IFIH1
entrez
64135
canonical
uniprot
Q9BYX4
canonical
ensembl
ENSG00000115267
resolver
ensp
ENSP00000497271
resolver
genesymbol
IFIH1
resolver
genesymbol_syn
MDA5
resolver
genesymbol_syn
RH116
resolver
hgnc
HGNC:18873
resolver
uniprot
Q2NKL6
resolver
uniprot
Q6DC96
resolver
uniprot
Q86X56
resolver
uniprot
Q96MX8
resolver
uniprot
Q9H3G6
resolver
uniprot_entry
IFIH1_HUMAN
resolver
uniprot_sec
Q2NKL6
resolver
uniprot_sec
Q6DC96
resolver
uniprot_sec
Q86X56
resolver
uniprot_sec
Q96MX8
resolver
uniprot_sec
Q9H3G6
resolver
amino_acid_sequence
MSNGYSTDENFRYLISCFRARVKMYIQVEPVLDYLTFLPAEVKEQIQRTVATSGNMQAVELLLSTLEKGVWHLGWTREFVEALRRTGSPLAARYMNPELTDLPSPSFENAHDEYLQLLNLLQPTLVDKLLVRDVLDKCMEEELLTIEDRNRIAAAENNGNESGVRELLKRIVQKENWFSAFLNVLRQTGNNELVQELTGSDCSESNAEIENLSQVDGPQVEEQLLSTTVQPNLEKEVWGMENNSSESSFADSSVVSESDTSLAEGSVSCLDESLGHNSNMGSDSGTMGSDSDEENVAARASPEPELQLRPYQMEVAQPALEGKNIIICLPTGSGKTRVAVYIAKDHLDKKKKASEPGKVIVLVNKVLLVEQLFRKEFQPFLKKWYRVIGLSGDTQLKISFPEVVKSCDIIISTAQILENSLLNLENGEDAGVQLSDFSLIIIDECHHTNKEAVYNNIMRHYLMQKLKNNRLKKENKPVIPLPQILGLTASPGVGGATKQAKAEEHILKLCANLDAFTIKTVKENLDQLKNQIQEPCKKFAIADATREDPFKEKLLEIMTRIQTYCQMSPMSDFGTQPYEQWAIQMEKKAAKEGNRKERVCAEHLRKYNEALQINDTIRMIDAYTHLETFYNEEKDKKFAVIEDDSDEGGDDEYCDGDEDEDDLKKPLKLDETDRFLMTLFFENNKMLKRLAENPEYENEKLTKLRNTIMEQYTRTEESARGIIFTKTRQSAYALSQWITENEKFAEVGVKAHHLIGAGHSSEFKPMTQNEQKEVISKFRTGKINLLIATTVAEEGLDIKECNIVIRYGLVTNEIAMVQARGRARADESTYVLVAHSGSGVIEHETVNDFREKMMYKAIHCVQNMKPEEYAHKILELQMQSIMEKKMKTKRNIAKHYKNNPSLITFLCKNCSVLACSGEDIHVIEKMHHVNMTPEFKELYIVRENKALQKKCADYQINGEIICKCGQAWGTMMVHKGLDLPCLKIRNFVVVFKNNSTKKQYKKWVELPITFPNLDYSECCLFSDED
uniprot
proteins
disease_involvement
DISEASE: Type 1 diabetes mellitus 19 (T1D19) [MIM:610155]: A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:16699517}. Note=Disease susceptibility may be associated with variants affecting the gene represented in this entry.; DISEASE: Note=IFIH1 is the CADM-140 autoantigen, involved in clinically amyopathic dermatomyositis (CADM). This is a chronic inflammatory disorder that shows typical skin manifestations of dermatomyositis but has no or little evidence of clinical myositis. Anti-CADM-140 antibodies appear to be specific to dermatomyositis, especially CADM. Patients with anti-CADM-140 antibodies frequently develop life-threatening acute progressive interstitial lung disease (ILD). {ECO:0000269|PubMed:19565506, ECO:0000269|PubMed:20015976}.; DISEASE: Aicardi-Goutieres syndrome 7 (AGS7) [MIM:615846]: A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood. {ECO:0000269|PubMed:24686847, ECO:0000269|PubMed:24995871}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Singleton-Merten syndrome 1 (SGMRT1) [MIM:182250]: An autosomal dominant