Full text data of ARF1
ARF1
[Confidence: low (only semi-automatic identification from reviews)]
ADP-ribosylation factor 1
ADP-ribosylation factor 1
UniProt
P84077
ID ARF1_HUMAN Reviewed; 181 AA.
AC P84077; P10947; P32889;
DT 16-AUG-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 1;
GN Name=ARF1;
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=2474826; DOI=10.1073/pnas.86.16.6101;
RA Bobak D.A., Nightingale M.S., Murtagh J.J. Jr., Price S.R., Moss J.,
RA Vaughan M.;
RT "Molecular cloning, characterization, and expression of human ADP-
RT ribosylation factors: two guanine nucleotide-dependent activators of
RT cholera toxin.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:6101-6105(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1899243;
RA Kahn R.A., Kern F.G., Clark J., Gelmann E.P., Rulka C.;
RT "Human ADP-ribosylation factors. A functionally conserved family of
RT GTP-binding proteins.";
RL J. Biol. Chem. 266:2606-2614(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1577740;
RA Lee C.M., Haun R.S., Tsai S.C., Moss J., Vaughan M.;
RT "Characterization of the human gene encoding ADP-ribosylation factor
RT 1, a guanine nucleotide-binding activator of cholera toxin.";
RL J. Biol. Chem. 267:9028-9034(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=9110174;
RA Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W.,
RA Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A.;
RT "Large-scale concatenation cDNA sequencing.";
RL Genome Res. 7:353-358(1997).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cervix, Eye, and Kidney;
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 PROTEIN SEQUENCE OF 20-30; 80-97 AND 118-142, AND MASS SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [10]
RP INTERACTION WITH HERC1.
RX PubMed=8861955;
RA Rosa J.L., Casaroli-Marano R.P., Buckler A.J., Vilaro S., Barbacid M.;
RT "p619, a giant protein related to the chromosome condensation
RT regulator RCC1, stimulates guanine nucleotide exchange on ARF1 and Rab
RT proteins.";
RL EMBO J. 15:4262-4273(1996).
RN [11]
RP INTERACTION WITH ASAP2.
RX PubMed=10022920;
RA Andreev J., Simon J.-P., Sabatini D.D., Kam J., Plowman G.,
RA Randazzo P.A., Schlessinger J.;
RT "Identification of a new Pyk2 target protein with Arf-GAP activity.";
RL Mol. Cell. Biol. 19:2338-2350(1999).
RN [12]
RP INTERACTION WITH PLEKHA8.
RX PubMed=15107860; DOI=10.1038/ncb1119;
RA Godi A., Di Campli A., Konstantakopoulos A., Di Tullio G.,
RA Alessi D.R., Kular G.S., Daniele T., Marra P., Lucocq J.M.,
RA De Matteis M.A.;
RT "FAPPs control Golgi-to-cell-surface membrane traffic by binding to
RT ARF and PtdIns(4)P.";
RL Nat. Cell Biol. 6:393-404(2004).
RN [13]
RP INTERACTION WITH ARHGAP21.
RX PubMed=17347647; DOI=10.1038/sj.emboj.7601634;
RA Menetrey J., Perderiset M., Cicolari J., Dubois T., Elkhatib N.,
RA El Khadali F., Franco M., Chavrier P., Houdusse A.;
RT "Structural basis for ARF1-mediated recruitment of ARHGAP21 to Golgi
RT membranes.";
RL EMBO J. 26:1953-1962(2007).
RN [14]
RP INTERACTION WITH PI4KB AND 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 [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT GLY-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP MYRISTOYLATION AT GLY-2.
RX PubMed=20213681; DOI=10.1002/pmic.200900783;
RA Suzuki T., Moriya K., Nagatoshi K., Ota Y., Ezure T., Ando E.,
RA Tsunasawa S., Utsumi T.;
RT "Strategy for comprehensive identification of human N-myristoylated
RT proteins using an insect cell-free protein synthesis system.";
RL Proteomics 10:1780-1793(2010).
RN [17]
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 [18]
RP INTERACTION WITH PLEKHA3.
RX PubMed=21454700; DOI=10.1074/jbc.M111.233015;
RA He J., Scott J.L., Heroux A., Roy S., Lenoir M., Overduin M.,
RA Stahelin R.V., Kutateladze T.G.;
RT "Molecular basis of phosphatidylinositol 4-phosphate and ARF1 GTPase
RT recognition by the FAPP1 pleckstrin homology (PH) domain.";
RL J. Biol. Chem. 286:18650-18657(2011).
RN [19]
RP MYRISTOYLATION AT GLY-2, AND DEMYRISTOYLATION.
RX PubMed=23535599; DOI=10.1038/nature12004;
RA Burnaevskiy N., Fox T.G., Plymire D.A., Ertelt J.M., Weigele B.A.,
RA Selyunin A.S., Way S.S., Patrie S.M., Alto N.M.;
RT "Proteolytic elimination of N-myristoyl modifications by the Shigella
RT virulence factor IpaJ.";
RL Nature 496:106-109(2013).
RN [20]
RP INTERACTION WITH PICK1 AND GRIA2.
RX PubMed=23889934; DOI=10.1016/j.neuron.2013.05.003;
RA Rocca D.L., Amici M., Antoniou A., Suarez E.B., Halemani N., Murk K.,
RA McGarvey J., Jaafari N., Mellor J.R., Collingridge G.L., Hanley J.G.;
RT "The small GTPase Arf1 modulates Arp2/3-mediated actin polymerization
RT via PICK1 to regulate synaptic plasticity.";
RL Neuron 79:293-307(2013).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=7990966; DOI=10.1038/372704a0;
RA Amor J.C., Harrison D.H., Kahn R.A., Ringe D.;
RT "Structure of the human ADP-ribosylation factor 1 complexed with
RT GDP.";
RL Nature 372:704-708(1994).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH RAT ARFGAP1
RP CATALYTIC DOMAIN.
RX PubMed=10102276; DOI=10.1016/S0092-8674(00)80598-X;
RA Goldberg J.;
RT "Structural and functional analysis of the ARF1-ARFGAP complex reveals
RT a role for coatomer in GTP hydrolysis.";
RL Cell 96:893-902(1999).
