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    RAPGEF4 Rap guanine nucleotide exchange factor 4 [ Homo sapiens (human) ]

    Gene ID: 11069, updated on 8-Apr-2018
    Official Symbol
    RAPGEF4provided by HGNC
    Official Full Name
    Rap guanine nucleotide exchange factor 4provided by HGNC
    Primary source
    HGNC:HGNC:16626
    See related
    Ensembl:ENSG00000091428 MIM:606058; Vega:OTTHUMG00000133677
    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; CGEF2; EPAC2; EPAC 2; Nbla00496; CAMP-GEFII
    Expression
    Biased expression in brain (RPKM 37.0), adrenal (RPKM 17.3) and 12 other tissues See more
    Orthologs
    Location:
    2q31.1
    Exon count:
    36
    Annotation release Status Assembly Chr Location
    109 current GRCh38.p12 (GCF_000001405.38) 2 NC_000002.12 (172735282..173052893)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (173600525..173917621)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC101929947 Neighboring gene integrin subunit alpha 6 Neighboring gene pyruvate dehydrogenase kinase 1 Neighboring gene RAPGEF4 antisense RNA 1 Neighboring gene aldehyde dehydrogenase 7 family member A1 pseudogene 2 Neighboring gene mitogen-activated protein kinase kinase kinase 20 Neighboring gene MAP3K20 antisense RNA 1 Neighboring gene VISTA enhancer hs242 Neighboring gene uncharacterized LOC105373743

    • Project title: 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 Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    NHGRI GWAS Catalog

    Description
    Genome-wide association meta-analysis identifies novel variants associated with fasting plasma glucose in East Asians.
    NHGRI GWA Catalog

