFPEGHSHPARKPPDYNVALQRSRMVARSSDTAGPSSVQQPHGHPTSSRPVNKPQWHKPNESDPRLAPYQSQGFSTEEDEDEQVSAV
uniprot
proteins
disease_involvement
DISEASE: Epilepsy, familial adult myoclonic, 7 (FAME7) [MIM:618075]: A form of familial myoclonic epilepsy, a neurologic disorder characterized by cortical hand tremors, myoclonic jerks and occasional generalized or focal seizures with a non-progressive or very slowly progressive disease course. Usually, myoclonic tremor is the presenting symptom, characterized by tremulous finger movements and myoclonic jerks of the limbs increased by action and posture. In a minority of patients, seizures are the presenting symptom. Some patients exhibit mild cognitive impairment. FAME7 inheritance is autosomal dominant. {ECO:0000269|PubMed:29507423}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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. Also acts 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:10548487, PubMed:10608844, 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. Also provides 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}.
uniprot
proteins
mass_dalton
167417
uniprot
proteins
mutagenesis
MUTAGEN 211; /note="K->R: Abolishes cAMP-binding."; /evidence="ECO:0000269|PubMed:10801446"; MUTAGEN 215; /note="R->D: Does not abolish cAMP-binding."; /evidence="ECO:0000269|PubMed:10801446"; MUTAGEN 396..399; /note="PLPF->AAA: Loss of cell membrane targeting."; /evidence="ECO:0000269|PubMed:10801446"; MUTAGEN 606..626; /note="Missing: Abolishes interaction with RAP1AGTP-bound form and translocation from the cytoplasm to the perinuclear region. Does not abolish GEF activity on RAP1A."; /evidence="ECO:0000269|PubMed:11359771"; MUTAGEN 898; /note="R->D: Does not inhibit interaction with NEDD4. Does not interact with HRAS. Reduces ubiquitination."; /evidence="ECO:0000269|PubMed:11598133"; MUTAGEN 1406; /note="Y->A: Abolishes interaction with NEDD4 and NEDD4-induced ubiquitination and degradation; when associated with A-1428."; /evidence="ECO:0000269|PubMed:11598133"; MUTAGEN 1428; /note="Y->A: Abolishes interaction with NEDD4 and NEDD4-induced ubiquitination and degradation; when associated with A-1406."; /evidence="ECO:0000269|PubMed:11598133"; MUTAGEN 1497..1499; /note="SAV->AAA: No loss of cell membrane targeting."; /evidence="ECO:0000269|PubMed:10801446
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated by NEDD4, leading to proteasomal degradation. {ECO:0000269|PubMed:11598133}.; PTM: Phosphorylation by PLK2 promotes its activity. {ECO:0000250}.
uniprot
proteins
protein_family
RAPGEF2 family
uniprot
proteins
pubmed
10548487
uniprot
proteins
pubmed
10608844
uniprot
proteins
pubmed
10608883
uniprot
proteins
pubmed
10801446
uniprot
proteins
pubmed
10934204
uniprot
proteins
pubmed
11168587
uniprot
proteins
pubmed
11359771
uniprot
proteins
pubmed
11598133
uniprot
proteins
pubmed
12391161
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
16272156
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17525332
uniprot
proteins
pubmed
17724123
uniprot
proteins
pubmed
18088087
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21840392
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23800469
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
29507423
uniprot
proteins
pubmed
9205841
uniprot
proteins
sequence_length
1499
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, perinuclear region. Cell membrane. Late endosome. Cell junction {ECO:0000250}. Note=Associated with the synaptic plasma membrane. Colocalizes with ADRB1 at the plasma membrane. Synaptosome. Enriched in synaptic plasma membrane and neuronal cell body. Colocalized with CTNNB1 at cell-cell contacts (By similarity). Localized diffusely in the cytoplasm before neuronal growth factor (NGF) stimulation. Recruited to late endosomes after NGF stimulation. Colocalized with the high affinity nerve growth factor receptor NTRK1 at late endosomes. Translocated to the perinuclear region in a RAP1A-dependent manner. Translocated to the cell membrane. {ECO:0000250}.
uniprot
proteins