CC -!- FUNCTION: GTP-binding protein that functions as an allosteric
CC activator of the cholera toxin catalytic subunit, an ADP-
CC ribosyltransferase. Involved in protein trafficking among
CC different compartments. Modulates vesicle budding and uncoating
CC within the Golgi complex. Deactivation induces the redistribution
CC of the entire Golgi complex to the endoplasmic reticulum,
CC suggesting a crucial role in protein trafficking. In its GTP-bound
CC form, its triggers the association with coat proteins with the
CC Golgi membrane. The hydrolysis of ARF1-bound GTP, which is
CC mediated by ARFGAPs proteins, is required for dissociation of coat
CC proteins from Golgi membranes and vesicles. The GTP-bound form
CC interacts with PICK1 to limit PICK1-mediated inhibition of Arp2/3
CC complex activity; the function is linked to AMPA receptor (AMPAR)
CC trafficking, regulation of synaptic plasicity of excitatory
CC synapses and spine shrinkage during long-term depression (LTD).
CC -!- SUBUNIT: Interacts with ARHGAP21, ASAP2, GGA1, HERC1, PRKCABP,
CC PIP5K1B, TMED2, PSCD2, TMED10 and GRIA2. Interacts with ARFGAP1,
CC which hydrolyzes GTP and thus, regulates its function. Interacts
CC with PI4KB in the Golgi complex. Interacts with NCS1/FREQ in the
CC Golgi and at the plasma membrane. Interacts with PLEKHA3.
CC Interacts with PLEKHA8; the interaction, together with
CC phosphatidylinositol 4-phosphate binding, is required for FAPP2-
CC mediated glucosylceramide transfer activity. Interacts (activated)
CC with PICK1 (via PDZ domain); the interaction blocks Arp2/3 complex
CC inhibition.
CC -!- INTERACTION:
CC Q99418:CYTH2; NbExp=4; IntAct=EBI-447171, EBI-448974;
CC O60271:SPAG9; NbExp=3; IntAct=EBI-447171, EBI-1023301;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus. Cytoplasm, perinuclear
CC region. Cell junction, synapse, synaptosome (By similarity). Cell
CC junction, synapse, postsynaptic cell membrane, postsynaptic
CC density (By similarity).
CC -!- PTM: Demyristoylated by S.flexneri cysteine protease IpaJ which
CC cleaves the peptide bond between N-myristoylated Gly-2 and Asn-3.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Arf family.
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DR EMBL; M36340; AAA35552.1; -; mRNA.
DR EMBL; M84326; AAA35512.1; -; mRNA.
DR EMBL; AF052179; AAC28623.1; -; mRNA.
DR EMBL; AF055002; AAC09356.1; -; mRNA.
DR EMBL; AF493881; AAM12595.1; -; mRNA.
DR EMBL; BT007393; AAP36057.1; -; mRNA.
DR EMBL; AL136379; CAI23120.1; -; Genomic_DNA.
DR EMBL; BC009247; AAH09247.1; -; mRNA.
DR EMBL; BC010429; AAH10429.1; -; mRNA.
DR EMBL; BC011358; AAH11358.1; -; mRNA.
DR EMBL; M84332; AAA35511.1; -; Genomic_DNA.
DR PIR; B40187; A33283.
DR RefSeq; NP_001019397.1; NM_001024226.1.
DR RefSeq; NP_001019398.1; NM_001024227.1.
DR RefSeq; NP_001019399.1; NM_001024228.1.
DR RefSeq; NP_001649.1; NM_001658.3.
DR UniGene; Hs.286221; -.
DR PDB; 1HUR; X-ray; 2.00 A; A/B=2-181.
DR PDB; 1RE0; X-ray; 2.40 A; A=18-181.
DR PDB; 1U81; NMR; -; A=18-180.
DR PDB; 3O47; X-ray; 2.80 A; A/B=11-181.
DR PDB; 4HMY; X-ray; 7.00 A; C=17-181.
DR PDBsum; 1HUR; -.
DR PDBsum; 1RE0; -.
DR PDBsum; 1U81; -.
DR PDBsum; 3O47; -.
DR PDBsum; 4HMY; -.
DR ProteinModelPortal; P84077; -.
DR SMR; P84077; 2-180.
DR DIP; DIP-31597N; -.
DR IntAct; P84077; 28.
DR MINT; MINT-4999599; -.
DR STRING; 9606.ENSP00000272102; -.
DR ChEMBL; CHEMBL5985; -.
DR PhosphoSite; P84077; -.
DR DMDM; 51316985; -.
DR PaxDb; P84077; -.
DR PeptideAtlas; P84077; -.
DR PRIDE; P84077; -.
DR DNASU; 375; -.
DR Ensembl; ENST00000272102; ENSP00000272102; ENSG00000143761.
DR Ensembl; ENST00000540651; ENSP00000442980; ENSG00000143761.
DR Ensembl; ENST00000541182; ENSP00000440005; ENSG00000143761.
DR GeneID; 375; -.
DR KEGG; hsa:375; -.
DR UCSC; uc001hrr.3; human.
DR CTD; 375; -.
DR GeneCards; GC01P228270; -.
DR H-InvDB; HIX0116279; -.
DR HGNC; HGNC:652; ARF1.
DR HPA; CAB007742; -.
DR MIM; 103180; gene.
DR neXtProt; NX_P84077; -.
DR PharmGKB; PA24934; -.
DR eggNOG; COG1100; -.
DR HOGENOM; HOG000163691; -.
DR HOVERGEN; HBG002073; -.
DR InParanoid; P84077; -.
DR KO; K07937; -.
DR OMA; QTTCATS; -.
DR OrthoDB; EOG77WWDV; -.
DR PhylomeDB; P84077; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; ARF1; human.
DR EvolutionaryTrace; P84077; -.
DR GeneWiki; ARF1; -.
DR GenomeRNAi; 375; -.
DR NextBio; 1569; -.
DR PRO; PR:P84077; -.
DR Bgee; P84077; -.
DR CleanEx; HS_ARF1; -.
DR Genevestigator; P84077; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; TAS:ProtInc.
DR GO; GO:0030017; C:sarcomere; IEA:Ensembl.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; TAS:ProtInc.
DR GO; GO:0005057; F:receptor signaling protein activity; TAS:ProtInc.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome.
