Full text data of AGO1
AGO1
(EIF2C1)
[Confidence: low (only semi-automatic identification from reviews)]
Protein argonaute-1; Argonaute1; hAgo1 (Argonaute RISC catalytic component 1; Eukaryotic translation initiation factor 2C 1; eIF-2C 1; eIF2C 1; Putative RNA-binding protein Q99)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Protein argonaute-1; Argonaute1; hAgo1 (Argonaute RISC catalytic component 1; Eukaryotic translation initiation factor 2C 1; eIF-2C 1; eIF2C 1; Putative RNA-binding protein Q99)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9UL18
ID AGO1_HUMAN Reviewed; 857 AA.
AC Q9UL18; Q5TA57; Q6P4S0;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 21-FEB-2006, sequence version 3.
DT 22-JAN-2014, entry version 114.
DE RecName: Full=Protein argonaute-1;
DE Short=Argonaute1;
DE Short=hAgo1;
DE AltName: Full=Argonaute RISC catalytic component 1;
DE AltName: Full=Eukaryotic translation initiation factor 2C 1;
DE Short=eIF-2C 1;
DE Short=eIF2C 1;
DE AltName: Full=Putative RNA-binding protein Q99;
GN Name=AGO1; Synonyms=EIF2C1;
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=10534406; DOI=10.1006/geno.1999.5951;
RA Koesters R., Adams V., Betts D., Moos R., Schmid M., Siermann A.,
RA Hassam S., Weitz S., Lichter P., Heitz P.U., von Knebel Doeberitz M.,
RA Briner J.;
RT "Human eukaryotic initiation factor EIF2C1 gene: cDNA sequence,
RT genomic organization, localization to chromosomal bands 1p34-p35, and
RT expression.";
RL Genomics 61:210-218(1999).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [4]
RP ASSOCIATION WITH MIRNA.
RX PubMed=15260970; DOI=10.1016/j.molcel.2004.07.007;
RA Meister G., Landthaler M., Patkaniowska A., Dorsett Y., Teng G.,
RA Tuschl T.;
RT "Human Argonaute2 mediates RNA cleavage targeted by miRNAs and
RT siRNAs.";
RL Mol. Cell 15:185-197(2004).
RN [5]
RP FUNCTION, INTERACTION WITH DICER1; MOV10; PRMT5 AND TNRC6B, AND
RP SUBCELLULAR LOCATION.
RX PubMed=16289642; DOI=10.1016/j.cub.2005.10.048;
RA Meister G., Landthaler M., Peters L., Chen P.Y., Urlaub H.,
RA Luehrmann R., Tuschl T.;
RT "Identification of novel argonaute-associated proteins.";
RL Curr. Biol. 15:2149-2155(2005).
RN [6]
RP FUNCTION.
RX PubMed=16936728; DOI=10.1038/nsmb1140;
RA Janowski B.A., Huffman K.E., Schwartz J.C., Ram R., Nordsell R.,
RA Shames D.S., Minna J.D., Corey D.R.;
RT "Involvement of AGO1 and AGO2 in mammalian transcriptional
RT silencing.";
RL Nat. Struct. Mol. Biol. 13:787-792(2006).
RN [7]
RP INTERACTION WITH DDX6 AND AGO2.
RX PubMed=16756390; DOI=10.1371/journal.pbio.0040210;
RA Chu C.-Y., Rana T.M.;
RT "Translation repression in human cells by microRNA-induced gene
RT silencing requires RCK/p54.";
RL PLoS Biol. 4:E210-E210(2006).
RN [8]
RP ASSOCIATION WITH POLYSOMES AND MNRP, AND INTERACTION WITH DDB1; DDX5;
RP DHX30; DHX36; DDX47; ELAVL1; HNRNPF; IGF2BP1; ILF3; MATR3; PABPC1;
RP RBM4; SART3; UPF1 AND YBX1.
RX PubMed=17932509; DOI=10.1038/sj.embor.7401088;
RA Hoeck J., Weinmann L., Ender C., Ruedel S., Kremmer E., Raabe M.,
RA Urlaub H., Meister G.;
RT "Proteomic and functional analysis of Argonaute-containing mRNA-
RT protein complexes in human cells.";
RL EMBO Rep. 8:1052-1060(2007).
RN [9]
RP FUNCTION.
RX PubMed=18771919; DOI=10.1016/j.cub.2008.07.072;
RA Wu L., Fan J., Belasco J.G.;
RT "Importance of translation and nonnucleolytic ago proteins for on-
RT target RNA interference.";
RL Curr. Biol. 18:1327-1332(2008).
RN [10]
RP INTERACTION WITH IMP8.
RX PubMed=19167051; DOI=10.1016/j.cell.2008.12.023;
RA Weinmann L., Hoeck J., Ivacevic T., Ohrt T., Muetze J., Schwille P.,
RA Kremmer E., Benes V., Urlaub H., Meister G.;
RT "Importin 8 is a gene silencing factor that targets argonaute proteins
RT to distinct mRNAs.";
RL Cell 136:496-507(2009).
RN [11]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH LIMD1; WTIP AND AJUBA.
RX PubMed=20616046; DOI=10.1073/pnas.0914987107;
RA James V., Zhang Y., Foxler D.E., de Moor C.H., Kong Y.W., Webb T.M.,
RA Self T.J., Feng Y., Lagos D., Chu C.Y., Rana T.M., Morley S.J.,
RA Longmore G.D., Bushell M., Sharp T.V.;
RT "LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for
RT microRNA-mediated gene silencing.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:12499-12504(2010).
RN [12]
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 [13]
RP INTERACTION WITH APOBEC3F; APOBEC3G AND APOBEC3H.
RX PubMed=22915799; DOI=10.1128/JVI.00595-12;
RA Phalora P.K., Sherer N.M., Wolinsky S.M., Swanson C.M., Malim M.H.;
RT "HIV-1 replication and APOBEC3 antiviral activity are not regulated by
RT P bodies.";
RL J. Virol. 86:11712-11724(2012).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 225-369, AND RNA-BINDING.
RX PubMed=15152257; DOI=10.1038/nature02519;
RA Ma J.-B., Ye K., Patel D.J.;
RT "Structural basis for overhang-specific small interfering RNA
RT recognition by the PAZ domain.";
RL Nature 429:318-322(2004).
CC -!- FUNCTION: Required for RNA-mediated gene silencing (RNAi). Binds
CC to short RNAs such as microRNAs (miRNAs) or short interfering RNAs
CC (siRNAs), and represses the translation of mRNAs which are
CC complementary to them. Lacks endonuclease activity and does not
CC appear to cleave target mRNAs. Also required for transcriptional
CC gene silencing (TGS) of promoter regions which are complementary
CC to bound short antigene RNAs (agRNAs).
