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Protein

ADP-ribosylation factor 6

Gene

ARF6

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

Functioni

GTP-binding protein involved in protein trafficking that regulates endocytic recycling and cytoskeleton remodeling (PubMed:11266366, PubMed:21170023, PubMed:16737952, PubMed:7589240, PubMed:18400762). Required for normal completion of mitotic cytokinesis (By similarity). Plays a role in the reorganization of the actin cytoskeleton and the formation of stress fibers (By similarity). 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 (PubMed:14978216). Plays an important role in membrane trafficking, during junctional remodeling and epithelial polarization. Regulates surface levels of adherens junction proteins such as CDH1 (By similarity).By similarity7 Publications
(Microbial infection) Functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase.1 Publication

Activity 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

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
MIMi600464 gene
neXtProtiNX_P62330

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
ProteomicsDBi57396
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 Expressed in 232 organ(s), highest expression level in esophagus squamous epithelium
CleanExiHS_ARF6
GenevisibleiP62330 HS

Organism-specific databases

HPAiCAB002778

Interactioni

Subunit structurei

Interacts with PIP5K1C (PubMed:12847086). Interacts with USP6 (via Rab-GAP TBC domain) (PubMed:15509780). Interacts with RAB11FIP3 and RAB11FIP4 (PubMed:16148947, PubMed:17030804, PubMed:17628206). Interacts with HERC1 (PubMed:15642342). Interacts with ARHGAP21 (PubMed:15793564). Interacts with ASAP3; the interaction is stabilized by calcium ions (PubMed:16737952, PubMed:20510928). Interacts with NCS1/FREQ at the plasma membrane (PubMed:17555535). Interacts with TBC1D24 (PubMed:20727515). Interacts with ECPAS (PubMed:20682791). Interacts with MICALL1 (PubMed:21951725). Interacts with SPAG9 homodimers, forming heterotetramers (PubMed:19644450). Interacts with CYTH3 (PubMed:23940353). Interacts with ASAP2 (By similarity). Interacts with UACA (By similarity). Interacts with KIF23, forming heterodimers and heterotetramers (By similarity). Interacts with GGA1 (By similarity). Interacts with C9orf72 (By similarity).By similarity15 Publications
(Microbial infection) 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.1 Publication
(Microbial infection) Interacts with EspG from enteropathogenic E.coli.2 Publications
(Microbial infection) Identified in a complex with RAB1A and EspG from enteropathogenic E.coli.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106877, 70 interactors
DIPiDIP-33352N
IntActiP62330, 26 interactors
MINTiP62330
STRINGi9606.ENSP00000298316

Structurei

Secondary structure

1175
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Cross-referencesi

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

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[»]
6BBPelectron microscopy35.00A2-173[»]
6BBQelectron microscopy35.00A2-173[»]
ProteinModelPortaliP62330
SMRiP62330
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106877, 70 interactors
DIPiDIP-33352N
IntActiP62330, 26 interactors
MINTiP62330
STRINGi9606.ENSP00000298316

Chemistry databases

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

PTM databases

iPTMnetiP62330
PhosphoSitePlusiP62330
SwissPalmiP62330

Polymorphism and mutation databases

BioMutaiARF6
DMDMi51316984

Proteomic databases

EPDiP62330
MaxQBiP62330
PaxDbiP62330
PeptideAtlasiP62330
PRIDEiP62330
ProteomicsDBi57396
TopDownProteomicsiP62330

Protocols and materials databases

DNASUi382
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi382
DisGeNETi382
EuPathDBiHostDB:ENSG00000165527.6
GeneCardsiARF6
HGNCiHGNC:659 ARF6
HPAiCAB002778
MIMi600464 gene
neXtProtiNX_P62330
OpenTargetsiENSG00000165527
PharmGKBiPA24942
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiARF6 human
EvolutionaryTraceiP62330
GeneWikiiARF6
GenomeRNAii382
PROiPR:P62330
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000165527 Expressed in 232 organ(s), highest expression level in esophagus squamous epithelium
CleanExiHS_ARF6
GenevisibleiP62330 HS

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
ProtoNetiSearch...

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: September 12, 2018
This is version 164 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
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Main funding by: National Institutes of Health

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