RIGI
entrez
23586
canonical
uniprot
O95786
canonical
ensembl
ENSG00000107201
resolver
ensp
ENSP00000369213
resolver
ensp
ENSP00000520439
resolver
ensp
ENSP00000566117
resolver
ensp
ENSP00000566118
resolver
enst
ENST00000715270
resolver
genesymbol
RIGI
resolver
genesymbol_syn
DDX58
resolver
hgnc
HGNC:19102
resolver
uniprot
A0AAQ5BIG4
resolver
uniprot
A2RU81
resolver
uniprot
Q5HYE1
resolver
uniprot
Q5VYT1
resolver
uniprot
Q9NT04
resolver
uniprot_entry
A0AAQ5BIG4_HUMAN
resolver
uniprot_entry
RIGI_HUMAN
resolver
uniprot_sec
A2RU81
resolver
uniprot_sec
Q5HYE1
resolver
uniprot_sec
Q5VYT1
resolver
uniprot_sec
Q9NT04
resolver
amino_acid_sequence
MTTEQRRSLQAFQDYIRKTLDPTYILSYMAPWFREEEVQYIQAEKNNKGPMEAATLFLKFLLELQEEGWFRGFLDALDHAGYSGLYEAIESWDFKKIEKLEEYRLLLKRLQPEFKTRIIPTDIISDLSECLINQECEEILQICSTKGMMAGAEKLVECLLRSDKENWPKTLKLALEKERNKFSELWIVEKGIKDVETEDLEDKMETSDIQIFYQEDPECQNLSENSCPPSEVSDTNLYSPFKPRNYQLELALPAMKGKNTIICAPTGCGKTFVSLLICEHHLKKFPQGQKGKVVFFANQIPVYEQQKSVFSKYFERHGYRVTGISGATAENVPVEQIVENNDIIILTPQILVNNLKKGTIPSLSIFTLMIFDECHNTSKQHPYNMIMFNYLDQKLGGSSGPLPQVIGLTASVGVGDAKNTDEALDYICKLCASLDASVIATVKHNLEELEQVVYKPQKFFRKVESRISDKFKYIIAQLMRDTESLAKRICKDLENLSQIQNREFGTQKYEQWIVTVQKACMVFQMPDKDEESRICKALFLYTSHLRKYNDALIISEHARMKDALDYLKDFFSNVRAAGFDEIEQDLTQRFEEKLQELESVSRDPSNENPKLEDLCFILQEEYHLNPETITILFVKTRALVDALKNWIEGNPKLSFLKPGILTGRGKTNQNTGMTLPAQKCILDAFKASGDHNILIATSVADEGIDIAQCNLVILYEYVGNVIKMIQTRGRGRARGSKCFLLTSNAGVIEKEQINMYKEKMMNDSILRLQTWDEAVFREKILHIQTHEKFIRDSQEKPKPVPDKENKKLLCRKCKALACYTADVRVIEECHYTVLGDAFKECFVSRPHPKPKQFSSFEKRAKIFCARQNCSHDWGIHVKYKTFEIPVIKIESFVVEDIATGVQTLYSKWKDFHFEKIPFDPAEMSK
uniprot
proteins
disease_involvement
DISEASE: Singleton-Merten syndrome 2 (SGMRT2) [MIM:616298]: A form of Singleton-Merten syndrome, an autosomal dominant disorder characterized by marked aortic calcification, dental anomalies, osteopenia, acro-osteolysis, and to a lesser extent glaucoma, psoriasis, muscle weakness, and joint laxity. Additional clinical manifestations include particular facial characteristics and abnormal joint and muscle ligaments. SGMRT2 is an atypical form characterized by variable expression of glaucoma, aortic calcification, and skeletal abnormalities, without dental anomalies. {ECO:0000269|PubMed:25620203}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.6.4.13
uniprot
proteins
function
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:15708988, PubMed:16125763, PubMed:16127453, PubMed:16153868, PubMed:17190814, PubMed:18636086, PubMed:19122199, PubMed:19211564, PubMed:24366338, PubMed:28469175, PubMed:29117565, PubMed:31006531, PubMed:34935440, PubMed:35263596, PubMed:36793726). 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.74). 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:24366338, ECO:0000269|PubMed:28469175, ECO:0000269|PubMed:29117565, ECO:0000269|PubMed:31006531, ECO:0000269|PubMed:34935440, ECO:0000269|PubMed:35263596, ECO:0000269|PubMed:36793726, ECO:0000269|Ref.74, ECO:0000303|PubMed:21616437, ECO:0000303|PubMed:21884169}.
