CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-016919
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Protein argonaute-2 
Protein Synonyms/Alias
 Argonaute2; mAgo2; Argonaute RISC catalytic component 2; Eukaryotic translation initiation factor 2C 2; eIF-2C 2; eIF2C 2; Piwi/argonaute family protein meIF2C2; Protein slicer 
Gene Name
 Ago2 
Gene Synonyms/Alias
 Eif2c2; Kiaa4215 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
249KSIEEQQKPLTDSQRubiquitination[1]
426ILYGGRNKAIATPVQubiquitination[1]
721TRLFCTDKNERVGKSubiquitination[1]
727DKNERVGKSGNIPAGubiquitination[1]
Reference
 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 
Functional Description
 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 (TNF-alpha) 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. 
Sequence Annotation
 DOMAIN 236 349 PAZ.
 DOMAIN 518 819 Piwi.
 METAL 598 598 Divalent metal cation (By similarity).
 METAL 670 670 Divalent metal cation (By similarity).
 METAL 808 808 Divalent metal cation (By similarity).
 MOD_RES 2 2 Nitrated tyrosine.
 MOD_RES 701 701 4-hydroxyproline (By similarity).  
Keyword
 Complete proteome; Cytoplasm; Developmental protein; Differentiation; Endonuclease; Hydrolase; Hydroxylation; Metal-binding; Nitration; Nuclease; Nucleus; Reference proteome; Repressor; Ribonucleoprotein; RNA-binding; RNA-mediated gene silencing; Transcription; Transcription regulation; Translation regulation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 860 AA 
Protein Sequence
MYSGAGPVLA SPAPTTSPIP GYAFKPPPRP DFGTTGRTIK LQANFFEMDI PKIDIYHYEL 60
DIKPEKCPRR VNREIVEHMV QHFKTQIFGD RKPVFDGRKN LYTAMPLPIG RDKVELEVTL 120
PGEGKDRIFK VSIKWVSCVS LQALHDALSG RLPSVPFETI QALDVVMRHL PSMRYTPVGR 180
SFFTASEGCS NPLGGGREVW FGFHQSVRPS LWKMMLNIDV SATAFYKAQP VIEFVCEVLD 240
FKSIEEQQKP LTDSQRVKFT KEIKGLKVEI THCGQMKRKY RVCNVTRRPA SHQTFPLQQE 300
SGQTVECTVA QYFKDRHKLV LRYPHLPCLQ VGQEQKHTYL PLEVCNIVAG QRCIKKLTDN 360
QTSTMIRATA RSAPDRQEEI SKLMRSASFN TDPYVREFGI MVKDEMTDVT GRVLQPPSIL 420
YGGRNKAIAT PVQGVWDMRN KQFHTGIEIK VWAIACFAPQ RQCTEVHLKS FTEQLRKISR 480
DAGMPIQGQP CFCKYAQGAD SVEPMFRHLK NTYAGLQLVV VILPGKTPVY AEVKRVGDTV 540
LGMATQCVQM KNVQRTTPQT LSNLCLKINV KLGGVNNILL PQGRPPVFQQ PVIFLGADVT 600
HPPAGDGKKP SIAAVVGSMD AHPNRYCATV RVQQHRQEII QDLAAMVREL LIQFYKSTRF 660
KPTRIIFYRD GVSEGQFQQV LHHELLAIRE ACIKLEKDYQ PGITFIVVQK RHHTRLFCTD 720
KNERVGKSGN IPAGTTVDTK ITHPTEFDFY LCSHAGIQGT SRPSHYHVLW DDNRFSSDEL 780
QILTYQLCHT YVRCTRSVSI PAPAYYAHLV AFRARYHLVD KEHDSAEGSH TSGQSNGRDH 840
QALAKAVQVH QDTLRTMYFA 860 
Gene Ontology
 GO:0000932; C:cytoplasmic mRNA processing body; IDA:MGI.
 GO:0035068; C:micro-ribonucleoprotein complex; ISS:UniProtKB.
 GO:0005845; C:mRNA cap binding complex; ISS:UniProtKB.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0005844; C:polysome; ISS:UniProtKB.
 GO:0016442; C:RNA-induced silencing complex; ISS:UniProtKB.
 GO:0070551; F:endoribonuclease activity, cleaving siRNA-paired mRNA; ISS:UniProtKB.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0003729; F:mRNA binding; IDA:MGI.
 GO:0000340; F:RNA 7-methylguanosine cap binding; ISS:UniProtKB.
 GO:0035197; F:siRNA binding; ISS:UniProtKB.
 GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
 GO:0035279; P:mRNA cleavage involved in gene silencing by miRNA; ISS:UniProtKB.
 GO:0035278; P:negative regulation of translation involved in gene silencing by miRNA; ISS:UniProtKB.
 GO:0045947; P:negative regulation of translational initiation; ISS:UniProtKB.
 GO:1900153; P:positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; IMP:UniProtKB.
 GO:0060213; P:positive regulation of nuclear-transcribed mRNA poly(A) tail shortening; IMP:UniProtKB.
 GO:0009791; P:post-embryonic development; IMP:MGI.
 GO:0031054; P:pre-miRNA processing; ISS:UniProtKB.
 GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 
Interpro
 IPR014811; DUF1785.
 IPR003100; PAZ.
 IPR003165; Piwi.
 IPR012337; RNaseH-like_dom. 
Pfam
 PF08699; DUF1785
 PF02170; PAZ
 PF02171; Piwi 
SMART
 SM00949; PAZ
 SM00950; Piwi 
PROSITE
 PS50821; PAZ
 PS50822; PIWI 
PRINTS