ARF6 ADP ribosylation factor 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ARF6provided by HGNC
Official Full Name: ADP ribosylation factor 6provided by HGNC
Primary source: HGNC:HGNC:659
See related: Ensembl:ENSG00000165527 MIM:600464
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
Summary: This gene encodes a member of the human ARF gene family, which is part of the RAS superfamily. The ARF genes encode small guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin and play a role in vesicular trafficking and as activators of phospholipase D. The product of this gene is localized to the plasma membrane, and regulates vesicular trafficking, remodelling of membrane lipids, and signaling pathways that lead to actin remodeling. A pseudogene of this gene is located on chromosome 7. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in esophagus (RPKM 54.5), colon (RPKM 38.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 14q21.3

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
109.20201120	current	GRCh38.p13 (GCF_000001405.39)	14	NC_000014.9 (49893082..49897054)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (50359736..50363772)

Chromosome 14 - NC_000014.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Small GTPase ARF6 Is a Coincidence-Detection Code for RPH3A Polarization in Neutrophil Polarization.
Title: Small GTPase ARF6 Is a Coincidence-Detection Code for RPH3A Polarization in Neutrophil Polarization.
Depletion of Arf6 compromises cross-presentation of immune complexes but not of soluble, phagocytosed or mannose receptor-targeted antigen, suggesting a role of Fc receptor-regulated Arf6 trafficking in cross-presentation of immune complexes.
Title: The role of MHC class I recycling and Arf6 in cross-presentation by murine dendritic cells.
Despite Iqsec2 normally acting to activate Arf6 substrate, authors demonstrate that mice modelling the loss of Iqsec2 function present with increased levels of activated Arf6. Authors contend that loss of Iqsec2 function leads to altered regulation of activated Arf6-mediated responses to synaptic signalling and immature synaptic networks.
Title: Heterozygous loss of function of <i>IQSEC2</i>/<i>Iqsec2</i> leads to increased activated Arf6 and severe neurocognitive seizure phenotype in females.
A novel redox-sensitive APE1-ARF6-MMP-14 signaling axis that mediates cellular invasion in esophageal adenocarcinoma.APE1 promotes ARF6 activity via interaction and redox function.
Title: APE1 Upregulates MMP-14 via Redox-Sensitive ARF6-Mediated Recycling to Promote Cell Invasion of Esophageal Adenocarcinoma.
High glucose-induced cholesterol accumulation and cellular injury in podocytes may be related to the recycling disorder of ABCA1 caused by the downexpression of Arf6 in diabetic kidney disease.
Title: Small GTPase Arf6 regulates diabetes-induced cholesterol accumulation in podocytes.
Results revealed that Arf6-mediated CD147 endocytic recycling is required for the malignant phenotypes of liver cancer.
Title: Arf6-driven endocytic recycling of CD147 determines HCC malignant phenotypes.
In human brain endothelial cells that were damaged by hypoxia plus IL-1beta, treatment with recombinant ANXA2 (rA2) rescued the expression of junctional proteins and decreased trans-endothelial permeability. The protective effects were mediated in part by interactions with F-actin and VE-cadherin, and the ability of rA2 to modulate signaling via Robo4 -paxillin- ARF6.
Title: Annexin A2 is a Robo4 ligand that modulates ARF6 activation-associated cerebral trans-endothelial permeability.
The Arf6 depletion promotes the loss of RhoB from endosomal membranes and leads to RhoB degradation through an endolysosomal pathway.
Title: Arf6 regulates RhoB subcellular localization to control cancer cell invasion.
ARF6 is necessary for PI3K and AKT activation in human cancer cells.A prometastatic role for ARF6 independent of tumor growth, which may help explain how melanoma spreads distantly from thin, early-stage primary tumors.ARF6 is aberrantly activated in melanoma patients.
Title: The Small GTPase ARF6 Activates PI3K in Melanoma to Induce a Prometastatic State.
Knockdown of ARF6, but not GEP100, decreased high-glucose-induced internalization of VEGFR2.
Title: GEP100/ARF6 regulates VEGFR2 signaling to facilitate high-glucose-induced epithelial-mesenchymal transition and cell permeability in retinal pigment epithelial cells.

Submit: New GeneRIF Correction See all GeneRIFs (159)

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

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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Replication interactions

Interaction	Pubs
Knockdown of ADP-ribosylation factor 6 (ARF6) by siRNAs significantly enhances HIV-1 replication in human acute monocytic leukemia cells	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Tandem affinity purification and mass spectrometry analysis identify ADP-ribosylation factor 6 (ARF6), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Envelope surface glycoprotein gp160, precursor	env	GDP-bound or GTP-bound inactive Arf6 mutants or siRNA-mediated Arf6 silencing inhibit HIV-1 envelope-induced membrane fusion, entry, and infection of T lymphocytes and permissive cells	PubMed
Gag-Pol	gag-pol	Tandem affinity purification and mass spectrometry analysis identify ADP-ribosylation factor 6 (ARF6), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Nef	nef	Tandem affinity purification and mass spectrometry analysis identify ADP-ribosylation factor 6 (ARF6), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
	nef	ARF6(T27N) and ARF6(Q67L) mutants induce significant reversal of HLA-I A2 downregulation by HIV-1 Nef through redistributing HLA-I A2 from the perinuclear vesicles to the peripheral punctate vesicles at the plasma membrane	PubMed
	nef	The interaction of HIV-1 Nef and phosphatidylinositol-3-kinase (PI3K) activates the expression of ADP-ribosylation factor 6 (ARF6) in human melanoma cells	PubMed
	nef	HIV-1 Nef-mediated downregulation of MHC-I has been reported to be regulated by ARF6, however a separate report indicates the apparent Arf6 dependency of Nef-mediated MHC class I down-modulation is due to nonspecific perturbations in membrane traffic	PubMed
Pr55(Gag)	gag	Tandem affinity purification and mass spectrometry analysis identify ADP-ribosylation factor 6 (ARF6), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
	gag	Overexpression of an active form of Arf6 (Arf6/Q67L), which induces the formation of PI(4,5)P2-enriched endosomal structures, severely reduces HIV-1 Gag virus production by redirecting Gag to PI(4,5)P2-enriched vesicles	PubMed

