Property Summary

NCBI Gene PubMed Count 41
PubMed Score 267.66
PubTator Score 54.09

Knowledge Summary


No data available


  Differential Expression (20)

Disease log2 FC p
nephrosclerosis 1.020 4.1e-03
urothelial carcinoma -1.400 4.4e-03
malignant mesothelioma -3.300 4.2e-09
ependymoma -4.100 3.7e-14
psoriasis -1.200 5.5e-04
astrocytoma -4.300 2.5e-04
glioblastoma -4.900 3.1e-05
oligodendroglioma -2.100 5.5e-13
medulloblastoma -4.800 9.7e-10
atypical teratoid / rhabdoid tumor -4.500 3.3e-10
medulloblastoma, large-cell -4.500 3.9e-06
primitive neuroectodermal tumor -2.300 7.8e-03
adrenocortical carcinoma -2.647 1.5e-03
non-small cell lung carcinoma -1.600 6.4e-28
lung cancer 1.600 2.3e-04
lung adenocarcinoma -1.600 9.3e-21
pediatric high grade glioma -2.500 2.6e-03
pilocytic astrocytoma -1.200 4.4e-02
lung carcinoma 1.400 5.6e-10
pituitary cancer 1.800 2.6e-05

 GWAS Trait (1)

Gene RIF (25)

26390815 Data show that Epac2 is activated by cAMP and changes its structure. It is involved in cAMP-mediated signal transduction through activation of the Ras-like small GTPase and is expressed mainly in brain, neuroendocrine and endocrine tissues. [review]
25683912 Identified a conserved nuclear pore localisation signal (NPLS; amino acids 764-838 of EPAC1) in the catalytic domains of the cAMP-sensors, EPAC1 and EPAC2A. EPAC1 and EPAC2, display distinct subcellular distributions.
25378661 CALR regulated by EPAC2 in endometrial glandular epithelial cells is critical for the expression of LIF and PTGS2-mediated production of PGE2 through cAMP signaling.
25187374 Follow-up replication analyses in up to an additional 21,345 participants identified three new fasting plasma glucose loci reaching genome-wide significance in or near PDK1-RAPGEF4, KANK1, and IGF1R.
25122553 EPAC1 and EPAC2 are critical signaling intermediates in osteoclast differentiation that permit RANKL-stimulated NFkB nuclear translocation and actin rearrangements
24586238 Prostaglandin E2-mediated HIV-1 inhibition requires the EPAC/RAP/RhoA signaling pathway by downregulation of HIV-1 CA production
24169561 EPAC2-mediated CRT expression is essential for the functional and morphological differentiation of endometrial stromal cells into decidual cells
23804752 data show the expression of EPAC is blunted in HPRT-deficient neuron-like cell lines and fibroblast cells from Lesch-Nyhan syndrome (LNS) patients; propose that the alterations in EPAC/RAP1 signaling and cell migration in HPRT deficiency are crucial for neuro-developmental events that may contribute to neurological dysfunctions in LNS
22363678 Cigarette smoke extract decreased Epac1 expression, but did not affect Epac2 and PKA expression.
21454623 Mechanism of intracellular cAMP sensor Epac2 activation: cAMP-induced conformational changes identified by amide hydrogen/deuterium exchange mass spectrometry
20663796 Epac2 & Epac1 signaling pathways may be associated with cAMP-mediated functional differentiation and syncytialization of trophoblasts. Expression of Epac2 & Epac 1 in placenta at different stages was investigated.
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
20233795 Studies demonstrate the occurrence of the EPAC2 splicing variant EPAC2B in adrenocortical cancer cells and reveal the involvement of EPAC2B in cAMP-induced effects on cytoskeleton integrity and cell migration.
20200953 Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
19739231 An important time-limited role is identified for hippocampal Epac2 signaling in cognition, opening new avenues to investigate the molecular mechanisms underlying memory retrieval.
19598235 Observational study of gene-disease association. (HuGE Navigator)
19553663 Substitution of the conserved phenylalanine 435 with glycine facilitates the hinge bending and leads to a constitutively active Epac2 capable of stimulating nucleotide exchange in the absence of cAMP.
19401682 Observational study of gene-disease association. (HuGE Navigator)
19086053 Observational study of gene-disease association. (HuGE Navigator)
18854429 Epac2 signaling plays a stimulatory role in pancreatic and intestinal endocrine cells, including proglucagon transcription and glucagon and GLP-1 production.
18495799 Epac1 and Epac2 were expressed at the brush border of proximal tubules cells and in the thick ascending limbs of Henle's loop.
17284589 Epac1 and Epac2 induce a potent activation of the Ca2+-sensitive big K+ channel, slight membrane hyperpolarization, and increased after-hyperpolarization in cultured cerebellar granule cells. These effects involve activation of Rap and p38 MAPK.
15202935 a novel protein-binding partner for EPAC1 and EPAC2, light chain 2 of MAP1A (microtubule-associated protein 1A)
14593429 variants were present in five families, where they segregate with the autistic phenotype.
12469113 Mutations in the hinge of Epac can uncouple cAMP binding from its exchange activity.

