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Protein

Protein argonaute-2

Gene

Ago2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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. Regulates lymphoid and erythroid development and function, and this is independent of endonuclease activity.UniRule annotation3 Publications

Catalytic activityi

Endonucleolytic cleavage to 5'-phosphomonoester.UniRule annotation

Cofactori

Mg2+By similarity, Mn2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi598Divalent metal cationUniRule annotation1
Metal bindingi670Divalent metal cationUniRule annotation1
Metal bindingi808Divalent metal cationUniRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Endonuclease, Hydrolase, Nuclease, Repressor, Ribonucleoprotein, RNA-binding
Biological processDifferentiation, RNA-mediated gene silencing, Transcription, Transcription regulation, Translation regulation
LigandMagnesium, Manganese, Metal-binding

Enzyme and pathway databases

ReactomeiR-MMU-203927 MicroRNA (miRNA) biogenesis
R-MMU-426486 Small interfering RNA (siRNA) biogenesis
R-MMU-426496 Post-transcriptional silencing by small RNAs
R-MMU-5578749 Transcriptional regulation by small RNAs

Names & Taxonomyi

Protein namesi
Recommended name:
Protein argonaute-2UniRule annotation (EC:3.1.26.n2UniRule annotation)
Short name:
Argonaute2UniRule annotation
Short name:
mAgo2
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
Piwi/argonaute family protein meIF2C2
Protein slicerUniRule annotation
Gene namesi
Name:Ago2
Synonyms:Eif2c2, Kiaa4215
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:2446632 Ago2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Embryonic death with a strong defect in neural tube closure and apparent cardiac failure.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001940581 – 860Protein argonaute-2Add BLAST860

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2Nitrated tyrosineCombined sources1
Modified residuei388PhosphoserineBy similarity1
Modified residuei7014-hydroxyprolineUniRule annotation1
Modified residuei829PhosphoserineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Hydroxylation, Nitration, Phosphoprotein

Proteomic databases

EPDiQ8CJG0
MaxQBiQ8CJG0
PaxDbiQ8CJG0
PeptideAtlasiQ8CJG0
PRIDEiQ8CJG0

PTM databases

iPTMnetiQ8CJG0
PhosphoSitePlusiQ8CJG0

Expressioni

Tissue specificityi

Ubiquitous expression in 9.5 day embryos with highest levels in forebrain, heart, limb buds, and branchial arches.1 Publication

Gene expression databases

BgeeiENSMUSG00000036698 Expressed in 246 organ(s), highest expression level in mesenteric lymph node
CleanExiMM_EIF2C2
GenevisibleiQ8CJG0 MM

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 (PubMed:16357216). 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 (By similarity). Interacts with TRIM71 (PubMed:19898466, PubMed:22508726, PubMed:22735451). 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). Interacts with FMR1. Interacts with ZFP36 (By similarity). Interacts with RC3H1; the interaction is RNA independent (PubMed:25697406). Interacts with FAM172A (PubMed:29311329). Found in a complex composed of AGO2, CHD7 and FAM172A (PubMed:29311329). Interacts with SND1 (By similarity).UniRule annotationBy similarity6 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi232092, 9 interactors
ComplexPortaliCPX-1073 RISC-loading complex, PRKRA variant
CPX-135 RISC-loading complex, TARBP2 variant
DIPiDIP-35014N
IntActiQ8CJG0, 55 interactors
STRINGi10090.ENSMUSP00000042207

Structurei

3D structure databases

ProteinModelPortaliQ8CJG0
SMRiQ8CJG0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini236 – 349PAZUniRule annotationAdd BLAST114
Domaini518 – 819PiwiUniRule annotationAdd BLAST302

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni312 – 317Interaction with guide RNABy similarity6
Regioni525 – 567Interaction with guide RNABy similarityAdd BLAST43
Regioni588 – 591Interaction with GW182 family membersSequence analysis4
Regioni651 – 661Interaction with GW182 family membersSequence analysisAdd BLAST11
Regioni710 – 711Interaction with guide RNABy similarity2
Regioni754 – 762Interaction with guide RNABy similarity9
Regioni791 – 813Interaction with guide RNABy similarityAdd 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).UniRule annotation

Sequence similaritiesi

Belongs to the argonaute family. Ago subfamily.UniRule annotation

Phylogenomic databases

eggNOGiKOG1041 Eukaryota
ENOG410XP07 LUCA
GeneTreeiENSGT00760000119148
HOGENOMiHOG000116043
HOVERGENiHBG006101
InParanoidiQ8CJG0
KOiK11593
OMAiSPDGYYH
OrthoDBiEOG091G020J
TreeFamiTF101510