uniprot
proteins
mass_dalton
106600
uniprot
proteins
mutagenesis
MUTAGEN 8; /note="S->E: Complete loss of MARCHF5-mediated degradation."; /evidence="ECO:0000269|PubMed:31881323"; MUTAGEN 55; /note="T->I: No IRF3 signaling activity. No effect on dsRNA binding."; /evidence="ECO:0000269|PubMed:15708988"; MUTAGEN 99; /note="K->R: Little or no effect on ubiquitination of the 2 CARD domain. Abolishes ubiquitination by RNF125."; /evidence="ECO:0000269|PubMed:17392790, ECO:0000269|PubMed:26471729"; MUTAGEN 154; /note="K->R: Reduction of ubiquitination. Reduction of INFB induction."; /evidence="ECO:0000269|PubMed:19484123"; MUTAGEN 164; /note="K->R: Reduction of ubiquitination. Reduction of INFB induction."; /evidence="ECO:0000269|PubMed:19484123"; MUTAGEN 169; /note="K->R: Little or no effect on ubiquitination of the 2 CARD domains."; /evidence="ECO:0000269|PubMed:17392790"; MUTAGEN 172; /note="K->R: Complete loss of ubiquitination. No interaction with MAVS/IPS1. No induction of IFN-beta."; /evidence="ECO:0000269|PubMed:17392790, ECO:0000269|PubMed:19484123"; MUTAGEN 181; /note="K->R: Little or no effect on ubiquitination of the 2 CARD domains."; /evidence="ECO:0000269|PubMed:17392790"; MUTAGEN 190; /note="K->R: Little or no effect on ubiquitination of the 2 CARD domains."; /evidence="ECO:0000269|PubMed:17392790"; MUTAGEN 193; /note="K->R: Little or no effect on ubiquitination of the 2 CARD domains."; /evidence="ECO:0000269|PubMed:17392790"; MUTAGEN 270; /note="K->A: No IRF3 signaling activity. Loss of dsRNA-induced ATPase activity. No effect on ds-RNA binding. Changed RIG-I signaling pathway."; /evidence="ECO:0000269|PubMed:15208624, ECO:0000269|PubMed:15708988, ECO:0000269|PubMed:19211564"; MUTAGEN 372..375; /note="DECH->AACA: Loss of dsRNA-induced ATPase activity. No effect on ds-RNA binding. Changed RIG-I signaling pathway."; /evidence="ECO:0000269|PubMed:19211564"; MUTAGEN 409..411; /note="TAS->AAA: Loss of dsRNA-induced ATPase activity. No effect on ds-RNA binding. Changed RIG-I signaling pathway."; /evidence="ECO:0000269|PubMed:19211564"; MUTAGEN 495; /note="N->Q: Complete loss of herpes simplex virus 1 UL37-mediated deamidation; when associated with Q-549."; /evidence="ECO:0000269|PubMed:27866900"; MUTAGEN 549; /note="N->Q: Complete loss of herpes simplex virus 1 UL37-mediated deamidation; when associated with Q-495."; /evidence="ECO:0000269|PubMed:27866900"; MUTAGEN 633..636; /note="FVKT->AVKA: Loss of dsRNA-induced ATPase activity. Changed RIG-I signaling pathway."; /evidence="ECO:0000269|PubMed:19211564"; MUTAGEN 697..701; /note="TSVAD->ASVAA: No effect on dsRNA-induced ATPase activity. Changed RIG-I signaling pathway."; /evidence="ECO:0000269|PubMed:19211564"; MUTAGEN 726..730; /note="QTRGR->ATRGA: Loss of dsRNA-induced ATPase activity. Changed RIG-I signaling pathway."; /evidence="ECO:0000269|PubMed:19211564"; MUTAGEN 788; /note="K->R: Decreased polyubiquitination. Loss of function in RIG-I signaling pathway. Decreased ubiquitination and function in RIG-I signaling pathway without effect on RNA-binding; when associated with R-849, R-851, R-888, R-907 and R-909."; /evidence="ECO:0000269|PubMed:23950712"; MUTAGEN 849; /note="K->R: Decreased ubiquitination and function in RIG-I signaling pathway without effect on RNA-binding; when associated with R-788, R-851, R-888, R-907 and R-909."; /evidence="ECO:0000269|PubMed:23950712"; MUTAGEN 851; /note="K->R: Decreased ubiquitination and function in RIG-I signaling pathway without effect on RNA-binding; when associated with R-788, R-849, R-888, R-907 and R-909."; /evidence="ECO:0000269|PubMed:23950712"; MUTAGEN 888; /note="K->R: Decreased ubiquitination and function in RIG-I signaling pathway without effect on RNA-binding; when associated with R-788, R-849, R-851, R-907 and R-909."; /evidence="ECO:0000269|PubMed:23950712"; MUTAGEN 907; /note="K->R: Decreased ubiquitination and function in RIG-I signaling pathway without effect on RNA-binding; when associated with R-788, R-849, R-851, R-888 and R-909."; /evidence="ECO:0000269|PubMed:23950712"; MUTAGEN 909; /note="K->Q: Acetylation-mimic mutant which abolishes the ability to inhibit viral replication."; /evidence="ECO:0000269|PubMed:26746851"; MUTAGEN 909; /note="K->R: Acetylation-resistant mutant which inhibits viral replication similar to the wild-type. Decreased ubiquitination and function in RIG-I signaling pathway without effect on RNA-binding; when associated with R-788, R-849, R-851, R-888 and R-907."; /evidence="ECO:0000269|PubMed:23950712, ECO:0000269|PubMed:26746851
