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 15-MAR-2017, entry version 112. 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; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; 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 RT proteins involved in stem cell differentiation."; RL Mol. Biol. Cell 10:3357-3372(1999). CC -!- FUNCTION: Required for RNA-mediated gene silencing (RNAi) by the CC RNA-induced silencing complex (RISC). The 'minimal RISC' appears CC to include AGO2 bound to a short guide RNA such as a microRNA CC (miRNA) or short interfering RNA (siRNA). These guide RNAs direct CC RISC to complementary mRNAs that are targets for RISC-mediated CC gene silencing. The precise mechanism of gene silencing depends on CC the degree of complementarity between the miRNA or siRNA and its CC target. Binding of RISC to a perfectly complementary mRNA CC generally results in silencing due to endonucleolytic cleavage of CC the mRNA specifically by AGO2. Binding of RISC to a partially CC complementary mRNA results in silencing through inhibition of CC translation, and this is independent of endonuclease activity. May CC inhibit translation initiation by binding to the 7-methylguanosine CC cap, thereby preventing the recruitment of the translation CC initiation factor eIF4-E. May also inhibit translation initiation CC via interaction with EIF6, which itself binds to the 60S ribosomal CC 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 CC (P-bodies), where mRNA degradation may subsequently occur. In some CC cases RISC-mediated translational repression is also observed for CC miRNAs that perfectly match the 3' untranslated region (3'-UTR). CC Can also up-regulate the translation of specific mRNAs under CC certain growth conditions. Binds to the AU element of the 3'-UTR CC of the TNF (TNF-alpha) mRNA and up-regulates translation under CC conditions of serum starvation. Also required for transcriptional CC gene silencing (TGS), in which short RNAs known as antigene RNAs CC or agRNAs direct the transcriptional repression of complementary CC promoter regions. {ECO:0000255|HAMAP-Rule:MF_03031}. CC -!- CATALYTIC ACTIVITY: Endonucleolytic cleavage to 5'- CC phosphomonoester. {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 CC TARBP2 during assembly of the RNA-induced silencing complex CC (RISC). Together, DICER1, AGO2 and TARBP2 constitute the trimeric CC RISC loading complex (RLC), or micro-RNA (miRNA) loading complex CC (miRLC). Within the RLC/miRLC, DICER1 and TARBP2 are required to CC process precursor miRNAs (pre-miRNAs) to mature miRNAs and then CC load them onto AGO2. AGO2 bound to the mature miRNA constitutes CC the minimal RISC and may subsequently dissociate from DICER1 and CC TARBP2. Note however that the term RISC has also been used to CC describe the trimeric RLC/miRLC. The formation of RISC complexes CC containing siRNAs rather than miRNAs appears to occur CC independently of DICER1. Interacts with AGO1. Also interacts with CC DDB1, DDX5, DDX6, DDX20, DHX30, DHX36, DDX47, DHX9, ELAVL, FXR1, CC GEMIN4, HNRNPF, IGF2BP1, ILF3, IMP8, MATR3, PABPC1, PRMT5, P4HA1, CC P4HB, RBM4, SART3, TNRC6A, TNRC6B, UPF1 and YBX1. Interacts with CC the P-body components DCP1A and XRN1. Associates with polysomes CC and messenger ribonucleoproteins (mNRPs). Interacts with RBM4; the CC interaction is modulated under stress-induced conditions, occurs CC under both cell proliferation and differentiation conditions and CC in an RNA- and phosphorylation-independent manner. Interacts with CC LIMD1, WTIP and AJUBA. Interacts with TRIM71. Interacts with CC APOBEC3G in an RNA-dependent manner. Interacts with APOBEC3A, CC APOBEC3C, APOBEC3F and APOBEC3H. Interacts with DICER1, TARBP2, CC EIF6, MOV10 and RPL7A (60S ribosome subunit); they form a large CC RNA-induced silencing complex (RISC). Interacts with FMR1. CC Interacts with ZFP36. {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 CC recruitment to P-bodies. Translocation to the nucleus requires CC IMP8. {ECO:0000255|HAMAP-Rule:MF_03031}. CC -!