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

Genomic context

Location:: 14q21.3

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	14	NC_000014.9 (49893018..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 FunctionsWhat's a GeneRIF?

Arf6 and caveolae are essential for hemidesmosome remodeling, notably in response to external mechanical cues.
Title: An Arf6- and caveolae-dependent pathway links hemidesmosome remodeling and mechanoresponse.
Data show that the ADP-ribosylation factor 6 (Arf6)-trafficking kinesin protein 1 (trak1) promote the anterograde trafficking of mitochondria.
Title: Arf6-driven cell invasion is intrinsically linked to TRAK1-mediated mitochondrial anterograde trafficking to avoid oxidative catastrophe.
Structural dynamics control allosteric activation of Grp1 and ARF6.
Title: Structural Dynamics Control Allosteric Activation of Cytohesin Family Arf GTPase Exchange Factors.
Arf6 appears to be necessary for both RhoA- and Rac1-driven cancer invasion
Title: Arf6 and its ZEB1-EPB41L5 mesenchymal axis are required for both mesenchymal- and amoeboid-type invasion of cancer cells.
By means of reducing the expression of Arf6 and subsequent signal transduction via NF-kappaB, miR-145 plays a role in inhibiting the secretion of inflammatory factors and then improving the inflammatory status.
Title: MiR-145 improves macrophage-mediated inflammation through targeting Arf6.
In Jurkat cells, the activities of two guanine nucleotide binding proteins, Arf6 and Rab22 (also known as Rab22a), influence CIE and conjugate formation.
Title: Arf6 and Rab22 mediate T cell conjugate formation by regulating clathrin-independent endosomal membrane trafficking.
The Arf6 is of particular interest,since it is believed to play a regulatory role in several cellular physiological functions, including cell-cell interactions(adhesiveness), motility, shape maintenance, and responses to environmental stimuli via cytoskeletal adaptations and vesicular trafficking.
Title: In focus in HCB.
computational study suggests that although curcumin to some extent binds with Tp receptor, yet the inhibition of Arf6GDP to Arf6GTP conversion appeared to be an important mechanism by which curcumin inhibits U46619-induced increase in PLD activity in PASMCs.
Title: Role of curcumin in PLD activation by Arf6-cytohesin1 signaling axis in U46619-stimulated pulmonary artery smooth muscle cells.
This study identifies a novel regulatory crosstalk between Ral and Arf6 that controls Ral function in cells.
Title: Ral-Arf6 crosstalk regulates Ral dependent exocyst trafficking and anchorage independent growth signalling.
ARHGAP24 may regulate pseudopod formation downstream of activated ARF6 in MDA-MB-231 human breast carcinoma cells.
Title: Role of ARHGAP24 in ADP Ribosylation Factor 6 (ARF6)-dependent Pseudopod Formation in Human Breast Carcinoma Cells.

Submit: New GeneRIF Correction See all GeneRIFs (142)