CC -!- SUBUNIT: Interacts with DDB1, DDX5, DDX6, DHX30, DHX36, DDX47,
CC DICER1, AGO2, ELAVL1, HNRNPF, IGF2BP1, ILF3, IMP8, MATR3, MOV10,
CC PABPC1, PRMT5, RBM4, SART3, TNRC6B, UPF1 and YBX1. Associates with
CC polysomes and messenger ribonucleoproteins (mNRPs). Interacts with
CC LIMD1, WTIP and AJUBA. Interacts with APOBEC3F, APOBEC3G and
CC APOBEC3H.
CC -!- INTERACTION:
CC Q9UPY3:DICER1; NbExp=5; IntAct=EBI-527363, EBI-395506;
CC O15397:IPO8; NbExp=2; IntAct=EBI-527363, EBI-358808;
CC Q8NDV7:TNRC6A; NbExp=4; IntAct=EBI-527363, EBI-2269715;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body.
CC -!- SIMILARITY: Belongs to the argonaute family. Ago subfamily.
CC -!- SIMILARITY: Contains 1 PAZ domain.
CC -!- SIMILARITY: Contains 1 Piwi domain.
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DR EMBL; AF093097; AAF00068.1; -; mRNA.
DR EMBL; AL139286; CAI22804.1; -; Genomic_DNA.
DR EMBL; BC063275; AAH63275.1; -; mRNA.
DR RefSeq; NP_036331.1; NM_012199.2.
DR UniGene; Hs.22867; -.
DR PDB; 1SI2; X-ray; 2.60 A; A=225-369.
DR PDB; 1SI3; X-ray; 2.60 A; A=225-369.
DR PDB; 4KRE; X-ray; 1.75 A; A=1-857.
DR PDB; 4KRF; X-ray; 2.10 A; A=1-857.
DR PDB; 4KXT; X-ray; 2.29 A; A=1-857.
DR PDBsum; 1SI2; -.
DR PDBsum; 1SI3; -.
DR PDBsum; 4KRE; -.
DR PDBsum; 4KRF; -.
DR PDBsum; 4KXT; -.
DR ProteinModelPortal; Q9UL18; -.
DR SMR; Q9UL18; 17-857.
DR DIP; DIP-29193N; -.
DR IntAct; Q9UL18; 179.
DR STRING; 9606.ENSP00000362300; -.
DR PhosphoSite; Q9UL18; -.
DR DMDM; 88984241; -.
DR PaxDb; Q9UL18; -.
DR PRIDE; Q9UL18; -.
DR Ensembl; ENST00000373204; ENSP00000362300; ENSG00000092847.
DR GeneID; 26523; -.
DR KEGG; hsa:26523; -.
DR UCSC; uc001bzk.3; human.
DR CTD; 26523; -.
DR GeneCards; GC01P036336; -.
DR HGNC; HGNC:3262; AGO1.
DR MIM; 606228; gene.
DR neXtProt; NX_Q9UL18; -.
DR PharmGKB; PA27693; -.
DR eggNOG; NOG279895; -.
DR HOGENOM; HOG000116043; -.
DR InParanoid; Q9UL18; -.
DR KO; K11593; -.
DR OMA; ENDILRT; -.
DR PhylomeDB; Q9UL18; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_120956; Cellular responses to stress.
DR Reactome; REACT_6900; Immune System.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; EIF2C1; human.
DR EvolutionaryTrace; Q9UL18; -.
DR GeneWiki; EIF2C1; -.
DR GenomeRNAi; 26523; -.
DR NextBio; 48846; -.
DR PRO; PR:Q9UL18; -.
DR ArrayExpress; Q9UL18; -.
DR Bgee; Q9UL18; -.
DR CleanEx; HS_EIF2C1; -.
DR Genevestigator; Q9UL18; -.
DR GO; GO:0000932; C:cytoplasmic mRNA processing body; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0035068; C:micro-ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0005844; C:polysome; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0010467; P:gene expression; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0035278; P:negative regulation of translation involved in gene silencing by miRNA; IDA:UniProtKB.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0007219; P:Notch signaling pathway; TAS:Reactome.
DR GO; GO:0000956; P:nuclear-transcribed mRNA catabolic process; IDA:UniProtKB.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR InterPro; IPR014811; DUF1785.
DR InterPro; IPR003100; PAZ_dom.
DR InterPro; IPR003165; Piwi.
DR InterPro; IPR012337; RNaseH-like_dom.
DR Pfam; PF08699; DUF1785; 1.
DR Pfam; PF02170; PAZ; 1.
DR Pfam; PF02171; Piwi; 1.
DR SMART; SM00949; PAZ; 1.
DR SMART; SM00950; Piwi; 1.
DR SUPFAM; SSF101690; SSF101690; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
DR PROSITE; PS50821; PAZ; 1.
DR PROSITE; PS50822; PIWI; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Cytoplasm; Reference proteome;
KW Repressor; Ribonucleoprotein; RNA-binding;
KW RNA-mediated gene silencing; Transcription; Transcription regulation;
KW Translation regulation.
FT CHAIN 1 857 Protein argonaute-1.
FT /FTId=PRO_0000194055.
FT DOMAIN 226 346 PAZ.
FT DOMAIN 515 816 Piwi.
FT CONFLICT 242 242 D -> N (in Ref. 3; AAH63275).
