Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9UKV8 (AGO2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 127. 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·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein argonaute-2

Short name=Argonaute2
Short name=hAgo2
EC=3.1.26.n2
Alternative name(s):
Argonaute RISC catalytic component 2
Eukaryotic translation initiation factor 2C 2
Short name=eIF-2C 2
Short name=eIF2C 2
PAZ Piwi domain protein
Short name=PPD
Protein slicer
Gene names
Name:AGO2
Synonyms:EIF2C2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length859 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Required for RNA-mediated gene silencing (RNAi) by the RNA-induced silencing complex (RISC). The 'minimal RISC' appears to include AGO2 bound to a short guide RNA such as a microRNA (miRNA) or short interfering RNA (siRNA). These guide RNAs direct RISC to complementary mRNAs that are targets for RISC-mediated gene silencing. The precise mechanism of gene silencing depends on the degree of complementarity between the miRNA or siRNA and its target. Binding of RISC to a perfectly complementary mRNA generally results in silencing due to endonucleolytic cleavage of the mRNA specifically by AGO2. Binding of RISC to a partially complementary mRNA results in silencing through inhibition of translation, and this is independent of endonuclease activity. May inhibit translation initiation by binding to the 7-methylguanosine cap, thereby preventing the recruitment of the translation initiation factor eIF4-E. May also inhibit translation initiation via interaction with EIF6, which itself binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit. The inhibition of translational initiation leads to the accumulation of the affected mRNA in cytoplasmic processing bodies (P-bodies), where mRNA degradation may subsequently occur. In some cases RISC-mediated translational repression is also observed for miRNAs that perfectly match the 3' untranslated region (3'-UTR). Can also up-regulate the translation of specific mRNAs under certain growth conditions. Binds to the AU element of the 3'-UTR of the TNF (TNF-alpha) mRNA and up-regulates translation under conditions of serum starvation. Also required for transcriptional gene silencing (TGS), in which short RNAs known as antigene RNAs or agRNAs direct the transcriptional repression of complementary promoter regions. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.18 Ref.19 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.39

Catalytic activity

Endonucleolytic cleavage to 5'-phosphomonoester. Ref.7 Ref.39

Cofactor

Magnesium or manganese. Ref.10

Enzyme regulation

Inhibited by EDTA. Ref.10

Subunit structure

Interacts with DICER1 through its Piwi domain and with TARBP2 during assembly of the RNA-induced silencing complex (RISC). Together, DICER1, AGO2 and TARBP2 constitute the trimeric RISC loading complex (RLC), or micro-RNA (miRNA) loading complex (miRLC). Within the RLC/miRLC, DICER1 and TARBP2 are required to process precursor miRNAs (pre-miRNAs) to mature miRNAs and then load them onto AGO2. AGO2 bound to the mature miRNA constitutes the minimal RISC and may subsequently dissociate from DICER1 and TARBP2. Note however that the term RISC has also been used to describe the trimeric RLC/miRLC. The formation of RISC complexes containing siRNAs rather than miRNAs appears to occur independently of DICER1. Interacts with AGO1. Also interacts with DDB1, DDX5, DDX6, DDX20, DHX30, DHX36, DDX47, DHX9, EIF6, ELAVL, FXR1, GEMIN4, HNRNPF, IGF2BP1, ILF3, IMP8, MATR3, MOV10, PABPC1, PRMT5, P4HA1, P4HB, RBM4, SART3, TNRC6A, TNRC6B, UPF1 and YBX1. Interacts with the P-body components DCP1A and XRN1. Associates with polysomes and messenger ribonucleoproteins (mNRPs). Interacts with RBM4; the interaction is modulated under stress-induced conditions, occurs under both cell proliferation and differentiation conditions and in an RNA- and phosphorylation-independent manner. Interacts with LIMD1, WTIP and AJUBA. Interacts with TRIM71. Interacts with APOBEC3G in an RNA-dependent manner. Interacts with APOBEC3A, APOBEC3C, APOBEC3F and APOBEC3H. Ref.6 Ref.9 Ref.11 Ref.12 Ref.14 Ref.16 Ref.19 Ref.21 Ref.22 Ref.23 Ref.25 Ref.26 Ref.27 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.36 Ref.37 Ref.38

