Gene Information
Gene Symbol
Entrez Gene ID
Gene Name
Signal transducer and activator of transcription 3
Chromosomal Location
The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein is activated through phosphorylation in response to various cytokines and growth factors including IFNs, EGF, IL5, IL6, HGF, LIF and BMP2. This protein mediates the expression of a variety of genes in response to cell stimuli, and thus plays a key role in many cellular processes such as cell growth and apoptosis. The small GTPase Rac1 has been shown to bind and regulate the activity of this protein. PIAS3 protein is a specific inhibitor of this protein. Mutations in this gene are associated with infantile-onset multisystem autoimmune disease and hyper-immunoglobulin E syndrome. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Sep 2015]
RefSeq DNA
RefSeq mRNA

Gene Ontology (GO)

GO ID Ontology Function Evidence Reference
GO:0000122 Biological process Negative regulation of transcription by RNA polymerase II TAS 8675499
GO:0006355 Biological process Regulation of transcription, DNA-templated IDA 15664994, 17344214
GO:0006606 Biological process Protein import into nucleus IDA 18234692
GO:0006952 Biological process Defense response IBA 21873635
GO:0007165 Biological process Signal transduction TAS 7512451, 10205054
Protein Information
Protein Name
Signal transducer and activator of transcription 3, DNA-binding protein APRF, acute-phase response factor
Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene (PubMed:17344214). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:12873986). Binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes. Activated by IL31 through IL31RA. Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg): deacetylation and oxidation of lysine residues by LOXL3, leads to disrupt STAT3 dimerization and inhibit its transcription activity. Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1 (PubMed:17344214). Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation (By similarity). May play an apoptotic role by transctivating BIRC5 expression under LEP activation (PubMed:18242580). Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity (PubMed:23084476). Plays a crucial role in basal beta cell functions, such as regulation of insulin secretion (By similarity).
Refseq Proteins
Pfam Accession Pfam ID
PF00017 SH2
PF01017 STAT_alpha
PF02864 STAT_bind
PF02865 STAT_int

EGFR tyrosine kinase inhibitor resistance
Chemokine signaling pathway
HIF-1 signaling pathway
FoxO signaling pathway
Signaling pathways regulating pluripotency of stem cells
JAK-STAT signaling pathway
Th17 cell differentiation
Prolactin signaling pathway
Adipocytokine signaling pathway
Insulin resistance
AGE-RAGE signaling pathway in diabetic complications
Hepatitis C
Hepatitis B
Human cytomegalovirus infection
Kaposi sarcoma-associated herpesvirus infection
Epstein-Barr virus infection
Pathways in cancer
Viral carcinogenesis
Proteoglycans in cancer
MicroRNAs in cancer
Pancreatic cancer
Acute myeloid leukemia
Non-small cell lung cancer
PD-L1 expression and PD-1 checkpoint pathway in cancer
Inflammatory bowel disease (IBD)


Interleukin-6 signaling
BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members
Interleukin-7 signaling
Signaling by SCF-KIT
Signaling by cytosolic FGFR1 fusion mutants
Downstream signal transduction
Senescence-Associated Secretory Phenotype (SASP)
POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation
Transcriptional regulation of pluripotent stem cells
Interleukin-10 signaling
Interleukin-4 and Interleukin-13 signaling
PTK6 Activates STAT3
Interleukin-20 family signaling
MET activates STAT3
Interleukin-15 signaling
Interleukin-35 Signalling
Interleukin-9 signaling
Interleukin-37 signaling
Interleukin-23 signaling
Interleukin-27 signaling
Interleukin-21 signaling
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants
Signaling by PDGFRA extracellular domain mutants

ENSP00000263640 Q04771 Q04771
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Associated Diseases

Disease groupDisease NameReferences
Cardiovascular Diseases
Myocardial Diseases
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Genetic Diseases

Association of serum and follicular fluid leptin concentrations with granulosa cell phosphorylated signal transducer and activator of transcription 3 expression in fertile patients with polycystic ovarian syndrome.

Li Mei-Gen, Ding Guo-Lian, Chen Xi-Jing, Lu Xi-Ping, Dong Li-Jun, Dong Min-Yue, Yang Xiao-Fu, Lu Xiu-E, Huang He-Feng
Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, 2 Xue Shi Road, Hangzhou, Zhejiang, 31006, China.
J Clin Endocrinol Metab. 2007 Dec;92(12):4771-6. doi: 10.1210/jc.2007-0978. Epub

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