P40616

SS
Gene name
ARL1
Protein name
ADP-ribosylation factor-like protein 1
Names
Species
Homo sapiens (Human)
KEGG Pathway
hsa:400
EC number
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

5 structures for P40616

Entry ID Method Resolution Chain Position Source
1UPT X-ray 170 A A/C/E/G 15-181 PDB
4DCN X-ray 301 A A/B 14-179 PDB
5EE5 X-ray 228 A B 15-181 PDB
5J5C X-ray 340 A A 16-181 PDB
AF-P40616-F1 Predicted AlphaFoldDB

95 variants for P40616

Variant ID(s) Position Change Description Diseaes Association Provenance
rs1351342399 3 G>R No gnomAD
rs745925566 4 F>V No ExAC
gnomAD
rs1565816628 5 F>L No Ensembl
rs199647502 8 I>M No 1000Genomes
ExAC
TOPMed
gnomAD
rs1444439963 8 I>V No TOPMed
gnomAD
rs889507227 15 T>S No Ensembl
rs1441918855 16 R>Q No gnomAD
rs1351775004 18 M>I No gnomAD
rs1871427614 18 M>T No TOPMed
gnomAD
COSM259508 19 R>K Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
TCGA novel 25 L>* Variant assessed as Somatic; HIGH impact. [NCI-TCGA] No NCI-TCGA
TCGA novel 31 T>I Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs747900626 33 I>V No ExAC
gnomAD
COSM4414439 35 Y>C Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs1409129413 36 R>K No gnomAD
rs997604444 38 Q>H No Ensembl
TCGA novel 41 E>* Variant assessed as Somatic; HIGH impact. [NCI-TCGA] No NCI-TCGA
rs1871426153 46 I>T No TOPMed
rs1871426258 46 I>V No TOPMed
rs866509393 47 P>H No Ensembl
TCGA novel 50 G>E Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs1871343910 51 F>V No Ensembl
rs759551539 55 T>M No ExAC
gnomAD
rs774423552 57 T>M No ExAC
gnomAD
rs1482235542 57 T>S No gnomAD
rs1871343274 58 Y>* No TOPMed
rs778166981 58 Y>C No Ensembl
rs778166981 58 Y>F No Ensembl
rs1318906358
COSM3416380
 59 K>E Variant assessed as Somatic; MODERATE impact. large_intestine [NCI-TCGA, Cosmic] No NCI-TCGA Cosmic
cosmic curated
NCI-TCGA
gnomAD
rs748085890 60 N>H No ExAC
gnomAD
rs2121120858 61 L>F No Ensembl
COSM933961 62 K>T Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs374438987 65 V>I No ESP
ExAC
gnomAD
rs374438987 65 V>L No ESP
ExAC
gnomAD
rs867932766 66 W>* No Ensembl
rs200228067 71 Q>* No 1000Genomes
ExAC
TOPMed
gnomAD
rs1565815927 72 T>A No Ensembl
COSM691648 83 S>* Variant assessed as Somatic; HIGH impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs1871295092 85 T>R No Ensembl
TCGA novel 86 D>Y Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
TCGA novel 88 V>A Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs1266416513 88 V>I No TOPMed
gnomAD
rs767639040 95 C>G No ExAC
gnomAD
rs1871294615 95 C>Y No Ensembl
rs774354950 97 R>* No ExAC
gnomAD
rs774354950 97 R>G No ExAC
gnomAD
rs1448134752 97 R>Q No gnomAD
COSM4877872 98 D>G Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs763085137 99 R>* No ExAC
gnomAD
COSM3416379
rs1033216289
 99 R>Q Variant assessed as Somatic; MODERATE impact. large_intestine [NCI-TCGA, Cosmic] No NCI-TCGA Cosmic
cosmic curated
Ensembl
NCI-TCGA
TCGA novel 100 I>L Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs1295096319 101 G>A No gnomAD
rs1295096319 101 G>D No gnomAD
rs1456165523 103 S>A No gnomAD
rs1337723460 103 S>Y No TOPMed
gnomAD
rs1871293520 104 K>E No gnomAD
COSM3398252 104 K>N Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
TCGA novel 105 S>L Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs1441455563 108 V>A No gnomAD
COSM933960
rs1159806718
 108 V>I Variant assessed as Somatic; MODERATE impact. endometrium [NCI-TCGA, Cosmic] No NCI-TCGA Cosmic
cosmic curated
NCI-TCGA
gnomAD
rs1871292475 111 L>V No TOPMed
rs745606476 116 L>P No ExAC
TOPMed
gnomAD
COSM4037997 117 R>G Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs770515193 118 K>R No ExAC
gnomAD
rs1871159041 122 V>M No gnomAD
rs1871158729 125 A>S No Ensembl
rs1871158598 125 A>V No Ensembl
rs1019490890 128 Q>* No Ensembl
rs777262033 130 M>V No ExAC
TOPMed
gnomAD
rs756672768 132 Q>R No ExAC
gnomAD
rs977321395 137 S>A No TOPMed
gnomAD
rs2121104863 138 E>D No Ensembl
rs199895049 139 M>I No ESP
ExAC
TOPMed
gnomAD
rs867593405 140 A>T No Ensembl
rs751810522 141 N>D No ExAC
TOPMed
gnomAD
rs1428802587 144 G>A No TOPMed
gnomAD
rs1428802587 144 G>E No TOPMed
gnomAD
rs1479033109 146 P>L No TOPMed
gnomAD
rs766628640 146 P>S No ExAC
TOPMed
gnomAD
rs1261457288 150 D>H No gnomAD
COSM2063365
rs1429217176
 151 R>Q Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
NCI-TCGA
TOPMed
rs1162530360 152 K>R No Ensembl
rs1193650336 156 F>L No gnomAD
rs1871156183 157 K>N No TOPMed
rs1443494961 158 T>M No gnomAD
rs981097493 161 T>A No TOPMed
gnomAD
rs1871155739 163 G>A No Ensembl
COSM278976 165 G>D Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs1871155507 165 G>S No Ensembl
rs750585373 169 A>S No ExAC
gnomAD
COSM430163 170 M>V Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs1352049388 172 W>* No gnomAD
rs900100900 178 K>E No Ensembl
rs761389991 181 Q>P No ExAC
TOPMed
gnomAD
COSM3810785 182 Q>Y Variant assessed as Somatic; HIGH impact. [NCI-TCGA] No NCI-TCGA Cosmic

