STAT6

Signal transducer and activator of transcription 6, interleukin-4 induced
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1OJ5​
Identifiers
Symbols	STAT6 ; D12S1644; IL-4-STAT; STAT6B; STAT6C
External IDs	OMIM: 601512 MGI: 103034 HomoloGene: 2373 ChEMBL: 5401 GeneCards: STAT6 Gene
Gene ontology Molecular function • RNA polymerase II core promoter sequence-specific DNA binding • transcription factor activity, sequence-specific DNA binding • signal transducer activity • protein binding • protein phosphatase binding • identical protein binding Cellular component • nuclear chromatin • nucleoplasm • cytoplasm • cytosol Biological process • negative regulation of transcription from RNA polymerase II promoter • T-helper 1 cell lineage commitment • negative regulation of type 2 immune response • transcription, DNA-templated • regulation of transcription from RNA polymerase II promoter • signal transduction • positive regulation of type I interferon production • mammary gland epithelial cell proliferation • interleukin-4-mediated signaling pathway • regulation of cell proliferation • innate immune response • positive regulation of transcription from RNA polymerase II promoter • positive regulation of isotype switching to IgE isotypes • mammary gland morphogenesis Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6778	20852
Ensembl	ENSG00000166888	ENSMUSG00000002147
UniProt	P42226	P52633
RefSeq (mRNA)	NM_001178078	NM_009284
RefSeq (protein)	NP_001171549	NP_033310
Location (UCSC)	Chr 12: 57.1 – 57.13 Mb	Chr 10: 127.64 – 127.66 Mb
PubMed search

Signal transducer and activator of transcription 6 (STAT6) is a human gene. The protein encoded by this gene is a member of the STAT family of transcription factors.^[1][2]

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. This protein plays a central role in exerting IL4 mediated biological responses. It is found to induce the expression of BCL2L1/BCL-X(L), which is responsible for the anti-apoptotic activity of IL4. Knockout studies in mice suggested the roles of this gene in differentiation of T helper 2 (Th2), expression of cell surface markers, and class switch of immunoglobulins.^[3]

Interactions

STAT6 has been shown to interact with:

• CREB-binding protein,^[4][5]
• EP300,^[4]
• IRF4,^[6]
• NFKB1,^[7]
• Nuclear receptor coactivator 1,^[5][8] and
• SND1.^[9]

Pathology

• Gene fusion
  • Recurrent somatic fusions of the two genes, NGFI-A–binding protein 2 (NAB2) and STAT6, located at chromosomal region 12q13, have been identified in solitary fibrous tumors.^[10]
• Amplification
  • STAT6 is amplified in a subset of dedifferentiated liposarcoma.^[11]

See also

• Interleukin 4

References

1. Leek JP, Hamlin PJ, Bell SM, Lench NJ (1997). "Assignment of the STAT6 gene (STAT6) to human chromosome band 12q13 by in situ hybridization". Cytogenetics and Cell Genetics 79 (3-4): 208–9. doi:10.1159/000134723. PMID 9605853.
2. Hou J, Schindler U, Henzel WJ, Ho TC, Brasseur M, McKnight SL (Sep 1994). "An interleukin-4-induced transcription factor: IL-4 Stat". Science 265 (5179): 1701–6. doi:10.1126/science.8085155. PMID 8085155.
3. "Entrez Gene: STAT6 signal transducer and activator of transcription 6, interleukin-4 induced".
4. McDonald C, Reich NC (Jul 1999). "Cooperation of the transcriptional coactivators CBP and p300 with Stat6". Journal of Interferon & Cytokine Research 19 (7): 711–22. doi:10.1089/107999099313550. PMID 10454341.
5. Litterst CM, Pfitzner E (Dec 2001). "Transcriptional activation by STAT6 requires the direct interaction with NCoA-1". The Journal of Biological Chemistry 276 (49): 45713–21. doi:10.1074/jbc.M108132200. PMID 11574547.
6. Gupta S, Jiang M, Anthony A, Pernis AB (Dec 1999). "Lineage-specific modulation of interleukin 4 signaling by interferon regulatory factor 4". The Journal of Experimental Medicine 190 (12): 1837–48. doi:10.1084/jem.190.12.1837. PMC 2195723. PMID 10601358.
7. Shen CH, Stavnezer J (Jun 1998). "Interaction of stat6 and NF-kappaB: direct association and synergistic activation of interleukin-4-induced transcription". Molecular and Cellular Biology 18 (6): 3395–404. doi:10.1128/mcb.18.6.3395. PMC 108921. PMID 9584180.
8. Litterst CM, Pfitzner E (Sep 2002). "An LXXLL motif in the transactivation domain of STAT6 mediates recruitment of NCoA-1/SRC-1". The Journal of Biological Chemistry 277 (39): 36052–60. doi:10.1074/jbc.M203556200. PMID 12138096.
9. Yang J, Aittomäki S, Pesu M, Carter K, Saarinen J, Kalkkinen N, Kieff E, Silvennoinen O (Sep 2002). "Identification of p100 as a coactivator for STAT6 that bridges STAT6 with RNA polymerase II". The EMBO Journal 21 (18): 4950–8. doi:10.1093/emboj/cdf463. PMC 126276. PMID 12234934.
10. Kabbinavar FF, Hambleton J, Mass RD, Hurwitz HI, Bergsland E, Sarkar S (Jun 2005). "Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer". Journal of Clinical Oncology 23 (16): 3706–12. doi:10.1200/JCO.2005.00.232. PMID 15867200.
11. Doyle LA, Tao D, Mariño-Enríquez A (Sep 2014). "STAT6 is amplified in a subset of dedifferentiated liposarcoma". Modern Pathology 27 (9): 1231–7. doi:10.1038/modpathol.2013.247. PMID 24457460.

