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Q9UKV8

- AGO2_HUMAN

UniProt

Q9UKV8 - AGO2_HUMAN

Protein

Protein argonaute-2

Gene

AGO2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 132 (01 Oct 2014)
      Sequence version 3 (05 May 2009)
      Previous versions | rss
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    Functioni

    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.23 Publications

    Catalytic activityi

    Endonucleolytic cleavage to 5'-phosphomonoester.2 PublicationsUniRule annotation

    Cofactori

    Magnesium or manganese.1 Publication

    Enzyme regulationi

    Inhibited by EDTA.1 Publication

    Kineticsi

    1. KM=1.1 nM for a synthetic 21-nucleotide single-stranded RNA2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi597 – 5971Divalent metal cationCurated
    Metal bindingi669 – 6691Divalent metal cationCurated
    Metal bindingi807 – 8071Divalent metal cationCurated

    GO - Molecular functioni

    1. endoribonuclease activity Source: Reactome
    2. endoribonuclease activity, cleaving siRNA-paired mRNA Source: UniProtKB
    3. metal ion binding Source: UniProtKB-KW
    4. miRNA binding Source: UniProtKB-HAMAP
    5. mRNA binding Source: Ensembl
    6. poly(A) RNA binding Source: UniProtKB
    7. protein binding Source: UniProtKB
    8. RNA 7-methylguanosine cap binding Source: UniProtKB
    9. siRNA binding Source: UniProtKB
    10. translation initiation factor activity Source: UniProtKB

    GO - Biological processi

    1. epidermal growth factor receptor signaling pathway Source: Reactome
    2. Fc-epsilon receptor signaling pathway Source: Reactome
    3. fibroblast growth factor receptor signaling pathway Source: Reactome
    4. gene expression Source: Reactome
    5. gene silencing by RNA Source: UniProtKB
    6. innate immune response Source: Reactome
    7. mRNA cleavage involved in gene silencing by miRNA Source: UniProtKB
    8. negative regulation of translational initiation Source: UniProtKB
    9. negative regulation of translation involved in gene silencing by miRNA Source: UniProtKB
    10. neurotrophin TRK receptor signaling pathway Source: Reactome
    11. Notch signaling pathway Source: Reactome
    12. phosphatidylinositol-mediated signaling Source: Reactome
    13. positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay Source: UniProtKB
    14. positive regulation of nuclear-transcribed mRNA poly(A) tail shortening Source: UniProtKB
    15. post-embryonic development Source: Ensembl
    16. pre-miRNA processing Source: UniProtKB
    17. regulation of transcription, DNA-templated Source: UniProtKB-KW
    18. RNA phosphodiester bond hydrolysis, endonucleolytic Source: GOC
    19. transcription, DNA-templated Source: UniProtKB-KW
    20. translation Source: UniProtKB
    21. translational initiation Source: GOC

    Keywords - Molecular functioni

    Endonuclease, Hydrolase, Nuclease, Repressor, Ribonucleoprotein

    Keywords - Biological processi

    RNA-mediated gene silencing, Transcription, Transcription regulation, Translation regulation

    Keywords - Ligandi

    Magnesium, Manganese, Metal-binding, RNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_118560. Small interfering RNA (siRNA) biogenesis.
    REACT_118568. Pre-NOTCH Transcription and Translation.
    REACT_118699. Post-transcriptional silencing by small RNAs.
    REACT_12417. MicroRNA (miRNA) biogenesis.
    REACT_172761. Ca2+ pathway.
    REACT_75829. PIP3 activates AKT signaling.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Protein argonaute-2UniRule annotation (EC:3.1.26.n2UniRule annotation)
    Short name:
    Argonaute2UniRule annotation
    Short name:
    hAgo2
    Alternative name(s):
    Argonaute RISC catalytic component 2
    Eukaryotic translation initiation factor 2C 2UniRule annotation
    Short name:
    eIF-2C 2UniRule annotation
    Short name:
    eIF2C 2UniRule annotation
    PAZ Piwi domain protein
    Short name:
    PPD
    Protein slicerUniRule annotation
    Gene namesi
    Name:AGO2
    Synonyms:EIF2C2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 8

    Organism-specific databases

    HGNCiHGNC:3263. AGO2.