FT STRAND 33 46
FT STRAND 51 62
FT HELIX 66 79
FT HELIX 81 85
FT STRAND 94 102
FT TURN 105 108
FT STRAND 110 115
FT STRAND 125 137
FT HELIX 138 147
FT HELIX 154 171
FT STRAND 172 175
FT STRAND 178 180
FT STRAND 189 191
FT STRAND 194 206
FT STRAND 208 223
FT HELIX 228 236
FT TURN 241 243
FT HELIX 250 260
FT STRAND 264 268
FT TURN 269 272
FT STRAND 276 286
FT TURN 287 289
FT STRAND 291 295
FT STRAND 301 305
FT HELIX 306 314
FT STRAND 323 328
FT HELIX 331 333
FT STRAND 335 338
FT HELIX 339 341
FT STRAND 342 344
FT HELIX 356 366
FT HELIX 370 384
FT HELIX 386 388
FT HELIX 390 394
FT STRAND 404 410
FT TURN 420 423
FT STRAND 448 453
FT TURN 457 459
FT HELIX 462 478
FT STRAND 488 492
FT HELIX 496 498
FT HELIX 499 509
FT STRAND 515 520
FT HELIX 526 535
FT TURN 536 538
FT STRAND 542 546
FT HELIX 547 551
FT HELIX 555 568
FT HELIX 578 580
FT HELIX 583 586
FT STRAND 589 597
FT STRAND 608 615
FT STRAND 617 620
FT STRAND 623 631
FT HELIX 640 655
FT STRAND 660 666
FT HELIX 671 673
FT HELIX 674 692
FT STRAND 699 706
FT STRAND 713 717
FT HELIX 718 720
FT TURN 723 726
FT STRAND 732 734
FT STRAND 736 739
FT STRAND 741 743
FT STRAND 745 749
FT STRAND 755 757
FT STRAND 761 768
FT HELIX 774 784
FT HELIX 799 814
FT HELIX 837 843
FT HELIX 848 851
SQ SEQUENCE 857 AA; 97214 MW; 1DBB524AE7CBAF66 CRC64;
MEAGPSGAAA GAYLPPLQQV FQAPRRPGIG TVGKPIKLLA NYFEVDIPKI DVYHYEVDIK
PDKCPRRVNR EVVEYMVQHF KPQIFGDRKP VYDGKKNIYT VTALPIGNER VDFEVTIPGE
GKDRIFKVSI KWLAIVSWRM LHEALVSGQI PVPLESVQAL DVAMRHLASM RYTPVGRSFF
SPPEGYYHPL GGGREVWFGF HQSVRPAMWK MMLNIDVSAT AFYKAQPVIE FMCEVLDIRN
IDEQPKPLTD SQRVRFTKEI KGLKVEVTHC GQMKRKYRVC NVTRRPASHQ TFPLQLESGQ
TVECTVAQYF KQKYNLQLKY PHLPCLQVGQ EQKHTYLPLE VCNIVAGQRC IKKLTDNQTS
TMIKATARSA PDRQEEISRL MKNASYNLDP YIQEFGIKVK DDMTEVTGRV LPAPILQYGG
RNRAIATPNQ GVWDMRGKQF YNGIEIKVWA IACFAPQKQC REEVLKNFTD QLRKISKDAG
MPIQGQPCFC KYAQGADSVE PMFRHLKNTY SGLQLIIVIL PGKTPVYAEV KRVGDTLLGM
ATQCVQVKNV VKTSPQTLSN LCLKINVKLG GINNILVPHQ RSAVFQQPVI FLGADVTHPP
AGDGKKPSIT AVVGSMDAHP SRYCATVRVQ RPRQEIIEDL SYMVRELLIQ FYKSTRFKPT
RIIFYRDGVP EGQLPQILHY ELLAIRDACI KLEKDYQPGI TYIVVQKRHH TRLFCADKNE
RIGKSGNIPA GTTVDTNITH PFEFDFYLCS HAGIQGTSRP SHYYVLWDDN RFTADELQIL
TYQLCHTYVR CTRSVSIPAP AYYARLVAFR ARYHLVDKEH DSGEGSHISG QSNGRDPQAL
AKAVQVHQDT LRTMYFA
//
ID AGO1_HUMAN Reviewed; 857 AA.
AC Q9UL18; Q5TA57; Q6P4S0;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 21-FEB-2006, sequence version 3.
DT 22-JAN-2014, entry version 114.
DE RecName: Full=Protein argonaute-1;
DE Short=Argonaute1;
DE Short=hAgo1;
DE AltName: Full=Argonaute RISC catalytic component 1;
DE AltName: Full=Eukaryotic translation initiation factor 2C 1;
DE Short=eIF-2C 1;
DE Short=eIF2C 1;
DE AltName: Full=Putative RNA-binding protein Q99;
GN Name=AGO1; Synonyms=EIF2C1;
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=10534406; DOI=10.1006/geno.1999.5951;
RA Koesters R., Adams V., Betts D., Moos R., Schmid M., Siermann A.,
RA Hassam S., Weitz S., Lichter P., Heitz P.U., von Knebel Doeberitz M.,
RA Briner J.;
RT "Human eukaryotic initiation factor EIF2C1 gene: cDNA sequence,
RT genomic organization, localization to chromosomal bands 1p34-p35, and
RT expression.";
RL Genomics 61:210-218(1999).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [4]
RP ASSOCIATION WITH MIRNA.
RX PubMed=15260970; DOI=10.1016/j.molcel.2004.07.007;
RA Meister G., Landthaler M., Patkaniowska A., Dorsett Y., Teng G.,
RA Tuschl T.;
RT "Human Argonaute2 mediates RNA cleavage targeted by miRNAs and
RT siRNAs.";
RL Mol. Cell 15:185-197(2004).
RN [5]
RP FUNCTION, INTERACTION WITH DICER1; MOV10; PRMT5 AND TNRC6B, AND
RP SUBCELLULAR LOCATION.
RX PubMed=16289642; DOI=10.1016/j.cub.2005.10.048;
RA Meister G., Landthaler M., Peters L., Chen P.Y., Urlaub H.,
RA Luehrmann R., Tuschl T.;
RT "Identification of novel argonaute-associated proteins.";
RL Curr. Biol. 15:2149-2155(2005).
RN [6]
RP FUNCTION.
RX PubMed=16936728; DOI=10.1038/nsmb1140;
RA Janowski B.A., Huffman K.E., Schwartz J.C., Ram R., Nordsell R.,
RA Shames D.S., Minna J.D., Corey D.R.;
RT "Involvement of AGO1 and AGO2 in mammalian transcriptional
RT silencing.";
RL Nat. Struct. Mol. Biol. 13:787-792(2006).
RN [7]
RP INTERACTION WITH DDX6 AND AGO2.
RX PubMed=16756390; DOI=10.1371/journal.pbio.0040210;
RA Chu C.-Y., Rana T.M.;
RT "Translation repression in human cells by microRNA-induced gene
RT silencing requires RCK/p54.";
RL PLoS Biol. 4:E210-E210(2006).
RN [8]
RP ASSOCIATION WITH POLYSOMES AND MNRP, AND INTERACTION WITH DDB1; DDX5;
RP DHX30; DHX36; DDX47; ELAVL1; HNRNPF; IGF2BP1; ILF3; MATR3; PABPC1;
RP RBM4; SART3; UPF1 AND YBX1.
RX PubMed=17932509; DOI=10.1038/sj.embor.7401088;
RA Hoeck J., Weinmann L., Ender C., Ruedel S., Kremmer E., Raabe M.,
RA Urlaub H., Meister G.;
RT "Proteomic and functional analysis of Argonaute-containing mRNA-
RT protein complexes in human cells.";
RL EMBO Rep. 8:1052-1060(2007).
RN [9]
RP FUNCTION.
RX PubMed=18771919; DOI=10.1016/j.cub.2008.07.072;
RA Wu L., Fan J., Belasco J.G.;
RT "Importance of translation and nonnucleolytic ago proteins for on-
RT target RNA interference.";
RL Curr. Biol. 18:1327-1332(2008).
RN [10]
RP INTERACTION WITH IMP8.
RX PubMed=19167051; DOI=10.1016/j.cell.2008.12.023;
RA Weinmann L., Hoeck J., Ivacevic T., Ohrt T., Muetze J., Schwille P.,
RA Kremmer E., Benes V., Urlaub H., Meister G.;
RT "Importin 8 is a gene silencing factor that targets argonaute proteins
RT to distinct mRNAs.";
RL Cell 136:496-507(2009).
RN [11]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH LIMD1; WTIP AND AJUBA.
