Type |
Details |
Score |
Publication |
First Author: |
Hoffmeyer A |
Year: |
2001 |
Journal: |
Mol Cell Biol |
Title: |
Gadd45gamma is dispensable for normal mouse development and T-cell proliferation. |
Volume: |
21 |
Issue: |
9 |
Pages: |
3137-43 |
|
•
•
•
•
•
|
Publication |
First Author: |
Naylor MJ |
Year: |
2003 |
Journal: |
J Biol Chem |
Title: |
The neuropeptide galanin augments lobuloalveolar development. |
Volume: |
278 |
Issue: |
31 |
Pages: |
29145-52 |
|
•
•
•
•
•
|
Publication |
First Author: |
Kazansky AV |
Year: |
1995 |
Journal: |
Mol Endocrinol |
Title: |
Regulation of mammary gland factor/Stat5a during mammary gland development. |
Volume: |
9 |
Issue: |
11 |
Pages: |
1598-609 |
|
•
•
•
•
•
|
Publication |
First Author: |
Meinke A |
Year: |
1996 |
Journal: |
Mol Cell Biol |
Title: |
Activation of different Stat5 isoforms contributes to cell-type-restricted signaling in response to interferons. |
Volume: |
16 |
Issue: |
12 |
Pages: |
6937-44 |
|
•
•
•
•
•
|
Publication |
First Author: |
Pericle F |
Year: |
1997 |
Journal: |
J Immunol |
Title: |
Immunocompromised tumor-bearing mice show a selective loss of STAT5a/b expression in T and B lymphocytes. |
Volume: |
159 |
Issue: |
6 |
Pages: |
2580-5 |
|
•
•
•
•
•
|
Publication |
First Author: |
John S |
Year: |
1999 |
Journal: |
Mol Cell Biol |
Title: |
The significance of tetramerization in promoter recruitment by Stat5. |
Volume: |
19 |
Issue: |
3 |
Pages: |
1910-8 |
|
•
•
•
•
•
|
Publication |
First Author: |
Li M |
Year: |
2003 |
Journal: |
Oncogene |
Title: |
Chemoprevention of mammary carcinogenesis in a transgenic mouse model by alpha-difluoromethylornithine (DFMO) in the diet is associated with decreased cyclin D1 activity. |
Volume: |
22 |
Issue: |
17 |
Pages: |
2568-72 |
|
•
•
•
•
•
|
Publication |
First Author: |
Bagheri-Yarmand R |
Year: |
2003 |
Journal: |
J Biol Chem |
Title: |
Activating transcription factor 4 overexpression inhibits proliferation and differentiation of mammary epithelium resulting in impaired lactation and accelerated involution. |
Volume: |
278 |
Issue: |
19 |
Pages: |
17421-9 |
|
•
•
•
•
•
|
Publication |
First Author: |
Wang RA |
Year: |
2003 |
Journal: |
J Cell Biol |
Title: |
Essential functions of p21-activated kinase 1 in morphogenesis and differentiation of mammary glands. |
Volume: |
161 |
Issue: |
3 |
Pages: |
583-92 |
|
•
•
•
•
•
|
Publication |
First Author: |
Petridou B |
Year: |
2003 |
Journal: |
Transgenic Res |
Title: |
Heterogeneous inducible mammary-specific expression of Jab/SOCS1 in lactating transgenic mice is associated with no obvious phenotype, even at the cellular level. |
Volume: |
12 |
Issue: |
6 |
Pages: |
693-706 |
|
•
•
•
•
•
|
Publication |
First Author: |
Moore MA |
Year: |
2005 |
Journal: |
Exp Hematol |
Title: |
Converging pathways in leukemogenesis and stem cell self-renewal. |
Volume: |
33 |
Issue: |
7 |
Pages: |
719-37 |
|
•
•
•
•
•
|
Publication |
First Author: |
Lavens D |
Year: |
2006 |
Journal: |
J Cell Sci |
Title: |
A complex interaction pattern of CIS and SOCS2 with the leptin receptor. |
Volume: |
119 |
Issue: |
Pt 11 |
Pages: |
2214-24 |
|
•
•
•
•
•
|
Publication |
First Author: |
Muraoka-Cook RS |
Year: |
2008 |
Journal: |
Mol Endocrinol |
Title: |
Prolactin and ErbB4/HER4 signaling interact via Janus kinase 2 to induce mammary epithelial cell gene expression differentiation. |
Volume: |
22 |
Issue: |
10 |
Pages: |
2307-21 |
|
•
•
•
•
•
|
Publication |
First Author: |
White UA |
Year: |
2016 |
Journal: |
Am J Physiol Endocrinol Metab |
Title: |
The modulation of adiponectin by STAT5-activating hormones. |
Volume: |
310 |
Issue: |
2 |
Pages: |
E129-36 |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
125
|
Fragment?: |
true |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
51
|
Fragment?: |
true |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
183
|
Fragment?: |
true |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
786
|
Fragment?: |
false |
|
•
•
•
•
•
|
Publication |
First Author: |
Wagner KU |
Year: |
2004 |
Journal: |
Mol Cell Biol |
Title: |
Impaired alveologenesis and maintenance of secretory mammary epithelial cells in Jak2 conditional knockout mice. |
Volume: |
24 |
Issue: |
12 |
Pages: |
5510-20 |
|
•
•
•
•
•
|
Publication |
