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    ARFGEF2 ARF guanine nucleotide exchange factor 2 [ Homo sapiens (human) ]

    Gene ID: 10564, updated on 10-Dec-2024

    Summary

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    Official Symbol
    ARFGEF2provided by HGNC
    Official Full Name
    ARF guanine nucleotide exchange factor 2provided by HGNC
    Primary source
    HGNC:HGNC:15853
    See related
    Ensembl:ENSG00000124198 MIM:605371; AllianceGenome:HGNC:15853
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    BIG2; PVNH2; dJ1164I10.1
    Summary
    ADP-ribosylation factors (ARFs) play an important role in intracellular vesicular trafficking. The protein encoded by this gene is involved in the activation of ARFs by accelerating replacement of bound GDP with GTP and is involved in Golgi transport. It contains a Sec7 domain, which may be responsible for its guanine-nucleotide exchange activity and also brefeldin A inhibition. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in thyroid (RPKM 19.9), adrenal (RPKM 14.6) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ARFGEF2 in Genome Data Viewer
    Location:
    20q13.13
    Exon count:
    39
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 20 NC_000020.11 (48921711..49036693)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 20 NC_060944.1 (50690875..50806194)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (47538248..47653230)

    Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105372646 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18022 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:47215027-47215985 Neighboring gene Sharpr-MPRA regulatory region 8803 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_60582 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:47235455-47235955 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:47235991-47236699 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12983 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18023 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18024 Neighboring gene Sharpr-MPRA regulatory region 6651 Neighboring gene ReSE screen-validated silencer GRCh37_chr20:47259130-47259274 Neighboring gene phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12984 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:47299567-47300316 Neighboring gene H3K27ac hESC enhancer GRCh37_chr20:47310619-47311119 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_60598 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_60600 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:47319614-47320114 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_60606 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18025 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18026 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18027 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18028 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12985 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18029 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18030 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18031 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18032 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18033 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18034 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:47339203-47340102 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18036 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:47364075-47364807 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:47365963-47366558 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18037 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:47374563-47375557 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12986 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18039 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:47379434-47380209 Neighboring gene ReSE screen-validated silencer GRCh37_chr20:47381423-47381601 Neighboring gene ReSE screen-validated silencer GRCh37_chr20:47388421-47388642 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18040 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18041 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18042 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18043 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18044 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18045 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12987 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:47410381-47411036 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:47411037-47411690 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:47414263-47414873 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:47415894-47416394 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:47435997-47436994 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18046 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18047 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12988 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12989 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18048 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18049 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18050 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:47474509-47475009 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18051 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12990 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12991 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12992 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18052 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18053 Neighboring gene synaptosome associated protein 23 pseudogene 1 Neighboring gene CSE1L divergent transcript

    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. West syndrome, microcephaly, grey matter heterotopia and hypoplasia of corpus callosum due to a novel ARFGEF2 mutation. Banne E, et al. J Med Genet, 2013 Nov. PMID 23812912
    2. BIG1 and BIG2: brefeldin A-inhibited guanine nucleotide-exchange proteins for ADP-ribosylation factors. Pacheco-Rodriguez G, et al. Methods Enzymol, 2002. PMID 11665623
    3. Overexpression of an ADP-ribosylation factor-guanine nucleotide exchange factor, BIG2, uncouples brefeldin A-induced adaptor protein-1 coat dissociation and membrane tubulation. Shinotsuka C, et al. J Biol Chem, 2002 Mar 15. PMID 11777925
    4. Elaborating the phenotypic spectrum associated with mutations in ARFGEF2: case study and literature review. Tanyalçin I, et al. Eur J Paediatr Neurol, 2013 Nov. PMID 23755938
    5. Brefeldin A-inhibited ADP-ribosylation factor activator BIG2 regulates cell migration via integrin β1 cycling and actin remodeling. Shen X, et al. Proc Natl Acad Sci U S A, 2012 Sep 4. PMID 22908276, Free PMC Article

