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O77503 (AGO2_RABIT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 84. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein argonaute-2

Short name=Argonaute2
EC=3.1.26.n2
Alternative name(s):
Argonaute RISC catalytic component 2
Eukaryotic translation initiation factor 2C 2
Short name=eIF-2C 2
Short name=eIF2C 2
Protein slicer
Gene names
Name:AGO2
Synonyms:EIF2C2
OrganismOryctolagus cuniculus (Rabbit) [Reference proteome]
Taxonomic identifier9986 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus

Protein attributes

Sequence length840 AA.
Sequence statusFragment.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Required for RNA-mediated gene silencing (RNAi) by the RNA-induced silencing complex (RISC). The 'minimal RISC' appears to include AGO2 bound to a short guide RNA such as a microRNA (miRNA) or short interfering RNA (siRNA). These guide RNAs direct RISC to complementary mRNAs that are targets for RISC-mediated gene silencing. The precise mechanism of gene silencing depends on the degree of complementarity between the miRNA or siRNA and its target. Binding of RISC to a perfectly complementary mRNA generally results in silencing due to endonucleolytic cleavage of the mRNA specifically by AGO2. Binding of RISC to a partially complementary mRNA results in silencing through inhibition of translation, and this is independent of endonuclease activity. May inhibit translation initiation by binding to the 7-methylguanosine cap, thereby preventing the recruitment of the translation initiation factor eIF4-E. May also inhibit translation initiation via interaction with EIF6, which itself binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit. The inhibition of translational initiation leads to the accumulation of the affected mRNA in cytoplasmic processing bodies (P-bodies), where mRNA degradation may subsequently occur. In some cases RISC-mediated translational repression is also observed for miRNAs that perfectly match the 3' untranslated region (3'-UTR). Can also up-regulate the translation of specific mRNAs under certain growth conditions. Binds to the AU element of the 3'-UTR of the TNF (TNF-alpha) mRNA and up-regulates translation under conditions of serum starvation. Also required for transcriptional gene silencing (TGS), in which short RNAs known as antigene RNAs or agRNAs direct the transcriptional repression of complementary promoter regions By similarity. HAMAP-Rule MF_03031

Catalytic activity

Endonucleolytic cleavage to 5'-phosphomonoester. HAMAP-Rule MF_03031

Subunit structure

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

Subcellular location

CytoplasmP-body By similarity. Nucleus By similarity. Note: Translational repression of mRNAs results in their recruitment to P-bodies. Translocation to the nucleus requires IMP8 By similarity. HAMAP-Rule MF_03031

Domain

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

Post-translational modification

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

Sequence similarities

Belongs to the argonaute family. Ago subfamily.

Contains 1 PAZ domain.

Contains 1 Piwi domain.

Sequence caution

The sequence AAC24323.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processRNA-mediated gene silencing
Transcription
Transcription regulation
Translation regulation
   Cellular componentCytoplasm
Nucleus
   LigandMetal-binding
RNA-binding
   Molecular functionEndonuclease
Hydrolase
Nuclease
Repressor
Ribonucleoprotein
   PTMHydroxylation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processRNA phosphodiester bond hydrolysis, endonucleolytic

Inferred from sequence or structural similarity. Source: GOC

gene silencing by RNA

Inferred from sequence or structural similarity. Source: UniProtKB

mRNA cleavage involved in gene silencing by miRNA

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of translation involved in gene silencing by miRNA

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of translational initiation

Inferred from sequence or structural similarity. Source: UniProtKB

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

Inferred from sequence or structural similarity. Source: UniProtKB

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

Inferred from sequence or structural similarity. Source: UniProtKB

pre-miRNA processing

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentRISC complex

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasmic mRNA processing body

Inferred from electronic annotation. Source: UniProtKB-SubCell

mRNA cap binding complex

Inferred from sequence or structural similarity. Source: UniProtKB

micro-ribonucleoprotein complex

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

polysome

Inferred from sequence or structural similarity. Source: UniProtKB

ribonucleoprotein complex

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionRNA 7-methylguanosine cap binding

Inferred from sequence or structural similarity. Source: UniProtKB

endoribonuclease activity, cleaving siRNA-paired mRNA

Inferred from sequence or structural similarity. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

siRNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain‹1 – 840›840Protein argonaute-2 HAMAP-Rule MF_03031
PRO_0000194059

Regions

Domain216 – 329114PAZ
Domain498 – 799302Piwi

Sites

Metal binding5781Divalent metal cation By similarity
Metal binding6501Divalent metal cation By similarity
Metal binding7881Divalent metal cation By similarity

Amino acid modifications

Modified residue68114-hydroxyproline By similarity

Experimental info

Non-terminal residue11

Sequences

Sequence LengthMass (Da)Tools
O77503 [UniParc].

