P62330

EV
Gene name
ARF6
Protein name
ADP-ribosylation factor 6
Names
EC 3.6.5.2
Species
Homo sapiens (Human)
KEGG Pathway
hsa:382
EC number
3.6.5.2: Acting on GTP; involved in cellular and subcellular movement
Protein Class
ADP RIBOSYLATION FACTOR-RELATED (PTHR11711)

Descriptions

Small GTPases couple their GDP/GTP structural cycle to cytosol/membrane alternation to function as versatile molecular switches in the cell. Membrane localization of their active, GTP-bound form is pivotal to their ability to propagate information, and this requires their post-translational modification by lipids.
Arf GTPases are modified by a myristate attached to their N-terminus, which is shielded by intramolecular interactions in their inactive state. The myristoylated N-terminus of Arf is autoinhibitory in solution and is displaced by membranes, priming Arf GTPases for activation by their GEFs. Replacement of the N-terminal myristate by a 6xHis-tag preserves autoinhibition, representing that membranes unlock the N-terminal region to facilitate subsequent activation.

Autoinhibitory domains (AIDs)

3-16 (N-terminal helix) EV

Target domain

16-138 (Small GTP-binding protein domain)

Relief mechanism

Ligand binding

Assay

Mutagenesis experiment

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

20 structures for P62330

Entry ID Method Resolution Chain Position Source
1E0S X-ray 228 A A 2-175 PDB
2A5D X-ray 180 A A 1-175 PDB
2A5F X-ray 202 A A 1-175 PDB
2A5G X-ray 266 A A 1-175 PDB
2BAO NMR - A 2-11 PDB
2BAU NMR - A 2-11 PDB
2J5X X-ray 280 A A/B 2-175 PDB
2W83 X-ray 193 A A/B/E 13-175 PDB
3LVQ X-ray 338 A E 11-175 PDB
3LVR X-ray 338 A E 11-175 PDB
3N5C X-ray 182 A A/B 14-175 PDB
3PCR X-ray 250 A B 14-175 PDB
4FME X-ray 410 A C/F 14-173 PDB
4KAX X-ray 185 A A 14-173 PDB
6BBP EM 3500 A A 2-173 PDB
6BBQ EM 3500 A A 2-173 PDB
6PAU X-ray 193 A C 3-9 PDB
7RK3 X-ray 205 A B 2-9 PDB
7XRD EM 390 A A/B/C/D 2-175 PDB
AF-P62330-F1 Predicted AlphaFoldDB