Subcellular location

CytoplasmP-body. Nucleus. Note: Translational repression of mRNAs results in their recruitment to P-bodies. Translocation to the nucleus requires IMP8. Ref.12 Ref.17 Ref.19 Ref.21 Ref.23 Ref.30 Ref.32 Ref.34 Ref.38

Domain

The Piwi domain may perform RNA cleavage by a mechanism similar to that of RNase H. However, while RNase H utilizes a triad of Asp-Asp-Glu (DDE) for metal ion coordination, this protein appears to utilize a triad of Asp-Asp-His (DDH). HAMAP-Rule MF_03031

Post-translational modification

Hydroxylated. 4-hydroxylation appears to enhance protein stability but is not required for miRNA-binding or endonuclease activity. HAMAP-Rule MF_03031

Sequence similarities

Belongs to the argonaute family. Ago subfamily.

Contains 1 PAZ domain.

Contains 1 Piwi domain.

Biophysicochemical properties

Kinetic parameters:

KM=1.1 nM for a synthetic 21-nucleotide single-stranded RNA Ref.7 Ref.18

Sequence caution

The sequence AAH07633.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence AAL76093.1 differs from that shown. Reason: cDNA contains a duplication of an internal sequence at the 5' end.

The sequence BC125214 differs from that shown. Reason: Frameshift at position 450.

Ontologies

Keywords
   Biological processRNA-mediated gene silencing
Transcription
Transcription regulation
Translation regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   LigandMagnesium
Manganese
Metal-binding
RNA-binding
   Molecular functionEndonuclease
Hydrolase
Nuclease
Repressor
Ribonucleoprotein
   PTMHydroxylation
Nitration
   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

RNA phosphodiester bond hydrolysis, endonucleolytic

Inferred from direct assay Ref.24. Source: GOC

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

gene silencing by RNA

Inferred from sequence or structural similarity. Source: UniProtKB

innate immune response

Traceable author statement. Source: Reactome

mRNA cleavage involved in gene silencing by miRNA

Inferred from direct assay Ref.24. Source: UniProtKB

negative regulation of translation involved in gene silencing by miRNA

Inferred from direct assay PubMed 17671087Ref.33. Source: UniProtKB

negative regulation of translational initiation

Inferred from direct assay Ref.24Ref.33. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

phosphatidylinositol-mediated signaling

Traceable author statement. Source: Reactome

positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of nuclear-transcribed mRNA poly(A) tail shortening

Inferred from sequence or structural similarity. Source: UniProtKB

post-embryonic development

Inferred from electronic annotation. Source: Ensembl

pre-miRNA processing

Inferred from direct assay PubMed 17671087. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

translation

Non-traceable author statement Ref.5. Source: UniProtKB

translational initiation

Non-traceable author statement Ref.5. Source: GOC

   Cellular_componentRISC complex

Inferred from direct assay Ref.16. Source: UniProtKB

cytoplasm

Inferred from direct assay PubMed 20014101. Source: MGI

cytoplasmic mRNA processing body

Inferred from direct assay Ref.38. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

