CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-023122
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Protein argonaute-2 
Protein Synonyms/Alias
 Argonaute2; hAgo2; Argonaute RISC catalytic component 2; Eukaryotic translation initiation factor 2C 2; eIF-2C 2; eIF2C 2; PAZ Piwi domain protein; PPD; Protein slicer 
Gene Name
 AGO2 
Gene Synonyms/Alias
 EIF2C2 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
248KSIEEQQKPLTDSQRubiquitination[1, 2]
355AGQRCIKKLTDNQTSubiquitination[2]
381DRQEEISKLMRSASFubiquitination[3]
425ILYGGRNKAIATPVQubiquitination[1, 2]
493QGQPCFCKYAQGADSubiquitination[2]
533TPVYAEVKRVGDTVLubiquitination[1]
550ATQCVQMKNVQRTTPubiquitination[2, 3, 4]
720TRLFCTDKNERVGKSubiquitination[2, 3]
726DKNERVGKSGNIPAGubiquitination[1, 2, 3]
844RDHQALAKAVQVHQDubiquitination[1, 2, 3]
Reference
 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [4] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094] 
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. 
Sequence Annotation
 DOMAIN 235 348 PAZ.
 DOMAIN 517 818 Piwi.
 METAL 597 597 Divalent metal cation (Probable).
 METAL 669 669 Divalent metal cation (Probable).
 METAL 807 807 Divalent metal cation (Probable).
 MOD_RES 2 2 Nitrated tyrosine (By similarity).
 MOD_RES 700 700 4-hydroxyproline.  
Keyword
 3D-structure; Alternative splicing; Complete proteome; Cytoplasm; 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
 859 AA 
Protein Sequence
MYSGAGPALA PPAPPPPIQG YAFKPPPRPD FGTSGRTIKL QANFFEMDIP KIDIYHYELD 60
IKPEKCPRRV NREIVEHMVQ HFKTQIFGDR KPVFDGRKNL YTAMPLPIGR DKVELEVTLP 120
GEGKDRIFKV SIKWVSCVSL QALHDALSGR LPSVPFETIQ ALDVVMRHLP SMRYTPVGRS 180
FFTASEGCSN PLGGGREVWF GFHQSVRPSL WKMMLNIDVS ATAFYKAQPV IEFVCEVLDF 240
KSIEEQQKPL TDSQRVKFTK EIKGLKVEIT HCGQMKRKYR VCNVTRRPAS HQTFPLQQES 300
GQTVECTVAQ YFKDRHKLVL RYPHLPCLQV GQEQKHTYLP LEVCNIVAGQ RCIKKLTDNQ 360
TSTMIRATAR SAPDRQEEIS KLMRSASFNT DPYVREFGIM VKDEMTDVTG RVLQPPSILY 420
GGRNKAIATP VQGVWDMRNK QFHTGIEIKV WAIACFAPQR QCTEVHLKSF TEQLRKISRD 480
AGMPIQGQPC FCKYAQGADS VEPMFRHLKN TYAGLQLVVV ILPGKTPVYA EVKRVGDTVL 540
GMATQCVQMK NVQRTTPQTL SNLCLKINVK LGGVNNILLP QGRPPVFQQP VIFLGADVTH 600
PPAGDGKKPS IAAVVGSMDA HPNRYCATVR VQQHRQEIIQ DLAAMVRELL IQFYKSTRFK 660
PTRIIFYRDG VSEGQFQQVL HHELLAIREA CIKLEKDYQP GITFIVVQKR HHTRLFCTDK 720
NERVGKSGNI PAGTTVDTKI THPTEFDFYL CSHAGIQGTS RPSHYHVLWD DNRFSSDELQ 780
ILTYQLCHTY VRCTRSVSIP APAYYAHLVA FRARYHLVDK EHDSAEGSHT SGQSNGRDHQ 840
ALAKAVQVHQ DTLRTMYFA 859 
Gene Ontology
 GO:0000932; C:cytoplasmic mRNA processing body; IDA:UniProtKB.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0035068; C:micro-ribonucleoprotein complex; IDA:UniProtKB.
 GO:0005845; C:mRNA cap binding complex; IDA:UniProtKB.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0005844; C:polysome; IDA:UniProtKB.
 GO:0016442; C:RNA-induced silencing complex; IDA:UniProtKB.
 GO:0070551; F:endoribonuclease activity, cleaving siRNA-paired mRNA; IDA:UniProtKB.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0003729; F:mRNA binding; IEA:Compara.
 GO:0000340; F:RNA 7-methylguanosine cap binding; IDA:UniProtKB.
 GO:0035197; F:siRNA binding; IDA:UniProtKB.
 GO:0003743; F:translation initiation factor activity; NAS:UniProtKB.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0035279; P:mRNA cleavage involved in gene silencing by miRNA; IDA:UniProtKB.
 GO:0035278; P:negative regulation of translation involved in gene silencing by miRNA; IDA:UniProtKB.
 GO:0045947; P:negative regulation of translational initiation; IDA:UniProtKB.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0007219; P:Notch signaling pathway; TAS:Reactome.
 GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
 GO:1900153; P:positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; ISS:UniProtKB.
 GO:0060213; P:positive regulation of nuclear-transcribed mRNA poly(A) tail shortening; ISS:UniProtKB.
 GO:0009791; P:post-embryonic development; IEA:Compara.
 GO:0031054; P:pre-miRNA processing; IDA: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