AGO3_MOUSE
ID AGO3_MOUSE Reviewed; 860 AA.
AC Q8CJF9; Q3TBP7;
DT 14-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Protein argonaute-3 {ECO:0000255|HAMAP-Rule:MF_03032};
DE Short=Argonaute3 {ECO:0000255|HAMAP-Rule:MF_03032};
DE Short=mAgo3;
DE EC=3.1.26.n2 {ECO:0000250|UniProtKB:Q9H9G7};
DE AltName: Full=Argonaute RISC catalytic component 3;
DE AltName: Full=Eukaryotic translation initiation factor 2C 3 {ECO:0000255|HAMAP-Rule:MF_03032};
DE Short=eIF-2C 3 {ECO:0000255|HAMAP-Rule:MF_03032};
DE Short=eIF2C 3 {ECO:0000255|HAMAP-Rule:MF_03032};
DE AltName: Full=Piwi/argonaute family protein meIF2C3;
GN Name=Ago3; Synonyms=Eif2c3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12526743; DOI=10.1016/s0960-9822(02)01394-5;
RA Doi N., Zenno S., Ueda R., Ohki-Hamazaki H., Ui-Tei K., Saigo K.;
RT "Short-interfering-RNA-mediated gene silencing in mammalian cells requires
RT Dicer and eIF2C translation initiation factors.";
RL Curr. Biol. 13:41-46(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NOD;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION.
RX PubMed=19174539; DOI=10.1101/gad.1749809;
RA Su H., Trombly M.I., Chen J., Wang X.;
RT "Essential and overlapping functions for mammalian Argonautes in microRNA
RT silencing.";
RL Genes Dev. 23:304-317(2009).
CC -!- FUNCTION: Required for RNA-mediated gene silencing (RNAi). Binds to
CC short RNAs such as microRNAs (miRNAs) and represses the translation of
CC mRNAs which are complementary to them. Proposed to be involved in
CC stabilization of small RNA derivates (siRNA) derived from processed RNA
CC polymerase III-transcribed Alu repeats containing a DR2 retinoic acid
CC response element (RARE) in stem cells and in the subsequent siRNA-
CC dependent degradation of a subset of RNA polymerase II-transcribed
CC coding mRNAs by recruiting a mRNA decapping complex involving EDC4
CC (PubMed:19174539). Possesses RNA slicer activity but only on select
CC RNAs bearing 5'- and 3'-flanking sequences to the region of guide-
CC target complementarity (By similarity). {ECO:0000255|HAMAP-
CC Rule:MF_03032, ECO:0000269|PubMed:19174539}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=endonucleolytic cleavage to 5'-phosphomonoester.;
CC EC=3.1.26.n2; Evidence={ECO:0000250|UniProtKB:Q9H9G7};
CC -!- SUBUNIT: Interacts with EIF4B, IMP8, PRMT5 and TNRC6B (By similarity).
CC Interacts with APOBEC3F, APOBEC3G and APOBEC3H. Interacts with EDC4 (By
CC similarity). {ECO:0000255|HAMAP-Rule:MF_03032}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000255|HAMAP-
CC Rule:MF_03032}.
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 AGO3 when it is engaged with a TDMD target.
CC {ECO:0000250|UniProtKB:Q9UKV8}.
CC -!- SIMILARITY: Belongs to the argonaute family. Ago subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03032}.
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DR EMBL; AB081473; BAC15768.1; -; mRNA.
DR EMBL; AK154436; BAE32586.1; -; mRNA.
DR EMBL; AK171118; BAE42260.1; -; mRNA.
DR EMBL; AL606976; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466552; EDL30287.1; -; Genomic_DNA.
DR EMBL; BC137964; AAI37965.1; -; mRNA.
DR CCDS; CCDS18652.1; -.
DR RefSeq; NP_700451.2; NM_153402.2.
DR AlphaFoldDB; Q8CJF9; -.
DR SMR; Q8CJF9; -.
DR BioGRID; 229499; 19.
DR IntAct; Q8CJF9; 3.
DR MINT; Q8CJF9; -.
DR STRING; 10090.ENSMUSP00000066633; -.
DR iPTMnet; Q8CJF9; -.
DR PhosphoSitePlus; Q8CJF9; -.
DR EPD; Q8CJF9; -.
DR MaxQB; Q8CJF9; -.
DR PaxDb; Q8CJF9; -.
DR PeptideAtlas; Q8CJF9; -.
DR PRIDE; Q8CJF9; -.
DR ProteomicsDB; 282030; -.
DR Antibodypedia; 31609; 176 antibodies from 30 providers.
DR DNASU; 214150; -.
DR Ensembl; ENSMUST00000069097; ENSMUSP00000066633; ENSMUSG00000028842.
DR GeneID; 214150; -.
DR KEGG; mmu:214150; -.
DR UCSC; uc008uth.2; mouse.
DR CTD; 192669; -.
DR MGI; MGI:2446634; Ago3.
DR VEuPathDB; HostDB:ENSMUSG00000028842; -.
DR eggNOG; KOG1041; Eukaryota.
DR GeneTree; ENSGT00940000155256; -.
DR HOGENOM; CLU_004544_4_3_1; -.
DR InParanoid; Q8CJF9; -.
DR OMA; KYIADSR; -.
DR OrthoDB; 159407at2759; -.
DR PhylomeDB; Q8CJF9; -.
DR TreeFam; TF101510; -.
DR Reactome; R-MMU-203927; MicroRNA (miRNA) biogenesis.
DR Reactome; R-MMU-426486; Small interfering RNA (siRNA) biogenesis.
DR Reactome; R-MMU-426496; Post-transcriptional silencing by small RNAs.
