AGO2
entrez
27161
canonical
uniprot
Q9UKV8
canonical
ensembl
ENSG00000123908
resolver
ensp
ENSP00000220592
resolver
ensp
ENSP00000430176
resolver
genesymbol
AGO2
resolver
genesymbol_syn
EIF2C2
resolver
hgnc
HGNC:3263
resolver
uniprot
Q8TCZ5
resolver
uniprot
Q8WV58
resolver
uniprot
Q96ID1
resolver
uniprot_entry
AGO2_HUMAN
resolver
uniprot_sec
Q8TCZ5
resolver
uniprot_sec
Q8WV58
resolver
uniprot_sec
Q96ID1
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by EDTA. {ECO:0000269|PubMed:15284456}.
uniprot
proteins
amino_acid_sequence
MYSGAGPALAPPAPPPPIQGYAFKPPPRPDFGTSGRTIKLQANFFEMDIPKIDIYHYELDIKPEKCPRRVNREIVEHMVQHFKTQIFGDRKPVFDGRKNLYTAMPLPIGRDKVELEVTLPGEGKDRIFKVSIKWVSCVSLQALHDALSGRLPSVPFETIQALDVVMRHLPSMRYTPVGRSFFTASEGCSNPLGGGREVWFGFHQSVRPSLWKMMLNIDVSATAFYKAQPVIEFVCEVLDFKSIEEQQKPLTDSQRVKFTKEIKGLKVEITHCGQMKRKYRVCNVTRRPASHQTFPLQQESGQTVECTVAQYFKDRHKLVLRYPHLPCLQVGQEQKHTYLPLEVCNIVAGQRCIKKLTDNQTSTMIRATARSAPDRQEEISKLMRSASFNTDPYVREFGIMVKDEMTDVTGRVLQPPSILYGGRNKAIATPVQGVWDMRNKQFHTGIEIKVWAIACFAPQRQCTEVHLKSFTEQLRKISRDAGMPIQGQPCFCKYAQGADSVEPMFRHLKNTYAGLQLVVVILPGKTPVYAEVKRVGDTVLGMATQCVQMKNVQRTTPQTLSNLCLKINVKLGGVNNILLPQGRPPVFQQPVIFLGADVTHPPAGDGKKPSIAAVVGSMDAHPNRYCATVRVQQHRQEIIQDLAAMVRELLIQFYKSTRFKPTRIIFYRDGVSEGQFQQVLHHELLAIREACIKLEKDYQPGITFIVVQKRHHTRLFCTDKNERVGKSGNIPAGTTVDTKITHPTEFDFYLCSHAGIQGTSRPSHYHVLWDDNRFSSDELQILTYQLCHTYVRCTRSVSIPAPAYYAHLVAFRARYHLVDKEHDSAEGSHTSGQSNGRDHQALAKAVQVHQDTLRTMYFA
uniprot
proteins
disease_involvement
DISEASE: Lessel-Kreienkamp syndrome (LESKRES) [MIM:619149]: An autosomal dominant disorder characterized by global developmental delay, intellectual disability of variable degree, and speech and language delay apparent from infancy or early childhood. Behavioral disorders are observed in most patients. Additional variable features include seizures, hypotonia, gait abnormalities, visual and cardiac defects, and non-specific facial dysmorphism. {ECO:0000269|PubMed:33199684}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.1.26.n2
uniprot
proteins
function
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. {ECO:0000250|UniProtKB:Q8CJG0, ECO:0000255|HAMAP-Rule:MF_03031, ECO:0000269|PubMed:15105377, ECO:0000269|PubMed:15260970, ECO:0000269|PubMed:15284456, ECO:0000269|PubMed:15337849, ECO:0000269|PubMed:15800637, ECO:0000269|PubMed:16081698, ECO:0000269|PubMed:16142218, ECO:0000269|PubMed:16271387, ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:16357216, ECO:0000269|PubMed:16756390, ECO:0000269|PubMed:16936728, ECO:0000269|PubMed:17382880, ECO:0000269|PubMed:17507929, ECO:0000269|PubMed:17524464, ECO:0000269|PubMed:17531811, ECO:0000269|PubMed:17932509, ECO:0000269|PubMed:18048652, ECO:0000269|PubMed:18178619, ECO:0000269|PubMed:18690212, ECO:0000269|PubMed:18771919, ECO:0000269|PubMed:19167051, ECO:0000269|PubMed:23746446, ECO:0000269|PubMed:37328606}.; FUNCTION: (Microbial infection) Upon Sars-CoV-2 infection, associates with viral miRNA-like small RNA, CoV2-miR-O7a, and may repress mRNAs, such as BATF2, to evade the IFN response. {ECO:0000269|PubMed:34903581}.
