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   05-OCT-2016, entry version 108.
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       {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   -!- SIMILARITY: Contains 1 PAZ domain. {ECO:0000255|HAMAP-
CC       Rule:MF_03031}.
CC   -!- SIMILARITY: Contains 1 Piwi domain. {ECO:0000255|HAMAP-
CC       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};
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DR   EMBL; AF195534; AAF12800.1; ALT_INIT; mRNA.
DR   RefSeq; NP_067608.1; NM_021597.1.
DR   UniGene; Rn.234328; -.
DR   ProteinModelPortal; Q9QZ81; -.
DR   BioGrid; 248738; 1.
DR   IntAct; Q9QZ81; 6.
DR   STRING; 10116.ENSRNOP00000011898; -.
DR   iPTMnet; Q9QZ81; -.
DR   PhosphoSite; 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:0000932; C:cytoplasmic mRNA processing body; IEA:UniProtKB-SubCell.
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:0005844; C:polysome; ISS:UniProtKB.
DR   GO; GO:0016442; C:RISC complex; IEA:UniProtKB-HAMAP.
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:0035198; F:miRNA binding; IEA:UniProtKB-HAMAP.
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. {ECO:0000255|HAMAP-
FT                                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
//