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

    Gene ID: 11069, updated on 10-Dec-2024

    Summary

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    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; AllianceGenome:HGNC:16626
    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
    Summary
    Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in Ras protein signal transduction; regulation of neurotransmitter receptor localization to postsynaptic specialization membrane; and regulation of postsynapse organization. Predicted to act upstream of or within with a positive effect on hormone secretion. Predicted to act upstream of or within adenylate cyclase-activating G protein-coupled receptor signaling pathway; regulation of exocytosis; and secretion by cell. Predicted to be located in membrane. Predicted to be active in several cellular components, including glutamatergic synapse; hippocampal mossy fiber to CA3 synapse; and postsynaptic density. Implicated in autistic disorder. [provided by Alliance of Genome Resources, Dec 2024]
    Expression
    Biased expression in brain (RPKM 37.0), adrenal (RPKM 17.3) and 12 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See RAPGEF4 in Genome Data Viewer
    Location:
    2q31.1
    Exon count:
    37
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (172735318..173052893)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (173221758..173539439)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (173600573..173917621)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_56072 Neighboring gene integrin subunit alpha 6 Neighboring gene PDK1 and ITGA6 antisense RNA 1 Neighboring gene Sharpr-MPRA regulatory region 994 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:173399678-173400178 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr2:173413559-173414301 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr2:173414302-173415043 Neighboring gene Sharpr-MPRA regulatory region 4236 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16763 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12111 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:173456666-173456873 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_56189 Neighboring gene pyruvate dehydrogenase kinase 1 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_56221 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_56231 Neighboring gene Sharpr-MPRA regulatory region 7042 Neighboring gene small nucleolar RNA U13 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_56260 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_56279 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_56293 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:173577807-173578364 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:173590766-173591266 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:173591267-173591767 Neighboring gene RAPGEF4 antisense RNA 1 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:173607526-173608725 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:173668092-173668282 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:173770903-173771408 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:173771409-173771912 Neighboring gene aldehyde dehydrogenase 7 family member A1 pseudogene 2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12112 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12113 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_56377 Neighboring gene mitogen-activated protein kinase kinase kinase 20 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_56397 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:174056283-174056864 Neighboring gene MAP3K20 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16764 Neighboring gene VISTA enhancer hs242 Neighboring gene NANOG hESC enhancer GRCh37_chr2:174129200-174129707 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16765 Neighboring gene uncharacterized LOC105373743

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. Mechanism of intracellular cAMP sensor Epac2 activation: cAMP-induced conformational changes identified by amide hydrogen/deuterium exchange mass spectrometry (DXMS). Li S, et al. J Biol Chem, 2011 May 20. PMID 21454623, Free PMC Article
    2. Structure and functional roles of Epac2 (Rapgef4). Sugawara K, et al. Gene, 2016 Jan 10. PMID 26390815, Free PMC Article
    3. Broad Impact of Exchange Protein Directly Activated by cAMP 2 (EPAC2) on Respiratory Viral Infections. Choi EJ, et al. Viruses, 2021 Jun 21. PMID 34205489, Free PMC Article
    4. The Epac2 coding gene (RAPGEF4) rs3769219 polymorphism is associated with protection against major depressive disorder in the Chinese Han population. Peng Q, et al. Neurosci Lett, 2020 Nov 1. PMID 32905835
    5. Functional roles of protein kinase A (PKA) and exchange protein directly activated by 3',5'-cyclic adenosine 5'-monophosphate (cAMP) 2 (EPAC2) in cAMP-mediated actions in adrenocortical cells. Aumo L, et al. Endocrinology, 2010 May. PMID 20233795

