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    ARHGEF6 Rac/Cdc42 guanine nucleotide exchange factor 6 [ Homo sapiens (human) ]

    Gene ID: 9459, updated on 27-Nov-2024

    Summary

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    Official Symbol
    ARHGEF6provided by HGNC
    Official Full Name
    Rac/Cdc42 guanine nucleotide exchange factor 6provided by HGNC
    Primary source
    HGNC:HGNC:685
    See related
    Ensembl:ENSG00000129675 MIM:300267; AllianceGenome:HGNC:685
    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
    PIXA; COOL2; MRX46; Cool-2; alphaPIX; alpha-PIX
    Summary
    Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein belongs to a family of cytoplasmic proteins that activate the Ras-like family of Rho proteins by exchanging bound GDP for GTP. It may form a complex with G proteins and stimulate Rho-dependent signals. This protein is activated by PI3-kinase. Mutations in this gene can cause X-chromosomal non-specific cognitive disability. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in fat (RPKM 22.0), lymph node (RPKM 16.8) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ARHGEF6 in Genome Data Viewer
    Location:
    Xq26.3
    Exon count:
    25
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (136665550..136780932, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (134974276..135089655, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (135747709..135863091, complement)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 892 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 21028 Neighboring gene CD40 ligand Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29992 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29993 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29994 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 21029 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 21030 Neighboring gene ReSE screen-validated silencer GRCh37_chrX:135849488-135849656 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29995 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29996 Neighboring gene RNA, U6 small nuclear 972, pseudogene Neighboring gene solute carrier family 25 member 6 pseudogene Neighboring gene ribosomal protein L7 pseudogene 56

    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. Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1 (supplement). Nomura N, et al. DNA Res, 1994. PMID 7584048
    2. The pathological significance and potential mechanism of ARHGEF6 in lung adenocarcinoma. Zheng T, et al. Comput Biol Med, 2023 May. PMID 37058762
    3. Clinical implication and potential function of ARHGEF6 in acute myeloid leukemia: An in vitro study. Li K, et al. PLoS One, 2023. PMID 37027440, Free PMC Article
    4. Comprehensive analysis identifies ARHGEF6 as a potential prognostic and immunological biomarker in lung adenocarcinoma. Wang N, et al. Comput Biol Med, 2023 Feb. PMID 36586227
    5. alphaPix interacts with Helicobacter pylori CagA to induce IL-8 expression in gastric epithelial cells. Lim JW, et al. Scand J Gastroenterol, 2009. PMID 19672789

    See all (84) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Fermitin family member 2 promotes melanoma progression by enhancing the binding of p-alpha-Pix to Rac1 to activate the MAPK pathway.
      Title: Fermitin family member 2 promotes melanoma progression by enhancing the binding of p-α-Pix to Rac1 to activate the MAPK pathway.
    2. The pathological significance and potential mechanism of ARHGEF6 in lung adenocarcinoma.
      Title: The pathological significance and potential mechanism of ARHGEF6 in lung adenocarcinoma.
    3. Clinical implication and potential function of ARHGEF6 in acute myeloid leukemia: An in vitro study.
      Title: Clinical implication and potential function of ARHGEF6 in acute myeloid leukemia: An in vitro study.
    4. Genetic Variants in ARHGEF6 Cause Congenital Anomalies of the Kidneys and Urinary Tract in Humans, Mice, and Frogs.
      Title: Genetic Variants in ARHGEF6 Cause Congenital Anomalies of the Kidneys and Urinary Tract in Humans, Mice, and Frogs.
    5. Comprehensive analysis identifies ARHGEF6 as a potential prognostic and immunological biomarker in lung adenocarcinoma.
      Title: Comprehensive analysis identifies ARHGEF6 as a potential prognostic and immunological biomarker in lung adenocarcinoma.
    6. In this first X chromosome-wide association study of adult patients with IBD, we identified an IBD susceptibility locus with genome-wide significance at rs2427870 on chrXq26.3, located 66 kbp upstream of CD40LG and 83.4 kbp upstream of ARHGEF6 [OR, 1.22; combined p = 3.79 x 10-15].
      Title: X Chromosome-wide Association Study Identifies a Susceptibility Locus for Inflammatory Bowel Disease in Koreans.
    7. we discuss recent findings in key physiological systems that exemplify current understanding of the function of this important regulatory complex. Further, we draw attention to gaps in crucial information that remain to be filled to allow a better understanding of the many roles of the GIT-PIX complex in health and disease
      Title: Expanding functions of GIT Arf GTPase-activating proteins, PIX Rho guanine nucleotide exchange factors and GIT-PIX complexes.
    8. show that ARHGEF6 is constitutively linked to GIT1, a GAP of Arf family small G proteins, and that ARHGEF6 phosphorylation enables binding of the 14-3-3 adaptor protein to the ARHGEF6/GIT1 complex
      Title: Cyclic Nucleotide-dependent Protein Kinases Target ARHGAP17 and ARHGEF6 Complexes in Platelets.
    9. The novel recycling regulator alpha-PIX and the degradation factor c-Cbl closely cooperate in the regulation of EGFR trafficking.
      Title: αPIX Is a Trafficking Regulator that Balances Recycling and Degradation of the Epidermal Growth Factor Receptor.
    10. c-Cbl negatively regulates alphaPix-mediated cell migration and invasion; the lack of c-Cbl in C6 and A172 glioma cells is responsible for their malignant behavior
      Title: c-Cbl regulates αPix-mediated cell migration and invasion.
    Submit: New GeneRIF Correction See all GeneRIFs (21)

