IFNA2
Ensembl | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 9: 21.38 – 21.39 Mb | Chr 4: 88.6 – 88.6 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Interferon alpha-2 is a protein that in humans is encoded by the IFNA2 gene.[5]
Protein family
Human
Type I IFNs form a family of several proteins: in humans, there are 13 α subtypes, 1 β subtype, 1 ω subtype and other less studied subtypes (κ and ε).[7] IFNα2 was the first subtype to be characterized in the early eighties. As a result, IFNα2 was widely used in basic research to elucidate biological activities, structure and mechanism of action of type I IFNs. IFNα2 was also the first IFN to be produced by the pharmaceutical industry for use as a drug. Thereby, IFNα2 is the best known type I IFN subtype. The properties of IFNα2 are widely shared by the other type I IFNs, although subtle differences exist.
Gene and protein
The
Synthesis
When a cell is infected by a virus, some components of the virus, mainly viral
Mechanism of action
Induced IFNα2 is secreted by the infected cells and acts locally as well as systemically on cells expressing a specific
- phosphorylation and activation of two enzymes of the Janus kinases or JAK family, TYK2 which is associated with IFNAR1 and JAK1 associated to IFNAR2;
- phosphorylation by the activated JAK kinases of key transcription factors, namely STAT1 and STAT2, members of the family Signal Transducer and Activator of Transcription (STAT protein);
- phosphorylated STAT1 and STAT2 bind IRF9 forming a complex named "IFN-Stimulated Gene Factor 3" (ISGF3). This complex translocates in the nucleus and initiates the transcription of the IFN-stimulated genes (ISGs).
ISGs encode proteins that modulate cellular functions. Following viral infection, many ISGs lead to the inhibition of the viral spread.[16] Several ISGs inhibit viral replication in the infected cells. Other ISGs protect neighbouring uninfected cells from being infected by inhibiting viral entry. Several hundreds of ISGs are known to be activated by type I IFNs[20] and are listed in a searchable database named interferome (http://www.interferome.org/).
Function
The broad spectrum of ISGs explains the wide range of biological activity of type I IFNs.[16][21][22][23][24] In addition to their antiviral activity, type I IFNs also inhibit the proliferation of cells and regulate the activation of the immune system.
Type I IFNs exert potent antitumor activity by several mechanisms such as:
- inhibition of the proliferation of cancer cells
- activation of the immune system which can eliminate tumor cells[25][26]
- increasing the antitumor activity of other antitumoral agents (
Type I IFNs can have detrimental effects during viral and non-viral infections (bacterial, parasitic, fungal). This is due in part by the ability of type I IFNs to polarize the immune system towards a specific type of response in order to interfere with virus infections.
When improperly regulated, IFN production or IFN-induced signalling can result in
Clinical significance
If given orally, IFNα2 is degraded by
Recombinant IFNα2 (α2a and α2b) has demonstrated efficiency in the treatment of patients diagnosed with some viral infections (such as chronic viral
Notes
Wikidata Q38486383 . |
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000188379 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000078354 - 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: IFNA2 interferon, alpha 2".
- PMID 25547990.
- S2CID 13600136.
- PMID 8001965.
- PMID 20357248.
- PMID 9417943.
- PMID 8994971.
- PMID 1694761.
- PMID 19349300.
- PMID 16214811.
- ISBN 978-3-0348-8346-7
- ^ PMID 25400632.
- PMID 21854986.
- S2CID 1472195.
- PMID 17969444.
- PMID 18049472.
- PMID 25630967.
- PMID 22365663.
- PMID 25614319.
- PMID 20837696.
- PMID 21930769.
- PMID 21930765.
- ^ PMID 21300764.
- ^ PMID 21482773.
- ^ PMID 21156650.
- PMID 22525889.
- ^ PMID 25578520.
- S2CID 20976432.
- PMID 24398568.
- ^ "Cuba's Contribution to Combating COVID-19". 12 March 2020.
Further reading
- Paul F, Pellegrini S, Uzé G (2015). "IFNA2: The prototypic human alpha interferon". Gene. 567 (2): 132–7. PMID 25982860.
External links
- Overview of all the structural information available in the PDB for UniProt: P01563 (Interferon alpha-2) at the PDBe-KB.
PDB gallery | |
|---|---|
|