Further reading

• Jiang H, Harris MB, Rothman P (Jun 2000). "IL-4/IL-13 signaling beyond JAK/STAT". The Journal of Allergy and Clinical Immunology 105 (6 Pt 1): 1063–70. doi:10.1067/mai.2000.107604. PMID 10856136.
• 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.
• Hou J, Schindler U, Henzel WJ, Ho TC, Brasseur M, McKnight SL (Sep 1994). "An interleukin-4-induced transcription factor: IL-4 Stat". Science 265 (5179): 1701–6. doi:10.1126/science.8085155. PMID 8085155.
• Takeda K, Tanaka T, Shi W, Matsumoto M, Minami M, Kashiwamura S, Nakanishi K, Yoshida N, Kishimoto T, Akira S (Apr 1996). "Essential role of Stat6 in IL-4 signalling". Nature 380 (6575): 627–30. doi:10.1038/380627a0. PMID 8602263.
• Shimoda K, van Deursen J, Sangster MY, Sarawar SR, Carson RT, Tripp RA, Chu C, Quelle FW, Nosaka T, Vignali DA, Doherty PC, Grosveld G, Paul WE, Ihle JN (Apr 1996). "Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stat6 gene". Nature 380 (6575): 630–3. doi:10.1038/380630a0. PMID 8602264.
• Kotanides H, Reich NC (Oct 1996). "Interleukin-4-induced STAT6 recognizes and activates a target site in the promoter of the interleukin-4 receptor gene". The Journal of Biological Chemistry 271 (41): 25555–61. doi:10.1074/jbc.271.41.25555. PMID 8810328.
• Mikita T, Campbell D, Wu P, Williamson K, Schindler U (Oct 1996). "Requirements for interleukin-4-induced gene expression and functional characterization of Stat6". Molecular and Cellular Biology 16 (10): 5811–20. doi:10.1128/mcb.16.10.5811. PMC 231582. PMID 8816495.
• Shen CH, Stavnezer J (Jun 1998). "Interaction of stat6 and NF-kappaB: direct association and synergistic activation of interleukin-4-induced transcription". Molecular and Cellular Biology 18 (6): 3395–404. doi:10.1128/mcb.18.6.3395. PMC 108921. PMID 9584180.
• Leek JP, Hamlin PJ, Bell SM, Lench NJ (1998). "Assignment of the STAT6 gene (STAT6) to human chromosome band 12q13 by in situ hybridization". Cytogenetics and Cell Genetics 79 (3-4): 208–9. doi:10.1159/000134723. PMID 9605853.
• Mikita T, Kurama M, Schindler U (Aug 1998). "Synergistic activation of the germline epsilon promoter mediated by Stat6 and C/EBP beta". Journal of Immunology 161 (4): 1822–8. PMID 9712049.
• Patel BK, Keck CL, O'Leary RS, Popescu NC, LaRochelle WJ (Sep 1998). "Localization of the human stat6 gene to chromosome 12q13.3-q14.1, a region implicated in multiple solid tumors". Genomics 52 (2): 192–200. doi:10.1006/geno.1998.5436. PMID 9782085.
• Zhu M, John S, Berg M, Leonard WJ (Jan 1999). "Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma-mediated signaling". Cell 96 (1): 121–30. doi:10.1016/S0092-8674(00)80965-4. PMID 9989503.
• McDonald C, Reich NC (Jul 1999). "Cooperation of the transcriptional coactivators CBP and p300 with Stat6". Journal of Interferon & Cytokine Research 19 (7): 711–22. doi:10.1089/107999099313550. PMID 10454341.
• Harris MB, Chang CC, Berton MT, Danial NN, Zhang J, Kuehner D, Ye BH, Kvatyuk M, Pandolfi PP, Cattoretti G, Dalla-Favera R, Rothman PB (Oct 1999). "Transcriptional repression of Stat6-dependent interleukin-4-induced genes by BCL-6: specific regulation of iepsilon transcription and immunoglobulin E switching". Molecular and Cellular Biology 19 (10): 7264–75. doi:10.1128/mcb.19.10.7264. PMC 84719. PMID 10490661.
• 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.
• Gupta S, Jiang M, Anthony A, Pernis AB (Dec 1999). "Lineage-specific modulation of interleukin 4 signaling by interferon regulatory factor 4". The Journal of Experimental Medicine 190 (12): 1837–48. doi:10.1084/jem.190.12.1837. PMC 2195723. PMID 10601358.
• Daniel C, Salvekar A, Schindler U (May 2000). "A gain-of-function mutation in STAT6". The Journal of Biological Chemistry 275 (19): 14255–9. doi:10.1074/jbc.C000129200. PMID 10747856.
• Arinobu Y, Sugimoto R, Akaiwa M, Arima K, Otsuka T, Hamasaki N, Izuhara K (Oct 2000). "Augmentation of signal transducer and activation of transcription (STAT)6 and STAT3 expression in stimulated B and T cells". Biochemical and Biophysical Research Communications 277 (2): 317–24. doi:10.1006/bbrc.2000.3674. PMID 11032724.
• Masuda A, Matsuguchi T, Yamaki K, Hayakawa T, Yoshikai Y (Jul 2001). "Interleukin-15 prevents mouse mast cell apoptosis through STAT6-mediated Bcl-xL expression". The Journal of Biological Chemistry 276 (28): 26107–13. doi:10.1074/jbc.M011475200. PMID 11369758.

External links

• STAT6 Transcription Factor at the US National Library of Medicine Medical Subject Headings (MeSH)