ID ARF6_HUMAN Reviewed; 175 AA. AC P62330; P26438; DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 25-JAN-2012, entry version 95. DE RecName: Full=ADP-ribosylation factor 6; GN Name=ARF6; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=91131565; PubMed=1993656; RA Tsuchiya M., Price S.R., Tsai S.-C., Moss J., Vaughan M.; RT "Molecular identification of ADP-ribosylation factor mRNAs and their RT expression in mammalian cells."; RL J. Biol. Chem. 266:2772-2777(1991). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Umbilical cord blood; RX MEDLINE=98318631; PubMed=9653160; DOI=10.1073/pnas.95.14.8175; RA Mao M., Fu G., Wu J.-S., Zhang Q.-H., Zhou J., Kan L.-X., Huang Q.-H., RA He K.-L., Gu B.-W., Han Z.-G., Shen Y., Gu J., Yu Y.-P., Xu S.-H., RA Wang Y.-X., Chen S.-J., Chen Z.; RT "Identification of genes expressed in human CD34(+) hematopoietic RT stem/progenitor cells by expressed sequence tags and efficient full- RT length cDNA cloning."; RL Proc. Natl. Acad. Sci. U.S.A. 95:8175-8180(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.; RT "cDNA clones of human proteins involved in signal transduction RT sequenced by the Guthrie cDNA resource center (www.cdna.org)."; RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Skin, and Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP MYRISTOYLATION AT GLY-2, FUNCTION, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF GLY-2. RX MEDLINE=96042026; PubMed=7589240; DOI=10.1006/excr.1995.1362; RA D'Souza-Schorey C., Stahl P.D.; RT "Myristoylation is required for the intracellular localization and RT endocytic function of ARF6."; RL Exp. Cell Res. 221:153-159(1995). RN [6] RP INTERACTION WITH PIP5K1C. RX PubMed=12847086; DOI=10.1083/jcb.200301006; RA Krauss M., Kinuta M., Wenk M.R., De Camilli P., Takei K., Haucke V.; RT "ARF6 stimulates clathrin/AP-2 recruitment to synaptic membranes by RT activating phosphatidylinositol phosphate kinase type Igamma."; RL J. Cell Biol. 162:113-124(2003). RN [7] RP INTERACTION WITH USP6. RX PubMed=15509780; DOI=10.1128/MCB.24.22.9752-9762.2004; RA Martinu L., Masuda-Robens J.M., Robertson S.E., Santy L.C., RA Casanova J.E., Chou M.M.; RT "The TBC (Tre-2/Bub2/Cdc16) domain protein TRE17 regulates plasma RT membrane-endosomal trafficking through activation of Arf6."; RL Mol. Cell. Biol. 24:9752-9762(2004). RN [8] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF THR-27 AND GLN-67. RX PubMed=14978216; DOI=10.1091/mbc.E03-07-0493; RA Gauthier-Campbell C., Bredt D.S., Murphy T.H., El-Husseini A.; RT "Regulation of dendritic branching and filopodia formation in RT hippocampal neurons by specific acylated protein motifs."; RL Mol. Biol. Cell 15:2205-2217(2004). RN [9] RP INTERACTION WITH RAB11FIP3 AND RAB11FIP4. RX PubMed=16148947; DOI=10.1038/sj.emboj.7600803; RA Fielding A.B., Schonteich E., Matheson J., Wilson G., Yu X., RA Hickson G.R., Srivastava S., Baldwin S.A., Prekeris R., Gould G.W.; RT "Rab11-FIP3 and FIP4 interact with Arf6 and the exocyst to control RT membrane traffic in cytokinesis."; RL EMBO J. 24:3389-3399(2005). RN [10] RP INTERACTION WITH HERC1. RX PubMed=15642342; DOI=10.1016/j.febslet.2004.11.095; RA Garcia-Gonzalo F.R., Bartrons R., Ventura F., Rosa J.L.; RT "Requirement of phosphatidylinositol-4,5-bisphosphate for HERC1- RT mediated guanine nucleotide release from ARF proteins."; RL FEBS Lett. 579:343-348(2005). RN [11] RP INTERACTION WITH ARHGAP21. RX PubMed=15793564; DOI=10.1038/ncb1244; RA Dubois T., Paleotti O., Mironov A.A. Jr., Fraisier V., Stradal T.E.B., RA De Matteis M.A., Franco M., Chavrier P.; RT "Golgi-localized GAP for Cdc42 functions downstream of ARF1 to control RT Arp2/3 complex and F-actin dynamics."; RL Nat. Cell Biol. 7:353-364(2005). RN [12] RP INTERACTION WITH RAB11FIP3 AND RAB11FIP4. RX PubMed=17030804; DOI=10.1073/pnas.0605357103; RA Shiba T., Koga H., Shin H.-W., Kawasaki M., Kato R., Nakayama K., RA Wakatsuki S.; RT "Structural basis for Rab11-dependent membrane recruitment of a family RT of Rab11-interacting protein 3 (FIP3)/Arfophilin-1."; RL Proc. Natl. Acad. Sci. U.S.A. 103:15416-15421(2006). RN [13] RP MUTAGENESIS OF THR-27, AND SUBCELLULAR LOCATION. RX PubMed=17398095; DOI=10.1016/j.cub.2007.03.007; RA Hofmann I., Thompson A., Sanderson C.M., Munro S.; RT "The Arl4 family of small G proteins can recruit the cytohesin Arf6 RT exchange factors to the plasma membrane."; RL Curr. Biol. 17:711-716(2007). RN [14] RP INTERACTION WITH RAB11FIP3. RX PubMed=17628206; DOI=10.1016/j.ejcb.2007.05.004; RA Schonteich E., Pilli M., Simon G.C., Matern H.T., Junutula J.R., RA Sentz D., Holmes R.K., Prekeris R.; RT "Molecular characterization of Rab11-FIP3 binding to ARF GTPases."; RL Eur. J. Cell Biol. 86:417-431(2007). RN [15] RP INTERACTION WITH NCS1, AND SUBCELLULAR LOCATION. RX PubMed=17555535; DOI=10.1111/j.1600-0854.2007.00594.x; RA Haynes L.P., Sherwood M.W., Dolman N.J., Burgoyne R.D.; RT "Specificity, promiscuity and localization of ARF protein interactions RT with NCS-1 and phosphatidylinositol-4 kinase-III beta."; RL Traffic 8:1080-1092(2007). RN [16] RP INTERACTION WITH TBC1D24. RX PubMed=20727515; DOI=10.1016/j.ajhg.2010.07.020; RA Falace A., Filipello F., La Padula V., Vanni N., Madia F., RA De Pietri Tonelli D., de Falco F.A., Striano P., Dagna Bricarelli F., RA Minetti C., Benfenati F., Fassio A., Zara F.; RT "TBC1D24, an ARF6-interacting protein, is mutated in familial RT infantile myoclonic epilepsy."; RL Am. J. Hum. Genet. 87:365-370(2010). RN [17] RP SUBCELLULAR LOCATION, AND INTERACTION WITH ECM29. RX PubMed=20682791; DOI=10.1074/jbc.M110.154120; RA Gorbea C., Pratt G., Ustrell V., Bell R., Sahasrabudhe S., RA Hughes R.E., Rechsteiner M.; RT "A protein interaction network for Ecm29 links the 26 S proteasome to RT molecular motors and endosomal components."; RL J. Biol. Chem. 285:31616-31633(2010). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), AND FUNCTION. RX MEDLINE=21174504; PubMed=11266366; DOI=10.1093/embo-reports/kve043; RA Pasqualato S., Menetrey J., Franco M., Cherfils J.; RT "The structural GDP/GTP cycle of human Arf6."; RL EMBO Rep. 2:234-238(2001). CC -!- FUNCTION: GTP-binding protein involved in protein trafficking; CC regulates endocytic recycling and cytoskeleton remodeling. May CC modulate vesicle budding and uncoating within the Golgi apparatus. CC Functions as an allosteric activator of the cholera toxin CC catalytic subunit, an ADP-ribosyltransferase. Involved in the CC regulation of dendritic spine development (By similarity). CC Contributes to the regulation of dendritic branching and filopodia CC extension. CC -!