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Protein

Protein argonaute-2

Gene

Ago2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 annotation

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

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

Names & Taxonomyi

Protein namesi
Recommended name:
Protein argonaute-2UniRule annotation (EC:3.1.26.n2UniRule annotation)
Short name:
Argonaute2UniRule annotation
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
Golgi ER protein 95 kDa
Short name:
GERp95
Protein slicerUniRule annotation
Gene namesi
Name:Ago2
Synonyms:Eif2c2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi621255. Ago2.

Subcellular locationi

  • CytoplasmP-body UniRule annotation
  • Nucleus UniRule annotation

  • Note: Translational repression of mRNAs results in their recruitment to P-bodies. Translocation to the nucleus requires IMP8.UniRule annotation

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001940601 – 860Protein argonaute-2Add BLAST860

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2Nitrated tyrosineUniRule annotationBy similarity1
Modified residuei388PhosphoserineBy similarity1
Modified residuei7014-hydroxyprolineUniRule annotation1
Modified residuei825PhosphoserineBy similarity1
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

PaxDbiQ9QZ81.
PeptideAtlasiQ9QZ81.
PRIDEiQ9QZ81.

PTM databases

iPTMnetiQ9QZ81.
PhosphoSitePlusiQ9QZ81.

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). Interacts with FMR1. Interacts with ZFP36.UniRule annotation

Protein-protein interaction databases

BioGridi248738. 1 interactor.
IntActiQ9QZ81. 6 interactors.
STRINGi10116.ENSRNOP00000011898.

Structurei

3D structure databases

ProteinModelPortaliQ9QZ81.
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
Contains 1 PAZ domain.UniRule annotation
Contains 1 Piwi domain.UniRule annotation

Phylogenomic databases

eggNOGiKOG1041. Eukaryota.
ENOG410XP07. LUCA.
HOGENOMiHOG000116043.
InParanoidiQ9QZ81.
KOiK11593.
PhylomeDBiQ9QZ81.

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]

Sequencei

Sequence statusi: Complete.

Q9QZ81-1 [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 ACIKLEKEYQ
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):97,318
Last modified:November 14, 2003 - v2
Checksum:iA5B0798C66481C9C
GO

Sequence cautioni

The sequence AAF12800 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF195534 mRNA. Translation: AAF12800.1. Different initiation.
RefSeqiNP_067608.1. NM_021597.1.
UniGeneiRn.234328.

Genome annotation databases

GeneIDi59117.
KEGGirno:59117.
UCSCiRGD:621255. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF195534 mRNA. Translation: AAF12800.1. Different initiation.
RefSeqiNP_067608.1. NM_021597.1.
UniGeneiRn.234328.

3D structure databases

ProteinModelPortaliQ9QZ81.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248738. 1 interactor.
IntActiQ9QZ81. 6 interactors.
STRINGi10116.ENSRNOP00000011898.

PTM databases

iPTMnetiQ9QZ81.
PhosphoSitePlusiQ9QZ81.

Proteomic databases

PaxDbiQ9QZ81.
PeptideAtlasiQ9QZ81.
PRIDEiQ9QZ81.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi59117.
KEGGirno:59117.
UCSCiRGD:621255. rat.

Organism-specific databases

CTDi27161.
RGDi621255. Ago2.

Phylogenomic databases

eggNOGiKOG1041. Eukaryota.
ENOG410XP07. LUCA.
HOGENOMiHOG000116043.
InParanoidiQ9QZ81.
KOiK11593.
PhylomeDBiQ9QZ81.

Miscellaneous databases

PROiQ9QZ81.

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_RAT
AccessioniPrimary (citable) accession number: Q9QZ81
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 14, 2003
Last modified: November 30, 2016
This is version 110 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

Was originally thought to be membrane-associated.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Translation initiation factors
    List of translation initiation factor entries
  2. 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.