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FLASH GENE
Symbol AGO2 contributors: mct - updated : 01-02-2018
HGNC name argonaute 2
HGNC id 3263
Location 8q24.3      Physical location : -
Synonym name
  • eukaryotic translation initiation factor 2C, 2
  • cancer susceptibility candidate 7
  • cancer susceptibility candidate 7 (non-protein coding)
  • long intergenic non-protein coding RNA 980
    • Synonym symbol(s) Q10, MGC3183, EIF2C2, CASC7, LINC00980, PPD
    DNA
    TYPE functioning gene
    STRUCTURE 54.14 kb     18 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    18 - 3520 - 859 - 2017 28839112
    - - 3418 - 825 - 2017 28839112
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivefemale systemuteruscervix   Homo sapiens
    Skin/Tegumentskin     Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...)
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal Mid and PIWI domains
  • one PIWI domain interacting with TARBP2 (Lima 2009)
  • a Mid domain that interact with small RNA molecules and proteins involved in translation
  • a PAZ domain at the C-terminus, (Piwi/argonaute/Zwille) domain, binding to ssRNAs with low affinity in a sequence-independent manner, and that could be a key regulator in AGO2-mediated miRNA-induced gene regulation
    • conjugated sumoylated
    HOMOLOGY
    Homologene
    FAMILY argonaute family
    CATEGORY RNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text nuclear import of Ago proteins in cells influenced by IPO8 (Weinmann 2009)
  • exhibits primarily as a nuclear protein in skin, normal cervix, and cervical cancer tissues, but not in larynx
  • subcellular distribution of AGO2 occurs in a cell type- and tissue context-dependent manner and may correlate with its various functions in regulation of gene expression
    • basic FUNCTION
  • playing an important role in the eukaryotic peptide chain initiation process
  • play a role in short-interfering-RNA-mediated gene silencing
  • playing an essential role for early embryonic postimplantation development but dispensable for the epigenetic silencing of the pericentromeric satellite sequence, imprinted genes, and Xist
  • in addition to its role as an endonuclease, may serve additional functions, namely facilitating the hybridization of the antisense RNA to the target RNA (Lima 2009)
  • regulates nonsense-mediated mRNA decay (NMD) by targeting CBP80/20 and EJC-bound mRNAs and thus inhibiting NMD (Choe 2010)
  • having original functions that are not related to miRNAs and translation repression
  • AGO1 and AGO2 facilitate spliceosome recruitment and modulate POLR2A elongation rate, thereby affecting alternative splicing
  • AGO2 is the catalytic center of the RNA-induced silencing complex (RISC) that recognizes and endonucleolytically cleaves messenger RNAs of complementary sequence
  • AGO2 and RNAi can serve as a robust model system for continued investigation into the HSP90AA1 chaperone cycle
  • AGO2 facilitates RAD51 recruitment and DNA double-strand break repair by homologous recombination
  • is a central effector of RNA interference (RNAi) pathways and regulates mammalian genes on a global level
  • CRBN binding partner AGO2 plays an important role in regulating multiple myeloma (MM) cell growth and survival
  • only AGO2 harbors nuclease activity
  • AGO1, AGO2 play a central role in the RNA interference (RNAi) pathway, which is a cytoplasmic mechanism important for post-transcriptional regulation of gene expression
  • is the major vehicle of microRNAs (miRNAs)-guided gene repression and silencing processes
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • part of a protein complex that enhances translation of a transcript that is regulated by an AU-rich element in serum-starved cells
  • DICER1 and Argonaute 1-4 proteins (EIF2C1, EIF2C2, EIF2C3, EIF2C4) are key components of the cytoplasmic enzyme machinery responsible for biogenesis and performance of microRNAs
  • PRKRA is associated with a ~500 kDa complex that contains DICER1, AGO2, and TARBP2 and it associates with DICER1 to facilitate the production of small interfering RNA
    • INTERACTION
    DNA
    RNA
  • AGO2 binding to tRNA genes has a novel and important regulatory role in human cells
    • small molecule
    protein
  • interact with DICER1
  • associate with the AU-rich elements (AREs) exclusively during translation activation
  • TNRC6A acted as a repressor in AGO2-mediated translational silencing
  • AGO2, PRKRA and TARBP2 were required for the efficient functioning of DICER1 in cells, and likely one of the roles of these proteins is to assure better synchronization of cleavages triggered by two RNase III domains of DICER1
  • TRIM71 associates with AGO2 and microRNAs, and represses expression of CDKN1A, a cyclin-dependent kinase inhibitor that negatively regulates the G1-S transition
  • APOBEC3G binds to a domain at the C terminus in MOV10, where it competitively inhibits the binding of AGO2 to that same domain
  • EIF4GI participates in the miRNA-mediated post-transcriptional gene silencing by promoting the association of AGO2 with the cap-binding complex
  • AGO2 very likely functions directly in mediating RAD51 accumulation at DSBs
  • IRF7 promotes glioma cell invasion and both chemoresistance and radioresistance through AGO2 inhibition
  • KRAS-AGO2 interaction is required for maximal mutant KRAS expression and cellular transformation
  • AGO2 is a CRBN binding partner and the steady-state levels of AGO2 were regulated by CRBN
  • interacting with GIGYF2 through the GYF domain
  • DDX17 and KHSRP influence AGO2 stability by regulating miRNA levels in the cell and that loss of DDX17/KHSRP results in a decrease of unloaded AGO2
  • ubiquitin-proteasome pathway is involved in AGO2 protein turnover
  • MOV10-FMR1-AGO2 complex regulates DICER1 expression, revealing a novel mechanism for regulation of miRNA production required for normal neuronal morphology
    • cell & other
  • cellular binding partners of miRNAs as well as other small RNAs and are therefore key components of miRNP (Weinmann 2009)
    • REGULATION
    Other phosphorylation significantly affects AGO2 activity
    AGO2 can be SUMOylated in mammalian cells by both SUMO1 and SUMO2
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility to Graves disease
    Variant & Polymorphism other AGO2 rs2292779 C carrier and C allele were associated with the intractability of Graves disease
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    AGO2 could be considered as a novel drug target for overcoming Immunomodulatory drugs (IMiDs) resistance in multiple myeloma (MM) cells
    ANIMAL & CELL MODELS