interferon-induced helicase C domain-containing protein 1; clinically amyopathic dermatomyositis autoantigen 140 kDa; CADM-140 autoantigen; helicase with 2 CARD domains; Helicard; interferon-induced with helicase C domain protein 1; melanoma differentiation-associated protein 5; MDA-5; murabutide down-regulated protein; RNA helicase-DEAD box protein 116 (IFIH1, MDA5, RH116)

Function: - RNA helicase that, through its ATP-dependent unwinding of RNA, may function to promote message degradation by specific Rnases - seems to have growth suppressive properties - role in innate immune defense against viruses - upon interaction with intracellular dsRNA produced during viral replication, triggers a transduction cascade involving MAVS/IPS1, which results in the activation of NF-kappa-B, IRF3 & IRF7 & the induction of the expression of antiviral cytokines such as IFN-beta & RANTES (CCL5) - ATPase activity is specifically induced by dsRNA - essential for the production of interferons in response to picornaviruses - 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 (putative) - interacts with MAVS - interacts with V protein of simian virus 5, human parainfluenza virus 2, Mumps virus, Sendai virus & Hendra virus - binding to paramyxoviruses V proteins prevents IFN-beta induction, & the further establishment of an antiviral state. - interacts with PCBP2 - interacts with NLRC5 Cofactor: Zn⁺² Structure: - belongs to the helicase family - contains 2 CARD domains - contains 1 helicase ATP-binding domain - contains 1 helicase C-terminal domain Compartment: - cytoplasm, nucleus (putative) - may be found in the nucleus, during apoptosis Alternative splicing: named isoforms=2 Expression: - widely expressed, at a low level - expressed at higher levels in placenta, pancreas & spleen - barely detectable in brain, testis & lung - induced by IFNB1/IFN-beta & TNF Pathology: - genetic variation in IFIH1 is associated with diabetes mellitus insulin-dependent type 19 - IFIH1 is the CADM-140 autoantigen found in patients with amyopathic dermatomyositis - in HIV-1 infected HeLa-CD4 cells, overexpression of IFIH1 results in a great increase in the level of secreted viral p24 protein Laboratory: - MDA5 Ab in serum - MDA5 IgG in serum

General

DEAD box ATP-dependent helicase phosphoprotein

Properties

SIZE: entity length = 1025 aa MW = 117 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: CARD domain {7-97} CARD domain {110-190} proteolytic site {208-209} proteolytic site {216-217} proteolytic site {251-252} Ser phosphorylation site {S289} Ser phosphorylation site {S301} helicase NAME: helicase SITE: 316-509 Ser phosphorylation site {S645} Helicase C-terminal {700-882} Zn+2-binding site SITE: 907-907 Zn+2-binding site SITE: 910-910 Zn+2-binding site SITE: 962-962 Zn+2-binding site SITE: 964-964

Database Correlations

OMIM correlations UniProt Q9BYX4 PFAM correlations Entrez Gene 64135 Kegg hsa:64135 ENZYME 3.6.4.13

References

UniProt :accession Q9BYX4