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P62330 (ARF6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
ADP-ribosylation factor 6
Gene names
Name:ARF6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length175 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

GTP-binding protein involved in protein trafficking; regulates endocytic recycling and cytoskeleton remodeling. May modulate vesicle budding and uncoating within the Golgi apparatus. Functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. Involved in the regulation of dendritic spine development By similarity. Contributes to the regulation of dendritic branching and filopodia extension. Ref.9 Ref.12 Ref.23

Subunit structure

Interacts with ARHGAP21, ASAP2, HERC1, PIP5K1C and UACA. 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. Ref.10 Ref.11 Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.19 Ref.20 Ref.21

Subcellular location

Golgi apparatus. Cell membrane; Lipid-anchor. Endosome membrane; Lipid-anchor. Cell membrane. Cell projectionfilopodium membrane; Lipid-anchor. Note: Recruited to the cell membrane in association with CYTH2 and ARL4C. Ref.9 Ref.12 Ref.17 Ref.19 Ref.21

Tissue specificity

Ubiquitous, with higher levels in heart, substantia nigra, and kidney. Ref.2

Sequence similarities

Belongs to the small GTPase superfamily. Arf family.

Ontologies

Keywords
   Biological processDifferentiation
ER-Golgi transport
Neurogenesis
Protein transport
Transport
   Cellular componentCell membrane
Cell projection
Endosome
Golgi apparatus
Membrane
   LigandGTP-binding
Nucleotide-binding
   PTMLipoprotein
Myristate
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from electronic annotation. Source: Compara

cell adhesion

Traceable author statement PubMed 10036235. Source: UniProtKB

cellular component movement

Traceable author statement PubMed 10036235. Source: UniProtKB

cortical actin cytoskeleton organization

Inferred from mutant phenotype PubMed 10913182. Source: UniProtKB

establishment of epithelial cell polarity

Inferred from electronic annotation. Source: Compara

liver development

Inferred from electronic annotation. Source: Compara

negative regulation of receptor-mediated endocytosis

Traceable author statement PubMed 9312003. Source: UniProtKB

positive regulation of actin filament polymerization

Inferred from mutant phenotype PubMed 10036235. Source: UniProtKB

positive regulation of establishment of protein localization to plasma membrane

Inferred from sequence or structural similarity. Source: BHF-UCL

protein localization to cell surface

Inferred from sequence or structural similarity. Source: BHF-UCL

protein transport

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of Rac protein signal transduction

Inferred from direct assay PubMed 10036235. Source: UniProtKB

regulation of dendritic spine development

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of filopodium assembly

Inferred from direct assay Ref.12. Source: UniProtKB

ruffle organization

Inferred from direct assay PubMed 10036235. Source: UniProtKB

small GTPase mediated signal transduction

Inferred from electronic annotation. Source: InterPro

vesicle-mediated transport

Traceable author statement PubMed 10913182. Source: UniProtKB

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: UniProtKB-SubCell

cell cortex

Inferred from direct assay PubMed 10913182. Source: UniProtKB

early endosome

Inferred from electronic annotation. Source: Compara

endosome

Inferred from direct assay Ref.21. Source: UniProtKB

endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

filopodium membrane

Inferred from direct assay Ref.12. Source: UniProtKB

recycling endosome

Inferred from electronic annotation. Source: Compara

ruffle

Inferred from direct assay PubMed 9312003. Source: UniProtKB

   Molecular_functionGTP binding

Traceable author statement PubMed 10913182. Source: UniProtKB

GTPase activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ARFIP2P533654EBI-638181,EBI-638194
ATP6V1C1P212834EBI-638181,EBI-988663

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 175175ADP-ribosylation factor 6
PRO_0000207400

Regions

Nucleotide binding20 – 278GTP By similarity
Nucleotide binding63 – 675GTP By similarity
Nucleotide binding122 – 1254GTP By similarity

Amino acid modifications

Lipidation21N-myristoyl glycine Ref.9

Experimental info

Mutagenesis21G → A: Fails to associate with membranes. Ref.9
Mutagenesis271T → N: Fails to associate with membranes. Does not inhibit filopodia formation. Ref.12 Ref.17
Mutagenesis671Q → L: Inhibits filopodia formation and dendritic branching. Ref.12

Secondary structure

.................................... 175
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P62330 [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: 49E38E59AEA52B98