DR GO; GO:0006878; P:cellular copper ion homeostasis; IMP:UniProtKB.
DR GO; GO:0048205; P:COPI coating of Golgi vesicle; TAS:Reactome.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; TAS:Reactome.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0050690; P:regulation of defense response to virus by virus; TAS:Reactome.
DR GO; GO:0006890; P:retrograde vesicle-mediated transport, Golgi to ER; TAS:Reactome.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR GO; GO:0016032; P:viral process; TAS:Reactome.
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; Acetylation; Cell junction; Cell membrane;
KW Complete proteome; Cytoplasm; Direct protein sequencing;
KW ER-Golgi transport; Golgi apparatus; GTP-binding; Lipoprotein;
KW Membrane; Myristate; Nucleotide-binding; Postsynaptic cell membrane;
KW Protein transport; Reference proteome; Synapse; Synaptosome;
KW Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 181 ADP-ribosylation factor 1.
FT /FTId=PRO_0000207378.
FT NP_BIND 24 31 GTP (By similarity).
FT NP_BIND 126 129 GTP (By similarity).
FT MOD_RES 2 2 N-acetylglycine; alternate.
FT LIPID 2 2 N-myristoyl glycine; alternate.
FT HELIX 6 9
FT STRAND 10 12
FT STRAND 14 16
FT STRAND 19 25
FT HELIX 30 36
FT STRAND 42 45
FT STRAND 49 51
FT STRAND 53 58
FT STRAND 61 67
FT HELIX 72 78
FT HELIX 79 82
FT STRAND 85 93
FT STRAND 97 99
FT HELIX 100 111
FT HELIX 114 116
FT STRAND 120 126
FT STRAND 131 134
FT HELIX 136 143
FT HELIX 145 147
FT STRAND 153 157
FT TURN 160 163
FT HELIX 166 179
SQ SEQUENCE 181 AA; 20697 MW; AAC773D4A60186B6 CRC64;
MGNIFANLFK GLFGKKEMRI LMVGLDAAGK TTILYKLKLG EIVTTIPTIG FNVETVEYKN
ISFTVWDVGG QDKIRPLWRH YFQNTQGLIF VVDSNDRERV NEAREELMRM LAEDELRDAV
LLVFANKQDL PNAMNAAEIT DKLGLHSLRH RNWYIQATCA TSGDGLYEGL DWLSNQLRNQ
K
//
ID ARF1_HUMAN Reviewed; 181 AA.
AC P84077; P10947; P32889;
DT 16-AUG-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 1;
GN Name=ARF1;
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=2474826; DOI=10.1073/pnas.86.16.6101;
RA Bobak D.A., Nightingale M.S., Murtagh J.J. Jr., Price S.R., Moss J.,
RA Vaughan M.;
RT "Molecular cloning, characterization, and expression of human ADP-
RT ribosylation factors: two guanine nucleotide-dependent activators of
RT cholera toxin.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:6101-6105(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1899243;
RA Kahn R.A., Kern F.G., Clark J., Gelmann E.P., Rulka C.;
RT "Human ADP-ribosylation factors. A functionally conserved family of
RT GTP-binding proteins.";
RL J. Biol. Chem. 266:2606-2614(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1577740;
RA Lee C.M., Haun R.S., Tsai S.C., Moss J., Vaughan M.;
RT "Characterization of the human gene encoding ADP-ribosylation factor
RT 1, a guanine nucleotide-binding activator of cholera toxin.";
RL J. Biol. Chem. 267:9028-9034(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=9110174;
RA Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W.,
RA Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A.;
RT "Large-scale concatenation cDNA sequencing.";
RL Genome Res. 7:353-358(1997).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cervix, Eye, and Kidney;
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 PROTEIN SEQUENCE OF 20-30; 80-97 AND 118-142, AND MASS SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [10]
RP INTERACTION WITH HERC1.
RX PubMed=8861955;
RA Rosa J.L., Casaroli-Marano R.P., Buckler A.J., Vilaro S., Barbacid M.;
RT "p619, a giant protein related to the chromosome condensation
RT regulator RCC1, stimulates guanine nucleotide exchange on ARF1 and Rab
RT proteins.";
RL EMBO J. 15:4262-4273(1996).
RN [11]
RP INTERACTION WITH ASAP2.
RX PubMed=10022920;
RA Andreev J., Simon J.-P., Sabatini D.D., Kam J., Plowman G.,
RA Randazzo P.A., Schlessinger J.;
RT "Identification of a new Pyk2 target protein with Arf-GAP activity.";
RL Mol. Cell. Biol. 19:2338-2350(1999).
RN [12]
RP INTERACTION WITH PLEKHA8.
RX PubMed=15107860; DOI=10.1038/ncb1119;
RA Godi A., Di Campli A., Konstantakopoulos A., Di Tullio G.,
RA Alessi D.R., Kular G.S., Daniele T., Marra P., Lucocq J.M.,
RA De Matteis M.A.;
RT "FAPPs control Golgi-to-cell-surface membrane traffic by binding to
RT ARF and PtdIns(4)P.";
RL Nat. Cell Biol. 6:393-404(2004).
RN [13]
RP INTERACTION WITH ARHGAP21.
RX PubMed=17347647; DOI=10.1038/sj.emboj.7601634;
RA Menetrey J., Perderiset M., Cicolari J., Dubois T., Elkhatib N.,
RA El Khadali F., Franco M., Chavrier P., Houdusse A.;
RT "Structural basis for ARF1-mediated recruitment of ARHGAP21 to Golgi
RT membranes.";
RL EMBO J. 26:1953-1962(2007).
RN [14]
RP INTERACTION WITH PI4KB AND 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 [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT GLY-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP MYRISTOYLATION AT GLY-2.
RX PubMed=20213681; DOI=10.1002/pmic.200900783;
RA Suzuki T., Moriya K., Nagatoshi K., Ota Y., Ezure T., Ando E.,
RA Tsunasawa S., Utsumi T.;
RT "Strategy for comprehensive identification of human N-myristoylated
RT proteins using an insect cell-free protein synthesis system.";
RL Proteomics 10:1780-1793(2010).
RN [17]
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 [18]
RP INTERACTION WITH PLEKHA3.
