RBCC

Full text data of ARF6

ARF6 [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
ADP-ribosylation factor 6

UniProt P62330
ID ARF6_HUMAN Reviewed; 175 AA.
AC P62330; P26438; Q6FGZ2;
DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 117.
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 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 [29]
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 [30]
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 [31]
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 [32]
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 [33]
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 [34]
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 [35]
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 [36]
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.
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 -!- 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.
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; Lipid-anchor (Probable). Cell projection, filopodium
CC membrane; Lipid-anchor. Midbody (By similarity). Cytoplasm (By
CC similarity). Cleavage furrow (By similarity). Note=Distributed
CC throughout the cytoplasm during metaphase. Transiently detected at
CC the ingressing cleavage furrow during mitotic cytokinesis.
CC Recruited to the midbody at later stages of cytokinesis; this
CC requires interaction with KIF23 (By similarity). Recruited to the
CC cell membrane in association with CYTH2 and ARL4C. Colocalizes
CC with DAB2IP at the plasma membrane and endocytic vesicles.
CC -!- TISSUE SPECIFICITY: Ubiquitous, with higher levels in heart,
CC substantia nigra, and kidney.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Arf family.
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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 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 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 DIP; DIP-33352N; -.
DR IntAct; P62330; 16.
DR MINT; MINT-4824639; -.
DR STRING; 9606.ENSP00000298316; -.
DR ChEMBL; CHEMBL5987; -.
DR PhosphoSite; P62330; -.
DR DMDM; 51316984; -.
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; GC14P050359; -.
DR HGNC; HGNC:659; ARF6.
DR HPA; CAB002778; -.
DR MIM; 600464; gene.
DR neXtProt; NX_P62330; -.
DR PharmGKB; PA24942; -.
DR eggNOG; COG1100; -.
DR HOGENOM; HOG000163691; -.
DR HOVERGEN; HBG002073; -.
DR InParanoid; P62330; -.
DR KO; K07941; -.
DR OMA; TELHRII; -.
DR OrthoDB; EOG7F5133; -.
DR SignaLink; P62330; -.
DR EvolutionaryTrace; P62330; -.
DR GeneWiki; ARF6; -.
DR GenomeRNAi; 382; -.
DR NextBio; 1599; -.
DR PRO; PR:P62330; -.
DR Bgee; P62330; -.
DR CleanEx; HS_ARF6; -.
DR Genevestigator; P62330; -.
DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB.
DR GO; GO:0005769; C:early endosome; IEA:Ensembl.
DR GO; GO:0030139; C:endocytic vesicle; IDA:UniProtKB.
DR GO; GO:0031527; C:filopodium membrane; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
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:0006915; P:apoptotic process; IEA:Ensembl.
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:0090162; P:establishment of epithelial cell polarity; IEA:Ensembl.
DR GO; GO:0001889; P:liver 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 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.
FT NP_BIND 41 44 GTP.
FT NP_BIND 63 67 GTP.
FT NP_BIND 122 125 GTP.
FT NP_BIND 155 156 GTP.
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 13 19
FT HELIX 26 35
FT STRAND 39 44
FT STRAND 45 54
FT STRAND 57 64
FT HELIX 65 67
FT HELIX 68 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 STRAND 125 128
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
//

MIM 600464
*RECORD*
*FIELD* NO
600464
*FIELD* TI
*600464 ADP-RIBOSYLATION FACTOR 6; ARF6
*FIELD* TX

GENE FAMILY

Intracellular membrane trafficking involves a series of membrane budding
read moreand fusion events. These are regulated by specific cytosolic and
membrane-associated protein factors, among which are a group of Ras-like
small guanosine triphosphatases (GTPases) called adenosine diphosphate
(ADP)-ribosylation factors (ARFs). These factors were originally
identified as cofactors required for the cholera toxin-catalyzed
ADP-ribosylation of Gs, alpha subunit (GNAS1; 139320); see
ADP-ribosylation factor-1 (ARF1; 103180). The ARF family consists of 15
structurally related gene products that include 6 ARF proteins and 11
ARF-like proteins. The ARF proteins are divided into 3 classes on the
basis of size and amino acid identity. ARF1, ARF2, and ARF3 (103190)
(181 amino acids) form class I; ARF4 and ARF5 (103188) (180 amino acids)
form class II; ARF6 (175 amino acids) forms class III.

GENE FUNCTION

D'Souza-Schorey et al. (1995) transiently expressed ARF6, ARF6 mutants,
and ARF1 in Chinese hamster ovary cells and assessed the effects on
receptor-mediated endocytosis. The authors demonstrated that ARF6,
unlike ARF1 which is localized to the Golgi apparatus, has a central
role in intra-Golgi transport, is localized to the cell periphery, and
that overexpression of ARF6 causes dramatic alterations in endocytic
traffic. Expression of a dominant-negative mutant of ARF6, thr27 to asn,
resulted in an intracellular distribution of transferrin receptors and
an inhibition of transferrin recycling to the cell surface. Cavenagh et
al. (1996) examined the subcellular distribution of ARF proteins and
demonstrated that ARF6 is uniquely localized to the plasma membranes in
Chinese hamster ovary cells. This result suggests that ARF6 is unlikely
to be involved in endocytic traffic.

