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Overview

Uniprot ID	Q8CJG0
Protein Name	Protein argonaute-2
Gene Name	Ago2
Organism	Mus musculus

Kla Sites from experimental identification

Position	Flanking peptide
92	TQIFGDRKPVFDGRK

Function

Required for RNA-mediated gene silencing (RNAi) by the RNA-induced silencing complex (RISC). The 'minimal RISC' appears to include AGO2 bound to a short guide RNA such as a microRNA (miRNA) or short interfering RNA (siRNA). These guide RNAs direct RISC to complementary mRNAs that are targets for RISC-mediated gene silencing. The precise mechanism of gene silencing depends on the degree of complementarity between the miRNA or siRNA and its target. Binding of RISC to a perfectly complementary mRNA generally results in silencing due to endonucleolytic cleavage of the mRNA specifically by AGO2. Binding of RISC to a partially complementary mRNA results in silencing through inhibition of translation, and this is independent of endonuclease activity. May inhibit translation initiation by binding to the 7-methylguanosine cap, thereby preventing the recruitment of the translation initiation factor eIF4-E. May also inhibit translation initiation via interaction with EIF6, which itself binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit. The inhibition of translational initiation leads to the accumulation of the affected mRNA in cytoplasmic processing bodies (P-bodies), where mRNA degradation may subsequently occur. In some cases RISC-mediated translational repression is also observed for miRNAs that perfectly match the 3' untranslated region (3'-UTR). Can also up-regulate the translation of specific mRNAs under certain growth conditions. Binds to the AU element of the 3'-UTR of the TNF mRNA and up-regulates translation under conditions of serum starvation. Also required for transcriptional gene silencing (TGS), in which short RNAs known as antigene RNAs or agRNAs direct the transcriptional repression of complementary promoter regions. Regulates lymphoid and erythroid development and function, and this is independent of endonuclease activity

Protein Sequence

10 MYSGAGPVLA 20 SPAPTTSPIP 30 GYAFKPPPRP 40 DFGTTGRTIK 50 LQANFFEMDI 60 PKIDIYHYEL 70 DIKPEKCPRR 80 VNREIVEHMV 90 QHFKTQIFGD 100 RKPVFDGRKN 110 LYTAMPLPIG 120 RDKVELEVTL 130 PGEGKDRIFK 140 VSIKWVSCVS 150 LQALHDALSG 160 RLPSVPFETI 170 QALDVVMRHL 180 PSMRYTPVGR 190 SFFTASEGCS 200 NPLGGGREVW 210 FGFHQSVRPS 220 LWKMMLNIDV 230 SATAFYKAQP 240 VIEFVCEVLD 250 FKSIEEQQKP 260 LTDSQRVKFT 270 KEIKGLKVEI 280 THCGQMKRKY 290 RVCNVTRRPA 300 SHQTFPLQQE 310 SGQTVECTVA 320 QYFKDRHKLV 330 LRYPHLPCLQ 340 VGQEQKHTYL 350 PLEVCNIVAG 360 QRCIKKLTDN 370 QTSTMIRATA 380 RSAPDRQEEI 390 SKLMRSASFN 400 TDPYVREFGI 410 MVKDEMTDVT 420 GRVLQPPSIL 430 YGGRNKAIAT 440 PVQGVWDMRN 450 KQFHTGIEIK 460 VWAIACFAPQ 470 RQCTEVHLKS 480 FTEQLRKISR 490 DAGMPIQGQP 500 CFCKYAQGAD 510 SVEPMFRHLK 520 NTYAGLQLVV 530 VILPGKTPVY 540 AEVKRVGDTV 550 LGMATQCVQM 560 KNVQRTTPQT 570 LSNLCLKINV 580 KLGGVNNILL 590 PQGRPPVFQQ 600 PVIFLGADVT 610 HPPAGDGKKP 620 SIAAVVGSMD 630 AHPNRYCATV 640 RVQQHRQEII 650 QDLAAMVREL 660 LIQFYKSTRF 670 KPTRIIFYRD 680 GVSEGQFQQV 690 LHHELLAIRE 700 ACIKLEKDYQ 710 PGITFIVVQK 720 RHHTRLFCTD 730 KNERVGKSGN 740 IPAGTTVDTK 750 ITHPTEFDFY 760 LCSHAGIQGT 770 SRPSHYHVLW 780 DDNRFSSDEL 790 QILTYQLCHT 800 YVRCTRSVSI 810 PAPAYYAHLV 820 AFRARYHLVD 830 KEHDSAEGSH 840 TSGQSNGRDH 850 QALAKAVQVH 860 QDTLRTMYFA