Family and domain databases

Gene3Di3.30.420.10, 1 hit
HAMAPiMF_03031 AGO2, 1 hit
InterProiView protein in InterPro
IPR028602 AGO2
IPR014811 ArgoL1
IPR032472 ArgoL2
IPR032473 Argonaute_Mid_dom
IPR032474 Argonaute_N
IPR003100 PAZ_dom
IPR036085 PAZ_dom_sf
IPR003165 Piwi
IPR012337 RNaseH-like_sf
IPR036397 RNaseH_sf
PfamiView protein in Pfam
PF08699 ArgoL1, 1 hit
PF16488 ArgoL2, 1 hit
PF16487 ArgoMid, 1 hit
PF16486 ArgoN, 1 hit
PF02170 PAZ, 1 hit
PF02171 Piwi, 1 hit
SMARTiView protein in SMART
SM01163 DUF1785, 1 hit
SM00949 PAZ, 1 hit
SM00950 Piwi, 1 hit
SUPFAMiSSF101690 SSF101690, 1 hit
SSF53098 SSF53098, 1 hit
PROSITEiView protein in PROSITE
PS50821 PAZ, 1 hit
PS50822 PIWI, 1 hit

Sequencei

Sequence statusi: Complete.

Q8CJG0-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MYSGAGPVLA SPAPTTSPIP GYAFKPPPRP DFGTTGRTIK LQANFFEMDI
60 70 80 90 100
PKIDIYHYEL DIKPEKCPRR VNREIVEHMV QHFKTQIFGD RKPVFDGRKN
110 120 130 140 150
LYTAMPLPIG RDKVELEVTL PGEGKDRIFK VSIKWVSCVS LQALHDALSG
160 170 180 190 200
RLPSVPFETI QALDVVMRHL PSMRYTPVGR SFFTASEGCS NPLGGGREVW
210 220 230 240 250
FGFHQSVRPS LWKMMLNIDV SATAFYKAQP VIEFVCEVLD FKSIEEQQKP
260 270 280 290 300
LTDSQRVKFT KEIKGLKVEI THCGQMKRKY RVCNVTRRPA SHQTFPLQQE
310 320 330 340 350
SGQTVECTVA QYFKDRHKLV LRYPHLPCLQ VGQEQKHTYL PLEVCNIVAG
360 370 380 390 400
QRCIKKLTDN QTSTMIRATA RSAPDRQEEI SKLMRSASFN TDPYVREFGI
410 420 430 440 450
MVKDEMTDVT GRVLQPPSIL YGGRNKAIAT PVQGVWDMRN KQFHTGIEIK
460 470 480 490 500
VWAIACFAPQ RQCTEVHLKS FTEQLRKISR DAGMPIQGQP CFCKYAQGAD
510 520 530 540 550
SVEPMFRHLK NTYAGLQLVV VILPGKTPVY AEVKRVGDTV LGMATQCVQM
560 570 580 590 600
KNVQRTTPQT LSNLCLKINV KLGGVNNILL PQGRPPVFQQ PVIFLGADVT
610 620 630 640 650
HPPAGDGKKP SIAAVVGSMD AHPNRYCATV RVQQHRQEII QDLAAMVREL
660 670 680 690 700
LIQFYKSTRF KPTRIIFYRD GVSEGQFQQV LHHELLAIRE ACIKLEKDYQ
710 720 730 740 750
PGITFIVVQK RHHTRLFCTD KNERVGKSGN IPAGTTVDTK ITHPTEFDFY
760 770 780 790 800
LCSHAGIQGT SRPSHYHVLW DDNRFSSDEL QILTYQLCHT YVRCTRSVSI
810 820 830 840 850
PAPAYYAHLV AFRARYHLVD KEHDSAEGSH TSGQSNGRDH QALAKAVQVH
860
QDTLRTMYFA
Length:860
Mass (Da):97,304
Last modified:July 27, 2011 - v3
Checksum:iA4E13C633846062C
GO

Sequence cautioni

The sequence AAH96465 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti65E → G in AAH96465 (PubMed:15489334).Curated1
Sequence conflicti67C → R in BAC15767 (PubMed:12526743).Curated1
Sequence conflicti129F → L in BAC15767 (PubMed:12526743).Curated1
Sequence conflicti360N → D in BAC15767 (PubMed:12526743).Curated1
Sequence conflicti563N → D in AAH96465 (PubMed:15489334).Curated1
Sequence conflicti711R → P in AAH96465 (PubMed:15489334).Curated1
Sequence conflicti761S → G in BAC15767 (PubMed:12526743).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB081472 mRNA Translation: BAC15767.1
BC096465 mRNA Translation: AAH96465.1 Different initiation.
BC128379 mRNA Translation: AAI28380.1
BC129922 mRNA Translation: AAI29923.1
AK220193 mRNA Translation: BAD90378.1
CCDSiCCDS37098.1
RefSeqiNP_694818.3, NM_153178.4
UniGeneiMm.23095
Mm.391971
Mm.440409
Mm.476931
Mm.486474
Mm.490340