    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

    Copy number response

    Description
    Copy number response
    Haploinsufficency

    No evidence available (Last evaluated 2012-04-25)

    ClinGen Genome Curation Page
    Triplosensitivity

    No evidence available (Last evaluated 2012-04-25)

    ClinGen Genome Curation Page

    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
    Nef nef HIV-1 Nef binding and activation of p62 PAK induces the interaction and phosphorylation of PIX with the Nef-PAK complex 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

    • KIAA0006

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables GTPase activator activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables guanyl-nucleotide exchange factor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables guanyl-nucleotide exchange factor activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables guanyl-nucleotide exchange factor activity TAS
    Traceable Author Statement
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in JNK cascade NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in apoptotic process NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in lamellipodium assembly IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in lamellipodium assembly ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in cell-cell junction IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    is_active_in lamellipodium IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in lamellipodium ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    rho guanine nucleotide exchange factor 6
    Names
    PAK-interacting exchange factor, alpha
    Rac/Cdc42 guanine exchange factor (GEF) 6
    Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6

    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_008873.1 RefSeqGene

      Range
      5413..120795
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001306177.2 → NP_001293106.1  rho guanine nucleotide exchange factor 6 isoform 2

      See identical proteins and their annotated locations for NP_001293106.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks two 5' exons and contains an alternate 5' terminal exon, compared to variant 1. These differences cause translation initiation at a downstream AUG and result in an isoform (2) with a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AK294929, AK295709, AL135783, BC033768
      Consensus CDS
      CCDS78509.1
      UniProtKB/TrEMBL
      B7Z3C7
      Related
      ENSP00000359654.1, ENST00000370620.5
      Conserved Domains (6) summary
      cd12060
      Location:8 → 65
      SH3_alphaPIX; Src Homology 3 domain of alpha-Pak Interactive eXchange factor
      cd00160
      Location:88 → 265
      RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.
      cd01225
      Location:296 → 393
      PH_Cool_Pix; Cloned out of library/PAK-interactive exchange factor pleckstrin homology (PH) domain
      pfam00169
      Location:313 → 394
      PH; PH domain
      pfam16523
      Location:527 → 613
      betaPIX_CC; betaPIX coiled coil
      pfam16614
      Location:419 → 524
      RhoGEF67_u2; Unstructured region two on RhoGEF 6 and 7

    2. NM_004840.3 → NP_004831.1  rho guanine nucleotide exchange factor 6 isoform 1

      See identical proteins and their annotated locations for NP_004831.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      BC033768, BC039856
      Consensus CDS
      CCDS14660.1
      UniProtKB/Swiss-Prot
      A6NMW9, A8K6S7, B1AL37, Q15052, Q15396, Q5JQ66, Q7Z3W1, Q86XH0
      UniProtKB/TrEMBL
      A0A2X0SSH0
      Related
      ENSP00000250617.6, ENST00000250617.7
      Conserved Domains (8) summary
      cd12060
      Location:162 → 219
      SH3_alphaPIX; Src Homology 3 domain of alpha-Pak Interactive eXchange factor
      cd00160
      Location:242 → 419
      RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.
      cd01225
      Location:450 → 547
      PH_Cool_Pix; Cloned out of library/PAK-interactive exchange factor pleckstrin homology (PH) domain
      pfam00169
      Location:467 → 548
      PH; PH domain
      pfam00307
      Location:3 → 105
      CH; Calponin homology (CH) domain
      pfam16523
      Location:681 → 767
      betaPIX_CC; betaPIX coiled coil
      pfam16614
      Location:573 → 678
      RhoGEF67_u2; Unstructured region two on RhoGEF 6 and 7
      pfam16615
      Location:115 → 160
      RhoGEF67_u1; Unstructured region one on RhoGEF 6 and 7

    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_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      136665550..136780932 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005262499.4 → XP_005262556.1  rho guanine nucleotide exchange factor 6 isoform X6

      UniProtKB/TrEMBL
      A0A2X0SSH0
      Conserved Domains (8) summary
      cd12060
      Location:162 → 219
      SH3_alphaPIX; Src Homology 3 domain of alpha-Pak Interactive eXchange factor
      cd00160
      Location:242 → 419
      RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.
      cd01225
      Location:450 → 547
      PH_Cool_Pix; Cloned out of library/PAK-interactive exchange factor pleckstrin homology (PH) domain
      pfam00169
      Location:467 → 548
      PH; PH domain
      pfam00307
      Location:3 → 105
      CH; Calponin homology (CH) domain
      pfam16523
      Location:632 → 718
      betaPIX_CC; betaPIX coiled coil
      pfam16614
      Location:572 → 629
      RhoGEF67_u2; Unstructured region two on RhoGEF 6 and 7
      pfam16615
      Location:115 → 160
      RhoGEF67_u1; Unstructured region one on RhoGEF 6 and 7