    Subcellular locationi

    CytoplasmP-body. Nucleus
    Note: Translational repression of mRNAs results in their recruitment to P-bodies. Translocation to the nucleus requires IMP8.

    GO - Cellular componenti

    1. cytoplasm Source: MGI
    2. cytoplasmic mRNA processing body Source: UniProtKB
    3. cytosol Source: Reactome
    4. membrane Source: UniProtKB
    5. micro-ribonucleoprotein complex Source: UniProtKB
    6. mRNA cap binding complex Source: UniProtKB
    7. nucleus Source: UniProtKB-SubCell
    8. polysome Source: UniProtKB
    9. ribonucleoprotein complex Source: UniProtKB
    10. RISC complex Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi140 – 1401L → W: No effect. 1 Publication
    Mutagenesisi470 – 4701F → 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. 2 Publications
    Mutagenesisi470 – 4701F → W: No effect on binding to the 7-methylguanosine cap of mRNA or inhibition of translation. 2 Publications
    Mutagenesisi505 – 5051F → 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. 2 Publications
    Mutagenesisi505 – 5051F → W: No effect on binding to the 7-methylguanosine cap of mRNA or inhibition of translation. 2 Publications
    Mutagenesisi533 – 5331K → A: Impairs RNA cleavage. 1 Publication
    Mutagenesisi545 – 5451Q → A: Impairs RNA cleavage. 1 Publication
    Mutagenesisi570 – 5701K → A: Impairs RNA cleavage. 1 Publication
    Mutagenesisi597 – 5971D → A: Abrogates RNA cleavage but does not affect binding to siRNA or translational repression. 3 Publications
    Mutagenesisi633 – 6331Q → A: No effect. 1 Publication
    Mutagenesisi633 – 6331Q → R: Abrogates RNA cleavage. Binds siRNA. 1 Publication
    Mutagenesisi634 – 6341H → P or A: Abrogates RNA cleavage. Binds siRNA. 1 Publication
    Mutagenesisi669 – 6691D → A: Abrogates RNA cleavage but does not affect binding to siRNA. 3 Publications
    Mutagenesisi673 – 6731E → A: Impairs RNA cleavage. 2 Publications
    Mutagenesisi673 – 6731E → G: No effect on RNA cleavage. 2 Publications
    Mutagenesisi676 – 6761F → A, I, M, R or Y: Impairs RNA cleavage. 1 Publication
    Mutagenesisi676 – 6761F → V: Abrogates RNA cleavage. 1 Publication
    Mutagenesisi682 – 6821H → Y: No effect. 1 Publication
    Mutagenesisi683 – 6831E → G: No effect on RNA cleavage. 1 Publication
    Mutagenesisi700 – 7001P → A: Reduced protein stability. 1 Publication
    Mutagenesisi704 – 7041F → Y: No effect. 1 Publication
    Mutagenesisi744 – 7441T → Y: No effect. 1 Publication
    Mutagenesisi807 – 8071H → A or R: Abrogates RNA cleavage. 2 Publications

    Organism-specific databases

    PharmGKBiPA27694.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 859859Protein argonaute-2PRO_0000194057Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21Nitrated tyrosineUniRule annotation
    Modified residuei700 – 70014-hydroxyproline1 PublicationUniRule annotation

    Post-translational modificationi

    Hydroxylated. 4-hydroxylation appears to enhance protein stability but is not required for miRNA-binding or endonuclease activity.1 PublicationUniRule annotation

    Keywords - PTMi

    Hydroxylation, Nitration

    Proteomic databases

    MaxQBiQ9UKV8.
    PaxDbiQ9UKV8.
    PRIDEiQ9UKV8.

