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9  structures 101  species 1  interaction 529  sequences 34  architectures

Family: STAT_int (PF02865)

Summary: STAT protein, protein interaction domain

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STAT protein, protein interaction 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

  1. 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

  2. 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

This tab holds annotation information from the InterPro database.

InterPro entry IPR013799

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 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.

Gene Ontology

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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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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(67)
Full
(529)
Representative proteomes UniProt
(1036)
NCBI
(2285)
Meta
(0)
RP15
(78)
RP35
(143)
RP55
(290)
RP75
(415)
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Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(67)
Full
(529)
Representative proteomes UniProt
(1036)
NCBI
(2285)
Meta
(0)
RP15
(78)
RP35
(143)
RP55
(290)
RP75
(415)
Alignment:
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Sequence:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(67)
Full
(529)
Representative proteomes UniProt
(1036)
NCBI
(2285)
Meta
(0)
RP15
(78)
RP35
(143)
RP55
(290)
RP75
(415)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

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.

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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 View help on the curation process

Seed source: Pfam-B_856 (release 3.0)
Previous IDs: STAT_prot;
Type: Domain
Author: Bateman A, Griffiths-Jones SR
Number in seed: 67
Number in full: 529
Average length of the domain: 116.60 aa
Average identity of full alignment: 38 %
Average coverage of the sequence by the domain: 15.95 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 26.0 26.0
Trusted cut-off 26.0 26.0
Noise cut-off 24.9 24.9
Model length: 123
Family (HMM) version: 15
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

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Interactions

There is 1 interaction for this family. More...

STAT_bind

Structures

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_int 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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