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    ARHGEF28 Rho guanine nucleotide exchange factor 28 [ Homo sapiens (human) ]

    Gene ID: 64283, updated on 5-Mar-2024

    Summary

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    Official Symbol
    ARHGEF28provided by HGNC
    Official Full Name
    Rho guanine nucleotide exchange factor 28provided by HGNC
    Primary source
    HGNC:HGNC:30322
    See related
    Ensembl:ENSG00000214944 MIM:612790; AllianceGenome:HGNC:30322
    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
    RIP2; RGNEF; p190RHOGEF
    Summary
    This gene encodes a member of the Rho guanine nucleotide exchange factor family. The encoded protein interacts with low molecular weight neurofilament mRNA and may be involved in the formation of amyotrophic lateral sclerosis neurofilament aggregates. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2010]
    Expression
    Broad expression in kidney (RPKM 8.5), thyroid (RPKM 7.2) and 21 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    5q13.2
    Exon count:
    38
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (73626196..73941990)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (74107540..74423332)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (72922021..73237815)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene H3K27ac hESC enhancers GRCh37_chr5:72860724-72861278 and GRCh37_chr5:72861279-72861833 Neighboring gene ankyrin repeat family A member 2 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:72895316-72895509 Neighboring gene UTP15 small subunit processome component Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16091 Neighboring gene uncharacterized LOC107986423 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr5:72989307-72989931 Neighboring gene NANOG hESC enhancer GRCh37_chr5:73042994-73043575 Neighboring gene Sharpr-MPRA regulatory region 14272 Neighboring gene Sharpr-MPRA regulatory region 14554 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr5:73091866-73093065 Neighboring gene RNA, U7 small nuclear 196 pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:73175472-73175972 Neighboring gene uncharacterized LOC105379034 Neighboring gene Sharpr-MPRA regulatory region 15608 Neighboring gene uncharacterized LOC124901003 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr5:73330922-73332121 Neighboring gene long intergenic non-protein coding RNA 2122

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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 Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Inclusion Formation and Toxicity of the ALS Protein RGNEF and Its Association with the Microtubule Network. Di Gregorio SE, et al. Int J Mol Sci, 2020 Aug 5. PMID 32764283, Free PMC Article
    2. Circular RNA circRGNEF promotes bladder cancer progression via miR-548/KIF2C axis regulation. Yang C, et al. Aging (Albany NY), 2020 Apr 19. PMID 32305958, Free PMC Article
    3. Rare, low-frequency and common coding variants of ARHGEF28 gene and their association with sporadic amyotrophic lateral sclerosis. Song Y, et al. Neurobiol Aging, 2020 Mar. PMID 31060816
    4. A novel overlapping NLS/NES region within the PH domain of Rho Guanine Nucleotide Exchange Factor (RGNEF) regulates its nuclear-cytoplasmic localization. Tavolieri MV, et al. Eur J Cell Biol, 2019 Jan. PMID 30482479
    5. Gastrin-stimulated Gα13 Activation of Rgnef Protein (ArhGEF28) in DLD-1 Colon Carcinoma Cells. Masià-Balagué M, et al. J Biol Chem, 2015 Jun 12. PMID 25922072, Free PMC Article

