AGO4_MOUSE
ID AGO4_MOUSE Reviewed; 861 AA.
AC Q8CJF8; Q4VBD7; Q6ZPM6; Q8BTF4;
DT 14-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 2.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Protein argonaute-4 {ECO:0000255|HAMAP-Rule:MF_03033};
DE Short=Argonaute4 {ECO:0000255|HAMAP-Rule:MF_03033};
DE Short=mAgo4;
DE AltName: Full=Argonaute RISC catalytic component 4;
DE AltName: Full=Eukaryotic translation initiation factor 2C 4 {ECO:0000255|HAMAP-Rule:MF_03033};
DE Short=eIF-2C 4 {ECO:0000255|HAMAP-Rule:MF_03033};
DE Short=eIF2C 4 {ECO:0000255|HAMAP-Rule:MF_03033};
DE AltName: Full=Piwi/argonaute family protein meIF2C4;
GN Name=Ago4; Synonyms=Eif2c4, Kiaa1567;
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] (ISOFORM 1).
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] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Testis;
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 MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Eye;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 144-861 (ISOFORM 2).
RC TISSUE=Pancreatic islet;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
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. Lacks endonuclease activity and
CC does not appear to cleave target mRNAs. {ECO:0000255|HAMAP-
CC Rule:MF_03033, ECO:0000269|PubMed:19174539}.
CC -!- SUBUNIT: Interacts with EIF4B, IMP8, PRMT5, TNRC6A and TNRC6B.
CC Interacts with ZFP36. {ECO:0000255|HAMAP-Rule:MF_03033}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000255|HAMAP-
CC Rule:MF_03033}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8CJF8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8CJF8-2; Sequence=VSP_036487;
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 AGO4 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_03033}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC26738.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC98205.2; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
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DR EMBL; AB081474; BAC15769.1; -; mRNA.
DR EMBL; AK030018; BAC26738.1; ALT_INIT; mRNA.
DR EMBL; AL606935; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC096023; AAH96023.1; -; mRNA.
DR EMBL; AK129395; BAC98205.2; ALT_SEQ; Transcribed_RNA.
DR CCDS; CCDS18654.1; -. [Q8CJF8-1]
DR RefSeq; NP_694817.2; NM_153177.3. [Q8CJF8-1]
DR AlphaFoldDB; Q8CJF8; -.
DR SMR; Q8CJF8; -.
DR BioGRID; 218348; 4.
DR STRING; 10090.ENSMUSP00000081312; -.
DR iPTMnet; Q8CJF8; -.
DR PhosphoSitePlus; Q8CJF8; -.
DR MaxQB; Q8CJF8; -.
DR PaxDb; Q8CJF8; -.
DR PeptideAtlas; Q8CJF8; -.
DR PRIDE; Q8CJF8; -.
DR ProteomicsDB; 285567; -. [Q8CJF8-1]
DR ProteomicsDB; 285568; -. [Q8CJF8-2]
DR Antibodypedia; 31591; 172 antibodies from 28 providers.
DR DNASU; 76850; -.
DR Ensembl; ENSMUST00000084289; ENSMUSP00000081312; ENSMUSG00000042500. [Q8CJF8-1]
DR GeneID; 76850; -.
DR KEGG; mmu:76850; -.
DR UCSC; uc008utk.2; mouse. [Q8CJF8-1]
DR CTD; 192670; -.
DR MGI; MGI:1924100; Ago4.
DR VEuPathDB; HostDB:ENSMUSG00000042500; -.
DR eggNOG; KOG1041; Eukaryota.
DR GeneTree; ENSGT00940000158729; -.
DR HOGENOM; CLU_004544_0_0_1; -.
DR InParanoid; Q8CJF8; -.
DR OMA; VGANRHY; -.
DR PhylomeDB; Q8CJF8; -.
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; 76850; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Ago4; mouse.
DR PRO; PR:Q8CJF8; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q8CJF8; protein.
DR Bgee; ENSMUSG00000042500; Expressed in skin of external ear and 214 other tissues.
DR Genevisible; Q8CJF8; MM.
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:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0000932; C:P-body; IDA:MGI.
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; IBA:GO_Central.
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:0008584; P:male gonad development; IMP:MGI.
DR GO; GO:0007140; P:male meiotic nuclear division; IMP:MGI.