    PTM databases

    PhosphoSiteiQ9UKV8.

    Expressioni

    Gene expression databases

    ArrayExpressiQ9UKV8.
    BgeeiQ9UKV8.
    CleanExiHS_EIF2C2.
    GenevestigatoriQ9UKV8.

    Organism-specific databases

    HPAiCAB019309.

    Interactioni

    Subunit structurei

    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.25 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CNOT7Q9UIV12EBI-528269,EBI-2105113
    DHX58Q96C102EBI-528269,EBI-744193
    DICER1Q9UPY313EBI-528269,EBI-395506
    EIF4EBP1Q135412EBI-528269,EBI-74090
    FKBP4Q027902EBI-528269,EBI-1047444
    GNB2L1P632442EBI-528269,EBI-296739
    IPO8O153974EBI-528269,EBI-358808
    LRRK2Q5S0073EBI-528269,EBI-5323863
    PTGES3Q151853EBI-528269,EBI-1049387
    TARBP2Q156335EBI-528269,EBI-978581
    TBK1Q9UHD22EBI-528269,EBI-356402
    TBKBP1A7MCY62EBI-528269,EBI-359969
    TNRC6AQ8NDV710EBI-528269,EBI-2269715
    TNRC6BQ9UPQ912EBI-528269,EBI-947158
    TNRC6CQ9HCJ03EBI-528269,EBI-6507625
    ZMAT3Q9HA385EBI-528269,EBI-2548480

    Protein-protein interaction databases

    BioGridi118041. 83 interactions.
    DIPiDIP-29194N.
    IntActiQ9UKV8. 174 interactions.
    MINTiMINT-1957975.

    Structurei

    Secondary structure

    1
    859
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi35 – 4814
    Beta strandi53 – 6311
    Helixi68 – 8114
    Helixi83 – 875
    Beta strandi96 – 1049
    Turni107 – 1104
    Beta strandi112 – 1165
    Beta strandi128 – 13912
    Helixi140 – 1489
    Beta strandi151 – 1533
    Helixi156 – 17318
    Beta strandi174 – 1774
    Beta strandi180 – 1823
    Beta strandi191 – 1933
    Beta strandi196 – 20813
    Beta strandi210 – 22516
    Helixi230 – 2389
    Helixi252 – 26211
    Beta strandi266 – 2705
    Beta strandi278 – 28811
    Turni289 – 2913
    Beta strandi293 – 2975
    Beta strandi299 – 3013
    Beta strandi303 – 3075
    Helixi308 – 3169
    Beta strandi325 – 3317
    Turni333 – 3364
    Beta strandi337 – 3404
    Helixi341 – 3433
    Beta strandi344 – 3463
    Beta strandi348 – 3514
    Helixi358 – 36811
    Helixi372 – 38615
    Helixi388 – 3903
    Helixi392 – 3965
    Beta strandi406 – 4127
    Beta strandi422 – 4243
    Beta strandi450 – 4556
    Turni459 – 4613
    Helixi464 – 48118
    Beta strandi490 – 4945
    Helixi498 – 5003
    Helixi501 – 51111
    Beta strandi517 – 5226
    Helixi528 – 53710
    Turni538 – 5403
    Beta strandi544 – 5485
    Helixi549 – 5535
    Helixi557 – 57115
    Helixi585 – 5884
    Beta strandi591 – 5999
    Beta strandi610 – 6178
    Beta strandi619 – 6224
    Beta strandi625 – 6339
    Helixi642 – 65716
    Beta strandi662 – 6709
    Helixi673 – 6753
    Helixi676 – 69419
    Beta strandi701 – 7088
    Beta strandi715 – 7195
    Helixi720 – 7223
    Turni725 – 7284
    Beta strandi734 – 7363
    Beta strandi738 – 7414
    Beta strandi743 – 7453
    Beta strandi747 – 7515
    Beta strandi757 – 7593
    Beta strandi763 – 7708
    Helixi776 – 78611
    Beta strandi793 – 7953
    Helixi801 – 81717
    Helixi842 – 8454
    Helixi850 – 8534
    Turni854 – 8585