First Author: |
Hewitt SC |
Year: |
2010 |
Journal: |
J Biol Chem |
Title: |
Estrogen-mediated regulation of Igf1 transcription and uterine growth involves direct binding of estrogen receptor alpha to estrogen-responsive elements. |
Volume: |
285 |
Issue: |
4 |
Pages: |
2676-85 |
|
•
•
•
•
•
|
Publication |
First Author: |
Bierie B |
Year: |
2003 |
Journal: |
Oncogene |
Title: |
Activation of beta-catenin in prostate epithelium induces hyperplasias and squamous transdifferentiation. |
Volume: |
22 |
Issue: |
25 |
Pages: |
3875-87 |
|
•
•
•
•
•
|
Publication |
First Author: |
Udy GB |
Year: |
1997 |
Journal: |
Proc Natl Acad Sci U S A |
Title: |
Requirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression. |
Volume: |
94 |
Issue: |
14 |
Pages: |
7239-44 |
|
•
•
•
•
•
|
Publication |
First Author: |
Starzynski RR |
Year: |
2006 |
Journal: |
Biochem J |
Title: |
STAT5 proteins are involved in down-regulation of iron regulatory protein 1 gene expression by nitric oxide. |
Volume: |
400 |
Issue: |
2 |
Pages: |
367-75 |
|
•
•
•
•
•
|
Publication |
First Author: |
Waxman DJ |
Year: |
2000 |
Journal: |
Novartis Found Symp |
Title: |
Growth hormone pulse-activated STAT5 signalling: a unique regulatory mechanism governing sexual dimorphism of liver gene expression. |
Volume: |
227 |
|
Pages: |
61-74; discussion 75-81 |
|
•
•
•
•
•
|
Publication |
First Author: |
Lécine P |
Year: |
1996 |
Journal: |
Mol Cell Biol |
Title: |
Elf-1 and Stat5 bind to a critical element in a new enhancer of the human interleukin-2 receptor alpha gene. |
Volume: |
16 |
Issue: |
12 |
Pages: |
6829-40 |
|
•
•
•
•
•
|
Publication |
First Author: |
Ilaria RL Jr |
Year: |
1999 |
Journal: |
Blood |
Title: |
Dominant negative mutants implicate STAT5 in myeloid cell proliferation and neutrophil differentiation. |
Volume: |
93 |
Issue: |
12 |
Pages: |
4154-66 |
|
•
•
•
•
•
|
Publication |
First Author: |
Matsumoto A |
Year: |
1999 |
Journal: |
Mol Cell Biol |
Title: |
Suppression of STAT5 functions in liver, mammary glands, and T cells in cytokine-inducible SH2-containing protein 1 transgenic mice. |
Volume: |
19 |
Issue: |
9 |
Pages: |
6396-407 |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
51
|
Fragment?: |
true |
|
•
•
•
•
•
|
Publication |
First Author: |
Levy DE |
Year: |
2002 |
Journal: |
Nat Rev Mol Cell Biol |
Title: |
Stats: transcriptional control and biological impact. |
Volume: |
3 |
Issue: |
9 |
Pages: |
651-62 |
|
•
•
•
•
•
|
Publication |
First Author: |
Shuai K |
Year: |
2003 |
Journal: |
Nat Rev Immunol |
Title: |
Regulation of JAK-STAT signalling in the immune system. |
Volume: |
3 |
Issue: |
11 |
Pages: |
900-11 |
|
•
•
•
•
•
|
Publication |
First Author: |
Takakuma K |
Year: |
2013 |
Journal: |
PLoS One |
Title: |
Novel multiplexed assay for identifying SH2 domain antagonists of STAT family proteins. |
Volume: |
8 |
Issue: |
8 |
Pages: |
e71646 |
|
•
•
•
•
•
|
Protein Domain |
Type: |
Family |
Description: |
The STAT protein (Signal Transducers and Activators of Transcription) family contains transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors, hence they act as signal transducers in the cytoplasm and transcription activators in the nucleus []. Binding of these factors to cell-surface receptors leads to receptor autophosphorylation at a tyrosine, the phosphotyrosine being recognised by the STAT SH2 domain, which mediates the recruitment of STAT proteins from the cytosol and their association with the activated receptor. The STAT proteins are then activated by phosphorylation via members of the JAK family of protein kinases, causing them to dimerise and translocated to the nucleus, where they bind to specific promoter sequences in target genes. In mammals, STATs comprise a family of seven structurally and functionally related proteins: Stat1, Stat2, Stat3, Stat4, Stat5a and Stat5b, Stat6. STAT proteins play a critical role in regulating innate and acquired host immune responses. Dysregulation of at least two STAT signalling cascades (i.e. Stat3 and Stat5) is associated with cellular transformation.Signalling through the JAK/STAT pathway is initiated when a cytokine binds to its corresponding receptor. This leads to conformational changes in the cytoplasmic portion of the receptor, initiating activation