Rapgef4 Rap guanine nucleotide exchange factor 4 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Rapgef4provided by RGD
Official Full Name: Rap guanine nucleotide exchange factor 4provided by RGD
Primary source: RGD:621886
See related: Ensembl:ENSRNOG00000001516 AllianceGenome:RGD:621886
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: CAMPS; Cgef2; Epac2; CAMP-GEFII
Summary: Enables cAMP binding activity and guanyl-nucleotide exchange factor activity. Involved in several processes, including animal organ development; positive regulation of neuronal action potential; and regulation of neurotransmitter receptor localization to postsynaptic specialization membrane. Located in several cellular components, including basolateral plasma membrane; brush border; and distal axon. Part of protein-containing complex. Is active in glutamatergic synapse and postsynaptic density. Human ortholog(s) of this gene implicated in autistic disorder. Orthologous to human RAPGEF4 (Rap guanine nucleotide exchange factor 4). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in Brain (RPKM 362.2), Adrenal (RPKM 149.7) and 5 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 3q23

Exon count:: 36

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	3	NC_086021.1 (77217024..77509933)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	3	NC_051338.1 (56809388..57101332)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	3	NC_005102.4 (58632338..58925127)

Chromosome 3 - NC_086021.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Exchange protein directly activated by cAMP 2 is required for corticotropin-releasing hormone-mediated spine loss.
Title: Exchange protein directly activated by cAMP 2 is required for corticotropin-releasing hormone-mediated spine loss.
Epac1/Epac2 and CaM can play a key role in arrhythmogenesis development under conditions of alcoholic cardiomyopathy.
Title: Epac Proteins and Calmodulin as Possible Arrhythmogenesis Trigger in Alcoholic Cardiomyopathy.
Data suggest that Rap2A is the obligate effector for Epac2 in mediating growth arrest and reversal of neurite extension through activation of MAP kinase signaling via protein phosphorylation/farnesylation in neuroendocrine cells. (Rap2A = RAS oncogene family member Rap2A; Epac2 = guanine nucleotide exchange factor Epac2)
Title: Guanine nucleotide exchange factor Epac2-dependent activation of the GTP-binding protein Rap2A mediates cAMP-dependent growth arrest in neuroendocrine cells.
Rap guanine nucleotide exchange factors Epac1 and Epac2 induces the phosphorylation of extracellular signal-regulated kinases ERK1/2 in pituitary tumor GH3 cells.
Title: Exchange proteins directly activated by cAMP induce the proliferation of rat anterior pituitary GH3 cells via the activation of extracellular signal-regulated kinase.
Data suggest activation of EPAC1/2 (exchange proteins activated by cAMP) and Rap1 (RAS-related GTP-binding protein 1) in hepatic stellate cells down-regulates proliferation and synthesis of a-smooth muscle actin/collagen I/collagen II in an in vitro model of alcoholic cirrhosis (AC); in AC, expression of EPAC1 is down-regulated but expression of EPAC2 is up-regulated; EPAC1 activation increases GTP-bound (activated) Rap1.
Title: EPAC activation inhibits acetaldehyde-induced activation and proliferation of hepatic stellate cell via Rap1.
Suggest that EPAC1/2 and RAP1 are the crucial factors for endometrial decidualization in rat pregnancy.
Title: Possible roles of the cAMP-mediators EPAC and RAP1 in decidualization of rat uterus.
Inhibition of adenylate cyclase (SQ-22536) abolished the positive interaction between stimuli and the Epac (exchange proteins activated by cAMP) activator 8-pCPT-2'-O-Me-cAMP reversed the effect of adenylate cyclase inhibition
Title: Cyclic AMP and Epac contribute to the genesis of the positive interaction between hypoxia and hypercapnia in the carotid body.
investigated whether PKA, Epac (isoforms -1, and -2_, and/or cytosolic oxidation, activate specific proteins required to produce a plasmalemmal seal
Title: Pathways for plasmalemmal repair mediated by PKA, Epac, and cytosolic oxidation in rat B104 cells in vitro and rat sciatic axons ex vivo.
these results provide evidence that Epac1 and Epac2 are differentially expressed within the retina and provide the framework for further functional studies of cAMP pathways within the retina
Title: Differential distribution of exchange proteins directly activated by cyclic AMP within the adult rat retina.
This study identify Epac2 promotes dynamic remodeling and depression of spiny synapses, disruption of which may contribute to some aspects of disease.
Title: Epac2 induces synapse remodeling and depression and its disease-associated forms alter spines.

