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O77503

- AGO2_RABIT

UniProt

O77503 - AGO2_RABIT

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Protein
Protein argonaute-2
Gene
AGO2, EIF2C2
Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed - 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 By similarity.UniRule annotation

Catalytic activityi

Endonucleolytic cleavage to 5'-phosphomonoester.UniRule annotation

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi578 – 5781Divalent metal cation By similarity
Metal bindingi650 – 6501Divalent metal cation By similarity
Metal bindingi788 – 7881Divalent metal cation By similarity

GO - Molecular functioni

  1. RNA 7-methylguanosine cap binding Source: UniProtKB
  2. endoribonuclease activity, cleaving siRNA-paired mRNA Source: UniProtKB
  3. metal ion binding Source: UniProtKB-KW
  4. siRNA binding Source: UniProtKB

GO - Biological processi

  1. RNA phosphodiester bond hydrolysis, endonucleolytic Source: GOC
  2. gene silencing by RNA Source: UniProtKB
  3. mRNA cleavage involved in gene silencing by miRNA Source: UniProtKB
  4. negative regulation of translation involved in gene silencing by miRNA Source: UniProtKB
  5. negative regulation of translational initiation Source: UniProtKB
  6. positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay Source: UniProtKB
  7. positive regulation of nuclear-transcribed mRNA poly(A) tail shortening Source: UniProtKB
  8. pre-miRNA processing Source: UniProtKB
  9. regulation of transcription, DNA-templated Source: UniProtKB-KW
  10. transcription, DNA-templated Source: UniProtKB-KW
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

Metal-binding, RNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Protein argonaute-2 (EC:3.1.26.n2)
Short name:
Argonaute2
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 namesi
Name:AGO2
Synonyms:EIF2C2
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
ProteomesiUP000001811: Unplaced

Subcellular locationi

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.UniRule annotation

GO - Cellular componenti

  1. RISC complex Source: UniProtKB
  2. cytoplasmic mRNA processing body Source: UniProtKB-SubCell
  3. mRNA cap binding complex Source: UniProtKB
  4. micro-ribonucleoprotein complex Source: UniProtKB
  5. nucleus Source: UniProtKB-SubCell
  6. polysome Source: UniProtKB
  7. ribonucleoprotein complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini‹1 – 840›840Protein argonaute-2UniRule annotation
PRO_0000194059Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei681 – 68114-hydroxyproline By similarity

Post-translational modificationi

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

Keywords - PTMi

Hydroxylation

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 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.

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000023891.

Structurei

3D structure databases

ProteinModelPortaliO77503.
SMRiO77503. Positions 203-370.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini216 – 329114PAZ
Add
BLAST
Domaini498 – 799302Piwi
Add
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) By similarity.UniRule annotation

Sequence similaritiesi

Contains 1 PAZ domain.
Contains 1 Piwi domain.

Phylogenomic databases

eggNOGiNOG279895.
HOGENOMiHOG000116043.

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]

Sequencei

Sequence statusi: Fragment.

O77503-1 [UniParc]FASTAAdd to Basket

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GYAFKPPPRP DFGTSGRTIK LQANFFEMDI PKIDIYHYEL DIKPEKCPRR    50
VNREIVEHMV QHFKAQIFGD RKPVFDGRKN LYTAMPLPIG REKVELEVTL 100
PGEGKDRIFK VSIKWVSCVS LQALHDALSG RLPSVPFETI QALDVVMRHL 150
PSMRYTPVGR SFFTASEGCS NPLGGGREVW FGFHQSVRPS LWKMMLNIDV 200
SATAFYKAQP VIEFVCEVLD FKSIEEQQKP LTDSQRVKFT KEIKGLKVEI 250
THCGQMKRKY RVCNVTRRPA SHQTFPLQQE SGQTVECTVA QYFKDRHKLV 300
LRYPHLPCLQ VGQEQKHTYL PLEVCNIVAG QRCIKKLTDN QTSTMIRATA 350
RSAPDRQEEI SKLMRSASFN TDPYVREFGI MVKDEMTDVT GRVLQPPSIL 400
YGGRNKAIAT PVQGVWDMRN KQFHTGIEIK VWAIACFAPQ RQCTEVHLKS 450
FTEQLRKISR DAGMPIQGQP CFCKYAQGAD SVGPMFRHLK NTYAGLQLVV 500
VILPGKTPVY AEVKRVGDTV LGMATQCVQM KNVQRTTPQT LSNLCLKINV 550
KLGGVNNILL PQGRPPVFQQ PVIFLGADVT HPPAGDGKKP SIAAVVGSMD 600
AHPNRYCATV RVQQHRQEII QDLAAMVREL LIQFYKSTRF KPTRIIFYRD 650
GVSEGQFQQV LHHELLAIRE ACIKLEKDYQ PGITFIVVQK RHHTRLFCTD 700
KNERVGKSGN IPAGTTVDTK ITHPTEFDFY LCSHAGIQGT SRPSHYHVLW 750
DDNRFSSDEL QILTYQLCHT YVRCTRSVSI PAPAYYAHLV AFRARYHLVD 800
KEHDSAEGSH TSGQSNGRDH QALAKAVQVH QDTLRTMYFA 840
Length:840
Mass (Da):95,306
Last modified:November 14, 2003 - v2
Checksum:i1E703F9E31391F29
GO

Sequence cautioni

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

Non-terminal residue

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Non-terminal residuei1 – 11

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF005355 mRNA. Translation: AAC24323.1. Different initiation.
PIRiPC6505. JC6569.
RefSeqiNP_001076179.1. NM_001082710.1.
UniGeneiOcu.1816.

Genome annotation databases

GeneIDi100009457.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF005355 mRNA. Translation: AAC24323.1 . Different initiation.
PIRi PC6505. JC6569.
RefSeqi NP_001076179.1. NM_001082710.1.
UniGenei Ocu.1816.

3D structure databases

ProteinModelPortali O77503.
SMRi O77503. Positions 203-370.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9986.ENSOCUP00000023891.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 100009457.

Organism-specific databases

CTDi 100935023.

Phylogenomic databases

eggNOGi NOG279895.
HOGENOMi HOG000116043.

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. "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.

Entry informationi

Entry nameiAGO2_RABIT
AccessioniPrimary (citable) accession number: O77503
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 14, 2003
Last modified: September 3, 2014
This is version 85 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Translation initiation factors
    List of translation initiation factor entries
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi