AGO2_RAT
ID AGO2_RAT Reviewed; 860 AA.
AC Q9QZ81;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 14-NOV-2003, sequence version 2.
DT 03-AUG-2022, entry version 140.
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=Golgi ER protein 95 kDa;
DE Short=GERp95;
DE AltName: Full=Protein slicer {ECO:0000255|HAMAP-Rule:MF_03031};
GN Name=Ago2; Synonyms=Eif2c2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Hepatoma;
RX PubMed=10512872; DOI=10.1091/mbc.10.10.3357;
RA Cikaluk D.E., Tahbaz N., Hendricks L.C., DiMattia G.E., Hansen D.,
RA Pilgrim D., Hobman T.C.;
RT "GERp95, a membrane-associated protein that belongs to a family of proteins
RT involved in stem cell differentiation.";
RL Mol. Biol. Cell 10:3357-3372(1999).
RN [2]
RP INTERACTION WITH AGO2 AND SND1.
RX PubMed=24882364; DOI=10.1016/j.febslet.2014.05.031;
RA Milochau A., Lagree V., Benassy M.N., Chaignepain S., Papin J.,
RA Garcia-Arcos I., Lajoix A., Monterrat C., Coudert L., Schmitter J.M.,
RA Ochoa B., Lang J.;
RT "Synaptotagmin 11 interacts with components of the RNA-induced silencing
RT complex RISC in clonal pancreatic beta-cells.";
RL FEBS Lett. 588:2217-2222(2014).
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 -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
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 (PubMed:24882364).
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 ECO:0000269|PubMed:24882364}.
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-388 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-825-Ser-
CC 835) 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 -!- CAUTION: Was originally thought to be membrane-associated.
CC {ECO:0000305|PubMed:10512872}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF12800.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF195534; AAF12800.1; ALT_INIT; mRNA.
DR RefSeq; NP_067608.1; NM_021597.1.
DR AlphaFoldDB; Q9QZ81; -.
DR SMR; Q9QZ81; -.
DR BioGRID; 248738; 1.
DR IntAct; Q9QZ81; 7.
DR MINT; Q9QZ81; -.
DR STRING; 10116.ENSRNOP00000011898; -.
DR iPTMnet; Q9QZ81; -.
DR PhosphoSitePlus; Q9QZ81; -.
DR jPOST; Q9QZ81; -.
DR PaxDb; Q9QZ81; -.
DR PeptideAtlas; Q9QZ81; -.
DR PRIDE; Q9QZ81; -.
DR GeneID; 59117; -.
DR UCSC; RGD:621255; rat.
DR CTD; 27161; -.
DR RGD; 621255; Ago2.
DR eggNOG; KOG1041; Eukaryota.
DR InParanoid; Q9QZ81; -.
DR OrthoDB; 159407at2759; -.
DR PhylomeDB; Q9QZ81; -.
DR Reactome; R-RNO-203927; MicroRNA (miRNA) biogenesis.
DR Reactome; R-RNO-426486; Small interfering RNA (siRNA) biogenesis.
DR Reactome; R-RNO-426496; Post-transcriptional silencing by small RNAs.
DR Reactome; R-RNO-5578749; Transcriptional regulation by small RNAs.
DR PRO; PR:Q9QZ81; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0030425; C:dendrite; ISO:RGD.
DR GO; GO:0070062; C:extracellular exosome; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:BHF-UCL.
DR GO; GO:0005845; C:mRNA cap binding complex; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0000932; C:P-body; ISO:RGD.
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:0001046; F:core promoter sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0003725; F:double-stranded RNA binding; ISO:RGD.
DR GO; GO:0004521; F:endoribonuclease activity; ISO:RGD.
DR GO; GO:0090624; F:endoribonuclease activity, cleaving miRNA-paired mRNA; ISO:RGD.
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:0035198; F:miRNA binding; ISO:RGD.
DR GO; GO:0003729; F:mRNA binding; ISO:RGD.
DR GO; GO:0098808; F:mRNA cap binding; ISO:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:RGD.
DR GO; GO:0000340; F:RNA 7-methylguanosine cap binding; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; ISO:RGD.
DR GO; GO:0000993; F:RNA polymerase II complex binding; ISO:RGD.