Submit: New GeneRIF Correction See all GeneRIFs (11)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D3Mco27 (e-PCR)
- UniSTS:239921

AU028588 (e-PCR)
- UniSTS:116024

AU026608 (e-PCR)
- UniSTS:114114

Rapgef4 (e-PCR), detects polymorphism
- UniSTS:507860

AU025014 (e-PCR)
- UniSTS:115681

RH144457 (e-PCR)
- UniSTS:233702

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables cAMP binding	IDA Inferred from Direct Assay more info	PubMed
enables cAMP binding	IEA Inferred from Electronic Annotation more info
enables cAMP binding	ISO Inferred from Sequence Orthology more info
enables cAMP binding	ISS Inferred from Sequence or Structural Similarity more info
enables guanyl-nucleotide exchange factor activity	IBA Inferred from Biological aspect of Ancestor more info
enables guanyl-nucleotide exchange factor activity	IDA Inferred from Direct Assay more info	PubMed
enables guanyl-nucleotide exchange factor activity	IEA Inferred from Electronic Annotation more info
enables guanyl-nucleotide exchange factor activity	ISO Inferred from Sequence Orthology more info
enables guanyl-nucleotide exchange factor activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	IDA Inferred from Direct Assay more info	PubMed
enables protein-macromolecule adaptor activity	IEA Inferred from Electronic Annotation more info
enables protein-macromolecule adaptor activity	ISO Inferred from Sequence Orthology more info
enables small GTPase binding	IEA Inferred from Electronic Annotation more info
enables small GTPase binding	ISO Inferred from Sequence Orthology more info
enables small GTPase binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in Ras protein signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in adenylate cyclase-activating G protein-coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within adenylate cyclase-activating G protein-coupled receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in adenylate cyclase-activating G protein-coupled receptor signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within adenylate cyclase-modulating G protein-coupled receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in calcium-ion regulated exocytosis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within calcium-ion regulated exocytosis	ISO Inferred from Sequence Orthology more info
involved_in cellular response to nerve growth factor stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in ganglion development	IEP Inferred from Expression Pattern more info	PubMed
involved_in heart development	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within_positive_effect hormone secretion	ISO Inferred from Sequence Orthology more info
involved_in insulin secretion	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within insulin secretion	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of synaptic transmission	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of insulin secretion	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of insulin secretion	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of neuronal action potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of smooth muscle cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of dendrite development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of exocytosis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of exocytosis	ISO Inferred from Sequence Orthology more info
involved_in regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of postsynapse organization	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of postsynapse organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of synaptic vesicle cycle	IEA Inferred from Electronic Annotation more info
involved_in regulation of synaptic vesicle cycle	ISO Inferred from Sequence Orthology more info
involved_in response to benzene	IEP Inferred from Expression Pattern more info	PubMed
involved_in small GTPase-mediated signal transduction	IEA Inferred from Electronic Annotation more info
involved_in spinal cord development	IEP Inferred from Expression Pattern more info	PubMed

Component	Evidence Code	Pubs
located_in apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in axon	IDA Inferred from Direct Assay more info	PubMed
located_in basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in brush border	IDA Inferred from Direct Assay more info	PubMed
located_in cone cell pedicle	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IEA Inferred from Electronic Annotation more info
is_active_in cytosol	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in dendrite	IDA Inferred from Direct Assay more info	PubMed
located_in dendritic spine	IDA Inferred from Direct Assay more info	PubMed
located_in excitatory synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	EXP Inferred from Experiment more info	PubMed
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	IMP Inferred from Mutant Phenotype more info	PubMed
located_in growth cone	IDA Inferred from Direct Assay more info	PubMed
located_in hippocampal mossy fiber to CA3 synapse	IEA Inferred from Electronic Annotation more info
is_active_in hippocampal mossy fiber to CA3 synapse	ISO Inferred from Sequence Orthology more info
located_in neuronal cell body	IDA Inferred from Direct Assay more info	PubMed
located_in photoreceptor inner segment	IDA Inferred from Direct Assay more info	PubMed
located_in photoreceptor outer segment	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in postsynaptic density	IDA Inferred from Direct Assay more info	PubMed
is_active_in presynapse	EXP Inferred from Experiment more info	PubMed
is_active_in presynapse	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: rap guanine nucleotide exchange factor 4