95 variants for P62330

Variant ID(s) Position Change Description Diseaes Association Provenance
rs1594840659 4 V>G No Ensembl
rs1441587738 4 V>M No TOPMed
gnomAD
rs61754358 6 S>C No Ensembl
rs2139188407 10 G>W No Ensembl
rs781260800 12 K>M No ExAC
gnomAD
rs1894482875 14 M>L No TOPMed
rs1363572999 14 M>T No TOPMed
gnomAD
rs61754359 15 R>W No Ensembl
rs1894483036 16 I>L No TOPMed
rs1404939560 17 L>H No gnomAD
rs61755560 20 G>R No Ensembl
TCGA novel 21 L>V Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs1566734372 23 A>V No Ensembl
rs1344588000 28 T>R No gnomAD
rs1894483649 28 T>S No TOPMed
rs753915241 29 I>V No ExAC
gnomAD
COSM278936 31 Y>H Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs750270041 32 K>R No Ensembl
rs1435904439 33 L>V No gnomAD
rs1894484094 36 G>D No Ensembl
rs1243745440 36 G>S No Ensembl
rs1481108894 38 S>L No gnomAD
rs762265071 38 S>T No ExAC
gnomAD
rs1894484362 43 P>L No Ensembl
TCGA novel 48 N>D Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs1894484554 51 T>A No gnomAD
rs754692332 53 T>A No ExAC
gnomAD
rs780782180
COSM3496140
 53 T>I Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
ExAC
NCI-TCGA
gnomAD
rs1346734179 54 Y>H No TOPMed
gnomAD
rs747694604 56 N>H No ExAC
gnomAD
rs1894484984 58 K>N No TOPMed
rs376013488 58 K>Q No ESP
TOPMed
rs1253347869 60 N>S Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
gnomAD
rs61755564 61 V>I No Ensembl
rs1594840787
RCV000851183
 63 D>N No ClinVar
Ensembl
dbSNP
rs1490823531 68 D>H No gnomAD
rs61734985 72 P>A No Ensembl
rs1894485689 76 H>R No Ensembl
rs1162940832 78 Y>C No TOPMed
gnomAD
rs1894485896 81 T>A No TOPMed
TCGA novel 82 Q>H Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs1833340982 82 Q>R No gnomAD
rs773030685 85 I>V No Ensembl
rs1448005974 88 V>A No gnomAD
rs1427100688 95 R>L No gnomAD
rs761927063 96 I>F No ExAC
gnomAD
rs1382867198 97 D>G No gnomAD
TCGA novel 97 D>N Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs1157616494 98 E>D No TOPMed
rs765630104 98 E>K No ExAC
gnomAD
rs61755567 100 R>C No Ensembl
rs1594840868 100 R>P No Ensembl
rs1594840880 101 Q>P No Ensembl
rs1324913167 102 E>D No gnomAD
rs1594840885 102 E>G No Ensembl
rs3100898 103 L>M No Ensembl
rs1594840892 104 H>P No Ensembl
rs61755568 105 R>H No TOPMed
gnomAD
rs61755568 105 R>L No TOPMed
gnomAD
rs1894487086 106 I>T No Ensembl
rs1315455519 108 N>S No gnomAD
rs1894487217 110 R>L No TOPMed
rs1894487250 111 E>D No Ensembl
rs61755569 114 D>E No Ensembl
rs1894487475 119 I>T No TOPMed
rs61755570 121 A>T No Ensembl
rs1594840920 127 P>R No Ensembl
rs1224751831 127 P>S No TOPMed
rs1259152476 128 D>E No TOPMed
gnomAD
TCGA novel 130 M>I Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs1894488140 130 M>K No TOPMed
rs752233598 130 M>L No ExAC
gnomAD
rs61755571 134 E>K No Ensembl
COSM955980 139 L>M Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
TCGA novel 140 G>A Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
COSM955981 140 G>C Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs61755572 143 R>W No Ensembl
rs61755573 145 R>Q No Ensembl
COSM4848300 145 R>W Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
COSM955982 150 Y>H Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs61755574 151 V>G No Ensembl
TCGA novel 152 Q>H Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
TCGA novel 153 P>S Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs1276304050 156 A>G No gnomAD
rs745683323 160 D>E No ExAC
TOPMed
gnomAD
rs61755575 163 Y>C No ExAC
TOPMed
gnomAD
rs61755575 163 Y>F No ExAC
TOPMed
gnomAD
rs748170831 166 L>F No ExAC
gnomAD
rs932585633 170 T>I No TOPMed
gnomAD
COSM469994 171 S>T Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs763451475 173 Y>C No ExAC
gnomAD
TCGA novel 174 K>N Variant assessed as Somatic; HIGH impact. [NCI-TCGA] No NCI-TCGA
COSM117694 174 K>R Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs1894489427 174 K>T No TOPMed
rs1244615425 176 S>L No gnomAD

No associated diseases with P62330

3 regional properties for P62330

Type Name Position InterPro Accession
domain Sterile alpha motif domain 127 - 198 IPR001660
domain Stromal interaction molecule, Orai1-activating region 339 - 439 IPR032393
domain Stromal interaction molecule 1, SAM domain 126 - 199 IPR037609

