MDA5

IFIH1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2RQB, 3B6E, 3GA3, 4GL2
Identifiers
Aliases	IFIH1, AGS7, Hlcd, IDDM19, MDA-5, MDA5, RLR-2, SGMRT1, interferon induced with helicase C domain 1, IMD95
External IDs	OMIM: 606951; MGI: 1918836; HomoloGene: 32535; GeneCards: IFIH1; OMA:IFIH1 - orthologs
Gene location (Human)
Chr.	Chromosome 2 (human)
End	162,318,684 bp
Gene location (Mouse)
Chr.	Chromosome 2 (mouse)
End	62,476,599 bp
RNA expression pattern
	Top expressed in
	palpebral conjunctiva; ; parotid gland; ; jejunal mucosa; ; monocyte; ; epithelium of nasopharynx; ; sperm; ; parietal pleura; ; visceral pleura; ; appendix; ; germinal epithelium;
	Top expressed in
	mucous cell of stomach; ; conjunctival fornix; ; jejunum; ; intestinal epithelium; ; left colon; ; left lobe of liver; ; Paneth cell; ; intestinal villus; ; vestibular membrane of cochlear duct; ; epithelium of small intestine;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	DNA binding; nucleotide binding; helicase activity; zinc ion binding; metal ion binding; protein binding; single-stranded RNA binding; RNA binding; double-stranded RNA binding; ribonucleoprotein complex binding; hydrolase activity; ATP binding; identical protein binding;
Cellular component	cytoplasm; cytosol; nucleus;
Biological process	positive regulation of interferon-alpha production; MDA-5 signaling pathway; immune system process; response to virus; protein sumoylation; cytoplasmic pattern recognition receptor signaling pathway in response to virus; negative regulation of type I interferon production; detection of virus; viral process; innate immune response; regulation of type III interferon production; positive regulation of interferon-beta production; protein deubiquitination; positive regulation of response to cytokine stimulus; cellular response to exogenous dsRNA; defense response to virus;
	Sources:Amigo / QuickGO
Orthologs
	64135
	71586
	ENSG00000115267
	ENSMUSG00000026896
	Q9BYX4
	Q8R5F7
	NM_022168
	NM_001164477; NM_027835
	NP_071451
	NP_001157949; NP_082111
	Wikidata
View/Edit Human	View/Edit Mouse

MDA5 (melanoma differentiation-associated protein 5) is a RIG-I-like receptor dsRNA helicase enzyme that is encoded by the IFIH1 gene in humans.^[5] MDA5 is part of the RIG-I-like receptor (RLR) family, which also includes RIG-I and LGP2, and functions as a pattern recognition receptor capable of detecting viruses. It is generally believed that MDA5 recognizes double stranded RNA (dsRNA) over 2000nts in length,^[6] however it has been shown that whilst MDA5 can detect and bind to cytoplasmic dsRNA, it is also activated by a high molecular weight RNA complex composed of ssRNA and dsRNA.^[7] For many viruses, effective MDA5-mediated antiviral responses are dependent on functionally active LGP2.^[8] The signaling cascades in MDA5 is initiated via CARD domain.^[9] Some observations made in cancer cells show that MDA5 also interacts with cellular RNA is able to induce an autoinflammatory response.^[10]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000115267 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000026896 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: IFIH1 interferon induced with helicase C domain 1".
^ Kato H, Takeuchi O, Mikamo-Satoh E, Hirai R, Kawai T, Matsushita K, et al. (July 2008). "Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5". The Journal of Experimental Medicine. 205 (7): 1601–10. doi:10.1084/jem.20080091. PMC 2442638. PMID 18591409.
^ Pichlmair A, Schulz O, Tan CP, Rehwinkel J, Kato H, Takeuchi O, et al. (October 2009). "Activation of MDA5 requires higher-order RNA structures generated during virus infection". Journal of Virology. 83 (20): 10761–9. doi:10.1128/JVI.00770-09. PMC 2753146. PMID 19656871.
^ Satoh T, Kato H, Kumagai Y, Yoneyama M, Sato S, Matsushita K, et al. (January 2010). "LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses". Proceedings of the National Academy of Sciences of the United States of America. 107 (4): 1512–7. Bibcode:2010PNAS..107.1512S. doi:10.1073/pnas.0912986107. PMC 2824407. PMID 20080593.
^ Takeuchi O, Akira S (February 2008). "MDA5/RIG-I and virus recognition". Current Opinion in Immunology. 20 (1): 17–22. doi:10.1016/j.coi.2008.01.002. PMID 18272355.
^ Dias Junior AG, Sampaio NG, Rehwinkel J (January 2019). "A Balancing Act: MDA5 in Antiviral Immunity and Autoinflammation". Trends in Microbiology. 27 (1): 75–85. doi:10.1016/j.tim.2018.08.007. PMC 6319154. PMID 30201512.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000115267 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000026896 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: IFIH1 interferon induced with helicase C domain 1".

[pmid18591409-6] Kato H, Takeuchi O, Mikamo-Satoh E, Hirai R, Kawai T, Matsushita K, et al. (July 2008). "Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5". The Journal of Experimental Medicine. 205 (7): 1601–10. doi:10.1084/jem.20080091. PMC 2442638. PMID 18591409.

[7] Pichlmair A, Schulz O, Tan CP, Rehwinkel J, Kato H, Takeuchi O, et al. (October 2009). "Activation of MDA5 requires higher-order RNA structures generated during virus infection". Journal of Virology. 83 (20): 10761–9. doi:10.1128/JVI.00770-09. PMC 2753146. PMID 19656871.

[Satoh_2010-8] Satoh T, Kato H, Kumagai Y, Yoneyama M, Sato S, Matsushita K, et al. (January 2010). "LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses". Proceedings of the National Academy of Sciences of the United States of America. 107 (4): 1512–7. Bibcode:2010PNAS..107.1512S. doi:10.1073/pnas.0912986107. PMC 2824407. PMID 20080593.

[9] Takeuchi O, Akira S (February 2008). "MDA5/RIG-I and virus recognition". Current Opinion in Immunology. 20 (1): 17–22. doi:10.1016/j.coi.2008.01.002. PMID 18272355.

[10] Dias Junior AG, Sampaio NG, Rehwinkel J (January 2019). "A Balancing Act: MDA5 in Antiviral Immunity and Autoinflammation". Trends in Microbiology. 27 (1): 75–85. doi:10.1016/j.tim.2018.08.007. PMC 6319154. PMID 30201512.

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