disorder with variable expression. Core features are marked aortic calcification, dental anomalies, osteopenia, acro-osteolysis, and to a lesser extent glaucoma, psoriasis, muscle weakness, and joint laxity. Dental anomalies include delayed eruption and immature root formation of anterior permanent teeth, early loss of permanent teeth due to short roots, acute root resorption, high caries, and aggressive alveolar bone loss. Additional clinical manifestations include particular facial characteristics and abnormal joint and muscle ligaments. {ECO:0000269|PubMed:25620204}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Immunodeficiency 95 (IMD95) [MIM:619773]: An autosomal recessive disorder characterized by the onset of recurrent and severe viral respiratory infections in infancy or early childhood, and impaired interferon production during viral infection. {ECO:0000269|PubMed:28606988, ECO:0000269|PubMed:29018476}. 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 which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and pro-inflammatory cytokines (PubMed:28594402, PubMed:32169843, PubMed:33727702). Its ligands include mRNA lacking 2'-O-methylation at their 5' cap and long-dsRNA (>1 kb in length) (PubMed:22160685). Upon ligand binding it associates with mitochondria antiviral signaling protein (MAVS/IPS1) which activates the IKK-related kinases: TBK1 and IKBKE which phosphorylate interferon regulatory factors: IRF3 and IRF7 which in turn activate transcription of antiviral immunological genes, including interferons (IFNs); IFN-alpha and IFN-beta. Responsible for detecting the Picornaviridae family members such as encephalomyocarditis virus (EMCV), mengo encephalomyocarditis virus (ENMG), and rhinovirus (PubMed:28606988). Detects coronavirus SARS-CoV-2 (PubMed:33440148, PubMed:33514628). Can also detect other viruses such as dengue virus (DENV), west Nile virus (WNV), and reovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome, such as vaccinia virus. Plays an important role in amplifying innate immune signaling through recognition of RNA metabolites that are produced during virus infection by ribonuclease L (RNase L). May play an important role in enhancing natural killer cell function and may be involved in growth inhibition and apoptosis in several tumor cell lines. {ECO:0000269|PubMed:14645903, ECO:0000269|PubMed:19211564, ECO:0000269|PubMed:19656871, ECO:0000269|PubMed:21217758, ECO:0000269|PubMed:21742966, ECO:0000269|PubMed:22160685, ECO:0000269|PubMed:28594402, ECO:0000269|PubMed:28606988, ECO:0000269|PubMed:29117565, ECO:0000269|PubMed:33440148, ECO:0000269|PubMed:33514628, ECO:0000269|PubMed:33727702}.