mRNA cap binding complex

Inferred from direct assay Ref.24. Source: UniProtKB

micro-ribonucleoprotein complex

Inferred from direct assay PubMed 17671087Ref.25. Source: UniProtKB

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

polysome

Inferred from direct assay Ref.25. Source: UniProtKB

ribonucleoprotein complex

Inferred from direct assay Ref.25. Source: UniProtKB

   Molecular_functionRNA 7-methylguanosine cap binding

Inferred from direct assay Ref.24. Source: UniProtKB

endoribonuclease activity

Inferred from experiment. Source: Reactome

endoribonuclease activity, cleaving siRNA-paired mRNA

Inferred from direct assay Ref.24. Source: UniProtKB

mRNA binding

Inferred from electronic annotation. Source: Ensembl

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

miRNA binding

Inferred from electronic annotation. Source: UniProtKB-HAMAP

poly(A) RNA binding

Inferred from direct assay PubMed 22658674PubMed 22681889. Source: UniProtKB

siRNA binding

Inferred from direct assay PubMed 17495927. Source: UniProtKB

translation initiation factor activity

Non-traceable author statement Ref.5. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UKV8-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9UKV8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     724-757: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 859859Protein argonaute-2 HAMAP-Rule MF_03031
PRO_0000194057

Regions

Domain235 – 348114PAZ
Domain517 – 818302Piwi
Region311 – 3166Interaction with guide RNA HAMAP-Rule MF_03031
Region524 – 56643Interaction with guide RNA HAMAP-Rule MF_03031
Region587 – 5904Interaction with GW182 family members Potential
Region650 – 66011Interaction with GW182 family members Potential
Region709 – 7102Interaction with guide RNA HAMAP-Rule MF_03031
Region753 – 7619Interaction with guide RNA HAMAP-Rule MF_03031
Region790 – 81223Interaction with guide RNA HAMAP-Rule MF_03031

Sites

Metal binding5971Divalent metal cation Probable
Metal binding6691Divalent metal cation Probable
Metal binding8071Divalent metal cation Probable

Amino acid modifications

Modified residue21Nitrated tyrosine By similarity
Modified residue70014-hydroxyproline Ref.30

Natural variations

Alternative sequence724 – 75734Missing in isoform 2.
VSP_037001

Experimental info

Mutagenesis1401L → W: No effect. Ref.10
Mutagenesis4701F → V: No effect on miRNA-binding or target mRNA cleavage. Abrogates binding to the 7-methylguanosine cap of mRNA and prevents inhibition of translation. Abolishes interaction with TNRC6C; when associated with V-505. Ref.24 Ref.36
Mutagenesis4701F → W: No effect on binding to the 7-methylguanosine cap of mRNA or inhibition of translation. Ref.24 Ref.36
Mutagenesis5051F → V: No effect on miRNA-binding or target mRNA cleavage. Abrogates binding to the 7-methylguanosine cap of mRNA and prevents inhibition of translation and abolishes interaction with TNRC6C; when associated with V-470. Ref.24 Ref.36
Mutagenesis5051F → W: No effect on binding to the 7-methylguanosine cap of mRNA or inhibition of translation. Ref.24 Ref.36
Mutagenesis5331K → A: Impairs RNA cleavage. Ref.15
Mutagenesis5451Q → A: Impairs RNA cleavage. Ref.15
Mutagenesis5701K → A: Impairs RNA cleavage. Ref.15
Mutagenesis5971D → A: Abrogates RNA cleavage but does not affect binding to siRNA or translational repression. Ref.10 Ref.18 Ref.29
Mutagenesis6331Q → A: No effect. Ref.10
Mutagenesis6331Q → R: Abrogates RNA cleavage. Binds siRNA. Ref.10
Mutagenesis6341H → P or A: Abrogates RNA cleavage. Binds siRNA. Ref.10
Mutagenesis6691D → A: Abrogates RNA cleavage but does not affect binding to siRNA. Ref.10 Ref.14 Ref.18
Mutagenesis6731E → A: Impairs RNA cleavage. Ref.18 Ref.39
Mutagenesis6731E → G: No effect on RNA cleavage. Ref.18 Ref.39
Mutagenesis6761F → A, I, M, R or Y: Impairs RNA cleavage. Ref.39
Mutagenesis6761F → V: Abrogates RNA cleavage. Ref.39
Mutagenesis6821H → Y: No effect. Ref.10
Mutagenesis6831E → G: No effect on RNA cleavage. Ref.18
Mutagenesis7001P → A: Reduced protein stability. Ref.30
Mutagenesis7041F → Y: No effect. Ref.10
Mutagenesis7441T → Y: No effect. Ref.10
Mutagenesis8071H → A or R: Abrogates RNA cleavage. Ref.18 Ref.39
Sequence conflict5641C → W in AAF13034. Ref.5
Sequence conflict5891Q → E in AAF13034. Ref.5
Sequence conflict6171S → R in AAF13034. Ref.5
Sequence conflict6371E → K in AAL76093. Ref.3

