STAT3: Polycystic Ovarian Syndrome Database

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STAT3

Gene Information

Gene Ontology (GO)

Protein Information

Associated Diseases

Pathways

References

Gene Information

Gene Symbol

STAT3

Aliases

ADMIO, ADMIO1, APRF, HIES

Entrez Gene ID

6774

Gene Name

Signal transducer and activator of transcription 3

Chromosomal Location

17q21.2

HGNC ID

HGNC:11364

Summary

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

NG_007370.1

RefSeq mRNA

NM_003150.4, NM_213662.2, NM_001369512.1, NM_001369513.1, NM_001369514.1, NM_001369516.1, NM_001369517.1, NM_001369518.1, NM_001369519.1, NM_001369520.1, NM_139276.2

e!Ensembl

Gene	ENSG00000168610
Transcript	ENST00000264657, ENST00000585517, ENST00000389272, ENST00000588969, ENST00000404395, ENST00000588065
Protein	ENSP00000264657, ENSP00000467000, ENSP00000373923, ENSP00000467985, ENSP00000384943, ENSP00000467173

Gene Ontology (GO)

Show/Hide all(65 )

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
GO:0007259	Biological process	JAK-STAT cascade	IBA	21873635
GO:0007259	Biological process	JAK-STAT cascade	TAS	15664994
GO:0007399	Biological process	Nervous system development	TAS	10205054
GO:0010507	Biological process	Negative regulation of autophagy	IDA	26962683
GO:0010628	Biological process	Positive regulation of gene expression	IDA	23820254
GO:0010628	Biological process	Positive regulation of gene expression	IMP	24255059
GO:0019221	Biological process	Cytokine-mediated signaling pathway	IBA	21873635
GO:0019221	Biological process	Cytokine-mediated signaling pathway	NAS	15664994
GO:0030335	Biological process	Positive regulation of cell migration	IMP	24846175
GO:0030522	Biological process	Intracellular receptor signaling pathway	IDA	17324931
GO:0032355	Biological process	Response to estradiol	IDA	12552091
GO:0032870	Biological process	Cellular response to hormone stimulus	IDA	12552091
GO:0033210	Biological process	Leptin-mediated signaling pathway	IBA	21873635
GO:0033210	Biological process	Leptin-mediated signaling pathway	IDA	17344214
GO:0035278	Biological process	MiRNA mediated inhibition of translation	IDA	23820254
GO:0042127	Biological process	Regulation of cell proliferation	IBA	21873635
GO:0043066	Biological process	Negative regulation of apoptotic process	IMP	22984561
GO:0043434	Biological process	Response to peptide hormone	IBA	21873635
GO:0044320	Biological process	Cellular response to leptin stimulus	IDA	17344214
GO:0044321	Biological process	Response to leptin	IDA	17344214
GO:0045648	Biological process	Positive regulation of erythrocyte differentiation	IMP	28283061
GO:0045893	Biological process	Positive regulation of transcription, DNA-templated	IDA	19390056
GO:0045893	Biological process	Positive regulation of transcription, DNA-templated	IMP	23066027
GO:0045944	Biological process	Positive regulation of transcription by RNA polymerase II	IBA	21873635
GO:0045944	Biological process	Positive regulation of transcription by RNA polymerase II	IDA	17324931
GO:0045944	Biological process	Positive regulation of transcription by RNA polymerase II	IGI	19754877, 24429361
GO:0045944	Biological process	Positive regulation of transcription by RNA polymerase II	IMP	16835372, 16946298
GO:0051726	Biological process	Regulation of cell cycle	IDA	17344214
GO:0060396	Biological process	Growth hormone receptor signaling pathway	IDA	10925297
GO:0060397	Biological process	JAK-STAT cascade involved in growth hormone signaling pathway	IBA	21873635
GO:0060397	Biological process	JAK-STAT cascade involved in growth hormone signaling pathway	IDA	12552091
GO:0070102	Biological process	Interleukin-6-mediated signaling pathway	IDA	12359225, 12552091, 17324931, 24429361
GO:0070102	Biological process	Interleukin-6-mediated signaling pathway	IMP	16835372, 16946298
GO:1902895	Biological process	Positive regulation of pri-miRNA transcription by RNA polymerase II	IDA	19390056, 23820254
GO:1904685	Biological process	Positive regulation of metalloendopeptidase activity	IGI	23820254
GO:2000637	Biological process	Positive regulation of gene silencing by miRNA	IDA	23820254
GO:0000790	Cellular component	Nuclear chromatin	IDA	16835372
GO:0005634	Cellular component	Nucleus	IBA	21873635
GO:0005634	Cellular component	Nucleus	IDA	10336453, 12444102, 17324931, 17360477, 18234692, 22783022, 24846175, 28065600
GO:0005667	Cellular component	Transcription factor complex	IDA	24429361
GO:0005737	Cellular component	Cytoplasm	IDA	17360477, 18234692, 22783022
GO:0005829	Cellular component	Cytosol	IBA	21873635
GO:0090575	Cellular component	RNA polymerase II transcription factor complex	IC	16835372
GO:0090575	Cellular component	RNA polymerase II transcription factor complex	IMP	16946298
GO:0000978	Molecular function	RNA polymerase II proximal promoter sequence-specific DNA binding	IBA	21873635
GO:0000978	Molecular function	RNA polymerase II proximal promoter sequence-specific DNA binding	IDA	19390056
GO:0000981	Molecular function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISM	19274049
GO:0000981	Molecular function	DNA-binding transcription factor activity, RNA polymerase II-specific	NAS	19274049
GO:0001103	Molecular function	RNA polymerase II repressing transcription factor binding	IPI	22783022
GO:0001228	Molecular function	DNA-binding transcription activator activity, RNA polymerase II-specific	IBA	21873635
GO:0001228	Molecular function	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	16835372
GO:0001228	Molecular function	DNA-binding transcription activator activity, RNA polymerase II-specific	IMP	16946298
GO:0003700	Molecular function	DNA-binding transcription factor activity	IDA	17344214
GO:0004879	Molecular function	Nuclear receptor activity	IDA	17324931
GO:0005515	Molecular function	Protein binding	IPI	8662591, 9864141, 10688651, 11536047, 11585385, 11940572, 11970898, 12867595, 14966128, 15286705, 15657067, 15764709, 15821101, 15998644, 16273093, 16306601, 16331268, 16364321, 16531398, 16568091, 18200042, 18234692, 18330356, 19345327, 19372587, 20133729, 20826784, 20871632, 20876
GO:0008134	Molecular function	Transcription factor binding	IPI	15664994, 24429361
GO:0019903	Molecular function	Protein phosphatase binding	IPI	12359225, 17360477
GO:0031490	Molecular function	Chromatin DNA binding	IDA	17344214
GO:0042802	Molecular function	Identical protein binding	IPI	7510216, 17676033, 21988832, 25609649
GO:0044212	Molecular function	Transcription regulatory region DNA binding	IDA	17324931