- DOMAIN: The Piwi domain may perform RNA cleavage by a mechanism CC similar to that of RNase H. However, while RNase H utilizes a CC triad of Asp-Asp-Glu (DDE) for metal ion coordination, this CC protein appears to utilize a triad of Asp-Asp-His (DDH). CC {ECO:0000255|HAMAP-Rule:MF_03031}. CC -!- PTM: Hydroxylated. 4-hydroxylation appears to enhance protein CC stability but is not required for miRNA-binding or endonuclease CC activity. {ECO:0000255|HAMAP-Rule:MF_03031}. 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=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF195534; AAF12800.1; ALT_INIT; mRNA. DR RefSeq; NP_067608.1; NM_021597.1. DR UniGene; Rn.234328; -. DR ProteinModelPortal; Q9QZ81; -. DR SMR; Q9QZ81; -. DR BioGrid; 248738; 1. DR IntAct; Q9QZ81; 6. DR STRING; 10116.ENSRNOP00000011898; -. DR iPTMnet; Q9QZ81; -. DR PhosphoSitePlus; Q9QZ81; -. DR PaxDb; Q9QZ81; -. DR PeptideAtlas; Q9QZ81; -. DR PRIDE; Q9QZ81; -. DR GeneID; 59117; -. DR KEGG; rno:59117; -. DR UCSC; RGD:621255; rat. DR CTD; 27161; -. DR RGD; 621255; Ago2. DR eggNOG; KOG1041; Eukaryota. DR eggNOG; ENOG410XP07; LUCA. DR HOGENOM; HOG000116043; -. DR InParanoid; Q9QZ81; -. DR KO; K11593; -. DR PhylomeDB; Q9QZ81; -. DR PRO; PR:Q9QZ81; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0030529; C:intracellular ribonucleoprotein complex; ISS:UniProtKB. DR GO; GO:0035068; C:micro-ribonucleoprotein complex; ISS:UniProtKB. 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; IEA:UniProtKB-SubCell. DR GO; GO:0000932; C:P-body; IEA:UniProtKB-SubCell. DR GO; GO:0005844; C:polysome; ISS:UniProtKB. DR GO; GO:0016442; C:RISC complex; IEA:InterPro. 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:0030154; P:cell differentiation; NAS:RGD. DR GO; GO:0031047; P:gene silencing by RNA; ISS:UniProtKB. DR GO; GO:0035278; P:miRNA mediated inhibition of translation; ISS:UniProtKB. DR GO; GO:0035279; P:mRNA cleavage involved in gene silencing by miRNA; 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:UniProtKB-KW. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. 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; IPR003165; Piwi. DR InterPro; IPR012337; RNaseH-like_dom. 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 2: Evidence at transcript level; KW Complete proteome; Cytoplasm; Endonuclease; Hydrolase; Hydroxylation; KW Magnesium; Manganese; Metal-binding; Nitration; Nuclease; Nucleus; KW Phosphoprotein; Reference proteome; Repressor; Ribonucleoprotein; KW RNA-binding; RNA-mediated gene silencing; Transcription; KW Transcription regulation; Translation regulation. FT CHAIN 1 860 Protein argonaute-2. FT /FTId=PRO_0000194060. FT DOMAIN 236 349 PAZ. {ECO:0000255|HAMAP-Rule:MF_03031}. FT DOMAIN 518 819 Piwi. {ECO:0000255|HAMAP-Rule:MF_03031}. FT REGION 312 317 Interaction with guide RNA. FT {ECO:0000250}. FT REGION 525 567 Interaction with guide RNA. FT {ECO:0000250}. FT REGION 588 591 Interaction with GW182 family members. FT {ECO:0000255}. FT REGION 651 661 Interaction with GW182 family members. FT {ECO:0000255}. FT REGION 710 711 Interaction with guide RNA. FT {ECO:0000250}. FT REGION 754 762 Interaction with guide RNA. FT {ECO:0000250}. FT REGION 791 813 Interaction with guide RNA. FT {ECO:0000250}. FT METAL 598 598 Divalent metal cation. FT {ECO:0000255|HAMAP-Rule:MF_03031}. FT METAL 670 670 Divalent metal cation. FT {ECO:0000255|HAMAP-Rule:MF_03031}. FT METAL 808 808 Divalent metal cation. FT {ECO:0000255|HAMAP-Rule:MF_03031}. FT MOD_RES 2 2 Nitrated tyrosine. FT {ECO:0000250|UniProtKB:Q8CJG0, FT ECO:0000255|HAMAP-Rule:MF_03031}. FT MOD_RES 388 388 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9UKV8}. FT MOD_RES 701 701 4-hydroxyproline. {ECO:0000255|HAMAP- FT Rule:MF_03031}. FT MOD_RES 825 825 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9H9G7}. FT MOD_RES 829 829 Phosphoserine. FT {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 //