ID ARF6_HUMAN Reviewed; 175 AA. AC P62330; P26438; Q6FGZ2; DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 16-SEP-2015, entry version 133. 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 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 [GENOMIC DNA], AND TISSUE SPECIFICITY. RX PubMed=14659046; DOI=10.1089/104454903770946719; RA Lebeda R.A., Johnson S.K., Stewart M.I., Haun R.S.; RT "Sequence, genomic organization, and expression of the human ADP- RT ribosylation factor 6 (ARF6) gene: a class III ARF."; RL DNA Cell Biol. 22:737-741(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Umbilical cord blood; RX 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 [4] 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Trachea; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] 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 [9] RP MYRISTOYLATION AT GLY-2, FUNCTION, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF GLY-2. RX 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 [10] RP ENZYME REGULATION. RC TISSUE=Leukocyte; RX PubMed=11062263; DOI=10.1083/jcb.151.3.627; RA Jackson T.R., Brown F.D., Nie Z., Miura K., Foroni L., Sun J., RA Hsu V.W., Donaldson J.G., Randazzo P.A.; RT "ACAPs are arf6 GTPase-activating proteins that function in the cell RT periphery."; RL J. Cell Biol. 151:627-638(2000). RN [11] 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 [12] 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 [13] 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 [14] 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 [15] 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 [16] 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 [17] RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF THR-27 AND GLN-67, AND RP INTERACTION WITH ASAP3. RX PubMed=16737952; DOI=10.1074/mcp.M600050-MCP200; RA Fang Z., Miao Y., Ding X., Deng H., Liu S., Wang F., Zhou R., RA Watson C., Fu C., Hu Q., Lillard J.W. Jr., Powell M., Chen Y., RA Forte J.G., Yao X.; RT "Proteomic identification and functional characterization of a novel RT ARF6 GTPase-activating protein, ACAP4."; RL Mol. Cell. Proteomics 5:1437-1449(2006). RN [18] 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 [19] 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 [20] 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 [21] 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 [22] RP FUNCTION, AND ENZYME REGULATION. RX PubMed=18400762; DOI=10.1074/jbc.M709717200; RA Ha V.L., Bharti S., Inoue H., Vass W.C., Campa F., Nie Z., RA de Gramont A., Ward Y., Randazzo P.A.; RT "ASAP3 is a focal adhesion-associated Arf GAP that functions in cell RT migration and invasion."; RL J. Biol. Chem. 283:14915-14926(2008). RN [23] 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 [24] RP SUBCELLULAR LOCATION. RX PubMed=19948740; DOI=10.1074/jbc.M109.069385; RA Wan T., Liu T., Zhang H., Tang S., Min W.; RT "AIP1 functions as Arf6-GAP to negatively regulate TLR4 signaling."; RL J. Biol. Chem. 285:3750-3757(2010). RN [25] 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 [26] 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 [27] RP INTERACTION WITH MICALL1, AND SUBCELLULAR LOCATION. RX PubMed=21951725; DOI=10.1111/j.1600-0854.2011.01294.x; RA Rahajeng J., Giridharan S.S., Cai B., Naslavsky N., Caplan S.; RT "MICAL-L1 