    See all (40) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Expression of a RhoA-Specific Guanine Nucleotide Exchange Factor, p190RhoGEF, in Mouse Macrophages Negatively Affects M1 Polarization and Inflammatory Responses.
      Title: Expression of a RhoA-Specific Guanine Nucleotide Exchange Factor, p190RhoGEF, in Mouse Macrophages Negatively Affects M1 Polarization and Inflammatory Responses.
    2. Circular RNA circRGNEF promotes bladder cancer progression via miR-548/KIF2C axis regulation.
      Title: Circular RNA circRGNEF promotes bladder cancer progression via miR-548/KIF2C axis regulation.
    3. Inclusion Formation and Toxicity of the ALS Protein RGNEF and Its Association with the Microtubule Network.
      Title: Inclusion Formation and Toxicity of the ALS Protein RGNEF and Its Association with the Microtubule Network.
    4. Rare, low-frequency and common coding variants of ARHGEF28 gene and their association with sporadic amyotrophic lateral sclerosis.
      Title: Rare, low-frequency and common coding variants of ARHGEF28 gene and their association with sporadic amyotrophic lateral sclerosis.
    5. A new role for Rgnef in ovarian cancer to facilitate NF-kappaB-mediated gene expression protecting cells from oxidative stress.
      Title: Rgnef promotes ovarian tumor progression and confers protection from oxidative stress.
    6. Data show interaction between activated Rac family small GTPase 1 (Rac1) and Rho guanine nucleotide exchange factor 28 (p190RhoGEF), suggeseting a potential mechanism for cross-talk regulation where Rac can directly effect stimulation of small GTP binding protein RhoA (RhoA).
      Title: Direct regulation of p190RhoGEF by activated Rho and Rac GTPases.
    7. a 23-amino acid region containing a bipartite nuclear localization signal (NLS) within the Pleckstrin Homology (PH) domain of RGNEF, which when deleted or mutated abolishes the nuclear localization of this protein.
      Title: A novel overlapping NLS/NES region within the PH domain of Rho Guanine Nucleotide Exchange Factor (RGNEF) regulates its nuclear-cytoplasmic localization.
    8. results show that Rgnef functions as an effector of Galpha13 signaling and that this linkage may mediate FAK activation in DLD-1 colon carcinoma cells
      Title: Gastrin-stimulated Gα13 Activation of Rgnef Protein (ArhGEF28) in DLD-1 Colon Carcinoma Cells.
    9. This study showed that ARHGEF28 gene exon 6/intron 6 junction mutations in Chinese amyotrophic lateral sclerosis cohort.
      Title: ARHGEF28 gene exon 6/intron 6 junction mutations in Chinese amyotrophic lateral sclerosis cohort.
    10. Study identified a heterozygous mutation in amyotrophic lateral sclerosis patients that is predicted to generate a premature truncated ARHGEF28 gene product. There were extensive regions of homozygosity in the ARHGEF28 gene in two familial ALS patients.
      Title: Detection of a novel frameshift mutation and regions with homozygosis within ARHGEF28 gene in familial amyotrophic lateral sclerosis.
    Submit: New GeneRIF Correction See all GeneRIFs (15)

    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

    EBI GWAS Catalog

    Description
    A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis.
    EBI GWAS Catalog
    Genetic predictors of fibrin D-dimer levels in healthy adults.
    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)

    Genotypes

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of 190 kDa guanine nucleotide exchange factor (RGNEF) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells 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

    Clone Names

    • FLJ21817, KIAA1998, DKFZp686P12164

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables RNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables guanyl-nucleotide exchange factor activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables guanyl-nucleotide exchange factor activity TAS
    Traceable Author Statement
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in cell morphogenesis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in central nervous system neuron axonogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in ephrin receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    involved_in neurofilament cytoskeleton organization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of Rho protein signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of small GTPase mediated signal transduction TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    rho guanine nucleotide exchange factor 28
    Names
    190 kDa guanine nucleotide exchange factor
    Rho guanine nucleotide exchange factor (GEF) 28
    Rho interacting protein 2
    rho-guanine nucleotide exchange factor

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_017198.2 RefSeqGene

      Range
      5039..320833
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001080479.3 → NP_001073948.2  rho guanine nucleotide exchange factor 28 isoform 1

      See identical proteins and their annotated locations for NP_001073948.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC091868, AC093283, AK094713, BC157846, CN478799
      Consensus CDS
      CCDS47231.2
      UniProtKB/TrEMBL
      A0A2X0U2G7
      Related
      ENSP00000441913.1, ENST00000545377.5
      Conserved Domains (5) summary
      smart00325
      Location:853 → 1042
      RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases
      cd00029
      Location:653 → 698
      C1; Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second ...
      cd14680
      Location:1087 → 1187
      PH_p190RhoGEF; Rho guanine nucleotide exchange factor Pleckstrin homology domain
      pfam00169
      Location:1123 → 1188
      PH; PH domain
      cl02529
      Location:153 → 216
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

