AGO2_RABIT
ID AGO2_RABIT Reviewed; 840 AA.
AC O77503;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 14-NOV-2003, sequence version 2.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Protein argonaute-2 {ECO:0000255|HAMAP-Rule:MF_03031};
DE Short=Argonaute2 {ECO:0000255|HAMAP-Rule:MF_03031};
DE EC=3.1.26.n2 {ECO:0000255|HAMAP-Rule:MF_03031};
DE AltName: Full=Argonaute RISC catalytic component 2;
DE AltName: Full=Eukaryotic translation initiation factor 2C 2 {ECO:0000255|HAMAP-Rule:MF_03031};
DE Short=eIF-2C 2 {ECO:0000255|HAMAP-Rule:MF_03031};
DE Short=eIF2C 2 {ECO:0000255|HAMAP-Rule:MF_03031};
DE AltName: Full=Protein slicer {ECO:0000255|HAMAP-Rule:MF_03031};
DE Flags: Fragment;
GN Name=AGO2; Synonyms=EIF2C2;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=9602122; DOI=10.1016/s0378-1119(98)00107-3;
RA Zou C., Zhang Z., Wu S., Osterman J.C.;
RT "Molecular cloning and characterization of a rabbit eIF2C protein.";
RL Gene 211:187-194(1998).
CC -!- FUNCTION: Required for RNA-mediated gene silencing (RNAi) by the RNA-
CC induced silencing complex (RISC). The 'minimal RISC' appears to include
CC AGO2 bound to a short guide RNA such as a microRNA (miRNA) or short
CC interfering RNA (siRNA). These guide RNAs direct RISC to complementary
CC mRNAs that are targets for RISC-mediated gene silencing. The precise
CC mechanism of gene silencing depends on the degree of complementarity
CC between the miRNA or siRNA and its target. Binding of RISC to a
CC perfectly complementary mRNA generally results in silencing due to
CC endonucleolytic cleavage of the mRNA specifically by AGO2. Binding of
CC RISC to a partially complementary mRNA results in silencing through
CC inhibition of translation, and this is independent of endonuclease
CC activity. May inhibit translation initiation by binding to the 7-
CC methylguanosine cap, thereby preventing the recruitment of the
CC translation initiation factor eIF4-E. May also inhibit translation
CC initiation via interaction with EIF6, which itself binds to the 60S
CC ribosomal subunit and prevents its association with the 40S ribosomal
CC subunit. The inhibition of translational initiation leads to the
CC accumulation of the affected mRNA in cytoplasmic processing bodies (P-
CC bodies), where mRNA degradation may subsequently occur. In some cases
CC RISC-mediated translational repression is also observed for miRNAs that
CC perfectly match the 3' untranslated region (3'-UTR). Can also up-
CC regulate the translation of specific mRNAs under certain growth
CC conditions. Binds to the AU element of the 3'-UTR of the TNF (TNF-
CC alpha) mRNA and up-regulates translation under conditions of serum
CC starvation. Also required for transcriptional gene silencing (TGS), in
CC which short RNAs known as antigene RNAs or agRNAs direct the
CC transcriptional repression of complementary promoter regions.
CC {ECO:0000255|HAMAP-Rule:MF_03031}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=endonucleolytic cleavage to 5'-phosphomonoester.;
CC EC=3.1.26.n2; Evidence={ECO:0000255|HAMAP-Rule:MF_03031};
CC -!- SUBUNIT: Interacts with DICER1 through its Piwi domain and with TARBP2
CC during assembly of the RNA-induced silencing complex (RISC). Together,
CC DICER1, AGO2 and TARBP2 constitute the trimeric RISC loading complex
CC (RLC), or micro-RNA (miRNA) loading complex (miRLC). Within the
CC RLC/miRLC, DICER1 and TARBP2 are required to process precursor miRNAs
CC (pre-miRNAs) to mature miRNAs and then load them onto AGO2. AGO2 bound
CC to the mature miRNA constitutes the minimal RISC and may subsequently
CC dissociate from DICER1 and TARBP2. Note however that the term RISC has
CC also been used to describe the trimeric RLC/miRLC. The formation of
CC RISC complexes containing siRNAs rather than miRNAs appears to occur
CC independently of DICER1. Interacts with AGO1. Also interacts with DDB1,
CC DDX5, DDX6, DDX20, DHX30, DHX36, DDX47, DHX9, ELAVL, FXR1, GEMIN4,
CC HNRNPF, IGF2BP1, ILF3, IMP8, MATR3, PABPC1, PRMT5, P4HA1, P4HB, RBM4,
CC SART3, TNRC6A, TNRC6B, UPF1 and YBX1. Interacts with the P-body
CC components DCP1A and XRN1. Associates with polysomes and messenger
CC ribonucleoproteins (mNRPs). Interacts with RBM4; the interaction is
CC modulated under stress-induced conditions, occurs under both cell
CC proliferation and differentiation conditions and in an RNA- and
CC phosphorylation-independent manner. Interacts with LIMD1, WTIP and
CC AJUBA. Interacts with TRIM71; the interaction increases in presence of
CC RNA. Interacts with APOBEC3G in an RNA-dependent manner. Interacts with
CC APOBEC3A, APOBEC3C, APOBEC3F and APOBEC3H. Interacts with DICER1,
CC TARBP2, EIF6, MOV10 and RPL7A (60S ribosome subunit); they form a large
CC RNA-induced silencing complex (RISC). Interacts with FMR1. Interacts
CC with ZFP36. Interacts with RC3H1; the interaction is RNA independent
CC (By similarity). Found in a complex composed of AGO2, CHD7 and FAM172A
CC (By similarity). Interacts with SND1 and SYT11 (By similarity).