DR BioGRID-ORCS; 214150; 0 hits in 71 CRISPR screens.
DR ChiTaRS; Ago3; mouse.
DR PRO; PR:Q8CJF9; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q8CJF9; protein.
DR Bgee; ENSMUSG00000028842; Expressed in animal zygote and 215 other tissues.
DR ExpressionAtlas; Q8CJF9; baseline and differential.
DR Genevisible; Q8CJF9; MM.
DR GO; GO:0000794; C:condensed nuclear chromosome; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0000932; C:P-body; IEA:UniProtKB-SubCell.
DR GO; GO:0016442; C:RISC complex; IDA:MGI.
DR GO; GO:0070578; C:RISC-loading complex; ISO:MGI.
DR GO; GO:0003725; F:double-stranded RNA binding; ISO:MGI.
DR GO; GO:0004521; F:endoribonuclease activity; ISS:UniProtKB.
DR GO; GO:0090624; F:endoribonuclease activity, cleaving miRNA-paired mRNA; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035198; F:miRNA binding; ISO:MGI.
DR GO; GO:0003723; F:RNA binding; IDA:MGI.
DR GO; GO:0003727; F:single-stranded RNA binding; ISO:MGI.
DR GO; GO:0035196; P:miRNA processing; ISO:MGI.
DR GO; GO:0035278; P:miRNA-mediated gene silencing by inhibition of translation; ISS:UniProtKB.
DR GO; GO:0006402; P:mRNA catabolic process; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IMP:BHF-UCL.
DR GO; GO:0031054; P:pre-miRNA processing; ISO:MGI.
DR GO; GO:0072091; P:regulation of stem cell proliferation; ISO:MGI.
DR GO; GO:0070922; P:RISC complex assembly; ISO:MGI.
DR GO; GO:0010501; P:RNA secondary structure unwinding; ISO:MGI.
DR CDD; cd04657; Piwi_ago-like; 1.
DR Gene3D; 3.30.420.10; -; 1.
DR HAMAP; MF_03032; AGO3; 1.
DR InterPro; IPR028603; AGO3.
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 2: Evidence at transcript level;
KW Acetylation; Cytoplasm; Endonuclease; Hydrolase; Metal-binding; Nuclease;
KW Phosphoprotein; Reference proteome; Ribonucleoprotein; RNA-binding;
KW RNA-mediated gene silencing; Translation regulation; Ubl conjugation.
FT CHAIN 1..860
FT /note="Protein argonaute-3"
FT /id="PRO_0000194062"
FT DOMAIN 236..349
FT /note="PAZ"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03032"
FT DOMAIN 518..819
FT /note="Piwi"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03032"
FT REGION 530..567
FT /note="Interaction with guide RNA"
FT /evidence="ECO:0000250|UniProtKB:Q9H9G7"
FT REGION 758..805
FT /note="Interaction with guide RNA"
FT /evidence="ECO:0000250|UniProtKB:Q9H9G7"
FT BINDING 598
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:Q9H9G7"
FT BINDING 638
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:Q9H9G7"
FT BINDING 670
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:Q9H9G7"
FT BINDING 808
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:Q9H9G7"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q9H9G7"
FT MOD_RES 825
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H9G7"
FT CONFLICT 70
FT /note="M -> K (in Ref. 1; BAC15768)"
FT /evidence="ECO:0000305"
FT CONFLICT 400
FT /note="F -> L (in Ref. 1; BAC15768)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 860 AA; 97277 MW; B457A31093BB5BB0 CRC64;
MEIGSAGPIG AQPLFIVPRR PGYGTMGKPI KLLANCFQVE IPKIDVYLYE VDIKPDKCPR
RVNREVVDSM VQHFKVTIFG DRRPVYDGKR SLYTANPLPV ATTGVDLDVT LPGEGGKDRP
FKVSVKFVSR VSWHLLHEAL AGGTLPEPLE LDKPVSTNPV HAVDVVLRHL PSMKYTPVGR
SFFSAPEGYD HPLGGGREVW FGFHQSVRPA MWKMMLNIDV SATAFYKAQP VIQFMCEVLD
IHNIDEQPRP LTDSHRVKFT KEIKGLKVEV THCGTMRRKY RVCNVTRRPA SHQTFPLQLE
NGQTVERTVA QYFREKYTLQ LKYPHLPCLQ VGQEQKHTYL PLEVCNIVAG QRCIKKLTDN
QTSTMIKATA RSAPDRQEEI SRLVRSANYE TDPFVQEFQF KVRDEMAHVT GRVLPAPMLQ
YGGRNRTVAT PSHGVWDMRG KQFHTGVEIK MWAIACFATQ RQCREEILKG FTDQLRKISK
DAGMPIQGQP CFCKYAQGAD SVEPMFRHLK NTYSGLQLII VILPGKTPVY AEVKRVGDTL
LGMATQCVQV KNVIKTSPQT LSNLCLKINV KLGGINNILV PHQRPSVFQQ PVIFLGADVT
HPPAGDGKKP SIAAVVGSMD AHPSRYCATV RVQRPRQEII QDLASMVREL LIQFYKSTRF
KPTRIIFYRD GVSEGQFRQV LYYELLAIRE ACISLEKDYQ PGITYIVVQK RHHTRLFCAD
RTERVGRSGN IPAGTTVDTD ITHPYEFDFY LCSHAGIQGT SRPSHYHVLW DDNFFTADEL
QLLTYQLCHT YVRCTRSVSI PAPAYYAHLV AFRARYHLVD KEHDSAEGSH VSGQSNGRDP
QALAKAVQIH QDTLRTMYFA