- SUBUNIT: Interacts with ARHGAP21, ASAP2, HERC1, PIP5K1C and UACA. CC Interacts with NCS1/FREQ at the plasma membrane. Interacts with CC RAB11FIP3 and RAB11FIP4. Interacts with USP6 (via Rab-GAP TBC CC domain). Interacts with ECM29. Interacts with TBC1D24. CC -!- INTERACTION: CC P53365:ARFIP2; NbExp=4; IntAct=EBI-638181, EBI-638194; CC P21283:ATP6V1C1; NbExp=4; IntAct=EBI-638181, EBI-988663; CC -!- SUBCELLULAR LOCATION: Golgi apparatus. Cell membrane; Lipid- CC anchor. Endosome membrane; Lipid-anchor. Cell membrane. Cell CC projection, filopodium membrane; Lipid-anchor. Note=Recruited to CC the cell membrane in association with CYTH2 and ARL4C. CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Arf family. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; M57763; AAA90928.1; -; mRNA. DR EMBL; AF047432; AAC39877.1; -; mRNA. DR EMBL; AF493885; AAM12599.1; -; mRNA. DR EMBL; BC002952; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; BC008918; AAH08918.1; -; mRNA. DR IPI; IPI00215920; -. DR PIR; B23741; B23741. DR RefSeq; NP_001654.1; NM_001663.3. DR UniGene; Hs.525330; -. DR UniGene; Hs.719973; -. DR PDB; 1E0S; X-ray; 2.28 A; A=2-175. DR PDB; 2A5D; X-ray; 1.80 A; A=2-174. DR PDB; 2A5F; X-ray; 2.02 A; A=2-174. DR PDB; 2A5G; X-ray; 2.66 A; A=2-174. DR PDB; 2BAO; NMR; -; A=2-11. DR PDB; 2BAU; NMR; -; A=2-11. DR PDB; 2J5X; X-ray; 2.80 A; A/B=1-175. DR PDB; 2W83; X-ray; 1.93 A; A/B/E=13-175. DR PDB; 3LVQ; X-ray; 3.38 A; E=11-175. DR PDB; 3LVR; X-ray; 3.38 A; E=11-175. DR PDB; 3N5C; X-ray; 1.82 A; A/B=14-175. DR PDB; 3PCR; X-ray; 2.50 A; B=14-175. DR PDBsum; 1E0S; -. DR PDBsum; 2A5D; -. DR PDBsum; 2A5F; -. DR PDBsum; 2A5G; -. DR PDBsum; 2BAO; -. DR PDBsum; 2BAU; -. DR PDBsum; 2J5X; -. DR PDBsum; 2W83; -. DR PDBsum; 3LVQ; -. DR PDBsum; 3LVR; -. DR PDBsum; 3N5C; -. DR PDBsum; 3PCR; -. DR ProteinModelPortal; P62330; -. DR SMR; P62330; 2-174. DR IntAct; P62330; 4. DR STRING; P62330; -. DR PhosphoSite; P62330; -. DR DMDM; 51316984; -. DR PeptideAtlas; P62330; -. DR PRIDE; P62330; -. DR Ensembl; ENST00000298316; ENSP00000298316; ENSG00000165527. DR GeneID; 382; -. DR KEGG; hsa:382; -. DR UCSC; uc001wxg.2; human. DR CTD; 382; -. DR GeneCards; GC14P050359; -. DR H-InvDB; HIX0011635; -. DR HGNC; HGNC:659; ARF6. DR HPA; CAB002778; -. DR MIM; 600464; gene. DR neXtProt; NX_P62330; -. DR PharmGKB; PA24942; -. DR eggNOG; prNOG17653; -. DR HOGENOM; HBG745225; -. DR HOVERGEN; HBG002073; -. DR InParanoid; P62330; -. DR OMA; WLTSNHK; -. DR OrthoDB; EOG4GQQ62; -. DR PhylomeDB; P62330; -. DR Pathway_Interaction_DB; arf6downstreampathway; Arf6 downstream pathway. DR Pathway_Interaction_DB; arf6cyclingpathway; Arf6 signaling events. DR Pathway_Interaction_DB; arf6_traffickingpathway; Arf6 trafficking events. DR Pathway_Interaction_DB; pi3kcipathway; Class I PI3K signaling events. DR Pathway_Interaction_DB; a4b1_paxdep_pathway; Paxillin-dependent events mediated by a4b1. DR Pathway_Interaction_DB; a4b1_paxindep_pathway; Paxillin-independent events mediated by a4b1 and a4b7. DR NextBio; 1599; -. DR ArrayExpress; P62330; -. DR Bgee; P62330; -. DR