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Q9UL18 (AGO1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein argonaute-1

Short name=Argonaute1
Short name=hAgo1
Alternative name(s):
Argonaute RISC catalytic component 1
Eukaryotic translation initiation factor 2C 1
Short name=eIF-2C 1
Short name=eIF2C 1
Putative RNA-binding protein Q99
Gene names
Name:AGO1
Synonyms:EIF2C1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length857 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) or short interfering RNAs (siRNAs), and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs. Also required for transcriptional gene silencing (TGS) of promoter regions which are complementary to bound short antigene RNAs (agRNAs). Ref.5 Ref.6 Ref.9

Subunit structure

Interacts with DDB1, DDX5, DDX6, DHX30, DHX36, DDX47, DICER1, AGO2, ELAVL1, HNRNPF, IGF2BP1, ILF3, IMP8, MATR3, MOV10, PABPC1, PRMT5, RBM4, SART3, TNRC6B, UPF1 and YBX1. Associates with polysomes and messenger ribonucleoproteins (mNRPs). Interacts with LIMD1, WTIP and AJUBA. Interacts with APOBEC3F, APOBEC3G and APOBEC3H. Ref.5 Ref.7 Ref.8 Ref.10 Ref.11 Ref.13

Subcellular location

CytoplasmP-body Ref.5 Ref.11.

Miscellaneous

Lacks RNA cleavage activity due to the absence of the conserved His at position 805, but also because it binds the RNA in a subtly different manner that precludes efficient cleavage.

Sequence similarities

Belongs to the argonaute family. Ago subfamily.

Contains 1 PAZ domain.

Contains 1 Piwi domain.

Ontologies

Keywords
   Biological processRNA-mediated gene silencing
Transcription
Transcription regulation
Translation regulation
   Cellular componentCytoplasm
   LigandRNA-binding
   Molecular functionRepressor
Ribonucleoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

Notch signaling pathway

Traceable author statement. Source: Reactome

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

gene expression

Traceable author statement. Source: Reactome

innate immune response

Traceable author statement. Source: Reactome

negative regulation of translation involved in gene silencing by miRNA

Inferred from direct assay Ref.9. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

nuclear-transcribed mRNA catabolic process

Inferred from direct assay Ref.9. Source: UniProtKB

phosphatidylinositol-mediated signaling

Traceable author statement. Source: Reactome

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 20014101. Source: MGI

cytoplasmic mRNA processing body

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Traceable author statement. Source: Reactome

micro-ribonucleoprotein complex

Inferred from direct assay Ref.8. Source: UniProtKB

polysome

Inferred from direct assay Ref.8. Source: UniProtKB

ribonucleoprotein complex

Inferred from direct assay Ref.8. Source: UniProtKB

   Molecular_functionRNA binding

Inferred from direct assay Ref.15. Source: UniProtKB

poly(A) RNA binding

Inferred from direct assay PubMed 22681889. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 857857Protein argonaute-1
PRO_0000194055

Regions

Domain226 – 346121PAZ
Domain515 – 816302Piwi
Region309 – 3146Interaction with guide RNA
Region522 – 56443Interaction with guide RNA
Region670 – 6756Impairs access of bound RNA to the active site
Region708 – 7125Interaction with guide RNA
Region751 – 7599Interaction with guide RNA
Region788 – 81326Interaction with guide RNA

Experimental info

Mutagenesis6701P → S: Confers modest RNA cleavage activity; when associated with Q-675 and H-805. Ref.15
Mutagenesis6741L → F: Confers modest RNA cleavage activity; when associated with H-805. Ref.16
Mutagenesis6751P → Q: Does not confer enzyme activity by itself. Confers low RNA cleavage activity; when associated with H-805. Confers modest RNA cleavage activity; when associated with S-670 and H-805. Ref.15
Mutagenesis8051R → H: Does not confer enzyme activity by itself. Confers modest RNA cleavage activity; when associated with F-674. Ref.15 Ref.16
Sequence conflict2421D → N in AAH63275. Ref.3

Secondary structure

..................................................................................................................................... 857
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9UL18 [UniParc].