FASTA17520,082
        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 

« Hide

References

« Hide 'large scale' references
[1]"Molecular identification of ADP-ribosylation factor mRNAs and their expression in mammalian cells."
Tsuchiya M., Price S.R., Tsai S.-C., Moss J., Vaughan M.
J. Biol. Chem. 266:2772-2777(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Sequence, genomic organization, and expression of the human ADP-ribosylation factor 6 (ARF6) gene: a class III ARF."
Lebeda R.A., Johnson S.K., Stewart M.I., Haun R.S.
DNA Cell Biol. 22:737-741(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY.
[3]"Identification of genes expressed in human CD34(+) hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning."
Mao M., Fu G., Wu J.-S., Zhang Q.-H., Zhou J., Kan L.-X., Huang Q.-H., He K.-L., Gu B.-W., Han Z.-G., Shen Y., Gu J., Yu Y.-P., Xu S.-H., Wang Y.-X., Chen S.-J., Chen Z.
Proc. Natl. Acad. Sci. U.S.A. 95:8175-8180(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Umbilical cord blood.
[4]"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
Puhl H.L. III, Ikeda S.R., Aronstam R.S.
Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Trachea.
[6]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Skin and Uterus.
[9]"Myristoylation is required for the intracellular localization and endocytic function of ARF6."
D'Souza-Schorey C., Stahl P.D.
Exp. Cell Res. 221:153-159(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: MYRISTOYLATION AT GLY-2, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF GLY-2.
[10]"ARF6 stimulates clathrin/AP-2 recruitment to synaptic membranes by activating phosphatidylinositol phosphate kinase type Igamma."
Krauss M., Kinuta M., Wenk M.R., De Camilli P., Takei K., Haucke V.
J. Cell Biol. 162:113-124(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PIP5K1C.
[11]"The TBC (Tre-2/Bub2/Cdc16) domain protein TRE17 regulates plasma membrane-endosomal trafficking through activation of Arf6."
Martinu L., Masuda-Robens J.M., Robertson S.E., Santy L.C., Casanova J.E., Chou M.M.
Mol. Cell. Biol. 24:9752-9762(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH USP6.
[12]"Regulation of dendritic branching and filopodia formation in hippocampal neurons by specific acylated protein motifs."
Gauthier-Campbell C., Bredt D.S., Murphy T.H., El-Husseini A.
Mol. Biol. Cell 15:2205-2217(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF THR-27 AND GLN-67.
[13]"Rab11-FIP3 and FIP4 interact with Arf6 and the exocyst to control membrane traffic in cytokinesis."
Fielding A.B., Schonteich E., Matheson J., Wilson G., Yu X., Hickson G.R., Srivastava S., Baldwin S.A., Prekeris R., Gould G.W.
EMBO J. 24:3389-3399(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAB11FIP3 AND RAB11FIP4.
[14]"Requirement of phosphatidylinositol-4,5-bisphosphate for HERC1-mediated guanine nucleotide release from ARF proteins."
Garcia-Gonzalo F.R., Bartrons R., Ventura F., Rosa J.L.
FEBS Lett. 579:343-348(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HERC1.
[15]"Golgi-localized GAP for Cdc42 functions downstream of ARF1 to control Arp2/3 complex and F-actin dynamics."
Dubois T., Paleotti O., Mironov A.A. Jr., Fraisier V., Stradal T.E.B., De Matteis M.A., Franco M., Chavrier P.
Nat. Cell Biol. 7:353-364(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ARHGAP21.
[16]"Structural basis for Rab11-dependent membrane recruitment of a family of Rab11-interacting protein 3 (FIP3)/Arfophilin-1."
Shiba T., Koga H., Shin H.-W., Kawasaki M., Kato R., Nakayama K., Wakatsuki S.
Proc. Natl. Acad. Sci. U.S.A. 103:15416-15421(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAB11FIP3 AND RAB11FIP4.
[17]"The Arl4 family of small G proteins can recruit the cytohesin Arf6 exchange factors to the plasma membrane."
Hofmann I., Thompson A., Sanderson C.M., Munro S.
Curr. Biol. 17:711-716(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF THR-27, SUBCELLULAR LOCATION.
[18]"Molecular characterization of Rab11-FIP3 binding to ARF GTPases."
Schonteich E., Pilli M., Simon G.C., Matern H.T., Junutula J.R., Sentz D., Holmes R.K., Prekeris R.
Eur. J. Cell Biol. 86:417-431(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAB11FIP3.
[19]"Specificity, promiscuity and localization of ARF protein interactions with NCS-1 and phosphatidylinositol-4 kinase-III beta."
Haynes L.P., Sherwood M.W., Dolman N.J., Burgoyne R.D.
Traffic 8:1080-1092(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NCS1, SUBCELLULAR LOCATION.
[20]"TBC1D24, an ARF6-interacting protein, is mutated in familial infantile myoclonic epilepsy."
Falace A., Filipello F., La Padula V., Vanni N., Madia F., De Pietri Tonelli D., de Falco F.A., Striano P., Dagna Bricarelli F., Minetti C., Benfenati F., Fassio A., Zara F.
Am. J. Hum. Genet. 87:365-370(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TBC1D24.
[21]"A protein interaction network for Ecm29 links the 26 S proteasome to molecular motors and endosomal components."
Gorbea C., Pratt G., Ustrell V., Bell R., Sahasrabudhe S., Hughes R.E., Rechsteiner M.
J. Biol. Chem. 285:31616-31633(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH ECM29.
[22]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]"The structural GDP/GTP cycle of human Arf6."
Pasqualato S., Menetrey J., Franco M., Cherfils J.
EMBO Rep. 2:234-238(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
IPIIPI00215920.
PIRB23741.
RefSeqNP_001654.1. NM_001663.3.
UniGeneHs.525330.
Hs.719973.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1E0SX-ray2.28A2-175[»]
2A5DX-ray1.80A2-174[»]
2A5FX-ray2.02A2-174[»]
2A5GX-ray2.66A2-174[»]
2BAONMR-A2-11[»]
2BAUNMR-A2-11[»]
2J5XX-ray2.80A/B1-175[»]
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[»]
ProteinModelPortalP62330.
ModBaseSearch...