RX PubMed=20616046; DOI=10.1073/pnas.0914987107;
RA James V., Zhang Y., Foxler D.E., de Moor C.H., Kong Y.W., Webb T.M.,
RA Self T.J., Feng Y., Lagos D., Chu C.Y., Rana T.M., Morley S.J.,
RA Longmore G.D., Bushell M., Sharp T.V.;
RT "LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for
RT microRNA-mediated gene silencing.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:12499-12504(2010).
RN [12]
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 [13]
RP INTERACTION WITH APOBEC3F; APOBEC3G AND APOBEC3H.
RX PubMed=22915799; DOI=10.1128/JVI.00595-12;
RA Phalora P.K., Sherer N.M., Wolinsky S.M., Swanson C.M., Malim M.H.;
RT "HIV-1 replication and APOBEC3 antiviral activity are not regulated by
RT P bodies.";
RL J. Virol. 86:11712-11724(2012).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 225-369, AND RNA-BINDING.
RX PubMed=15152257; DOI=10.1038/nature02519;
RA Ma J.-B., Ye K., Patel D.J.;
RT "Structural basis for overhang-specific small interfering RNA
RT recognition by the PAZ domain.";
RL Nature 429:318-322(2004).
CC -!- FUNCTION: Required for RNA-mediated gene silencing (RNAi). Binds
CC to short RNAs such as microRNAs (miRNAs) or short interfering RNAs
CC (siRNAs), and represses the translation of mRNAs which are
CC complementary to them. Lacks endonuclease activity and does not
CC appear to cleave target mRNAs. Also required for transcriptional
CC gene silencing (TGS) of promoter regions which are complementary
CC to bound short antigene RNAs (agRNAs).
CC -!- SUBUNIT: Interacts with DDB1, DDX5, DDX6, DHX30, DHX36, DDX47,
CC DICER1, AGO2, ELAVL1, HNRNPF, IGF2BP1, ILF3, IMP8, MATR3, MOV10,
CC PABPC1, PRMT5, RBM4, SART3, TNRC6B, UPF1 and YBX1. Associates with
CC polysomes and messenger ribonucleoproteins (mNRPs). Interacts with
CC LIMD1, WTIP and AJUBA. Interacts with APOBEC3F, APOBEC3G and
CC APOBEC3H.
CC -!- INTERACTION:
CC Q9UPY3:DICER1; NbExp=5; IntAct=EBI-527363, EBI-395506;
CC O15397:IPO8; NbExp=2; IntAct=EBI-527363, EBI-358808;
CC Q8NDV7:TNRC6A; NbExp=4; IntAct=EBI-527363, EBI-2269715;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body.
CC -!- SIMILARITY: Belongs to the argonaute family. Ago subfamily.
CC -!- SIMILARITY: Contains 1 PAZ domain.
CC -!- SIMILARITY: Contains 1 Piwi domain.
CC -----------------------------------------------------------------------
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DR EMBL; AF093097; AAF00068.1; -; mRNA.
DR EMBL; AL139286; CAI22804.1; -; Genomic_DNA.
DR EMBL; BC063275; AAH63275.1; -; mRNA.
DR RefSeq; NP_036331.1; NM_012199.2.
DR UniGene; Hs.22867; -.
DR PDB; 1SI2; X-ray; 2.60 A; A=225-369.
DR PDB; 1SI3; X-ray; 2.60 A; A=225-369.
DR PDB; 4KRE; X-ray; 1.75 A; A=1-857.
DR PDB; 4KRF; X-ray; 2.10 A; A=1-857.
DR PDB; 4KXT; X-ray; 2.29 A; A=1-857.
DR PDBsum; 1SI2; -.
DR PDBsum; 1SI3; -.
DR PDBsum; 4KRE; -.
DR PDBsum; 4KRF; -.
DR PDBsum; 4KXT; -.
DR ProteinModelPortal; Q9UL18; -.
DR SMR; Q9UL18; 17-857.
DR DIP; DIP-29193N; -.
DR IntAct; Q9UL18; 179.
DR STRING; 9606.ENSP00000362300; -.
DR PhosphoSite; Q9UL18; -.
DR DMDM; 88984241; -.
DR PaxDb; Q9UL18; -.
DR PRIDE; Q9UL18; -.
DR Ensembl; ENST00000373204; ENSP00000362300; ENSG00000092847.
DR GeneID; 26523; -.
DR KEGG; hsa:26523; -.
DR UCSC; uc001bzk.3; human.
DR CTD; 26523; -.
DR GeneCards; GC01P036336; -.
DR HGNC; HGNC:3262; AGO1.
DR MIM; 606228; gene.
DR neXtProt; NX_Q9UL18; -.
DR PharmGKB; PA27693; -.
DR eggNOG; NOG279895; -.
DR HOGENOM; HOG000116043; -.
DR InParanoid; Q9UL18; -.
DR KO; K11593; -.
DR OMA; ENDILRT; -.
DR PhylomeDB; Q9UL18; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_120956; Cellular responses to stress.
DR Reactome; REACT_6900; Immune System.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; EIF2C1; human.
DR EvolutionaryTrace; Q9UL18; -.
DR GeneWiki; EIF2C1; -.
DR GenomeRNAi; 26523; -.
DR NextBio; 48846; -.
DR PRO; PR:Q9UL18; -.
DR ArrayExpress; Q9UL18; -.
DR Bgee; Q9UL18; -.
DR CleanEx; HS_EIF2C1; -.
DR Genevestigator; Q9UL18; -.
DR GO; GO:0000932; C:cytoplasmic mRNA processing body; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0035068; C:micro-ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0005844; C:polysome; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0010467; P:gene expression; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0035278; P:negative regulation of translation involved in gene silencing by miRNA; IDA:UniProtKB.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0007219; P:Notch signaling pathway; TAS:Reactome.
DR GO; GO:0000956; P:nuclear-transcribed mRNA catabolic process; IDA:UniProtKB.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR InterPro; IPR014811; DUF1785.
DR InterPro; IPR003100; PAZ_dom.
DR InterPro; IPR003165; Piwi.
DR InterPro; IPR012337; RNaseH-like_dom.
DR Pfam; PF08699; DUF1785; 1.
DR Pfam; PF02170; PAZ; 1.
DR Pfam; PF02171; Piwi; 1.
DR SMART; SM00949; PAZ; 1.
DR SMART; SM00950; Piwi; 1.
DR SUPFAM; SSF101690; SSF101690; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
DR PROSITE; PS50821; PAZ; 1.
DR PROSITE; PS50822; PIWI; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Cytoplasm; Reference proteome;
KW Repressor; Ribonucleoprotein; RNA-binding;
KW RNA-mediated gene silencing; Transcription; Transcription regulation;
KW Translation regulation.
FT CHAIN 1 857 Protein argonaute-1.
FT /FTId=PRO_0000194055.
FT DOMAIN 226 346 PAZ.
FT DOMAIN 515 816 Piwi.
FT CONFLICT 242 242 D -> N (in Ref. 3; AAH63275).