CC Interacts with CLNK (By similarity). Interacts with GARRE1 (By
CC similarity). {ECO:0000250|UniProtKB:Q8CJG0,
CC ECO:0000250|UniProtKB:Q9UKV8, ECO:0000255|HAMAP-Rule:MF_03031}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000255|HAMAP-
CC Rule:MF_03031}. Nucleus {ECO:0000255|HAMAP-Rule:MF_03031}.
CC Note=Translational repression of mRNAs results in their recruitment to
CC P-bodies. Translocation to the nucleus requires IMP8.
CC {ECO:0000255|HAMAP-Rule:MF_03031}.
CC -!- DOMAIN: The Piwi domain may perform RNA cleavage by a mechanism similar
CC to that of RNase H. However, while RNase H utilizes a triad of Asp-Asp-
CC Glu (DDE) for metal ion coordination, this protein appears to utilize a
CC triad of Asp-Asp-His (DDH). {ECO:0000255|HAMAP-Rule:MF_03031}.
CC -!- PTM: Hydroxylated. 4-hydroxylation appears to enhance protein stability
CC but is not required for miRNA-binding or endonuclease activity.
CC {ECO:0000255|HAMAP-Rule:MF_03031}.
CC -!- PTM: Ubiquitinated on surface-exposed lysines by a SCF-like E3
CC ubiquitin-protein ligase complex containing ZSWIM8 during target-
CC directed microRNA degradation (TDMD), a process that mediates
CC degradation of microRNAs (miRNAs). Ubiquitination by the SCF-like E3
CC ubiquitin-protein ligase complex containing ZSWIM8 leads to its
CC subsequent degradation, thereby exposing miRNAs for degradation. ZSWIM8
CC recognizes and binds AGO2 when it is engaged with a TDMD target.
CC {ECO:0000250|UniProtKB:Q9UKV8}.
CC -!- PTM: Phosphorylation at Ser-368 by AKT3; leads to up-regulate
CC translational repression of microRNA target and down-regulate
CC endonucleolytic cleavage. {ECO:0000250|UniProtKB:Q9UKV8}.
CC -!- PTM: A phosphorylation cycle of C-terminal serine cluster (Ser-805-Ser-
CC 815) regulates the release of target mRNAs. Target-binding leads to
CC phosphorylation of these residues by CSNK1A1, which reduces the
CC affinity of AGO2 for mRNA and enables target release. The ANKRD52-PPP6C
CC phosphatase complex dephosphorylates the residues, which primes AGO2
CC for binding a new target. {ECO:0000250|UniProtKB:Q9UKV8}.
CC -!- SIMILARITY: Belongs to the argonaute family. Ago subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03031}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC24323.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF005355; AAC24323.1; ALT_INIT; mRNA.
DR PIR; PC6505; JC6569.
DR RefSeq; NP_001076179.1; NM_001082710.1.
DR AlphaFoldDB; O77503; -.
DR SMR; O77503; -.
DR STRING; 9986.ENSOCUP00000005257; -.
DR PRIDE; O77503; -.
DR GeneID; 100009457; -.
DR KEGG; ocu:100009457; -.
DR CTD; 27161; -.
DR eggNOG; KOG1041; Eukaryota.
DR InParanoid; O77503; -.
DR OrthoDB; 1321296at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005845; C:mRNA cap binding complex; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000932; C:P-body; IEA:UniProtKB-SubCell.
DR GO; GO:0005844; C:polysome; ISS:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; ISS:UniProtKB.
DR GO; GO:0016442; C:RISC complex; ISS:UniProtKB.
DR GO; GO:0070578; C:RISC-loading complex; ISS:UniProtKB.
DR GO; GO:0070551; F:endoribonuclease activity, cleaving siRNA-paired mRNA; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000340; F:RNA 7-methylguanosine cap binding; ISS:UniProtKB.
DR GO; GO:0035197; F:siRNA binding; ISS:UniProtKB.
DR GO; GO:0031047; P:gene silencing by RNA; ISS:UniProtKB.
DR GO; GO:0035278; P:miRNA-mediated gene silencing by inhibition of translation; ISS:UniProtKB.
DR GO; GO:0035279; P:miRNA-mediated gene silencing by mRNA destabilization; ISS:UniProtKB.
