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

    Gene ID: 10411, updated on 4-Jan-2025

    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. Implicated in nicotine dependence. Biomarker of congestive heart failure. [provided by Alliance of Genome Resources, Jan 2025]
    Expression
    Broad expression in fat (RPKM 15.0), thyroid (RPKM 13.2) and 22 other tissues See more
    Orthologs
    NEW
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    Genomic context

    See RAPGEF3 in Genome Data Viewer
    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_000012.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6256 Neighboring gene RNA polymerase II associated protein 3 Neighboring gene H3K27ac hESC enhancers GRCh37_chr12:48099027-48099528 and GRCh37_chr12:48099529-48100028 Neighboring gene RPAP3 divergent transcript Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6258 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6259 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4394 Neighboring gene endonuclease, poly(U) specific Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4395 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr12:48131928-48133127 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6260 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6261 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:48146243-48146784 Neighboring gene Sharpr-MPRA regulatory region 8178 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6262 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6263 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:48151874-48152542 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:48152543-48153211 Neighboring gene solute carrier family 48 member 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:48167242-48167748 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:48167749-48168253 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4398 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4399 Neighboring gene histone deacetylase 7 Neighboring gene uncharacterized LOC124902926 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6264 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4400 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6266 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6265 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6267 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:48211237-48211897 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:48212615-48213188 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4402 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4403 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:48214527-48215448 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6268 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6269 Neighboring gene long intergenic non-protein coding RNA 2354

    Genomic regions, transcripts, and products

    Expression

    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    HIV-1 interactions

    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

    Pathways from PubChem

    Interactions

    General gene information

    Clone Names

    • MGC21410

    Gene Ontology Provided by GOA

    Process Evidence Code Pubs
    involved_in Rap protein signal transduction PubMed 
    involved_in Ras protein signal transduction  
    involved_in adaptive immune response  
    involved_in adenylate cyclase-activating G protein-coupled receptor signaling pathway PubMed 
    involved_in angiogenesis  
    involved_in associative learning  
    involved_in cellular response to cAMP PubMed 
    involved_in establishment of endothelial barrier PubMed 
    involved_in intracellular signal transduction PubMed 
    involved_in negative regulation of syncytium formation by plasma membrane fusion PubMed 
    involved_in positive regulation of GTPase activity PubMed 
    involved_in positive regulation of angiogenesis PubMed 
    involved_in positive regulation of protein export from nucleus PubMed 
    involved_in positive regulation of stress fiber assembly PubMed 
    involved_in positive regulation of syncytium formation by plasma membrane fusion PubMed 
    involved_in regulation of actin cytoskeleton organization PubMed 
    involved_in regulation of angiogenesis PubMed 
    involved_in regulation of insulin secretion  
    involved_in regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction PubMed 
    involved_in signal transduction PubMed 
    Component Evidence Code Pubs
    colocalizes_with cortical actin cytoskeleton PubMed 
    located_in endomembrane system  
    located_in extracellular exosome PubMed 
    located_in filopodium PubMed 
    located_in lamellipodium PubMed 
    located_in membrane PubMed 
    located_in microvillus PubMed 
    colocalizes_with plasma membrane PubMed 
    located_in plasma membrane  

    General protein information

    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)

    NEW Try the new Transcript table

    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)

    1. 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 ...
    2. 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 ...
    3. 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

    1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      47734363..47758880 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. 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 ...
    2. 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 ...
    3. 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 ...
    4. 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. ...
    5. XM_047428081.1 → XP_047284037.1  rap guanine nucleotide exchange factor 3 isoform X3

      UniProtKB/TrEMBL
      Q569L6
    6. XM_017018688.3 → XP_016874177.1  rap guanine nucleotide exchange factor 3 isoform X5

      Related
      ENSP00000378764.3, ENST00000395358.7

    RNA

    1. XR_001748551.3 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      47695675..47720196 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054370767.1 → XP_054226742.1  rap guanine nucleotide exchange factor 3 isoform X1

      UniProtKB/TrEMBL
      Q569L6
    2. XM_054370768.1 → XP_054226743.1  rap guanine nucleotide exchange factor 3 isoform X2

      UniProtKB/TrEMBL
      Q569L6
    3. XM_054370770.1 → XP_054226745.1  rap guanine nucleotide exchange factor 3 isoform X4

      UniProtKB/TrEMBL
      Q569L6
    4. XM_054370772.1 → XP_054226747.1  rap guanine nucleotide exchange factor 3 isoform X6

      UniProtKB/TrEMBL
      B3KWQ0
    5. XM_054370769.1 → XP_054226744.1  rap guanine nucleotide exchange factor 3 isoform X3

      UniProtKB/TrEMBL
      Q569L6
    6. XM_054370771.1 → XP_054226746.1  rap guanine nucleotide exchange factor 3 isoform X5

    RNA

    1. XR_008488507.1 RNA Sequence

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