    See all (85) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. BIG1 and BIG2 knockdown significantly decreased the levels of VEGF mRNA and protein in glioblastoma U251 cells and HUVECs. Furthermore, depletion of BIG1 and BIG2 inhibited HUVEC angiogenesis by diminishing cell migration.
      Title: Involvement of BIG1 and BIG2 in regulating VEGF expression and angiogenesis.
    2. Both phospholipase D activity and vesicular trafficking were required for effects of BIG1 and BIG2 on beta-catenin activation. Levels of PKA-phosphorylated beta-catenin S675 and beta-catenin association with PKA, BIG1, and BIG2 were also diminished after BIG1/BIG2 depletion.
      Title: Enhancement of β-catenin activity by BIG1 plus BIG2 via Arf activation and cAMP signals.
    3. Description of a novel ARFGEF2 mutation in five related patients presenting with West syndrome, microcephaly, periventricular heterotopia and thin corpus callosum.
      Title: West syndrome, microcephaly, grey matter heterotopia and hypoplasia of corpus callosum due to a novel ARFGEF2 mutation.
    4. The clinical phenotype associated with mutations in ARFGEF2 is relatively homogeneous in the families report.
      Title: Elaborating the phenotypic spectrum associated with mutations in ARFGEF2: case study and literature review.
    5. Arf guanine nucleotide-exchange factors BIG1 and BIG2 regulate nonmuscle myosin IIA activity by anchoring myosin phosphatase complex.
      Title: Arf guanine nucleotide-exchange factors BIG1 and BIG2 regulate nonmuscle myosin IIA activity by anchoring myosin phosphatase complex.
    6. an early acting GEF (GBF1) activates ARFs that mediate recruitment of late acting GEFs (BIG1/2) to coordinate coating events within the pre-Golgi/Golgi/TGN continuum.
      Title: The Sec7 guanine nucleotide exchange factor GBF1 regulates membrane recruitment of BIG1 and BIG2 guanine nucleotide exchange factors to the trans-Golgi network (TGN).
    7. Brefeldin A-inhibited ADP-ribosylation factor activator BIG2 regulates cell migration via integrin beta1 cycling and actin remodeling.
      Title: Brefeldin A-inhibited ADP-ribosylation factor activator BIG2 regulates cell migration via integrin β1 cycling and actin remodeling.
    8. Up-regulation of ARFGEF2 is associated with the Huntington's disease.
      Title: ADP-ribosylation factor guanine nucleotide-exchange factor 2 (ARFGEF2): a new potential biomarker in Huntington's disease.
    9. BIG1 and BIG2 have roles in endomembrane organization
      Title: Specific functions of BIG1 and BIG2 in endomembrane organization.
    10. Results describe a child with a severe choreadystonic movement disorder, bilateral periventricular nodular heterotopia (BPNH), and secondary microcephaly based on compound heterozygosity for two new ARFGEF2 mutations.
      Title: Movement disorder and neuronal migration disorder due to ARFGEF2 mutation.
    Submit: New GeneRIF Correction See all GeneRIFs (19)

    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

    Associated conditions

    Description Tests
    Periventricular heterotopia with microcephaly, autosomal recessive
    MedGen: C1842563 OMIM: 608097 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    Genome-wide association study of proneness to anger.
    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
    Vpu vpu HIV-1 Vpu is identified to have a physical interaction with ADP-ribosylation factor guanine nucleotide-exchange factor 2 (ARFGEF2; BIG2) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses 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

    Homology

    Clone Names

    • FLJ23723

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables GABA receptor binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables guanyl-nucleotide exchange factor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables myosin binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein kinase A regulatory subunit binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in Golgi to plasma membrane transport IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in endomembrane system organization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in endosome organization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in exocytosis IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within intracellular signal transduction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of tumor necrosis factor production IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in receptor recycling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of ARF protein signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in GABA-ergic synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    		  
    located_in Golgi membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in asymmetric synapse ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in axonemal microtubule ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in centrosome IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytoplasmic vesicle ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in dendritic spine ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in glutamatergic synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
    		  
    located_in membrane HDA PubMed 
    located_in membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in microtubule organizing center IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in perinuclear region of cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in presynapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in recycling endosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in symmetric synapse ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in trans-Golgi network ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    brefeldin A-inhibited guanine nucleotide-exchange protein 2
    Names
    ADP ribosylation factor guanine nucleotide exchange factor 2
    ADP-ribosylation factor guanine nucleotide-exchange factor 2 (brefeldin A-inhibited)
    brefeldin A-inhibited GEP 2

    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.

    Genomic

    1. NG_011490.2 RefSeqGene

      Range
      4974..119956
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001410846.1 → NP_001397775.1  brefeldin A-inhibited guanine nucleotide-exchange protein 2 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AL049537, AL121903
      Consensus CDS
      CCDS93055.1
      UniProtKB/TrEMBL
      A0A7P0T7Z2, A0A7P0TA34
      Related
      ENSP00000504888.1, ENST00000679436.1

    2. NM_006420.3 → NP_006411.2  brefeldin A-inhibited guanine nucleotide-exchange protein 2 isoform 1

      See identical proteins and their annotated locations for NP_006411.2

      Status: REVIEWED

      Source sequence(s)
      AB209397, AK074303, AL049537, AL121903, BC050449
      Consensus CDS
      CCDS13411.1
      UniProtKB/Swiss-Prot
      Q5TFT9, Q9NTS1, Q9Y6D5
      UniProtKB/TrEMBL
      A0A7P0TA34
      Related
      ENSP00000360985.4, ENST00000371917.5
      Conserved Domains (5) summary
      PLN03076
      Location:11 → 1711
      PLN03076; ARF guanine nucleotide exchange factor (ARF-GEF); Provisional
      pfam01369
      Location:643 → 827
      Sec7; Sec7 domain
      pfam09324
      Location:1167 → 1248
      DUF1981; Domain of unknown function (DUF1981)
      pfam12783
      Location:370 → 524
      Sec7_N; Guanine nucleotide exchange factor in Golgi transport N-terminal
      pfam16213
      Location:28 → 198
      DCB; Dimerization and cyclophilin-binding domain of Mon2

    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_000020.11 Reference GRCh38.p14 Primary Assembly

      Range
      48921711..49036693
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047439832.1 → XP_047295788.1  brefeldin A-inhibited guanine nucleotide-exchange protein 2 isoform X1

      UniProtKB/TrEMBL
      A0A7P0TA34
      Related
      ENST00000679542.1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060944.1 Alternate T2T-CHM13v2.0

      Range
      50690875..50806194
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054322843.1 → XP_054178818.1  brefeldin A-inhibited guanine nucleotide-exchange protein 2 isoform X1

      UniProtKB/TrEMBL
      A0A7P0TA34
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9Y6D5.3 GenPept UniProtKB/Swiss-Prot:Q9Y6D5

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