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Protein

Protein argonaute-2

Gene

AGO2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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.UniRule annotation23 Publications

Catalytic activityi

Endonucleolytic cleavage to 5'-phosphomonoester.UniRule annotation2 Publications

Cofactori

Mg2+1 Publication, Mn2+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)DescriptionActionsGraphical viewLength
    Metal bindingi597Divalent metal cationCurated1
    Metal bindingi669Divalent metal cationCurated1
    Metal bindingi807Divalent metal cationCurated1

    GO - Molecular functioni

    • bidentate ribonuclease III activity Source: UniProtKB-EC
    • core promoter binding Source: BHF-UCL
    • double-stranded RNA binding Source: BHF-UCL
    • endoribonuclease activity Source: BHF-UCL
    • endoribonuclease activity, cleaving miRNA-paired mRNA Source: BHF-UCL
    • endoribonuclease activity, cleaving siRNA-paired mRNA Source: UniProtKB
    • metal ion binding Source: UniProtKB-KW
    • miRNA binding Source: BHF-UCL
    • mRNA binding Source: Ensembl
    • poly(A) RNA binding Source: UniProtKB
    • protein C-terminus binding Source: BHF-UCL
    • RNA 7-methylguanosine cap binding Source: UniProtKB
    • RNA polymerase II core binding Source: BHF-UCL
    • single-stranded RNA binding Source: BHF-UCL
    • siRNA binding Source: UniProtKB
    • translation initiation factor activity Source: UniProtKB

    GO - Biological processi

    Complete GO annotation...

    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

    BioCyciZFISH:ENSG00000123908-MONOMER.
    ReactomeiR-HSA-1257604. PIP3 activates AKT signaling.
    R-HSA-1912408. Pre-NOTCH Transcription and Translation.
    R-HSA-203927. MicroRNA (miRNA) biogenesis.
    R-HSA-4086398. Ca2+ pathway.
    R-HSA-426486. Small interfering RNA (siRNA) biogenesis.
    R-HSA-426496. Post-transcriptional silencing by small RNAs.
    R-HSA-5578749. Transcriptional regulation by small RNAs.
    R-HSA-5628897. TP53 Regulates Metabolic Genes.
    R-HSA-5687128. MAPK6/MAPK4 signaling.
    SIGNORiQ9UKV8.

    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
    Proteomesi
    • UP000005640 Componenti: 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

    • cytoplasm Source: BHF-UCL
    • cytoplasmic mRNA processing body Source: UniProtKB
    • cytosol Source: Reactome
    • dendrite Source: Ensembl
    • intracellular ribonucleoprotein complex Source: UniProtKB
    • membrane Source: UniProtKB
    • micro-ribonucleoprotein complex Source: UniProtKB
    • mRNA cap binding complex Source: UniProtKB
    • nucleoplasm Source: Reactome
    • nucleus Source: BHF-UCL
    • polysome Source: UniProtKB
    • RISC complex Source: BHF-UCL
    • RISC-loading complex Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi140L → W: No effect. 1 Publication1
    Mutagenesisi470F → 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 Publications1
    Mutagenesisi470F → W: No effect on binding to the 7-methylguanosine cap of mRNA or inhibition of translation. 2 Publications1
    Mutagenesisi505F → 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 Publications1
    Mutagenesisi505F → W: No effect on binding to the 7-methylguanosine cap of mRNA or inhibition of translation. 2 Publications1
    Mutagenesisi533K → A: Impairs RNA cleavage. 1 Publication1
    Mutagenesisi545Q → A: Impairs RNA cleavage. 1 Publication1
    Mutagenesisi570K → A: Impairs RNA cleavage. 1 Publication1
    Mutagenesisi597D → A: Abrogates RNA cleavage but does not affect binding to siRNA or translational repression. 3 Publications1
    Mutagenesisi633Q → A: No effect. 1 Publication1
    Mutagenesisi633Q → R: Abrogates RNA cleavage. Binds siRNA. 1 Publication1
    Mutagenesisi634H → P or A: Abrogates RNA cleavage. Binds siRNA. 1 Publication1
    Mutagenesisi669D → A: Abrogates RNA cleavage but does not affect binding to siRNA. 3 Publications1
    Mutagenesisi673E → A: Impairs RNA cleavage. 2 Publications1
    Mutagenesisi673E → G: No effect on RNA cleavage. 2 Publications1
    Mutagenesisi676F → A, I, M, R or Y: Impairs RNA cleavage. 1 Publication1
    Mutagenesisi676F → V: Abrogates RNA cleavage. 1 Publication1
    Mutagenesisi682H → Y: No effect. 1 Publication1
    Mutagenesisi683E → G: No effect on RNA cleavage. 1 Publication1
    Mutagenesisi700P → A: Reduced protein stability. 1 Publication1
    Mutagenesisi704F → Y: No effect. 1 Publication1
    Mutagenesisi744T → Y: No effect. 1 Publication1
    Mutagenesisi807H → A or R: Abrogates RNA cleavage. 2 Publications1

    Organism-specific databases

    DisGeNETi27161.
    OpenTargetsiENSG00000123908.
    PharmGKBiPA27694.