Protein Information

Protein Name

Signal transducer and activator of transcription 3, DNA-binding protein APRF, acute-phase response factor

Function

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

NP_003141.2, NP_998827.1, NP_001356441.1, NP_001356442.1, NP_001356443.1, NP_001356445.1, NP_001356446.1, NP_001356447.1, NP_001356448.1, NP_001356449.1, NP_644805.1

UniProt

P40763

PDB

5U5S, 5AX3

Pfam

Pfam Accession	Pfam ID
PF00017	SH2
PF01017	STAT_alpha
PF02864	STAT_bind
PF02865	STAT_int

Pathways
	KEGG	Reactome
	EGFR tyrosine kinase inhibitor resistance Chemokine signaling pathway HIF-1 signaling pathway FoxO signaling pathway Necroptosis 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 Toxoplasmosis Hepatitis C Hepatitis B Measles 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

Interactions

STRING	MINT	IntAct
ENSP00000263640	Q04771	Q04771

View interactions

Associated Diseases

Show/Hide all(12 )

Disease group	Disease Name	References
Cardiovascular Diseases
	Cardiomyopathy	24448315, 10618415
	Atherosclerosis	19330073
	Myocardial Diseases	10618415, 24448315
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
	Genetic Diseases	18602572, 20159255, 25359994, 17881745, 22751495, 28073828, 26394394, 26343524, 22520845, 29180260, 25038750
	Craniosynostosis	20159255
	Congenital diaphragmatic hernia	25812446
Digestive System Diseases
	Inflammatory Bowel Diseases	23128233, 28067908, 26192919, 27569725
	Crohn Disease	26974007, 23266558, 28067908, 18587394, 26192919
	Colitis	26192919, 26974007, 28067908, 18438405, 20228799
	Chronic hepatitis	22879914
	Cholangitis	26974007
	Liver Cirrhosis	22879914
Ear Or Mastoid Diseases
Ear Or Mastoid Diseases	Meniere Disease	28787010
Endocrine System Diseases
	Ketosis-prone diabetes	25038750
	Diabetes Mellitus	25038750
	Brittle diabetes	25038750
	PCOS	17895321
Immune System Diseases
	Hyperimmunoglobulin E syndrome	17881745, 17676033, 26293184, 23342295, 20159255, 21792878, 18602572, 20032313, 27226025, 20816194, 18706697, 27980540, 18978467, 25038750, 26384563, 28492532, 17942886, 22030463, 25359994, 20301786, 29077208, 4161105, 27799162
	Autoimmune Diseases	25359994, 25038750, 28073828
	Juvenile arthritis	19565504
	Still Disease	19565504
	Autoimmune Diabetes	25038750
Musculoskeletal Diseases
Musculoskeletal Diseases	Spondylitis	26974007
Neoplasms
	Adenocarcinoma	26432044, 19028472
	Lung Cancer	21549414
	Carcinoma	16316942, 26432044, 17566705, 19028472
	Multiple Sclerosis	20159113, 21833088, 24076602, 22190364
	Medulloblastoma	19001435
	Leukemia	24090995, 19796711
	Head Neoplasms	27064016
	Stomach Cancer	23382965
	Prostate cancer	25970160, 14975756, 16427044
	Ovarian Cancer	21909139
	Pancreatic Neoplasm	22348037, 23845849
	Anaplastic Carcinoma	16316942
	Endometrial Cancer	25061499
	Liver Cancer	12957465
	Lymphoma	26192917, 22155737
	Breast Cancer	14975756
	Cancer Metastasis	21549414
	Cervical Cancer	25061499
	Myeloid Leukemia	19796711
	Colonic Neoplasms	19028472
	Cribriform Carcinoma	26432044, 19028472
	Gastric Cancer	23382965
Nervous System Diseases
	Cerebral Ischemia	17901229
	Cerebral Artery Infarction	21940958
	Brain Infarction	21940958
	Middle Cerebral Artery Syndrome	21940958
	Cerebral Thrombosis	21940958
Psychiatric/Brain disorders
	Memory Disorders	17928813
	Mental Depression	20410598
Respiratory Tract Diseases
Respiratory Tract Diseases	Asthma	21150878
Skin and Connective Tissue Diseases
	Dermatitis	26482879
	Psoriasis	23143594, 26974007
	Pustulosis	23143594

References

PMID: 17895321

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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