uniprot
proteins
mass_dalton
97208
uniprot
proteins
mutagenesis
MUTAGEN 140; /note="L->W: No effect."; /evidence="ECO:0000269|PubMed:15284456"; MUTAGEN 470; /note="F->V: No effect on miRNA-binding or target mRNA cleavage. Abrogates binding to the 7-methylguanosine cap of mRNA and prevents inhibition of translation. Abolishes interaction with TNRC6C; when associated with V-505."; /evidence="ECO:0000269|PubMed:17524464, ECO:0000269|PubMed:21981923"; MUTAGEN 470; /note="F->W: No effect on binding to the 7-methylguanosine cap of mRNA or inhibition of translation."; /evidence="ECO:0000269|PubMed:17524464, ECO:0000269|PubMed:21981923"; MUTAGEN 505; /note="F->V: No effect on miRNA-binding or target mRNA cleavage. Abrogates binding to the 7-methylguanosine cap of mRNA and prevents inhibition of translation and abolishes interaction with TNRC6C; when associated with V-470."; /evidence="ECO:0000269|PubMed:17524464, ECO:0000269|PubMed:21981923"; MUTAGEN 505; /note="F->W: No effect on binding to the 7-methylguanosine cap of mRNA or inhibition of translation."; /evidence="ECO:0000269|PubMed:17524464, ECO:0000269|PubMed:21981923"; MUTAGEN 533; /note="K->A: Impairs RNA cleavage."; /evidence="ECO:0000269|PubMed:15800629"; MUTAGEN 545; /note="Q->A: Impairs RNA cleavage."; /evidence="ECO:0000269|PubMed:15800629"; MUTAGEN 570; /note="K->A: Impairs RNA cleavage."; /evidence="ECO:0000269|PubMed:15800629"; MUTAGEN 597; /note="D->A: Abrogates RNA cleavage but does not affect binding to siRNA or translational repression."; /evidence="ECO:0000269|PubMed:15284456, ECO:0000269|PubMed:15800637, ECO:0000269|PubMed:18771919"; MUTAGEN 633; /note="Q->A: No effect."; /evidence="ECO:0000269|PubMed:15284456"; MUTAGEN 633; /note="Q->R: Abrogates RNA cleavage. Binds siRNA."; /evidence="ECO:0000269|PubMed:15284456"; MUTAGEN 634; /note="H->P,A: Abrogates RNA cleavage. Binds siRNA."; /evidence="ECO:0000269|PubMed:15284456"; MUTAGEN 669; /note="D->A: Abrogates RNA cleavage but does not affect binding to siRNA."; /evidence="ECO:0000269|PubMed:15284456, ECO:0000269|PubMed:15800637, ECO:0000269|PubMed:16357216"; MUTAGEN 673; /note="E->A: Impairs RNA cleavage."; /evidence="ECO:0000269|PubMed:15800637, ECO:0000269|PubMed:23746446"; MUTAGEN 673; /note="E->G: No effect on RNA cleavage."; /evidence="ECO:0000269|PubMed:15800637, ECO:0000269|PubMed:23746446"; MUTAGEN 676; /note="F->A,I,M,R,Y: Impairs RNA cleavage."; /evidence="ECO:0000269|PubMed:23746446"; MUTAGEN 676; /note="F->V: Abrogates RNA cleavage."; /evidence="ECO:0000269|PubMed:23746446"; MUTAGEN 682; /note="H->Y: No effect."; /evidence="ECO:0000269|PubMed:15284456"; MUTAGEN 683; /note="E->G: No effect on RNA cleavage."; /evidence="ECO:0000269|PubMed:15800637"; MUTAGEN 700; /note="P->A: Reduced protein stability."; /evidence="ECO:0000269|PubMed:18690212"; MUTAGEN 704; /note="F->Y: No effect."; /evidence="ECO:0000269|PubMed:15284456"; MUTAGEN 744; /note="T->Y: No effect."; /evidence="ECO:0000269|PubMed:15284456"; MUTAGEN 807; /note="H->A,R: Abrogates RNA cleavage."; /evidence="ECO:0000269|PubMed:15800637, ECO:0000269|PubMed:23746446
uniprot
proteins
post_translational_modification