    See all (68) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
    2. Pancreatic cancer-derived exosomal microRNA-19a induces beta-cell dysfunction by targeting ADCY1 and EPAC2.
      Title: Pancreatic cancer-derived exosomal microRNA-19a induces β-cell dysfunction by targeting ADCY1 and EPAC2.
    3. 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.
    4. Epac: new emerging cAMP-binding protein.
      Title: Epac: new emerging cAMP-binding protein.
    5. Broad Impact of Exchange Protein Directly Activated by cAMP 2 (EPAC2) on Respiratory Viral Infections.
      Title: Broad Impact of Exchange Protein Directly Activated by cAMP 2 (EPAC2) on Respiratory Viral Infections.
    6. The Epac2 coding gene (RAPGEF4) rs3769219 polymorphism is associated with protection against major depressive disorder in the Chinese Han population.
      Title: The Epac2 coding gene (RAPGEF4) rs3769219 polymorphism is associated with protection against major depressive disorder in the Chinese Han population.
    7. The authors conclude that Epac2/cAMP controls fusion pore expansion and thus the balance of hormone and transmitter release during insulin granule exocytosis.
      Title: Fusion pore regulation by cAMP/Epac2 controls cargo release during insulin exocytosis.
    8. Through isoform-specific gene knockdown, the authors found that EPAC2, but not EPAC1, plays a dominant role in controlling RSV replication and virus-induced host responses.
      Title: Exchange Proteins Directly Activated by cAMP and Their Roles in Respiratory Syncytial Virus Infection.
    9. Cyclic AMP (cAMP), a secondary messenger responsible for various physiological processes regulates cell metabolism by activating Protein kinase A (PKA) and by targeting exchange protein directly activated by cAMP (EPAC). EPAC is present in two isoforms EPAC1 and EPAC2, which exhibit different tissue distribution and is involved in GDP/GTP exchange along with activating Rap1- and Rap2-mediated signaling pathways.
      Title: Insights into exchange factor directly activated by cAMP (EPAC) as potential target for cancer treatment.
    10. Study identifies Epac2-Rap1 signaling as a novel feedback mechanism in the heart, which controls mitochondrial reactive oxygen species production.
      Title: Epac2-Rap1 Signaling Regulates Reactive Oxygen Species Production and Susceptibility to Cardiac Arrhythmias.
    Submit: New GeneRIF Correction See all GeneRIFs (34)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

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

    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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    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

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cAMP binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    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 ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein-macromolecule adaptor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables small GTPase binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in G protein-coupled receptor signaling pathway TAS
    Traceable Author Statement
    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 IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in calcium-ion regulated exocytosis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in insulin secretion IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of insulin secretion IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of exocytosis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of insulin secretion TAS
    Traceable Author Statement
    more info
    		  
    involved_in regulation of synaptic vesicle cycle IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cytosol IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in hippocampal mossy fiber to CA3 synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    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

    NCBI Reference Sequences (RefSeq)

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    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_001100397.2 → NP_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)
      AC009484, AC019046, AC104086
      Consensus CDS
      CCDS42776.1
      UniProtKB/TrEMBL
      B7Z9P9
      Related
      ENSP00000380276.3, ENST00000397087.7
      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

    2. NM_001282899.2 → NP_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)
      AC009484, AC019046, AC104086
      Consensus CDS
      CCDS63060.1
      UniProtKB/TrEMBL
      B7Z9P9
      Related
      ENSP00000440250.1, ENST00000540783.5
      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

    3. NM_001282900.2 → NP_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)
      AC009484, AC019046, AC104086
      Consensus CDS
      CCDS63061.1
      UniProtKB/TrEMBL
      B7Z9P9
      Related
      ENSP00000440135.1, ENST00000538974.5
      Conserved Domains (4) summary
      smart00147
      Location:597 → 838
      RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
      cd00038
      Location:185 → 296
      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:35 → 163
      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:328 → 434
      RasGEF_N; RasGEF N-terminal motif

    4. NM_001282901.2 → NP_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)
      AC009484, AC019046, AC104086
      Consensus CDS
      CCDS74604.1
      UniProtKB/TrEMBL
      B7Z278, B7Z9P9
      Related
      ENSP00000438011.1, ENST00000535187.5
      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

    5. NM_001375864.1 → NP_001362793.1  rap guanine nucleotide exchange factor 4 isoform f

      Status: VALIDATED

      Source sequence(s)
      AC009484, AC018712, AC019046, AC104086
      UniProtKB/TrEMBL
      X5D9F4
      Conserved Domains (4) summary
      cd06224
      Location:494 → 619
      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 ...
      smart00147
      Location:758 → 999
      RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
      cd00038
      Location:33 → 148
      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:196 → 324
      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 ...