    2. NM_001177693.2 → NP_001171164.1  rho guanine nucleotide exchange factor 28 isoform 2

      See identical proteins and their annotated locations for NP_001171164.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame exon in the coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
      Source sequence(s)
      AC093283, AK094713, BC171850, CN478799
      Consensus CDS
      CCDS54870.1
      UniProtKB/Swiss-Prot
      B2RXG7, B4E3K4, B5MDA3, B7ZW32, E9PC75, Q8N1W1, Q8NCM7, Q96E37, Q9H6L3, Q9H6W0
      UniProtKB/TrEMBL
      A0A2X0U2G7
      Related
      ENSP00000441436.1, ENST00000513042.7
      Conserved Domains (5) summary
      smart00325
      Location:853 → 1042
      RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases
      cd00029
      Location:653 → 698
      C1; Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second ...
      cd14680
      Location:1087 → 1187
      PH_p190RhoGEF; Rho guanine nucleotide exchange factor Pleckstrin homology domain
      pfam00169
      Location:1123 → 1188
      PH; PH domain
      cl02529
      Location:153 → 216
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

    3. NM_001244364.2 → NP_001231293.1  rho guanine nucleotide exchange factor 28 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) has multiple differences, compared to variant 1. These differences result in a distinct 5' UTR and cause translation initiation at an alternate start codon, compared to variant 1. The encoded protein (isoform 3) is shorter and has a distinct N-terminus, compared to isoform 1.
      Source sequence(s)
      AC093283, AK025470, AK304761, BG696752
      Consensus CDS
      CCDS58957.1
      UniProtKB/Swiss-Prot
      Q8N1W1
      Related
      ENSP00000296799.4, ENST00000296799.8
      Conserved Domains (4) summary
      smart00325
      Location:540 → 729
      RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases
      cd00029
      Location:340 → 385
      C1; Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second ...
      cd14680
      Location:774 → 874
      PH_p190RhoGEF; Rho guanine nucleotide exchange factor Pleckstrin homology domain
      pfam00169
      Location:810 → 875
      PH; PH domain

    4. NM_001388076.1 → NP_001375005.1  rho guanine nucleotide exchange factor 28 isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC008387, AC026702, AC091868, AC093283, KF457926
      UniProtKB/TrEMBL
      A0A2X0U2G7
      Conserved Domains (3) summary
      smart00325
      Location:755 → 944
      RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases
      cd20876
      Location:548 → 608
      C1_p190RhoGEF; protein kinase C conserved region 1 (C1 domain) found in 190 kDa guanine nucleotide exchange factor (p190RhoGEF) and similar proteins
      cl17171
      Location:989 → 1089
      PH-like; Pleckstrin homology-like domain

    5. NM_001388078.1 → NP_001375007.1  rho guanine nucleotide exchange factor 28 isoform 5

      Status: REVIEWED

      Source sequence(s)
      AC008387, AC026702, AC091868, AC093283, KF457926
      Consensus CDS
      CCDS93734.1
      UniProtKB/TrEMBL
      A0A2X0U2G7
      Related
      ENSP00000296794.6, ENST00000296794.10
      Conserved Domains (3) summary
      smart00325
      Location:853 → 1042
      RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases
      cd14680
      Location:1087 → 1187
      PH_p190RhoGEF; Rho guanine nucleotide exchange factor Pleckstrin homology domain
      cd20876
      Location:646 → 706
      C1_p190RhoGEF; protein kinase C conserved region 1 (C1 domain) found in 190 kDa guanine nucleotide exchange factor (p190RhoGEF) and similar proteins

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      73626196..73941990
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      74107540..74423332
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_022448.1: Suppressed sequence

      Description
      NM_022448.1: This RefSeq was removed because currently there is support for the transcript but not for the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8N1W1.3 GenPept UniProtKB/Swiss-Prot:Q8N1W1

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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