RX PubMed=21454700; DOI=10.1074/jbc.M111.233015;
RA He J., Scott J.L., Heroux A., Roy S., Lenoir M., Overduin M.,
RA Stahelin R.V., Kutateladze T.G.;
RT "Molecular basis of phosphatidylinositol 4-phosphate and ARF1 GTPase
RT recognition by the FAPP1 pleckstrin homology (PH) domain.";
RL J. Biol. Chem. 286:18650-18657(2011).
RN [19]
RP MYRISTOYLATION AT GLY-2, AND DEMYRISTOYLATION.
RX PubMed=23535599; DOI=10.1038/nature12004;
RA Burnaevskiy N., Fox T.G., Plymire D.A., Ertelt J.M., Weigele B.A.,
RA Selyunin A.S., Way S.S., Patrie S.M., Alto N.M.;
RT "Proteolytic elimination of N-myristoyl modifications by the Shigella
RT virulence factor IpaJ.";
RL Nature 496:106-109(2013).
RN [20]
RP INTERACTION WITH PICK1 AND GRIA2.
RX PubMed=23889934; DOI=10.1016/j.neuron.2013.05.003;
RA Rocca D.L., Amici M., Antoniou A., Suarez E.B., Halemani N., Murk K.,
RA McGarvey J., Jaafari N., Mellor J.R., Collingridge G.L., Hanley J.G.;
RT "The small GTPase Arf1 modulates Arp2/3-mediated actin polymerization
RT via PICK1 to regulate synaptic plasticity.";
RL Neuron 79:293-307(2013).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=7990966; DOI=10.1038/372704a0;
RA Amor J.C., Harrison D.H., Kahn R.A., Ringe D.;
RT "Structure of the human ADP-ribosylation factor 1 complexed with
RT GDP.";
RL Nature 372:704-708(1994).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH RAT ARFGAP1
RP CATALYTIC DOMAIN.
RX PubMed=10102276; DOI=10.1016/S0092-8674(00)80598-X;
RA Goldberg J.;
RT "Structural and functional analysis of the ARF1-ARFGAP complex reveals
RT a role for coatomer in GTP hydrolysis.";
RL Cell 96:893-902(1999).
CC -!- FUNCTION: GTP-binding protein that functions as an allosteric
CC activator of the cholera toxin catalytic subunit, an ADP-
CC ribosyltransferase. Involved in protein trafficking among
CC different compartments. Modulates vesicle budding and uncoating
CC within the Golgi complex. Deactivation induces the redistribution
CC of the entire Golgi complex to the endoplasmic reticulum,
CC suggesting a crucial role in protein trafficking. In its GTP-bound
CC form, its triggers the association with coat proteins with the
CC Golgi membrane. The hydrolysis of ARF1-bound GTP, which is
CC mediated by ARFGAPs proteins, is required for dissociation of coat
CC proteins from Golgi membranes and vesicles. The GTP-bound form
CC interacts with PICK1 to limit PICK1-mediated inhibition of Arp2/3
CC complex activity; the function is linked to AMPA receptor (AMPAR)
CC trafficking, regulation of synaptic plasicity of excitatory
CC synapses and spine shrinkage during long-term depression (LTD).
CC -!- SUBUNIT: Interacts with ARHGAP21, ASAP2, GGA1, HERC1, PRKCABP,
CC PIP5K1B, TMED2, PSCD2, TMED10 and GRIA2. Interacts with ARFGAP1,
CC which hydrolyzes GTP and thus, regulates its function. Interacts
CC with PI4KB in the Golgi complex. Interacts with NCS1/FREQ in the
CC Golgi and at the plasma membrane. Interacts with PLEKHA3.
CC Interacts with PLEKHA8; the interaction, together with
CC phosphatidylinositol 4-phosphate binding, is required for FAPP2-
CC mediated glucosylceramide transfer activity. Interacts (activated)
CC with PICK1 (via PDZ domain); the interaction blocks Arp2/3 complex
CC inhibition.
CC -!- INTERACTION:
CC Q99418:CYTH2; NbExp=4; IntAct=EBI-447171, EBI-448974;
CC O60271:SPAG9; NbExp=3; IntAct=EBI-447171, EBI-1023301;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus. Cytoplasm, perinuclear
CC region. Cell junction, synapse, synaptosome (By similarity). Cell
CC junction, synapse, postsynaptic cell membrane, postsynaptic
CC density (By similarity).
CC -!- PTM: Demyristoylated by S.flexneri cysteine protease IpaJ which
CC cleaves the peptide bond between N-myristoylated Gly-2 and Asn-3.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Arf family.
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DR EMBL; M36340; AAA35552.1; -; mRNA.
DR EMBL; M84326; AAA35512.1; -; mRNA.
DR EMBL; AF052179; AAC28623.1; -; mRNA.
DR EMBL; AF055002; AAC09356.1; -; mRNA.
DR EMBL; AF493881; AAM12595.1; -; mRNA.
DR EMBL; BT007393; AAP36057.1; -; mRNA.
DR EMBL; AL136379; CAI23120.1; -; Genomic_DNA.
DR EMBL; BC009247; AAH09247.1; -; mRNA.
DR EMBL; BC010429; AAH10429.1; -; mRNA.
DR EMBL; BC011358; AAH11358.1; -; mRNA.
DR EMBL; M84332; AAA35511.1; -; Genomic_DNA.
DR PIR; B40187; A33283.
DR RefSeq; NP_001019397.1; NM_001024226.1.
DR RefSeq; NP_001019398.1; NM_001024227.1.
DR RefSeq; NP_001019399.1; NM_001024228.1.
DR RefSeq; NP_001649.1; NM_001658.3.
DR UniGene; Hs.286221; -.
DR PDB; 1HUR; X-ray; 2.00 A; A/B=2-181.
DR PDB; 1RE0; X-ray; 2.40 A; A=18-181.
DR PDB; 1U81; NMR; -; A=18-180.
DR PDB; 3O47; X-ray; 2.80 A; A/B=11-181.
DR PDB; 4HMY; X-ray; 7.00 A; C=17-181.
DR PDBsum; 1HUR; -.
DR PDBsum; 1RE0; -.
DR PDBsum; 1U81; -.
