View source for STAT protein

{{Short description|Family of intracellular transcription factors}}
{{More citations needed|date=August 2010}}
[[File:Stat domain structure.png|thumb|350px|right|Domains and covalent modification sites of STAT proteins.]]
{{Infobox protein family
| Symbol = STAT_alpha
| Name = STAT protein, all-alpha domain
| image =
| width =
| caption =
| Pfam= PF01017
| InterPro= IPR013800
| SMART=
| Prosite =
| SCOP = 1bgf
| TCDB =
| OPM family=
| OPM protein= 
| PDB= 
}}
{{Infobox protein family
| Symbol = STAT_bind
| Name = STAT protein, DNA binding domain
| image =
| width =
| caption =
| Pfam= PF02864
| InterPro= IPR013801
| SMART=
| Prosite =
| SCOP = 1bgf
| TCDB =
| OPM family=
| OPM protein=
| PDB=
}}
{{Infobox protein family
| Symbol = STAT_int
| Name = STAT protein, protein interaction domain
| image =
| width =
| caption =
| Pfam= PF02865
| InterPro= IPR013799
| SMART=
| Prosite =
| SCOP = 1bgf
| TCDB =
| OPM family=
| OPM protein=
| PDB={{PDB3|1yvl}}A:2-122, {{PDB3|1bgf}}A:2-122
}}
{{Infobox protein family
| Symbol = Dict-STAT-coil
| Name = Dictyostelium STAT, coiled coil
| image = PDB 1uur EBI.jpg
| width = 
| caption = structure of an activated dictyostelium stat in its DNA-unbound form
| Pfam = PF09267
| Pfam_clan =  
| InterPro = IPR015347
| SMART = 
| PROSITE = 
| MEROPS = 
| SCOP = 1uur
| TCDB = 
| OPM family = 
| OPM protein = 
| CAZy = 
| CDD = 
}}
Members of the '''signal transducer and activator of transcription''' ('''STAT''') '''protein family''' are intracellular [[transcription factor]]s that mediate many aspects of cellular [[Immunity (medical)|immunity]], [[cellular proliferation|proliferation]], [[apoptosis]] and [[differentiation (cellular)|differentiation]]. They are primarily activated by membrane receptor-associated [[Janus kinase]]s (JAK). Dysregulation of this pathway is frequently observed in primary tumors and leads to increased [[angiogenesis]] which enhances the survival of [[tumor]]s and [[immunosuppression]]. [[Gene knockout]] studies have provided evidence that STAT proteins are involved in the development and function of the [[immune system]] and play a role in maintaining [[immune tolerance]] and tumor surveillance.

==STAT family==
The first two STAT proteins were identified in the [[interferon]] system. There are seven mammalian STAT family members that have been identified: [[STAT1]], [[STAT2]], [[STAT3]], [[STAT4]], [[STAT5]] ([[STAT5A]] and [[STAT5B]]), and [[STAT6]].  
STAT1 homodimers are involved in type II interferon signalling, and bind to the '''GAS''' (Interferon-'''G'''amma '''A'''ctivated '''S'''equence) promoter to induce expression of [[interferon stimulated gene]]s (ISG).  In type I interferon signaling, STAT1-STAT2 heterodimer combines with '''IRF'''9 ('''I'''nterferon '''R'''esponse '''F'''actor) to form '''ISGF'''3 ('''I'''nterferon '''S'''timulated '''G'''ene '''F'''actor), which binds to the '''ISRE''' ('''I'''nterferon-'''S'''timulated '''R'''esponse '''E'''lement) promoter to induce ISG expression.

==Structure==
All seven STAT proteins share a common structural motif consisting of an [[N-terminal]] domain followed by a [[coiled-coil]], [[DNA-binding domain]], linker, [[SH2 domain|Src homology 2 (SH2)]], and a [[C-terminal]] [[transactivation|transactivation domain]]. Much research has focused on elucidating the roles each of these domains play in regulating different STAT isoforms. Both the N-terminal and SH2 domains mediate homo or heterodimer formation, while the coiled-coil domain functions partially as a [[nuclear localization signal]] (NLS). Transcriptional activity and DNA association are determined by the transactivation and DNA-binding domains, respectively.


==Activation==
Extracellular binding of [[cytokine]]s or [[growth factor]]s induce activation of receptor-associated [[Janus kinase]]s, which phosphorylate a specific tyrosine residue within the STAT protein promoting [[protein dimer|dimerization]] via their [[SH2 domain]]s. The phosphorylated dimer is then actively transported to the nucleus via an [[importin|importin α/β]] ternary complex. Originally, STAT proteins were described as ''latent'' [[cytoplasmic]] transcription factors as phosphorylation was thought to be required for nuclear retention. However, unphosphorylated STAT proteins also shuttle between the cytosol and nucleus, and play a role in gene expression. Once STAT reaches the nucleus, it binds to a consensus DNA-recognition motif called gamma-activated sites (GAS) in the [[promotor (biology)|promoter]] region of [[cytokine]]-[[inducible gene]]s and activates transcription. The STAT protein can be dephosphorylated by nuclear [[phosphatases]], which leads to inactivation of STAT and subsequent transport out of the nucleus by an [[exportin]]-[[Ran (gene)|RanGTP]] complex.

==See also==
*[[JAK-STAT pathway]]
*[[DNA-binding protein]]
*[[STAT Inhibitors]]

==Additional images==
<gallery>
 Image:Jakstat pathway.svg|Key steps of the [[JAK-STAT pathway]]
 Image:PDB 1bgf EBI.jpg|Structure of the amino-terminal protein interaction domain of STAT-4.<ref name="pmid9461439">{{cite journal |vauthors=Vinkemeier U, Moarefi I, Darnell JE, Kuriyan J |title=Structure of the amino-terminal protein interaction domain of STAT-4 |journal=Science |volume=279 |issue=5353 |pages=1048–52 |date=February 1998 |pmid=9461439 |doi= 10.1126/science.279.5353.1048|bibcode=1998Sci...279.1048V }}</ref>
</gallery>

==References==
{{Reflist}}

==External links==
* {{MeshName|STAT+Transcription+Factors}}
* [http://www.sdbonline.org/fly/gene/marelle.htm ''Drosophila'' ''Signal-transducer and activator of transcription protein at 92E'' - The Interactive Fly]

{{Transcription factors|g4}}
{{JAK-STAT signaling pathway}}
{{Cytokine receptor modulators}}
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{{DEFAULTSORT:Stat Protein}}
[[Category:Gene expression]]
[[Category:Immune system]]
[[Category:Protein families]]
[[Category:Transcription factors]]
[[Category:Signal transduction]]