DR GO; GO:0003727; F:single-stranded RNA binding; ISO:RGD.
DR GO; GO:0035197; F:siRNA binding; ISS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; NAS:RGD.
DR GO; GO:0031047; P:gene silencing by RNA; ISS:UniProtKB.
DR GO; GO:0010586; P:miRNA metabolic process; ISO:RGD.
DR GO; GO:0035196; P:miRNA processing; ISO:RGD.
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:0042985; P:negative regulation of amyloid precursor protein biosynthetic process; IMP:ARUK-UCL.
DR GO; GO:0045947; P:negative regulation of translational initiation; ISS:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
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:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045975; P:positive regulation of translation, ncRNA-mediated; ISO:RGD.
DR GO; GO:1901165; P:positive regulation of trophoblast cell migration; ISO:RGD.
DR GO; GO:0009791; P:post-embryonic development; ISO:RGD.
DR GO; GO:0031054; P:pre-miRNA processing; ISS:UniProtKB.
DR GO; GO:0070922; P:RISC complex assembly; ISO:RGD.
DR GO; GO:0010501; P:RNA secondary structure unwinding; ISO:RGD.
DR GO; GO:0030422; P:siRNA processing; ISO:RGD.
DR GO; GO:0090625; P:siRNA-mediated gene silencing by mRNA destabilization; ISO:RGD.
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; Endonuclease; Hydrolase; Hydroxylation; Magnesium; Manganese;
KW Metal-binding; Nitration; 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..860
FT /note="Protein argonaute-2"
FT /id="PRO_0000194060"
FT DOMAIN 236..349
FT /note="PAZ"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03031"
FT DOMAIN 518..819
FT /note="Piwi"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03031"
FT REGION 312..317
FT /note="Interaction with guide RNA"
FT /evidence="ECO:0000250"
FT REGION 525..567
FT /note="Interaction with guide RNA"
FT /evidence="ECO:0000250"
FT REGION 588..591
FT /note="Interaction with GW182 family members"
FT /evidence="ECO:0000255"
FT REGION 651..661
FT /note="Interaction with GW182 family members"
FT /evidence="ECO:0000255"
FT REGION 710..711
FT /note="Interaction with guide RNA"
FT /evidence="ECO:0000250"
FT REGION 754..762
FT /note="Interaction with guide RNA"
FT /evidence="ECO:0000250"
FT REGION 791..813
FT /note="Interaction with guide RNA"
FT /evidence="ECO:0000250"
FT BINDING 598
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03031"
FT BINDING 670
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03031"
FT BINDING 808
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03031"
FT MOD_RES 2
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q8CJG0, ECO:0000255|HAMAP-
FT Rule:MF_03031"
FT MOD_RES 388
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKV8"
FT MOD_RES 701
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03031"
FT MOD_RES 825
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKV8"
FT MOD_RES 829
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKV8"
FT MOD_RES 832
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKV8"
FT MOD_RES 835
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKV8"
SQ SEQUENCE 860 AA; 97318 MW; A5B0798C66481C9C CRC64;
MYSGAGPVLA SPAPTTSPIP GYAFKPPPRP DFGTTGRTIK LQANFFEMDI PKIDIYHYEL
DIKPEKCPRR VNREIVEHMV QHFKTQIFGD RKPVFDGRKN LYTAMPLPIG RDKVELEVTL
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 SVEPMFRHLK NTYAGLQLVV VILPGKTPVY AEVKRVGDTV
LGMATQCVQM KNVQRTTPQT LSNLCLKINV KLGGVNNILL PQGRPPVFQQ PVIFLGADVT
HPPAGDGKKP SIAAVVGSMD AHPNRYCATV RVQQHRQEII QDLAAMVREL LIQFYKSTRF
KPTRIIFYRD GVSEGQFQQV LHHELLAIRE ACIKLEKEYQ PGITFIVVQK RHHTRLFCTD
KNERVGKSGN IPAGTTVDTK ITHPTEFDFY LCSHAGIQGT SRPSHYHVLW DDNRFSSDEL
QILTYQLCHT YVRCTRSVSI PAPAYYAHLV AFRARYHLVD KEHDSAEGSH TSGQSNGRDH
QALAKAVQVH QDTLRTMYFA