Names: Rap guanine nucleotide exchange factor (GEF) 4; cAMP-regulated guanine nucleotide exchange factor II; epac 2; exchange factor directly activated by cAMP 2; exchange protein directly activated by cAMP 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001100642.1 → NP_001094112.1 rap guanine nucleotide exchange factor 4

Status: VALIDATED

Source sequence(s)

JAXUCZ010000003

UniProtKB/TrEMBL

A0A8I6B2Y4, D3KR63, F1LQ26

Related

ENSRNOP00000010630.8, ENSRNOT00000010630.8

Conserved Domains (4) summary

smart00147
Location:768 → 1009

RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases

cd00038
Location:43 → 158

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

cd04437
Location:206 → 334

DEP_Epac; DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in Epac-like proteins. Epac (exchange proteins directly activated by cAMP) proteins are GEFs (guanine-nucleotide-exchange factors) for the small GTPases, Rap1 and Rap2. They are directly regulated by ...

pfam00618
Location:499 → 605

RasGEF_N; RasGEF N-terminal motif

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCr8

Genomic

NC_086021.1 Reference GRCr8

Range

77217024..77509933

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_039104344.2 → XP_038960272.1 rap guanine nucleotide exchange factor 4 isoform X1

UniProtKB/TrEMBL

A0A8I6A857, A0A8I6B2Y4

Related

ENSRNOP00000087630.1

Conserved Domains (4) summary

smart00147
Location:750 → 991

RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases

cd00038
Location:43 → 158

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

cd04437
Location:188 → 316

DEP_Epac; DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in Epac-like proteins. Epac (exchange proteins directly activated by cAMP) proteins are GEFs (guanine-nucleotide-exchange factors) for the small GTPases, Rap1 and Rap2. They are directly regulated by ...

pfam00618
Location:481 → 587

RasGEF_N; RasGEF N-terminal motif
XM_039104345.2 → XP_038960273.1 rap guanine nucleotide exchange factor 4 isoform X2

UniProtKB/TrEMBL

A0A8I6GEV8, A0A8I6GLW9

Related

ENSRNOP00000086379.1

Conserved Domains (4) summary

smart00147
Location:624 → 865

RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases

cd00038
Location:212 → 323

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

cd04437
Location:62 → 190

DEP_Epac; DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in Epac-like proteins. Epac (exchange proteins directly activated by cAMP) proteins are GEFs (guanine-nucleotide-exchange factors) for the small GTPases, Rap1 and Rap2. They are directly regulated by ...

pfam00618
Location:355 → 461

RasGEF_N; RasGEF N-terminal motif
XM_039104346.2 → XP_038960274.1 rap guanine nucleotide exchange factor 4 isoform X4

UniProtKB/TrEMBL

A0A8I6GLW9

Conserved Domains (4) summary

smart00147
Location:606 → 847

RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases

cd00038
Location:194 → 305

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

cd04437
Location:44 → 172

DEP_Epac; DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in Epac-like proteins. Epac (exchange proteins directly activated by cAMP) proteins are GEFs (guanine-nucleotide-exchange factors) for the small GTPases, Rap1 and Rap2. They are directly regulated by ...

pfam00618
Location:337 → 443

RasGEF_N; RasGEF N-terminal motif
XM_063283144.1 → XP_063139214.1 rap guanine nucleotide exchange factor 4 isoform X3

UniProtKB/TrEMBL

A0A8I6GLW9
XM_063283145.1 → XP_063139215.1 rap guanine nucleotide exchange factor 4 isoform X5

UniProtKB/TrEMBL

A0A8I6GLW9
XM_063283146.1 → XP_063139216.1 rap guanine nucleotide exchange factor 4 isoform X5

UniProtKB/TrEMBL

A0A8I6GLW9
XM_063283147.1 → XP_063139217.1 rap guanine nucleotide exchange factor 4 isoform X5

UniProtKB/TrEMBL

A0A8I6GLW9