Last modified February 21, 2006. Version 3.
Checksum: 1DBB524AE7CBAF66

FASTA85797,214
        10         20         30         40         50         60 
MEAGPSGAAA GAYLPPLQQV FQAPRRPGIG TVGKPIKLLA NYFEVDIPKI DVYHYEVDIK 

        70         80         90        100        110        120 
PDKCPRRVNR EVVEYMVQHF KPQIFGDRKP VYDGKKNIYT VTALPIGNER VDFEVTIPGE 

       130        140        150        160        170        180 
GKDRIFKVSI KWLAIVSWRM LHEALVSGQI PVPLESVQAL DVAMRHLASM RYTPVGRSFF 

       190        200        210        220        230        240 
SPPEGYYHPL GGGREVWFGF HQSVRPAMWK MMLNIDVSAT AFYKAQPVIE FMCEVLDIRN 

       250        260        270        280        290        300 
IDEQPKPLTD SQRVRFTKEI KGLKVEVTHC GQMKRKYRVC NVTRRPASHQ TFPLQLESGQ 

       310        320        330        340        350        360 
TVECTVAQYF KQKYNLQLKY PHLPCLQVGQ EQKHTYLPLE VCNIVAGQRC IKKLTDNQTS 

       370        380        390        400        410        420 
TMIKATARSA PDRQEEISRL MKNASYNLDP YIQEFGIKVK DDMTEVTGRV LPAPILQYGG 

       430        440        450        460        470        480 
RNRAIATPNQ GVWDMRGKQF YNGIEIKVWA IACFAPQKQC REEVLKNFTD QLRKISKDAG 

       490        500        510        520        530        540 
MPIQGQPCFC KYAQGADSVE PMFRHLKNTY SGLQLIIVIL PGKTPVYAEV KRVGDTLLGM 

       550        560        570        580        590        600 
ATQCVQVKNV VKTSPQTLSN LCLKINVKLG GINNILVPHQ RSAVFQQPVI FLGADVTHPP 

       610        620        630        640        650        660 
AGDGKKPSIT AVVGSMDAHP SRYCATVRVQ RPRQEIIEDL SYMVRELLIQ FYKSTRFKPT 

       670        680        690        700        710        720 
RIIFYRDGVP EGQLPQILHY ELLAIRDACI KLEKDYQPGI TYIVVQKRHH TRLFCADKNE 

       730        740        750        760        770        780 
RIGKSGNIPA GTTVDTNITH PFEFDFYLCS HAGIQGTSRP SHYYVLWDDN RFTADELQIL 

       790        800        810        820        830        840 
TYQLCHTYVR CTRSVSIPAP AYYARLVAFR ARYHLVDKEH DSGEGSHISG QSNGRDPQAL 

