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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

STAT3 Gene

protein-coding GIFtS: 72
GCID: GC17M040465

signal transducer and activator of transcription 3 (acute-phase...

Explore 210 diseases affiliated with
STAT3 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Signal Transducer And Activator Of Transcription 3 (Acute-Phase Response Factor)¹ ²
APRF¹ ² ³ ⁵
Acute-Phase Response Factor² ³
HIES² ⁵
DNA-Binding Protein APRF²
Signal Transducer And Activator Of Transcription 3²

External Ids:	HGNC: 11364¹	Entrez Gene: 6774²	Ensembl: ENSG00000168610⁷	OMIM: 102582⁵	UniProtKB: P40763³

Export aliases for STAT3 gene to outside databases

Previous GC identifers: GC17M040032 GC17M042622 GC17M040375 GC17M040840 GC17M037718 GC17M036231

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for STAT3:

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. Three alternatively spliced

transcript variants encoding distinct isoforms have been described. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: STAT3_HUMAN, P40763

Function: Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF and

other growth factors. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the

interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes. Activated

by IL31 through IL31RA

summary for STAT3:

STATs (signal transducers and activators of transcription) are a family of 7 transcription factors that form

part of the JAK-STAT signaling cascade. This cascade is the basis of the signal transduction mechanism for

many cytokine receptors. Once activated by phosphorylation by JAKs, STATs translocate to the nucleus.

Accumulation of STATs in the nucleus is both rapid and tightly controlled. A number of factors regulate the

JAK-STAT pathway including STAT dephosphorylation by phosphatases, altered nuclear import-export dynamics of

STAT, and STAT gene activation antagonists such as SOCS (suppressors of cytokine signaling) and PIAS

(Protein Inhibitors of Activated STATs).

Gene Wiki entry for STAT3

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000017.10 NC_018928.1 NT_010783.15

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the STAT3 gene promoter:
CREB deltaCREB
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 3): STAT3 promoter sequence

Search SABiosciences Chromatin IP Primers for STAT3

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat STAT3

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 17q21.31 Ensembl cytogenetic band: 17q21.2 HGNC cytogenetic band: 17q21

STAT3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
STAT3 gene location

GeneLoc information about chromosome 17 GeneLoc Exon Structure

GeneLoc location for GC17M040465: view genomic region (about GC identifiers)

Start:	40,465,342 bp from pter	End:	40,540,586 bp from pter
Size:	75,245 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: STAT3_HUMAN, P40763 (See protein sequence)

Recommended Name: Signal transducer and activator of transcription 3

Size: 770 amino acids; 88068 Da

Subunit: Forms a homodimer or a heterodimer with a related family member (at least STAT1). Interacts with IL31RA,

NCOA1, PELP1, SIPAR, SOCS7, STATIP1 and TMF1. Interacts with HCV core protein. Interacts with IL23R in presence of

IL23. Interacts (via SH2 domain) with NLK. Interacts with ARL2BP; the interaction is enhanced by LIF and JAK1

expression (By similarity). Interacts with KPNA4 and KPNA5; KPNA4 may be the primary mediator of nuclear import (By

similarity). Interacts with CAV2; the interaction is increased on insulin-induced tyrosine phosphorylation of CAV2 and

leads to STAT3 activation (By similarity). Interacts with ARL2BP; interaction is enhanced with ARL2. Interacts with

NEK6 (By similarity). Binds to CDK9 when activated and nuclear. Interacts with BMX. Interacts with ZIPK/DAPK3.