of receptor associated members of the JAK family of kinases. The JAKs, in turn, mediate phosphorylation at the specific receptor tyrosine residues, which then serve as docking sites for STATs and other signalling molecules. Once recruited to the receptor, STATs also become phosphorylated by JAKs, on a single tyrosine residue. Activated STATs dissociate from the receptor, dimerise, translocate to the nucleus and bind to members of the GAS (gamma activated site) family of enhancers.The seven STAT proteins identified in mammals range in size from 750 and 850 amino acids. The chromosomal distribution of these STATs, as well as the identification of STATs in more primitive eukaryotes, suggest that this family arose from a single primordial gene. STATs share 6 structurally and functionally conserved domains including: an N-terminal domain (ND) that strengthens interactions between STAT dimers on adjacent DNA-binding sites; a coiled-coil STAT domain (CCD) that is implicated in protein-protein interactions; a DNA-binding domain (DBD) with an immunoglobulin-like fold similar to p53 tumour suppressor protein; an EF-hand-like linker domain connecting the DNA-binding and SH2 domains; an SH2 domain () that acts as a phosphorylation-dependent switch to control receptor recognition and DNA-binding; and a C-terminal transactivation domain [, , ]. The crystal structure of the N terminus of Stat4 reveals a dimer. The interface of this dimer is formed by a ring-shaped element consisting of five short helices. Several studies suggest that this N-terminal dimerisation promotes cooperativity of binding to tandem GAS elements and with the transcriptional coactivator CBP/p300. |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
793
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
154
|
Fragment?: |
true |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
113
|
Fragment?: |
true |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
797
|
Fragment?: |
false |
|
•
•
•
•
•
|
Publication |
First Author: |
Chen CC |
Year: |
2012 |
Journal: |
Genes Dev |
Title: |
Autocrine prolactin induced by the Pten-Akt pathway is required for lactation initiation and provides a direct link between the Akt and Stat5 pathways. |
Volume: |
26 |
Issue: |
19 |
Pages: |
2154-68 |
|
•
•
•
•
•
|
Publication |
First Author: |
Kisseleva T |
Year: |
2002 |
Journal: |
Gene |
Title: |
Signaling through the JAK/STAT pathway, recent advances and future challenges. |
Volume: |
285 |
Issue: |
1-2 |
Pages: |
1-24 |
|
•
•
•
•
•
|
Publication |
First Author: |
Chen X |
Year: |
1998 |
Journal: |
Cell |
Title: |
Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to DNA. |
Volume: |
93 |
Issue: |
5 |
Pages: |
827-39 |
|
•
•
•
•
•
|
Publication |
First Author: |
Mao X |
Year: |
2005 |
Journal: |
Mol Cell |
Title: |
Structural bases of unphosphorylated STAT1 association and receptor binding. |
Volume: |
17 |
Issue: |
6 |
Pages: |
761-71 |
|
•
•
•
•
•
|
Publication |
First Author: |
Ren Z |
Year: |
2008 |
Journal: |
Biochem Biophys Res Commun |
Title: |
Crystal structure of unphosphorylated STAT3 core fragment. |
Volume: |
374 |
Issue: |
1 |
Pages: |
1-5 |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
277
|
Fragment?: |
true |
|
•
•
•
•
•
|
Publication |
First Author: |
Soler-Lopez M |
Year: |
2004 |
Journal: |
Mol Cell |
Title: |
Structure of an activated Dictyostelium STAT in its DNA-unbound form. |
Volume: |
13 |
Issue: |
6 |
Pages: |
791-804 |
|
•
•
•
•
•
|
Protein Domain |
Type: |
Homologous_superfamily |
Description: |
The STAT protein (Signal Transducers and Activators of Transcription) family contains transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors, hence they act as signal transducers in the cytoplasm and transcription activators in the nucleus []. Binding of these factors to cell-surface receptors leads to receptor autophosphorylation at a tyrosine, the phosphotyrosine being recognised by the STAT SH2 domain, which mediates the recruitment of STAT proteins from the cytosol and their association with the activated receptor. The STAT proteins are then activated by phosphorylation via members of the JAK family of protein kinases, causing them to dimerise and translocated to the nucleus, where they bind to specific promoter