ISG20

ISG20
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1WLJ
Identifiers
Aliases	ISG20 , CD25, HEM45, interferon stimulated exonuclease gene 20kDa, interferon stimulated exonuclease gene 20
External IDs	OMIM: 604533; MGI: 1928895; HomoloGene: 31081; GeneCards: ISG20; OMA:ISG20 - orthologs
Gene location (Human) Chr. Chromosome 15 (human) [1] Band 15q26.1 Start 88,635,670 bp [1] End 88,656,483 bp [1]
Gene location (Mouse) Chr. Chromosome 7 (mouse) [2] Band 7|7 D2 Start 78,563,172 bp [2] End 78,570,144 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in spleen blood granulocyte lymph node cartilage tissue appendix duodenum jejunal mucosa epithelium of nasopharynx right lung Top expressed in tibiofemoral joint blood spermatid islet of Langerhans spleen decidua right lung lobe gastrula thymus fetal liver hematopoietic progenitor cell More reference expression data BioGPS More reference expression data
Gene ontology Molecular function 3'-5'-exoribonuclease activity single-stranded DNA 3'-5' exodeoxyribonuclease activity exoribonuclease II activity metal ion binding U3 snoRNA binding U2 snRNA binding RNA binding nucleic acid binding U1 snRNA binding nuclease activity exonuclease activity hydrolase activity Cellular component cytoplasm Cajal body PML body nucleoplasm nucleolus nucleus Biological process immune system process response to virus RNA catabolic process negative regulation of viral genome replication DNA catabolic process, exonucleolytic defense response to virus type I interferon signaling pathway rRNA processing innate immune response cell population proliferation RNA phosphodiester bond hydrolysis, exonucleolytic Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3669 57444 Ensembl ENSG00000172183 ENSMUSG00000039236 UniProt Q96AZ6 Q9JL16 RefSeq (mRNA) NM_001303233 NM_001303234 NM_001303235 NM_001303236 NM_001303237 NM_002201 NM_001113527 NM_001291220 NM_001291221 NM_020583 RefSeq (protein) NP_001290162 NP_001290163 NP_001290164 NP_001290165 NP_001290166 NP_002192 NP_001106999 NP_001278149 NP_001278150 NP_065608 Location (UCSC) Chr 15: 88.64 – 88.66 Mb Chr 7: 78.56 – 78.57 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Interferon-stimulated gene 20 kDa protein is a protein that in humans is encoded by the ISG20 gene. ^{[5] [6] [7]} It belongs to the ISG family of proteins, which are typically stimulated by type I interferon as a response to viral infection.

Structure and Function

At a molecular level ISG20 is an RNA exonuclease, which under normal physiological conditions contributes to the antiviral response of the host ^[8] . It belongs to the Rex4 exonucleases subfamily and is evolutionarily related to yeast REXO4.

It is classified as a member of the DEDDh exonuclease family, defined by a conserved catalytic core consisting of three aspartate residues and one glutamate residue distributed across the Exo I–III motifs, together with an additional conserved histidine residue essential for activity ^[9] .

It is enzymatically capable of degrading single-stranded RNA and single-stranded DNA alike ^[10] .

Disocvery

ISG20 was discovered in 1997 by Céline Gongora at the Institude for Molecular Genetics (IGMM) within the University of Montpellier. The new protein was discovered through differential display in IFNα/β treated human cells ^[11] .

Later it was showed that ISG20 expression is drived directly by ssDNA and ssRNA signalling through NF-kB pathways, leading to a more robust expression of ISG20, than through the interferon pathway ^[12] .

Cancer Involvement

It has been observed that ISG20 shows somewhat opposing activity in different types of cancers. While it drives cell proliferation in breast cancer, AML, glioma, cervical cancer, renal cancer, liver cancer and oral cancer, it has been shown to inhibit cell proliferation in ovarian cancer ^[13] .

While the mechanism of action is not fully understood, it is thought that in the majority of cases where ISG20 has a proliferative effect, thyroid hormone stimulation causes the secretion of ISG20, which in turn contributes to proliferation, stimulates migration and drives angiogenesis. The proliferative effect is mediated via metalloproteinase MMP-9 pathway by accelerating the G1/S transition, while the stimulation of expression of extracellular matrix degrading enzymes drives migration and invasion. Angiogenesis is mediated by Interleukin 8 and the JAK/STAT Pathway ^[14] .