Interacts with PIAS3; the interaction occurs on stimulation by IL6, CNTF or OSM and inhibits the DNA binding activity

of STAT3. In prostate cancer cells, interacts with STAT3 and promotes DNA binding activity of STAT3. Interacts with

STMN3, antagonizing its microtubule-destabilizing activity. Interacts with the 'Lys-129' acetylated form of

BIRC5/survivin. Interacts with FER

Subcellular location: Cytoplasm. Nucleus. Note=Shuttles between the nucleus and the cytoplasm. Translocated into the

nucleus upon tyrosine phosphorylation and dimerization, in response to signaling by activated FGFR1, FGFR2, FGFR3 or

FGFR4. Constitutive nuclear presence is independent of tyrosine phosphorylation. Predominantly present in the

cytoplasm without stimuli. Upon leukemia inhibitory factor (LIF) stimulation, accumulates in the nucleus. The complex

composed of BART and ARL2 plays an important role in the nuclear translocation and retention of STAT3. Identified in a

complex with LYN and PAG1

Miscellaneous: Involved in the gp130-mediated signaling pathway

Secondary accessions: A8K7B8 O14916 Q9BW54

Alternative splicing: 2 isoforms: P40763-1 P40763-2 (Contains a phosphotyrosine at position 704)

Explore the universe of human proteins at neXtProt for STAT3: NX_P40763

Post-translational modifications:

Tyrosine phosphorylated upon stimulation with EGF. Tyrosine phosphorylated in response to constitutively activated

FGFR1, FGFR2, FGFR3 and FGFR4 (By similarity). Activated through tyrosine phosphorylation by BMX. Tyrosine

phosphorylated in response to IL6, IL11, LIF, CNTF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha and OSM. Activated KIT

promotes phosphorylation on tyrosine residues and subsequent translocation to the nucleus. Phosphorylated on serine

upon DNA damage, probably by ATM or ATR. Serine phosphorylation is important for the formation of stable DNA-binding

STAT3 homodimers and maximal transcriptional activity. ARL2BP may participate in keeping the phosphorylated state of

STAT3 within the nucleus. Upon LPS challenge, phosphorylated within the nucleus by IRAK1. Upon erythropoietin

treatment, phosphorylated on Ser-727 by RPS6KA5. Phosphoryation at Tyr-705 by PTK6 or FER leads to an increase of its

transcriptional activity¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P40763

STAT3 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (3 alternative transcripts):

NP_003141.2 NP_644805.1 NP_998827.1

ENSEMBL proteins:

ENSP00000264657 ENSP00000467000 ENSP00000373923 ENSP00000467985 ENSP00000384943

ENSP00000467173

Reactome Protein details: P40763
Human Recombinant Protein Products for STAT3:

	EMD Millipore Purified and/or Recombinant STAT3 Protein
	Browse R&D Systems for human recombinant proteins
	Browse recombinant and purified proteins available from Enzo Life Sciences
	OriGene Purified Proteins (see all 2): STAT3 OriGene Protein Over-expression Lysate (see all 2): STAT3 OriGene Custom Protein Services for STAT3
	GenScript Custom Purified and Recombinant Proteins Services for STAT3
	Novus Biologicals STAT3 Proteins Novus Biologicals STAT3 Lysates
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for STAT3

Gene Ontology (GO): 5/6 cellular component terms (GO ID links to tree view) (see all 6): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005634	nucleus	ISS	--
GO:0005654	nucleoplasm	TAS	--
GO:0005730	NOT nucleolus	IDA	--
GO:0005737	cytoplasm	ISS	--
GO:0005829	cytosol	TAS	--

STAT3 for ontologies About GeneDecksing

STAT3 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of STAT3
	R&D Systems Antibodies for STAT3
	Cell Signaling Technology (CST) Antibodies for STAT3
	OriGene Antibodies (see all 9): STAT3 OriGene Custom Antibody Services for STAT3
	GenScript Custom Superior Antibodies Services for STAT3
	Novus Biologicals STAT3 Antibodies
	Abcam antibodies for STAT3
	Uscn Antibodies for STAT3
	ThermoFisher Antibody for STAT3

Assay Products for STAT3:

	EMD Millipore Kits and Assays for the Analysis of STAT3
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	R&D Systems ELISAs for STAT3 (see all)
	GenScript Custom Assay Services for STAT3
	Cell Signaling Technology (CST) Sandwich ELISA Kits for STAT3
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for STAT3