uniprot
proteins
mass_dalton
116689
uniprot
proteins
mutagenesis
MUTAGEN 23; /note="K->A: Loss of ISGylation, loss of oligomerization, strongly reduced signaling activity and IFNB induction, loss of virus replication restriction, no effect on phosphorylation or RNA-binding; when associated with A-43."; /evidence="ECO:0000269|PubMed:33727702, ECO:0000269|PubMed:40184173"; MUTAGEN 43; /note="K->A: Loss of ISGylation, loss of oligomerization, strongly reduced signaling activity and IFNB induction, loss of virus replication restriction, no effect on phosphorylation or RNA-binding; when associated with A-23."; /evidence="ECO:0000269|PubMed:33727702, ECO:0000269|PubMed:40184173"; MUTAGEN 68; /note="K->A: No effect on ISGylation or signaling activity and IFNB induction."; /evidence="ECO:0000269|PubMed:33727702"; MUTAGEN 74..75; /note="GW->AA: Loss of oligomerization."; /evidence="ECO:0000269|PubMed:33727702"; MUTAGEN 88; /note="S->A: Increases ISGylation. No effect on signaling activity and IFNB induction."; /evidence="ECO:0000269|PubMed:23499489, ECO:0000269|PubMed:33727702"; MUTAGEN 88; /note="S->E,D: Loss of signaling activity and IFNB induction. Reduced ISGylation. Loss of virus replication restriction."; /evidence="ECO:0000269|PubMed:23499489, ECO:0000269|PubMed:33727702"; MUTAGEN 88; /note="S->R: No effect on signaling activity and IFNB induction."; /evidence="ECO:0000269|PubMed:23499489, ECO:0000269|PubMed:33727702"; MUTAGEN 251; /note="D->A: No cleavage and no acceleration of DNA degradation."; /evidence="ECO:0000269|PubMed:12015121"; MUTAGEN 335; /note="K->A: Loss of dsRNA-induced ATPase activity. No effect on RNA binding. Changed MDA-5 signaling pathway."; /evidence="ECO:0000269|PubMed:19211564"; MUTAGEN 443..446; /note="DECH->AACA: Loss of dsRNA-induced ATPase activity. No effect on RNA binding. Changed MDA-5 signaling pathway."; /evidence="ECO:0000269|PubMed:19211564"; MUTAGEN 444; /note="E->A: No acceleration of DNA degradation, no binding to ATP, and no helicase activity."; /evidence="ECO:0000269|PubMed:12015121"; MUTAGEN 488..490; /note="TAS->AAA: Loss of dsRNA-induced ATPase activity. No effect on RNA binding. Changed MDA-5 signaling pathway."; /evidence="ECO:0000269|PubMed:19211564"; MUTAGEN 789..793; /note="TTVAE->ATVAA: Loss of dsRNA-induced ATPase activity. Loss of MDA-5 signaling pathway."; /evidence="ECO:0000269|PubMed:19211564"; MUTAGEN 818..822; /note="QARGR->AARGA: Loss of dsRNA-induced ATPase activity. No effect on MDA-5 signaling pathway."; /evidence="ECO:0000269|PubMed:19211564"; MUTAGEN 828; /note="S->A: Promotes multimerization after polyI:C stimulation; greatly enhances signaling."; /evidence="ECO:0000269|PubMed:25865883"; MUTAGEN 828; /note="S->D: Inhibits multimerization after polyI:C stimulation."; /evidence="ECO:0000269|PubMed:25865883"; MUTAGEN 829; /note="T->A: Moderately increases signaling."; /evidence="ECO:0000269|PubMed:25865883"; MUTAGEN 841..842; /note="IE->RR: Loss of oligomerization."; /evidence="ECO:0000269|PubMed:33727702"; MUTAGEN 848..849; /note="DF->AA: Loss of oligomerization."; /evidence="ECO:0000269|PubMed:33727702
uniprot
proteins
post_translational_modification
PTM: Sumoylated. Sumoylation positively regulates its role in type I interferon induction and is enhanced by PIAS2-beta. {ECO:0000269|PubMed:21156324}.; PTM: Ubiquitinated by RNF125, leading to its degradation by the proteasome (PubMed:17460044). USP17/UPS17L2-dependent deubiquitination positively regulates the receptor (PubMed:20368735). Ubiquitinated by TRIM25 via 'Lys-63'-linked ubiquitination, promoting activation of IFIH1/MDA5 (PubMed:30193849). Ubiquitinated by TRIM40 via 'Lys-48'-linked ubiquitination; leading to proteasomal degradation (PubMed:29117565). Ubiquitinated by TRIM65 via 'Lys-63'-linked ubiquitination, promoting activation