uniprot
proteins
post_translational_modification
PTM: Phosphorylated in resting cells and dephosphorylated in RNA virus-infected cells. Phosphorylation at Thr-770, Ser-854 and Ser-855 results in inhibition of its activity while dephosphorylation at these sites results in its activation. {ECO:0000269|PubMed:21068236}.; PTM: Ubiquitinated. 'Lys-63' ubiquitination by RNF135, which occurs after RNA-binding and homodimerization, releases the autoinhibition of the CARD domains by the RLR CTR domain, an essential step in the activation of the RIG-I signaling pathway (PubMed:23950712, PubMed:28469175, PubMed:31006531). Lys-172 is the critical site of ubiquitination for MAVS/IPS1 binding and to induce anti-viral signal transduction (PubMed:17392790, PubMed:30193849). Lys-154, Lys-164 and Lys-172 are shared sites for RNF135-mediated and TRIM4-mediated ubiquitination (PubMed:19017631, PubMed:19484123, PubMed:24755855). Also undergoes 'Lys-48' ubiquitination at Lys-181 by RNF125 that leads to proteasomal degradation (PubMed:17460044, PubMed:26471729). 'Lys-48' ubiquitination follows viral infection and is enhanced by 'Lys-63'-linked ubiquitination of the CARD domains that promotes interaction with VCP/p97 and subsequent recruitment of RNF125 (PubMed:17460044, PubMed:26471729). Within a negative feedback loop involving SIGLEC10 and PTPN11, 'Lys-48' ubiquitination at Lys-812 by CBL also elicits the proteasomal degradation of RIGI (By similarity). Deubiquitinated by CYLD, a protease that selectively cleaves 'Lys-63'-linked ubiquitin chains (PubMed:18636086). Also probably deubiquitinated by USP17L2/USP17 that cleaves 'Lys-48'- and 'Lys-63'-linked ubiquitin chains and positively regulates the receptor (PubMed:20368735). Ubiquitinated by TRIM40 via 'Lys-48'-linked ubiquitination; leading to proteasomal degradation (PubMed:29117565). Deubiquitinated by USP27X that cleaves 'Lys-63'-linked ubiquitin chains and inhibits the innate immune receptor activity (PubMed:32027733). Deubiquitinated by USP3 that also cleaves 'Lys-63'-linked ubiquitin chains and inhibits the innate immune receptor activity (PubMed:24366338). Undergoes 'Lys-48'-linked ubiquitination catalyzed by MARCHF5 at Lys-193 and Lys-203, leading to proteasomal degradation (PubMed:31881323). {ECO:0000250|UniProtKB:Q6Q899, ECO:0000269|PubMed:17392790, ECO:0000269|PubMed:17460044, ECO:0000269|PubMed:18636086, ECO:0000269|PubMed:19017631, ECO:0000269|PubMed:19484123, ECO:0000269|PubMed:20368735, ECO:0000269|PubMed:23950712, ECO:0000269|PubMed:24366338, ECO:0000269|PubMed:24755855, ECO:0000269|PubMed:26471729, ECO:0000269|PubMed:29117565, ECO:0000269|PubMed:30193849, ECO:0000269|PubMed:31006531, ECO:0000269|PubMed:32027733}.; PTM: Phosphorylated at Ser-8 and Thr-170; these phosphorylations suppresse the TRIM25-mediated 'Lys-63'-linked ubiquitination of RIG-I and thereby prevents RIG-I downstream signaling. Dephosphorylated by phosphatases PPP1CA/PPP1CC; this step is essential to activate RIGI and initiate downstream signaling. {ECO:0000269|PubMed:23499489}.; PTM: ISGylated. Conjugated to ubiquitin-like protein ISG15 upon IFN-beta stimulation. ISGylation negatively regulates its function in antiviral signaling response. {ECO:0000269|PubMed:16009940, ECO:0000269|PubMed:18057259, ECO:0000269|PubMed:20368735}.; PTM: Sumoylated, probably by MUL1; inhibiting its polyubiquitination. {ECO:0000269|PubMed:20368735, ECO:0000269|PubMed:23399697}.; PTM: Acetylated in response to RNA virus infection (PubMed:26746851). Deacetylated by HDAC6 in the presence of viral mRNAs which is required for detection of viral RNA by RIGI (PubMed:26746851). {ECO:0000269|PubMed:26746851}.; PTM: (Microbial infection) Deamidated on Asn-495 and Asn-549 by herpes simplex virus 1 protein UL37. These modifications eliminate RIGI detection of viral RNA and restriction of viral replication. {ECO:0000269|PubMed:27866900}.; PTM: Degraded via selective autophagy following interaction with IRGM (PubMed:32715615). IRGM promotes RIGI recruitment to autophagosome membranes, promoting its SQSTM1/p62-dependent autophagic degradation (PubMed:32715615). {ECO:0000269|PubMed:32715615}.; PTM: (Microbial infection) Cleaved by the protease 3C of coxsackievirus B3, poliovirus and enterovirus 71 allowing the virus to disrupt the host type I interferon production. {ECO:0000269|PubMed:24390337}.; PTM: (Microbial infection) Phosphorylated at Ser-8 by herpes simplex virus 1 protein US3 leading to inhibition of critical RIGI activation steps. {ECO:0000269|PubMed:34935440}.