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

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

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Arf6 downstream pathway, organism-specific biosystem (from Pathway Interaction Database)
Arf6 downstream pathway, organism-specific biosystem
Arf6 downstream pathway
Arf6 signaling events, organism-specific biosystem (from Pathway Interaction Database)
Arf6 signaling events, organism-specific biosystem
Arf6 signaling events
Arf6 trafficking events, organism-specific biosystem (from Pathway Interaction Database)
Arf6 trafficking events, organism-specific biosystem
Arf6 trafficking events
Class I PI3K signaling events, organism-specific biosystem (from Pathway Interaction Database)
Class I PI3K signaling events, organism-specific biosystem
Class I PI3K signaling events
Clathrin-mediated endocytosis, organism-specific biosystem (from REACTOME)
Clathrin-mediated endocytosis, organism-specific biosystemClathrin-mediated endocytosis (CME) is one of a number of process that control the uptake of material from the plasma membrane, and leads to the formation of clathrin-coated vesicles (Pearse et al, 1...
E-cadherin signaling in the nascent adherens junction, organism-specific biosystem (from Pathway Interaction Database)
E-cadherin signaling in the nascent adherens junction, organism-specific biosystem
E-cadherin signaling in the nascent adherens junction
EGF/EGFR Signaling Pathway, organism-specific biosystem (from WikiPathways)
EGF/EGFR Signaling Pathway, organism-specific biosystemEpidermal growth factor receptor (EGFR) also known as ErbB1/HER1 is a member of the ErbB family of receptor tyrosine kinases which also includes ErbB2 (Neu, HER2), ErbB3 (HER3) and ErbB4 (HER4). Sev...
Endocytosis, organism-specific biosystem (from KEGG)
Endocytosis, organism-specific biosystemEndocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins en...
Endocytosis, conserved biosystem (from KEGG)
Endocytosis, conserved biosystemEndocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins en...
Fc gamma R-mediated phagocytosis, organism-specific biosystem (from KEGG)
Fc gamma R-mediated phagocytosis, organism-specific biosystemPhagocytosis plays an essential role in host-defense mechanisms through the uptake and destruction of infectious pathogens. Specialized cell types including macrophages, neutrophils, and monocytes ta...
Fc gamma R-mediated phagocytosis, conserved biosystem (from KEGG)
Fc gamma R-mediated phagocytosis, conserved biosystemPhagocytosis plays an essential role in host-defense mechanisms through the uptake and destruction of infectious pathogens. Specialized cell types including macrophages, neutrophils, and monocytes ta...
Insulin Signaling, organism-specific biosystem (from WikiPathways)
Insulin Signaling, organism-specific biosystemInsulin signaling influences energy metabolism as well as growth. The presence of insulin signals the fed state, and this signal is passed via the AKT branch, which leads to the uptake of glucose fro...
MET receptor recycling, organism-specific biosystem (from REACTOME)
MET receptor recycling, organism-specific biosystemActivated MET receptor is subject to recycling from the plasma membrane through the endosomal compartment and back to the plasma membrane (Peschard et al. 2001, Hammond et al. 2001, Petrelli et al. 2...
Membrane Trafficking, organism-specific biosystem (from REACTOME)
Membrane Trafficking, organism-specific biosystemThe secretory membrane system allows a cell to regulate delivery of newly synthesized proteins, carbohydrates, and lipids to the cell surface, a necessity for growth and homeostasis. The system is ma...
Paxillin-dependent events mediated by a4b1, organism-specific biosystem (from Pathway Interaction Database)
Paxillin-dependent events mediated by a4b1, organism-specific biosystem
Paxillin-dependent events mediated by a4b1
Paxillin-independent events mediated by a4b1 and a4b7, organism-specific biosystem (from Pathway Interaction Database)
Paxillin-independent events mediated by a4b1 and a4b7, organism-specific biosystem
Paxillin-independent events mediated by a4b1 and a4b7
Phospholipase D signaling pathway, organism-specific biosystem (from KEGG)
Phospholipase D signaling pathway, organism-specific biosystemPhospholipase D (PLD) is an essential enzyme responsible for the production of the lipid second messenger phosphatidic acid (PA), which is involved in fundamental cellular processes, including membra...
Phospholipase D signaling pathway, conserved biosystem (from KEGG)
Phospholipase D signaling pathway, conserved biosystemPhospholipase D (PLD) is an essential enzyme responsible for the production of the lipid second messenger phosphatidic acid (PA), which is involved in fundamental cellular processes, including membra...
Ras signaling pathway, organism-specific biosystem (from KEGG)
Ras signaling pathway, organism-specific biosystemThe Ras proteins are GTPases that function as molecular switches for signaling pathways regulating cell proliferation, survival, growth, migration, differentiation or cytoskeletal dynamism. Ras prote...
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by MET, organism-specific biosystem (from REACTOME)
Signaling by MET, organism-specific biosystemMET is a receptor tyrosine kinase (RTK) (Cooper et al. 1984, Park et al. 1984) activated by binding to its ligand, Hepatocyte growth factor/Scatter factor (HGF/SF) (Bottaro et al. 1991, Naldini et al...
Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met), organism-specific biosystem (from Pathway Interaction Database)
Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met), organism-specific biosystem
Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
Stabilization and expansion of the E-cadherin adherens junction, organism-specific biosystem (from Pathway Interaction Database)
Stabilization and expansion of the E-cadherin adherens junction, organism-specific biosystem
Stabilization and expansion of the E-cadherin adherens junction
TBC/RABGAPs, organism-specific biosystem (from REACTOME)
TBC/RABGAPs, organism-specific biosystemRab GTPases are peripheral membrane proteins involved in membrane trafficking. Often through their indirect interactions with coat components, motors, tethering factors and SNAREs, the Rab GTPases se...
Vesicle-mediated transport, organism-specific biosystem (from REACTOME)
Vesicle-mediated transport, organism-specific biosystemThe transit of proteins and other cargo through the cell requires a cellular transport process in which transported substances are moved in membrane-bounded vesicles. Transported substances are enclo...

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: 228 organisms have orthologs with human gene ARF6
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
GTP binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
GTP binding	TAS Traceable Author Statement more info	PubMed
GTPase activity	TAS Traceable Author Statement more info	PubMed
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 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
positive regulation of actin filament polymerization	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of adherens junction organization	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
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	IEA Inferred from Electronic Annotation more info
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	IBA Inferred from Biological aspect of Ancestor 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
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

NP_001654.1

EC 3.6.5.1

EC 3.6.5.2

EC 3.6.5.3

EC 3.6.5.4

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.