DR GO; GO:0045947; P:negative regulation of translational initiation; ISS:UniProtKB.
DR GO; GO:1900153; P:positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; ISS:UniProtKB.
DR GO; GO:0060213; P:positive regulation of nuclear-transcribed mRNA poly(A) tail shortening; ISS:UniProtKB.
DR GO; GO:0031054; P:pre-miRNA processing; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:InterPro.
DR CDD; cd04657; Piwi_ago-like; 1.
DR Gene3D; 3.30.420.10; -; 1.
DR HAMAP; MF_03031; AGO2; 1.
DR InterPro; IPR028602; AGO2.
DR InterPro; IPR014811; ArgoL1.
DR InterPro; IPR032472; ArgoL2.
DR InterPro; IPR032473; Argonaute_Mid_dom.
DR InterPro; IPR032474; Argonaute_N.
DR InterPro; IPR003100; PAZ_dom.
DR InterPro; IPR036085; PAZ_dom_sf.
DR InterPro; IPR003165; Piwi.
DR InterPro; IPR045246; Piwi_ago-like.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR036397; RNaseH_sf.
DR Pfam; PF08699; ArgoL1; 1.
DR Pfam; PF16488; ArgoL2; 1.
DR Pfam; PF16487; ArgoMid; 1.
DR Pfam; PF16486; ArgoN; 1.
DR Pfam; PF02170; PAZ; 1.
DR Pfam; PF02171; Piwi; 1.
DR SMART; SM01163; DUF1785; 1.
DR SMART; SM00949; PAZ; 1.
DR SMART; SM00950; Piwi; 1.
DR SUPFAM; SSF101690; SSF101690; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
DR PROSITE; PS50821; PAZ; 1.
DR PROSITE; PS50822; PIWI; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Direct protein sequencing; Endonuclease; Hydrolase;
KW Hydroxylation; Metal-binding; Nuclease; Nucleus; Phosphoprotein;
KW Reference proteome; Repressor; Ribonucleoprotein; RNA-binding;
KW RNA-mediated gene silencing; Transcription; Transcription regulation;
KW Translation regulation; Ubl conjugation.
FT CHAIN <1..840
FT /note="Protein argonaute-2"
FT /id="PRO_0000194059"
FT DOMAIN 216..329
FT /note="PAZ"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03031"
FT DOMAIN 498..799
FT /note="Piwi"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03031"
FT BINDING 578
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03031"
FT BINDING 650
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03031"
FT BINDING 788
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03031"
FT MOD_RES 368
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKV8"
FT MOD_RES 681
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03031"
FT MOD_RES 805
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKV8"
FT MOD_RES 809
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKV8"
FT MOD_RES 812
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKV8"
FT MOD_RES 815
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKV8"
FT NON_TER 1
SQ SEQUENCE 840 AA; 95306 MW; 1E703F9E31391F29 CRC64;
GYAFKPPPRP DFGTSGRTIK LQANFFEMDI PKIDIYHYEL DIKPEKCPRR VNREIVEHMV
QHFKAQIFGD RKPVFDGRKN LYTAMPLPIG REKVELEVTL PGEGKDRIFK VSIKWVSCVS
LQALHDALSG RLPSVPFETI QALDVVMRHL PSMRYTPVGR SFFTASEGCS NPLGGGREVW
FGFHQSVRPS LWKMMLNIDV SATAFYKAQP VIEFVCEVLD FKSIEEQQKP LTDSQRVKFT
KEIKGLKVEI THCGQMKRKY RVCNVTRRPA SHQTFPLQQE SGQTVECTVA QYFKDRHKLV
LRYPHLPCLQ VGQEQKHTYL PLEVCNIVAG QRCIKKLTDN QTSTMIRATA RSAPDRQEEI
SKLMRSASFN TDPYVREFGI MVKDEMTDVT GRVLQPPSIL YGGRNKAIAT PVQGVWDMRN
KQFHTGIEIK VWAIACFAPQ RQCTEVHLKS FTEQLRKISR DAGMPIQGQP CFCKYAQGAD
SVGPMFRHLK NTYAGLQLVV VILPGKTPVY AEVKRVGDTV LGMATQCVQM KNVQRTTPQT
LSNLCLKINV KLGGVNNILL PQGRPPVFQQ PVIFLGADVT HPPAGDGKKP SIAAVVGSMD
AHPNRYCATV RVQQHRQEII QDLAAMVREL LIQFYKSTRF KPTRIIFYRD GVSEGQFQQV
LHHELLAIRE ACIKLEKDYQ PGITFIVVQK RHHTRLFCTD KNERVGKSGN IPAGTTVDTK
ITHPTEFDFY LCSHAGIQGT SRPSHYHVLW DDNRFSSDEL QILTYQLCHT YVRCTRSVSI
PAPAYYAHLV AFRARYHLVD KEHDSAEGSH TSGQSNGRDH QALAKAVQVH QDTLRTMYFA