PTM: Hydroxylated. 4-hydroxylation appears to enhance protein stability but is not required for miRNA-binding or endonuclease activity. {ECO:0000255|HAMAP-Rule:MF_03031, ECO:0000269|PubMed:18690212}.; PTM: Ubiquitinated on surface-exposed lysines by a SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 during target-directed microRNA degradation (TDMD), a process that mediates degradation of microRNAs (miRNAs) (PubMed:33184234, PubMed:33184237). Ubiquitination by the SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 leads to its subsequent degradation, thereby exposing miRNAs for degradation (PubMed:33184234, PubMed:33184237). ZSWIM8 recognizes and binds AGO2 when it is engaged with a TDMD target (PubMed:33184237). {ECO:0000269|PubMed:33184234, ECO:0000269|PubMed:33184237}.; PTM: Phosphorylated. A phosphorylation cycle of C-terminal serine cluster (Ser-824-Ser-834) regulates the release of target mRNAs. Target-binding leads to phosphorylation of these residues by CSNK1A1, which reduces the affinity of AGO2 for mRNA and enables target release. The ANKRD52-PPP6C phosphatase complex dephosphorylates the residues, which primes AGO2 for binding a new target. {ECO:0000269|PubMed:28114302}.; PTM: Phosphorylation at Ser-387 by AKT3; leads to up-regulate translational repression of microRNA target and down-regulate endonucleolytic cleavage. {ECO:0000269|PubMed:23603119}.
uniprot
proteins
protein_family
Ago subfamily
uniprot
proteins
protein_family
Argonaute family
uniprot
proteins
pubmed
10534406
uniprot
proteins
pubmed
11914277
uniprot
proteins
pubmed
14508492
uniprot
proteins
pubmed
14703574
uniprot
proteins
pubmed
14749716
uniprot
proteins
pubmed
15105377
uniprot
proteins
pubmed
15260970
uniprot
proteins
pubmed
15284456
uniprot
proteins
pubmed
15337849
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15766526
uniprot
proteins
pubmed
15800629
uniprot
proteins
pubmed
15800637
uniprot
proteins
pubmed
15908945
uniprot
proteins
pubmed
15973356
uniprot
proteins
pubmed
16081698
uniprot
proteins
pubmed
16142218
uniprot
proteins
pubmed
16271387
uniprot
proteins
pubmed
16289642
uniprot
proteins
pubmed
16357216
uniprot
proteins
pubmed
16421571
uniprot
proteins
pubmed
16699599
uniprot
proteins
pubmed
16756390
uniprot
proteins
pubmed
16936728
uniprot
proteins
pubmed
17382880
uniprot
proteins
pubmed
17507929
uniprot
proteins
pubmed
17524464
uniprot
proteins
pubmed
17531811
uniprot
proteins
pubmed
17932509
uniprot
proteins
pubmed
18048652
uniprot
proteins
pubmed
18178619
uniprot
proteins
pubmed
18690212
uniprot
proteins
pubmed
18771919
uniprot
proteins
pubmed
19167051
uniprot
proteins
pubmed
19801630
uniprot
proteins
pubmed
20505670
uniprot
proteins
pubmed
20616046
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21475248
uniprot
proteins
pubmed
21981923
uniprot
proteins
pubmed
22539551
uniprot
proteins
pubmed
22682761
uniprot
proteins
pubmed
22791714
uniprot
proteins
pubmed
22915799
uniprot
proteins
pubmed
23125361
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23603119
uniprot
proteins
pubmed
23746446
uniprot
proteins
pubmed
24726324
uniprot
proteins
pubmed
25697406
uniprot
proteins
pubmed
26009488
uniprot
proteins
pubmed
28114302
uniprot
proteins
pubmed
28546213
uniprot
proteins
pubmed
29395067
uniprot
proteins
pubmed
30258011
uniprot
proteins
pubmed
31400113
uniprot
proteins
pubmed
32213613
uniprot
proteins
pubmed
33184234
uniprot
proteins
pubmed
33184237
uniprot
proteins
pubmed
33199684
uniprot
proteins
pubmed
34903581
uniprot
proteins
pubmed
37328606
uniprot
proteins
sequence_length
859
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000269|PubMed:23125361, ECO:0000269|PubMed:23603119, ECO:0000269|PubMed:31400113, ECO:0000269|PubMed:33199684}. Nucleus {ECO:0000269|PubMed:23125361}. Note=Translational repression of mRNAs results in their recruitment to P-bodies. Translocation to the nucleus requires IMP8.
uniprot
proteins