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Protein

ADP-ribosylation factor 6

Gene

ARF6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

GTP-binding protein involved in protein trafficking that regulates endocytic recycling and cytoskeleton remodeling. Required for normal completion of mitotic cytokinesis. Plays a role in the reorganization of the actin cytoskeleton and the formation of stress fibers. May also modulate vesicle budding and uncoating within the Golgi apparatus. Involved in the regulation of dendritic spine development, contributing to the regulation of dendritic branching and filopodia extension. Involved in epithelial polarization (By similarity).Functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase.By similarity7 Publications

Enzyme regulationi

Activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP). Activated by ASAP3. Inactivated by ACAP1 and ACAP2.2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi23 – 28GTP5 Publications6
Nucleotide bindingi41 – 44GTP5 Publications4
Nucleotide bindingi63 – 67GTP5 Publications5
Nucleotide bindingi122 – 125GTP5 Publications4
Nucleotide bindingi155 – 156GTP5 Publications2

GO - Molecular functioni

  • GTPase activity Source: ProtInc
  • GTP binding Source: UniProtKB
  • protein N-terminus binding Source: Ensembl
  • thioesterase binding Source: UniProtKB

GO - Biological processi

  • cell adhesion Source: UniProtKB
  • cell cycle Source: UniProtKB-KW
  • cell division Source: UniProtKB-KW
  • cortical actin cytoskeleton organization Source: UniProtKB
  • establishment of epithelial cell polarity Source: Ensembl
  • hepatocyte apoptotic process Source: Ensembl
  • liver development Source: Ensembl
  • membrane organization Source: Reactome
  • movement of cell or subcellular component Source: UniProtKB
  • myeloid cell apoptotic process Source: Ensembl
  • negative regulation of dendrite development Source: Ensembl
  • negative regulation of receptor-mediated endocytosis Source: UniProtKB
  • positive regulation of actin filament polymerization Source: UniProtKB
  • positive regulation of protein localization to plasma membrane Source: BHF-UCL
  • protein localization to cell surface Source: BHF-UCL
  • protein localization to endosome Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • regulation of dendritic spine development Source: UniProtKB
  • regulation of filopodium assembly Source: UniProtKB
  • regulation of Rac protein signal transduction Source: UniProtKB
  • ruffle organization Source: UniProtKB
  • small GTPase mediated signal transduction Source: InterPro
  • vesicle-mediated transport Source: UniProtKB

Keywordsi

Biological processCell cycle, Cell division, Differentiation, ER-Golgi transport, Neurogenesis, Protein transport, Transport
LigandGTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-8854214. TBC/RABGAPs.
R-HSA-8856828. Clathrin-mediated endocytosis.
R-HSA-8875656. MET receptor recycling.
SignaLinkiP62330.
SIGNORiP62330.

Names & Taxonomyi

Protein namesi
Recommended name:
ADP-ribosylation factor 6
Gene namesi
Name:ARF6Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000165527.6.
HGNCiHGNC:659. ARF6.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Endosome, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi2G → A: Fails to associate with membranes. 1 Publication1
Mutagenesisi27T → N: Fails to associate with membranes. Does not inhibit filopodia formation. 3 Publications1
Mutagenesisi67Q → L: Inhibits filopodia formation and dendritic branching. 2 Publications1

Organism-specific databases

DisGeNETi382.
OpenTargetsiENSG00000165527.
PharmGKBiPA24942.

Chemistry databases

ChEMBLiCHEMBL5987.
DrugBankiDB01864. 5'-Guanosine-Diphosphate-Monothiophosphate.
DB04315. Guanosine-5'-Diphosphate.
DB08231. MYRISTIC ACID.

Polymorphism and mutation databases

BioMutaiARF6.
DMDMi51316984.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00002074002 – 175ADP-ribosylation factor 6Add BLAST174

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine2 Publications1

Keywords - PTMi

Lipoprotein, Myristate

Proteomic databases

EPDiP62330.
MaxQBiP62330.
PaxDbiP62330.
PeptideAtlasiP62330.
PRIDEiP62330.
TopDownProteomicsiP62330.

PTM databases

iPTMnetiP62330.
PhosphoSitePlusiP62330.
SwissPalmiP62330.

Expressioni

Tissue specificityi

Ubiquitous, with higher levels in heart, substantia nigra, and kidney.1 Publication

Gene expression databases

BgeeiENSG00000165527.
CleanExiHS_ARF6.
GenevisibleiP62330. HS.

Organism-specific databases

HPAiCAB002778.

