P18085

EV
Gene name
ARF4 (ARF2)
Protein name
ADP-ribosylation factor 4
Names
Species
Homo sapiens (Human)
KEGG Pathway
hsa:378
EC number
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

16-140 (Small GTP-binding protein domain)

Relief mechanism

Ligand binding

Assay

Mutagenesis experiment

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

2 structures for P18085

Entry ID Method Resolution Chain Position Source
1Z6X X-ray 270 A A/B 1-180 PDB
AF-P18085-F1 Predicted AlphaFoldDB

97 variants for P18085

Variant ID(s) Position Change Description Diseaes Association Provenance
COSM1424901 1 M>? Variant assessed as Somatic; HIGH impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs1316437277 4 T>I No TOPMed
gnomAD
rs1447051765 5 I>T No gnomAD
rs769987303 5 I>V No ExAC
gnomAD
rs2070199209 8 L>F No TOPMed
rs922610512 10 S>F No TOPMed
rs1317538168 11 R>* No gnomAD
rs1224376043 11 R>Q No gnomAD
rs777601584 14 G>R No ExAC
gnomAD
rs777601584 14 G>S No ExAC
gnomAD
rs1221145627 14 G>V No gnomAD
rs2070198866 15 K>R No TOPMed
rs772174333 20 I>L No ExAC
TOPMed
gnomAD
COSM4119552 22 M>V Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs1161084466 23 V>A No gnomAD
rs1327085319 23 V>I No TOPMed
gnomAD
rs748165241 24 G>R No ExAC
gnomAD
rs1385837777 26 D>G No gnomAD
COSM3596712 26 D>N Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs2153408996 31 T>I No Ensembl
rs768064782 34 L>R No ExAC
gnomAD
rs1485460096 39 L>V No Ensembl
rs748926137 41 E>V No ExAC
gnomAD
rs779606925 42 I>M No ExAC
TOPMed
gnomAD
rs2070012656 43 V>I No gnomAD
rs755833114 46 I>V No ExAC
gnomAD
TCGA novel
rs1575784499
 50 G>= Variant assessed as Somatic; LOW impact. [NCI-TCGA] No NCI-TCGA
Ensembl
COSM3596711 52 N>D Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs867291321 55 T>A No Ensembl
rs1281054796 56 V>A No gnomAD
rs772444015 57 E>D No ExAC
gnomAD
rs1406321497 57 E>K No gnomAD
rs748613969 59 K>E No ExAC
gnomAD
rs2070006405 60 N>H No Ensembl
rs2070006325
COSM98335
 61 I>V upper_aerodigestive_tract Variant assessed as Somatic; MODERATE impact. [Cosmic, NCI-TCGA] No NCI-TCGA Cosmic
cosmic curated
TOPMed
rs2070006252 64 T>I No Ensembl
rs11550597
VAR_048317
 68 V>A No UniProt
Ensembl
dbSNP
TCGA novel 73 R>S Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs1413759346 73 R>T No gnomAD
rs1212221932 74 I>V No Ensembl
rs2070005963 80 H>N No TOPMed
rs1174556160 84 N>S No gnomAD
rs1432985527 85 T>N No TOPMed
gnomAD
rs1283496925 88 L>P No TOPMed
gnomAD
rs1409029602 88 L>V No TOPMed
gnomAD
rs1575781288 89 I>T No Ensembl
rs1347064982 91 V>M No TOPMed
gnomAD
TCGA novel 94 S>R Variant assessed as Somatic; HIGH impact. [NCI-TCGA] No NCI-TCGA
COSM1424900 95 N>D Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs367913501 95 N>K No ESP
ExAC
TOPMed
gnomAD
rs2069918493 96 D>N No gnomAD
rs748489377 97 R>H No ExAC
TOPMed
gnomAD
rs748489377 97 R>P No ExAC
TOPMed
gnomAD
rs2069918463 97 R>S No TOPMed
rs938032119 98 E>G No gnomAD
COSM1047705 99 R>I Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
COSM4818693 99 R>K Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs1245184248 100 I>F No TOPMed
gnomAD
rs2069918261 102 E>K No Ensembl
rs1380540189 103 V>A No gnomAD
rs760385965 113 V>I No ExAC
gnomAD
rs774513747 119 A>T No ExAC
gnomAD
rs1166933486 125 A>V No TOPMed
gnomAD
TCGA novel 126 N>S Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs2069894050 127 K>R No TOPMed
TCGA novel 129 D>Y Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
TCGA novel 133 A>D Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs749709237 135 A>S No ExAC
gnomAD
rs749709237 135 A>T No ExAC
gnomAD
rs1396134797 135 A>V No Ensembl
rs776097507 136 I>V No ExAC
TOPMed
gnomAD
rs1296191890 138 E>D No gnomAD
rs2069893692 140 T>P No Ensembl
rs770467489 141 D>N No ExAC
gnomAD
rs1349818124 143 L>V No gnomAD
rs1258860922 144 G>R No gnomAD
rs781482985 146 Q>H No ExAC
gnomAD
rs1559782595 146 Q>R No Ensembl
COSM167927
rs747265204
 149 R>C Variant assessed as Somatic; MODERATE impact. large_intestine endometrium [NCI-TCGA, Cosmic] No NCI-TCGA Cosmic
cosmic curated
ExAC
NCI-TCGA
TOPMed
gnomAD
COSM192729
rs777379437
 149 R>H Variant assessed as Somatic; MODERATE impact. large_intestine [NCI-TCGA, Cosmic] No cosmic curated
ExAC
NCI-TCGA
TOPMed
gnomAD
rs777379437 149 R>P No ExAC
TOPMed
gnomAD
rs747265204 149 R>S No ExAC
TOPMed
gnomAD
rs2069893249 151 R>G No TOPMed
rs2069893216 151 R>T No TOPMed
rs2069850932 155 V>L No Ensembl
rs1575778588 156 Q>K No Ensembl
rs1259731167 157 A>D No TOPMed
rs1468535094 164 T>A No gnomAD
rs2069850570 167 Y>F No Ensembl
rs1172787098 170 L>F No gnomAD
COSM1047704 171 D>G Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs80056234 174 S>A No gnomAD
rs2153408211 175 N>D No Ensembl
rs778744712
COSM1692892
 180 R>C Variant assessed as Somatic; MODERATE impact. skin [NCI-TCGA, Cosmic] No NCI-TCGA Cosmic
cosmic curated
ExAC
NCI-TCGA
TOPMed
gnomAD
rs754842478 180 R>H No ExAC
gnomAD
rs1559781566 181 R>Q No Ensembl
rs138912511 181 R>S No ESP
TOPMed

