STAT5A: Signal Transducer and Activator of Transcription 5A
A critical transcription factor mediating cytokine and growth factor signaling, with emerging roles in cancer, immune regulation, and hematopoiesis.
Gene Information Card
| Symbol | STAT5A |
|---|---|
| Full Name | Signal Transducer and Activator of Transcription 5A |
| Gene Type | Protein coding |
| Chromosomal Location | 17q21.2 |
| NCBI Gene ID | 6776 ncbi.nlm.nih.gov/gene/6776 |
| Ensembl ID | ENSG00000126561 |
| UniProt ID | P42229 |
| OMIM ID | 601511 |
| HGNC ID | 11366 |
| Aliases | MGF, STAT5 |
Description
STAT5A (Signal Transducer and Activator of Transcription 5A) is a member of the STAT family of transcription factors. It is a key mediator of signal transduction for various cytokines, growth factors, and hormones, including prolactin, erythropoietin, thrombopoietin, and interleukins (e.g., IL-2, IL-3, IL-5, GM-CSF). Upon ligand binding to cell surface receptors, receptor-associated JAK kinases phosphorylate STAT5A, leading to its dimerization and translocation to the nucleus, where it regulates the transcription of target genes involved in cell proliferation, differentiation, apoptosis, and immune responses. STAT5A is critical for normal mammary gland development, hematopoiesis, and immune function. Dysregulation of STAT5A signaling is implicated in various cancers and inflammatory diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | Constitutive activation of STAT5A (via phosphorylation) promotes cell proliferation, survival, and tumor progression. It can act as a tumor promoter in certain contexts, though its role can be context-dependent. | PMID: 21685335; PMID: 30061373 |
| Prostate Cancer | Nuclear STAT5A expression is associated with high-grade tumors and poor prognosis. It drives tumor growth and metastasis by regulating genes involved in cell cycle and survival. | PMID: 24958155; PMID: 28341605 |
| Chronic Myeloid Leukemia (CML) | STAT5A is a critical downstream effector of the BCR-ABL fusion oncoprotein. Its constitutive activation contributes to leukemogenesis and resistance to therapy. | PMID: 22039264; PMID: 23223431 |
| Myeloproliferative Neoplasms (MPNs) | Activating mutations in JAK2 (e.g., JAK2 V617F) lead to constitutive STAT5A activation, contributing to abnormal hematopoiesis in polycythemia vera, essential thrombocythemia, and primary myelofibrosis. | PMID: 16081684; PMID: 16166538 |
| Rheumatoid Arthritis | STAT5A is activated in synovial tissue and contributes to the inflammatory response by regulating cytokine and chemokine production. | PMID: 22508288 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 31.1 | High |
| Spleen | 26.8 | High |
| Lymph Node | 25.4 | High |
| Thymus | 22.3 | High |
| Lung | 18.5 | Medium |
| Mammary Gland | 15.2 | Medium |
| Liver | 8.7 | Low |
| Brain | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (CML) | 35.2 | High expression; reflects constitutive activation in CML. |
| MCF7 (Breast Cancer) | 28.4 | High expression; involved in estrogen receptor signaling crosstalk. |
| Jurkat (T-cell leukemia) | 22.1 | High expression; critical for IL-2 signaling. |
| HepG2 (Liver Cancer) | 12.3 | Moderate expression; involved in growth hormone signaling. |
| A549 (Lung Cancer) | 8.9 | Low to moderate expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| N642H | Missense | Rare (<0.1%) | Gain-of-function mutation; enhances transcriptional activity and is found in some leukemias and lymphomas. |
| V712E | Missense | Rare (<0.1%) | Gain-of-function mutation; observed in T-cell prolymphocytic leukemia. |
| T628S | Missense | Rare (<0.1%) | Potential gain-of-function; identified in some solid tumors. |
| Q706L | Missense | Rare (<0.1%) | Gain-of-function; associated with increased STAT5A activity in vitro. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in STAT5A are rare and often result in impaired immune function, particularly affecting T-cell and NK-cell responses. Complete knockout in mice leads to defective mammary gland development and impaired hematopoiesis.
Gain of Function (GOF)
Gain-of-function mutations, such as N642H and V712E, lead to constitutive activation of STAT5A, promoting uncontrolled cell proliferation and survival. These are frequently observed in hematological malignancies and some solid tumors.
Dominant Negative (DN)
Dominant-negative mutations can interfere with the function of wild-type STAT5A and other STAT proteins, disrupting normal cytokine signaling. These are less characterized but can contribute to immune dysregulation.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • protein homodimerization activity | • protein heterodimerization activity |
| • signal transducer activity | • cytokine receptor binding |
| • regulation of transcription by RNA polymerase II | • cell population proliferation |
| • apoptotic process | • immune response |
| • mammary gland development | • JAK-STAT cascade |
Pathways
• JAK-STAT signaling pathway
• Prolactin signaling pathway
• ErbB signaling pathway
• Chemokine signaling pathway
• Growth hormone signaling
• IL-2 signaling pathway
• IL-3 signaling pathway
• IL-5 signaling pathway
• GM-CSF signaling pathway
• Erythropoietin signaling pathway
Protein Summary
STAT5A is a 794-amino acid protein (~90 kDa) that functions as a latent transcription factor. It contains several conserved domains: an N-terminal domain involved in dimerization, a coiled-coil domain, a DNA-binding domain, a linker domain, an SH2 domain critical for receptor recruitment and dimerization, and a C-terminal transactivation domain. Upon activation by JAK kinases, STAT5A is phosphorylated at a conserved tyrosine residue (Tyr694), promoting its homodimerization or heterodimerization with STAT5B. The dimer translocates to the nucleus and binds to gamma-interferon activation site (GAS) motifs in the promoters of target genes. STAT5A also undergoes other post-translational modifications, including serine phosphorylation, acetylation, and methylation, which modulate its activity. It plays a central role in mediating the effects of prolactin on mammary gland development and lactation, and is essential for the maintenance of normal immune cell function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| STAT5A Knockout HEK293 Cell Line | EDJ-KQ538 | Human | 6776 | Details Get a Quote |
| STAT5A Knockout A-549 Cell Line | EDJ-KQ18904 | Human | 6776 | Details Get a Quote |
| STAT5A Knockout HeLa Cell Line | EDJ-KQ18905 | Human | 6776 | Details Get a Quote |
| STAT5A Knockout HCT 116 Cell Line | EDJ-KQ71540 | Human | 6776 | Details Get a Quote |
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