Protein-protein interaction databases

IntActP62330. 6 interactions.
STRING9606.ENSP00000298316.

PTM databases

PhosphoSiteP62330.

Polymorphism databases

DMDM51316984.

Proteomic databases

PaxDbP62330.
PeptideAtlasP62330.
PRIDEP62330.

Protocols and materials databases

DNASU382.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000298316; ENSP00000298316; ENSG00000165527.
GeneID382.
KEGGhsa:382.
UCSCuc001wxg.4. human.

Organism-specific databases

CTD382.
GeneCardsGC14P050359.
HGNCHGNC:659. ARF6.
HPACAB002778.
MIM600464. gene.
neXtProtNX_P62330.
PharmGKBPA24942.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1100.
HOGENOMHOG000163691.
HOVERGENHBG002073.
InParanoidP62330.
KOK07941.
OMADREMKDA.
OrthoDBEOG4GQQ62.

Enzyme and pathway databases

Pathway_Interaction_DBarf6downstreampathway. Arf6 downstream pathway.
arf6cyclingpathway. Arf6 signaling events.
arf6_traffickingpathway. Arf6 trafficking events.
pi3kcipathway. Class I PI3K signaling events.
a4b1_paxdep_pathway. Paxillin-dependent events mediated by a4b1.
a4b1_paxindep_pathway. Paxillin-independent events mediated by a4b1 and a4b7.

Gene expression databases

ArrayExpressP62330.
BgeeP62330.
CleanExHS_ARF6.
GenevestigatorP62330.
GermOnlineENSG00000165527. Homo sapiens.

Family and domain databases

InterProIPR005225. Small_GTP-bd_dom.
IPR024156. Small_GTPase_ARF.
IPR006689. Small_GTPase_ARF/SAR.
[Graphical view]
PfamPF00025. Arf. 1 hit.
[Graphical view]
PRINTSPR00328. SAR1GTPBP.
SMARTSM00177. ARF. 1 hit.
[Graphical view]
TIGRFAMsTIGR00231. small_GTP. 1 hit.
PROSITEPS51417. ARF. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChEMBLCHEMBL5987.
EvolutionaryTraceP62330.
GenomeRNAi382.
NextBio1599.
SOURCESearch...

Entry information

Entry nameARF6_HUMAN
AccessionPrimary (citable) accession number: P62330
Secondary accession number(s): P26438, Q6FGZ2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 5, 2004
Last sequence update: January 23, 2007
Last modified: May 1, 2013
This is version 109 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families