STAT5A

STAT5A is a latent cytoplasmic signal transducer and sequence-specific transcription factor of the STAT family, and a close paralog of STAT5B (~90-95% identity). It is built from an N-terminal oligomerization domain, a coiled-coil domain, a p53-like DNA-binding domain, a linker, an SH2 domain, and a C-terminal transactivation domain. STAT5A is activated downstream of numerous cytokine and hormone receptors: the common gamma-chain cytokines IL-2, IL-4, IL-7, IL-9 and IL-15 (via JAK1/JAK3), IL-3/IL-5/GM-CSF, prolactin, growth hormone, erythropoietin and thrombopoietin (via JAK2), and oncogenic tyrosine kinases such as KIT and FLT3. Receptor-associated JAK kinases phosphorylate STAT5A on Tyr-694; the phosphorylated protein dimerizes through reciprocal SH2-phosphotyrosine interactions (forming homodimers, higher-order tetramers, and heterodimers with STAT5B or STAT3), translocates from the cytoplasm to the nucleus, and binds gamma-activated sequence (GAS) DNA elements to activate RNA polymerase II transcription of target genes, recruiting coactivators such as NCOA1/SRC-1 and CBP/p300. Tyrosine phosphorylation is required for DNA binding and dimerization, and serine phosphorylation for maximal transcriptional activity; signaling is terminated by SOCS/CIS proteins, phosphatases, and nuclear export. STAT5A is the mammary-predominant STAT5 paralog and a central effector of prolactin-PRLR-JAK2 signaling driving alveolar differentiation and milk-protein expression during lactation, and it also contributes, largely redundantly with STAT5B, to hematopoietic and lymphoid cell proliferation, survival and differentiation and to immune homeostasis.

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.