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O77503

- AGO2_RABIT

UniProt

O77503 - AGO2_RABIT

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Protein

Protein argonaute-2

Gene

AGO2

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).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
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-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. cytoplasm Source: UniProtKB-KW
  2. micro-ribonucleoprotein complex Source: UniProtKB
  3. mRNA cap binding complex Source: UniProtKB
  4. nucleus Source: UniProtKB-KW
  5. polysome Source: UniProtKB
  6. ribonucleoprotein complex Source: UniProtKB
  7. RISC 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-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.
InParanoidiO77503.

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

        10         20         30         40         50
GYAFKPPPRP DFGTSGRTIK LQANFFEMDI PKIDIYHYEL DIKPEKCPRR
60 70 80 90 100
VNREIVEHMV QHFKAQIFGD RKPVFDGRKN LYTAMPLPIG REKVELEVTL
110 120 130 140 150
PGEGKDRIFK VSIKWVSCVS LQALHDALSG RLPSVPFETI QALDVVMRHL
160 170 180 190 200
PSMRYTPVGR SFFTASEGCS NPLGGGREVW FGFHQSVRPS LWKMMLNIDV
210 220 230 240 250
SATAFYKAQP VIEFVCEVLD FKSIEEQQKP LTDSQRVKFT KEIKGLKVEI
260 270 280 290 300
THCGQMKRKY RVCNVTRRPA SHQTFPLQQE SGQTVECTVA QYFKDRHKLV
310 320 330 340 350
LRYPHLPCLQ VGQEQKHTYL PLEVCNIVAG QRCIKKLTDN QTSTMIRATA
360 370 380 390 400
RSAPDRQEEI SKLMRSASFN TDPYVREFGI MVKDEMTDVT GRVLQPPSIL
410 420 430 440 450
YGGRNKAIAT PVQGVWDMRN KQFHTGIEIK VWAIACFAPQ RQCTEVHLKS
460 470 480 490 500
FTEQLRKISR DAGMPIQGQP CFCKYAQGAD SVGPMFRHLK NTYAGLQLVV
510 520 530 540 550
VILPGKTPVY AEVKRVGDTV LGMATQCVQM KNVQRTTPQT LSNLCLKINV
560 570 580 590 600
KLGGVNNILL PQGRPPVFQQ PVIFLGADVT HPPAGDGKKP SIAAVVGSMD
610 620 630 640 650
AHPNRYCATV RVQQHRQEII QDLAAMVREL LIQFYKSTRF KPTRIIFYRD
660 670 680 690 700
GVSEGQFQQV LHHELLAIRE ACIKLEKDYQ PGITFIVVQK RHHTRLFCTD
710 720 730 740 750
KNERVGKSGN IPAGTTVDTK ITHPTEFDFY LCSHAGIQGT SRPSHYHVLW
760 770 780 790 800
DDNRFSSDEL QILTYQLCHT YVRCTRSVSI PAPAYYAHLV AFRARYHLVD
810 820 830 840
KEHDSAEGSH TSGQSNGRDH QALAKAVQVH QDTLRTMYFA
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. Curated

Experimental Info

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

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.
InParanoidi O77503.

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 29, 2014
This is version 87 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