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    DisProtiDP00736.
    ProteinModelPortaliQ9UKV8.
    SMRiQ9UKV8. Positions 23-859.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9UKV8.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini235 – 348114PAZUniRule annotationAdd
    BLAST
    Domaini517 – 818302PiwiUniRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni311 – 3166Interaction with guide RNA
    Regioni524 – 56643Interaction with guide RNAAdd
    BLAST
    Regioni587 – 5904Interaction with GW182 family membersSequence Analysis
    Regioni650 – 66011Interaction with GW182 family membersSequence AnalysisAdd
    BLAST
    Regioni709 – 7102Interaction with guide RNA
    Regioni753 – 7619Interaction with guide RNA
    Regioni790 – 81223Interaction with guide RNAAdd
    BLAST

    Domaini

    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).

    Sequence similaritiesi

    Belongs to the argonaute family. Ago subfamily.UniRule annotation
    Contains 1 PAZ domain.UniRule annotation
    Contains 1 Piwi domain.UniRule annotation

    Phylogenomic databases

    eggNOGiNOG279895.
    HOGENOMiHOG000116043.
    InParanoidiQ9UKV8.
    KOiK11593.
    OMAiVQGYAFK.
    OrthoDBiEOG7HHWRC.
    PhylomeDBiQ9UKV8.
    TreeFamiTF101510.

    Family and domain databases

    Gene3Di3.30.420.10. 1 hit.
    HAMAPiMF_03031. AGO2.
    InterProiIPR028602. AGO2.
    IPR014811. DUF1785.
    IPR003100. PAZ_dom.
    IPR003165. Piwi.
    IPR012337. RNaseH-like_dom.
    [Graphical view]
    PfamiPF08699. DUF1785. 1 hit.
    PF02170. PAZ. 1 hit.
    PF02171. Piwi. 1 hit.
    [Graphical view]
    SMARTiSM00949. PAZ. 1 hit.
    SM00950. Piwi. 1 hit.
    [Graphical view]
    SUPFAMiSSF101690. SSF101690. 1 hit.
    SSF53098. SSF53098. 1 hit.
    PROSITEiPS50821. PAZ. 1 hit.
    PS50822. PIWI. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q9UKV8-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MYSGAGPALA PPAPPPPIQG YAFKPPPRPD FGTSGRTIKL QANFFEMDIP    50
    KIDIYHYELD IKPEKCPRRV NREIVEHMVQ HFKTQIFGDR KPVFDGRKNL 100
    YTAMPLPIGR DKVELEVTLP GEGKDRIFKV SIKWVSCVSL QALHDALSGR 150
    LPSVPFETIQ ALDVVMRHLP SMRYTPVGRS FFTASEGCSN PLGGGREVWF 200
    GFHQSVRPSL WKMMLNIDVS ATAFYKAQPV IEFVCEVLDF KSIEEQQKPL 250
    TDSQRVKFTK EIKGLKVEIT HCGQMKRKYR VCNVTRRPAS HQTFPLQQES 300
    GQTVECTVAQ YFKDRHKLVL RYPHLPCLQV GQEQKHTYLP LEVCNIVAGQ 350
    RCIKKLTDNQ TSTMIRATAR SAPDRQEEIS KLMRSASFNT DPYVREFGIM 400
    VKDEMTDVTG RVLQPPSILY GGRNKAIATP VQGVWDMRNK QFHTGIEIKV 450
    WAIACFAPQR QCTEVHLKSF TEQLRKISRD AGMPIQGQPC FCKYAQGADS 500
    VEPMFRHLKN TYAGLQLVVV ILPGKTPVYA EVKRVGDTVL GMATQCVQMK 550
    NVQRTTPQTL SNLCLKINVK LGGVNNILLP QGRPPVFQQP VIFLGADVTH 600
    PPAGDGKKPS IAAVVGSMDA HPNRYCATVR VQQHRQEIIQ DLAAMVRELL 650
    IQFYKSTRFK PTRIIFYRDG VSEGQFQQVL HHELLAIREA CIKLEKDYQP 700
    GITFIVVQKR HHTRLFCTDK NERVGKSGNI PAGTTVDTKI THPTEFDFYL 750
    CSHAGIQGTS RPSHYHVLWD DNRFSSDELQ ILTYQLCHTY VRCTRSVSIP 800
    APAYYAHLVA FRARYHLVDK EHDSAEGSHT SGQSNGRDHQ ALAKAVQVHQ 850
    DTLRTMYFA 859
    Length:859
    Mass (Da):97,208
    Last modified:May 5, 2009 - v3
    Checksum:i5C8552C43FC81345
    GO
    Isoform 2 (identifier: Q9UKV8-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         724-757: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:825
    Mass (Da):93,620
    Checksum:i464C15B9413608D4
    GO

