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

Gene ID: 9459, updated on 3-Apr-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
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Genomic context

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Location:
Xq26.3
Exon count:
25
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (136665550..136780932, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (134974276..135089655, complement)
105.20220307 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. The pathological significance and potential mechanism of ARHGEF6 in lung adenocarcinoma. Zheng T, et al. Comput Biol Med, 2023 May. PMID 37058762
  2. 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
  3. 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
  4. 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
  5. Interaction between the Helicobacter pylori CagA and alpha-Pix in gastric epithelial AGS cells. Baek HY, et al. Ann N Y Acad Sci, 2007 Jan. PMID 17405911

See all (80) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. The pathological significance and potential mechanism of ARHGEF6 in lung adenocarcinoma.
    Title: The pathological significance and potential mechanism of ARHGEF6 in lung adenocarcinoma.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. results suggest that low doses of chlorambucil and very low doses of chronic oxidative stress together kill Cbl-resistant ovarian carcinoma cells and ARHGEF6 signaling may have an instrumental role in induction of apoptosis in Cbl(cos) cells.
    Title: Gene network analysis of oxidative stress-mediated drug sensitivity in resistant ovarian carcinoma cells.
Submit: New GeneRIF Correction See all GeneRIFs (20)

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)

Genotypes

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_2023_10

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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