DegronMD - O95786(DDX58)

FUNCTION: Innate immune receptor that senses cytoplasmic viral nucleic acids and activates a downstream signaling cascade leading to the production of type I interferons and pro-inflammatory cytokines (PubMed:15208624, PubMed:16125763, PubMed:15708988, PubMed:16127453, PubMed:16153868, PubMed:17190814, PubMed:18636086, PubMed:19122199, PubMed:19211564, PubMed:29117565, PubMed:28469175, PubMed:31006531). Forms a ribonucleoprotein complex with viral RNAs on which it homooligomerizes to form filaments (PubMed:15208624, PubMed:15708988). The homooligomerization allows the recruitment of RNF135 an E3 ubiquitin-protein ligase that activates and amplifies the RIG-I-mediated antiviral signaling in an RNA length-dependent manner through ubiquitination-dependent and -independent mechanisms (PubMed:28469175, PubMed:31006531). Upon activation, associates with mitochondria antiviral signaling protein (MAVS/IPS1) that activates the IKK-related kinases TBK1 and IKBKE which in turn phosphorylate the interferon regulatory factors IRF3 and IRF7, activating transcription of antiviral immunological genes including the IFN-alpha and IFN-beta interferons (PubMed:28469175, PubMed:31006531). Ligands include 5'-triphosphorylated ssRNAs and dsRNAs but also short dsRNAs (<1 kb in length) (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). In addition to the 5'-triphosphate moiety, blunt-end base pairing at the 5'-end of the RNA is very essential (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). Overhangs at the non-triphosphorylated end of the dsRNA RNA have no major impact on its activity (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). A 3'overhang at the 5'triphosphate end decreases and any 5'overhang at the 5' triphosphate end abolishes its activity (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). Detects both positive and negative strand RNA viruses including members of the families Paramyxoviridae: Human respiratory syncytial virus and measles virus (MeV), Rhabdoviridae: vesicular stomatitis virus (VSV), Orthomyxoviridae: influenza A and B virus, Flaviviridae: Japanese encephalitis virus (JEV), hepatitis C virus (HCV), dengue virus (DENV) and west Nile virus (WNV) (PubMed:21616437, PubMed:21884169). It also detects rotaviruses and reoviruses (PubMed:21616437, PubMed:21884169). Detects and binds to SARS-CoV-2 RNAs which is inhibited by m6A RNA modifications (Ref.65). Also involved in antiviral signaling in response to viruses containing a dsDNA genome such as Epstein-Barr virus (EBV) (PubMed:19631370). Detects dsRNA produced from non-self dsDNA by RNA polymerase III, such as Epstein-Barr virus-encoded RNAs (EBERs). May play important roles in granulocyte production and differentiation, bacterial phagocytosis and in the regulation of cell migration. {ECO:0000269|PubMed:15208624, ECO:0000269|PubMed:15708988, ECO:0000269|PubMed:16125763, ECO:0000269|PubMed:16127453, ECO:0000269|PubMed:16153868, ECO:0000269|PubMed:17190814, ECO:0000269|PubMed:18636086, ECO:0000269|PubMed:19122199, ECO:0000269|PubMed:19211564, ECO:0000269|PubMed:19576794, ECO:0000269|PubMed:19609254, ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:21742966, ECO:0000269|PubMed:28469175, ECO:0000269|PubMed:29117565, ECO:0000269|PubMed:31006531, ECO:0000269|Ref.65, ECO:0000303|PubMed:21616437, ECO:0000303|PubMed:21884169}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.E153D	TCGA-19-5956	GBM	TCGA	DKENW	DEG_APCC_KENBOX_2	163:167	Mutation rewiring degron network	0.0556
p.R730T	TCGA-AZ-6605	COAD	TCGA	IQTRGRGRAR	SCF_FBXL2	725:734	Mutation altering degron motif	0.6765
p.P168S	TCGA-BR-7707	STAD	TCGA	DKENW	DEG_APCC_KENBOX_2	163:167	Mutation rewiring degron network	0.3056
p.S736R	TCGA-WK-A8XO	SARC	TCGA	IQTRGRGRAR	SCF_FBXL2	725:734	Mutation rewiring degron network	0.2778
p.H741Y	DO1262	BRCA	ICGC	IQTRGRGRAR	SCF_FBXL2	725:734	Mutation rewiring degron network	0.1389
p.Q175K	DO228976	LICA	ICGC	DKENW	DEG_APCC_KENBOX_2	163:167	Mutation rewiring degron network	0.1111
p.Q175K	DO37971	SKCM	ICGC	DKENW	DEG_APCC_KENBOX_2	163:167	Mutation rewiring degron network	0.1111
p.Q165K	DO229036	LICA	ICGC	DKENW	DEG_APCC_KENBOX_2	163:167	Mutation altering degron motif	0.6944
p.I164V	DO26490	LUSC	ICGC	DKENW	DEG_APCC_KENBOX_2	163:167	Mutation altering degron motif	0.7076
p.A729S	DO51407	PRAD	ICGC	IQTRGRGRAR	SCF_FBXL2	725:734	Mutation altering degron motif	0.7588
p.L155F	DO51407	PRAD	ICGC	DKENW	DEG_APCC_KENBOX_2	163:167	Mutation rewiring degron network	0.1111
p.Q739K	DO229245	THCA	ICGC	IQTRGRGRAR	SCF_FBXL2	725:734	Mutation rewiring degron network	0.1944
p.D718Y	DO40884	UCEC	ICGC	IQTRGRGRAR	SCF_FBXL2	725:734	Mutation rewiring degron network	0.1389
p.L177R	DO41903	UCEC	ICGC	DKENW	DEG_APCC_KENBOX_2	163:167	Mutation blocking ubiquitination signal	0.5
p.E742K	DO42793	UCEC	ICGC	IQTRGRGRAR	SCF_FBXL2	725:734	Mutation rewiring degron network	0.1111
p.K743T	DO43971	UCEC	ICGC	IQTRGRGRAR	SCF_FBXL2	725:734	Mutation rewiring degron network	0.0833
p.M715I	DO43971	UCEC	ICGC	IQTRGRGRAR	SCF_FBXL2	725:734	Mutation rewiring degron network	0.0556
p.N744D	SIDM00449	B-Lymphoblastic Leukemia	GDSC	IQTRGRGRAR	SCF_FBXL2	725:734	Mutation rewiring degron network	0.0556
p.N744D	RCH-ACV	haematopoietic and lymphoid tissue	COSMIC	IQTRGRGRAR	SCF_FBXL2	725:734	Mutation rewiring degron network	0.0556

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

DDX58

UniProt ID: O95786

Entrez ID: 23586

Protein name: Antiviral innate immune response receptor RIG-I (ATP-dependent RNA helicase DDX58) (EC 3.6.4.13) (DEAD box protein 58) (RIG-I-like receptor 1) (RLR-1) (Retinoic acid-inducible gene 1 protein) (RIG-1) (Retinoic acid-inducible gene I protein) (RIG-I)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for DDX58 in