FT STRAND 33 46
FT STRAND 51 62
FT HELIX 66 79
FT HELIX 81 85
FT STRAND 94 102
FT TURN 105 108
FT STRAND 110 115
FT STRAND 125 137
FT HELIX 138 147
FT HELIX 154 171
FT STRAND 172 175
FT STRAND 178 180
FT STRAND 189 191
FT STRAND 194 206
FT STRAND 208 223
FT HELIX 228 236
FT TURN 241 243
FT HELIX 250 260
FT STRAND 264 268
FT TURN 269 272
FT STRAND 276 286
FT TURN 287 289
FT STRAND 291 295
FT STRAND 301 305
FT HELIX 306 314
FT STRAND 323 328
FT HELIX 331 333
FT STRAND 335 338
FT HELIX 339 341
FT STRAND 342 344
FT HELIX 356 366
FT HELIX 370 384
FT HELIX 386 388
FT HELIX 390 394
FT STRAND 404 410
FT TURN 420 423
FT STRAND 448 453
FT TURN 457 459
FT HELIX 462 478
FT STRAND 488 492
FT HELIX 496 498
FT HELIX 499 509
FT STRAND 515 520
FT HELIX 526 535
FT TURN 536 538
FT STRAND 542 546
FT HELIX 547 551
FT HELIX 555 568
FT HELIX 578 580
FT HELIX 583 586
FT STRAND 589 597
FT STRAND 608 615
FT STRAND 617 620
FT STRAND 623 631
FT HELIX 640 655
FT STRAND 660 666
FT HELIX 671 673
FT HELIX 674 692
FT STRAND 699 706
FT STRAND 713 717
FT HELIX 718 720
FT TURN 723 726
FT STRAND 732 734
FT STRAND 736 739
FT STRAND 741 743
FT STRAND 745 749
FT STRAND 755 757
FT STRAND 761 768
FT HELIX 774 784
FT HELIX 799 814
FT HELIX 837 843
FT HELIX 848 851
SQ SEQUENCE 857 AA; 97214 MW; 1DBB524AE7CBAF66 CRC64;
MEAGPSGAAA GAYLPPLQQV FQAPRRPGIG TVGKPIKLLA NYFEVDIPKI DVYHYEVDIK
PDKCPRRVNR EVVEYMVQHF KPQIFGDRKP VYDGKKNIYT VTALPIGNER VDFEVTIPGE
GKDRIFKVSI KWLAIVSWRM LHEALVSGQI PVPLESVQAL DVAMRHLASM RYTPVGRSFF
SPPEGYYHPL GGGREVWFGF HQSVRPAMWK MMLNIDVSAT AFYKAQPVIE FMCEVLDIRN
IDEQPKPLTD SQRVRFTKEI KGLKVEVTHC GQMKRKYRVC NVTRRPASHQ TFPLQLESGQ
TVECTVAQYF KQKYNLQLKY PHLPCLQVGQ EQKHTYLPLE VCNIVAGQRC IKKLTDNQTS
TMIKATARSA PDRQEEISRL MKNASYNLDP YIQEFGIKVK DDMTEVTGRV LPAPILQYGG
RNRAIATPNQ GVWDMRGKQF YNGIEIKVWA IACFAPQKQC REEVLKNFTD QLRKISKDAG
MPIQGQPCFC KYAQGADSVE PMFRHLKNTY SGLQLIIVIL PGKTPVYAEV KRVGDTLLGM
ATQCVQVKNV VKTSPQTLSN LCLKINVKLG GINNILVPHQ RSAVFQQPVI FLGADVTHPP
AGDGKKPSIT AVVGSMDAHP SRYCATVRVQ RPRQEIIEDL SYMVRELLIQ FYKSTRFKPT
RIIFYRDGVP EGQLPQILHY ELLAIRDACI KLEKDYQPGI TYIVVQKRHH TRLFCADKNE
RIGKSGNIPA GTTVDTNITH PFEFDFYLCS HAGIQGTSRP SHYYVLWDDN RFTADELQIL
TYQLCHTYVR CTRSVSIPAP AYYARLVAFR ARYHLVDKEH DSGEGSHISG QSNGRDPQAL
AKAVQVHQDT LRTMYFA
//
MIM
606228
*RECORD*
*FIELD* NO
606228
*FIELD* TI
*606228 EUKARYOTIC TRANSLATION INITIATION FACTOR 2C, SUBUNIT 1; EIF2C1
;;GERP95;;
EIF2C;;
read moreARGONAUTE 1; AGO1
*FIELD* TX
DESCRIPTION
The human eukaryotic initiation factor 2C1 (EIF2C1) gene belongs to a
multigene family in human. It is highly conserved during evolution,
sharing about 90% identity with rabbit Eif2c and 70% identity with plant
EGO1 at the amino acid level. EIF2C stimulates formation of a ternary
complex composed of EIF2, initiation methionyl-tRNA(I) (Met-tRNA), and
GTP.
CLONING
Koesters et al. (1999) isolated a EIF2C1 cDNA from a human fetal kidney
cDNA library. To obtain genomic sequence information, they isolated a P1
genomic clone containing the EIF2C1 locus. The human EIF2C1 gene encodes
a protein of 857 amino acids. The 2,571-bp open reading frame is flanked
by 238 bp of 5-prime sequence and an extremely large 3-prime
untranslated region with multiple short repeated segments composed of
mono-, tri-, or quatronucleotides interspersed throughout. Northern blot
analysis demonstrated that the human EIF2C1 gene is ubiquitously
expressed at low to medium levels. Differential polyadenylation and
splicing resulted in a complex transcriptional pattern.
BIOCHEMICAL FEATURES
Martinez et al. (2002) demonstrated that a single-stranded small
interfering RNA (siRNA) resides in the human RNA-induced silencing
complex (RISC) together with the EIF2C1 and/or EIF2C2 (606229) proteins.
RISC could be rapidly formed in HeLa cell cytoplasmic extract
supplemented with 21-nucleotide siRNA duplexes, but also by adding
single-stranded antisense RNAs, which range in size between 19 and 29
nucleotides.
- Crystal Structure
Yan et al. (2003) reported the nuclear magnetic resonance solution
structure of the PAZ domain from Drosophila Argonaute-1. The structure
consists of a left-handed, 6-stranded beta-barrel capped at 1 end by 2
alpha-helices and wrapped on 1 side by a distinctive appendage, which
comprises a long beta-hairpin and a short alpha-helix. Using structural
and biochemical analyses, Yan et al. (2003) demonstrated that the PAZ
domain binds a 5-nucleotide RNA with a 1:1 stoichiometry. Yan et al.
(2003) mapped the RNA-binding surface to the open face of the
beta-barrel, which contains amino acids conserved in the PAZ domain
family, and defined a 5-prime-to-3-prime orientation of single-stranded
RNA bound within that site. Yan et al. (2003) also showed that PAZ
domains from different human Argonaute proteins (AGO1; PIWIL1, 605571;
and AGO2, 606229) also bind RNA, establishing a conserved function for
this domain.