is a tubular endosomal membrane hub that connects Rab35 and RT Arf6 with Rab8a."; RL Traffic 13:82-93(2012). RN [28] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [29] RP X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) IN COMPLEX WITH GDP. RX PubMed=10881192; DOI=10.1038/75863; RA Menetrey J., Macia E., Pasqualato S., Franco M., Cherfils J.; RT "Structure of Arf6-GDP suggests a basis for guanine nucleotide RT exchange factors specificity."; RL Nat. Struct. Biol. 7:466-469(2000). RN [30] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH GTP ANALOG, AND RP FUNCTION. RX 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). RN [31] RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH GTP AND RP V.CHOLERAE ENTEROTOXIN SUBUNIT A1, SUBUNIT, AND FUNCTION. RX PubMed=16099990; DOI=10.1126/science.1113398; RA O'Neal C.J., Jobling M.G., Holmes R.K., Hol W.G.; RT "Structural basis for the activation of cholera toxin by human ARF6- RT GTP."; RL Science 309:1093-1096(2005). RN [32] RP STRUCTURE BY NMR OF 2-11. RX PubMed=16839550; DOI=10.1016/j.febslet.2006.06.086; RA Gizachew D., Oswald R.; RT "NMR structural studies of the myristoylated N-terminus of ADP RT ribosylation factor 6 (Arf6)."; RL FEBS Lett. 580:4296-4301(2006). RN [33] RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 13-175 IN COMPLEX WITH GTP RP AND SPAG9, AND INTERACTION WITH SPAG9. RX PubMed=19644450; DOI=10.1038/emboj.2009.209; RA Isabet T., Montagnac G., Regazzoni K., Raynal B., El Khadali F., RA England P., Franco M., Chavrier P., Houdusse A., Menetrey J.; RT "The structural basis of Arf effector specificity: the crystal RT structure of ARF6 in a complex with JIP4."; RL EMBO J. 28:2835-2845(2009). RN [34] RP X-RAY CRYSTALLOGRAPHY (3.38 ANGSTROMS) OF 11-175 IN COMPLEX WITH GDP RP ASAP3 AND CALCIUM IONS, AND INTERACTION WITH ASAP3. RX PubMed=20510928; DOI=10.1016/j.cell.2010.03.051; RA Ismail S.A., Vetter I.R., Sot B., Wittinghofer A.; RT "The structure of an Arf-ArfGAP complex reveals a Ca2+ regulatory RT mechanism."; RL Cell 141:812-821(2010). RN [35] RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 14-175 IN COMPLEX WITH GTP RP AND E.COLI ESPG, FUNCTION, AND SUBUNIT. RX PubMed=21170023; DOI=10.1038/nature09593; RA Selyunin A.S., Sutton S.E., Weigele B.A., Reddick L.E., Orchard R.C., RA Bresson S.M., Tomchick D.R., Alto N.M.; RT "The assembly of a GTPase-kinase signalling complex by a bacterial RT catalytic scaffold."; RL Nature 469:107-111(2011). RN [36] RP X-RAY CRYSTALLOGRAPHY (4.10 ANGSTROMS) OF 14-173 IN COMPLEX WITH GTP; RP RAB1A AND E.COLI ESPG, AND SUBUNIT. RX PubMed=22939626; DOI=10.1016/j.cell.2012.06.050; RA Dong N., Zhu Y., Lu Q., Hu L., Zheng Y., Shao F.; RT "Structurally distinct bacterial TBC-like GAPs link Arf GTPase to Rab1 RT inactivation to counteract host defenses."; RL Cell 150:1029-1041(2012). RN [37] RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 14-173 IN COMPLEX WITH CYTH3 RP AND GTP, AND SUBUNIT. RX PubMed=23940353; DOI=10.1073/pnas.1301883110; RA Malaby A.W., van den Berg B., Lambright D.G.; RT "Structural basis for membrane recruitment and allosteric activation RT of cytohesin family Arf GTPase exchange factors."; RL Proc. Natl. Acad. Sci. U.S.A. 110:14213-14218(2013). CC -!