DR PDBsum; 3O47; -.
DR PDBsum; 4HMY; -.
DR ProteinModelPortal; P84077; -.
DR SMR; P84077; 2-180.
DR DIP; DIP-31597N; -.
DR IntAct; P84077; 28.
DR MINT; MINT-4999599; -.
DR STRING; 9606.ENSP00000272102; -.
DR ChEMBL; CHEMBL5985; -.
DR PhosphoSite; P84077; -.
DR DMDM; 51316985; -.
DR PaxDb; P84077; -.
DR PeptideAtlas; P84077; -.
DR PRIDE; P84077; -.
DR DNASU; 375; -.
DR Ensembl; ENST00000272102; ENSP00000272102; ENSG00000143761.
DR Ensembl; ENST00000540651; ENSP00000442980; ENSG00000143761.
DR Ensembl; ENST00000541182; ENSP00000440005; ENSG00000143761.
DR GeneID; 375; -.
DR KEGG; hsa:375; -.
DR UCSC; uc001hrr.3; human.
DR CTD; 375; -.
DR GeneCards; GC01P228270; -.
DR H-InvDB; HIX0116279; -.
DR HGNC; HGNC:652; ARF1.
DR HPA; CAB007742; -.
DR MIM; 103180; gene.
DR neXtProt; NX_P84077; -.
DR PharmGKB; PA24934; -.
DR eggNOG; COG1100; -.
DR HOGENOM; HOG000163691; -.
DR HOVERGEN; HBG002073; -.
DR InParanoid; P84077; -.
DR KO; K07937; -.
DR OMA; QTTCATS; -.
DR OrthoDB; EOG77WWDV; -.
DR PhylomeDB; P84077; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; ARF1; human.
DR EvolutionaryTrace; P84077; -.
DR GeneWiki; ARF1; -.
DR GenomeRNAi; 375; -.
DR NextBio; 1569; -.
DR PRO; PR:P84077; -.
DR Bgee; P84077; -.
DR CleanEx; HS_ARF1; -.
DR Genevestigator; P84077; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; TAS:ProtInc.
DR GO; GO:0030017; C:sarcomere; IEA:Ensembl.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; TAS:ProtInc.
DR GO; GO:0005057; F:receptor signaling protein activity; TAS:ProtInc.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome.
DR GO; GO:0006878; P:cellular copper ion homeostasis; IMP:UniProtKB.
DR GO; GO:0048205; P:COPI coating of Golgi vesicle; TAS:Reactome.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; TAS:Reactome.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0050690; P:regulation of defense response to virus by virus; TAS:Reactome.
DR GO; GO:0006890; P:retrograde vesicle-mediated transport, Golgi to ER; TAS:Reactome.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR GO; GO:0016032; P:viral process; TAS:Reactome.
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; Acetylation; Cell junction; Cell membrane;
KW Complete proteome; Cytoplasm; Direct protein sequencing;
KW ER-Golgi transport; Golgi apparatus; GTP-binding; Lipoprotein;
KW Membrane; Myristate; Nucleotide-binding; Postsynaptic cell membrane;
KW Protein transport; Reference proteome; Synapse; Synaptosome;
KW Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 181 ADP-ribosylation factor 1.
FT /FTId=PRO_0000207378.
FT NP_BIND 24 31 GTP (By similarity).
FT NP_BIND 126 129 GTP (By similarity).
FT MOD_RES 2 2 N-acetylglycine; alternate.
FT LIPID 2 2 N-myristoyl glycine; alternate.
FT HELIX 6 9
FT STRAND 10 12
FT STRAND 14 16
FT STRAND 19 25
FT HELIX 30 36
FT STRAND 42 45
FT STRAND 49 51
FT STRAND 53 58
FT STRAND 61 67
FT HELIX 72 78
FT HELIX 79 82
FT STRAND 85 93
FT STRAND 97 99
FT HELIX 100 111
FT HELIX 114 116
FT STRAND 120 126
FT STRAND 131 134
FT HELIX 136 143
FT HELIX 145 147
FT STRAND 153 157
FT TURN 160 163
FT HELIX 166 179
SQ SEQUENCE 181 AA; 20697 MW; AAC773D4A60186B6 CRC64;
MGNIFANLFK GLFGKKEMRI LMVGLDAAGK TTILYKLKLG EIVTTIPTIG FNVETVEYKN
ISFTVWDVGG QDKIRPLWRH YFQNTQGLIF VVDSNDRERV NEAREELMRM LAEDELRDAV
LLVFANKQDL PNAMNAAEIT DKLGLHSLRH RNWYIQATCA TSGDGLYEGL DWLSNQLRNQ
K
//
MIM
103180
*RECORD*
*FIELD* NO
103180
*FIELD* TI
*103180 ADP-RIBOSYLATION FACTOR 1; ARF1
*FIELD* TX
DESCRIPTION
ADP-ribosylation factors (ARFs), such as ARF1, are small guanine
read morenucleotide-binding proteins that enhance the enzymatic activities of
cholera toxin. ARFs are essential and ubiquitous in eukaryotes, being
involved in vesicular transport and functioning as activators of
phospholipase D. The functions of ARF proteins in membrane traffic and
organelle integrity are intimately tied to their reversible association
with membranes and specific interactions with membrane phospholipids. A
common feature of these functions is their regulation by the binding and
hydrolysis of GTP (summary by Bobak et al. (1989) and Amor et al.
(1994)).
CLONING
Bobak et al. (1989) cloned 2 ARF cDNAs, ARF1 and ARF3 (103190), from a
human cerebellum library. Based on deduced amino acid sequences and
patterns of hybridization of cDNA and oligonucleotide probes with
mammalian brain poly(A)+ RNA, human ARF1 is the homolog of bovine ARF1.
Human ARF3, however, appeared to represent a newly identified, third
type of ARF, which differs from bovine ARF1 and bovine ARF2. Peng et al.
(1989) also reported cloning of ADP-ribosylation factor.
Lee et al. (1992) found that human ARF1 is identical to its bovine
counterpart, has a distinctive pattern of tissue and developmental
expression, and is encoded by an mRNA of approximately 1.9 kb.