sequences in target genes. In mammals, STATs comprise a family of seven structurally and functionally related proteins: Stat1, Stat2, Stat3, Stat4, Stat5a and Stat5b, Stat6. STAT proteins play a critical role in regulating innate and acquired host immune responses. Dysregulation of at least two STAT signalling cascades (i.e. Stat3 and Stat5) is associated with cellular transformation.Signalling through the JAK/STAT pathway is initiated when a cytokine binds to its corresponding receptor. This leads to conformational changes in the cytoplasmic portion of the receptor, initiating activation of receptor associated members of the JAK family of kinases. The JAKs, in turn, mediate phosphorylation at the specific receptor tyrosine residues, which then serve as docking sites for STATs and other signalling molecules. Once recruited to the receptor, STATs also become phosphorylated by JAKs, on a single tyrosine residue. Activated STATs dissociate from the receptor, dimerise, translocate to the nucleus and bind to members of the GAS (gamma activated site) family of enhancers.The seven STAT proteins identified in mammals range in size from 750 and 850 amino acids. The chromosomal distribution of these STATs, as well as the identification of STATs in more primitive eukaryotes, suggest that this family arose from a single primordial gene. STATs share 6 structurally and functionally conserved domains including: an N-terminal domain (ND) that strengthens interactions between STAT dimers on adjacent DNA-binding sites; a coiled-coil STAT domain (CCD) that is implicated in protein-protein interactions; a DNA-binding domain (DBD) with an immunoglobulin-like fold similar to p53 tumour suppressor protein; an EF-hand-like linker domain connecting the DNA-binding and SH2 domains; an SH2 domain () that acts as a phosphorylation-dependent switch to control receptor recognition and DNA-binding; and a C-terminal transactivation domain [, , ]. The crystal structure of the N terminus of Stat4 reveals a dimer. The interface of this dimer is formed by a ring-shaped element consisting of five short helices. Several studies suggest that this N-terminal dimerisation promotes cooperativity of binding to tandem GAS elements and with the transcriptional coactivator CBP/p300.This superfamily represents the N terminus part of the p53-like DNA-binding domain of STAT proteins. Both the DNA-binding domain and the linker domain help determine DNA-specificity. |
|
•
•
•
•
•
|
Protein Domain |
Type: |
Domain |
Description: |
The STAT protein (Signal Transducers and Activators of Transcription) family contains transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors, hence they act as signal transducers in the cytoplasm and transcription activators in the nucleus []. Binding of these factors to cell-surface receptors leads to receptor autophosphorylation at a tyrosine, the phosphotyrosine being recognised by the STAT SH2 domain, which mediates the recruitment of STAT proteins from the cytosol and their association with the activated receptor. The STAT proteins are then activated by phosphorylation via members of the JAK family of protein kinases, causing them to dimerise and translocated to the nucleus, where they bind to specific promoter sequences in target genes. In mammals, STATs comprise a family of seven structurally and functionally related proteins: Stat1, Stat2, Stat3, Stat4, Stat5a and Stat5b, Stat6. STAT proteins play a critical role in regulating innate and acquired host immune responses. Dysregulation of at least two STAT signalling cascades (i.e. Stat3 and Stat5) is associated with cellular transformation.Signalling through the JAK/STAT pathway is initiated when a cytokine binds to its corresponding receptor. This leads to conformational changes in the cytoplasmic portion of the receptor, initiating activation of receptor associated members of the JAK family of kinases. The JAKs, in turn, mediate phosphorylation at the specific receptor tyrosine residues, which then serve as docking sites for STATs and other signalling molecules. Once recruited to the receptor, STATs also become phosphorylated by JAKs, on a single tyrosine residue. Activated STATs dissociate from the receptor, dimerise, translocate to the nucleus and bind