Summary: STAT protein, all-alpha domain
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This is the Wikipedia entry entitled "STAT protein". More...
STAT protein Edit Wikipedia article
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This article needs additional citations for verification. (August 2010) |
| STAT protein, all-alpha domain | |||||||||
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| Identifiers | |||||||||
| Symbol | STAT_alpha | ||||||||
| Pfam | PF01017 | ||||||||
| InterPro | IPR013800 | ||||||||
| SCOP | 1bgf | ||||||||
| SUPERFAMILY | 1bgf | ||||||||
| OPM protein | 1bg1 | ||||||||
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| STAT protein, DNA binding domain | |||||||||
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| Identifiers | |||||||||
| Symbol | STAT_bind | ||||||||
| Pfam | PF02864 | ||||||||
| InterPro | IPR013801 | ||||||||
| SCOP | 1bgf | ||||||||
| SUPERFAMILY | 1bgf | ||||||||
| OPM protein | 1bg1 | ||||||||
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| STAT protein, protein interaction domain | |||||||||
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| Identifiers | |||||||||
| Symbol | STAT_int | ||||||||
| Pfam | PF02865 | ||||||||
| InterPro | IPR013799 | ||||||||
| SCOP | 1bgf | ||||||||
| SUPERFAMILY | 1bgf | ||||||||
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| Dictyostelium STAT, coiled coil | |||||||||
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structure of an activated dictyostelium stat in its DNA-unbound form |
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| Identifiers | |||||||||
| Symbol | Dict-STAT-coil | ||||||||
| Pfam | PF09267 | ||||||||
| InterPro | IPR015347 | ||||||||
| SCOP | 1uur | ||||||||
| SUPERFAMILY | 1uur | ||||||||
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The STAT protein (Signal Transducer and Activator of Transcription, or Signal Transduction And transcription) regulates many aspects of growth, survival and differentiation in cells. The transcription factors of this family are activated by Janus kinase (or 'Just Another Kinase', JAK) and dysregulation of this pathway is frequently observed in primary tumours and leads to increased angiogenesis, enhanced survival of tumours 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 tumour surveillance.
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[edit] STAT family
The first two STAT proteins were identified in the interferon system. There are seven mammalian STAT family members which 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-Gamma Activated Sequence) promoter to induce expression of ISG (Interferon Stimulated Genes). In type I interferon signaling, STAT1-STAT2 heterodimer combines with IRF9 (Interferon Response Factor) to form ISGF3 (Interferon Stimulated Gene Factor), which binds to the ISRE (Interferon Stimulated Response Element) promoter to induce ISG expression.
[edit] Function
STAT proteins were originally described as latent cytoplasmic transcription factors that require phosphorylation for nuclear retention. The unphosphorylated STAT proteins shuttles between cytosol and the nucleus waiting for its activation signal. Once the activated transcription factors reaches the nucleus it binds to consensus DNA-recognition motif called gamma activated sites (GAS) in the promoter region of cytokine inducible genes and activates transcription of these genes.
[edit] Activation
Extracellular binding of cytokines induces activation of the intracellular Janus kinase that phosphorylates a specific tyrosine residue in the STAT protein which promotes the dimerization of STAT monomers via their SH2 domain. The phosphorylated dimer is then actively transported in the nucleus via importin a/b and RanGDP complex. Once inside the nucleus the active STAT dimer binds to cytokine inducible promoter regions of genes containing gamma activated site (GAS) motif and activate transcription of these genes. The STAT protein can be dephosphorylated by nuclear phosphatases which leads to inactivation of STAT and the transcription factor becomes transported out of the nucleus by exportin crm1/RanGTP.
[edit] See also
[edit] Additional images
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Key steps of the JAK-STAT pathway
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Structure of the amino-terminal protein interaction domain of STAT-4.[1]
[edit] References
- ^ Vinkemeier U, Moarefi I, Darnell JE, Kuriyan J (February 1998). "Structure of the amino-terminal protein interaction domain of STAT-4". Science 279 (5353): 1048–52. doi:10.1126/science.279.5353.1048. PMID 9461439.
[edit] External links
- STAT Transcription Factors at the US National Library of Medicine Medical Subject Headings (MeSH)
- Drosophila Signal-transducer and activator of transcription protein at 92E - The Interactive Fly
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This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
STAT protein, all-alpha domain Provide feedback
STAT proteins (Signal Transducers and Activators of Transcription) are a family of transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors. STAT proteins also include an SH2 domain PF00017.
Literature references
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Becker S, Groner B, Muller CW; , Nature 1998;394:145-151.: Three-dimensional structure of the Stat3beta homodimer bound to DNA. PUBMED:9671298 EPMC:9671298
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Vinkemeier U, Moarefi I, Darnell JE Jr, Kuriyan J; , Science 1998;279:1048-1052.: Structure of the amino-terminal protein interaction domain of STAT-4. PUBMED:9461439 EPMC:9461439
External database links
| HOMSTRAD: | STAT |
| PANDIT: | PF01017 |
| Pseudofam: | PF01017 |
| SCOP: | 1bgf |
| SYSTERS: | STAT_alpha |
This tab holds annotation information from the InterPro database.
InterPro entry IPR013800
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 [PUBMED:12039028]. 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 structurally and functionally conserved domains including: an N-terminal domain that strengthens interactions between STAT dimers on adjacent DNA-binding sites; a coiled-coil STAT domain that is implicated in protein-protein interactions; a DNA-binding domain 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 (INTERPRO) that acts as a phosphorylation-dependent switch to control receptor recognition and DNA-binding; and a C-terminal transactivation domain [PUBMED:9630226]. 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.
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
| Cellular component | nucleus (GO:0005634) |
| Molecular function | signal transducer activity (GO:0004871) |
| sequence-specific DNA binding transcription factor activity (GO:0003700) | |
| Biological process | signal transduction (GO:0007165) |
| regulation of transcription, DNA-dependent (GO:0006355) |
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Alignments
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| Seed (26) |
Full (626) |
Representative proteomes | NCBI (569) |
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| RP15 (34) |
RP35 (51) |
RP55 (117) |
RP75 (231) |
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| PP/heatmap | 1 | |||||||
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| Seed (26) |
Full (626) |
Representative proteomes | NCBI (569) |
Meta (0) |
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| RP15 (34) |
RP35 (51) |
RP55 (117) |
RP75 (231) |
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| Raw Stockholm | ||||||||
| Gzipped | ||||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
External links
MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
| Seed source: | Pfam-B_856 (release 3.0) |
| Previous IDs: | STAT; |
| Type: | Family |
| Author: | Bateman A, Griffiths-Jones SR |
| Number in seed: | 26 |
| Number in full: | 626 |
| Average length of the domain: | 170.90 aa |
| Average identity of full alignment: | 31 % |
| Average coverage of the sequence by the domain: | 24.35 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 182 | ||||||||||||
| Family (HMM) version: | 15 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Interactions
There is 1 interaction for this family. More...
STAT_bindStructures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the STAT_alpha domain has been found. There are 9 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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Archea
Eukaryota
Bacteria
Other sequences
Viruses
Unclassified
Viroids
Unclassified sequence