GENE FUNCTION
Coatomer, or COPI (see 601924), is a heptameric protein recruited to
membranes by ARF1. Coat assembly helps in the transport of budding off
membrane between the endoplasmic reticulum (ER) and Golgi apparatus.
Using fluorescence microscopy, Presley et al. (2002) showed that guanine
nucleotide exchange-activated ARF1 at the Golgi membrane recruits and
binds cytoplasmic COPI to the membranes. Photobleaching experiments
demonstrated that COPI remains at the membranes after ARF1-GTP has been
hydrolyzed by ARFGAP1 (608377). COPI binds to membrane cargo,
soluble-cargo receptors, or other Golgi proteins. Uncoating, or the
release of COPI from Golgi membranes to the cytoplasm, then occurs,
which can be inhibited by aluminum fluoride. Presley et al. (2002)
concluded from their kinetic and biochemical analyses that COPI and ARF1
continuously bind and release from Golgi membranes, allowing the
membrane at these sites to recruit cargo, alter their phospholipid
composition, and become larger, phase-separated domains.
Endocytosis of glycosylphosphatidyl inositol (GPI)-anchored proteins and
the fluid phase takes place primarily through a dynamin (see DNM1;
602377)- and clathrin (see CLTC; 118955)-independent, CDC42
(116952)-regulated pinocytic mechanism. In Chinese hamster ovary cells,
Kumari and Mayor (2008) found that reduced activity or levels of Arf1
inhibited GPI-anchored protein and fluid-phase endocytosis without
affecting other clathrin-dependent or -independent endocytic pathways.
Arf1 was activated at distinct sites on the plasma membrane, and it
recruited the CDC42 GTPase-activating protein Arhgap10 (609746) to the
plasma membrane, thereby modulating cell surface Cdc42 dynamics. Kumari
and Mayor (2008) concluded that ARF1 regulates both endocytosis and
secretion and may provide a mechanism for crosstalk between these
processes.
Using a yeast genetic screen for substrates of the Shigella flexneri
type III effector protein IpaJ, Burnaevskiy et al. (2013) identified
Arf1 and Arf2 (ARF4; 601177). Mass spectrometric analysis showed that
IpaJ cleaved the peptide bond between myristoylated gly2 and asn3 of
human ARF1. Further analysis showed that IpaJ cleaved numerous
N-myristoylated proteins with various functions. Burnaevskiy et al.
(2013) concluded that IpaJ is a cysteine protease that cleaves the
N-myrisoylated glycine from ARF1, possibly as the substrate cycles
between activity-dependent conformational states. They proposed that
cleavage of lipidated proteins may be a mechanism of microbial
pathogenesis.
BIOCHEMICAL FEATURES
Amor et al. (1994) described the 3-dimensional structure of full-length
human ARF1 in its GDP-bound nonmyristoylated form.
Mossessova et al. (1998) reported the crystal structure of the catalytic
Sec7 homology domain of ARNO (602488), a human guanine nucleotide
exchange factor (GEF) for ARF1, determined at 2.2-angstrom resolution.
The Sec7 domain is an elongated, all-helical protein with a distinctive
hydrophobic groove that is phylogenetically conserved. Structure-based
mutagenesis identifies the groove and an adjacent conserved loop as the
ARF-interacting surface. The sites of Sec7 domain interaction on ARF1
have subsequently been mapped, by protein footprinting experiments, to
the switch 1 and switch 2 GTPase regions, leading to a model for the
interaction between ARF GTPases and Sec7 domain exchange factors.
Nucleotide dissociation from small G protein-GEF complexes involves
transient GDP-bound intermediates. In the case of ARF proteins, small G
proteins that regulate membrane traffic in eukaryotic cells, such
intermediates can be trapped either by the natural inhibitor brefeldin A
or by charge reversal at the catalytic glutamate of the Sec7 domain of
their GEFs. Renault et al. (2003) reported the crystal structure of
these intermediates, which shows that membrane recruitment of ARF and
nucleotide dissociation are separate reactions stimulated by the Sec7
domain. The reactions proceed through sequential rotations of the
Arf-GDP core towards the Sec7 catalytic site, and are blocked by
interfacial binding of brefeldin A and unproductive stabilization of GDP
by charge reversal.
GENE STRUCTURE
Lee et al. (1992) determined that the ARF1 gene has 4 introns and spans
approximately 16.5 kb. Exon 1 (46 bp) contains only untranslated
sequence. The 5-prime flanking region has a high GC content but no TATA
or CAAT box, as found in housekeeping genes. The authors stated that the
2 human class I ARF genes, ARF1 and ARF3, have similar exon/intron
organizations and use GC-rich promoters.
MAPPING
Hirai et al. (1996) obtained an expressed sequence tag related to the
ARF1 gene and used fluorescence in situ hybridization to assign ARF1 to
1q42.
*FIELD* RF
1. Amor, J. C.; Harrison, D. H.; Kahn, R. A.; Ringe, D.: Structure
of the human ADP-ribosylation factor 1 complexed with GDP. Nature 372:
704-708, 1994.
2. Bobak, D. A.; Nightingale, M. S.; Murtagh, J. J.; Price, S. R.;
Moss, J.; Vaughan, M.: Molecular cloning, characterization, and expression
of human ADP-ribosylation factors: two guanine nucleotide-dependent
activators of cholera toxin. Proc. Nat. Acad. Sci. 86: 6101-6105,
1989.
3. Burnaevskiy, N.; Fox, T. G.; Plymire, D. A.; Ertelt, J. M.; Weigele,
B. A., Selyunin, A. S.; Way, S. S.; Patrie, S. M.; Alto, N. M.: Proteolytic
elimination of N-myristoyl modifications by the Shigella virulence
factor IpaJ. Nature 496: 106-109, 2013.
4. Hirai, M.; Kusuda, J.; Hashimoto, K.: Assignment of human ADP
ribosylation factor (ARF) genes ARF1 and ARF3 to chromosomes 1q42
and 12q13, respectively. Genomics 34: 263-265, 1996.
5. Kumari, S.; Mayor, S.: ARF1 is directly involved in dynamin-independent
endocytosis. Nature Cell Biol. 10: 30-41, 2008.