Studying rat hippocampal neurons in culture, Hernandez-Deviez et al.
(2002) determined that dendritic arbor development is regulated by
complex interactions of ARNO (602488), ARF6, and RAC1 (602048).
Activation of ARNO and ARF6 resulted in signaling through RAC1 that
suppressed dendritic branching.

By coimmunoprecipitation studies in COS-7 cells, Falace et al. (2010)
found that TBC1D24 (613577) binds ARF6 and acts as a negative regulator
of ARF6. The intensity of the coimmunoprecipitated band increased in the
presence of inactive GDP-locked ARF6, indicating a GDP-dependent
interaction.

Zhu et al. (2012) showed that the direct, immediate, and disruptive
effects of IL1-beta (IL1B; 147720) on endothelial stability in a human
in vitro cell model are NF-kappa-B (see 164011)-independent and are
instead the result of signaling through the small GTPase ARF6 and its
activator ARF nucleotide-binding site opener (ARNO; 602488). Moreover,
Zhu et al. (2012) showed that ARNO binds directly to the adaptor protein
MYD88 (602170), and thus proposed MYD88-ARNO-ARF6 as a proximal IL1-beta
signaling pathway distinct from that mediated by NF-kappa-B. Finally,
Zhu et al. (2012) showed that SecinH3 (182115), an inhibitor of ARF
guanine nucleotide exchange factors such as ARNO, enhances vascular
stability and significantly improves outcomes in animal models of
inflammatory arthritis and acute inflammation.

BIOCHEMICAL FEATURES

- Crystal Structure

O'Neal et al. (2005) determined the 1.8-angstrom crystal structure of
the cholera toxin A1 subunit in complex with human GTP-bound ARF6. Their
studies revealed that the binding of the human activator elicits
dramatic changes in CTA1 loop regions that allow nicotinamide adenine
dinucleotide (NAD+) to bind to the active site. The extensive
toxin:ARF-GTP interface surface mimics the ARF-GTP recognition of normal
cellular protein partners, which suggests that the toxin has evolved to
exploit promiscuous binding properties of ARFs.

*FIELD* RF
1. Cavenagh, M. M.; Whitney, J. A.; Carroll, K.; Zhang, C.; Boman,
A. L.; Rosenwald., A. G.; Mellman, I.; Kahn, R. A.: Intracellular
distribution of Arf proteins in mammalian cells. J. Biol. Chem. 271:
21767-21774, 1996.

2. D'Souza-Schorey, C.; Li, G.; Colombo, M. I.; Stahl, P. D.: A regulatory
role for ARF6 in receptor-mediated endocytosis. Science 267: 1175-1178,
1995.

3. 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.: TBC1D24, an
ARF6-interacting protein, is mutated in familial infantile myoclonic
epilepsy. Am. J. Hum. Genet. 87: 365-370, 2010.

4. Hernandez-Deviez, D. J.; Casanova, J. E.; Wilson, J. M.: Regulation
of dendritic development by the ARF exchange factor ARNO. Nature
Neurosci. 5: 623-624, 2002.

5. O'Neal, C. J.; Jobling, M. G.; Holmes, R. K.; Hol, W. G. J.: Structural
basis for the activation of cholera toxin by human ARF6-GTP. Science 309:
1093-1096, 2005.

6. Zhu, W.; London, N. R.; Gibson, C. C.; Davis, C. T.; Tong, Z.;
Sorenson, L. K.; Shi, D. S.; Guo, J.; Smith, M. C. P.; Grossmann,
A. H.; Thomas, K. R.; Li, D. Y.: Interleukin receptor activates a
MYD88-ARNO-ARF6 cascade to disrupt vascular stability. Nature 492:
252-255, 2012.

*FIELD* CN
Ada Hamosh - updated: 1/29/2013
Cassandra L. Kniffin - updated: 10/20/2010
Ada Hamosh - updated: 9/7/2005
Cassandra L. Kniffin - updated: 2/5/2003
Victor A. McKusick - updated: 10/15/1998

*FIELD* CD
Victor A. McKusick: 3/23/1995

*FIELD* ED
alopez: 02/06/2013
terry: 1/29/2013
wwang: 10/25/2010
ckniffin: 10/20/2010
wwang: 8/18/2010
alopez: 9/13/2005
terry: 9/7/2005
carol: 2/14/2003
ckniffin: 2/5/2003
carol: 10/26/1998
terry: 10/15/1998
dkim: 9/11/1998
dkim: 6/26/1998
alopez: 4/15/1997
alopez: 4/14/1997
alopez: 4/9/1997
mark: 3/24/1995
mark: 3/23/1995

RBCC Red Blood Cell Collection

Full text data of ARF6