Functions

Description
EC Number 3.6.5.2 Acting on GTP; involved in cellular and subcellular movement
Subcellular Localization
  • Cytoplasm, cytosol
  • Cell membrane ; Lipid-anchor
  • Endosome membrane ; Lipid-anchor
  • Recycling endosome membrane ; Lipid-anchor
  • Cell projection, filopodium membrane ; Lipid-anchor
  • Cell projection, ruffle
  • Cleavage furrow
  • Midbody, Midbody ring
  • Early endosome membrane ; Lipid-anchor
  • Golgi apparatus, trans-Golgi network membrane ; Lipid-anchor
  • Distributed uniformly on the plasma membrane, as well as throughout the cytoplasm during metaphase
  • Subsequently concentrated at patches in the equatorial region at the onset of cytokinesis, and becomes distributed in the equatorial region concurrent with cleavage furrow ingression
  • In late stages of cytokinesis, concentrates at the midbody ring/Flemming body (PubMed:23603394)
  • Recruitment to the midbody ring requires both activation by PSD/EFA6A and interaction with KIF23/MKLP1 (PubMed:23603394)
  • After abscission of the intercellular bridge, incorporated into one of the daughter cells as a midbody remnant and localizes to punctate structures beneath the plasma membrane (PubMed:23603394)
  • Recruited to the cell membrane in association with CYTH2 and ARL4C (PubMed:17398095)
  • Colocalizes with DAB2IP at the plasma membrane and endocytic vesicles (PubMed:19948740)
  • Myristoylation is required for proper localization to membranes: myristoylation on Lys-3 allows ARF6 to remain on membranes during the GTPase cycle (PubMed:32103017, PubMed:7589240)
PANTHER Family PTHR11711 ADP RIBOSYLATION FACTOR-RELATED
PANTHER Subfamily PTHR11711:SF322 ADP-RIBOSYLATION FACTOR 6
PANTHER Protein Class G-protein
PANTHER Pathway Category Integrin signalling pathway
Arf6
Huntington disease
ARF

18 GO annotations of cellular component

Name Definition
cell cortex The region of a cell that lies just beneath the plasma membrane and often, but not always, contains a network of actin filaments and associated proteins.
cleavage furrow The cleavage furrow is a plasma membrane invagination at the cell division site. The cleavage furrow begins as a shallow groove and eventually deepens to divide the cytoplasm.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
early endosome membrane The lipid bilayer surrounding an early endosome.
endocytic vesicle A membrane-bounded intracellular vesicle formed by invagination of the plasma membrane around an extracellular substance. Endocytic vesicles fuse with early endosomes to deliver the cargo for further sorting.
endosome A vacuole to which materials ingested by endocytosis are delivered.
extracellular exosome A vesicle that is released into the extracellular region by fusion of the limiting endosomal membrane of a multivesicular body with the plasma membrane. Extracellular exosomes, also simply called exosomes, have a diameter of about 40-100 nm.
filopodium membrane The portion of the plasma membrane surrounding a filopodium.
Flemming body A cell part that is the central region of the midbody characterized by a gap in alpha-tubulin staining. It is a dense structure of antiparallel microtubules from the central spindle in the middle of the intercellular bridge.
focal adhesion A cell-substrate junction that anchors the cell to the extracellular matrix and that forms a point of termination of actin filaments. In insects focal adhesion has also been referred to as hemi-adherens junction (HAJ).
glutamatergic synapse A synapse that uses glutamate as a neurotransmitter.
Golgi apparatus A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways.
membrane A lipid bilayer along with all the proteins and protein complexes embedded in it and attached to it.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
postsynapse The part of a synapse that is part of the post-synaptic cell.
presynapse The part of a synapse that is part of the presynaptic cell.
recycling endosome membrane The lipid bilayer surrounding a recycling endosome.
ruffle Projection at the leading edge of a crawling cell; the protrusions are supported by a microfilament meshwork.

6 GO annotations of molecular function

Name Definition
G protein activity A molecular function regulator that cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular processes. Intrinsic GTPase activity returns the G protein to its GDP-bound state. The return to the GDP-bound state can be accelerated by the action of a GTPase-activating protein (GAP).
GDP binding Binding to GDP, guanosine 5'-diphosphate.
GTP binding Binding to GTP, guanosine triphosphate.
GTPase activity Catalysis of the reaction
signaling adaptor activity The binding activity of a molecule that brings together two or more molecules in a signaling pathway, permitting those molecules to function in a coordinated way. Adaptor molecules themselves do not have catalytic activity.
thioesterase binding Binding to a thioesterase.