6. Lee, C.-M.; Haun, R. S.; Tsai, S.-C.; Moss, J.; Vaughan, M.: Characterization
of the human gene encoding ADP-ribosylation factor 1, a guanine nucleotide-binding
activator of cholera toxin. J. Biol. Chem. 267: 9028-9034, 1992.
7. Mossessova, E.; Gulbis, J. M.; Goldberg, J.: Structure of the
guanine nucleotide exchange factor Sec7 domain of human Arno and analysis
of the interaction with ARF GTPase. Cell 92: 415-423, 1998.
8. Peng, Z. G.; Calvert, I.; Clark, J.; Helman, L.; Kahn, R.; Kung,
H. F.: Molecular cloning, sequence analysis and mRNA expression of
human ADP-ribosylation factor. Biofactors 2: 45-49, 1989.
9. Presley, J. F.; Ward, T. H.; Pfeifer, A. C.; Siggia, E. D.; Phair,
R. D.; Lippincott-Schwartz, J.: Dissection of COPI and Arf1 dynamics
in vivo and role in Golgi membrane transport. Nature 417: 187-193,
2002.
10. Renault, L.; Guibert, B.; Cherfils, J.: Structural snapshots
of the mechanism and inhibition of a guanine nucleotide exchange factor. Nature 426:
525-530, 2003.
*FIELD* CN
Paul J. Converse - updated: 5/8/2013
Patricia A. Hartz - updated: 1/6/2009
Ada Hamosh - updated: 12/30/2003
Paul J. Converse - updated: 5/10/2002
Stylianos E. Antonarakis - updated: 4/1/1998
Lori M. Kelman - updated: 8/22/1996
*FIELD* CD
Victor A. McKusick: 9/26/1989
*FIELD* ED
carol: 08/01/2013
mgross: 5/8/2013
mgross: 1/8/2009
terry: 1/6/2009
mgross: 8/1/2005
alopez: 12/31/2003
terry: 12/30/2003
mgross: 5/10/2002
terry: 11/13/1998
carol: 7/23/1998
dkim: 6/26/1998
carol: 4/1/1998
alopez: 7/9/1997
joanna: 4/10/1997
mark: 8/22/1996
terry: 8/22/1996
mark: 8/21/1996
mark: 1/5/1996
terry: 1/3/1996
terry: 1/6/1995
carol: 9/23/1994
supermim: 3/16/1992
carol: 7/5/1990
supermim: 3/20/1990
ddp: 10/26/1989
*RECORD*
*FIELD* NO
103180
*FIELD* TI
*103180 ADP-RIBOSYLATION FACTOR 1; ARF1
*FIELD* TX
DESCRIPTION
ADP-ribosylation factors (ARFs), such as ARF1, are small guanine
read morenucleotide-binding proteins that enhance the enzymatic activities of
cholera toxin. ARFs are essential and ubiquitous in eukaryotes, being
involved in vesicular transport and functioning as activators of
phospholipase D. The functions of ARF proteins in membrane traffic and
organelle integrity are intimately tied to their reversible association
with membranes and specific interactions with membrane phospholipids. A
common feature of these functions is their regulation by the binding and
hydrolysis of GTP (summary by Bobak et al. (1989) and Amor et al.
(1994)).
CLONING
Bobak et al. (1989) cloned 2 ARF cDNAs, ARF1 and ARF3 (103190), from a
human cerebellum library. Based on deduced amino acid sequences and
patterns of hybridization of cDNA and oligonucleotide probes with
mammalian brain poly(A)+ RNA, human ARF1 is the homolog of bovine ARF1.
Human ARF3, however, appeared to represent a newly identified, third
type of ARF, which differs from bovine ARF1 and bovine ARF2. Peng et al.
(1989) also reported cloning of ADP-ribosylation factor.
Lee et al. (1992) found that human ARF1 is identical to its bovine
counterpart, has a distinctive pattern of tissue and developmental
expression, and is encoded by an mRNA of approximately 1.9 kb.
GENE FUNCTION
Coatomer, or COPI (see 601924), is a heptameric protein recruited to
membranes by ARF1. Coat assembly helps in the transport of budding off
membrane between the endoplasmic reticulum (ER) and Golgi apparatus.
Using fluorescence microscopy, Presley et al. (2002) showed that guanine
nucleotide exchange-activated ARF1 at the Golgi membrane recruits and
binds cytoplasmic COPI to the membranes. Photobleaching experiments
demonstrated that COPI remains at the membranes after ARF1-GTP has been
hydrolyzed by ARFGAP1 (608377). COPI binds to membrane cargo,
soluble-cargo receptors, or other Golgi proteins. Uncoating, or the
release of COPI from Golgi membranes to the cytoplasm, then occurs,
which can be inhibited by aluminum fluoride. Presley et al. (2002)
concluded from their kinetic and biochemical analyses that COPI and ARF1
continuously bind and release from Golgi membranes, allowing the
membrane at these sites to recruit cargo, alter their phospholipid
composition, and become larger, phase-separated domains.
Endocytosis of glycosylphosphatidyl inositol (GPI)-anchored proteins and
the fluid phase takes place primarily through a dynamin (see DNM1;
602377)- and clathrin (see CLTC; 118955)-independent, CDC42
(116952)-regulated pinocytic mechanism. In Chinese hamster ovary cells,
Kumari and Mayor (2008) found that reduced activity or levels of Arf1
inhibited GPI-anchored protein and fluid-phase endocytosis without
affecting other clathrin-dependent or -independent endocytic pathways.
Arf1 was activated at distinct sites on the plasma membrane, and it
recruited the CDC42 GTPase-activating protein Arhgap10 (609746) to the
plasma membrane, thereby modulating cell surface Cdc42 dynamics. Kumari
and Mayor (2008) concluded that ARF1 regulates both endocytosis and
secretion and may provide a mechanism for crosstalk between these
processes.
Using a yeast genetic screen for substrates of the Shigella flexneri
type III effector protein IpaJ, Burnaevskiy et al. (2013) identified
Arf1 and Arf2 (ARF4; 601177). Mass spectrometric analysis showed that
IpaJ cleaved the peptide bond between myristoylated gly2 and asn3 of
human ARF1. Further analysis showed that IpaJ cleaved numerous
N-myristoylated proteins with various functions. Burnaevskiy et al.
