P62330 (ARF6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
ADP-ribosylation factor 6

Gene names

Name:

ARF6

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	175 AA.
Sequence status	Complete.
Protein existence	Evidence 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 projection › filopodium 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 process	Differentiation ER-Golgi transport Neurogenesis Protein transport Transport
Cellular component	Cell membrane Cell projection Endosome Golgi apparatus Membrane
Ligand	GTP-binding Nucleotide-binding
PTM	Lipoprotein Myristate
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic 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_component	Golgi 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_function	GTP 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
ARFIP2	P53365	4	EBI-638181,EBI-638194
ATP6V1C1	P21283	4	EBI-638181,EBI-988663

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 175

175

ADP-ribosylation factor 6

PRO_0000207400

Regions

Nucleotide binding

20 – 27

8

GTP By similarity

Nucleotide binding

63 – 67

5

GTP By similarity

Nucleotide binding

122 – 125

4

GTP By similarity

Amino acid modifications

Lipidation

2

1

N-myristoyl glycine Ref.9

Experimental info

Mutagenesis

2

1

G → A: Fails to associate with membranes. Ref.9

Mutagenesis

27

1

T → N: Fails to associate with membranes. Does not inhibit filopodia formation. Ref.12 Ref.17

Mutagenesis

67

1

Q → L: Inhibits filopodia formation and dendritic branching. Ref.12

Secondary structure

1

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175

Helix Strand Turn

Details...

Helix

3 – 9

7

Beta strand

13 – 19

7

Helix

26 – 35

10

Beta strand

39 – 44

6

Beta strand

45 – 54

10

Beta strand

57 – 64

8

Helix

65 – 67

3

Helix

68 – 77

10

Turn

78 – 80

3

Beta strand

83 – 89

7

Helix

93 – 95

3

Helix

96 – 107

12

Helix

110 – 112

3

Beta strand

116 – 122

7

Beta strand

125 – 128

4

Helix

132 – 138

7

Helix

141 – 143

3

Beta strand

149 – 153

5

Turn

156 – 159

4

Helix

162 – 172

11

Sequences

	Sequence		Length	Mass (Da)
	P62330 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 49E38E59AEA52B98	FASTA	175	20,082
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.

IPI

IPI00215920.

PIR

B23741.

RefSeq

NP_001654.1. NM_001663.3.

UniGene

Hs.525330.
Hs.719973.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1E0S	X-ray	2.28	A	2-175	[»]
2A5D	X-ray	1.80	A	2-174	[»]
2A5F	X-ray	2.02	A	2-174	[»]
2A5G	X-ray	2.66	A	2-174	[»]
2BAO	NMR	-	A	2-11	[»]
2BAU	NMR	-	A	2-11	[»]
2J5X	X-ray	2.80	A/B	1-175	[»]
2W83	X-ray	1.93	A/B/E	13-175	[»]
3LVQ	X-ray	3.38	E	11-175	[»]
3LVR	X-ray	3.38	E	11-175	[»]
3N5C	X-ray	1.82	A/B	14-175	[»]
3PCR	X-ray	2.50	B	14-175	[»]
4FME	X-ray	4.10	C/F	14-173	[»]

ProteinModelPortal

P62330.

ModBase

Search...

Protein-protein interaction databases

IntAct

P62330. 6 interactions.

STRING

9606.ENSP00000298316.

PTM databases

PhosphoSite

P62330.

Polymorphism databases

DMDM

51316984.

Proteomic databases

PaxDb

P62330.

PeptideAtlas

P62330.

PRIDE

P62330.

Protocols and materials databases

DNASU

382.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000298316; ENSP00000298316; ENSG00000165527.

GeneID

382.

KEGG

hsa:382.

UCSC

uc001wxg.4. human.

Organism-specific databases

CTD

382.

GeneCards

GC14P050359.

HGNC

HGNC:659. ARF6.

HPA

CAB002778.

MIM

600464. gene.

neXtProt

NX_P62330.

PharmGKB

PA24942.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1100.

HOGENOM

HOG000163691.

HOVERGEN

HBG002073.

InParanoid

P62330.

KO

K07941.

OMA

DREMKDA.

OrthoDB

EOG4GQQ62.

Enzyme and pathway databases

Pathway_Interaction_DB

arf6downstreampathway. 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

ArrayExpress

P62330.

Bgee

P62330.

CleanEx

HS_ARF6.

Genevestigator

P62330.

GermOnline

ENSG00000165527. Homo sapiens.

Family and domain databases

InterPro

IPR005225. Small_GTP-bd_dom.
IPR024156. Small_GTPase_ARF.
IPR006689. Small_GTPase_ARF/SAR.
[Graphical view]

Pfam

PF00025. Arf. 1 hit.
[Graphical view]

PRINTS

PR00328. SAR1GTPBP.

SMART

SM00177. ARF. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00231. small_GTP. 1 hit.

PROSITE

PS51417. ARF. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL5987.

EvolutionaryTrace

P62330.

GenomeRNAi

382.

NextBio

1599.

SOURCE

Search...

Entry information

Entry name

ARF6_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.