Ma et al. (2004) reported the 2.6-angstrom crystal structure of the PAZ
domain from human Argonaute eIF2c1 bound to both ends of a 9-mer
siRNA-like duplex. In a sequence-independent manner, PAZ anchors the
2-nucleotide 3-prime overhang of the siRNA-like duplex within a highly
conserved binding pocket, and secures the duplex by binding the
7-nucleotide phosphodiester backbone of the overhang-containing strand
and capping the 5-prime-terminal residue of the complementary strand. On
the basis of the structure and on binding assays, Ma et al. (2004)
proposed that PAZ might serve as an siRNA end-binding module for siRNA
transfer in the RNA silencing pathway, and as an anchoring site for the
3-prime end of guide RNA within silencing effector complexes.
Song et al. (2004) reported the crystal structure of the Argonaute
protein from Pyrococcus furiosus at 2.25-angstrom resolution. The
structure revealed a crescent-shaped base made up of the amino-terminal,
middle, and PIWI domains. The Piwi Argonaute Zwille (PAZ) domain is held
above the base by a stalk-like region. The PIWI domain is similar to
ribonuclease H (see 604123), with a conserved active site
aspartate-aspartate-glutamate motif, strongly implicating Argonaute as
'slicer,' the enzyme that cleaves mRNA as directed by siRNA. The
architecture of the molecule and the placement of the PAZ and PIWI
domains define a groove for substrate binding and suggested a mechanism
for siRNA-guided mRNA cleavage.
GENE FUNCTION
In S. pombe, Volpe et al. (2002) deleted the argonaute, dicer (606241),
and RNA-dependent RNA polymerase gene homologs, which encode part of the
machinery responsible for RNA interference. Deletion resulted in the
aberrant accumulation of complementary transcripts from centromeric
heterochromatic repeats. This was accompanied by transcription of
derepression of transgenes integrated at the centromere, loss of histone
H3 (see 602810) lysine-9 methylation, and impairment of centromere
function. Volpe et al. (2002) proposed that double-stranded RNA arising
from centromeric repeats targets formation and maintenance of
heterochromatin through RNA interference.
AU-rich elements (AREs) in the 3-prime UTRs of unstable mRNAs dictate
their degradation. Using an RNA interference-based screen in Drosophila
S2 cells, Jing et al. (2005) found that Dicer-1, Ago1, and Ago2,
components involved in microRNA (miRNA) processing and function, were
required for rapid decay of mRNA containing AREs of tumor necrosis
factor-alpha (TNF; 191160). The requirement for Dicer in the instability
of ARE-containing mRNA (ARE-RNA) was confirmed in HeLa cells. Jing et
al. (2005) showed that miRNA16 (miR16), a human miRNA containing an
UAAAUAUU sequence that is complementary to the ARE sequence, was
required for ARE-RNA turnover. The role of miR16 in ARE-RNA decay was
sequence-specific and required the ARE-binding protein tristetraprolin
(TTP, or ZFP36; 190700). TTP did not directly bind miR16, but interacted
through association with Ago/EIF2C family members to complex with miR16
and assist in the targeting of ARE. Jing et al. (2005) concluded that
miRNA targeting of ARE appears to be an essential step in ARE-mediated
mRNA degradation.
Chi et al. (2009) used HITS-CLIP (high-throughout sequencing of RNAs
isolated by crosslinking immunoprecipitation) to covalently crosslink
native Ago protein-RNA complexes in postnatal day-13 (P13) mouse brain.
They obtained 2 simultaneous data sets, Ago-miRNA and Ago-mRNA binding
sites, that were combined with bioinformatic analysis to identify
interaction sites between miRNA and target mRNA. Chi et al. (2009)
validated genomewide interaction maps for miR124 (MIR124-1; 609327) and
generated additional maps for the 20 most abundant miRNAs present in P13
mouse brain. They concluded that Ago HITS-CLIP provides a general
platform for exploring the specificity and range of miRNA action in
vivo, and that it identifies precise sequences for targeting clinically
relevant miRNA-mRNA interactions.
Zisoulis et al. (2012) showed that the miRNA-induced silencing complex
(miRISC) also targets and regulates noncoding RNAs that serve as
substrates for the miRNA-processing pathway. They found that the
Argonaute protein in C. elegans, ALG1, binds to a specific site at the
3-prime end of let-7 (605386) miRNA primary transcripts and promotes
downstream processing events. This interaction is mediated by mature
let-7 miRNA through a conserved complementary site in its own primary
transcript, thus creating a positive-feedback loop. Zisoulis et al.
(2012) further showed that ALG1 associates with let-7 primary
transcripts in nuclear fractions. Argonaute also binds let-7 primary
transcripts in human cells, demonstrating that the miRNA pathway targets
noncoding RNAs in addition to protein-coding mRNAs across species.
Moreover, their studies in C. elegans revealed a novel role for
Argonaute in promoting biogenesis of a targeted transcript, expanding
the functions of the miRNA pathway in gene regulation. The discovery of
autoregulation of let-7 biogenesis established a new mechanism for
controlling miRNA expression.
GENE STRUCTURE
Koesters et al. (1999) determined that the EIF2C1 gene consists of 19
exons within approximately 50 kb.
MAPPING
Koesters et al. (1999) mapped the EIF2C1 gene to chromosome 1p35-p34 by
fluorescence in situ hybridization. This region is frequently lost in
human malignancies, including Wilms tumors.
*FIELD* RF
1. Chi, S. W.; Zang, J. B.; Mele, A.; Darnell, R. B.: Argonaute HITS-CLIP
decodes microRNA-mRNA interaction maps. Nature 460: 479-486, 2009.
2. Jing, Q.; Huang, S.; Guth, S.; Zarubin, T.; Motoyama, A.; Chen,
J.; Di Padova, F.; Lin, S.-C.; Gram, H.; Han, J.: Involvement of
microRNA in AU-rich element-mediated mRNA instability. Cell 120:
623-634, 2005.
3. Koesters, R.; Adams, V.; Betts, D.; Moos, R.; Schmid, M.; Siermann,
A.; Hassam, S.; Weitz, S.; Lichter, P.; Heitz, P. U.; von Knebel Doeberitz,
M.; Briner, J.: Human eukaryotic initiation factor EIF2C1 gene: cDNA
sequence, genomic organization, localization to chromosomal bands
1q34-p35, and expression. Genomics 61: 210-218, 1999.
4. Ma, J.-B.; Ye, K.; Patel, D. J.: Structural basis for overhang-specific
small interfering RNA recognition by the PAZ domain. Nature 429:
318-322, 2004.
5. Martinez, J.; Patkaniowska, A.; Urlaub, H.; Luhrmann, R.; Tuschi,
T.: Single-stranded antisense siRNAs guide target RNA cleavage in
RNAi. Cell 110: 563-574, 2002.
