Summary
STAT5B is a member of STAT family. It plays a critical role as a signal transducer in the JAK/STAT signaling pathway. It is activated by JAK kinases but can also be activated by other cytokines and growth factors. Phosphorylation causes STAT5B to dimerize which results in nuclear translocation and regulation of target gene transcription.
The amino acids sequence of STAT5B in FASTA format was obtained from the National Center of Biotechnology Information (NCBI) for further analyses.
FASTA files，PhosphoELM, Scansite and NetwoKIN was used to find the phosphorylation sites. Though STAT proteins can be phosphorylated at tyrosine, serine and thymine. Phospho-tyrosine is a key element for the formation of homo- or hetero-dimers of STAT proteins which translocate to the nucleus.
STAT5B has similar structural organization as other homologs. Based on the FASTA sequences, BLAST analyses and Multiple Sequence Alignments were carried out to demonstrate the domains that are highly conserved within the STAT proteins and across many species such as Mus Musculus, Xenopus Laevis. These conserved domains are:
1. N-terminal domain which helps to stabilize the dimerization of STAT proteins and plays an essential role in the nuclear translocation of STAT5B
2. The coiled coil domain which is a helix containing heptad repeats that can act as a dimerization tag and a Nuclear Localization Sequence.
3. DNA binding domain which forms a loop to interact with the major groove of the DNA
4.SH2 domain which acts as a docking site to phospho-tyrosine and important for STATdimerization.
For structural analysis, pdb files were obtained from the Protein Databank. These files were annotated, and the different domains were highlighted using Pymol. Domains were presented individually (seen on the ‘Domains’ page) and presented within the whole structure of STAT5B (seen on the ‘Home’ page).
STAT5B plays an essential role in T-cell activation and regulation of cell death. Therefore, the dysfunction of STAT5B is related to defective immune responses and human cancers.