O77503 (AGO2_RABIT) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 82. History...
Names and origin
|Protein names||Recommended name:|
Argonaute RISC catalytic component 2
Eukaryotic translation initiation factor 2C 2
Short name=eIF-2C 2
Short name=eIF2C 2
|Organism||Oryctolagus cuniculus (Rabbit) [Reference proteome]|
|Taxonomic identifier||9986 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus|
|Sequence length||840 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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
Endonucleolytic cleavage to 5'-phosphomonoester. HAMAP-Rule MF_03031
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 a 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.
Cytoplasm › P-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
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
Hydroxylated. 4-hydroxylation appears to enhance protein stability but is not required for miRNA-binding or endonuclease activity By similarity. HAMAP-Rule MF_03031
Contains 1 PAZ domain.
Contains 1 Piwi domain.
The sequence AAC24323.1 differs from that shown. Reason: Erroneous initiation.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||‹1 – 840||›840||Protein argonaute-2 HAMAP-Rule MF_03031||PRO_0000194059|
|Domain||216 – 329||114||PAZ|
|Domain||498 – 799||302||Piwi|
|Metal binding||578||1||Divalent metal cation By similarity|
|Metal binding||650||1||Divalent metal cation By similarity|
|Metal binding||788||1||Divalent metal cation By similarity|
Amino acid modifications
|Modified residue||681||1||4-hydroxyproline By similarity|
|AF005355 mRNA. Translation: AAC24323.1. Different initiation.|
|PIR||JC6569. PC6505. |
|RefSeq||NP_001076179.1. NM_001082710.1. |
3D structure databases
|SMR||O77503. Positions 203-370. |
Protein-protein interaction databases
Protocols and materials databases
Genome annotation databases
Family and domain databases
|HAMAP||MF_03031. AGO2. |
|InterPro||IPR028602. AGO2. |
|Pfam||PF08699. DUF1785. 1 hit. |
PF02170. PAZ. 1 hit.
PF02171. Piwi. 1 hit.
|SMART||SM00949. PAZ. 1 hit. |
SM00950. Piwi. 1 hit.
|SUPFAM||SSF101690. SSF101690. 1 hit. |
SSF53098. SSF53098. 1 hit.
|PROSITE||PS50821. PAZ. 1 hit. |
PS50822. PIWI. 1 hit.
|Accession||Primary (citable) accession number: O77503|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|