Genome annotation databases

EnsembliENSMUST00000044113; ENSMUSP00000042207; ENSMUSG00000036698
GeneIDi239528
KEGGimmu:239528
UCSCiuc007wbu.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB081472 mRNA Translation: BAC15767.1
BC096465 mRNA Translation: AAH96465.1 Different initiation.
BC128379 mRNA Translation: AAI28380.1
BC129922 mRNA Translation: AAI29923.1
AK220193 mRNA Translation: BAD90378.1
CCDSiCCDS37098.1
RefSeqiNP_694818.3, NM_153178.4
UniGeneiMm.23095
Mm.391971
Mm.440409
Mm.476931
Mm.486474
Mm.490340

3D structure databases

ProteinModelPortaliQ8CJG0
SMRiQ8CJG0
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi232092, 9 interactors
ComplexPortaliCPX-1073 RISC-loading complex, PRKRA variant
CPX-135 RISC-loading complex, TARBP2 variant
DIPiDIP-35014N
IntActiQ8CJG0, 55 interactors
STRINGi10090.ENSMUSP00000042207

PTM databases

iPTMnetiQ8CJG0
PhosphoSitePlusiQ8CJG0

Proteomic databases

EPDiQ8CJG0
MaxQBiQ8CJG0
PaxDbiQ8CJG0
PeptideAtlasiQ8CJG0
PRIDEiQ8CJG0

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000044113; ENSMUSP00000042207; ENSMUSG00000036698
GeneIDi239528
KEGGimmu:239528
UCSCiuc007wbu.2 mouse

Organism-specific databases

CTDi27161
MGIiMGI:2446632 Ago2
RougeiSearch...

Phylogenomic databases

eggNOGiKOG1041 Eukaryota
ENOG410XP07 LUCA
GeneTreeiENSGT00760000119148
HOGENOMiHOG000116043
HOVERGENiHBG006101
InParanoidiQ8CJG0
KOiK11593
OMAiSPDGYYH
OrthoDBiEOG091G020J
TreeFamiTF101510

Enzyme and pathway databases

ReactomeiR-MMU-203927 MicroRNA (miRNA) biogenesis
R-MMU-426486 Small interfering RNA (siRNA) biogenesis
R-MMU-426496 Post-transcriptional silencing by small RNAs
R-MMU-5578749 Transcriptional regulation by small RNAs

Miscellaneous databases

ChiTaRSiAgo2 mouse
PROiPR:Q8CJG0
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000036698 Expressed in 246 organ(s), highest expression level in mesenteric lymph node
CleanExiMM_EIF2C2
GenevisibleiQ8CJG0 MM

Family and domain databases

Gene3Di3.30.420.10, 1 hit
HAMAPiMF_03031 AGO2, 1 hit
InterProiView protein in InterPro
IPR028602 AGO2
IPR014811 ArgoL1
IPR032472 ArgoL2
IPR032473 Argonaute_Mid_dom
IPR032474 Argonaute_N
IPR003100 PAZ_dom
IPR036085 PAZ_dom_sf
IPR003165 Piwi
IPR012337 RNaseH-like_sf
IPR036397 RNaseH_sf
PfamiView protein in Pfam
PF08699 ArgoL1, 1 hit
PF16488 ArgoL2, 1 hit
PF16487 ArgoMid, 1 hit
PF16486 ArgoN, 1 hit
PF02170 PAZ, 1 hit
PF02171 Piwi, 1 hit
SMARTiView protein in SMART
SM01163 DUF1785, 1 hit
SM00949 PAZ, 1 hit
SM00950 Piwi, 1 hit
SUPFAMiSSF101690 SSF101690, 1 hit
SSF53098 SSF53098, 1 hit
PROSITEiView protein in PROSITE
PS50821 PAZ, 1 hit
PS50822 PIWI, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiAGO2_MOUSE
AccessioniPrimary (citable) accession number: Q8CJG0
Secondary accession number(s): A1A563, Q4VAB3, Q571J6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 14, 2003
Last sequence update: July 27, 2011
Last modified: November 7, 2018
This is version 143 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Translation initiation factors
    List of translation initiation factor entries
  3. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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