RAPGEF3 Rap guanine nucleotide exchange factor 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: RAPGEF3provided by HGNC
Official Full Name: Rap guanine nucleotide exchange factor 3provided by HGNC
Primary source: HGNC:HGNC:16629
See related: Ensembl:ENSG00000079337 MIM:606057; AllianceGenome:HGNC:16629
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: EPAC; EPAC1; bcm910; HSU79275; CAMP-GEFI
Summary: Enables guanyl-nucleotide exchange factor activity and protein domain specific binding activity. Involved in several processes, including Rap protein signal transduction; cellular response to cAMP; and regulation of syncytium formation by plasma membrane fusion. Located in several cellular components, including filopodium; lamellipodium; and microvillus. Biomarker of congestive heart failure. [provided by Alliance of Genome Resources, Nov 2024]
Expression: Broad expression in fat (RPKM 15.0), thyroid (RPKM 13.2) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q13.11

Exon count:: 30

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (47734363..47758880, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (47695675..47720196, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (48128146..48152663, complement)

Chromosome 12 - NC_000012.12 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: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Protein SUMOylation promotes cAMP-independent EPAC1 activation.
Title: Protein SUMOylation promotes cAMP-independent EPAC1 activation.
EPAC1 enhances brown fat growth and beige adipogenesis.
Title: EPAC1 enhances brown fat growth and beige adipogenesis.
Cyclic AMP induces reversible EPAC1 condensates that regulate histone transcription.
Title: Cyclic AMP induces reversible EPAC1 condensates that regulate histone transcription.
EPAC Regulates Melanoma Growth by Stimulating mTORC1 Signaling and Loss of EPAC Signaling Dependence Correlates with Melanoma Progression.
Title: EPAC Regulates Melanoma Growth by Stimulating mTORC1 Signaling and Loss of EPAC Signaling Dependence Correlates with Melanoma Progression.
Absence of EPAC1 Signaling to Stabilize CFTR in Intestinal Organoids.
Title: Absence of EPAC1 Signaling to Stabilize CFTR in Intestinal Organoids.
Origin and Isoform Specific Functions of Exchange Proteins Directly Activated by cAMP: A Phylogenetic Analysis.
Title: Origin and Isoform Specific Functions of Exchange Proteins Directly Activated by cAMP: A Phylogenetic Analysis.
Identification and Characterization of an Affimer Affinity Reagent for the Detection of the cAMP Sensor, EPAC1.
Title: Identification and Characterization of an Affimer Affinity Reagent for the Detection of the cAMP Sensor, EPAC1.
Epac: new emerging cAMP-binding protein.
Title: Epac: new emerging cAMP-binding protein.
Multiple Rap1 effectors control Epac1-mediated tightening of endothelial junctions.
Title: Multiple Rap1 effectors control Epac1-mediated tightening of endothelial junctions.
GRKs and Epac1 Interaction in Cardiac Remodeling and Heart Failure.
Title: GRKs and Epac1 Interaction in Cardiac Remodeling and Heart Failure.

Submit: New GeneRIF Correction See all GeneRIFs (148)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of Rap guanine nucleotide exchange factor (GEF) 3 (RAPGEF3; CAMP-GEFI) by siRNA enhances the early stages of HIV-1 replication in HeLa-CD4 cells infected with viral pseudotypes HIV89.6R and HIV8.2N	PubMed
Knockdown of Rap guanine nucleotide exchange factor 3 (RAPGEF3; CAMP-GEFI) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
capsid	gag	Prostaglandin E2-mediated HIV-1 inhibition requires the EPAC/RAP/RhoA signaling pathway by downregulation of HIV-1 CA production	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D12S1212E (e-PCR)
- UniSTS:151467

WI-22224 (e-PCR)
- UniSTS:69072

Rapgef3 (e-PCR), detects polymorphism
- UniSTS:507859

RH91422 (e-PCR)
- UniSTS:87009

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cAMP binding	TAS Traceable Author Statement more info
enables guanyl-nucleotide exchange factor activity	EXP Inferred from Experiment more info	PubMed
enables guanyl-nucleotide exchange factor activity	IBA Inferred from Biological aspect of Ancestor more info
enables guanyl-nucleotide exchange factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in Rap protein signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in Ras protein signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in adaptive immune response	TAS Traceable Author Statement more info
involved_in adenylate cyclase-activating G protein-coupled receptor signaling pathway	NAS Non-traceable Author Statement more info	PubMed
involved_in angiogenesis	IEA Inferred from Electronic Annotation more info
involved_in associative learning	IEA Inferred from Electronic Annotation more info
involved_in cellular response to cAMP	IDA Inferred from Direct Assay more info	PubMed
involved_in establishment of endothelial barrier	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of syncytium formation by plasma membrane fusion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of GTPase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein export from nucleus	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of stress fiber assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of syncytium formation by plasma membrane fusion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of actin cytoskeleton organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of insulin secretion	TAS Traceable Author Statement more info
involved_in regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
colocalizes_with cortical actin cytoskeleton	IDA Inferred from Direct Assay more info	PubMed
located_in endomembrane system	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in filopodium	IDA Inferred from Direct Assay more info	PubMed
located_in lamellipodium	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	TAS Traceable Author Statement more info	PubMed
located_in microvillus	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: rap guanine nucleotide exchange factor 3

Names: 9330170P05Rik; EPAC 1; Rap guanine nucleotide exchange factor (GEF) 3; Rap1 guanine-nucleotide-exchange factor directly activated by cAMP; cAMP-regulated guanine nucleotide exchange factor I; exchange factor directly activated by cAMP 1; exchange protein directly activated by cAMP 1