Secondary structure

........................................................................................................................................ 859
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 5, 2009. Version 3.
Checksum: 5C8552C43FC81345

FASTA85997,208
        10         20         30         40         50         60 
MYSGAGPALA PPAPPPPIQG YAFKPPPRPD FGTSGRTIKL QANFFEMDIP KIDIYHYELD 

        70         80         90        100        110        120 
IKPEKCPRRV NREIVEHMVQ HFKTQIFGDR KPVFDGRKNL YTAMPLPIGR DKVELEVTLP 

       130        140        150        160        170        180 
GEGKDRIFKV SIKWVSCVSL QALHDALSGR LPSVPFETIQ ALDVVMRHLP SMRYTPVGRS 

       190        200        210        220        230        240 
FFTASEGCSN PLGGGREVWF GFHQSVRPSL WKMMLNIDVS ATAFYKAQPV IEFVCEVLDF 

       250        260        270        280        290        300 
KSIEEQQKPL TDSQRVKFTK EIKGLKVEIT HCGQMKRKYR VCNVTRRPAS HQTFPLQQES 

       310        320        330        340        350        360 
GQTVECTVAQ YFKDRHKLVL RYPHLPCLQV GQEQKHTYLP LEVCNIVAGQ RCIKKLTDNQ 

       370        380        390        400        410        420 
TSTMIRATAR SAPDRQEEIS KLMRSASFNT DPYVREFGIM VKDEMTDVTG RVLQPPSILY 

       430        440        450        460        470        480 
GGRNKAIATP VQGVWDMRNK QFHTGIEIKV WAIACFAPQR QCTEVHLKSF TEQLRKISRD 

       490        500        510        520        530        540 
AGMPIQGQPC FCKYAQGADS VEPMFRHLKN TYAGLQLVVV ILPGKTPVYA EVKRVGDTVL 

       550        560        570        580        590        600 
GMATQCVQMK NVQRTTPQTL SNLCLKINVK LGGVNNILLP QGRPPVFQQP VIFLGADVTH 

       610        620        630        640        650        660 
PPAGDGKKPS IAAVVGSMDA HPNRYCATVR VQQHRQEIIQ DLAAMVRELL IQFYKSTRFK 

       670        680        690        700        710        720 
PTRIIFYRDG VSEGQFQQVL HHELLAIREA CIKLEKDYQP GITFIVVQKR HHTRLFCTDK 

       730        740        750        760        770        780 
NERVGKSGNI PAGTTVDTKI THPTEFDFYL CSHAGIQGTS RPSHYHVLWD DNRFSSDELQ 

       790        800        810        820        830        840 
ILTYQLCHTY VRCTRSVSIP APAYYAHLVA FRARYHLVDK EHDSAEGSHT SGQSNGRDHQ 

       850 
ALAKAVQVHQ DTLRTMYFA 

« Hide

Isoform 2 [UniParc].

Checksum: 464C15B9413608D4
Show »