    Sequence cautioni

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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti564 – 5641C → W in AAF13034. (PubMed:10534406)Curated
    Sequence conflicti589 – 5891Q → E in AAF13034. (PubMed:10534406)Curated
    Sequence conflicti617 – 6171S → R in AAF13034. (PubMed:10534406)Curated
    Sequence conflicti637 – 6371E → K in AAL76093. (PubMed:11914277)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei724 – 75734Missing in isoform 2. 1 PublicationVSP_037001Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS55279.1. [Q9UKV8-2]
    CCDS6380.1. [Q9UKV8-1]
    RefSeqiNP_001158095.1. NM_001164623.1. [Q9UKV8-2]
    NP_036286.2. NM_012154.3. [Q9UKV8-1]
    UniGeneiHs.743313.

    Genome annotation databases

    EnsembliENST00000220592; ENSP00000220592; ENSG00000123908. [Q9UKV8-1]
    ENST00000519980; ENSP00000430176; ENSG00000123908. [Q9UKV8-2]
    GeneIDi27161.
    KEGGihsa:27161.
    UCSCiuc003yvn.3. human. [Q9UKV8-1]
    uc010meo.3. human. [Q9UKV8-2]

    Polymorphism databases

    DMDMi229463006.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS55279.1. [Q9UKV8-2 ]
    CCDS6380.1. [Q9UKV8-1 ]
    RefSeqi NP_001158095.1. NM_001164623.1. [Q9UKV8-2 ]
    NP_036286.2. NM_012154.3. [Q9UKV8-1 ]
    UniGenei Hs.743313.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3LUC X-ray 1.69 A/B/C 439-575 [» ]
    3LUD X-ray 2.10 A/B/C 439-575 [» ]
    3LUG X-ray 1.85 A/B/C 439-575 [» ]
    3LUH X-ray 2.00 A/B/C 439-575 [» ]
    3LUJ X-ray 1.80 A/B/C 439-575 [» ]
    3LUK X-ray 1.70 A/B/C 439-575 [» ]
    3QX8 X-ray 2.30 A/B/C 439-575 [» ]
    3QX9 X-ray 2.00 A/B/C 439-575 [» ]
    4F3T X-ray 2.25 A 1-859 [» ]
    4OLA X-ray 2.30 A 1-859 [» ]
    4OLB X-ray 2.90 A 1-859 [» ]
    DisProti DP00736.
    ProteinModelPortali Q9UKV8.
    SMRi Q9UKV8. Positions 23-859.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 118041. 83 interactions.
    DIPi DIP-29194N.
    IntActi Q9UKV8. 174 interactions.
    MINTi MINT-1957975.

