Rapgef4 Rap guanine nucleotide exchange factor (GEF) 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Rapgef4provided by MGI
Official Full Name: Rap guanine nucleotide exchange factor (GEF) 4provided by MGI
Primary source: MGI:MGI:1917723
See related: Ensembl:ENSMUSG00000049044 AllianceGenome:MGI:1917723
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Epac2; EPAC 2; Epac-2; mKIAA4040; 1300003D15Rik; 5730402K07Rik; 6330581N18Rik
Summary: Enables cAMP binding activity; guanyl-nucleotide exchange factor activity; and small GTPase binding activity. Involved in regulation of synaptic vesicle cycle. Acts upstream of or within adenylate cyclase-activating G protein-coupled receptor signaling pathway; regulation of exocytosis; and secretion by cell. Located in cytosol and hippocampal mossy fiber to CA3 synapse. Is expressed in several structures, including adrenal gland; ganglia; heart; lung; and metanephros. 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 cortex adult (RPKM 46.5), frontal lobe adult (RPKM 40.1) and 5 other tissues See more
Orthologs: human all
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Genomic context

Location:: 2 C3; 2 42.9 cM

Exon count:: 35

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	2	NC_000068.8 (71811559..72087818)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	2	NC_000068.7 (71981215..72257474)

Chromosome 2 - NC_000068.8 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Epac-2 ameliorates spontaneous colitis in Il-10(-/-) mice by protecting the intestinal barrier and suppressing NF-kappaB/MAPK signalling.
Title: Epac-2 ameliorates spontaneous colitis in Il-10(-/-) mice by protecting the intestinal barrier and suppressing NF-κB/MAPK signalling.
Epac1-/- and Epac2-/- mice exhibit deficient epithelial Na+ channel regulation and impaired urinary Na+ conservation.
Title: Epac1-/- and Epac2-/- mice exhibit deficient epithelial Na+ channel regulation and impaired urinary Na+ conservation.
Exchange Protein Directly Activated by cAMP 2 Enhances Respiratory Syncytial Virus-Induced Pulmonary Disease in Mice.
Title: Exchange Protein Directly Activated by cAMP 2 Enhances Respiratory Syncytial Virus-Induced Pulmonary Disease in Mice.
Autophagy activity contributes to the impairment of social recognition in Epac2(-/-) mice.
Title: Autophagy activity contributes to the impairment of social recognition in Epac2(-/-) mice.
Regulation of Mitochondrial Function by Epac2 Contributes to Acute Inflammatory Hyperalgesia.
Title: Regulation of Mitochondrial Function by Epac2 Contributes to Acute Inflammatory Hyperalgesia.
Mice depleted for Exchange Proteins Directly Activated by cAMP (Epac) exhibit irregular liver regeneration in response to partial hepatectomy.
Title: Mice depleted for Exchange Proteins Directly Activated by cAMP (Epac) exhibit irregular liver regeneration in response to partial hepatectomy.
The present data suggest that a PKA-independent cAMP signaling pathway via Epac2 may be party to adult neurogenesis.
Title: Cell-specific expression of Epac2 in the subventricular and subgranular zones.
When glucose metabolism induces insulin secretion, it also increases formation of Golgi-derived microtubules (GDMTs), notably with the same biphasic kinetics as insulin exocytosis. Furthermore, GDMT nucleation is controlled by a glucose signal-transduction pathway through cAMP and its effector EPAC2.
Title: Regulation of Glucose-Dependent Golgi-Derived Microtubules by cAMP/EPAC2 Promotes Secretory Vesicle Biogenesis in Pancreatic β Cells.
Barr1 can directly interact with Epac2; sulfonylureas such as glibenclamide promote Barr1/Epac2 complex formation, triggering enhanced Rap1 signaling and insulin secretion
Title: β-Cell-intrinsic β-arrestin 1 signaling enhances sulfonylurea-induced insulin secretion.
Epac has a protecting effect on asthmatic airway inflammation and airway remodeling, and reduces airway smooth muscle cells proliferation by inhibiting SOCE.
Title: Exchange protein directly activated by cAMP (Epac) protects against airway inflammation and airway remodeling in asthmatic mice.