uniprot
proteins
protein_family
Helicase family
uniprot
proteins
protein_family
RLR subfamily
uniprot
proteins
pubmed
11890704
uniprot
proteins
pubmed
15164053
uniprot
proteins
pubmed
15181474
uniprot
proteins
pubmed
15208624
uniprot
proteins
pubmed
15219805
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15708988
uniprot
proteins
pubmed
16009940
uniprot
proteins
pubmed
16125763
uniprot
proteins
pubmed
16127453
uniprot
proteins
pubmed
16153868
uniprot
proteins
pubmed
16281057
uniprot
proteins
pubmed
17190814
uniprot
proteins
pubmed
17392790
uniprot
proteins
pubmed
17460044
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18057259
uniprot
proteins
pubmed
18242112
uniprot
proteins
pubmed
18243112
uniprot
proteins
pubmed
18636086
uniprot
proteins
pubmed
18724357
uniprot
proteins
pubmed
19017631
uniprot
proteins
pubmed
19122199
uniprot
proteins
pubmed
19193793
uniprot
proteins
pubmed
19211564
uniprot
proteins
pubmed
19419966
uniprot
proteins
pubmed
19484123
uniprot
proteins
pubmed
19576794
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19609254
uniprot
proteins
pubmed
19631370
uniprot
proteins
pubmed
20007272
uniprot
proteins
pubmed
20127681
uniprot
proteins
pubmed
20368735
uniprot
proteins
pubmed
20434986
uniprot
proteins
pubmed
20950133
uniprot
proteins
pubmed
21068236
uniprot
proteins
pubmed
21102435
uniprot
proteins
pubmed
21175414
uniprot
proteins
pubmed
21233210
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21616437
uniprot
proteins
pubmed
21742966
uniprot
proteins
pubmed
21791617
uniprot
proteins
pubmed
21813773
uniprot
proteins
pubmed
21884169
uniprot
proteins
pubmed
22152002
uniprot
proteins
pubmed
22301138
uniprot
proteins
pubmed
22607805
uniprot
proteins
pubmed
23399697
uniprot
proteins
pubmed
23499489
uniprot
proteins
pubmed
23843640
uniprot
proteins
pubmed
23950712
uniprot
proteins
pubmed
24366338
uniprot
proteins
pubmed
24390337
uniprot
proteins
pubmed
24478431
uniprot
proteins
pubmed
24755855
uniprot
proteins
pubmed
25018021
uniprot
proteins
pubmed
25228397
uniprot
proteins
pubmed
25620203
uniprot
proteins
pubmed
26471729
uniprot
proteins
pubmed
26746851
uniprot
proteins
pubmed
27312109
uniprot
proteins
pubmed
27824081
uniprot
proteins
pubmed
27866900
uniprot
proteins
pubmed
28469175
uniprot
proteins
pubmed
29117565
uniprot
proteins
pubmed
29288164
uniprot
proteins
pubmed
29321315
uniprot
proteins
pubmed
30193849
uniprot
proteins
pubmed
31006531
uniprot
proteins
pubmed
31881323
uniprot
proteins
pubmed
32027733
uniprot
proteins
pubmed
32715615
uniprot
proteins
pubmed
34313226
uniprot
proteins
pubmed
34935440
uniprot
proteins
pubmed
35263596
uniprot
proteins
pubmed
36793726
uniprot
proteins
pubmed
39037956
uniprot
proteins
sequence_length
925
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm. Cell projection, ruffle membrane. Cytoplasm, cytoskeleton. Cell junction, tight junction. Note=Colocalized with TRIM25 at cytoplasmic perinuclear bodies. Associated with the actin cytoskeleton at membrane ruffles.
uniprot
proteins