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{{Infobox_gene}}
{{Infobox_gene}}


'''Signal transducer and activator of transcription 2''' is a [[protein]] that in humans is encoded by the ''STAT2'' [[gene]].<ref name="pmid7885841">{{cite journal | vauthors = Yan R, Qureshi S, Zhong Z, Wen Z, Darnell JE | title = The genomic structure of the STAT genes: multiple exons in coincident sites in Stat1 and Stat2 | journal = Nucleic Acids Research | volume = 23 | issue = 3 | pages = 459–63 | date = Feb 1995 | pmid = 7885841 | pmc = 306697 | doi = 10.1093/nar/23.3.459 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: STAT2 signal transducer and activator of transcription 2, 113kDa| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6773}}</ref> It is a member of the [[STAT protein]] family. This protein is critical to the biological response of type I interferons (IFNs).<ref name=":0">{{Cite journal|last=Park|first=Christopher|last2=Li|first2=Suzanne|last3=Cha|first3=Edward|last4=Schindler|first4=Christian|date=2000-12-01|title=Immune Response in Stat2 Knockout Mice|url=https://www.cell.com/immunity/abstract/S1074-7613(00)00077-7|journal=Immunity|language=English|volume=13|issue=6|pages=795–804|doi=10.1016/S1074-7613(00)00077-7|issn=1074-7613|pmid=11163195}}</ref>
'''Signal transducer and activator of transcription 2''' is a [[protein]] that in humans is encoded by the ''STAT2'' [[gene]].<ref name="pmid7885841">{{cite journal | vauthors = Yan R, Qureshi S, Zhong Z, Wen Z, Darnell JE | title = The genomic structure of the STAT genes: multiple exons in coincident sites in Stat1 and Stat2 | journal = Nucleic Acids Research | volume = 23 | issue = 3 | pages = 459–63 | date = Feb 1995 | pmid = 7885841 | pmc = 306697 | doi = 10.1093/nar/23.3.459 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: STAT2 signal transducer and activator of transcription 2, 113kDa| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6773}}</ref> It is a member of the [[STAT protein]] family. This protein is critical to the biological response of type I interferons (IFNs).<ref name=":0">{{Cite journal|last=Park|first=Christopher|last2=Li|first2=Suzanne|last3=Cha|first3=Edward|last4=Schindler|first4=Christian|date=2000-12-01|title=Immune Response in Stat2 Knockout Mice|url=https://www.cell.com/immunity/abstract/S1074-7613(00)00077-7|journal=Immunity|language=English|volume=13|issue=6|pages=795–804|doi=10.1016/S1074-7613(00)00077-7|issn=1074-7613|pmid=11163195}}</ref> STAT2 sequence identity between mouse and human is only 68%.<ref>{{Cite journal|last=Park|first=C.|last2=Lecomte|first2=M. J.|last3=Schindler|first3=C.|date=1999-11-01|title=Murine Stat2 is uncharacteristically divergent|url=https://pubmed.ncbi.nlm.nih.gov/10518610/|journal=Nucleic Acids Research|volume=27|issue=21|pages=4191–4199|doi=10.1093/nar/27.21.4191|issn=1362-4962|pmid=10518610}}</ref>


== Function ==
== Function ==
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* [[STAT1]].<ref name = pmid8621447>{{cite journal | vauthors = Li X, Leung S, Qureshi S, Darnell JE, Stark GR | title = Formation of STAT1-STAT2 heterodimers and their role in the activation of IRF-1 gene transcription by interferon-alpha | journal = The Journal of Biological Chemistry | volume = 271 | issue = 10 | pages = 5790–4 | date = Mar 1996 | pmid = 8621447 | doi = 10.1074/jbc.271.10.5790| doi-access = free }}</ref><ref name = pmid10446176>{{cite journal | vauthors = Dumler I, Kopmann A, Wagner K, Mayboroda OA, Jerke U, Dietz R, Haller H, Gulba DC | title = Urokinase induces activation and formation of Stat4 and Stat1-Stat2 complexes in human vascular smooth muscle cells | journal = The Journal of Biological Chemistry | volume = 274 | issue = 34 | pages = 24059–65 | date = Aug 1999 | pmid = 10446176 | doi = 10.1074/jbc.274.34.24059| doi-access = free }}</ref><ref name = pmid12048190>{{cite journal | vauthors = Fagerlund R, Mélen K, Kinnunen L, Julkunen I | title = Arginine/lysine-rich nuclear localization signals mediate interactions between dimeric STATs and importin alpha 5 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 33 | pages = 30072–8 | date = Aug 2002 | pmid = 12048190 | doi = 10.1074/jbc.M202943200 | doi-access = free }}</ref>
* [[STAT1]].<ref name = pmid8621447>{{cite journal | vauthors = Li X, Leung S, Qureshi S, Darnell JE, Stark GR | title = Formation of STAT1-STAT2 heterodimers and their role in the activation of IRF-1 gene transcription by interferon-alpha | journal = The Journal of Biological Chemistry | volume = 271 | issue = 10 | pages = 5790–4 | date = Mar 1996 | pmid = 8621447 | doi = 10.1074/jbc.271.10.5790| doi-access = free }}</ref><ref name = pmid10446176>{{cite journal | vauthors = Dumler I, Kopmann A, Wagner K, Mayboroda OA, Jerke U, Dietz R, Haller H, Gulba DC | title = Urokinase induces activation and formation of Stat4 and Stat1-Stat2 complexes in human vascular smooth muscle cells | journal = The Journal of Biological Chemistry | volume = 274 | issue = 34 | pages = 24059–65 | date = Aug 1999 | pmid = 10446176 | doi = 10.1074/jbc.274.34.24059| doi-access = free }}</ref><ref name = pmid12048190>{{cite journal | vauthors = Fagerlund R, Mélen K, Kinnunen L, Julkunen I | title = Arginine/lysine-rich nuclear localization signals mediate interactions between dimeric STATs and importin alpha 5 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 33 | pages = 30072–8 | date = Aug 2002 | pmid = 12048190 | doi = 10.1074/jbc.M202943200 | doi-access = free }}</ref>
{{Div col end}}
{{Div col end}}

