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FLASH GENE
Symbol ARF6 contributors: mct - updated : 28-04-2017
HGNC name ADP-ribosylation factor 6
HGNC id 659
Location 14q21.3      Physical location : 50.359.735 - 50.363.771
Synonym symbol(s) DKFZp564M0264
EC.number 3.6.5.1/3.6.5.2/3.6.5.3
DNA
TYPE functioning gene
STRUCTURE 4.04 kb     2 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence cytosine-phosphate-guanine/HTF
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
2 - 3939 - 175 - - 14659046
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Digestivemouthtongue  highly
Lymphoid/Immunelymph node   highly
Reproductivemale systemtestis  highly Homo sapiens
Urinarybladder   highly
 kidney   highly
cells
SystemCellPubmedSpeciesStageRna symbol
Reproductivespermatozoa Homo sapiens
cell lineage
cell lines
fluid/secretion in sperm
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
HOMOLOGY
interspecies homolog to C.elegans
Homologene
FAMILY
  • small GTPase superfamily, Ras-like protein family
  • ADP-ribosylation factors (ARF) family
    • CATEGORY transcription factor , transport
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    text
  • localizes to the plasma membrane and endosomal compartments
  • important in cytokinesis and localizes to the midbody
    • basic FUNCTION
  • activator of PIP5K1A, phospholipase D
  • GTP binding protein, allosteric activator of cholera toxin, with ADP-ribosyltransferase activity
  • involved in vesicular trafficking
  • regulating membrane movements between plasma membrane and endosomal compartments in non polarized cells
  • implicated to function in membrane ruffling and cell motility, endocytosis, exocytosis, and membrane recycling
  • playing a pivotal role in breast cancer invasive activities
  • involved in the regulation of dendritic spine development and maintenance
  • regulates multiple cellular processes, including endocytosis, secretion, phagocytosis, cell adhesion, and cell migration
  • may regulate the conversion of filopodia to dendritic spines and the stability of both early and mature spines
  • possible involvement of PSD-ARF6 signaling in the karyokinesis and cytokinesis
  • involved in neurite formation through ARL4D and CYTH2
  • regulates endocytic recycling to the bridge during cytokinesis and is required for abscission
  • with ARF1, load GTP in a membrane-curvature-dependent manner and stabilize, or further facilitate, changes in membrane curvature through the insertion of an amphipathic helix
  • key player in mammalian peroxisome biogenesis
  • critical upstream signaling element in the activation of phospholipase D necessary to produce the fusogenic lipids required for exocytosis
  • small GTPase ARF6 having a central role in regulating membrane traffic and actin dynamics, and its activity has been demonstrated to be involved in neurite elaboration
  • EGF-induced ARF6 expression plays a significant role in glioma cell proliferation
  • ARF6/MAPK8IP3 signaling regulates neurite morphogenesis
  • critical regulator of C2C12 myoblast fusion and participates in the regulation of phospholipase D activities that trigger both phospholipids production and actin cytoskeleton reorganization at fusion sites
  • involvement in carcinogenesis and metastasis highlights the importance of the presented structure in general and the Ca2+-binding pocket in particular as it may give clues for designing inhibitors for therapeutic applications
  • regulates the processes of endocytosis and endocytic recycling in concert with various effector molecules and other small GTPases
  • is implicated in angiogenesis
  • novel function of ARF6 in the internalization of P2Y purinoceptors and importance of this small GTPase upon platelet ADP receptor function
  • ARF6 and CYTH1 are required for migration of primary Schwann cells
  • regulates neuronal differentiation through an effect on glucosylceramide synthase and glucosylceramide levels
  • reorganizes the actin cytoskeleton through the regulation of RAC1 activity
  • regulates membrane trafficking and cytoskeleton rearrangements at the plasma membrane (PM) by cycling between the GTP-bound active and GDP-bound inactive conformations
  • activity-dependent dynamic changes in ARF6-mediated spine structures may play a role in structural plasticity of mature neurons
  • is required for calcium and diacylglycerol-induced exocytosis in sperm
  • importance of ARF6 as a key factor for human sperm exocytosis and fertilization
    • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS endocytosis transport , cellular trafficking transport
    text regulated membrane traffick essential in adherens junction and epithelial cell migration turnover
    PATHWAY
    metabolism
    signaling
  • IQSEC1-ARF6-ASAP1-cortactin pathway is essential for angiogenesis activities, including cell migration and tubular formation
  • PSD-ARF6 pathway may play a specific role at a subcompartment of perisynaptic photoreceptor processes
    • a component
  • ARF6/MAPK8IP3 signaling regulates neurite morphogenesis
  • ARF6 forms a complex with MICALL1 and plays a role in its recruitment to tubular endosome
