Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

O77503

- AGO2_RABIT

UniProt

O77503 - AGO2_RABIT

Protein

Protein argonaute-2

Gene

AGO2

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 86 (01 Oct 2014)
      Sequence version 2 (14 Nov 2003)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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.By similarity

    Catalytic activityi

    Endonucleolytic cleavage to 5'-phosphomonoester.UniRule annotation

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi578 – 5781Divalent metal cationUniRule annotation
    Metal bindingi650 – 6501Divalent metal cationUniRule annotation
    Metal bindingi788 – 7881Divalent metal cationUniRule annotation

    GO - Molecular functioni

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

    GO - Biological processi

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

    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-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
    Protein slicerUniRule annotation
    Gene namesi
    Name:AGO2
    Synonyms:EIF2C2
    OrganismiOryctolagus cuniculus (Rabbit)
    Taxonomic identifieri9986 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
    ProteomesiUP000001811: Unplaced

    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

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

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

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

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei681 – 68114-hydroxyprolineUniRule annotation

    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

    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.By similarity

    Protein-protein interaction databases

    STRINGi9986.ENSOCUP00000023891.

    Structurei

    3D structure databases

    ProteinModelPortaliO77503.
    SMRiO77503. Positions 203-370.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini216 – 329114PAZUniRule annotationAdd
    BLAST
    Domaini498 – 799302PiwiUniRule annotationAdd
    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).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

    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

    « Hide

    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.

    Experimental Info

    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 27161.

    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: October 1, 2014
    This is version 86 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