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0033391	chromatoid body
Biological Process	GO:0031054	pre-miRNA processing
Biological Process	GO:0043488	regulation of mRNA stability
Biological Process	GO:0090128	regulation of synapse maturation
Biological Process	GO:0031047	regulatory ncRNA-mediated gene silencing
Biological Process	GO:0035194	regulatory ncRNA-mediated post-transcriptional gene silencing
Biological Process	GO:0070922	RISC complex assembly
Biological Process	GO:0043489	RNA stabilization
Biological Process	GO:0030422	siRNA processing
Biological Process	GO:0090625	siRNA-mediated gene silencing by mRNA destabilization
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0036464	cytoplasmic ribonucleoprotein granule
Cellular Component	GO:0010494	cytoplasmic stress granule
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0030425	dendrite
Cellular Component	GO:0070062	extracellular exosome
Cellular Component	GO:0098978	glutamatergic synapse
Cellular Component	GO:0005794	Golgi apparatus
Cellular Component	GO:0016020	membrane
Cellular Component	GO:0005739	mitochondrion
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0043186	P granule
Cellular Component	GO:0000932	P-body
Cellular Component	GO:0071546	pi-body
Cellular Component	GO:0098794	postsynapse
Cellular Component	GO:1990904	ribonucleoprotein complex
Cellular Component	GO:0016442	RISC complex
Cellular Component	GO:0070578	RISC-loading complex
Molecular Function	GO:0001046	core promoter sequence-specific DNA binding
Molecular Function	GO:0003725	double-stranded RNA binding
Molecular Function	GO:0090624	endoribonuclease activity, cleaving miRNA-paired mRNA
Molecular Function	GO:0070551	endoribonuclease activity, cleaving siRNA-paired mRNA
Molecular Function	GO:0030544	Hsp70 protein binding
Molecular Function	GO:0051879	Hsp90 protein binding
Molecular Function	GO:0046872	metal ion binding
Molecular Function	GO:0035198	miRNA binding
Molecular Function	GO:0035925	mRNA 3'-UTR AU-rich region binding
Molecular Function	GO:0003729	mRNA binding
Molecular Function	GO:0098808	mRNA cap binding
Molecular Function	GO:1905172	RISC complex binding
Molecular Function	GO:0000340	RNA 7-methylguanosine cap binding
Molecular Function	GO:0003723	RNA binding
Molecular Function	GO:0004521	RNA endonuclease activity
Molecular Function	GO:0000993	RNA polymerase II complex binding
Molecular Function	GO:0003727	single-stranded RNA binding
Molecular Function	GO:0035197	siRNA binding
Biological Process	GO:0030154	cell differentiation
Biological Process	GO:0006351	DNA-templated transcription
Biological Process	GO:0010467	gene expression
Biological Process	GO:0010586	miRNA metabolic process
Biological Process	GO:0035196	miRNA processing
Biological Process	GO:0035278	miRNA-mediated gene silencing by inhibition of translation
Biological Process	GO:0035279	miRNA-mediated gene silencing by mRNA destabilization
Biological Process	GO:0042985	negative regulation of amyloid precursor protein biosynthetic process
Biological Process	GO:0045947	negative regulation of translational initiation
Biological Process	GO:0033962	P-body assembly
Biological Process	GO:0045766	positive regulation of angiogenesis
Biological Process	GO:0010628	positive regulation of gene expression
Biological Process	GO:1900153	positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
Biological Process	GO:0060213	positive regulation of nuclear-transcribed mRNA poly(A) tail shortening
Biological Process	GO:1900370	positive regulation of post-transcriptional gene silencing by RNA
Biological Process	GO:0045944	positive regulation of transcription by RNA polymerase II
Biological Process	GO:0045727	positive regulation of translation
Biological Process	GO:1901165	positive regulation of trophoblast cell migration
Biological Process	GO:0009791	post-embryonic development

Reference

[1] Wu D, Tang Y, Li X, Xiong S, Zhang Z et al.. Characterization of protein lactylation in healthy and ischemic mouse hearts.. Front Cardiovasc Med 12:1644886. 2025. PMID: 41089239.