FASTA82593,620

References

« Hide 'large scale' references
[1]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]"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] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 239-859 (ISOFORM 1).
Tissue: Brain and Eye.
[3]"miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs."
Mourelatos Z., Dostie J., Paushkin S., Sharma A., Charroux B., Abel L., Rappsilber J., Mann M., Dreyfuss G.
Genes Dev. 16:720-728(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 47-859 (ISOFORM 1).
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 275-859 (ISOFORM 1).
[5]"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] OF 483-859 (ISOFORM 1).
[6]"Characterization of the interactions between mammalian PAZ PIWI domain proteins and Dicer."
Tahbaz N., Kolb F.A., Zhang H., Jaronczyk K., Filipowicz W., Hobman T.C.
EMBO Rep. 5:189-194(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DICER1.
[7]"RISC is a 5' phosphomonoester-producing RNA endonuclease."
Martinez J., Tuschl T.
Genes Dev. 18:975-980(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
[8]"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: FUNCTION.
[9]"Tethering of human Ago proteins to mRNA mimics the miRNA-mediated repression of protein synthesis."
Pillai R.S., Artus C.G., Filipowicz W.
RNA 10:1518-1525(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH GEMIN4.
[10]"Argonaute2 is the catalytic engine of mammalian RNAi."
Liu J., Carmell M.A., Rivas F.V., Marsden C.G., Thomson J.M., Song J.-J., Hammond S.M., Joshua-Tor L., Hannon G.J.
Science 305:1437-1441(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, MUTAGENESIS OF LEU-140; ASP-597; GLN-633; HIS-634; ASP-669; HIS-682; PHE-704 AND THR-744, COFACTOR.
[11]"Human RISC couples microRNA biogenesis and posttranscriptional gene silencing."
Gregory R.I., Chendrimada T.P., Cooch N., Shiekhattar R.
Cell 123:631-640(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DICER1 AND TARBP2.
[12]"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 DDX20; DICER1; GEMIN4; MOV10; PRMT5 AND TNRC6B, SUBCELLULAR LOCATION.
[13]"TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts with Dicer and functions in RNA silencing."
Haase A.D., Jaskiewicz L., Zhang H., Laine S., Sack R., Gatignol A., Filipowicz W.
EMBO Rep. 6:961-967(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[14]"A human, ATP-independent, RISC assembly machine fueled by pre-miRNA."
Maniataki E., Mourelatos Z.
Genes Dev. 19:2979-2990(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DICER1 AND TARBP2, MUTAGENESIS OF ASP-669.
[15]"Structural basis for 5'-end-specific recognition of guide RNA by the A. fulgidus Piwi protein."
Ma J.-B., Yuan Y.-R., Meister G., Pei Y., Tuschl T., Patel D.J.
Nature 434:666-670(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF LYS-533; GLN-545 AND LYS-570.
[16]"TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing."
Chendrimada T.P., Gregory R.I., Kumaraswamy E., Norman J., Cooch N., Nishikura K., Shiekhattar R.
Nature 436:740-744(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DICER1 AND TARBP2.
[17]"Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies."
Sen G.L., Blau H.M.
Nat. Cell Biol. 7:633-636(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[18]"Purified Argonaute2 and an siRNA form recombinant human RISC."
Rivas F.V., Tolia N.H., Song J.-J., Aragon J.P., Liu J., Hannon G.J., Joshua-Tor L.
Nat. Struct. Mol. Biol. 12:340-349(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ASP-597; ASP-669; GLU-673; GLU-683 AND HIS-807.
[19]"Inhibition of translational initiation by Let-7 MicroRNA in human cells."
Pillai R.S., Bhattacharyya S.N., Artus C.G., Zoller T., Cougot N., Basyuk E., Bertrand E., Filipowicz W.
Science 309:1573-1576(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DCP1A AND XRN1, SUBCELLULAR LOCATION.
[20]"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.
[21]"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: FUNCTION, INTERACTION WITH DDX6 AND AGO1, SUBCELLULAR LOCATION.
[22]"Human retroviral host restriction factors APOBEC3G and APOBEC3F localize to mRNA processing bodies."
Wichroski M.J., Robb G.B., Rana T.M.
PLoS Pathog. 2:E41-E41(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH APOBEC3G.
[23]"AU-rich-element-mediated upregulation of translation by FXR1 and Argonaute 2."
Vasudevan S., Steitz J.A.
Cell 128:1105-1118(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH FXR1, SUBCELLULAR LOCATION.
[24]"An mRNA m7G cap binding-like motif within human Ago2 represses translation."
Kiriakidou M., Tan G.S., Lamprinaki S., De Planell-Saguer M., Nelson P.T., Mourelatos Z.
Cell 129:1141-1151(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF PHE-470 AND PHE-505.
[25]"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: FUNCTION, ASSOCIATION WITH POLYSOMES AND MNRP, INTERACTION WITH DDB1; DDX5; DHX30; DHX36; DDX47; ELAVL1; HNRNPF; IGF2BP1; ILF3; MATR3; PABPC1; RBM4; SART3; UPF1 AND YBX1.