No associated diseases with P40616

1 regional properties for P40616

Type Name Position InterPro Accession
domain Small GTP-binding protein domain 16 - 171 IPR005225

Functions

Description
EC Number
Subcellular Localization
  • Golgi apparatus membrane ; Peripheral membrane protein ; Cytoplasmic side
  • Golgi apparatus, trans-Golgi network membrane
  • Membrane ; Lipid-anchor
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

6 GO annotations of cellular component

Name Definition
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.
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.
Golgi membrane The lipid bilayer surrounding any of the compartments of the Golgi apparatus.
trans-Golgi network The network of interconnected tubular and cisternal structures located within the Golgi apparatus on the side distal to the endoplasmic reticulum, from which secretory vesicles emerge. The trans-Golgi network is important in the later stages of protein secretion where it is thought to play a key role in the sorting and targeting of secreted proteins to the correct destination.
trans-Golgi network membrane The lipid bilayer surrounding any of the compartments that make up the trans-Golgi network.

6 GO annotations of molecular function

Name Definition
enzyme activator activity Binds to and increases the activity of an enzyme.
GTP binding Binding to GTP, guanosine triphosphate.
GTPase activity Catalysis of the reaction
metal ion binding Binding to a metal ion.
phospholipase D activator activity Binds to and increases the activity of the enzyme phospholipase D.
protein domain specific binding Binding to a specific domain of a protein.

6 GO annotations of biological process

Name Definition
Golgi organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of the Golgi apparatus.
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.
protein localization to Golgi apparatus A process in which a protein is transported to, or maintained in, a location within the Golgi apparatus.
retrograde transport, endosome to Golgi The directed movement of membrane-bounded vesicles from endosomes back to the trans-Golgi network where they are recycled for further rounds of transport.
toxin metabolic process The chemical reactions and pathways involving a toxin, a poisonous compound (typically a protein) that is produced by cells or organisms and that can cause disease when introduced into the body or tissues of an organism.
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.

14 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q8N4G2 ARL14 ADP-ribosylation factor-like protein 14 Homo sapiens (Human) SS
Q969Q4 ARL11 ADP-ribosylation factor-like protein 11 Homo sapiens (Human) PR
Q8IVW1 ARL17A ADP-ribosylation factor-like protein 17 Homo sapiens (Human) SS
P49703 ARL4D ADP-ribosylation factor-like protein 4D Homo sapiens (Human) PR
P62330 ARF6 ADP-ribosylation factor 6 Homo sapiens (Human) EV
Q9H0F7 ARL6 ADP-ribosylation factor-like protein 6 Homo sapiens (Human) SS
P18085 ARF4 ADP-ribosylation factor 4 Homo sapiens (Human) EV
P84085 ARF5 ADP-ribosylation factor 5 Homo sapiens (Human) EV
P61204 ARF3 ADP-ribosylation factor 3 Homo sapiens (Human) EV
P84077 ARF1 ADP-ribosylation factor 1 Homo sapiens (Human) EV
Q9Y689 ARL5A ADP-ribosylation factor-like protein 5A Homo sapiens (Human) SS
A6NH57 ARL5C Putative ADP-ribosylation factor-like protein 5C Homo sapiens (Human) SS
Q96KC2 ARL5B ADP-ribosylation factor-like protein 5B Homo sapiens (Human) SS
P40940 ARF3 ADP-ribosylation factor 3 Arabidopsis thaliana (Mouse-ear cress) SS
10 20 30 40 50 60
MGGFFSSIFS SLFGTREMRI LILGLDGAGK TTILYRLQVG EVVTTIPTIG FNVETVTYKN
70 80 90 100 110 120
LKFQVWDLGG QTSIRPYWRC YYSNTDAVIY VVDSCDRDRI GISKSELVAM LEEEELRKAI
130 140 150 160 170 180
LVVFANKQDM EQAMTSSEMA NSLGLPALKD RKWQIFKTSA TKGTGLDEAM EWLVETLKSR
Q