    Polymorphism and mutation databases

    BioMutaiAGO2.
    DMDMi229463006.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001940571 – 859Protein argonaute-2Add BLAST859

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei2Nitrated tyrosineUniRule annotationBy similarity1
    Modified residuei387PhosphoserineCombined sources1
    Modified residuei7004-hydroxyprolineUniRule annotation1 Publication1
    Modified residuei824PhosphoserineBy similarity1
    Modified residuei828PhosphoserineCombined sources1

    Post-translational modificationi

    Hydroxylated. 4-hydroxylation appears to enhance protein stability but is not required for miRNA-binding or endonuclease activity.UniRule annotation1 Publication

    Keywords - PTMi

    Hydroxylation, Nitration, Phosphoprotein

    Proteomic databases

    EPDiQ9UKV8.
    PaxDbiQ9UKV8.
    PeptideAtlasiQ9UKV8.
    PRIDEiQ9UKV8.

    PTM databases

    iPTMnetiQ9UKV8.
    PhosphoSitePlusiQ9UKV8.
    SwissPalmiQ9UKV8.

    Expressioni

    Gene expression databases

    BgeeiENSG00000123908.
    CleanExiHS_EIF2C2.
    ExpressionAtlasiQ9UKV8. baseline and differential.
    GenevisibleiQ9UKV8. HS.

    Organism-specific databases

    HPAiCAB019309.
    HPA058075.

    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, ELAVL, FXR1, GEMIN4, HNRNPF, IGF2BP1, ILF3, IMP8, MATR3, 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. Interacts with DICER1, TARBP2, EIF6, MOV10 and RPL7A (60S ribosome subunit); they form a large RNA-induced silencing complex (RISC) (PubMed:17507929). Interacts with FMR1 (PubMed:14703574). Interacts with ZFP36 (PubMed:15766526).UniRule annotation27 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CNOT7Q9UIV12EBI-528269,EBI-2105113
    DHX58Q96C102EBI-528269,EBI-744193
    DICER1Q9UPY319EBI-528269,EBI-395506
    EIF4EBP1Q135412EBI-528269,EBI-74090
    FKBP4Q027902EBI-528269,EBI-1047444
    GNL3Q9BVP23EBI-528269,EBI-641642
    IPO8O153974EBI-528269,EBI-358808
    LRRK2Q5S0073EBI-528269,EBI-5323863
    MTDHQ86UE43EBI-528269,EBI-1046588
    PRKRAO755695EBI-528269,EBI-713955
    PTGES3Q151853EBI-528269,EBI-1049387
    RACK1P632442EBI-528269,EBI-296739
    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

    GO - Molecular functioni

    • protein C-terminus binding Source: BHF-UCL
    • RNA polymerase II core binding Source: BHF-UCL

    Protein-protein interaction databases

    BioGridi118041. 90 interactors.
    DIPiDIP-29194N.
    IntActiQ9UKV8. 178 interactors.
    MINTiMINT-1957975.
    STRINGi9606.ENSP00000220592.