- FUNCTION: GTP-binding protein involved in protein trafficking that CC regulates endocytic recycling and cytoskeleton remodeling. CC Required for normal completion of mitotic cytokinesis. Plays a CC role in the reorganization of the actin cytoskeleton and the CC formation of stress fibers. May also modulate vesicle budding and CC uncoating within the Golgi apparatus. Involved in the regulation CC of dendritic spine development, contributing to the regulation of CC dendritic branching and filopodia extension. Functions as an CC allosteric activator of the cholera toxin catalytic subunit, an CC ADP-ribosyltransferase. {ECO:0000269|PubMed:11266366, CC ECO:0000269|PubMed:14978216, ECO:0000269|PubMed:16099990, CC ECO:0000269|PubMed:16737952, ECO:0000269|PubMed:18400762, CC ECO:0000269|PubMed:21170023, ECO:0000269|PubMed:7589240}. CC -!- ENZYME REGULATION: Activation is generally mediated by a guanine CC exchange factor (GEF), while inactivation through hydrolysis of CC bound GTP is catalyzed by a GTPase activating protein (GAP). CC Activated by ASAP3. Inactivated by ACAP1 and ACAP2. CC {ECO:0000269|PubMed:11062263, ECO:0000269|PubMed:18400762}. CC -!- SUBUNIT: Interacts with ARHGAP21, ASAP2, ASAP3, HERC1, PIP5K1C and CC UACA. The interaction with ASAP3 is stabilized by calcium ions. 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. Interacts CC with MICALL1. Interacts with KIF23, forming heterodimers and CC heterotetramers. Interacts with GGA1 and RAB11FIP4. Interacts with CC SPAG9 homodimers, forming heterotetramers. Interacts with CYTH3. CC Interacts with EspG from enteropathogenic E.coli. Identified in a CC complex with RAB1A and EspG from enteropathogenic E.coli. CC Interacts with the V.cholerae enterotoxin subunit A1; this causes CC a conformation change so that the toxin can bind NAD and catalyze CC the ADP-ribosylation of Gs alpha. {ECO:0000269|PubMed:10881192, CC ECO:0000269|PubMed:11266366, ECO:0000269|PubMed:12847086, CC ECO:0000269|PubMed:15509780, ECO:0000269|PubMed:15642342, CC ECO:0000269|PubMed:15793564, ECO:0000269|PubMed:16099990, CC ECO:0000269|PubMed:16148947, ECO:0000269|PubMed:16737952, CC ECO:0000269|PubMed:17030804, ECO:0000269|PubMed:17555535, CC ECO:0000269|PubMed:17628206, ECO:0000269|PubMed:19644450, CC ECO:0000269|PubMed:20510928, ECO:0000269|PubMed:20682791, CC ECO:0000269|PubMed:20727515, ECO:0000269|PubMed:21170023, CC ECO:0000269|PubMed:21951725, ECO:0000269|PubMed:22939626, CC ECO:0000269|PubMed:23940353}. CC -!- INTERACTION: CC P53365:ARFIP2; NbExp=4; IntAct=EBI-638181, EBI-638194; CC P21283:ATP6V1C1; NbExp=4; IntAct=EBI-638181, EBI-988663; CC Q02241:KIF23; NbExp=23; IntAct=EBI-638181, EBI-306852; CC O60271:SPAG9; NbExp=8; IntAct=EBI-638181, EBI-1023301; CC -!- SUBCELLULAR LOCATION: Golgi apparatus. Cell membrane; Lipid- CC anchor. Endosome membrane; Lipid-anchor. Recycling endosome CC membrane {ECO:0000305}; Lipid-anchor {ECO:0000305}. Cell CC projection, filopodium membrane; Lipid-anchor. Midbody CC {ECO:0000250}. Cytoplasm {ECO:0000250}. Cleavage furrow CC {ECO:0000250}. Note=Distributed throughout the cytoplasm during CC metaphase. Transiently detected at the ingressing cleavage furrow CC during mitotic cytokinesis. Recruited to the midbody at later CC stages of cytokinesis; this requires interaction with KIF23 (By CC similarity). Recruited to the cell membrane in association with CC CYTH2 and ARL4C. Colocalizes with DAB2IP at the plasma membrane CC and endocytic