    PTM databases

    PhosphoSitei Q9UKV8.

    Polymorphism databases

    DMDMi 229463006.

    Proteomic databases

    MaxQBi Q9UKV8.
    PaxDbi Q9UKV8.
    PRIDEi Q9UKV8.

    Protocols and materials databases

    DNASUi 27161.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000220592 ; ENSP00000220592 ; ENSG00000123908 . [Q9UKV8-1 ]
    ENST00000519980 ; ENSP00000430176 ; ENSG00000123908 . [Q9UKV8-2 ]
    GeneIDi 27161.
    KEGGi hsa:27161.
    UCSCi uc003yvn.3. human. [Q9UKV8-1 ]
    uc010meo.3. human. [Q9UKV8-2 ]

    Organism-specific databases

    CTDi 27161.
    GeneCardsi GC08M141542.
    HGNCi HGNC:3263. AGO2.
    HPAi CAB019309.
    MIMi 606229. gene.
    neXtProti NX_Q9UKV8.
    PharmGKBi PA27694.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG279895.
    HOGENOMi HOG000116043.
    InParanoidi Q9UKV8.
    KOi K11593.
    OMAi VQGYAFK.
    OrthoDBi EOG7HHWRC.
    PhylomeDBi Q9UKV8.
    TreeFami TF101510.

    Enzyme and pathway databases

    Reactomei REACT_118560. Small interfering RNA (siRNA) biogenesis.
    REACT_118568. Pre-NOTCH Transcription and Translation.
    REACT_118699. Post-transcriptional silencing by small RNAs.
    REACT_12417. MicroRNA (miRNA) biogenesis.
    REACT_172761. Ca2+ pathway.
    REACT_75829. PIP3 activates AKT signaling.

    Miscellaneous databases

    ChiTaRSi EIF2C2. human.
    EvolutionaryTracei Q9UKV8.
    GeneWikii EIF2C2.
    GenomeRNAii 27161.
    NextBioi 49946.
    PROi Q9UKV8.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9UKV8.
    Bgeei Q9UKV8.
    CleanExi HS_EIF2C2.
    Genevestigatori Q9UKV8.

    Family and domain databases

    Gene3Di 3.30.420.10. 1 hit.
    HAMAPi MF_03031. AGO2.
    InterProi IPR028602. AGO2.
    IPR014811. DUF1785.
    IPR003100. PAZ_dom.
    IPR003165. Piwi.
    IPR012337. RNaseH-like_dom.
    [Graphical view ]
    Pfami PF08699. DUF1785. 1 hit.
    PF02170. PAZ. 1 hit.
    PF02171. Piwi. 1 hit.
    [Graphical view ]
    SMARTi SM00949. PAZ. 1 hit.
    SM00950. Piwi. 1 hit.
    [Graphical view ]
    SUPFAMi SSF101690. SSF101690. 1 hit.
    SSF53098. SSF53098. 1 hit.
    PROSITEi PS50821. PAZ. 1 hit.
    PS50822. PIWI. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. 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. 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. 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. 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. 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. Cited for: FUNCTION, INTERACTION WITH DICER1; P4HA1; P4HB; TNRC6A AND TNRC6B, SUBCELLULAR LOCATION, HYDROXYLATION AT PRO-700, MUTAGENESIS OF PRO-700.
    31. 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. Cited for: SUBCELLULAR LOCATION, INTERACTION WITH LIMD1; WTIP AND AJUBA.
    35. 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.

    Entry informationi

    Entry nameiAGO2_HUMAN
    AccessioniPrimary (citable) accession number: Q9UKV8
    Secondary accession number(s): Q8TCZ5, Q8WV58, Q96ID1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: May 5, 2009
    Last modified: October 1, 2014
    This is version 132 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 8
      Human chromosome 8: entries, gene names and cross-references to MIM
    2. Translation initiation factors
      List of translation initiation factor entries
    3. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    4. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3