P62331

SS
Gene name
Arf6
Protein name
ADP-ribosylation factor 6
Names
EC 3.6.5.2
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:11845
EC number
3.6.5.2: Acting on GTP; involved in cellular and subcellular movement
Protein Class

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.<br>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) SS

Target domain

16-138 (Small GTP-binding protein domain)

Relief mechanism

Ligand binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

2 structures for P62331

Entry ID Method Resolution Chain Position Source
3VHX X-ray 281 A A/C/E/G 13-175 PDB
AF-P62331-F1 Predicted AlphaFoldDB

2 variants for P62331

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3403407285 74 W>L No EVA
rs3403186581 120 F>S No EVA

No associated diseases with P62331

1 regional properties for P62331

Type Name Position InterPro Accession
domain Small GTP-binding protein domain 12 - 139 IPR005225

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 (By similarity)
  • 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 (By similarity)
  • In late stages of cytokinesis, concentrates at the midbody ring/Flemming body (By similarity)
  • Recruitment to the midbody ring requires both activation by PSD/EFA6A and interaction with KIF23/MKLP1 (By similarity)
  • 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:22522702)
  • Recruited to the cell membrane in association with CYTH2 and ARL4C (By similarity)
  • Colocalizes with DAB2IP at the plasma membrane and endocytic vesicles (By similarity)
  • Myristoylation is required for proper localization to membranes: myristoylation on Lys-3 allows ARF6 to remain on membranes during the GTPase cycle (By similarity)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

20 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.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
early endosome A membrane-bounded organelle that receives incoming material from primary endocytic vesicles that have been generated by clathrin-dependent and clathrin-independent endocytosis; vesicles fuse with the early endosome to deliver cargo for sorting into recycling or degradation pathways.
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.
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.
myelin sheath An electrically insulating fatty layer that surrounds the axons of many neurons. It is an outgrowth of glial cells
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 An organelle consisting of a network of tubules that functions in targeting molecules, such as receptors transporters and lipids, to the plasma membrane.
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.

34 GO annotations of biological process

Name Definition
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.
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.
protein transport The directed movement of proteins into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
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 neuron projection development Any process that modulates 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).
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.
regulation of toll-like receptor 4 signaling pathway Any process that modulates the frequency, rate, or extent of toll-like receptor 4 signaling pathway.
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.

15 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
P62330 ARF6 ADP-ribosylation factor 6 Homo sapiens (Human) EV
P84084 Arf5 ADP-ribosylation factor 5 Mus musculus (Mouse) SS
P61750 Arf4 ADP-ribosylation factor 4 Mus musculus (Mouse) SS
Q99PE9 Arl4d ADP-ribosylation factor-like protein 4D Mus musculus (Mouse) PR
Q6P068 Arl5c ADP-ribosylation factor-like protein 5C Mus musculus (Mouse) SS
Q80ZU0 Arl5a ADP-ribosylation factor-like protein 5A Mus musculus (Mouse) SS
P61205 Arf3 ADP-ribosylation factor 3 Mus musculus (Mouse) SS
Q9D4P0 Arl5b ADP-ribosylation factor-like protein 5B Mus musculus (Mouse) SS
P84078 Arf1 ADP-ribosylation factor 1 Mus musculus (Mouse) SS
Q8BSL7 Arf2 ADP-ribosylation factor 2 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