vesicles. {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Ubiquitous, with higher levels in heart, CC substantia nigra, and kidney. {ECO:0000269|PubMed:14659046}. CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Arf family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M57763; AAA90928.1; -; mRNA. DR EMBL; AY296206; AAP50257.1; -; Genomic_DNA. DR EMBL; AF047432; AAC39877.1; -; mRNA. DR EMBL; AF493885; AAM12599.1; -; mRNA. DR EMBL; AK313790; BAG36527.1; -; mRNA. DR EMBL; CR541964; CAG46762.1; -; mRNA. DR EMBL; CH471078; EAW65740.1; -; Genomic_DNA. DR EMBL; BC002952; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; BC008918; AAH08918.1; -; mRNA. DR CCDS; CCDS9695.1; -. 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=1-175. DR PDB; 2A5F; X-ray; 2.02 A; A=1-175. DR PDB; 2A5G; X-ray; 2.66 A; A=1-175. DR PDB; 2BAO; NMR; -; A=2-11. DR PDB; 2BAU; NMR; -; A=2-11. DR PDB; 2J5X; X-ray; 2.80 A; A/B=2-175. 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 PDB; 4FME; X-ray; 4.10 A; C/F=14-173. DR PDB; 4KAX; X-ray; 1.85 A; A=14-173. 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 PDBsum; 4FME; -. DR PDBsum; 4KAX; -. DR ProteinModelPortal; P62330; -. DR SMR; P62330; 12-174. DR BioGrid; 106877; 53. DR DIP; DIP-33352N; -. DR IntAct; P62330; 16. DR MINT; MINT-4824639; -. DR STRING; 9606.ENSP00000298316; -. DR ChEMBL; CHEMBL5987; -. DR PhosphoSite; P62330; -. DR BioMuta; ARF6; -. DR DMDM; 51316984; -. DR MaxQB; P62330; -. DR PaxDb; P62330; -. DR PeptideAtlas; P62330; -. DR PRIDE; P62330; -. DR DNASU; 382; -. DR Ensembl; ENST00000298316; ENSP00000298316; ENSG00000165527. DR GeneID; 382; -. DR KEGG; hsa:382; -. DR UCSC; uc001wxg.4; human. DR CTD; 382; -. DR GeneCards; GC14P049895; -. DR HGNC; HGNC:659; ARF6. DR HPA; CAB002778; -. DR MIM; 600464; gene. DR neXtProt; NX_P62330; -. DR PharmGKB; PA24942; -. DR eggNOG; COG1100; -. DR GeneTree; ENSGT00780000121855; -. DR HOGENOM; HOG000163691; -. DR HOVERGEN; HBG002073; -. DR InParanoid; P62330; -. DR KO; K07941; -. DR OMA; QPACATT; -. DR OrthoDB; EOG7F5133; -. DR PhylomeDB; P62330; -. DR TreeFam; TF300808; -. DR SignaLink; P62330; -. DR EvolutionaryTrace; P62330; -. DR GeneWiki; ARF6; -. DR GenomeRNAi; 382; -. DR NextBio; 1599; -. DR PRO; PR:P62330; -. DR Proteomes; UP000005640; Chromosome 14. DR Bgee; P62330; -. DR CleanEx; HS_ARF6; -. DR Genevisible; P62330; HS. DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB. DR GO; GO:0032154; C:cleavage furrow; IEA:UniProtKB-SubCell. DR GO; GO:0005769; C:early endosome; IEA:Ensembl. DR GO; GO:0030139; C:endocytic vesicle; IDA:UniProtKB. DR GO; GO:0005768; C:endosome; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0031527; C:filopodium membrane; IDA:UniProtKB. DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0030496; C:midbody; IEA:UniProtKB-SubCell. DR GO; GO:0043209; C:myelin sheath; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB. 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:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0030866; P:cortical actin cytoskeleton organization; IMP:UniProtKB. DR GO; GO:0090162; P:establishment of epithelial cell polarity; IEA:Ensembl. DR GO; GO:0097284; P:hepatocyte apoptotic process; IEA:Ensembl. DR GO; GO:0001889; P:liver development; IEA:Ensembl. DR GO; GO:0006928; P:movement of cell or subcellular component; TAS:UniProtKB. DR GO; GO:0033028; P:myeloid cell apoptotic process; IEA:Ensembl. DR GO; GO:2000171; P:negative regulation of dendrite development; IEA:Ensembl. 