CleanEx; HS_ARF6; -. DR Genevestigator; P62330; -. DR GermOnline; ENSG00000165527; Homo sapiens. DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB. DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0031527; C:filopodium membrane; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell. DR GO; GO:0005624; C:membrane fraction; TAS:ProtInc. DR GO; GO:0001726; C:ruffle; IDA:UniProtKB. DR GO; GO:0005525; F:GTP binding; TAS:UniProtKB. DR GO; GO:0003924; F:GTPase activity; TAS:ProtInc. DR GO; GO:0031996; F:thioesterase binding; IPI:UniProtKB. DR GO; GO:0007155; P:cell adhesion; TAS:UniProtKB. DR GO; GO:0006928; P:cellular component movement; TAS:UniProtKB. DR GO; GO:0030866; P:cortical actin cytoskeleton organization; IMP:UniProtKB. DR GO; GO:0048261; P:negative regulation of receptor-mediated endocytosis; TAS:UniProtKB. DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IMP:UniProtKB. DR GO; GO:0090004; P:positive regulation of establishment of protein localization in plasma membrane; ISS:BHF-UCL. DR GO; GO:0034394; P:protein localization at cell surface; ISS:BHF-UCL. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR GO; GO:0060998; P:regulation of dendritic spine development; ISS:UniProtKB. DR GO; GO:0051489; P:regulation of filopodium assembly; IDA:UniProtKB. DR GO; GO:0035020; P:regulation of Rac protein signal transduction; IDA:UniProtKB. DR GO; GO:0031529; P:ruffle organization; IDA:UniProtKB. DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro. DR GO; GO:0016192; P:vesicle-mediated transport; TAS:UniProtKB. DR InterPro; IPR005225; Small_GTP-bd_dom. DR InterPro; IPR024156; Small_GTPase_ARF. DR InterPro; IPR006689; Small_GTPase_ARF/SAR. DR KO; K07941; -. DR PANTHER; PTHR11711; ARF/SAR; 1. DR Pfam; PF00025; Arf; 1. DR PRINTS; PR00328; SAR1GTPBP. DR SMART; SM00177; ARF; 1. DR TIGRFAMs; TIGR00231; Small_GTP; 1. DR PROSITE; PS51417; ARF; 1. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Cell projection; Complete proteome; KW Differentiation; Endosome; ER-Golgi transport; Golgi apparatus; KW GTP-binding; Lipoprotein; Membrane; Myristate; Neurogenesis; KW Nucleotide-binding; Protein transport; Reference proteome; Transport. FT INIT_MET 1 1 Removed. FT CHAIN 2 175 ADP-ribosylation factor 6. FT /FTId=PRO_0000207400. FT NP_BIND 20 27 GTP (By similarity). FT NP_BIND 63 67 GTP (By similarity). FT NP_BIND 122 125 GTP (By similarity). FT LIPID 2 2 N-myristoyl glycine. FT MUTAGEN 2 2 G->A: Fails to associate with membranes. FT MUTAGEN 27 27 T->N: Fails to associate with membranes. FT Does not inhibit filopodia formation. FT MUTAGEN 67 67 Q->L: Inhibits filopodia formation and FT dendritic branching. FT HELIX 3 9 FT STRAND 14 21 FT HELIX 26 32 FT STRAND 39 44 FT STRAND 47 54 FT STRAND 57 65 FT HELIX 68 70 FT HELIX 71 74 FT HELIX 75 77 FT TURN 78 80 FT STRAND 83 89 FT HELIX 93 95 FT HELIX 96 107 FT HELIX 110 112 FT STRAND 116 122 FT HELIX 132 138 FT HELIX 141 143 FT STRAND 149 153 FT TURN 156 159 FT HELIX 162 172 SQ SEQUENCE 175 AA; 20082 MW; 49E38E59AEA52B98 CRC64; MGKVLSKIFG NKEMRILMLG LDAAGKTTIL YKLKLGQSVT TIPTVGFNVE TVTYKNVKFN VWDVGGQDKI RPLWRHYYTG TQGLIFVVDC ADRDRIDEAR QELHRIINDR EMRDAIILIF ANKQDLPDAM KPHEIQEKLG LTRIRDRNWY VQPSCATSGD GLYEGLTWLT SNYKS //