No associated diseases with P18085

7 regional properties for P18085

Type Name Position InterPro Accession
domain CARD domain 439 - 529 IPR001315
repeat BIR repeat 27 - 98 IPR001370-1
repeat BIR repeat 167 - 237 IPR001370-2
repeat BIR repeat 253 - 324 IPR001370-3
domain Zinc finger, RING-type 557 - 592 IPR001841
domain BIRC2/BIRC3, UBA domain 377 - 421 IPR041933
domain BIRC2/3-like, UBA domain 374 - 426 IPR048875

Functions

Description
EC Number
Subcellular Localization
  • Golgi apparatus
  • Membrane ; Lipid-anchor
PANTHER Family PTHR11711 ADP RIBOSYLATION FACTOR-RELATED
PANTHER Subfamily PTHR11711:SF110 ADP-RIBOSYLATION FACTOR 4
PANTHER Protein Class G-protein
PANTHER Pathway Category Huntington disease
ARF

8 GO annotations of cellular component

Name Definition
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
dendritic spine A small, membranous protrusion from a dendrite that forms a postsynaptic compartment, typically receiving input from a single presynapse. They function as partially isolated biochemical and an electrical compartments. Spine morphology is variable:they can be thin, stubby, mushroom, or branched, with a continuum of intermediate morphologies. They typically terminate in a bulb shape, linked to the dendritic shaft by a restriction. Spine remodeling is though to be involved in synaptic plasticity.
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.
glutamatergic synapse A synapse that uses glutamate as a neurotransmitter.
Golgi membrane The lipid bilayer surrounding any of the compartments of the Golgi apparatus.
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.
ruffle membrane The portion of the plasma membrane surrounding a ruffle.

6 GO annotations of molecular function

Name Definition
epidermal growth factor receptor binding Binding to an epidermal growth factor receptor.
GTP binding Binding to GTP, guanosine triphosphate.
GTPase activity Catalysis of the reaction
guanyl-nucleotide exchange factor activity Stimulates the exchange of GDP to GTP on a signaling GTPase, changing its conformation to its active form. Guanine nucleotide exchange factors (GEFs) act by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP), which is more abundant in the cell under normal cellular physiological conditions.
NAD+-protein-arginine ADP-ribosyltransferase activity Catalysis of the reaction
phospholipase D activator activity Binds to and increases the activity of the enzyme phospholipase D.

16 GO annotations of biological process

Name Definition
apical protein localization Any process in which a protein is transported to, or maintained in, apical regions of the cell.
cell migration The controlled self-propelled movement of a cell from one site to a destination guided by molecular cues.
cilium assembly The assembly of a cilium, a specialized eukaryotic organelle that consists of a filiform extrusion of the cell surface. Each cilium is bounded by an extrusion of the cytoplasmic membrane, and contains a regular longitudinal array of microtubules, anchored basally in a centriole.
dendritic spine development The process whose specific outcome is the progression of the dendritic spine over time, from its formation to the mature structure. A dendritic spine is a protrusion from a dendrite and a specialized subcellular compartment involved in synaptic transmission.
endoplasmic reticulum to Golgi vesicle-mediated transport The directed movement of substances from the endoplasmic reticulum (ER) to the Golgi, mediated by COP II vesicles. Small COP II coated vesicles form from the ER and then fuse directly with the cis-Golgi. Larger structures are transported along microtubules to the cis-Golgi.
establishment or maintenance of epithelial cell apical/basal polarity Any cellular process that results in the specification, formation or maintenance of the apicobasal polarity of an epithelial cell.
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.
learning Any process in an organism in which a relatively long-lasting adaptive behavioral change occurs as the result of experience.
negative regulation of apoptotic process Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process.
positive regulation of transcription by RNA polymerase II Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
protein localization to cilium A process in which a protein is transported to, or maintained in, a location within a cilium.
regulation of cilium assembly Any process that modulates the frequency, rate or extent of cilium assembly.
regulation of postsynapse organization Any process that modulates the physical form of a postsynapse.
regulation of reactive oxygen species metabolic process Any process that modulates the frequency, rate or extent of reactive oxygen species metabolic process.
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum The directed movement of substances from the Golgi back to the endoplasmic reticulum, mediated by vesicles bearing specific protein coats such as COPI or COG.
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.