to members of the GAS (gamma activated site) family of enhancers.The seven STAT proteins identified in mammals range in size from 750 and 850 amino acids. The chromosomal distribution of these STATs, as well as the identification of STATs in more primitive eukaryotes, suggest that this family arose from a single primordial gene. STATs share 6 structurally and functionally conserved domains including: an N-terminal domain (ND) that strengthens interactions between STAT dimers on adjacent DNA-binding sites; a coiled-coil STAT domain (CCD) that is implicated in protein-protein interactions; a DNA-binding domain (DBD) with an immunoglobulin-like fold similar to p53 tumour suppressor protein; an EF-hand-like linker domain connecting the DNA-binding and SH2 domains; an SH2 domain () that acts as a phosphorylation-dependent switch to control receptor recognition and DNA-binding; and a C-terminal transactivation domain [, , ]. The crystal structure of the N terminus of Stat4 reveals a dimer. The interface of this dimer is formed by a ring-shaped element consisting of five short helices. Several studies suggest that this N-terminal dimerisation promotes cooperativity of binding to tandem GAS elements and with the transcriptional coactivator CBP/p300.This entry represents a domain found in Dictyostelium STAT proteins. This domain adopts a structure consisting of four long α-helices, folded into a coiled coil. It is responsible for nuclear export of the protein []. |
|
•
•
•
•
•
|
Protein Domain |
Type: |
Homologous_superfamily |
Description: |
The STAT protein (Signal Transducers and Activators of Transcription) family contains transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors, hence they act as signal transducers in the cytoplasm and transcription activators in the nucleus []. Binding of these factors to cell-surface receptors leads to receptor autophosphorylation at a tyrosine, the phosphotyrosine being recognised by the STAT SH2 domain, which mediates the recruitment of STAT proteins from the cytosol and their association with the activated receptor. The STAT proteins are then activated by phosphorylation via members of the JAK family of protein kinases, causing them to dimerise and translocated to the nucleus, where they bind to specific promoter sequences in target genes. In mammals, STATs comprise a family of seven structurally and functionally related proteins: Stat1, Stat2, Stat3, Stat4, Stat5a and Stat5b, Stat6. STAT proteins play a critical role in regulating innate and acquired host immune responses. Dysregulation of at least two STAT signalling cascades (i.e. Stat3 and Stat5) is associated with cellular transformation.Signalling through the JAK/STAT pathway is initiated when a cytokine binds to its corresponding receptor. This leads to conformational changes in the cytoplasmic portion of the receptor, initiating activation of receptor associated members of the JAK family of kinases. The JAKs, in turn, mediate phosphorylation at the specific receptor tyrosine residues, which then serve as docking sites for STATs and other signalling molecules. Once recruited to the receptor, STATs also become phosphorylated by JAKs, on a single tyrosine residue. Activated STATs dissociate from the receptor, dimerise, translocate to the nucleus and bind to members of the GAS (gamma activated site) family of enhancers.The seven STAT proteins identified in mammals range in size from 750 and 850 amino acids. The chromosomal distribution of these STATs, as well as the identification of STATs in more primitive eukaryotes, suggest that this family arose from a single primordial gene. STATs share 6 structurally and functionally conserved domains including: an N-terminal domain (ND) that strengthens interactions between STAT dimers on adjacent DNA-binding sites; a coiled-coil STAT domain (CCD) that is implicated in protein-protein interactions; a DNA-binding domain (DBD) with an immunoglobulin-like fold similar to p53 tumour suppressor protein; an EF-hand-like linker domain connecting the DNA-binding and SH2 domains; an SH2 domain () that acts as a phosphorylation-dependent switch to control receptor recognition and DNA-binding; and a C-terminal transactivation domain [, , ]. The crystal structure of the N terminus of Stat4 reveals a dimer. The interface of this dimer is formed by a ring-shaped element consisting of five short helices. Several studies suggest that this N-terminal dimerisation promotes cooperativity of binding to tandem GAS elements and with the transcriptional coactivator CBP/p300.This entry represents a domain consisting of four long helices that forms a bundle with a left-handed twist (coiled coil), in a right-handed superhelix. |