    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

    • Adaptive Immune System, organism-specific biosystem (from REACTOME)
      Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
    • Adrenergic signaling in cardiomyocytes, organism-specific biosystem (from KEGG)
      Adrenergic signaling in cardiomyocytes, organism-specific biosystemCardiac myocytes express at least six subtypes of adrenergic receptor (AR) which include three subtypes of beta-AR (beta-1, beta-2, beta-3) and three subtypes of the alpha-1-AR (alpha-1A, alpha-1B, a...
    • Adrenergic signaling in cardiomyocytes, conserved biosystem (from KEGG)
      Adrenergic signaling in cardiomyocytes, conserved biosystemCardiac myocytes express at least six subtypes of adrenergic receptor (AR) which include three subtypes of beta-AR (beta-1, beta-2, beta-3) and three subtypes of the alpha-1-AR (alpha-1A, alpha-1B, a...
    • Glucagon-like Peptide-1 (GLP1) regulates insulin secretion, organism-specific biosystem (from REACTOME)
      Glucagon-like Peptide-1 (GLP1) regulates insulin secretion, organism-specific biosystemGlucagon-like Peptide-1 (GLP-1) is secreted by L-cells in the intestine in response to glucose and fatty acids. GLP-1 circulates to the beta cells of the pancreas where it binds a G-protein coupled r...
    • Hemostasis, organism-specific biosystem (from REACTOME)
      Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • Insulin secretion, organism-specific biosystem (from KEGG)
      Insulin secretion, organism-specific biosystemPancreatic beta cells are specialised endocrine cells that continuously sense the levels of blood sugar and other fuels and, in response, secrete insulin to maintain normal fuel homeostasis. Glucose-...
    • Integration of energy metabolism, organism-specific biosystem (from REACTOME)
      Integration of energy metabolism, organism-specific biosystemMany hormones that affect individual physiological processes including the regulation of appetite, absorption, transport, and oxidation of foodstuffs influence energy metabolism pathways. While insul...
    • Integrin alphaIIb beta3 signaling, organism-specific biosystem (from REACTOME)
      Integrin alphaIIb beta3 signaling, organism-specific biosystemAt the sites of vascular injury bioactive molecules such as thrombin, ADP, collagen, fibrinogen and thrombospondin are generated, secreted or exposed. These stimuli activate platelets, converting the...
    • Leukocyte transendothelial migration, organism-specific biosystem (from KEGG)
      Leukocyte transendothelial migration, organism-specific biosystemLeukocyte migaration from the blood into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endothelial cell adhesion molecules (C...
    • Leukocyte transendothelial migration, conserved biosystem (from KEGG)
      Leukocyte transendothelial migration, conserved biosystemLeukocyte migaration from the blood into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endothelial cell adhesion molecules (C...
    • Metabolism, organism-specific biosystem (from REACTOME)
      Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
    • Phospholipase D signaling pathway, organism-specific biosystem (from KEGG)
      Phospholipase D signaling pathway, organism-specific biosystemPhospholipase D (PLD) is an essential enzyme responsible for the production of the lipid second messenger phosphatidic acid (PA), which is involved in fundamental cellular processes, including membra...
    • Phospholipase D signaling pathway, conserved biosystem (from KEGG)
      Phospholipase D signaling pathway, conserved biosystemPhospholipase D (PLD) is an essential enzyme responsible for the production of the lipid second messenger phosphatidic acid (PA), which is involved in fundamental cellular processes, including membra...
    • Platelet Aggregation (Plug Formation), organism-specific biosystem (from REACTOME)
      Platelet Aggregation (Plug Formation), organism-specific biosystemThe tethering of platelets to the site of vascular injury is the first step in the formation of a platelet thrombus. Firm adhesion of these tethered platelets, as well as the additional recruitment o...
    • Platelet activation, signaling and aggregation, organism-specific biosystem (from REACTOME)
      Platelet activation, signaling and aggregation, organism-specific biosystemPlatelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists (released or generated at the sites of vascular trauma) to cognate receptors on the pla...
    • Rap1 signaling pathway, organism-specific biosystem (from KEGG)
      Rap1 signaling pathway, organism-specific biosystemRap1 is a small GTPase that controls diverse processes, such as cell adhesion, cell-cell junction formation and cell polarity. Like all G proteins, Rap1 cycles between an inactive GDP-bound and an ac...
    • Rap1 signaling pathway, conserved biosystem (from KEGG)
      Rap1 signaling pathway, conserved biosystemRap1 is a small GTPase that controls diverse processes, such as cell adhesion, cell-cell junction formation and cell polarity. Like all G proteins, Rap1 cycles between an inactive GDP-bound and an ac...
    • Rap1 signalling, organism-specific biosystem (from REACTOME)
      Rap1 signalling, organism-specific biosystemRap1 (Ras-proximate-1) is a small G protein in the Ras superfamily. Like all G proteins, Rap1 is activated when bound GDP is exchanged for GTP. Rap1 is targeted to lipid membranes by the covalent att...
    • Regulation of insulin secretion, organism-specific biosystem (from REACTOME)
      Regulation of insulin secretion, organism-specific biosystemPancreatic beta cells integrate signals from several metabolites and hormones to control the secretion of insulin. In general, glucose triggers insulin secretion while other factors can amplify or in...
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • cAMP signaling pathway, organism-specific biosystem (from KEGG)
      cAMP signaling pathway, organism-specific biosystemcAMP is one of the most common and universal second messengers, and its formation is promoted by adenylyl cyclase (AC) activation after ligation of G protein-coupled receptors (GPCRs) by ligands incl...
    • cAMP signaling pathway, conserved biosystem (from KEGG)
      cAMP signaling pathway, conserved biosystemcAMP is one of the most common and universal second messengers, and its formation is promoted by adenylyl cyclase (AC) activation after ligation of G protein-coupled receptors (GPCRs) by ligands incl...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    Ras GTPase binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    Ras guanyl-nucleotide exchange factor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    cAMP binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    guanyl-nucleotide exchange factor activity EXP
    Inferred from Experiment
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    G-protein coupled receptor signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    cAMP-mediated signaling IEA
    Inferred from Electronic Annotation
    more info
     
    calcium ion regulated exocytosis IEA
    Inferred from Electronic Annotation
    more info
     
    insulin secretion IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of exocytosis IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of insulin secretion TAS
    Traceable Author Statement
    more info
     
    small GTPase mediated signal transduction IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    cytosol IEA
    Inferred from Electronic Annotation
    more info
     
    membrane TAS
    Traceable Author Statement
    more info
    PubMed 
    plasma membrane TAS
    Traceable Author Statement
    more info
     
    Preferred Names
    rap guanine nucleotide exchange factor 4
    Names
    RAP guanine-nucleotide-exchange factor (GEF) 4
    Rap guanine nucleotide exchange factor (GEF) 4
    cAMP-regulated guanine nucleotide exchange factor II
    exchange factor directly activated by cAMP 2
    exchange protein directly activated by cAMP 2
    putative protein product of Nbla00496

    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_001100397.1NP_001093867.1  rap guanine nucleotide exchange factor 4 isoform b

      See identical proteins and their annotated locations for NP_001093867.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in its 5' UTR, lacks several exons in the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (b) has a distinct N-terminus and is shorter than isoform a.
      Source sequence(s)
      AB027471, BC024004, BC040183, BQ184791
      Consensus CDS
      CCDS42776.1
      UniProtKB/Swiss-Prot
      Q8WZA2
      Related
      ENSP00000380276.3, OTTHUMP00000165045, ENST00000397087.7, OTTHUMT00000257867
      Conserved Domains (4) summary
      smart00147
      Location:624865
      RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
      cd00038
      Location:212323
      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:62190
      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:355461
      RasGEF_N; RasGEF N-terminal motif
    2. NM_001282899.1NP_001269828.1  rap guanine nucleotide exchange factor 4 isoform c