33 GO annotations of biological process

Name Definition
cell adhesion The attachment of a cell, either to another cell or to an underlying substrate such as the extracellular matrix, via cell adhesion molecules.
cell cycle The progression of biochemical and morphological phases and events that occur in a cell during successive cell replication or nuclear replication events. Canonically, the cell cycle comprises the replication and segregation of genetic material followed by the division of the cell, but in endocycles or syncytial cells nuclear replication or nuclear division may not be followed by cell division.
cell differentiation The cellular developmental process in which a relatively unspecialized cell, e.g. embryonic or regenerative cell, acquires specialized structural and/or functional features that characterize a specific cell. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state.
cell division The process resulting in division and partitioning of components of a cell to form more cells; may or may not be accompanied by the physical separation of a cell into distinct, individually membrane-bounded daughter cells.
cellular response to nerve growth factor stimulus A process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a nerve growth factor stimulus.
cortical actin cytoskeleton organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of actin-based cytoskeletal structures in the cell cortex, i.e. just beneath the plasma membrane.
endocytic recycling The directed movement of membrane-bounded vesicles from endosomes back to the plasma membrane, a trafficking pathway that promotes the recycling of internalized transmembrane proteins.
erythrocyte apoptotic process Any apoptotic process in an erythrocyte.
establishment of epithelial cell polarity The specification and formation of anisotropic intracellular organization of an epithelial cell.
hepatocyte apoptotic process Any apoptotic process in a hepatocyte, the main structural component of the liver.
intracellular protein transport The directed movement of proteins in a cell, including the movement of proteins between specific compartments or structures within a cell, such as organelles of a eukaryotic cell.
liver development The process whose specific outcome is the progression of the liver over time, from its formation to the mature structure. The liver is an exocrine gland which secretes bile and functions in metabolism of protein and carbohydrate and fat, synthesizes substances involved in the clotting of the blood, synthesizes vitamin A, detoxifies poisonous substances, stores glycogen, and breaks down worn-out erythrocytes.
maintenance of postsynaptic density structure A process which maintains the organization and the arrangement of proteins in the presynaptic density.
negative regulation of dendrite development Any process that stops, prevents, or reduces the frequency, rate or extent of dendrite development.
negative regulation of protein localization to cell surface Any process that stops, prevents, or reduces the frequency, rate or extent of protein localization to the cell surface.
negative regulation of receptor-mediated endocytosis Any process that stops, prevents, or reduces the frequency, rate or extent of receptor mediated endocytosis, the uptake of external materials by cells, utilizing receptors to ensure specificity of transport.
nervous system development The process whose specific outcome is the progression of nervous tissue over time, from its formation to its mature state.
positive regulation of actin filament polymerization Any process that activates or increases the frequency, rate or extent of actin polymerization.
positive regulation of focal adhesion disassembly Any process that activates or increases the frequency, rate or extent of disaggregation of a focal adhesion into its constituent components.
positive regulation of keratinocyte migration Any process that activates or increases the frequency, rate or extent of keratinocyte migration.
positive regulation of neuron projection development Any process that increases the rate, frequency or extent of neuron projection development. Neuron projection development is the process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites).
positive regulation of protein localization to plasma membrane Any process that activates or increases the frequency, rate or extent of protein localization to plasma membrane.
positive regulation of protein secretion Any process that activates or increases the frequency, rate or extent of the controlled release of a protein from a cell.
protein localization to cell surface A process in which a protein is transported to, or maintained in, a location within the external part of the cell wall and/or plasma membrane.
protein localization to endosome A process in which a protein is transported to, or maintained in, a location within an endosome.
protein localization to plasma membrane A process in which a protein is transported to, or maintained in, a specific location in the plasma membrane.
regulation of dendritic spine development Any process that modulates the rate, frequency, or extent of dendritic spine development, the process whose specific outcome is the progression of the dendritic spine over time, from its formation to the mature structure.
regulation of filopodium assembly Any process that modulates the frequency, rate or extent of the assembly of a filopodium, a thin, stiff protrusion extended by the leading edge of a motile cell such as a crawling fibroblast or amoeba, or an axonal growth cone.
regulation of presynapse assembly Any process that modulates the frequency, rate or extent of presynapse assembly.
regulation of Rac protein signal transduction Any process that modulates the frequency, rate or extent of Rac protein signal transduction.
ruffle assembly The aggregation, arrangement and bonding together of a set of components to form a ruffle, a projection at the leading edge of a crawling cell; the protrusions are supported by a microfilament meshwork. The formation of ruffles (also called membrane ruffling) is thought to be controlled by a group of enzymes known as Rho GTPases, specifically RhoA, Rac1 and cdc42.
synaptic vesicle endocytosis A vesicle-mediated transport process, in which the synaptic vesicle membrane constituents are retrieved from the presynaptic membrane on the axon terminal after neurotransmitter secretion by exocytosis. Synaptic vesicle endocytosis can occur via clathrin-dependent and clathrin-independent mechanisms.
vesicle-mediated transport A cellular transport process in which transported substances are moved in membrane-bounded vesicles; transported substances are enclosed in the vesicle lumen or located in the vesicle membrane. The process begins with a step that directs a substance to the forming vesicle, and includes vesicle budding and coating. Vesicles are then targeted to, and fuse with, an acceptor membrane.

