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ARF6 ARF GTPase 6 [ Homo sapiens (human) ]

Gene ID: 382, updated on 9-Apr-2026

Summary

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Official Symbol: ARF6provided by HGNC
Official Full Name: ARF GTPase 6provided by HGNC
Primary source: HGNC:HGNC:659
See related: Ensembl:ENSG00000165527 MIM:600464; AllianceGenome:HGNC:659
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: all
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Genomic context

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See ARF6 in Genome Data Viewer

Location:: 14q21.3

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2025_08	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (49893082..49897054)
RS_2025_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (44098298..44102268)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (50359800..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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

CD24 promotes metastasis and chemoresistance by directly targeting Arf6-ERK pathway in esophageal squamous cell carcinoma.
Title: CD24 promotes metastasis and chemoresistance by directly targeting Arf6-ERK pathway in esophageal squamous cell carcinoma.
ARF6 promotes Streptococcus suis suilysin induced apoptosis in HBMECs.
Title: ARF6 promotes Streptococcus suis suilysin induced apoptosis in HBMECs.
HUNK inhibits cargo uptake and lysosomal traffic in the caveolar pathway via the AGAP3/ARF6.
Title: HUNK inhibits cargo uptake and lysosomal traffic in the caveolar pathway via the AGAP3/ARF6.
Enterovirus 71 enters human brain microvascular endothelial cells through an ARF6-mediated endocytic pathway.
Title: Enterovirus 71 enters human brain microvascular endothelial cells through an ARF6-mediated endocytic pathway.
ARF6 is a host factor for SARS-CoV-2 infection in vitro.
Title: ARF6 is a host factor for SARS-CoV-2 infection in vitro.
Regulatory imbalance between LRRK2 kinase, PPM1H phosphatase, and ARF6 GTPase disrupts the axonal transport of autophagosomes.
Title: Regulatory imbalance between LRRK2 kinase, PPM1H phosphatase, and ARF6 GTPase disrupts the axonal transport of autophagosomes.
KRAS, MYC, and ARF6: inseparable relationships cooperatively promote cancer malignancy and immune evasion.
Title: KRAS, MYC, and ARF6: inseparable relationships cooperatively promote cancer malignancy and immune evasion.
Pals1 functions in redundancy with SMAP1 to inhibit Arf6 in order to prevent Rac1-dependent colorectal cancer cell migration and invasion.
Title: Pals1 functions in redundancy with SMAP1 to inhibit Arf6 in order to prevent Rac1-dependent colorectal cancer cell migration and invasion.
A positive feedback loop of ARF6 activates ERK1/2 signaling pathway via DUSP6 silencing to promote pancreatic cancer progression.
Title: A positive feedback loop of ARF6 activates ERK1/2 signaling pathway via DUSP6 silencing to promote pancreatic cancer progression.
LncRNA FOXD3-AS1 promotes breast cancer progression by mediating ARF6.
Title: LncRNA FOXD3-AS1 promotes breast cancer progression by mediating ARF6.

Submit: New GeneRIF Correction See all GeneRIFs (179)

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)

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

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

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

Gene Ontology Provided by GOA

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

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

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

General protein information

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Preferred Names: ADP-ribosylation factor 6

Names: ADP ribosylation factor 6

NP_001654.1

EC 3.6.5.2

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.