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

STAT3 for domains About GeneDecksing

5/9 InterPro domains/families (see all 9):

IPR013801 STAT_TF_DNA-bd

IPR008967 p53-like_TF_DNA-bd

IPR011992 EF-hand-like_dom

IPR013800 STAT_TF_alpha

IPR000980 SH2

Graphical View of Domain Structure for InterPro Entry P40763

ProtoNet protein and cluster: P40763

1 Blocks protein family: IPB001217 STAT protein

UniProtKB/Swiss-Prot: STAT3_HUMAN, P40763

Similarity: Belongs to the transcription factor STAT family

Similarity: Contains 1 SH2 domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, Sirion Biotech, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, Sirion Biotech, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Molecular Function:

UniProtKB/Swiss-Prot Summary: STAT3_HUMAN, P40763

Function: Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF and

other growth factors. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the

interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes. Activated

by IL31 through IL31RA

Genatlas biochemistry entry for STAT3:

signal transducer and activator of transcription 3,homologous to p91,component of the interferon stimulated gene factor

3 complexes,involved in IL6 and related cytokines induced signal transduction by JAK kinases,also involved in the G1

to S cell cycle transition,induced by IL6ST (GP130),playing a critical role in the maintenance of an undifferentiated

ES phenotype,widely expressed,located in the cytoplasm and translocated to the nucleus after tyrosine

phosphorylation,inhibited by protein phosphatase 2D,persistently activated in many cancers and transformed cell lines

and required in cell culture for transformation and blocking of apoptosis

Gene Ontology (GO): 5/15 molecular function terms (GO ID links to tree view) (see all 15): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000981	sequence-specific DNA binding RNA polymerase II transcription factor activity	--	--
GO:0001103	RNA polymerase II repressing transcription factor binding	IPI	--
GO:0003677	DNA binding	ISS	--
GO:0003700	sequence-specific DNA binding transcription factor activity	TAS	7512451
GO:0004871	signal transducer activity	TAS	7512451

STAT3 for ontologies About GeneDecksing

Phenotypes:
1 GenomeRNAi human phenotype for STAT3:

Upregulation of NF-kappaB path

15/23 MGI mutant phenotypes (inferred from 13 alleles) (MGI details for Stat3) (see all 23):

adipose tissue	behavior/neurological	cardiovascular system	cellular	digestive/alimentary
embryogenesis	endocrine/exocrine gland	growth/size	hematopoietic system	homeostasis/metabolism
immune system	integument	liver/biliary system	mortality/aging	muscle

STAT3 for phenotypes About GeneDecksing

Animal Models:
Mouse knock-outs for STAT3: Stat3^tm1Aki Stat3^tm1.1Xyfu Stat3^tm2Vpo Stat3^tm3Vpo Stat3^tm1Desi

inGenious Targeting Laboratory - Customizable classic, inducible, and humanized mouse model solutions for STAT3

		10/1386 SABiosciences Target genes for STAT3 (see all 1386):
		A1BG A1CF AADACL3 ABCB4 ABHD1 ABHD3 ABL1 ACAA1 ACAD11 ACCS

miRNA Products:		miRTarBase miRNAs that target STAT3: hsa-mir-125b (MIRT005006), hsa-mir-20b (MIRT000497)

		OriGene 3'-UTR Clone (see all 3): STAT3 Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat STAT3
		8/80 QIAGEN miScript miRNA Assays for microRNAs that regulate STAT3 (see all 80):
		hsa-miR-548j hsa-miR-3938 hsa-miR-106a hsa-miR-138-2* hsa-miR-519a hsa-miR-629* hsa-miR-93 hsa-miR-298

		SwitchGear 3'UTR luciferase reporter plasmid: STAT3 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for STAT3 (see all 7) OriGene shRNA RFP: STAT3 OriGene siRNA: STAT3
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat STAT3
		Sirion Biotech Custom design and validation of potent shRNA sequences against STAT3