Interactioni

Subunit structurei

Interacts with ARHGAP21, ASAP2, ASAP3, HERC1, PIP5K1C and UACA. The interaction with ASAP3 is stabilized by calcium ions. Interacts with NCS1/FREQ at the plasma membrane. Interacts with RAB11FIP3 and RAB11FIP4. Interacts with USP6 (via Rab-GAP TBC domain). Interacts with ECM29. Interacts with TBC1D24. Interacts with MICALL1. Interacts with KIF23, forming heterodimers and heterotetramers. Interacts with GGA1 and RAB11FIP4. Interacts with SPAG9 homodimers, forming heterotetramers. Interacts with CYTH3. Interacts with EspG from enteropathogenic E.coli. Identified in a complex with RAB1A and EspG from enteropathogenic E.coli. Interacts with the V.cholerae enterotoxin subunit A1; this causes a conformation change so that the toxin can bind NAD and catalyze the ADP-ribosylation of Gs alpha.20 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein N-terminus binding Source: Ensembl
  • thioesterase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi106877. 65 interactors.
DIPiDIP-33352N.
IntActiP62330. 23 interactors.
MINTiMINT-4824639.
STRINGi9606.ENSP00000298316.

Structurei

Secondary structure

1175
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 9Combined sources7
Beta strandi13 – 19Combined sources7
Helixi26 – 35Combined sources10
Beta strandi39 – 44Combined sources6
Beta strandi45 – 54Combined sources10
Beta strandi57 – 64Combined sources8
Helixi65 – 67Combined sources3
Helixi68 – 77Combined sources10
Turni78 – 80Combined sources3
Beta strandi83 – 89Combined sources7
Helixi93 – 95Combined sources3
Helixi96 – 107Combined sources12
Helixi110 – 112Combined sources3
Beta strandi116 – 122Combined sources7
Beta strandi125 – 128Combined sources4
Helixi132 – 138Combined sources7
Helixi141 – 143Combined sources3
Beta strandi149 – 153Combined sources5
Turni156 – 159Combined sources4
Helixi162 – 172Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1E0SX-ray2.28A2-175[»]
2A5DX-ray1.80A1-175[»]
2A5FX-ray2.02A1-175[»]
2A5GX-ray2.66A1-175[»]
2BAONMR-A2-11[»]
2BAUNMR-A2-11[»]
2J5XX-ray2.80A/B2-175[»]
2W83X-ray1.93A/B/E13-175[»]
3LVQX-ray3.38E11-175[»]
3LVRX-ray3.38E11-175[»]
3N5CX-ray1.82A/B14-175[»]
3PCRX-ray2.50B14-175[»]
4FMEX-ray4.10C/F14-173[»]
4KAXX-ray1.85A14-173[»]
ProteinModelPortaliP62330.
SMRiP62330.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP62330.

Family & Domainsi

Sequence similaritiesi

Belongs to the small GTPase superfamily. Arf family.Curated

Phylogenomic databases

eggNOGiKOG0071. Eukaryota.
ENOG410XP1U. LUCA.
GeneTreeiENSGT00780000121855.
HOGENOMiHOG000163691.
HOVERGENiHBG002073.
InParanoidiP62330.
KOiK07941.
OMAiIQDREMK.
OrthoDBiEOG091G0OXD.
PhylomeDBiP62330.
TreeFamiTF300808.

Family and domain databases

InterProiView protein in InterPro
IPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR024156. Small_GTPase_ARF.
IPR006689. Small_GTPase_ARF/SAR.
PfamiView protein in Pfam
PF00025. Arf. 1 hit.
PRINTSiPR00328. SAR1GTPBP.
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiView protein in PROSITE
PS51417. ARF. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P62330-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGKVLSKIFG NKEMRILMLG LDAAGKTTIL YKLKLGQSVT TIPTVGFNVE
60 70 80 90 100
TVTYKNVKFN VWDVGGQDKI RPLWRHYYTG TQGLIFVVDC ADRDRIDEAR
110 120 130 140 150
QELHRIINDR EMRDAIILIF ANKQDLPDAM KPHEIQEKLG LTRIRDRNWY
160 170
VQPSCATSGD GLYEGLTWLT SNYKS
Length:175
Mass (Da):20,082
Last modified:January 23, 2007 - v2
Checksum:i49E38E59AEA52B98
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M57763 mRNA. Translation: AAA90928.1.
AY296206 Genomic DNA. Translation: AAP50257.1.
AF047432 mRNA. Translation: AAC39877.1.
AF493885 mRNA. Translation: AAM12599.1.
AK313790 mRNA. Translation: BAG36527.1.
CR541964 mRNA. Translation: CAG46762.1.
CH471078 Genomic DNA. Translation: EAW65740.1.
BC002952 mRNA. No translation available.
BC008918 mRNA. Translation: AAH08918.1.
CCDSiCCDS9695.1.
PIRiB23741.
RefSeqiNP_001654.1. NM_001663.3.
UniGeneiHs.525330.
Hs.719973.

Genome annotation databases

EnsembliENST00000298316; ENSP00000298316; ENSG00000165527.
GeneIDi382.
KEGGihsa:382.
UCSCiuc001wxg.5. human.

Similar proteinsi

Entry informationi

Entry nameiARF6_HUMAN
AccessioniPrimary (citable) accession number: P62330
Secondary accession number(s): P26438, Q6FGZ2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 5, 2004
Last sequence update: January 23, 2007
Last modified: October 25, 2017
This is version 156 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families