    6. NM_001375865.1 → NP_001362794.1  rap guanine nucleotide exchange factor 4 isoform g

      Status: VALIDATED

      Source sequence(s)
      AC009484, AC018712, AC019046, AC104086
      UniProtKB/TrEMBL
      X5D9F4
      Conserved Domains (4) summary
      smart00147
      Location:757 → 998
      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

    7. NM_001375866.1 → NP_001362795.1  rap guanine nucleotide exchange factor 4 isoform h

      Status: VALIDATED

      Source sequence(s)
      AC009484, AC018712, AC019046, AC104086
      UniProtKB/TrEMBL
      X5D7N4, X5D9F4
      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

    8. NM_001375867.1 → NP_001362796.1  rap guanine nucleotide exchange factor 4 isoform i

      Status: VALIDATED

      Source sequence(s)
      AC009484, AC018712, AC019046, AC104086
      UniProtKB/TrEMBL
      X5D9F4
      Conserved Domains (4) summary
      smart00147
      Location:737 → 978
      RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
      cd00038
      Location:325 → 436
      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:175 → 303
      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:468 → 574
      RasGEF_N; RasGEF N-terminal motif

    9. NM_001375868.1 → NP_001362797.1  rap guanine nucleotide exchange factor 4 isoform j

      Status: VALIDATED

      Source sequence(s)
      AC009484, AC018712, AC019046, AC104086
      UniProtKB/TrEMBL
      X5D9F4
      Conserved Domains (4) summary
      smart00147
      Location:719 → 960
      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

    10. NM_001375869.1 → NP_001362798.1  rap guanine nucleotide exchange factor 4 isoform k

      Status: VALIDATED

      Source sequence(s)
      AC009484, AC018712, AC019046, AC104086
      UniProtKB/TrEMBL
      X5D9F4
      Conserved Domains (4) summary
      smart00147
      Location:768 → 958
      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

    11. NM_001375870.1 → NP_001362799.1  rap guanine nucleotide exchange factor 4 isoform l

      Status: VALIDATED

      Source sequence(s)
      AC009484, AC018712, AC019046, AC104086
      UniProtKB/TrEMBL
      X5D9F4
      Conserved Domains (4) summary
      smart00147
      Location:768 → 929
      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

    12. NM_001375871.1 → NP_001362800.1  rap guanine nucleotide exchange factor 4 isoform m

      Status: VALIDATED

      Source sequence(s)
      AC009484, AC018712, AC019046, AC104086
      UniProtKB/TrEMBL
      X5D9F4
      Conserved Domains (4) summary
      smart00147
      Location:701 → 942
      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

    13. NM_001375872.1 → NP_001362801.1  rap guanine nucleotide exchange factor 4 isoform n

      Status: VALIDATED

      Source sequence(s)
      AC009484, AC018712, AC019046, AC104086
      Consensus CDS
      CCDS92899.1
      UniProtKB/TrEMBL
      E9PB94, X5D9F4
      Related
      ENSP00000387104.1, ENST00000409036.5
      Conserved Domains (4) summary
      smart00147
      Location:768 → 941
      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

    14. NM_001375873.1 → NP_001362802.1  rap guanine nucleotide exchange factor 4 isoform o

      Status: VALIDATED

      Source sequence(s)
      AC009484, AC018712, AC019046, AC104086
      UniProtKB/TrEMBL
      X5D9F4
      Conserved Domains (4) summary
      smart00147
      Location:750 → 940
      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

    15. NM_001375874.1 → NP_001362803.1  rap guanine nucleotide exchange factor 4 isoform p

      Status: VALIDATED

      Source sequence(s)
      AC009484, AC018712, AC019046, AC104086
      UniProtKB/TrEMBL
      X5D9F4
      Conserved Domains (4) summary
      smart00147
      Location:750 → 911
      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

    16. NM_001375875.1 → NP_001362804.1  rap guanine nucleotide exchange factor 4 isoform q

      Status: VALIDATED

      Source sequence(s)
      AC009484, AC018712, AC104086
      UniProtKB/TrEMBL
      B7Z2Q8
      Conserved Domains (2) summary
      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 ...

    17. NM_001375876.1 → NP_001362805.1  rap guanine nucleotide exchange factor 4 isoform r

      Status: VALIDATED

      Source sequence(s)
      AC009484, AC018712, AC104086
      Conserved Domains (2) summary
      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 ...