(2013) concluded that IpaJ is a cysteine protease that cleaves the
N-myrisoylated glycine from ARF1, possibly as the substrate cycles
between activity-dependent conformational states. They proposed that
cleavage of lipidated proteins may be a mechanism of microbial
pathogenesis.
BIOCHEMICAL FEATURES
Amor et al. (1994) described the 3-dimensional structure of full-length
human ARF1 in its GDP-bound nonmyristoylated form.
Mossessova et al. (1998) reported the crystal structure of the catalytic
Sec7 homology domain of ARNO (602488), a human guanine nucleotide
exchange factor (GEF) for ARF1, determined at 2.2-angstrom resolution.
The Sec7 domain is an elongated, all-helical protein with a distinctive
hydrophobic groove that is phylogenetically conserved. Structure-based
mutagenesis identifies the groove and an adjacent conserved loop as the
ARF-interacting surface. The sites of Sec7 domain interaction on ARF1
have subsequently been mapped, by protein footprinting experiments, to
the switch 1 and switch 2 GTPase regions, leading to a model for the
interaction between ARF GTPases and Sec7 domain exchange factors.
Nucleotide dissociation from small G protein-GEF complexes involves
transient GDP-bound intermediates. In the case of ARF proteins, small G
proteins that regulate membrane traffic in eukaryotic cells, such
intermediates can be trapped either by the natural inhibitor brefeldin A
or by charge reversal at the catalytic glutamate of the Sec7 domain of
their GEFs. Renault et al. (2003) reported the crystal structure of
these intermediates, which shows that membrane recruitment of ARF and
nucleotide dissociation are separate reactions stimulated by the Sec7
domain. The reactions proceed through sequential rotations of the
Arf-GDP core towards the Sec7 catalytic site, and are blocked by
interfacial binding of brefeldin A and unproductive stabilization of GDP
by charge reversal.
GENE STRUCTURE
Lee et al. (1992) determined that the ARF1 gene has 4 introns and spans
approximately 16.5 kb. Exon 1 (46 bp) contains only untranslated
sequence. The 5-prime flanking region has a high GC content but no TATA
or CAAT box, as found in housekeeping genes. The authors stated that the
2 human class I ARF genes, ARF1 and ARF3, have similar exon/intron
organizations and use GC-rich promoters.
MAPPING
Hirai et al. (1996) obtained an expressed sequence tag related to the
ARF1 gene and used fluorescence in situ hybridization to assign ARF1 to
1q42.
*FIELD* RF
1. Amor, J. C.; Harrison, D. H.; Kahn, R. A.; Ringe, D.: Structure
of the human ADP-ribosylation factor 1 complexed with GDP. Nature 372:
704-708, 1994.
2. Bobak, D. A.; Nightingale, M. S.; Murtagh, J. J.; Price, S. R.;
Moss, J.; Vaughan, M.: Molecular cloning, characterization, and expression
of human ADP-ribosylation factors: two guanine nucleotide-dependent
activators of cholera toxin. Proc. Nat. Acad. Sci. 86: 6101-6105,
1989.
3. Burnaevskiy, N.; Fox, T. G.; Plymire, D. A.; Ertelt, J. M.; Weigele,
B. A., Selyunin, A. S.; Way, S. S.; Patrie, S. M.; Alto, N. M.: Proteolytic
elimination of N-myristoyl modifications by the Shigella virulence
factor IpaJ. Nature 496: 106-109, 2013.
4. Hirai, M.; Kusuda, J.; Hashimoto, K.: Assignment of human ADP
ribosylation factor (ARF) genes ARF1 and ARF3 to chromosomes 1q42
and 12q13, respectively. Genomics 34: 263-265, 1996.
5. Kumari, S.; Mayor, S.: ARF1 is directly involved in dynamin-independent
endocytosis. Nature Cell Biol. 10: 30-41, 2008.
6. Lee, C.-M.; Haun, R. S.; Tsai, S.-C.; Moss, J.; Vaughan, M.: Characterization
of the human gene encoding ADP-ribosylation factor 1, a guanine nucleotide-binding
activator of cholera toxin. J. Biol. Chem. 267: 9028-9034, 1992.
7. Mossessova, E.; Gulbis, J. M.; Goldberg, J.: Structure of the
guanine nucleotide exchange factor Sec7 domain of human Arno and analysis
of the interaction with ARF GTPase. Cell 92: 415-423, 1998.
8. Peng, Z. G.; Calvert, I.; Clark, J.; Helman, L.; Kahn, R.; Kung,
H. F.: Molecular cloning, sequence analysis and mRNA expression of
human ADP-ribosylation factor. Biofactors 2: 45-49, 1989.
9. Presley, J. F.; Ward, T. H.; Pfeifer, A. C.; Siggia, E. D.; Phair,
R. D.; Lippincott-Schwartz, J.: Dissection of COPI and Arf1 dynamics
in vivo and role in Golgi membrane transport. Nature 417: 187-193,
2002.
10. Renault, L.; Guibert, B.; Cherfils, J.: Structural snapshots
of the mechanism and inhibition of a guanine nucleotide exchange factor. Nature 426:
525-530, 2003.
*FIELD* CN
Paul J. Converse - updated: 5/8/2013
Patricia A. Hartz - updated: 1/6/2009
Ada Hamosh - updated: 12/30/2003
Paul J. Converse - updated: 5/10/2002
Stylianos E. Antonarakis - updated: 4/1/1998
Lori M. Kelman - updated: 8/22/1996
*FIELD* CD
Victor A. McKusick: 9/26/1989
*FIELD* ED
carol: 08/01/2013
mgross: 5/8/2013
mgross: 1/8/2009
terry: 1/6/2009
mgross: 8/1/2005
alopez: 12/31/2003
terry: 12/30/2003
mgross: 5/10/2002
terry: 11/13/1998
carol: 7/23/1998
dkim: 6/26/1998
carol: 4/1/1998
alopez: 7/9/1997
joanna: 4/10/1997
mark: 8/22/1996
terry: 8/22/1996
mark: 8/21/1996
mark: 1/5/1996
terry: 1/3/1996
terry: 1/6/1995
carol: 9/23/1994
supermim: 3/16/1992
carol: 7/5/1990
supermim: 3/20/1990
ddp: 10/26/1989