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_001098531.4 → NP_001092001.2 rap guanine nucleotide exchange factor 3 isoform a

Status: VALIDATED

Description

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

Source sequence(s)

AC004241

Consensus CDS

CCDS41775.1

UniProtKB/Swiss-Prot

A8K2G5, E7EQC8, O95398, O95634, Q8WVN0

UniProtKB/TrEMBL

Q569L6

Related

ENSP00000395708.2, ENST00000449771.7

Conserved Domains (4) summary

cd06224
Location:392 → 511

REM; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately ...

cd00038
Location:247 → 356

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 ...

cd00155
Location:658 → 890

RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. ...

cd04437
Location:100 → 223

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 ...
NM_001098532.2 → NP_001092002.1 rap guanine nucleotide exchange factor 3 isoform b

See identical proteins and their annotated locations for NP_001092002.1

Status: VALIDATED

Description

Transcript Variant: This variant (3) contains an alternate 5' end and differs in the 5' UTR, compared to variant 1. These differences cause translation initiation at a downstream AUG and an isoform (b) with a shorter N-terminus compared to isoform a. Variants 2 and 3 encode the same isoform.

Source sequence(s)

AC004241, AK092448, BQ007070, CN294139, DB179165, DB278856, U79275

Consensus CDS

CCDS31784.1

UniProtKB/TrEMBL

Q569L6

Conserved Domains (5) summary

cd06224
Location:350 → 469

REM; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately ...

COG0664
Location:226 → 304

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

cd00038
Location:205 → 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 ...

cd00155
Location:616 → 848

RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. ...

cd04437
Location:58 → 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 ...
NM_006105.5 → NP_006096.2 rap guanine nucleotide exchange factor 3 isoform b

See identical proteins and their annotated locations for NP_006096.2

Status: VALIDATED

Description

Transcript Variant: This variant (2) contains an alternate 5' exon and differs in the 5' UTR, compared to variant 1. These differences cause translation initiation at a downstream AUG and an isoform (b) with a shorter N-terminus compared to isoform a. Variants 2 and 3 encode the same isoform.

Source sequence(s)

AC004241, AK092448, BQ007070, CN294139, DA629958, U79275

Consensus CDS

CCDS31784.1

UniProtKB/TrEMBL

Q569L6

Related

ENSP00000384521.2, ENST00000405493.6

Conserved Domains (5) summary

cd06224
Location:350 → 469

REM; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately ...

COG0664
Location:226 → 304

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

cd00038
Location:205 → 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 ...

cd00155
Location:616 → 848

RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. ...

cd04437
Location:58 → 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 ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

47734363..47758880 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011537752.3 → XP_011536054.1 rap guanine nucleotide exchange factor 3 isoform X1

UniProtKB/TrEMBL

Q569L6

Conserved Domains (5) summary

cd06224
Location:407 → 526

REM; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately ...

COG0664
Location:283 → 361

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

cd00038
Location:262 → 371

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 ...

cd00155
Location:673 → 905

RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. ...

cd04437
Location:100 → 238

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 ...
XM_011537755.2 → XP_011536057.1 rap guanine nucleotide exchange factor 3 isoform X2

UniProtKB/TrEMBL

Q569L6

Conserved Domains (5) summary

cd06224
Location:365 → 484

REM; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately ...

COG0664
Location:241 → 319

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

cd00038
Location:220 → 329

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 ...

cd00155
Location:631 → 863

RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. ...

cd04437
Location:58 → 196

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 ...
XM_011537758.3 → XP_011536060.1 rap guanine nucleotide exchange factor 3 isoform X4

UniProtKB/TrEMBL

Q569L6

Conserved Domains (5) summary

cd06224
Location:248 → 367

REM; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately ...

COG0664
Location:124 → 202

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

cd00038
Location:103 → 212

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 ...

cd00155
Location:514 → 746

RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. ...

cl02442
Location:32 → 79

DEP; DEP domain, named after Dishevelled, Egl-10, and Pleckstrin, where this domain was first discovered. The function of this domain is still not clear, but it is believed to be important for the membrane association of the signaling proteins in which it is ...
XM_005268571.4 → XP_005268628.1 rap guanine nucleotide exchange factor 3 isoform X6

UniProtKB/TrEMBL

B3KWQ0

Conserved Domains (2) summary

cd06224
Location:1 → 83

REM; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately ...

cd00155
Location:230 → 462

RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. ...
XM_047428081.1 → XP_047284037.1 rap guanine nucleotide exchange factor 3 isoform X3
XM_017018688.3 → XP_016874177.1 rap guanine nucleotide exchange factor 3 isoform X5

Related

ENSP00000378764.3, ENST00000395358.7

RNA

XR_001748551.3 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060936.1 Alternate T2T-CHM13v2.0

Range

47695675..47720196 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054370767.1 → XP_054226742.1 rap guanine nucleotide exchange factor 3 isoform X1
XM_054370768.1 → XP_054226743.1 rap guanine nucleotide exchange factor 3 isoform X2
XM_054370770.1 → XP_054226745.1 rap guanine nucleotide exchange factor 3 isoform X4
XM_054370772.1 → XP_054226747.1 rap guanine nucleotide exchange factor 3 isoform X6
XM_054370769.1 → XP_054226744.1 rap guanine nucleotide exchange factor 3 isoform X3
XM_054370771.1 → XP_054226746.1 rap guanine nucleotide exchange factor 3 isoform X5