    Structurei

    Secondary structure

    1859
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi35 – 48Combined sources14
    Beta strandi53 – 63Combined sources11
    Helixi68 – 81Combined sources14
    Turni82 – 86Combined sources5
    Beta strandi96 – 104Combined sources9
    Turni107 – 110Combined sources4
    Beta strandi113 – 117Combined sources5
    Beta strandi122 – 124Combined sources3
    Beta strandi128 – 139Combined sources12
    Helixi140 – 147Combined sources8
    Beta strandi150 – 153Combined sources4
    Helixi156 – 167Combined sources12
    Helixi170 – 173Combined sources4
    Beta strandi174 – 177Combined sources4
    Beta strandi180 – 183Combined sources4
    Beta strandi191 – 193Combined sources3
    Beta strandi196 – 207Combined sources12
    Beta strandi210 – 225Combined sources16
    Helixi230 – 238Combined sources9
    Helixi243 – 245Combined sources3
    Helixi252 – 262Combined sources11
    Beta strandi266 – 268Combined sources3
    Beta strandi278 – 288Combined sources11
    Turni289 – 291Combined sources3
    Beta strandi293 – 297Combined sources5
    Beta strandi299 – 301Combined sources3
    Beta strandi303 – 307Combined sources5
    Helixi308 – 316Combined sources9
    Beta strandi325 – 331Combined sources7
    Turni333 – 336Combined sources4
    Beta strandi337 – 340Combined sources4
    Helixi341 – 343Combined sources3
    Beta strandi344 – 346Combined sources3
    Beta strandi348 – 351Combined sources4
    Helixi358 – 368Combined sources11
    Helixi372 – 386Combined sources15
    Helixi388 – 390Combined sources3
    Helixi392 – 396Combined sources5
    Beta strandi406 – 412Combined sources7
    Turni422 – 425Combined sources4
    Beta strandi450 – 455Combined sources6
    Turni459 – 461Combined sources3
    Helixi464 – 480Combined sources17
    Beta strandi490 – 494Combined sources5
    Helixi498 – 500Combined sources3
    Helixi501 – 511Combined sources11
    Beta strandi517 – 522Combined sources6
    Helixi528 – 537Combined sources10
    Turni538 – 540Combined sources3
    Beta strandi544 – 548Combined sources5
    Helixi550 – 553Combined sources4
    Helixi557 – 570Combined sources14
    Helixi580 – 582Combined sources3
    Helixi585 – 588Combined sources4
    Beta strandi591 – 599Combined sources9
    Turni603 – 605Combined sources3
    Beta strandi610 – 617Combined sources8
    Beta strandi619 – 622Combined sources4
    Beta strandi625 – 633Combined sources9
    Helixi642 – 657Combined sources16
    Beta strandi662 – 669Combined sources8
    Helixi673 – 675Combined sources3
    Helixi676 – 694Combined sources19
    Beta strandi701 – 709Combined sources9
    Beta strandi710 – 712Combined sources3
    Beta strandi715 – 719Combined sources5
    Helixi720 – 722Combined sources3
    Turni725 – 728Combined sources4
    Beta strandi734 – 736Combined sources3
    Beta strandi738 – 741Combined sources4
    Beta strandi743 – 745Combined sources3
    Beta strandi747 – 751Combined sources5
    Beta strandi757 – 759Combined sources3
    Beta strandi763 – 770Combined sources8
    Helixi776 – 786Combined sources11
    Beta strandi793 – 795Combined sources3
    Helixi801 – 816Combined sources16
    Turni817 – 820Combined sources4
    Helixi837 – 846Combined sources10
    Turni850 – 854Combined sources5

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB 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[»]
    4W5NX-ray2.90A1-859[»]
    4W5OX-ray1.80A1-859[»]
    4W5QX-ray3.10A1-859[»]
    4W5RX-ray2.50A1-859[»]
    4W5TX-ray2.50A1-859[»]
    4Z4CX-ray2.30A1-859[»]
    4Z4DX-ray1.60A1-859[»]
    4Z4EX-ray1.80A1-859[»]
    4Z4FX-ray2.80A1-859[»]
    4Z4GX-ray2.70A1-859[»]
    4Z4HX-ray2.50A1-859[»]
    4Z4IX-ray2.80A1-859[»]
    5JS1X-ray2.50A1-859[»]
    5JS2X-ray2.95A1-859[»]
    5KI6X-ray2.15A1-859[»]
    DisProtiDP00736.
    ProteinModelPortaliQ9UKV8.
    SMRiQ9UKV8.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9UKV8.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini235 – 348PAZUniRule annotationAdd BLAST114
    Domaini517 – 818PiwiUniRule annotationAdd BLAST302

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni311 – 316Interaction with guide RNA6
    Regioni524 – 566Interaction with guide RNAAdd BLAST43
    Regioni587 – 590Interaction with GW182 family membersSequence analysis4
    Regioni650 – 660Interaction with GW182 family membersSequence analysisAdd BLAST11
    Regioni709 – 710Interaction with guide RNA2
    Regioni753 – 761Interaction with guide RNA9
    Regioni790 – 812Interaction with guide RNAAdd BLAST23

    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

    eggNOGiKOG1041. Eukaryota.
    ENOG410XP07. LUCA.
    GeneTreeiENSGT00760000119148.
    HOGENOMiHOG000116043.
    InParanoidiQ9UKV8.
    KOiK11593.
    OMAiIPGYAFK.
    OrthoDBiEOG091G020J.
    PhylomeDBiQ9UKV8.
    TreeFamiTF101510.

