Part:BBa_K4160005
STAT3 (Signal Transducer and Activator of Transcription 3)
Signal Transducer and Activator of Transcription 3 (STAT3) (Figure 1) is part of the STAT family. Phosphorylation of STAT3 leads to dimerization and activation of the STAT protein, which is important for mature hematopoietic cell production.1 In these cells, STAT proteins influence cellular survival, proliferation, and lineage-specific differentiation.1
Figure 1 | 3D structure of STAT3. (PDB: 6NUQ)2
Sequence and Features
- 10INCOMPATIBLE WITH RFC[10]Illegal EcoRI site found at 1226
Illegal XbaI site found at 478
Illegal PstI site found at 360
Illegal PstI site found at 1221
Illegal PstI site found at 2158 - 12INCOMPATIBLE WITH RFC[12]Illegal EcoRI site found at 1226
Illegal PstI site found at 360
Illegal PstI site found at 1221
Illegal PstI site found at 2158 - 21INCOMPATIBLE WITH RFC[21]Illegal EcoRI site found at 1226
Illegal BglII site found at 565
Illegal BamHI site found at 1145 - 23INCOMPATIBLE WITH RFC[23]Illegal EcoRI site found at 1226
Illegal XbaI site found at 478
Illegal PstI site found at 360
Illegal PstI site found at 1221
Illegal PstI site found at 2158 - 25INCOMPATIBLE WITH RFC[25]Illegal EcoRI site found at 1226
Illegal XbaI site found at 478
Illegal PstI site found at 360
Illegal PstI site found at 1221
Illegal PstI site found at 2158 - 1000INCOMPATIBLE WITH RFC[1000]Illegal BsaI.rc site found at 1331
Illegal BsaI.rc site found at 1370
Usage and Biology
STAT3 originates from Homo sapiens (human) and mediates cellular responses to interleukins and growth factors.2 The N-terminal domain of STAT proteins facilitates STAT oligomerization. This is important for increasing the stability and association with regulatory proteins.3 In addition, STAT contains a coiled-coil domain, that provides an anchoring domain for regulatory proteins, and a DNA-binding sequence that recognizes a specific DNA sequence, the STAT promotor (BBa_K4160006).3 Furthermore, STAT includes an SRC-homology 2 (SH2) domain, which is a transcriptional activation domain. This domain binds to phosphotyrosine (pY) residues of activated tyrosine kinases, which results in the phosphorylation of STAT proteins. In addition, SH2 domains contribute to the dimerization of STAT, which is essential for DNA binding.3
Activation of STAT
STAT3 is activated through receptor-associated kinase Janus Kinases (JAKs). Cellular responses, including growth factors or interleukins, interact with cytokine receptors on the cellular membrane. Consequently, these receptors will dimerize and induce activation of JAK proteins.3 Activated JAKs phosphorylate the cytokine receptors, which enables binding sites for the SH2 domains of STAT proteins.3 Inactivated STAT will be recruited and phosphorylated by tyrosine residues of the cytoplasmic region of the cytokine receptors. This phosphorylation results in the dimerization of STAT. Consequently, STAT will enter the nucleus and bind to the STAT promoter, which is located upstream of STAT target genes.3
GEMS system
TU-Eindhoven 2022 used this part as a transcription factor for the Generalized Extracellular Molecule Sensor (GEMS) system. Upon dimerization of the GEMS receptor (BBa_K4160008), IL-6RB (BBa_K4160002) domains are activated and induce downstream signaling of the JAK/STAT pathway, which results in STAT-induced gene expression.
Characterization
Characterization of STAT as the transcription factor in the GEMS system can be found on the BBa_K4160008 page.
References
| biology | Homo sapiens |
| protein | STAT3 |