DegronMD - Q9UKV8(AGO2)

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 (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. {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}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.G96S	TCGA-4Z-AA82	BLCA	TCGA	DGRKNLYTAMP	CBL_PTK	95:105	Mutation altering degron motif	0.5882
p.G96S	DO218987	BLCA	ICGC	DGRKNLYTAMP	CBL_PTK	95:105	Mutation altering degron motif	0.5882
p.E114D	TCGA-A8-A09Z	BRCA	TCGA	DGRKNLYTAMP	CBL_PTK	95:105	Mutation rewiring degron network	0.0833
p.E114D	DO5521	BRCA	ICGC	DGRKNLYTAMP	CBL_PTK	95:105	Mutation rewiring degron network	0.0833
p.Y857C	TCGA-AX-A060	UCEC	TCGA	VQVHQD	LIG_APCC_ABBA_1	846:851	Mutation rewiring degron network	0.1667
p.P107L	TCGA-B5-A0JY	UCEC	TCGA	DGRKNLYTAMP	CBL_PTK	95:105	Mutation rewiring degron network	0.2778
p.P107L	TCGA-EO-A3B0	UCEC	TCGA	DGRKNLYTAMP	CBL_PTK	95:105	Mutation rewiring degron network	0.2778
p.P107L	DO219773	UCEC	ICGC	DGRKNLYTAMP	CBL_PTK	95:105	Mutation rewiring degron network	0.2778
p.P107L	DO43041	UCEC	ICGC	DGRKNLYTAMP	CBL_PTK	95:105	Mutation rewiring degron network	0.2778
p.A845V	TCGA-CG-5721	STAD	TCGA	VQVHQD	LIG_APCC_ABBA_1	846:851	Mutation rewiring degron network	0.3056
p.A845V	SIDM01051	Ovarian Carcinoma	GDSC	VQVHQD	LIG_APCC_ABBA_1	846:851	Mutation rewiring degron network	0.3056
p.A845V	SIDM00999	Bladder Carcinoma	GDSC	VQVHQD	LIG_APCC_ABBA_1	846:851	Mutation rewiring degron network	0.3056
p.A845V	ACH-000936	Ovarian Cancer	CCLE	VQVHQD	LIG_APCC_ABBA_1	846:851	Mutation rewiring degron network	0.3056
p.A845V	ACH-000973	Bladder Cancer	CCLE	VQVHQD	LIG_APCC_ABBA_1	846:851	Mutation rewiring degron network	0.3056
p.A845V	639-V	urinary tract	COSMIC	VQVHQD	LIG_APCC_ABBA_1	846:851	Mutation rewiring degron network	0.3056
p.A845V	EFO-27	ovary	COSMIC	VQVHQD	LIG_APCC_ABBA_1	846:851	Mutation rewiring degron network	0.3056
p.R97S	TCGA-VS-A9UM	CESC	TCGA	DGRKNLYTAMP	CBL_PTK	95:105	Mutation altering degron motif	0.6316
p.R97S	DO51644	CESC	ICGC	DGRKNLYTAMP	CBL_PTK	95:105	Mutation altering degron motif	0.6316
p.K112N	TCGA-ZF-A9R0	BLCA	TCGA	DGRKNLYTAMP	CBL_PTK	95:105	Mutation substituting flanking lysine	0.25
p.V93M	DO222500	ESCA	ICGC	DGRKNLYTAMP	CBL_PTK	95:105	Mutation rewiring degron network	0.2778
p.D111E	DO228974	LICA	ICGC	DGRKNLYTAMP	CBL_PTK	95:105	Mutation rewiring degron network	0.1667
p.T102K	DO229019	LICA	ICGC	DGRKNLYTAMP	CBL_PTK	95:105	Mutation altering degron motif	0.7306
p.P107T	DO229037	LICA	ICGC	DGRKNLYTAMP	CBL_PTK	95:105	Mutation rewiring degron network	0.2778
p.L853P	SIDM00878	Breast Carcinoma	GDSC	VQVHQD	LIG_APCC_ABBA_1	846:851	Mutation rewiring degron network	0.2778
p.L853P	HCC1569	breast	COSMIC	VQVHQD	LIG_APCC_ABBA_1	846:851	Mutation rewiring degron network	0.2778
p.V846I	SIDM01228	Melanoma	GDSC	VQVHQD	LIG_APCC_ABBA_1	846:851	Mutation altering degron motif	0.5965
p.V846I	ACH-000931	Skin Cancer	CCLE	VQVHQD	LIG_APCC_ABBA_1	846:851	Mutation altering degron motif	0.5965
p.V846I	ACH-001024	Skin Cancer	CCLE	VQVHQD	LIG_APCC_ABBA_1	846:851	Mutation altering degron motif	0.5965
p.V846I	CHL-1	skin	COSMIC	VQVHQD	LIG_APCC_ABBA_1	846:851	Mutation altering degron motif	0.5965
p.E114G	SIDM00901	Endometrial Carcinoma	GDSC	DGRKNLYTAMP	CBL_PTK	95:105	Mutation rewiring degron network	0.0833
p.E114G	ACH-000940	Endometrial/Uterine Cancer	CCLE	DGRKNLYTAMP	CBL_PTK	95:105	Mutation rewiring degron network	0.0833
p.E114G	AN3-CA	endometrium	COSMIC	DGRKNLYTAMP	CBL_PTK	95:105	Mutation rewiring degron network	0.0833
p.D89N	ACH-001561	Lung Cancer	CCLE	DGRKNLYTAMP	CBL_PTK	95:105	Mutation rewiring degron network	0.1667

Kaplan plot for AGO2 in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

AGO2

UniProt ID: Q9UKV8

Entrez ID: 27161

Protein name: Protein argonaute-2 (Argonaute2) (hAgo2) (EC 3.1.26.n2) (Argonaute RISC catalytic component 2) (Eukaryotic translation initiation factor 2C 2) (eIF-2C 2) (eIF2C 2) (PAZ Piwi domain protein) (PPD) (Protein slicer)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for AGO2 in