[26]"RNA helicase A interacts with RISC in human cells and functions in RISC loading."
Robb G.B., Rana T.M.
Mol. Cell 26:523-537(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DHX9.
[27]"MicroRNA silencing through RISC recruitment of eIF6."
Chendrimada T.P., Finn K.J., Ji X., Baillat D., Gregory R.I., Liebhaber S.A., Pasquinelli A.E., Shiekhattar R.
Nature 447:823-828(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH DICER1; EIF6; MOV10 AND TARBP2, ASSOCIATION WITH THE 60S RIBOSOME.
[28]"Switching from repression to activation: microRNAs can up-regulate translation."
Vasudevan S., Tong Y., Steitz J.A.
Science 318:1931-1934(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[29]"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, MUTAGENESIS OF ASP-597.
[30]"Prolyl 4-hydroxylation regulates Argonaute 2 stability."
Qi H.H., Ongusaha P.P., Myllyharju J., Cheng D., Pakkanen O., Shi Y., Lee S.W., Peng J., Shi Y.
Nature 455:421-424(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DICER1; P4HA1; P4HB; TNRC6A AND TNRC6B, SUBCELLULAR LOCATION, HYDROXYLATION AT PRO-700, MUTAGENESIS OF PRO-700.
[31]"In vitro reconstitution of the human RISC-loading complex."
MacRae I.J., Ma E., Zhou M., Robinson C.V., Doudna J.A.
Proc. Natl. Acad. Sci. U.S.A. 105:512-517(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DICER1 AND TARBP2.
[32]"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: FUNCTION, INTERACTION WITH IMP8, SUBCELLULAR LOCATION.
[33]"RNA-binding motif protein 4 translocates to cytoplasmic granules and suppresses translation via argonaute2 during muscle cell differentiation."
Lin J.C., Tarn W.Y.
J. Biol. Chem. 284:34658-34665(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RBM4.
[34]"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.
[35]"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].
[36]"GW182 proteins directly recruit cytoplasmic deadenylase complexes to miRNA targets."
Braun J.E., Huntzinger E., Fauser M., Izaurralde E.
Mol. Cell 44:120-133(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TNRC6C, MUTAGENESIS OF PHE-470 AND PHE-505.
[37]"APOBEC3G inhibits microRNA-mediated repression of translation by interfering with the interaction between Argonaute-2 and MOV10."
Liu C., Zhang X., Huang F., Yang B., Li J., Liu B., Luo H., Zhang P., Zhang H.
J. Biol. Chem. 287:29373-29383(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MOV10.
[38]"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: SUBCELLULAR LOCATION, INTERACTION WITH APOBEC3A; APOBEC3C; APOBEC3F; APOBEC3G AND APOBEC3H.
[39]"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: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF GLU-673; PHE-676 AND HIS-807.
[40]"Structural basis for 5'-nucleotide base-specific recognition of guide RNA by human AGO2."
Frank F., Sonenberg N., Nagar B.
Nature 465:818-822(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.69 ANGSTROMS) OF 439-575 IN COMPLEX WITH AMP; CMP; GMP AND PHOSPHATE.
[41]"Structural analysis of 5'-mRNA-cap interactions with the human AGO2 MID domain."
Frank F., Fabian M.R., Stepinski J., Jemielity J., Darzynkiewicz E., Sonenberg N., Nagar B.
EMBO Rep. 12:415-420(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 439-575 IN COMPLEX WITH 7-MGTPG AND ATP.
[42]"The structure of human argonaute-2 in complex with miR-20a."
Elkayam E., Kuhn C.D., Tocilj A., Haase A.D., Greene E.M., Hannon G.J., Joshua-Tor L.
Cell 150:100-110(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH MIRNA-20A, GUIDE RNA-BINDING.
[43]"The crystal structure of human Argonaute2."
Schirle N.T., MacRae I.J.
Science 336:1037-1040(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH RNA AND L-TRYPTOPHAN, GUIDE RNA-BINDING.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AC067931 Genomic DNA. No translation available.
AC107375 Genomic DNA. No translation available.
BC007633 mRNA. Translation: AAH07633.1. Different initiation.
BC018727 mRNA. Translation: AAH18727.2.
BC125214 mRNA. No translation available.
AY077717 mRNA. Translation: AAL76093.1. Sequence problems.
BT007229 mRNA. Translation: AAP35893.1.
AF121255 mRNA. Translation: AAF13034.2.
RefSeqNP_001158095.1. NM_001164623.1.
NP_036286.2. NM_012154.3.
UniGeneHs.743313.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3LUCX-ray1.69A/B/C439-575[»]
3LUDX-ray2.10A/B/C439-575[»]
3LUGX-ray1.85A/B/C439-575[»]
3LUHX-ray2.00A/B/C439-575[»]
3LUJX-ray1.80A/B/C439-575[»]
3LUKX-ray1.70A/B/C439-575[»]
3QX8X-ray2.30A/B/C439-575[»]
3QX9X-ray2.00A/B/C439-575[»]
4F3TX-ray2.25A1-859[»]
4OLAX-ray2.30A1-859[»]
4OLBX-ray2.90A1-859[»]
DisProtDP00736.
ProteinModelPortalQ9UKV8.
SMRQ9UKV8. Positions 23-859.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118041. 60 interactions.
DIPDIP-29194N.
IntActQ9UKV8. 173 interactions.
MINTMINT-1957975.