of IFIH1/MDA5 (PubMed:28594402). {ECO:0000269|PubMed:17460044, ECO:0000269|PubMed:20368735, ECO:0000269|PubMed:28594402, ECO:0000269|PubMed:29117565, ECO:0000269|PubMed:30193849}.; PTM: ISGylated by ISG15 (PubMed:33727702, PubMed:40184173). ISGylation increases upon infection with dengue (DENV) or Zika (ZIKV) viruses (PubMed:33727702). ISGylation at Lys-23 and Lys-43 is dependent of dephosphorylation at Ser-88, regulates mitochondrial translocation and oligomerization (PubMed:33727702, PubMed:40184173). Essential for IFIH1/MDA5-mediated cytokine responses and restriction of virus replication (PubMed:33727702, PubMed:40184173). {ECO:0000269|PubMed:33727702, ECO:0000269|PubMed:40184173}.; PTM: Phosphorylated at Ser-88 (PubMed:23499489, PubMed:33727702). Dephosphorylated by phosphatases PPP11CA/PPP11CC; dephosphorylation precedes and is required for ISGylation (PubMed:23499489, PubMed:33727702). {ECO:0000269|PubMed:23499489, ECO:0000269|PubMed:33727702}.; PTM: During apoptosis, processed into 3 cleavage products. The helicase-containing fragment, once liberated from the CARD domains, translocate from the cytoplasm to the nucleus. The processed protein significantly sensitizes cells to DNA degradation. {ECO:0000250|UniProtKB:Q8R5F7}.; PTM: (Microbial infection) Cleaved and inactivated by the protease 2A of coxsackievirus B3, poliovirus and enterovirus 71 allowing the virus to disrupt the host type I interferon production. {ECO:0000269|PubMed:24390337}.
uniprot
proteins
protein_family
Helicase family
uniprot
proteins
protein_family
RLR subfamily
uniprot
proteins
pubmed
11805321
uniprot
proteins
pubmed
12015121
uniprot
proteins
pubmed
14645903
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15563593
uniprot
proteins
pubmed
16127453
uniprot
proteins
pubmed
16177806
uniprot
proteins
pubmed
16699517
uniprot
proteins
pubmed
17460044
uniprot
proteins
pubmed
17600090
uniprot
proteins
pubmed
17709747
uniprot
proteins
pubmed
19211564
uniprot
proteins
pubmed
19380577
uniprot
proteins
pubmed
19403670
uniprot
proteins
pubmed
19531363
uniprot
proteins
pubmed
19565506
uniprot
proteins
pubmed
19656871
uniprot
proteins
pubmed
19881509
uniprot
proteins
pubmed
20015976
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20127681
uniprot
proteins
pubmed
20368735
uniprot
proteins
pubmed
20434986
uniprot
proteins
pubmed
20950133
uniprot
proteins
pubmed
21156324
uniprot
proteins
pubmed
21217758
uniprot
proteins
pubmed
21245900
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21616437
uniprot
proteins
pubmed
21742966
uniprot
proteins
pubmed
21791617
uniprot
proteins
pubmed
21884169
uniprot
proteins
pubmed
22160685
uniprot
proteins
pubmed
22301138
uniprot
proteins
pubmed
23499489
uniprot
proteins
pubmed
23711367
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24390337
uniprot
proteins
pubmed
24686847
uniprot
proteins
pubmed
24995871
uniprot
proteins
pubmed
25228397
uniprot
proteins
pubmed
25620204
uniprot
proteins
pubmed
25865883
uniprot
proteins
pubmed
27312109
uniprot
proteins
pubmed
28424289
uniprot
proteins
pubmed
28594402
uniprot
proteins
pubmed
28606988
uniprot
proteins
pubmed
29018476
uniprot
proteins
pubmed
29117565
uniprot
proteins
pubmed
30193849
uniprot
proteins
pubmed
30312637
uniprot
proteins
pubmed
32169843
uniprot
proteins
pubmed
33440148
uniprot
proteins
pubmed
33514628
uniprot
proteins
pubmed
33727702
uniprot
proteins
pubmed
40184173
uniprot
proteins
sequence_length
1025
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11805321, ECO:0000269|PubMed:14645903, ECO:0000269|PubMed:32169843, ECO:0000269|PubMed:33727702}. Nucleus {ECO:0000305}. Mitochondrion {ECO:0000269|PubMed:33727702}. Note=Upon viral RNA stimulation and ISGylation, translocates from cytosol to mitochondrion. May be found in the nucleus, during apoptosis.
uniprot
proteins