STAT2

Signal transducer and activator of transcription 2, 113kDa
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2KA4​
Identifiers
Symbols	STAT2 ; ISGF-3; P113; STAT113
External IDs	OMIM: 600556 MGI: 103039 HomoloGene: 3952 GeneCards: STAT2 Gene
Gene ontology Molecular function • DNA binding • transcription factor activity, sequence-specific DNA binding • signal transducer activity • protein binding • identical protein binding Cellular component • nucleoplasm • cytoplasm • cytosol • plasma membrane Biological process • positive regulation of defense response to virus by host • transcription, DNA-templated • regulation of transcription from RNA polymerase II promoter • JAK-STAT cascade • viral process • cytokine-mediated signaling pathway • defense response to virus • type I interferon signaling pathway • regulation of type I interferon-mediated signaling pathway • activation of mitophagy in response to mitochondrial depolarization Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6773	20847
Ensembl	ENSG00000170581	ENSMUSG00000040033
UniProt	P52630	Q9QXJ2
RefSeq (mRNA)	NM_005419	NM_019963
RefSeq (protein)	NP_005410	NP_064347
Location (UCSC)	Chr 12: 56.34 – 56.36 Mb	Chr 10: 128.27 – 128.29 Mb
PubMed search

Signal transducer and activator of transcription 2 is a protein that in humans is encoded by the STAT2 gene.^[1][2] It is a member of the STAT protein family.

Function

The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. In response to interferon (IFN), this protein forms a complex with STAT1 and IFN regulatory factor family protein p48 (IRF9), in which this protein acts as a transactivator, but lacks the ability to bind DNA directly. Transcription adaptor P300/CBP (EP300/CREBBP) has been shown to interact specifically with this protein, which is thought to be involved in the process of blocking IFN-alpha response by adenovirus.^[2]

Interactions

STAT2 has been shown to interact with:

• CREB-binding protein,^[3]
• IFNAR1^[4][5][6]
• IFNAR2,^[4][7]
• IRF9,^[8][9]
• MED14,^[10]
• SMARCA4,^[11] and
• STAT1.^[12][13][14]

References

1. Yan R, Qureshi S, Zhong Z, Wen Z, Darnell JE (Feb 1995). "The genomic structure of the STAT genes: multiple exons in coincident sites in Stat1 and Stat2". Nucleic Acids Research 23 (3): 459–63. doi:10.1093/nar/23.3.459. PMC 306697. PMID 7885841.
2. "Entrez Gene: STAT2 signal transducer and activator of transcription 2, 113kDa".
3. Bhattacharya S, Eckner R, Grossman S, Oldread E, Arany Z, D'Andrea A, Livingston DM (Sep 1996). "Cooperation of Stat2 and p300/CBP in signalling induced by interferon-alpha". Nature 383 (6598): 344–7. doi:10.1038/383344a0. PMID 8848048.
4. Li X, Leung S, Kerr IM, Stark GR (Apr 1997). "Functional subdomains of STAT2 required for preassociation with the alpha interferon receptor and for signaling". Molecular and Cellular Biology 17 (4): 2048–56. doi:10.1128/mcb.17.4.2048. PMC 232052. PMID 9121453.
5. Uddin S, Chamdin A, Platanias LC (Oct 1995). "Interaction of the transcriptional activator Stat-2 with the type I interferon receptor". The Journal of Biological Chemistry 270 (42): 24627–30. doi:10.1074/jbc.270.42.24627. PMID 7559568.
6. Yan H, Krishnan K, Greenlund AC, Gupta S, Lim JT, Schreiber RD, Schindler CW, Krolewski JJ (Mar 1996). "Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) acts as a docking site for the latent form of the 113 kDa STAT2 protein". The EMBO Journal 15 (5): 1064–74. PMC 450004. PMID 8605876.
7. Nguyen VP, Saleh AZ, Arch AE, Yan H, Piazza F, Kim J, Krolewski JJ (Mar 2002). "Stat2 binding to the interferon-alpha receptor 2 subunit is not required for interferon-alpha signaling". The Journal of Biological Chemistry 277 (12): 9713–21. doi:10.1074/jbc.M111161200. PMID 11786546.
8. Horvath CM, Stark GR, Kerr IM, Darnell JE (Dec 1996). "Interactions between STAT and non-STAT proteins in the interferon-stimulated gene factor 3 transcription complex". Molecular and Cellular Biology 16 (12): 6957–64. doi:10.1128/mcb.16.12.6957. PMC 231699. PMID 8943351.
9. Martinez-Moczygemba M, Gutch MJ, French DL, Reich NC (Aug 1997). "Distinct STAT structure promotes interaction of STAT2 with the p48 subunit of the interferon-alpha-stimulated transcription factor ISGF3". The Journal of Biological Chemistry 272 (32): 20070–6. doi:10.1074/jbc.272.32.20070. PMID 9242679.
10. Lau JF, Nusinzon I, Burakov D, Freedman LP, Horvath CM (Jan 2003). "Role of metazoan mediator proteins in interferon-responsive transcription". Molecular and Cellular Biology 23 (2): 620–8. doi:10.1128/mcb.23.2.620-628.2003. PMC 151539. PMID 12509459.
11. Huang M, Qian F, Hu Y, Ang C, Li Z, Wen Z (Oct 2002). "Chromatin-remodelling factor BRG1 selectively activates a subset of interferon-alpha-inducible genes". Nature Cell Biology 4 (10): 774–81. doi:10.1038/ncb855. PMID 12244326.
12. Li X, Leung S, Qureshi S, Darnell JE, Stark GR (Mar 1996). "Formation of STAT1-STAT2 heterodimers and their role in the activation of IRF-1 gene transcription by interferon-alpha". The Journal of Biological Chemistry 271 (10): 5790–4. doi:10.1074/jbc.271.10.5790. PMID 8621447.
13. Dumler I, Kopmann A, Wagner K, Mayboroda OA, Jerke U, Dietz R, Haller H, Gulba DC (Aug 1999). "Urokinase induces activation and formation of Stat4 and Stat1-Stat2 complexes in human vascular smooth muscle cells". The Journal of Biological Chemistry 274 (34): 24059–65. doi:10.1074/jbc.274.34.24059. PMID 10446176.
14. Fagerlund R, Mélen K, Kinnunen L, Julkunen I (Aug 2002). "Arginine/lysine-rich nuclear localization signals mediate interactions between dimeric STATs and importin alpha 5". The Journal of Biological Chemistry 277 (33): 30072–8. doi:10.1074/jbc.M202943200. PMID 12048190.

Further reading

• Cebulla CM, Miller DM, Sedmak DD (2000). "Viral inhibition of interferon signal transduction". Intervirology 42 (5-6): 325–30. doi:10.1159/000053968. PMID 10702714.
• Kisseleva T, Bhattacharya S, Braunstein J, Schindler CW (Feb 2002). "Signaling through the JAK/STAT pathway, recent advances and future challenges". Gene 285 (1-2): 1–24. doi:10.1016/S0378-1119(02)00398-0. PMID 12039028.
• Fu XY, Schindler C, Improta T, Aebersold R, Darnell JE (Aug 1992). "The proteins of ISGF-3, the interferon alpha-induced transcriptional activator, define a gene family involved in signal transduction". Proceedings of the National Academy of Sciences of the United States of America 89 (16): 7840–3. doi:10.1073/pnas.89.16.7840. PMC 49807. PMID 1502204.
• Uddin S, Chamdin A, Platanias LC (Oct 1995). "Interaction of the transcriptional activator Stat-2 with the type I interferon receptor". The Journal of Biological Chemistry 270 (42): 24627–30. doi:10.1074/jbc.270.42.24627. PMID 7559568.
• Marrero MB, Schieffer B, Paxton WG, Heerdt L, Berk BC, Delafontaine P, Bernstein KE (May 1995). "Direct stimulation of Jak/STAT pathway by the angiotensin II AT1 receptor". Nature 375 (6528): 247–50. doi:10.1038/375247a0. PMID 7746328.
• Sugiyama T, Nishio Y, Kishimoto T, Akira S (Mar 1996). "Identification of alternative splicing form of Stat2". FEBS Letters 381 (3): 191–4. doi:10.1016/0014-5793(96)00121-4. PMID 8601453.
• Yan H, Krishnan K, Greenlund AC, Gupta S, Lim JT, Schreiber RD, Schindler CW, Krolewski JJ (Mar 1996). "Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) acts as a docking site for the latent form of the 113 kDa STAT2 protein". The EMBO Journal 15 (5): 1064–74. PMC 450004. PMID 8605876.
• Gupta S, Yan H, Wong LH, Ralph S, Krolewski J, Schindler C (Mar 1996). "The SH2 domains of Stat1 and Stat2 mediate multiple interactions in the transduction of IFN-alpha signals". The EMBO Journal 15 (5): 1075–84. PMC 450005. PMID 8605877.
• Li X, Leung S, Qureshi S, Darnell JE, Stark GR (Mar 1996). "Formation of STAT1-STAT2 heterodimers and their role in the activation of IRF-1 gene transcription by interferon-alpha". The Journal of Biological Chemistry 271 (10): 5790–4. doi:10.1074/jbc.271.10.5790. PMID 8621447.
• Bhattacharya S, Eckner R, Grossman S, Oldread E, Arany Z, D'Andrea A, Livingston DM (Sep 1996). "Cooperation of Stat2 and p300/CBP in signalling induced by interferon-alpha". Nature 383 (6598): 344–7. doi:10.1038/383344a0. PMID 8848048.
• Horvath CM, Stark GR, Kerr IM, Darnell JE (Dec 1996). "Interactions between STAT and non-STAT proteins in the interferon-stimulated gene factor 3 transcription complex". Molecular and Cellular Biology 16 (12): 6957–64. doi:10.1128/mcb.16.12.6957. PMC 231699. PMID 8943351.
• Bluyssen HA, Levy DE (Feb 1997). "Stat2 is a transcriptional activator that requires sequence-specific contacts provided by stat1 and p48 for stable interaction with DNA". The Journal of Biological Chemistry 272 (7): 4600–5. doi:10.1074/jbc.272.7.4600. PMID 9020188.
• Li X, Leung S, Kerr IM, Stark GR (Apr 1997). "Functional subdomains of STAT2 required for preassociation with the alpha interferon receptor and for signaling". Molecular and Cellular Biology 17 (4): 2048–56. doi:10.1128/mcb.17.4.2048. PMC 232052. PMID 9121453.
• Martinez-Moczygemba M, Gutch MJ, French DL, Reich NC (Aug 1997). "Distinct STAT structure promotes interaction of STAT2 with the p48 subunit of the interferon-alpha-stimulated transcription factor ISGF3". The Journal of Biological Chemistry 272 (32): 20070–6. doi:10.1074/jbc.272.32.20070. PMID 9242679.
• Mowen K, David M (Nov 1998). "Role of the STAT1-SH2 domain and STAT2 in the activation and nuclear translocation of STAT1". The Journal of Biological Chemistry 273 (46): 30073–6. doi:10.1074/jbc.273.46.30073. PMID 9804758.
• Dumler I, Kopmann A, Wagner K, Mayboroda OA, Jerke U, Dietz R, Haller H, Gulba DC (Aug 1999). "Urokinase induces activation and formation of Stat4 and Stat1-Stat2 complexes in human vascular smooth muscle cells". The Journal of Biological Chemistry 274 (34): 24059–65. doi:10.1074/jbc.274.34.24059. PMID 10446176.
• Paulson M, Pisharody S, Pan L, Guadagno S, Mui AL, Levy DE (Sep 1999). "Stat protein transactivation domains recruit p300/CBP through widely divergent sequences". The Journal of Biological Chemistry 274 (36): 25343–9. doi:10.1074/jbc.274.36.25343. PMID 10464260.
• Gupta S, Jiang M, Pernis AB (Oct 1999). "IFN-alpha activates Stat6 and leads to the formation of Stat2:Stat6 complexes in B cells". Journal of Immunology 163 (7): 3834–41. PMID 10490982.
• Vila-Coro AJ, Rodríguez-Frade JM, Martín De Ana A, Moreno-Ortíz MC, Martínez-A C, Mellado M (Oct 1999). "The chemokine SDF-1alpha triggers CXCR4 receptor dimerization and activates the JAK/STAT pathway". FASEB Journal 13 (13): 1699–710. PMID 10506573.

External links

• STAT2 Transcription Factor at the US National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook STAT2

This article incorporates text from the United States National Library of Medicine, which is in the public domain.