    18. NM_007023.4 → NP_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)
      AC009484, AC018712, AC019046, AC104086
      Consensus CDS
      CCDS42775.1
      UniProtKB/Swiss-Prot
      B2R7R3, B7Z283, B7Z3T6, B7Z912, O95636, Q8IXK6, Q8TAA4, Q8WZA2
      UniProtKB/TrEMBL
      X5D9F4
      Related
      ENSP00000380271.3, ENST00000397081.8
      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

    RNA

    1. NR_164739.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AC009484, AC018712, AC019046, AC104086

    2. NR_164740.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AC009484, AC018712, AC019046, AC104086

    3. NR_164741.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AC009484, AC018712, AC019046, AC104086

    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_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      172735318..173052893
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047443030.1 → XP_047298986.1  rap guanine nucleotide exchange factor 4 isoform X4

      UniProtKB/TrEMBL
      B7Z9P9

    2. XM_006712205.4 → XP_006712268.1  rap guanine nucleotide exchange factor 4 isoform X6

      See identical proteins and their annotated locations for XP_006712268.1

      UniProtKB/TrEMBL
      B7Z9P9
      Conserved Domains (4) summary
      smart00147
      Location:597 → 838
      RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
      cd00038
      Location:185 → 296
      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:35 → 163
      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:328 → 434
      RasGEF_N; RasGEF N-terminal motif

    3. XM_017003196.3 → XP_016858685.1  rap guanine nucleotide exchange factor 4 isoform X1

      UniProtKB/TrEMBL
      X5D9F4

    4. XM_047443028.1 → XP_047298984.1  rap guanine nucleotide exchange factor 4 isoform X2

      UniProtKB/TrEMBL
      B7Z9P9

    5. XM_017003197.2 → XP_016858686.1  rap guanine nucleotide exchange factor 4 isoform X5

      UniProtKB/TrEMBL
      B7Z9P9

    6. XM_047443029.1 → XP_047298985.1  rap guanine nucleotide exchange factor 4 isoform X3

      UniProtKB/TrEMBL
      B7Z9P9

    7. XM_047443032.1 → XP_047298988.1  rap guanine nucleotide exchange factor 4 isoform X8

      UniProtKB/TrEMBL
      B7Z9P9

    8. XM_047443033.1 → XP_047298989.1  rap guanine nucleotide exchange factor 4 isoform X9

      UniProtKB/TrEMBL
      B7Z278, B7Z9P9

    9. XM_047443031.1 → XP_047298987.1  rap guanine nucleotide exchange factor 4 isoform X7

      UniProtKB/TrEMBL
      B7Z9P9

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      173221758..173539439
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054340254.1 → XP_054196229.1  rap guanine nucleotide exchange factor 4 isoform X4

      UniProtKB/TrEMBL
      B7Z9P9

    2. XM_054340256.1 → XP_054196231.1  rap guanine nucleotide exchange factor 4 isoform X6

      UniProtKB/TrEMBL
      B7Z9P9

    3. XM_054340251.1 → XP_054196226.1  rap guanine nucleotide exchange factor 4 isoform X1

      UniProtKB/TrEMBL
      X5D9F4

    4. XM_054340252.1 → XP_054196227.1  rap guanine nucleotide exchange factor 4 isoform X2

      UniProtKB/TrEMBL
      B7Z9P9

    5. XM_054340255.1 → XP_054196230.1  rap guanine nucleotide exchange factor 4 isoform X5

      UniProtKB/TrEMBL
      B7Z9P9

    6. XM_054340253.1 → XP_054196228.1  rap guanine nucleotide exchange factor 4 isoform X3

      UniProtKB/TrEMBL
      B7Z9P9

    7. XM_054340258.1 → XP_054196233.1  rap guanine nucleotide exchange factor 4 isoform X8

      UniProtKB/TrEMBL
      B7Z9P9

    8. XM_054340257.1 → XP_054196232.1  rap guanine nucleotide exchange factor 4 isoform X7

      UniProtKB/TrEMBL
      B7Z9P9

    9. XM_054340259.1 → XP_054196234.1  rap guanine nucleotide exchange factor 4 isoform X9

      UniProtKB/TrEMBL
      B7Z278, B7Z9P9
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8WZA2.1 GenPept UniProtKB/Swiss-Prot:Q8WZA2

    Gene LinkOut

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