PTM databases

PhosphoSiteQ9UKV8.

Polymorphism databases

DMDM229463006.

Proteomic databases

PaxDbQ9UKV8.
PRIDEQ9UKV8.

Protocols and materials databases

DNASU27161.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000220592; ENSP00000220592; ENSG00000123908. [Q9UKV8-1]
ENST00000519980; ENSP00000430176; ENSG00000123908. [Q9UKV8-2]
GeneID27161.
KEGGhsa:27161.
UCSCuc003yvn.3. human. [Q9UKV8-1]
uc010meo.3. human. [Q9UKV8-2]

Organism-specific databases

CTD27161.
GeneCardsGC08M141542.
HGNCHGNC:3263. AGO2.
HPACAB019309.
MIM606229. gene.
neXtProtNX_Q9UKV8.
PharmGKBPA27694.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG279895.
HOGENOMHOG000116043.
InParanoidQ9UKV8.
KOK11593.
OMAVQGYAFK.
OrthoDBEOG7HHWRC.
PhylomeDBQ9UKV8.
TreeFamTF101510.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpressQ9UKV8.
BgeeQ9UKV8.
CleanExHS_EIF2C2.
GenevestigatorQ9UKV8.

Family and domain databases

Gene3D3.30.420.10. 1 hit.
HAMAPMF_03031. AGO2.
InterProIPR028602. AGO2.
IPR014811. 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

ChiTaRSEIF2C2. human.
EvolutionaryTraceQ9UKV8.
GeneWikiEIF2C2.
GenomeRNAi27161.
NextBio49946.
PROQ9UKV8.
SOURCESearch...

Entry information

Entry nameAGO2_HUMAN
AccessionPrimary (citable) accession number: Q9UKV8
Secondary accession number(s): Q8TCZ5, Q8WV58, Q96ID1
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 5, 2009
Last modified: April 16, 2014
This is version 127 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 8

Human chromosome 8: entries, gene names and cross-references to MIM