Last modified November 14, 2003. Version 2.
Checksum: 1E703F9E31391F29

FASTA84095,306
        10         20         30         40         50         60 
GYAFKPPPRP DFGTSGRTIK LQANFFEMDI PKIDIYHYEL DIKPEKCPRR VNREIVEHMV 

        70         80         90        100        110        120 
QHFKAQIFGD RKPVFDGRKN LYTAMPLPIG REKVELEVTL PGEGKDRIFK VSIKWVSCVS 

       130        140        150        160        170        180 
LQALHDALSG RLPSVPFETI QALDVVMRHL PSMRYTPVGR SFFTASEGCS NPLGGGREVW 

       190        200        210        220        230        240 
FGFHQSVRPS LWKMMLNIDV SATAFYKAQP VIEFVCEVLD FKSIEEQQKP LTDSQRVKFT 

       250        260        270        280        290        300 
KEIKGLKVEI THCGQMKRKY RVCNVTRRPA SHQTFPLQQE SGQTVECTVA QYFKDRHKLV 

       310        320        330        340        350        360 
LRYPHLPCLQ VGQEQKHTYL PLEVCNIVAG QRCIKKLTDN QTSTMIRATA RSAPDRQEEI 

       370        380        390        400        410        420 
SKLMRSASFN TDPYVREFGI MVKDEMTDVT GRVLQPPSIL YGGRNKAIAT PVQGVWDMRN 

       430        440        450        460        470        480 
KQFHTGIEIK VWAIACFAPQ RQCTEVHLKS FTEQLRKISR DAGMPIQGQP CFCKYAQGAD 

       490        500        510        520        530        540 
SVGPMFRHLK NTYAGLQLVV VILPGKTPVY AEVKRVGDTV LGMATQCVQM KNVQRTTPQT 

       550        560        570        580        590        600 
LSNLCLKINV KLGGVNNILL PQGRPPVFQQ PVIFLGADVT HPPAGDGKKP SIAAVVGSMD 

       610        620        630        640        650        660 
AHPNRYCATV RVQQHRQEII QDLAAMVREL LIQFYKSTRF KPTRIIFYRD GVSEGQFQQV 

       670        680        690        700        710        720 
LHHELLAIRE ACIKLEKDYQ PGITFIVVQK RHHTRLFCTD KNERVGKSGN IPAGTTVDTK 

       730        740        750        760        770        780 
ITHPTEFDFY LCSHAGIQGT SRPSHYHVLW DDNRFSSDEL QILTYQLCHT YVRCTRSVSI 

       790        800        810        820        830        840 
PAPAYYAHLV AFRARYHLVD KEHDSAEGSH TSGQSNGRDH QALAKAVQVH QDTLRTMYFA 

« Hide

References

[1]"Molecular cloning and characterization of a rabbit eIF2C protein."
Zou C., Zhang Z., Wu S., Osterman J.C.
Gene 211:187-194(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
Tissue: Liver.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF005355 mRNA. Translation: AAC24323.1. Different initiation.
PIRJC6569. PC6505.
RefSeqNP_001076179.1. NM_001082710.1.
UniGeneOcu.1816.

3D structure databases

ProteinModelPortalO77503.
SMRO77503. Positions 203-370.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9986.ENSOCUP00000023891.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID100009457.

Organism-specific databases

CTD100082977.

Phylogenomic databases

eggNOGNOG279895.
HOGENOMHOG000116043.

Family and domain databases

Gene3D3.30.420.10. 1 hit.
HAMAPMF_03031. AGO2.
InterProIPR028602. AGO2.
IPR014811. DUF1785.
IPR003100. PAZ_dom.
IPR003165. Piwi.
IPR012337. RNaseH-like_dom.
[Graphical view]
PfamPF08699. DUF1785. 1 hit.
PF02170. PAZ. 1 hit.
PF02171. Piwi. 1 hit.
[Graphical view]
SMARTSM00949. PAZ. 1 hit.
SM00950. Piwi. 1 hit.
[Graphical view]
SUPFAMSSF101690. SSF101690. 1 hit.
SSF53098. SSF53098. 1 hit.
PROSITEPS50821. PAZ. 1 hit.
PS50822. PIWI. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameAGO2_RABIT
AccessionPrimary (citable) accession number: O77503
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 14, 2003
Last modified: April 16, 2014
This is version 84 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Translation initiation factors

List of translation initiation factor entries