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 to plasma membrane; ISS:BHF-UCL. DR GO; GO:0034394; P:protein localization to cell surface; ISS:BHF-UCL. DR GO; GO:0036010; P:protein localization to endosome; IMP:UniProtKB. 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 Gene3D; 3.40.50.300; -; 1. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR005225; Small_GTP-bd_dom. DR InterPro; IPR024156; Small_GTPase_ARF. DR InterPro; IPR006689; Small_GTPase_ARF/SAR. DR Pfam; PF00025; Arf; 1. DR PRINTS; PR00328; SAR1GTPBP. DR SMART; SM00177; ARF; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR TIGRFAMs; TIGR00231; small_GTP; 1. DR PROSITE; PS51417; ARF; 1. PE 1: Evidence at protein level; KW 3D-structure; Cell cycle; Cell division; Cell membrane; KW Cell projection; Complete proteome; Cytoplasm; Differentiation; KW Endosome; ER-Golgi transport; Golgi apparatus; GTP-binding; KW Lipoprotein; Membrane; Myristate; Neurogenesis; Nucleotide-binding; KW 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 23 28 GTP. {ECO:0000269|PubMed:16099990, FT ECO:0000269|PubMed:19644450, FT ECO:0000269|PubMed:21170023, FT ECO:0000269|PubMed:22939626, FT ECO:0000269|PubMed:23940353}. FT NP_BIND 41 44 GTP. {ECO:0000269|PubMed:16099990, FT ECO:0000269|PubMed:19644450, FT ECO:0000269|PubMed:21170023, FT ECO:0000269|PubMed:22939626, FT ECO:0000269|PubMed:23940353}. FT NP_BIND 63 67 GTP. {ECO:0000269|PubMed:16099990, FT ECO:0000269|PubMed:19644450, FT ECO:0000269|PubMed:21170023, FT ECO:0000269|PubMed:22939626, FT ECO:0000269|PubMed:23940353}. FT NP_BIND 122 125 GTP. {ECO:0000269|PubMed:16099990, FT ECO:0000269|PubMed:19644450, FT ECO:0000269|PubMed:21170023, FT ECO:0000269|PubMed:22939626, FT ECO:0000269|PubMed:23940353}. FT NP_BIND 155 156 GTP. {ECO:0000269|PubMed:16099990, FT ECO:0000269|PubMed:19644450, FT ECO:0000269|PubMed:21170023, FT ECO:0000269|PubMed:22939626, FT ECO:0000269|PubMed:23940353}. FT LIPID 2 2 N-myristoyl glycine. FT {ECO:0000269|PubMed:7589240}. FT MUTAGEN 2 2 G->A: Fails to associate with membranes. FT {ECO:0000269|PubMed:7589240}. FT MUTAGEN 27 27 T->N: Fails to associate with membranes. FT Does not inhibit filopodia formation. FT {ECO:0000269|PubMed:14978216, FT ECO:0000269|PubMed:16737952, FT ECO:0000269|PubMed:17398095}. FT MUTAGEN 67 67 Q->L: Inhibits filopodia formation and FT dendritic branching. FT {ECO:0000269|PubMed:14978216, FT ECO:0000269|PubMed:16737952}. FT HELIX 3 9 {ECO:0000244|PDB:1E0S}. FT STRAND 13 19 {ECO:0000244|PDB:2A5D}. FT HELIX 26 35 {ECO:0000244|PDB:2A5D}. FT STRAND 39 44 {ECO:0000244|PDB:1E0S}. FT STRAND 45 54 {ECO:0000244|PDB:2A5D}. FT STRAND 57 64 {ECO:0000244|PDB:2A5D}. FT HELIX 65 67 {ECO:0000244|PDB:3N5C}. FT HELIX 68 77 {ECO:0000244|PDB:2A5D}. FT TURN 78 80 {ECO:0000244|PDB:1E0S}. FT STRAND 83 89 {ECO:0000244|PDB:2A5D}. FT HELIX 93 95 {ECO:0000244|PDB:2A5D}. FT HELIX 96 107 {ECO:0000244|PDB:2A5D}. FT HELIX 110 112 {ECO:0000244|PDB:2A5D}. FT STRAND 116 122 {ECO:0000244|PDB:2A5D}. FT STRAND 125 128 {ECO:0000244|PDB:3LVQ}. FT HELIX 132 138 {ECO:0000244|PDB:2A5D}. FT HELIX 141 143 {ECO:0000244|PDB:2A5D}. FT STRAND 149 153 {ECO:0000244|PDB:2A5D}. FT TURN 156 159 {ECO:0000244|PDB:2A5D}. FT HELIX 162 172 {ECO:0000244|PDB:2A5D}. 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 //