== STAT2 deficiency ==

==== '''''STAT2-/- mice''''' ====
Deficiency of STAT2 is associated with increassed proliferation of M1, M2 or M1/M2 fenotype expressing macrophages during bacterial infection.<ref>{{Cite journal|last=Gopal|first=Radha|last2=Lee|first2=Benjamin|last3=McHugh|first3=Kevin J.|last4=Rich|first4=Helen E.|last5=Ramanan|first5=Krishnaveni|last6=Mandalapu|first6=Sivanarayana|last7=Clay|first7=Michelle E.|last8=Seger|first8=Philip J.|last9=Enelow|first9=Richard I.|last10=Manni|first10=Michelle L.|last11=Robinson|first11=Keven M.|date=2018-09-25|title=STAT2 Signaling Regulates Macrophage Phenotype During Influenza and Bacterial Super-Infection|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178135/|journal=Frontiers in Immunology|volume=9|doi=10.3389/fimmu.2018.02151|issn=1664-3224|pmc=6178135|pmid=30337919}}</ref>


== References ==
== References ==

Revision as of 12:05, 25 May 2021

STAT2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSTAT2, ISGF-3, P113, STAT113, IMD44, signal transducer and activator of transcription 2, PTORCH3
External IDsOMIM: 600556; MGI: 103039; HomoloGene: 3952; GeneCards: STAT2; OMA:STAT2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

6773

20847

Ensembl

ENSG00000170581

ENSMUSG00000040033

UniProt

P52630

Q9WVL2

RefSeq (mRNA)

NM_019963

RefSeq (protein)

NP_005410
NP_938146

n/a

Location (UCSC)Chr 12: 56.34 – 56.36 MbChr 10: 128.11 – 128.13 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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. This protein is critical to the biological response of type I interferons (IFNs).[7] STAT2 sequence identity between mouse and human is only 68%.[8]

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 IFN, this protein forms a complex with STAT1 and IFN regulatory factor family protein p48 (IRF9) and form ISGF-3 (IFN-stimulated gene factor-3), in which this protein acts as a transactivator, but lacks the ability to bind DNA directly.[9] ISGF-3 proceeds the activation of genes via the IFN-stimulated response element (ISRE). ISRE-driven genes include Ly-6C, the double-stranded RNA kinase (PKR), 2´ to 5´ oligoadenylate synthase (OAS), MX and potentially MHC class I.[10] 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]

STAT2 knockout mice are unresponsive to type I IFN and extremelly vulnerable to viral infection. They indicate the loss of the type I IFN autocrine loop and several defects in macrophages and T cell responses. Stat2-/- cells show differences in the biological response to IFN-α.[7]

Interactions

STAT2 has been shown to interact with:

STAT2 deficiency

STAT2-/- mice

Deficiency of STAT2 is associated with increassed proliferation of M1, M2 or M1/M2 fenotype expressing macrophages during bacterial infection.[23]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000170581 – Ensembl, May 2017
  2. ^ a b c 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. ^ a b "Entrez Gene: STAT2 signal transducer and activator of transcription 2, 113kDa".
  7. ^ a b Park, Christopher; Li, Suzanne; Cha, Edward; Schindler, Christian (2000-12-01). "Immune Response in Stat2 Knockout Mice". Immunity. 13 (6): 795–804. doi:10.1016/S1074-7613(00)00077-7. ISSN 1074-7613. PMID 11163195.
  8. ^ Park, C.; Lecomte, M. J.; Schindler, C. (1999-11-01). "Murine Stat2 is uncharacteristically divergent". Nucleic Acids Research. 27 (21): 4191–4199. doi:10.1093/nar/27.21.4191. ISSN 1362-4962. PMID 10518610.
  9. ^ Schindler, C. "Cytokines and STAT signaling". Adv Pharmacol. 47: 113–74.
  10. ^ Lee, Chien-Kuo; Gimeno, Ramon; Levy, David E. (1999-11-15). "Differential Regulation of Constitutive Major Histocompatibility Complex Class I Expression in T and B Lymphocytes". The Journal of Experimental Medicine. 190 (10): 1451–1464. ISSN 0022-1007. PMC 2195695. PMID 10562320.
  11. ^ 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.
  12. ^ a b 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.
  13. ^ 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.
  14. ^ 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.
  15. ^ 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.
  16. ^ 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.
  17. ^ 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.
  18. ^ 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.
  19. ^ 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.
  20. ^ 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.
  21. ^ 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.
  22. ^ 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.
  23. ^ Gopal, Radha; Lee, Benjamin; McHugh, Kevin J.; Rich, Helen E.; Ramanan, Krishnaveni; Mandalapu, Sivanarayana; Clay, Michelle E.; Seger, Philip J.; Enelow, Richard I.; Manni, Michelle L.; Robinson, Keven M. (2018-09-25). "STAT2 Signaling Regulates Macrophage Phenotype During Influenza and Bacterial Super-Infection". Frontiers in Immunology. 9. doi:10.3389/fimmu.2018.02151. ISSN 1664-3224. PMC 6178135. PMID 30337919.{{cite journal}}: CS1 maint: unflagged free DOI (link)

Further reading

External links


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

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