    Family and domain databases

    Gene3Di3.30.420.10. 1 hit.
    HAMAPiMF_03031. AGO2. 1 hit.
    InterProiIPR028602. AGO2.
    IPR014811. ArgoL1.
    IPR032472. ArgoL2.
    IPR032473. Argonaute_Mid_dom.
    IPR032474. Argonaute_N.
    IPR003100. PAZ_dom.
    IPR003165. Piwi.
    IPR012337. RNaseH-like_dom.
    [Graphical view]
    PfamiPF08699. ArgoL1. 1 hit.
    PF16488. ArgoL2. 1 hit.
    PF16487. ArgoMid. 1 hit.
    PF16486. ArgoN. 1 hit.
    PF02170. PAZ. 1 hit.
    PF02171. Piwi. 1 hit.
    [Graphical view]
    SMARTiSM01163. DUF1785. 1 hit.
    SM00949. 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. AlignAdd to basket

    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

            10         20         30         40         50
    MYSGAGPALA PPAPPPPIQG YAFKPPPRPD FGTSGRTIKL QANFFEMDIP
    60 70 80 90 100
    KIDIYHYELD IKPEKCPRRV NREIVEHMVQ HFKTQIFGDR KPVFDGRKNL
    110 120 130 140 150
    YTAMPLPIGR DKVELEVTLP GEGKDRIFKV SIKWVSCVSL QALHDALSGR
    160 170 180 190 200
    LPSVPFETIQ ALDVVMRHLP SMRYTPVGRS FFTASEGCSN PLGGGREVWF
    210 220 230 240 250
    GFHQSVRPSL WKMMLNIDVS ATAFYKAQPV IEFVCEVLDF KSIEEQQKPL
    260 270 280 290 300
    TDSQRVKFTK EIKGLKVEIT HCGQMKRKYR VCNVTRRPAS HQTFPLQQES
    310 320 330 340 350
    GQTVECTVAQ YFKDRHKLVL RYPHLPCLQV GQEQKHTYLP LEVCNIVAGQ
    360 370 380 390 400
    RCIKKLTDNQ TSTMIRATAR SAPDRQEEIS KLMRSASFNT DPYVREFGIM
    410 420 430 440 450
    VKDEMTDVTG RVLQPPSILY GGRNKAIATP VQGVWDMRNK QFHTGIEIKV
    460 470 480 490 500
    WAIACFAPQR QCTEVHLKSF TEQLRKISRD AGMPIQGQPC FCKYAQGADS
    510 520 530 540 550
    VEPMFRHLKN TYAGLQLVVV ILPGKTPVYA EVKRVGDTVL GMATQCVQMK
    560 570 580 590 600
    NVQRTTPQTL SNLCLKINVK LGGVNNILLP QGRPPVFQQP VIFLGADVTH
    610 620 630 640 650
    PPAGDGKKPS IAAVVGSMDA HPNRYCATVR VQQHRQEIIQ DLAAMVRELL
    660 670 680 690 700
    IQFYKSTRFK PTRIIFYRDG VSEGQFQQVL HHELLAIREA CIKLEKDYQP
    710 720 730 740 750
    GITFIVVQKR HHTRLFCTDK NERVGKSGNI PAGTTVDTKI THPTEFDFYL
    760 770 780 790 800
    CSHAGIQGTS RPSHYHVLWD DNRFSSDELQ ILTYQLCHTY VRCTRSVSIP
    810 820 830 840 850
    APAYYAHLVA FRARYHLVDK EHDSAEGSHT SGQSNGRDHQ ALAKAVQVHQ

    DTLRTMYFA
    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 AAH07633 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
    The sequence AAL76093 differs from that shown. cDNA contains a duplication of an internal sequence at the 5' end.Curated
    The sequence BC125214 differs from that shown. Reason: Frameshift at position 450.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti564C → W in AAF13034 (PubMed:10534406).Curated1
    Sequence conflicti589Q → E in AAF13034 (PubMed:10534406).Curated1
    Sequence conflicti617S → R in AAF13034 (PubMed:10534406).Curated1
    Sequence conflicti637E → K in AAL76093 (PubMed:11914277).Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_037001724 – 757Missing in isoform 2. 1 PublicationAdd BLAST34