References

1. GRCh38: Ensembl release 89: ENSG00000172183 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000039236 – 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.
5. Gongora C, David G, Pintard L, Tissot C, Hua TD, Dejean A, Mechti N (Aug 1997). "Molecular cloning of a new interferon-induced PML nuclear body-associated protein". The Journal of Biological Chemistry. 272 (31): 19457–63. doi: 10.1074/jbc.272.31.19457 . PMID   9235947.
6. Mattei MG, Tissot C, Gongora C, Mechti N (Jun 1998). "Assignment of ISG20 encoding a new interferon-induced PML nuclear body-associated protein, to chromosome 15q26 by in situ hybridization". Cytogenetics and Cell Genetics. 79 (3–4): 286–7. doi:10.1159/000134745. PMID   9605874.
7. "Entrez Gene: ISG20 interferon stimulated exonuclease gene 20kDa".
8. Weiss, CM (2018). "The Interferon-Induced Exonuclease ISG20 Exerts Antiviral Activity through Upregulation of Type I Interferon Response Proteins". mSphere. 19 (5). doi: 10.1128/mSphere.00209-18 .
9. Zuo, Y (2001). "Exoribonuclease superfamilies: structural analysis and phylogenetic distribution". Nucleic Acids Research. 29 (5). 1017-1026. doi: 10.1093/nar/29.5.1017 .
10. Zheng, Z (2017). "Interferon-stimulated gene 20-kDa protein (ISG20) in infection and disease: Review and outlook". Intractable Rare Dis Res. 6 (1): 35–40. doi: 10.5582/irdr.2017.01004 .
11. Gongora, Céline (1997). "Molecular Cloning of a New Interferon-induced PML Nuclear Body-associated Protein". J Biol Chem. 277 (31). Elsevier: 19457–19463. doi: 10.1074/jbc.272.31.19457 .
12. Espert, L (2004). "The exonuclease ISG20 is directly induced by synthetic dsRNA via NF-kappaB and IRF1 activation". Oncogene. 23. Nature: 4636–4640. doi:10.1038/sj.onc.1207586.
13. Zhu, X (2025). "ISG20: The multifaceted 'molecular star' in cancer research (Review)". Oncology Reports. 54 (5). Spandidos Publications. doi: 10.3892/or.2025.8985 .
14. Zhu, X (2025). "ISG20: The multifaceted 'molecular star' in cancer research (Review)". Oncology Reports. 54 (5). Spandidos Publications. doi: 10.3892/or.2025.8985 .

Further reading

• Pentecost BT (Jan 1998). "Expression and estrogen regulation of the HEM45 MRNA in human tumor lines and in the rat uterus". The Journal of Steroid Biochemistry and Molecular Biology. 64 (1–2): 25–33. doi:10.1016/S0960-0760(97)00140-4. PMID   9569007. S2CID   23325745.
• Nguyen LH, Espert L, Mechti N, Wilson DM (Jun 2001). "The human interferon- and estrogen-regulated ISG20/HEM45 gene product degrades single-stranded RNA and DNA in vitro". Biochemistry. 40 (24): 7174–9. doi:10.1021/bi010141t. PMID   11401564.
• Izmailova E, Bertley FM, Huang Q, Makori N, Miller CJ, Young RA, Aldovini A (Feb 2003). "HIV-1 Tat reprograms immature dendritic cells to express chemoattractants for activated T cells and macrophages". Nature Medicine. 9 (2): 191–7. doi:10.1038/nm822. PMID   12539042. S2CID   26145639.
• Espert L, Degols G, Gongora C, Blondel D, Williams BR, Silverman RH, Mechti N (May 2003). "ISG20, a new interferon-induced RNase specific for single-stranded RNA, defines an alternative antiviral pathway against RNA genomic viruses". The Journal of Biological Chemistry. 278 (18): 16151–8. doi: 10.1074/jbc.M209628200 . PMID   12594219.
• Horio T, Murai M, Inoue T, Hamasaki T, Tanaka T, Ohgi T (Nov 2004). "Crystal structure of human ISG20, an interferon-induced antiviral ribonuclease". FEBS Letters. 577 (1–2): 111–6. Bibcode:2004FEBSL.577..111H. doi: 10.1016/j.febslet.2004.09.074 . PMID   15527770.