|
•
•
•
•
•
|
Protein Domain |
Type: |
Domain |
Description: |
The STAT protein (Signal Transducers and Activators of Transcription) family contains transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors, hence they act as signal transducers in the cytoplasm and transcription activators in the nucleus []. Binding of these factors to cell-surface receptors leads to receptor autophosphorylation at a tyrosine, the phosphotyrosine being recognised by the STAT SH2 domain, which mediates the recruitment of STAT proteins from the cytosol and their association with the activated receptor. The STAT proteins arethen activated by phosphorylation via members of the JAK family of protein kinases, causing them to dimerise and translocated to the nucleus, where they bind to specific promoter sequences in target genes. In mammals, STATs comprise a family of seven structurally and functionally related proteins: Stat1, Stat2, Stat3, Stat4, Stat5a and Stat5b, Stat6. STAT proteins play a critical role in regulating innate and acquired host immune responses. Dysregulation of at least two STAT signalling cascades (i.e. Stat3 and Stat5) is associated with cellular transformation.Signalling through the JAK/STAT pathway is initiated when a cytokine binds to its corresponding receptor. This leads to conformational changes in the cytoplasmic portion of the receptor, initiating activation of receptor associated members of the JAK family of kinases. The JAKs, in turn, mediate phosphorylation at the specific receptor tyrosine residues, which then serve as docking sites for STATs and other signalling molecules. Once recruited to the receptor, STATs also become phosphorylated by JAKs, on a single tyrosine residue. Activated STATs dissociate from the receptor, dimerise, translocate to the nucleus and bind to members of the GAS (gamma activated site) family of enhancers.The seven STAT proteins identified in mammals range in size from 750 and 850 amino acids. The chromosomal distribution of these STATs, as well as the identification of STATs in more primitive eukaryotes, suggest that this family arose from a single primordial gene. STATs share 6 structurally and functionally conserved domains including: an N-terminal domain (ND) that strengthens interactions between STAT dimers on adjacent DNA-binding sites; a coiled-coil STAT domain (CCD) that is implicated in protein-protein interactions; a DNA-binding domain (DBD) with an immunoglobulin-like fold similar to p53 tumour suppressor protein; an EF-hand-like linker domain connecting the DNA-binding and SH2 domains; an SH2 domain () that acts as a phosphorylation-dependent switch to control receptor recognition and DNA-binding; and a C-terminal transactivation domain [, , ]. The crystal structure of the N terminus of Stat4 reveals a dimer. The interface of this dimer is formed by a ring-shaped element consisting of five short helices. Several studies suggest that this N-terminal dimerisation promotes cooperativity of binding to tandem GAS elements and with the transcriptional coactivator CBP/p300.This entry represents the DNA-binding domain, which has an immunoglobulin-like structural fold. |
|
•
•
•
•
•
|
Protein Domain |
Type: |
Domain |
Description: |