19 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P40994 ARF3 ADP-ribosylation factor 3 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) SS
P26990 ARF6 ADP-ribosylation factor 6 Gallus gallus (Chicken) SS
P40946 Arf6 ADP-ribosylation factor 6 Drosophila melanogaster (Fruit fly) SS
P84085 ARF5 ADP-ribosylation factor 5 Homo sapiens (Human) EV
A6NH57 ARL5C Putative ADP-ribosylation factor-like protein 5C Homo sapiens (Human) SS
Q969Q4 ARL11 ADP-ribosylation factor-like protein 11 Homo sapiens (Human) PR
P18085 ARF4 ADP-ribosylation factor 4 Homo sapiens (Human) EV
P49703 ARL4D ADP-ribosylation factor-like protein 4D Homo sapiens (Human) PR
Q8N4G2 ARL14 ADP-ribosylation factor-like protein 14 Homo sapiens (Human) SS
Q96KC2 ARL5B ADP-ribosylation factor-like protein 5B Homo sapiens (Human) SS
P84077 ARF1 ADP-ribosylation factor 1 Homo sapiens (Human) EV
Q8IVW1 ARL17A ADP-ribosylation factor-like protein 17 Homo sapiens (Human) SS
Q9H0F7 ARL6 ADP-ribosylation factor-like protein 6 Homo sapiens (Human) SS
P40616 ARL1 ADP-ribosylation factor-like protein 1 Homo sapiens (Human) SS
P61204 ARF3 ADP-ribosylation factor 3 Homo sapiens (Human) EV
Q9Y689 ARL5A ADP-ribosylation factor-like protein 5A Homo sapiens (Human) SS
P62331 Arf6 ADP-ribosylation factor 6 Mus musculus (Mouse) SS
Q007T5 ARF6 ADP-ribosylation factor 6 Sus scrofa (Pig) SS
P62332 Arf6 ADP-ribosylation factor 6 Rattus norvegicus (Rat) SS
10 20 30 40 50 60
MGKVLSKIFG NKEMRILMLG LDAAGKTTIL YKLKLGQSVT TIPTVGFNVE TVTYKNVKFN
70 80 90 100 110 120
VWDVGGQDKI RPLWRHYYTG TQGLIFVVDC ADRDRIDEAR QELHRIINDR EMRDAIILIF
130 140 150 160 170
ANKQDLPDAM KPHEIQEKLG LTRIRDRNWY VQPSCATSGD GLYEGLTWLT SNYKS