      See identical proteins and their annotated locations for NP_001269828.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) differs in its 5' UTR, lacks several exons in the 5' coding region, and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (c) is shorter at the N-terminus, compared to isoform a.
      Source sequence(s)
      AK316072, BQ184791, DC335305, U78516
      Consensus CDS
      CCDS63060.1
      UniProtKB/Swiss-Prot
      Q8WZA2
      Related
      ENSP00000440250.1, ENST00000540783.5
      Conserved Domains (4) summary
      smart00147
      Location:615856
      RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
      cd00038
      Location:203314
      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:53181
      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:346452
      RasGEF_N; RasGEF N-terminal motif
    3. NM_001282900.1NP_001269829.1  rap guanine nucleotide exchange factor 4 isoform d

      See identical proteins and their annotated locations for NP_001269829.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) differs in its 5' UTR, lacks several exons in the 5' coding region, initiates translation at a downstream in-frame start codon, and lacks an additional in-frame exon in the 5' coding region, compared to variant 1. The encoded isoform (d) is shorter at the N-terminus, compared to isoform a.
      Source sequence(s)
      AK296340, BQ184791, DC335305, U78516
      Consensus CDS
      CCDS63061.1
      UniProtKB/Swiss-Prot
      Q8WZA2
      Related
      ENSP00000440135.1, ENST00000538974.5
      Conserved Domains (4) summary
      smart00147
      Location:597838
      RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
      cd00038
      Location:185296
      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:35163
      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:328434
      RasGEF_N; RasGEF N-terminal motif
    4. NM_001282901.1NP_001269830.1  rap guanine nucleotide exchange factor 4 isoform e

      See identical proteins and their annotated locations for NP_001269830.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (5) differs in its 5' UTR, lacks several exons in the 5' coding region, and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (e) is shorter at the N-terminus, compared to isoform a.
      Source sequence(s)
      AK294433, AK311575, BQ184791, U78516
      Consensus CDS
      CCDS74604.1
      UniProtKB/Swiss-Prot
      Q8WZA2
      UniProtKB/TrEMBL
      B7Z278
      Related
      ENSP00000438011.1, ENST00000535187.5
      Conserved Domains (4) summary
      smart00147
      Location:548789
      RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
      cd00038
      Location:136247
      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:1114
      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:279385
      RasGEF_N; RasGEF N-terminal motif
    5. NM_007023.3NP_008954.2  rap guanine nucleotide exchange factor 4 isoform a

      See identical proteins and their annotated locations for NP_008954.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
      Source sequence(s)
      AB027471, BC024004, BI546558, BQ184791, DB471672
      Consensus CDS
      CCDS42775.1
      UniProtKB/Swiss-Prot
      Q8WZA2
      Related
      ENSP00000380271.3, OTTHUMP00000165043, ENST00000397081.7, OTTHUMT00000257864
      Conserved Domains (4) summary
      smart00147
      Location:7681009
      RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
      cd00038
      Location:43158
      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:206334
      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:499605
      RasGEF_N; RasGEF N-terminal motif

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

    Reference GRCh38.p12 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p12 Primary Assembly

      Range
      172735282..173052893
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006712205.3XP_006712268.1  rap guanine nucleotide exchange factor 4 isoform X5

      See identical proteins and their annotated locations for XP_006712268.1

      UniProtKB/Swiss-Prot
      Q8WZA2
      Conserved Domains (4) summary
      smart00147
      Location:597838
      RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
      cd00038
      Location:185296
      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:35163
      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:328434
      RasGEF_N; RasGEF N-terminal motif
    2. XM_005246246.3XP_005246303.1  rap guanine nucleotide exchange factor 4 isoform X1

      See identical proteins and their annotated locations for XP_005246303.1

      UniProtKB/TrEMBL
      X5D7N4
      Conserved Domains (4) summary
      smart00147
      Location:750991
      RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
      cd00038
      Location:43158
      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:188316
      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:481587
      RasGEF_N; RasGEF N-terminal motif
    3. XM_011510505.3XP_011508807.1  rap guanine nucleotide exchange factor 4 isoform X3

      Conserved Domains (5) summary
      smart00147
      Location:638879
      RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
      COG0664
      Location:221328
      Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]
      cd00038
      Location:226337
      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:76204
      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:369475
      RasGEF_N; RasGEF N-terminal motif
    4. XM_017003196.2XP_016858685.1  rap guanine nucleotide exchange factor 4 isoform X2

    5. XM_017003197.1XP_016858686.1  rap guanine nucleotide exchange factor 4 isoform X4

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