  • MYD88-CYTH2-ARF6 is a valid target for inflammatory conditions confirming a relevant role for manipulation of this pathway to modulate inflammatory processes and in the treatment of disease
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • DDEF1 as an effector of GTP-ARF6 in breast cancer invasion
  • role for GULP1 as a positive regulator of ARF6, and GULP1 is a modifier of cellular ARF6-GTP through regulation of ACAP1
  • RAB11FIP3 and ARF6 binding is required for the targeting of ARF6 to the cleavage furrow during cytokinesis
  • PSD act as a guanine nucleotide exchange factor (GEF) for ARF6
  • VEZT was able to bind specifically to GTP-ARF6 among the ARF family
  • interacting with SPAG9
  • likely RAB35 regulates actin-dependent phagosome formation by recruiting ACAP2, which might control actin remodeling and membrane traffic through ARF6
  • is an important mediator of cytoskeleton and cell motility, which is regulated by PLCB3-dependent membrane translocation of the guanine nucleotide exchange factors (GEFs)
  • oncogenic potential of USP6 is linked to its ability to integrate cell migration and cytokinesis by regulating ARF6/ACAP1
  • TBC1D10A interacts with SYTL1 to coordinate RAB8A and ARF6 membrane trafficking
  • ARF6 activated by the LHCGR through the cytohesin family of guanine nucleotide exchange factors mediates the receptor internalization and signaling
  • in addition to ARF6, endogenous IQSEC1 also activates the class II Arfs, ARF4 and ARF5, and surprisingly, ARF5 mediates integrin internalization
  • ARF6 inactivation by expression of ACAP1 leads to increased recycling of ITGB1 to the neuronal surface and to increased anterograde axonal transport
  • novel function of ARF6 in the internalization of P2RY1, P2RY12 purinoceptors, demonstrating the integral importance of this small GTPase upon platelet ADP receptor function
  • GRASP interacts with CYTH3, which catalyses nucleotide exchange on and activation of ARF6
  • CYTH2 binds directly to the adaptor protein MYD88, and likely MYD88-CYTH2-ARF6 is a proximal IL1B signalling pathway distinct from that mediated by NFKB1
  • interplay between RAB35 and ARF6 controls cargo recycling to coordinate cell adhesion and migration
  • RAC1 has been reported to function downstream of ARF6 to control membrane ruffling and cell migration
  • changes in ARF6 and RAC1 activities are necessary but not sufficient for ARAP2 to promote the growth of Focal adhesions (FAs)
  • through regulation of ARF6, ARAP2 may control the recycling of integrins or other adhesion components, leading to a change in the adhesion turnover
  • PSD participates in activation of ARF6 around the cleavage furrow during cytokinesis
  • APBB1 via its first phosphotyrosine binding (PTB) domain, binds to the small GTPase ADP-ribosylation factor 6 (ARF6)
  • SNX1 is an ARF6-specific guanine nucleotide exchange factor that is abundantly expressed in the brain
  • critical role for ARF6 in regulating TICAM2/TICAM1-dependent TLR4 signaling
  • ARHGAP24 binds to ARF6 through its pleckstrin homology domain
  • plays a role in EDN1 promoted endothelial cell migration, and acts upstream of ERK in EDN1-induced lipolysis
  • MAPK8IP3 and SPAG9 control ARF6 localization to the midbody by forming a tripartite complex of MAPK8IP3/SPAG9, active ARF6, and kinesin-1
  • PSD3 specifically catalyzed the GTP loading of ARF6 in mammalian cells
  • CYTH2 activates ARF6 in a PI3K dependent manner and then the active ARF6 causes phosphorylation of ERK1/2 during preadipocyte migration
  • CYTH2 interaction with the RALBP1 N-terminus regulates cell spreading and motility via PI3K and ARF6, independent of RALBP1 control of RAC1
  • is a GTPase-activating protein (GAP) that inactivates ARF6 and RHOA small GTPases
  • RALBP1 acts as a scaffold at recycling endosomes by binding activated RRAS, recruiting CYTH2 to activate ARF6, thereby contributing to cell spreading and migration
  • ARF6 functions as a downstream molecule of DNM2 in clathrin-mediated endocytosis (CME)
  • novel ARF6 activation mechanism by DNM2 through PSD4 and PSD3 in CME in a manner dependent upon the GTPase activity of DNM2
  • both ARF6 activation through GRIN2B-IQSEC2 during early development and the transition from IQSEC2- to IQSEC1-dependent ARF6 signaling induced by the GRIN2B subunit switch are critical for the development of mature glutamatergic synapses
  • ARF6-independent endocytic pathways may contribute to ABCA1 recycling and efflux of intracellular cholesterol
  • IQSEC1 is a guanine nucleotide exchange factor for ADP-ribosylation factor 6 (ARF6), a critical GTPase that regulates endosomal trafficking and actin cytoskeleton remodeling
  • ELMOD1 acts as a GTPase-activating protein for ARF6 in hair cells, and its developmentally regulated GAP activity is required to stabilize apical structures of hair cells
  • by inactivating ARF6, ELMOD1 apparently controls the extent of actin remodeling in hair cells
    • cell & other
    REGULATION
    activated by the GTPase activating protein CENTB1, CENTB2
    by GTP-exchange factors (GEFs) such as CYTH2
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS