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   22-FEB-2012, entry version 73.
DE   RecName: Full=Protein argonaute-2;
DE            Short=Argonaute2;
DE            EC=3.1.26.n2;
DE   AltName: Full=Eukaryotic translation initiation factor 2C 2;
DE            Short=eIF-2C 2;
DE            Short=eIF2C 2;
DE   AltName: Full=Golgi ER protein 95 kDa;
DE            Short=GERp95;
DE   AltName: Full=Protein slicer;
GN   Name=Eif2c2; Synonyms=Ago2;
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   MEDLINE=99443791; PubMed=10512872;
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 EIF2C2/AGO2 bound to a short guide RNA such as a
CC       microRNA (miRNA) or short interfering RNA (siRNA). These guide
CC       RNAs direct RISC to complementary mRNAs that are targets for RISC-
CC       mediated gene silencing. The precise mechanism of gene silencing
CC       depends on the degree of complementarity between the miRNA or
CC       siRNA and its target. Binding of RISC to a perfectly complementary
CC       mRNA generally results in silencing due to endonucleolytic
CC       cleavage of the mRNA specifically by EIF2C2/AGO2. Binding of RISC
CC       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
CC       60S ribosomal subunit and prevents its association with the 40S
CC       ribosomal subunit. The inhibition of translational initiation
CC       leads to the accumulation of the affected mRNA in cytoplasmic
CC       processing bodies (P-bodies), where mRNA degradation may
CC       subsequently occur. In some cases RISC-mediated translational
CC       repression is also observed for miRNAs that perfectly match the 3'
CC       untranslated region (3'-UTR). Can also upregulate the translation
CC       of specific mRNAs under certain growth conditions. Binds to the AU
CC       element of the 3'-UTR of the TNF (TNF-alpha) mRNA and upregulates
CC       translation under conditions of serum starvation. Also required
CC       for transcriptional gene silencing (TGS), in which short RNAs
CC       known as antigene RNAs or agRNAs direct the transcriptional
CC       repression of complementary promoter regions (By similarity).
CC   -!- CATALYTIC ACTIVITY: Endonucleolytic cleavage to 5'-
CC       phosphomonoester.
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, EIF2C2/AGO2 and TARBP2 constitute the
CC       trimeric RISC loading complex (RLC), or micro-RNA (miRNA) loading
CC       complex (miRLC). Within the RLC/miRLC, DICER1 and TARBP2 are
CC       required to process precursor miRNAs (pre-miRNAs) to mature miRNAs
CC       and then load them onto EIF2C2/AGO2. EIF2C2/AGO2 bound to the
CC       mature miRNA constitutes the minimal RISC and may subsequently
CC       dissociate from DICER1 and TARBP2. Note however that the term RISC
CC       has also been used to describe the trimeric RLC/miRLC. The
CC       formation of RISC complexes containing siRNAs rather than miRNAs
CC       appears to occur independently of DICER1. Interacts with
CC       EIF2C1/AGO1. Also interacts with DDB1, DDX5, DDX6, DDX20, DHX30,
CC       DHX36, DDX47, DHX9, EIF6, ELAVL, FXR1, GEMIN4, HNRNPF, IGF2BP1,
CC       ILF3, IMP8, MATR3, MOV10, PABPC1, PRMT5, P4HA1, P4HB, RBM4, SART3,
CC       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
CC       is modulated under stress-induced conditions, occurs under both
CC       cell proliferation and differentiation conditions and in a RNA-
CC       and phosphorylation-independent manner (By similarity).
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, P-body (By similarity). Nucleus
CC       (By similarity). Note=Translational repression of mRNAs results in
CC       their recruitment to P-bodies. Translocation to the nucleus
CC       requires IMP8 (By similarity).
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 triad
CC       of Asp-Asp-Glu (DDE) for metal ion coordination, this protein
CC       appears to utilize a triad of Asp-Asp-His (DDH) (By similarity).
CC   -!- PTM: Hydroxylated. 4-hydroxylation appears to enhance protein
CC       stability but is not required for miRNA-binding or endonuclease
CC       activity (By similarity).
CC   -!- SIMILARITY: Belongs to the argonaute family. Ago subfamily.
CC   -!- SIMILARITY: Contains 1 PAZ domain.
CC   -!- SIMILARITY: Contains 1 Piwi domain.
CC   -!- CAUTION: Was originally (PubMed:10512872) thought to be membrane-
CC       associated.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAF12800.1; Type=Erroneous initiation;
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DR   EMBL; AF195534; AAF12800.1; ALT_INIT; mRNA.
DR   IPI; IPI00214529; -.
DR   RefSeq; NP_067608.1; NM_021597.1.
DR   UniGene; Rn.35512; -.
DR   ProteinModelPortal; Q9QZ81; -.
DR   SMR; Q9QZ81; 223-390.
DR   STRING; Q9QZ81; -.
DR   GeneID; 59117; -.
DR   KEGG; rno:59117; -.
DR   CTD; 27161; -.
DR   RGD; 621255; Eif2c2.
DR   eggNOG; NOG279895; -.
DR   InParanoid; Q9QZ81; -.
DR   KO; K11593; -.
DR   OrthoDB; EOG4229J0; -.
DR   NextBio; 611775; -.
DR   ArrayExpress; Q9QZ81; -.
DR   Genevestigator; Q9QZ81; -.
DR   GermOnline; ENSRNOG00000008533; Rattus norvegicus.
DR   GO; GO:0000932; C:cytoplasmic mRNA processing body; IEA:UniProtKB-SubCell.
DR   GO; GO:0035068; C:micro-ribonucleoprotein complex; ISS:UniProtKB.
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:RNA-induced silencing 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:0035279; P:mRNA cleavage involved in gene silencing by miRNA; ISS:UniProtKB.
DR   GO; GO:0035278; P:negative regulation of translation involved in gene silencing by miRNA; ISS:UniProtKB.
DR   GO; GO:0045947; P:negative regulation of translational initiation; ISS:UniProtKB.
DR   GO; GO:0031054; P:pre-miRNA processing; ISS:UniProtKB.
DR   GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
DR   GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR   InterPro; IPR014811; DUF1785.
DR   InterPro; IPR003100; PAZ.
DR   InterPro; IPR003165; Piwi.
DR   InterPro; IPR012337; RNaseH-like_dom.
DR   Pfam; PF08699; DUF1785; 1.
DR   Pfam; PF02170; PAZ; 1.
DR   Pfam; PF02171; Piwi; 1.
DR   SMART; SM00949; PAZ; 1.
DR   SMART; SM00950; Piwi; 1.
DR   SUPFAM; SSF101690; PAZ; 1.
DR   SUPFAM; SSF53098; RNaseH_fold; 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   Metal-binding; Nitration; Nuclease; Nucleus; Reference proteome;
KW   Repressor; Ribonucleoprotein; RNA-binding;
KW   RNA-mediated gene silencing; Transcription; Transcription regulation;
KW   Translation regulation.
FT   CHAIN         1    860       Protein argonaute-2.
FT                                /FTId=PRO_0000194060.
FT   DOMAIN      236    349       PAZ.
FT   DOMAIN      518    819       Piwi.
FT   METAL       598    598       Divalent metal cation (By similarity).
FT   METAL       670    670       Divalent metal cation (By similarity).
FT   METAL       808    808       Divalent metal cation (By similarity).
FT   MOD_RES       2      2       Nitrated tyrosine (By similarity).
FT   MOD_RES     701    701       4-hydroxyproline (By similarity).
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
//