48 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q2KJ96 ARL5A ADP-ribosylation factor-like protein 5A Bos taurus (Bovine) SS
P84081 ARF2 ADP-ribosylation factor 2 Bos taurus (Bovine) SS
P84080 ARF1 ADP-ribosylation factor 1 Bos taurus (Bovine) SS
Q0VC18 ARL4D ADP-ribosylation factor-like protein 4D Bos taurus (Bovine) PR
Q3SZF2 ARF4 ADP-ribosylation factor 4 Bos taurus (Bovine) SS
P49702 ARF5 ADP-ribosylation factor 5 Gallus gallus (Chicken) SS
P61209 Arf1 ADP-ribosylation factor 1 Drosophila melanogaster (Fruit fly) SS
P40945 Arf4 ADP ribosylation factor 4 Drosophila melanogaster (Fruit fly) SS
A6NH57 ARL5C Putative ADP-ribosylation factor-like protein 5C Homo sapiens (Human) SS
P49703 ARL4D ADP-ribosylation factor-like protein 4D Homo sapiens (Human) PR
P84077 ARF1 ADP-ribosylation factor 1 Homo sapiens (Human) EV
P84085 ARF5 ADP-ribosylation factor 5 Homo sapiens (Human) EV
Q8N4G2 ARL14 ADP-ribosylation factor-like protein 14 Homo sapiens (Human) SS
Q969Q4 ARL11 ADP-ribosylation factor-like protein 11 Homo sapiens (Human) PR
Q96KC2 ARL5B ADP-ribosylation factor-like protein 5B Homo sapiens (Human) SS
P62330 ARF6 ADP-ribosylation factor 6 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
P49076 ARF1 ADP-ribosylation factor Zea mays (Maize) SS
P84084 Arf5 ADP-ribosylation factor 5 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
P61750 Arf4 ADP-ribosylation factor 4 Mus musculus (Mouse) SS
P51824 ADP-ribosylation factor 1 Solanum tuberosum (Potato) SS
P84082 Arf2 ADP-ribosylation factor 2 Rattus norvegicus (Rat) SS
P51646 Arl5a ADP-ribosylation factor-like protein 5A Rattus norvegicus (Rat) SS
P84083 Arf5 ADP-ribosylation factor 5 Rattus norvegicus (Rat) SS
P36407 Trim23 E3 ubiquitin-protein ligase TRIM23 Rattus norvegicus (Rat) SS
P61206 Arf3 ADP-ribosylation factor 3 Rattus norvegicus (Rat) SS
P84079 Arf1 ADP-ribosylation factor 1 Rattus norvegicus (Rat) SS
P61751 Arf4 ADP-ribosylation factor 4 Rattus norvegicus (Rat) SS
P51823 ARF ADP-ribosylation factor 2 Oryza sativa subsp. japonica (Rice) SS
Q06396 Os01g0813400 ADP-ribosylation factor 1 Oryza sativa subsp. japonica (Rice) SS
Q10943 arf-1.2 ADP-ribosylation factor 1-like 2 Caenorhabditis elegans SS
P34212 arl-5 ADP-ribosylation factor-like protein 5 Caenorhabditis elegans SS
P40940 ARF3 ADP-ribosylation factor 3 Arabidopsis thaliana (Mouse-ear cress) SS
P36397 ARF1 ADP-ribosylation factor 1 Arabidopsis thaliana (Mouse-ear cress) SS
P0DH91 ARF2-B ADP-ribosylation factor 2-B Arabidopsis thaliana (Mouse-ear cress) SS
Q9LQC8 ARF2-A ADP-ribosylation factor 2-A Arabidopsis thaliana (Mouse-ear cress) SS
Q5M9P8 arl6 ADP-ribosylation factor-like protein 6 Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MGLTISSLFS RLFGKKQMRI LMVGLDAAGK TTILYKLKLG EIVTTIPTIG FNVETVEYKN
70 80 90 100 110 120
ICFTVWDVGG QDRIRPLWKH YFQNTQGLIF VVDSNDRERI QEVADELQKM LLVDELRDAV
130 140 150 160 170
LLLFANKQDL PNAMAISEMT DKLGLQSLRN RTWYVQATCA TQGTGLYEGL DWLSNELSKR