6. Song, J.-J.; Smith, S. K.; Hannon, G. J.; Joshua-Tor, L.: Crystal
structure of Argonaute and its implications for RISC slicer activity. Science 305:
1434-1437, 2004.
7. Volpe, T. A.; Kidner, C.; Hall, I. M.; Teng, G.; Grewal, S. I.
S.; Martienssen, R. A.: Regulation of heterochromatic silencing and
histone H3 lysine-9 methylation by RNAi. Science 297: 1833-1837,
2002.
8. Yan, K. S.; Yan, S.; Farooq, A.; Han, A.; Zeng, L.; Zhou, M.-M.
: Structure and conserved RNA binding of the PAZ domain. Nature 426:
468-474, 2003. Note: Erratum: Nature 427: 265 only, 2004.
9. Zisoulis, D. G.; Kai, Z. S.; Chang, R. K.; Pasquinelli, A. E.:
Autoregulation of microRNA biogenesis by let-7 and Argonaute. Nature 486:
541-544, 2012.
*FIELD* CN
Ada Hamosh - updated: 7/17/2012
Ada Hamosh - updated: 8/10/2009
Ada Hamosh - updated: 2/1/2006
Stylianos E. Antonarakis - updated: 3/28/2005
Ada Hamosh - updated: 6/22/2004
Ada Hamosh - updated: 12/3/2003
Ada Hamosh - updated: 11/20/2002
Stylianos E. Antonarakis - updated: 9/13/2002
*FIELD* CD
Ada Hamosh: 8/28/2001
*FIELD* ED
mgross: 02/05/2013
terry: 12/21/2012
alopez: 7/19/2012
terry: 7/17/2012
mgross: 8/10/2009
terry: 8/10/2009
alopez: 5/23/2006
terry: 5/15/2006
alopez: 2/2/2006
terry: 2/1/2006
mgross: 3/28/2005
alopez: 6/22/2004
terry: 6/22/2004
alopez: 12/4/2003
terry: 12/3/2003
cwells: 11/20/2002
terry: 11/18/2002
mgross: 11/15/2002
mgross: 9/13/2002
alopez: 9/18/2001
alopez: 8/28/2001
*RECORD*
*FIELD* NO
606228
*FIELD* TI
*606228 EUKARYOTIC TRANSLATION INITIATION FACTOR 2C, SUBUNIT 1; EIF2C1
;;GERP95;;
EIF2C;;
read moreARGONAUTE 1; AGO1
*FIELD* TX
DESCRIPTION
The human eukaryotic initiation factor 2C1 (EIF2C1) gene belongs to a
multigene family in human. It is highly conserved during evolution,
sharing about 90% identity with rabbit Eif2c and 70% identity with plant
EGO1 at the amino acid level. EIF2C stimulates formation of a ternary
complex composed of EIF2, initiation methionyl-tRNA(I) (Met-tRNA), and
GTP.
CLONING
Koesters et al. (1999) isolated a EIF2C1 cDNA from a human fetal kidney
cDNA library. To obtain genomic sequence information, they isolated a P1
genomic clone containing the EIF2C1 locus. The human EIF2C1 gene encodes
a protein of 857 amino acids. The 2,571-bp open reading frame is flanked
by 238 bp of 5-prime sequence and an extremely large 3-prime
untranslated region with multiple short repeated segments composed of
mono-, tri-, or quatronucleotides interspersed throughout. Northern blot
analysis demonstrated that the human EIF2C1 gene is ubiquitously
expressed at low to medium levels. Differential polyadenylation and
splicing resulted in a complex transcriptional pattern.
BIOCHEMICAL FEATURES
Martinez et al. (2002) demonstrated that a single-stranded small
interfering RNA (siRNA) resides in the human RNA-induced silencing
complex (RISC) together with the EIF2C1 and/or EIF2C2 (606229) proteins.
RISC could be rapidly formed in HeLa cell cytoplasmic extract
supplemented with 21-nucleotide siRNA duplexes, but also by adding
single-stranded antisense RNAs, which range in size between 19 and 29
nucleotides.
- Crystal Structure
Yan et al. (2003) reported the nuclear magnetic resonance solution
structure of the PAZ domain from Drosophila Argonaute-1. The structure
consists of a left-handed, 6-stranded beta-barrel capped at 1 end by 2
alpha-helices and wrapped on 1 side by a distinctive appendage, which
comprises a long beta-hairpin and a short alpha-helix. Using structural
and biochemical analyses, Yan et al. (2003) demonstrated that the PAZ
domain binds a 5-nucleotide RNA with a 1:1 stoichiometry. Yan et al.
(2003) mapped the RNA-binding surface to the open face of the
beta-barrel, which contains amino acids conserved in the PAZ domain
family, and defined a 5-prime-to-3-prime orientation of single-stranded
RNA bound within that site. Yan et al. (2003) also showed that PAZ
domains from different human Argonaute proteins (AGO1; PIWIL1, 605571;
and AGO2, 606229) also bind RNA, establishing a conserved function for
this domain.
Ma et al. (2004) reported the 2.6-angstrom crystal structure of the PAZ
domain from human Argonaute eIF2c1 bound to both ends of a 9-mer
siRNA-like duplex. In a sequence-independent manner, PAZ anchors the
2-nucleotide 3-prime overhang of the siRNA-like duplex within a highly
conserved binding pocket, and secures the duplex by binding the
7-nucleotide phosphodiester backbone of the overhang-containing strand
and capping the 5-prime-terminal residue of the complementary strand. On
the basis of the structure and on binding assays, Ma et al. (2004)
proposed that PAZ might serve as an siRNA end-binding module for siRNA
transfer in the RNA silencing pathway, and as an anchoring site for the
3-prime end of guide RNA within silencing effector complexes.
Song et al. (2004) reported the crystal structure of the Argonaute
protein from Pyrococcus furiosus at 2.25-angstrom resolution. The
structure revealed a crescent-shaped base made up of the amino-terminal,
middle, and PIWI domains. The Piwi Argonaute Zwille (PAZ) domain is held
above the base by a stalk-like region. The PIWI domain is similar to
ribonuclease H (see 604123), with a conserved active site
aspartate-aspartate-glutamate motif, strongly implicating Argonaute as
'slicer,' the enzyme that cleaves mRNA as directed by siRNA. The
architecture of the molecule and the placement of the PAZ and PIWI
domains define a groove for substrate binding and suggested a mechanism
for siRNA-guided mRNA cleavage.
GENE FUNCTION
In S. pombe, Volpe et al. (2002) deleted the argonaute, dicer (606241),
and RNA-dependent RNA polymerase gene homologs, which encode part of the
machinery responsible for RNA interference. Deletion resulted in the
aberrant accumulation of complementary transcripts from centromeric
heterochromatic repeats. This was accompanied by transcription of
derepression of transgenes integrated at the centromere, loss of histone
H3 (see 602810) lysine-9 methylation, and impairment of centromere
function. Volpe et al. (2002) proposed that double-stranded RNA arising
from centromeric repeats targets formation and maintenance of
heterochromatin through RNA interference.