AA Sequence

QDVRSYVRQLNVIDNQRTLSQMSHRLEPRRP                                           981 - 1011

Text Mined References (43)

PMID Year Title
26390815 2016 Structure and functional roles of Epac2 (Rapgef4).
25683912 2015 The cAMP sensors, EPAC1 and EPAC2, display distinct subcellular distributions despite sharing a common nuclear pore localisation signal.
25416956 2014 A proteome-scale map of the human interactome network.
25378661 2015 EPAC2-mediated calreticulin regulates LIF and COX2 expression in human endometrial glandular cells.
25187374 2015 Genome-wide association meta-analysis identifies novel variants associated with fasting plasma glucose in East Asians.
25122553 2014 Activation of EPAC1/2 is essential for osteoclast formation by modulating NF?B nuclear translocation and actin cytoskeleton rearrangements.
24722188 2014 Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism.
24169561 2014 The role of exchange protein directly activated by cyclic AMP 2-mediated calreticulin expression in the decidualization of human endometrial stromal cells.
23804752 2013 Deficiency of the purine metabolic gene HPRT dysregulates microRNA-17 family cluster and guanine-based cellular functions: a role for EPAC in Lesch-Nyhan syndrome.
22363678 2012 Anti-inflammatory role of the cAMP effectors Epac and PKA: implications in chronic obstructive pulmonary disease.
21454623 2011 Mechanism of intracellular cAMP sensor Epac2 activation: cAMP-induced conformational changes identified by amide hydrogen/deuterium exchange mass spectrometry (DXMS).
20663796 2010 Possible role of the exchange protein directly activated by cyclic AMP (Epac) in the cyclic AMP-dependent functional differentiation and syncytialization of human placental BeWo cells.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20233795 2010 Functional roles of protein kinase A (PKA) and exchange protein directly activated by 3',5'-cyclic adenosine 5'-monophosphate (cAMP) 2 (EPAC2) in cAMP-mediated actions in adrenocortical cells.
20200953 2010 Genome-wide pleiotropy of osteoporosis-related phenotypes: the Framingham Study.
19739231 2010 Exchange protein activated by cyclic AMP 2 (Epac2) plays a specific and time-limited role in memory retrieval.
19598235 2009 Genes related to sex steroids, neural growth, and social-emotional behavior are associated with autistic traits, empathy, and Asperger syndrome.
19553663 2009 Mechanism of Epac activation: structural and functional analyses of Epac2 hinge mutants with constitutive and reduced activities.
19401682 2010 High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L-DOCK4 gene region in autism susceptibility.
19086053 2009 Identification of new putative susceptibility genes for several psychiatric disorders by association analysis of regulatory and non-synonymous SNPs of 306 genes involved in neurotransmission and neurodevelopment.
18854429 2009 Epac is involved in cAMP-stimulated proglucagon expression and hormone production but not hormone secretion in pancreatic alpha- and intestinal L-cell lines.
18495799 2008 Renal expression of exchange protein directly activated by cAMP (Epac) 1 and 2.
17284589 2007 Exchange protein activated by cAMP (Epac) mediates cAMP activation of p38 MAPK and modulation of Ca2+-dependent K+ channels in cerebellar neurons.
16713569 2006 A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration.
16076873 2005 Multiple roles of Rap1 in hematopoietic cells: complementary versus antagonistic functions.
15815621 2005 Generation and annotation of the DNA sequences of human chromosomes 2 and 4.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15334074 2004 CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formation.
15202935 2004 Exchange protein directly activated by cAMP (EPAC) interacts with the light chain (LC) 2 of MAP1A.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14660679 2004 Interaction of ATP sensor, cAMP sensor, Ca2+ sensor, and voltage-dependent Ca2+ channel in insulin granule exocytosis.
14593429 2003 Screening of nine candidate genes for autism on chromosome 2q reveals rare nonsynonymous variants in the cAMP-GEFII gene.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12469113 2003 Structure and regulation of the cAMP-binding domains of Epac2.
12384139 2002 Ras and relatives--job sharing and networking keep an old family together.
11707077 2001 Characterization of the gene EPAC2: structure, chromosomal localization, tissue expression, and identification of the liver-specific isoform.
11598134 2001 Critical role of cAMP-GEFII--Rim2 complex in incretin-potentiated insulin secretion.
11438518 2001 Direct interaction of the Rab3 effector RIM with Ca2+ channels, SNAP-25, and synaptotagmin.
11056535 2000 cAMP-GEFII is a direct target of cAMP in regulated exocytosis.
10777494 2000 Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs.
9856955 1998 A family of cAMP-binding proteins that directly activate Rap1.
9789079 1998 A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.