    2. XM_047442672.1 → XP_047298628.1  rho guanine nucleotide exchange factor 6 isoform X4

    3. XM_011531413.3 → XP_011529715.1  rho guanine nucleotide exchange factor 6 isoform X3

      UniProtKB/TrEMBL
      A0A2X0SSH0
      Conserved Domains (8) summary
      cd12060
      Location:162 → 219
      SH3_alphaPIX; Src Homology 3 domain of alpha-Pak Interactive eXchange factor
      cd00160
      Location:242 → 419
      RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.
      cd01225
      Location:450 → 547
      PH_Cool_Pix; Cloned out of library/PAK-interactive exchange factor pleckstrin homology (PH) domain
      pfam00169
      Location:467 → 548
      PH; PH domain
      pfam00307
      Location:3 → 105
      CH; Calponin homology (CH) domain
      pfam16523
      Location:685 → 771
      betaPIX_CC; betaPIX coiled coil
      pfam16614
      Location:578 → 682
      RhoGEF67_u2; Unstructured region two on RhoGEF 6 and 7
      pfam16615
      Location:115 → 160
      RhoGEF67_u1; Unstructured region one on RhoGEF 6 and 7

    4. XM_011531412.4 → XP_011529714.1  rho guanine nucleotide exchange factor 6 isoform X2

      UniProtKB/TrEMBL
      A0A2X0SSH0
      Conserved Domains (8) summary
      cd12060
      Location:162 → 219
      SH3_alphaPIX; Src Homology 3 domain of alpha-Pak Interactive eXchange factor
      cd00160
      Location:269 → 446
      RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.
      cd01225
      Location:477 → 574
      PH_Cool_Pix; Cloned out of library/PAK-interactive exchange factor pleckstrin homology (PH) domain
      pfam00169
      Location:494 → 575
      PH; PH domain
      pfam00307
      Location:3 → 105
      CH; Calponin homology (CH) domain
      pfam16523
      Location:708 → 794
      betaPIX_CC; betaPIX coiled coil
      pfam16614
      Location:600 → 705
      RhoGEF67_u2; Unstructured region two on RhoGEF 6 and 7
      pfam16615
      Location:115 → 160
      RhoGEF67_u1; Unstructured region one on RhoGEF 6 and 7

    5. XM_017029975.3 → XP_016885464.1  rho guanine nucleotide exchange factor 6 isoform X1

      UniProtKB/TrEMBL
      A0A2X0SSH0

    6. XM_047442675.1 → XP_047298631.1  rho guanine nucleotide exchange factor 6 isoform X9

    7. XM_047442674.1 → XP_047298630.1  rho guanine nucleotide exchange factor 6 isoform X8

    8. XM_047442673.1 → XP_047298629.1  rho guanine nucleotide exchange factor 6 isoform X7

    9. XM_011531415.3 → XP_011529717.1  rho guanine nucleotide exchange factor 6 isoform X5

      UniProtKB/TrEMBL
      A0A2X0SSH0
      Conserved Domains (7) summary
      cd12060
      Location:105 → 162
      SH3_alphaPIX; Src Homology 3 domain of alpha-Pak Interactive eXchange factor
      cd00160
      Location:212 → 389
      RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.
      cd01225
      Location:420 → 517
      PH_Cool_Pix; Cloned out of library/PAK-interactive exchange factor pleckstrin homology (PH) domain
      pfam00169
      Location:437 → 518
      PH; PH domain
      pfam16523
      Location:651 → 737
      betaPIX_CC; betaPIX coiled coil
      pfam16614
      Location:543 → 648
      RhoGEF67_u2; Unstructured region two on RhoGEF 6 and 7
      pfam16615
      Location:58 → 103
      RhoGEF67_u1; Unstructured region one on RhoGEF 6 and 7

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      134974276..135089655 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054328173.1 → XP_054184148.1  rho guanine nucleotide exchange factor 6 isoform X6

    2. XM_054328171.1 → XP_054184146.1  rho guanine nucleotide exchange factor 6 isoform X4

    3. XM_054328170.1 → XP_054184145.1  rho guanine nucleotide exchange factor 6 isoform X3

    4. XM_054328169.1 → XP_054184144.1  rho guanine nucleotide exchange factor 6 isoform X2

    5. XM_054328168.1 → XP_054184143.1  rho guanine nucleotide exchange factor 6 isoform X1

    6. XM_054328176.1 → XP_054184151.1  rho guanine nucleotide exchange factor 6 isoform X9

    7. XM_054328175.1 → XP_054184150.1  rho guanine nucleotide exchange factor 6 isoform X8

    8. XM_054328174.1 → XP_054184149.1  rho guanine nucleotide exchange factor 6 isoform X7

    9. XM_054328172.1 → XP_054184147.1  rho guanine nucleotide exchange factor 6 isoform X5

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q15052.2 GenPept UniProtKB/Swiss-Prot:Q15052

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