The STAT protein (Signal Transducers and Activators of Transcription) family contains transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors, hence they act as signal transducers in the cytoplasm and transcription activators in the nucleus []. Binding of these factors to cell-surface receptors leads to receptor autophosphorylation at a tyrosine, the phosphotyrosine being recognised by the STAT SH2 domain, which mediates the recruitment of STAT proteins from the cytosol and their association with the activated receptor. The STAT proteins are then activated by phosphorylation via members of the JAK family of protein kinases, causing them to dimerise and translocated to the nucleus, where they bind to specific promoter sequences in target genes. In mammals, STATs comprise a family of seven structurally and functionally related proteins: Stat1, Stat2, Stat3, Stat4, Stat5a and Stat5b, Stat6. STAT proteins play a critical role in regulating innate and acquired host immune responses. Dysregulation of at least two STAT signalling cascades (i.e. Stat3 and Stat5) is associated with cellular transformation.Signalling through the JAK/STAT pathway is initiated when a cytokine binds to its corresponding receptor. This leads to conformational changes in the cytoplasmic portion of the receptor, initiating activation of receptor associated members of the JAK family of kinases. The JAKs, in turn, mediate phosphorylation at the specific receptor tyrosine residues, which then serve as docking sites for STATs and other signalling molecules. Once recruited to the receptor, STATs also become phosphorylated by JAKs, on a single tyrosine residue. Activated STATs dissociate from the receptor, dimerise, translocate to the nucleus and bind to members of the GAS (gamma activated site) family of enhancers.The seven STAT proteins identified in mammals range in size from 750 and 850 amino acids. The chromosomal distribution of these STATs, as well as the identification of STATs in more primitive eukaryotes, suggest that this family arose from a single primordial gene. STATs share 6 structurally and functionally conserved domains including: an N-terminal domain (ND) that strengthens interactions between STAT dimers on adjacent DNA-binding sites; a coiled-coil STAT domain (CCD) that is implicated in protein-protein interactions; a DNA-binding domain (DBD) with an immunoglobulin-like fold similar to p53 tumour suppressor protein; an EF-hand-like linker domain connecting the DNA-binding and SH2 domains; an SH2 domain () that acts as a phosphorylation-dependent switch to control receptor recognition and DNA-binding; and a C-terminal transactivation domain [, , ]. The crystal structure of the N terminus of Stat4 reveals a dimer. The interface of this dimer is formed by a ring-shaped element consisting of five short helices. Several studies suggest that this N-terminal dimerisation promotes cooperativity of binding to tandem GAS elements and with the transcriptional coactivator CBP/p300.This entry represents the all-alpha helical domain, which consists of four long helices arranged in a bundle with a left-handed twist (coiled-coil), which in turn forms a right-handed superhelix. |
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Protein Domain |
Type: |
Domain |
Description: |
The STAT protein (Signal Transducers and Activators of Transcription) family contains transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors, hence they act as signal transducers in the cytoplasm and transcription activators in the nucleus []. Binding of these factors to cell-surface receptors leads to receptor autophosphorylation at a tyrosine, the phosphotyrosine being recognised by the STAT SH2 domain, which mediates the recruitment of STAT proteins from the cytosol and their association with the activated receptor. The STAT proteins are then activated by phosphorylation via members of the JAK family of protein kinases, causing them to dimerise and translocated to the nucleus, where they bind to specific promoter sequences in target genes. In mammals, STATs comprise a family of seven structurally and functionally related proteins: Stat1, Stat2, Stat3, Stat4, Stat5a and Stat5b, Stat6. STAT proteins play a critical role in regulating innate and acquired host immune responses. Dysregulation of at least two STAT signalling cascades (i.e. Stat3 and Stat5) is associated with cellular transformation.Signalling through the JAK/STAT pathway is initiated when a cytokine binds to its corresponding receptor. This leads to conformational changes in the cytoplasmic portion of the receptor, initiating activation of receptor associated members of the JAK family of kinases. The JAKs, in turn, mediate phosphorylation at the specific receptor tyrosine residues, which then serve as docking sites for STATs and other signalling molecules. Once