AU-rich elements (AREs) in the 3-prime UTRs of unstable mRNAs dictate
their degradation. Using an RNA interference-based screen in Drosophila
S2 cells, Jing et al. (2005) found that Dicer-1, Ago1, and Ago2,
components involved in microRNA (miRNA) processing and function, were
required for rapid decay of mRNA containing AREs of tumor necrosis
factor-alpha (TNF; 191160). The requirement for Dicer in the instability
of ARE-containing mRNA (ARE-RNA) was confirmed in HeLa cells. Jing et
al. (2005) showed that miRNA16 (miR16), a human miRNA containing an
UAAAUAUU sequence that is complementary to the ARE sequence, was
required for ARE-RNA turnover. The role of miR16 in ARE-RNA decay was
sequence-specific and required the ARE-binding protein tristetraprolin
(TTP, or ZFP36; 190700). TTP did not directly bind miR16, but interacted
through association with Ago/EIF2C family members to complex with miR16
and assist in the targeting of ARE. Jing et al. (2005) concluded that
miRNA targeting of ARE appears to be an essential step in ARE-mediated
mRNA degradation.
Chi et al. (2009) used HITS-CLIP (high-throughout sequencing of RNAs
isolated by crosslinking immunoprecipitation) to covalently crosslink
native Ago protein-RNA complexes in postnatal day-13 (P13) mouse brain.
They obtained 2 simultaneous data sets, Ago-miRNA and Ago-mRNA binding
sites, that were combined with bioinformatic analysis to identify
interaction sites between miRNA and target mRNA. Chi et al. (2009)
validated genomewide interaction maps for miR124 (MIR124-1; 609327) and
generated additional maps for the 20 most abundant miRNAs present in P13
mouse brain. They concluded that Ago HITS-CLIP provides a general
platform for exploring the specificity and range of miRNA action in
vivo, and that it identifies precise sequences for targeting clinically
relevant miRNA-mRNA interactions.
Zisoulis et al. (2012) showed that the miRNA-induced silencing complex
(miRISC) also targets and regulates noncoding RNAs that serve as
substrates for the miRNA-processing pathway. They found that the
Argonaute protein in C. elegans, ALG1, binds to a specific site at the
3-prime end of let-7 (605386) miRNA primary transcripts and promotes
downstream processing events. This interaction is mediated by mature
let-7 miRNA through a conserved complementary site in its own primary
transcript, thus creating a positive-feedback loop. Zisoulis et al.
(2012) further showed that ALG1 associates with let-7 primary
transcripts in nuclear fractions. Argonaute also binds let-7 primary
transcripts in human cells, demonstrating that the miRNA pathway targets
noncoding RNAs in addition to protein-coding mRNAs across species.
Moreover, their studies in C. elegans revealed a novel role for
Argonaute in promoting biogenesis of a targeted transcript, expanding
the functions of the miRNA pathway in gene regulation. The discovery of
autoregulation of let-7 biogenesis established a new mechanism for
controlling miRNA expression.
GENE STRUCTURE
Koesters et al. (1999) determined that the EIF2C1 gene consists of 19
exons within approximately 50 kb.
MAPPING
Koesters et al. (1999) mapped the EIF2C1 gene to chromosome 1p35-p34 by
fluorescence in situ hybridization. This region is frequently lost in
human malignancies, including Wilms tumors.
*FIELD* RF
1. Chi, S. W.; Zang, J. B.; Mele, A.; Darnell, R. B.: Argonaute HITS-CLIP
decodes microRNA-mRNA interaction maps. Nature 460: 479-486, 2009.
2. Jing, Q.; Huang, S.; Guth, S.; Zarubin, T.; Motoyama, A.; Chen,
J.; Di Padova, F.; Lin, S.-C.; Gram, H.; Han, J.: Involvement of
microRNA in AU-rich element-mediated mRNA instability. Cell 120:
623-634, 2005.
3. Koesters, R.; Adams, V.; Betts, D.; Moos, R.; Schmid, M.; Siermann,
A.; Hassam, S.; Weitz, S.; Lichter, P.; Heitz, P. U.; von Knebel Doeberitz,
M.; Briner, J.: Human eukaryotic initiation factor EIF2C1 gene: cDNA
sequence, genomic organization, localization to chromosomal bands
1q34-p35, and expression. Genomics 61: 210-218, 1999.
4. Ma, J.-B.; Ye, K.; Patel, D. J.: Structural basis for overhang-specific
small interfering RNA recognition by the PAZ domain. Nature 429:
318-322, 2004.
5. Martinez, J.; Patkaniowska, A.; Urlaub, H.; Luhrmann, R.; Tuschi,
T.: Single-stranded antisense siRNAs guide target RNA cleavage in
RNAi. Cell 110: 563-574, 2002.
6. Song, J.-J.; Smith, S. K.; Hannon, G. J.; Joshua-Tor, L.: Crystal
structure of Argonaute and its implications for RISC slicer activity. Science 305:
1434-1437, 2004.
7. Volpe, T. A.; Kidner, C.; Hall, I. M.; Teng, G.; Grewal, S. I.
S.; Martienssen, R. A.: Regulation of heterochromatic silencing and
histone H3 lysine-9 methylation by RNAi. Science 297: 1833-1837,
2002.
8. Yan, K. S.; Yan, S.; Farooq, A.; Han, A.; Zeng, L.; Zhou, M.-M.
: Structure and conserved RNA binding of the PAZ domain. Nature 426:
468-474, 2003. Note: Erratum: Nature 427: 265 only, 2004.
9. Zisoulis, D. G.; Kai, Z. S.; Chang, R. K.; Pasquinelli, A. E.:
Autoregulation of microRNA biogenesis by let-7 and Argonaute. Nature 486:
541-544, 2012.
*FIELD* CN
Ada Hamosh - updated: 7/17/2012
Ada Hamosh - updated: 8/10/2009
Ada Hamosh - updated: 2/1/2006
Stylianos E. Antonarakis - updated: 3/28/2005
Ada Hamosh - updated: 6/22/2004
Ada Hamosh - updated: 12/3/2003
Ada Hamosh - updated: 11/20/2002
Stylianos E. Antonarakis - updated: 9/13/2002
*FIELD* CD
Ada Hamosh: 8/28/2001
*FIELD* ED
mgross: 02/05/2013
terry: 12/21/2012
alopez: 7/19/2012
terry: 7/17/2012
mgross: 8/10/2009
terry: 8/10/2009
alopez: 5/23/2006
terry: 5/15/2006
alopez: 2/2/2006
terry: 2/1/2006
mgross: 3/28/2005
alopez: 6/22/2004
terry: 6/22/2004
alopez: 12/4/2003
terry: 12/3/2003
cwells: 11/20/2002
terry: 11/18/2002
mgross: 11/15/2002
mgross: 9/13/2002
alopez: 9/18/2001
alopez: 8/28/2001