DR GO; GO:0010586; P:miRNA metabolic process; IMP: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:0043066; P:negative regulation of apoptotic process; IMP:MGI.
DR GO; GO:0031054; P:pre-miRNA processing; ISO:MGI.
DR GO; GO:0022604; P:regulation of cell morphogenesis; IMP:MGI.
DR GO; GO:0070922; P:RISC complex assembly; ISO:MGI.
DR GO; GO:0010501; P:RNA secondary structure unwinding; ISO:MGI.
DR GO; GO:0007130; P:synaptonemal complex assembly; IMP:MGI.
DR CDD; cd04657; Piwi_ago-like; 1.
DR Gene3D; 3.30.420.10; -; 1.
DR HAMAP; MF_03033; AGO4; 1.
DR InterPro; IPR028604; AGO4.
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 Alternative splicing; Cytoplasm; Reference proteome; Ribonucleoprotein;
KW RNA-binding; RNA-mediated gene silencing; Translation regulation;
KW Ubl conjugation.
FT CHAIN 1..861
FT /note="Protein argonaute-4"
FT /id="PRO_0000194064"
FT DOMAIN 225..338
FT /note="PAZ"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03033"
FT DOMAIN 509..820
FT /note="Piwi"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03033"
FT REGION 825..846
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 399..460
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14621295"
FT /id="VSP_036487"
FT CONFLICT 128
FT /note="V -> A (in Ref. 1; BAC15769)"
FT /evidence="ECO:0000305"
FT CONFLICT 541
FT /note="V -> I (in Ref. 1; BAC15769)"
FT /evidence="ECO:0000305"
FT CONFLICT 570
FT /note="L -> P (in Ref. 1; BAC15769)"
FT /evidence="ECO:0000305"
FT CONFLICT 622
FT /note="R -> W (in Ref. 1; BAC15769)"
FT /evidence="ECO:0000305"
FT CONFLICT 631
FT /note="T -> A (in Ref. 1; BAC15769)"
FT /evidence="ECO:0000305"
FT CONFLICT 649
FT /note="R -> W (in Ref. 5; BAC98205)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 861 AA; 97037 MW; 5C570D5A22414E14 CRC64;
MEALGPGPPA SLFQPPRRPG LGTVGKPIRL LANHFQVQIP KIDVYHYDVD IKPEKRPRRV
NREVVDTMVR HFKMQIFGDR QPGYDGKRNM YTAHPLPIGR DRIDMEVTLP GEGKDQTFKV
SVQWVSVVSL QLLLEALAGH LNEVPDDSVQ ALDVITRHLP SMRYTPVGRS FFSPPEGYYH
PLGGGREVWF GFHQSVRPAM WNMMLNIDVS ATAFYRAQPI IEFMCEVLDI QNINEQTKPL
TDSQRVKFTK EIRGLKVEVT HCGQMKRKYR VCNVTRRPAS HQTFPLQLEN GQAMECTVAQ
YFKQKYSLQL KHPHLPCLQV GQEQKHTYLP LEVCNIVAGQ RCIKKLTDNQ TSTMIKATAR
SAPDRQEEIS RLVKSNSMVG GPDPYLKEFG IVVHNEMTEL TGRVLPAPML QYGGRNKTVA
TPSQGVWDMR GKQFYAGIEI KVWAVACFAP QKQCREDLLK SFTDQLRKIS KDAGMPIQGQ
PCFCKYAQGA DSVEPMFKHL KMTYVGLQLI VVILPGKTPV YAEVKRVGDT LLGMATQCVQ
VKNVVKTSPQ TLSNLCLKMN AKLGGINNVL VPHQRPSVFQ QPVIFLGADV THPPAGDGKK
PSIAAVVGSM DGHPSRYCAT VRVQTSRQEI TQELLYSQEV VQDLTSMARE LLIQFYKSTR
FKPTRIIYYR GGVSEGQMKQ VAWPELIAIR KACISLEEDY RPGITYIVVQ KRHHTRLFCA
DKMERVGKSG NVPAGTTVDS TVTHPSEFDF YLCSHAGIQG TSRPSHYQVL WDDNCFTADE
LQLLTYQLCH TYVRCTRSVS IPAPAYYARL VAFRARYHLV DKDHDSAEGS HVSGQSNGRD
PQALAKAVQI HHDTQHTMYF A