recruited to the receptor, STATs also become phosphorylated by JAKs, on a singletyrosine residue. Activated STATs dissociate from the receptor, dimerise, translocate to the nucleus and bind to members of the GAS (gamma activated site) family of enhancers.The seven STAT proteins identified in mammals range in size from 750 and 850 amino acids. The chromosomal distribution of these STATs, as well as the identification of STATs in more primitive eukaryotes, suggest that this family arose from a single primordial gene. STATs share 6 structurally and functionally conserved domains including: an N-terminal domain (ND) that strengthens interactions between STAT dimers on adjacent DNA-binding sites; a coiled-coil STAT domain (CCD) that is implicated in protein-protein interactions; a DNA-binding domain (DBD) with an immunoglobulin-like fold similar to p53 tumour suppressor protein; an EF-hand-like linker domain connecting the DNA-binding and SH2 domains; an SH2 domain () that acts as a phosphorylation-dependent switch to control receptor recognition and DNA-binding; and a C-terminal transactivation domain [, , ]. The crystal structure of the N terminus of Stat4 reveals a dimer. The interface of this dimer is formed by a ring-shaped element consisting of five short helices. Several studies suggest that this N-terminal dimerisation promotes cooperativity of binding to tandem GAS elements and with the transcriptional coactivator CBP/p300.This entry represents the N-terminal domain, which is responsible for protein interactions. This domain has a multi-helical structure that can be subdivided into two structural sub-domains. |
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Protein |
Organism: |
Mus musculus/domesticus |
Length: |
749
|
Fragment?: |
false |
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•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
923
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
770
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
749
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
837
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
858
|
Fragment?: |
true |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
922
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
749
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
744
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
925
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
837
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
770
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
749
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
770
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
722
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
748
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
923
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
755
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
749
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
466
|
Fragment?: |
true |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
770
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
749
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
931
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
755
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
712
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
748
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
671
|
Fragment?: |
true |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
374
|
Fragment?: |
true |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
131
|
Fragment?: |
true |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
441
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
254
|
Fragment?: |
false |
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
252
|
Fragment?: |
false |
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•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
243
|
Fragment?: |
true |
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•
•
•
•
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Publication |
First Author: |
Gerhard DS |
Year: |
2004 |
Journal: |
Genome Res |
Title: |
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |
Volume: |
14 |
Issue: |
10B |
Pages: |
2121-7 |
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