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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

RH80260 (e-PCR)
- UniSTS:85506

ARF6_719 (e-PCR)
- UniSTS:277010

SHGC-64115 (e-PCR)
- UniSTS:48227

SHGC-2638 (e-PCR)
- UniSTS:68266

D14S793 (e-PCR)
- UniSTS:153530

SHGC-64342 (e-PCR)
- UniSTS:9452

Homology

Homologs of the ARF6 gene: The ARF6 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, S.cerevisiae, K.lactis, E.gossypii, S.pombe, M.oryzae, N.crassa, and frog.
Orthologs from Annotation Pipeline: 333 organisms have orthologs with human gene ARF6
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
GDP binding	IDA Inferred from Direct Assay more info	PubMed
GTP binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
GTP binding	IDA Inferred from Direct Assay more info	PubMed
GTP binding	TAS Traceable Author Statement more info	PubMed
GTPase activity	IEA Inferred from Electronic Annotation more info
protein N-terminus binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
thioesterase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
cell adhesion	TAS Traceable Author Statement more info	PubMed
cell cycle	IEA Inferred from Electronic Annotation more info
cell differentiation	IEA Inferred from Electronic Annotation more info
cell division	IEA Inferred from Electronic Annotation more info
cellular response to nerve growth factor stimulus	IEA Inferred from Electronic Annotation more info
cortical actin cytoskeleton organization	IDA Inferred from Direct Assay more info	PubMed
cortical actin cytoskeleton organization	IMP Inferred from Mutant Phenotype more info	PubMed
endocytic recycling	IDA Inferred from Direct Assay more info	PubMed
establishment of epithelial cell polarity	IEA Inferred from Electronic Annotation more info
hepatocyte apoptotic process	IEA Inferred from Electronic Annotation more info
intracellular protein transport	IBA Inferred from Biological aspect of Ancestor more info	PubMed
liver development	IEA Inferred from Electronic Annotation more info
maintenance of postsynaptic density structure	IEA Inferred from Electronic Annotation more info
myeloid cell apoptotic process	IEA Inferred from Electronic Annotation more info
negative regulation of dendrite development	IEA Inferred from Electronic Annotation more info
negative regulation of protein localization to cell surface	IEA Inferred from Electronic Annotation more info
negative regulation of receptor-mediated endocytosis	TAS Traceable Author Statement more info	PubMed
nervous system development	IEA Inferred from Electronic Annotation more info
positive regulation of actin filament polymerization	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of focal adhesion disassembly	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of keratinocyte migration	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of protein localization to plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of protein secretion	IMP Inferred from Mutant Phenotype more info	PubMed
protein localization to cell surface	ISS Inferred from Sequence or Structural Similarity more info
protein localization to endosome	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein localization to endosome	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of Rac protein signal transduction	IDA Inferred from Direct Assay more info	PubMed
regulation of dendritic spine development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of dendritic spine development	ISS Inferred from Sequence or Structural Similarity more info
regulation of filopodium assembly	IDA Inferred from Direct Assay more info	PubMed
regulation of presynapse assembly	IEA Inferred from Electronic Annotation more info
ruffle assembly	IDA Inferred from Direct Assay more info	PubMed
synaptic vesicle endocytosis	IEA Inferred from Electronic Annotation more info
vesicle-mediated transport	IBA Inferred from Biological aspect of Ancestor more info	PubMed
vesicle-mediated transport	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
Flemming body	IDA Inferred from Direct Assay more info	PubMed
Golgi apparatus	IEA Inferred from Electronic Annotation more info
cell cortex	IDA Inferred from Direct Assay more info	PubMed
cleavage furrow	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytosol	IDA Inferred from Direct Assay more info	PubMed
early endosome membrane	IEA Inferred from Electronic Annotation more info
endocytic vesicle	IBA Inferred from Biological aspect of Ancestor more info	PubMed
endocytic vesicle	IDA Inferred from Direct Assay more info	PubMed
endosome	IDA Inferred from Direct Assay more info	PubMed
endosome	TAS Traceable Author Statement more info	PubMed
extracellular exosome	HDA more info	PubMed
filopodium membrane	IDA Inferred from Direct Assay more info	PubMed
focal adhesion	HDA more info	PubMed
glutamatergic synapse	IEA Inferred from Electronic Annotation more info
membrane	HDA more info	PubMed
membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info	PubMed
presynapse	IEA Inferred from Electronic Annotation more info
recycling endosome membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
recycling endosome membrane	IDA Inferred from Direct Assay more info	PubMed
recycling endosome membrane	TAS Traceable Author Statement more info
ruffle	IBA Inferred from Biological aspect of Ancestor more info	PubMed
ruffle	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: ADP-ribosylation factor 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.