Submit: New GeneRIF Correction See all GeneRIFs (42)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Gene trapped (1)
Targeted (10) 1 citation
Endonuclease-mediated (2)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:225103

D10Mit157.2 (e-PCR), detects polymorphism
- UniSTS:126061

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

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables cAMP binding	IDA Inferred from Direct Assay more info	PubMed
enables cAMP binding	ISO Inferred from Sequence Orthology 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	ISO Inferred from Sequence Orthology more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	ISO Inferred from Sequence Orthology more info
enables protein-macromolecule adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables small GTPase binding	IPI Inferred from Physical Interaction more info	PubMed

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

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

General protein information

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Preferred Names: rap guanine nucleotide exchange factor 4

Names: cAMP-GEFII; cAMP-dependent Rap1 guanine-nucleotide exchange factor; cAMP-regulated guanine nucleotide exchange factor IIB; 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_001204165.1 → NP_001191094.1 rap guanine nucleotide exchange factor 4 isoform 1

See identical proteins and their annotated locations for NP_001191094.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AK220281, BP767789

Consensus CDS

CCDS57176.1

UniProtKB/Swiss-Prot

Q8VIP9, Q9CW52, Q9EQZ6, Q9Z1P0

UniProtKB/TrEMBL

A2ASW4, Q571A8

Related

ENSMUSP00000088336.6, ENSMUST00000090826.12

Conserved Domains (5) summary

smart00147
Location:768 → 1009

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

COG0664
Location:38 → 158

Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]

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
NM_001204166.1 → NP_001191095.1 rap guanine nucleotide exchange factor 4 isoform 3

See identical proteins and their annotated locations for NP_001191095.1

Status: VALIDATED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon in an alternate exon, compared to variant 1. The encoded isoform (3) has a distinct N-terminus and is shorter than isoform 1.

Source sequence(s)

AB445011, AK004874, BP767789, CK622268

Consensus CDS

CCDS57177.1

UniProtKB/TrEMBL

A2ASW8, Q571A8

Related

ENSMUSP00000028525.6, ENSMUST00000028525.6

Conserved Domains (5) summary

smart00147
Location:624 → 865

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

COG0664
Location:207 → 314

Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]

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
NM_001204167.1 → NP_001191096.1 rap guanine nucleotide exchange factor 4 isoform 4

Status: VALIDATED

Description

Transcript Variant: This variant (4) differs in the 3' UTR and lacks a portion of the 3' coding region, compared to variant 1. The encoded isoform (4) has a distinct C-terminus and is shorter than isoform 1.

Source sequence(s)

AK017479, AK220281, AL929498

UniProtKB/TrEMBL

Q9CS95

Conserved Domains (2) summary

COG0664
Location:38 → 158

Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]

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 ...
NM_001355478.1 → NP_001342407.1 rap guanine nucleotide exchange factor 4 isoform 5

Status: VALIDATED

Description

Transcript Variant: This variant (5) differs in the 5' UTR, lacks a portion of the 5' coding region, lacks an alternate in-frame exon, and initiates translation at a downstream start codon in an alternate exon, compared to variant 1. The encoded isoform (5) has a distinct N-terminus and is shorter than isoform 1.

Source sequence(s)

AL928617, AL928699, AL929498

UniProtKB/TrEMBL

Q571A8

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
NM_019688.2 → NP_062662.1 rap guanine nucleotide exchange factor 4 isoform 2

See identical proteins and their annotated locations for NP_062662.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an exon in the 5' coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.

Source sequence(s)

AF115480, AK004874, AK220281, BP767789

Consensus CDS

CCDS16120.1

UniProtKB/TrEMBL

Q571A8

Related

ENSMUSP00000099759.4, ENSMUST00000102698.10

Conserved Domains (5) summary

smart00147
Location:750 → 991

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

COG0664
Location:38 → 158

Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]

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

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000068.8 Reference GRCm39 C57BL/6J

Range

71811559..72087818

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_030251899.2 → XP_030107759.1 rap guanine nucleotide exchange factor 4 isoform X1

UniProtKB/TrEMBL

Q571A8

Conserved Domains (4) summary

smart00147
Location:615 → 856

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

cd00038
Location:203 → 314

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:53 → 181

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:346 → 452

RasGEF_N; RasGEF N-terminal motif
XM_006499938.5 → XP_006500001.1 rap guanine nucleotide exchange factor 4 isoform X3

Conserved Domains (4) summary

smart00147
Location:548 → 789

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

cd00038
Location:136 → 247

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:1 → 114

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:279 → 385

RasGEF_N; RasGEF N-terminal motif
XM_036162415.1 → XP_036018308.1 rap guanine nucleotide exchange factor 4 isoform X2

UniProtKB/TrEMBL

Q571A8

Related

ENSMUST00000153887.8

Conserved Domains (4) summary

smart00147
Location:596 → 837

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

cd00038
Location:184 → 295

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:34 → 162

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:327 → 433

RasGEF_N; RasGEF N-terminal motif