       850 
AKAVQVHQDT LRTMYFA 

« Hide

References

« Hide 'large scale' references
[1]"Human eukaryotic initiation factor EIF2C1 gene: cDNA sequence, genomic organization, localization to chromosomal bands 1p34-p35, and expression."
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.
Genomics 61:210-218(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[4]"Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs."
Meister G., Landthaler M., Patkaniowska A., Dorsett Y., Teng G., Tuschl T.
Mol. Cell 15:185-197(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION WITH MIRNA.
[5]"Identification of novel argonaute-associated proteins."
Meister G., Landthaler M., Peters L., Chen P.Y., Urlaub H., Luehrmann R., Tuschl T.
Curr. Biol. 15:2149-2155(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DICER1; MOV10; PRMT5 AND TNRC6B, SUBCELLULAR LOCATION.
[6]"Involvement of AGO1 and AGO2 in mammalian transcriptional silencing."
Janowski B.A., Huffman K.E., Schwartz J.C., Ram R., Nordsell R., Shames D.S., Minna J.D., Corey D.R.
Nat. Struct. Mol. Biol. 13:787-792(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Translation repression in human cells by microRNA-induced gene silencing requires RCK/p54."
Chu C.-Y., Rana T.M.
PLoS Biol. 4:E210-E210(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DDX6 AND AGO2.
[8]"Proteomic and functional analysis of Argonaute-containing mRNA-protein complexes in human cells."
Hoeck J., Weinmann L., Ender C., Ruedel S., Kremmer E., Raabe M., Urlaub H., Meister G.
EMBO Rep. 8:1052-1060(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION WITH POLYSOMES AND MNRP, INTERACTION WITH DDB1; DDX5; DHX30; DHX36; DDX47; ELAVL1; HNRNPF; IGF2BP1; ILF3; MATR3; PABPC1; RBM4; SART3; UPF1 AND YBX1.
[9]"Importance of translation and nonnucleolytic ago proteins for on-target RNA interference."
Wu L., Fan J., Belasco J.G.
Curr. Biol. 18:1327-1332(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Importin 8 is a gene silencing factor that targets argonaute proteins to distinct mRNAs."
Weinmann L., Hoeck J., Ivacevic T., Ohrt T., Muetze J., Schwille P., Kremmer E., Benes V., Urlaub H., Meister G.
Cell 136:496-507(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IMP8.
[11]"LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for microRNA-mediated gene silencing."
James V., Zhang Y., Foxler D.E., de Moor C.H., Kong Y.W., Webb T.M., Self T.J., Feng Y., Lagos D., Chu C.Y., Rana T.M., Morley S.J., Longmore G.D., Bushell M., Sharp T.V.
Proc. Natl. Acad. Sci. U.S.A. 107:12499-12504(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH LIMD1; WTIP AND AJUBA.
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"HIV-1 replication and APOBEC3 antiviral activity are not regulated by P bodies."
Phalora P.K., Sherer N.M., Wolinsky S.M., Swanson C.M., Malim M.H.
J. Virol. 86:11712-11724(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH APOBEC3F; APOBEC3G AND APOBEC3H.
[14]"Structural basis for overhang-specific small interfering RNA recognition by the PAZ domain."
Ma J.-B., Ye K., Patel D.J.
Nature 429:318-322(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 225-369, RNA-BINDING.
[15]"Eukaryote-specific insertion elements control human ARGONAUTE slicer activity."
Nakanishi K., Ascano M., Gogakos T., Ishibe-Murakami S., Serganov A.A., Briskin D., Morozov P., Tuschl T., Patel D.J.
Cell Rep. 3:1893-1900(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.29 ANGSTROMS) IN COMPLEX WITH RNA, RNA-BINDING, MUTAGENESIS OF PRO-670; PRO-675 AND ARG-805, LACK OF CATALYTIC ACTIVITY.
[16]"The making of a slicer: activation of human Argonaute-1."
Faehnle C.R., Elkayam E., Haase A.D., Hannon G.J., Joshua-Tor L.
Cell Rep. 3:1901-1909(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH RNA, LACK OF CATALYTIC ACTIVITY, MUTAGENESIS OF LEU-674 AND ARG-805.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF093097 mRNA. Translation: AAF00068.1.
AL139286 Genomic DNA. Translation: CAI22804.1.
BC063275 mRNA. Translation: AAH63275.1.
RefSeqNP_036331.1. NM_012199.2.
UniGeneHs.22867.
Hs.656677.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1SI2X-ray2.60A225-369[»]
1SI3X-ray2.60A225-369[»]
4KREX-ray1.75A1-857[»]
4KRFX-ray2.10A1-857[»]
4KXTX-ray2.29A1-857[»]
ProteinModelPortalQ9UL18.
SMRQ9UL18. Positions 17-857.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117726. 26 interactions.
DIPDIP-29193N.
IntActQ9UL18. 179 interactions.
STRING9606.ENSP00000362300.

PTM databases

PhosphoSiteQ9UL18.

Polymorphism databases

DMDM88984241.

Proteomic databases

PaxDbQ9UL18.
PRIDEQ9UL18.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000373204; ENSP00000362300; ENSG00000092847.
GeneID26523.
KEGGhsa:26523.
UCSCuc001bzk.3. human.

Organism-specific databases

CTD26523.
GeneCardsGC01P036336.
HGNCHGNC:3262. AGO1.
MIM606228. gene.
neXtProtNX_Q9UL18.
PharmGKBPA27693.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG279895.
HOGENOMHOG000116043.
InParanoidQ9UL18.
KOK11593.
OMAENDILRT.
PhylomeDBQ9UL18.
TreeFamTF101510.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_120956. Cellular responses to stress.
REACT_6900. Immune System.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpressQ9UL18.
BgeeQ9UL18.
CleanExHS_EIF2C1.
GenevestigatorQ9UL18.

Family and domain databases

Gene3D3.30.420.10. 1 hit.
InterProIPR014811. DUF1785.
IPR003100. PAZ_dom.
IPR003165. Piwi.
IPR012337. RNaseH-like_dom.
[Graphical view]
PfamPF08699. DUF1785. 1 hit.
PF02170. PAZ. 1 hit.
PF02171. Piwi. 1 hit.
[Graphical view]
SMARTSM00949. PAZ. 1 hit.
SM00950. Piwi. 1 hit.
[Graphical view]
SUPFAMSSF101690. SSF101690. 1 hit.
SSF53098. SSF53098. 1 hit.
PROSITEPS50821. PAZ. 1 hit.
PS50822. PIWI. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSEIF2C1. human.
EvolutionaryTraceQ9UL18.
GeneWikiEIF2C1.
GenomeRNAi26523.
NextBio48846.
PROQ9UL18.
SOURCESearch...

Entry information

Entry nameAGO1_HUMAN
AccessionPrimary (citable) accession number: Q9UL18
Secondary accession number(s): Q5TA57, Q6P4S0
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: February 21, 2006
Last modified: April 16, 2014
This is version 117 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Translation initiation factors

List of translation initiation factor entries

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM