STAT2

Signal transducer and activator of transcription 2 is a protein that in humans is encoded by the STAT2 gene.[5][6] It is a member of the STAT protein family.

STAT2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2KA4
Identifiers
Aliases	STAT2, ISGF-3, P113, STAT113, IMD44, signal transducer and activator of transcription 2, PTORCH3
External IDs	OMIM: 600556 MGI: 103039 HomoloGene: 3952 GeneCards: STAT2
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q13.3 Start 56,341,597 bp[1] End 56,360,167 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10 D3|10 76.5 cM Start 128,270,559 bp[2] End 128,292,849 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • DNA binding • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • GO:0001948 protein binding • identical protein binding • ubiquitin-like protein ligase binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific • signal transducer activity • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific Cellular component • cell membrane • nucleoplasm • cell nucleus • cytoplasm • cytosol Biological process • JAK-STAT cascade • regulation of transcription, DNA-templated • regulation of transcription from RNA polymerase II promoter • transcription, DNA-templated • GO:0022415 viral process • signal transduction • regulation of protein phosphorylation • defense response to virus • regulation of mitochondrial fission • type I interferon signaling pathway • cytokine-mediated signaling pathway • defense response • regulation of cell proliferation • response to peptide hormone • positive regulation of transcription from RNA polymerase II promoter Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	6773	20847
Ensembl	ENSG00000170581	ENSMUSG00000040033
UniProt	P52630	Q9WVL2
RefSeq (mRNA)	NM_005419 NM_198332	NM_019963
RefSeq (protein)	NP_005410 NP_938146	n/a
Location (UCSC)	Chr 12: 56.34 – 56.36 Mb	Chr 10: 128.27 – 128.29 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[6]

Interactions

STAT2 has been shown to interact with:

• CREB-binding protein,[7]
• IFNAR1[8][9][10]
• IFNAR2,[8][11]
• IRF9,[12][13]
• MED14,[14]
• SMARCA4,[15] and
• STAT1.[16][17][18]

References

1. GRCh38: Ensembl release 89: ENSG00000170581 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000040033 - 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. 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.
6. "Entrez Gene: STAT2 signal transducer and activator of transcription 2, 113kDa".
7. 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. Bibcode:1996Natur.383..344B. doi:10.1038/383344a0. PMID 8848048. S2CID 4306588.
8. 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.
9. 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.
10. 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. doi:10.1002/j.1460-2075.1996.tb00444.x. PMC 450004. PMID 8605876.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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. S2CID 251794.
16. 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.
17. 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.
18. 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. S2CID 22135982.
• 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. Bibcode:1992PNAS...89.7840F. 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. Bibcode:1995Natur.375..247M. doi:10.1038/375247a0. PMID 7746328. S2CID 4272223.
• 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. S2CID 12860058.
• 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. doi:10.1002/j.1460-2075.1996.tb00444.x. 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. doi:10.1002/j.1460-2075.1996.tb00445.x. 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. Bibcode:1996Natur.383..344B. doi:10.1038/383344a0. PMID 8848048. S2CID 4306588.
• 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. doi:10.1096/fasebj.13.13.1699. PMID 10506573. S2CID 13251398.

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.