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    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.
    UCSCiuc003yvm.5. human. [Q9UKV8-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    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.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB 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[»]
    4W5NX-ray2.90A1-859[»]
    4W5OX-ray1.80A1-859[»]
    4W5QX-ray3.10A1-859[»]
    4W5RX-ray2.50A1-859[»]
    4W5TX-ray2.50A1-859[»]
    4Z4CX-ray2.30A1-859[»]
    4Z4DX-ray1.60A1-859[»]
    4Z4EX-ray1.80A1-859[»]
    4Z4FX-ray2.80A1-859[»]
    4Z4GX-ray2.70A1-859[»]
    4Z4HX-ray2.50A1-859[»]
    4Z4IX-ray2.80A1-859[»]
    5JS1X-ray2.50A1-859[»]
    5JS2X-ray2.95A1-859[»]
    5KI6X-ray2.15A1-859[»]
    DisProtiDP00736.
    ProteinModelPortaliQ9UKV8.
    SMRiQ9UKV8.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi118041. 90 interactors.
    DIPiDIP-29194N.
    IntActiQ9UKV8. 178 interactors.
    MINTiMINT-1957975.
    STRINGi9606.ENSP00000220592.

    PTM databases

    iPTMnetiQ9UKV8.
    PhosphoSitePlusiQ9UKV8.
    SwissPalmiQ9UKV8.

    Polymorphism and mutation databases

    BioMutaiAGO2.
    DMDMi229463006.

    Proteomic databases

    EPDiQ9UKV8.
    PaxDbiQ9UKV8.
    PeptideAtlasiQ9UKV8.
    PRIDEiQ9UKV8.

    Protocols and materials databases

    DNASUi27161.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000220592; ENSP00000220592; ENSG00000123908. [Q9UKV8-1]
    ENST00000519980; ENSP00000430176; ENSG00000123908. [Q9UKV8-2]
    GeneIDi27161.
    KEGGihsa:27161.
    UCSCiuc003yvm.5. human. [Q9UKV8-1]

    Organism-specific databases

    CTDi27161.
    DisGeNETi27161.
    GeneCardsiAGO2.
    HGNCiHGNC:3263. AGO2.
    HPAiCAB019309.
    HPA058075.
    MIMi606229. gene.
    neXtProtiNX_Q9UKV8.
    OpenTargetsiENSG00000123908.
    PharmGKBiPA27694.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1041. Eukaryota.
    ENOG410XP07. LUCA.
    GeneTreeiENSGT00760000119148.
    HOGENOMiHOG000116043.
    InParanoidiQ9UKV8.
    KOiK11593.
    OMAiIPGYAFK.
    OrthoDBiEOG091G020J.
    PhylomeDBiQ9UKV8.
    TreeFamiTF101510.

    Enzyme and pathway databases

    BioCyciZFISH:ENSG00000123908-MONOMER.
    ReactomeiR-HSA-1257604. PIP3 activates AKT signaling.
    R-HSA-1912408. Pre-NOTCH Transcription and Translation.
    R-HSA-203927. MicroRNA (miRNA) biogenesis.
    R-HSA-4086398. Ca2+ pathway.
    R-HSA-426486. Small interfering RNA (siRNA) biogenesis.
    R-HSA-426496. Post-transcriptional silencing by small RNAs.
    R-HSA-5578749. Transcriptional regulation by small RNAs.
    R-HSA-5628897. TP53 Regulates Metabolic Genes.
    R-HSA-5687128. MAPK6/MAPK4 signaling.
    SIGNORiQ9UKV8.

    Miscellaneous databases

    EvolutionaryTraceiQ9UKV8.
    GeneWikiiEIF2C2.
    GenomeRNAii27161.
    PROiQ9UKV8.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000123908.
    CleanExiHS_EIF2C2.
    ExpressionAtlasiQ9UKV8. baseline and differential.
    GenevisibleiQ9UKV8. HS.

    Family and domain databases

    Gene3Di3.30.420.10. 1 hit.
    HAMAPiMF_03031. AGO2. 1 hit.
    InterProiIPR028602. AGO2.
    IPR014811. ArgoL1.
    IPR032472. ArgoL2.
    IPR032473. Argonaute_Mid_dom.
    IPR032474. Argonaute_N.
    IPR003100. PAZ_dom.
    IPR003165. Piwi.
    IPR012337. RNaseH-like_dom.
    [Graphical view]
    PfamiPF08699. ArgoL1. 1 hit.
    PF16488. ArgoL2. 1 hit.
    PF16487. ArgoMid. 1 hit.
    PF16486. ArgoN. 1 hit.
    PF02170. PAZ. 1 hit.
    PF02171. Piwi. 1 hit.
    [Graphical view]
    SMARTiSM01163. DUF1785. 1 hit.
    SM00949. 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]
    ProtoNetiSearch...

    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: November 30, 2016
    This is version 157 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

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.