Gene Editing Products:			DNA2.0 Custom Protein Engineering Service for STAT3
			Sirion Biotech Customized adenovirus for overexpression of STAT3 Sirion Biotech Customized adenovirus for potent knockdown of STAT3

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for STAT3 (see all 7) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for STAT3 (see all 3) OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 3): STAT3 (NM_139276)
		Sino Biological Human cDNA Clone for STAT3
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for STAT3
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat STAT3

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for STAT3
		Search LifeMap BioReagents cell lines for STAT3
		Sirion Biotech Customized stable knockdown cell line services for STAT3 Sirion Biotech Customized inducible knockdown cell line services for STAT3 Sirion Biotech Customized stable overexpressing cell line services for STAT3 Sirion Biotech Customized inducible overexpressing cell line services for STAT3

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for STAT3

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/94 super-pathways (see all 94) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

IL-9 Signaling Pathways

8/11 pathways (see all 11)
IL-9 Signaling Pathways	1.00	IL-9 Signaling Pathway	0.42
IL-21 Signaling Pathways	0.90	Immune response_IL-9 signaling pathway	0.42
IL-7 Signaling Pathways	0.90	Immune response IL-9 signaling pathway	0.42
Common Cytokine Receptor Gamma-Chain Family Signaling Pathways	0.90	IL-7 Signaling Pathway	0.38

Development_PDGF signaling via STATs and NF-kB

8/10 pathways (see all 10)
Development_PDGF signaling via STATs and NF-kB	1.00	Development Angiopoietin - Tie2 signaling	0.38
Development PDGF signaling via STATs and NF-kB	1.00	Immune response_IL-10 signaling pathway	0.28
Immune response_IL-23 signaling pathway	0.44	Immune response IL-10 signaling pathway	0.28
Immune response IL-23 signaling pathway	0.41	IL23-mediated signaling events	0.15

Development_CNTF receptor signaling

Development_CNTF receptor signaling	1.00	Immune response IL-6 signaling pathway	0.30
Development CNTF receptor signaling	1.00	Development_Leptin signaling via JAK/STAT and MAPK cascades	0.25
ErbB2/ErbB3 signaling events	0.31	Development Leptin signaling via JAK/STAT and MAPK cascades	0.25
Immune response_IL-6 signaling pathway	0.30

Signaling by FGFR

Signaling by FGFR in disease	0.91	NGF signalling via TRKA from the plasma membrane	0.70
Downstream signal transduction	0.84	Signalling by NGF	0.52
Signaling by PDGF	0.72

Development_Prolactin receptor signaling

	Development_Prolactin receptor signaling	1.00			Prolactin Signaling Pathway	0.39
	Development Prolactin receptor signaling	1.00			Leptin signaling pathway	0.32

Pathway sources
See GeneCards unified pathways
Show all pathways

5/21 EMD Millipore Pathways for STAT3 (see all 21)

	Chemotaxis CXCR4 signaling pathway
	Transcription Androgen Receptor nuclear signaling
	Development Leptin signaling via JAK/STAT and MAPK cascades
	Immune response IL-9 signaling pathway
	Immune response IL-12 signaling pathway

5/9 R&D Systems Pathways for STAT3 (see all 9)

	IL-21 Signaling Pathways
	IL-21 Signaling and its Primary Biological Effects in Different Immune Cell Types
	IL-2 Signaling Pathways
	IL-7 Signaling Pathways
	Common Cytokine Receptor Gamma-Chain Family Signaling Pathways

5/34 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for STAT3 (see all 34)

	MAPK Signaling
	FLT3 Signaling
	IL-10 Pathway
	G-AlphaI Signaling
	PDGF Pathway

1 Cell Signaling Technology (CST) Pathway for STAT3

Jak/Stat Pathway

1 Tocris Bioscience Pathway for STAT3

MAPK Pathway

5/24 GeneGo (Thomson Reuters) Pathways for STAT3 (see all 24)

	Development Leptin signaling via JAK/STAT and MAPK cascades
	Development CNTF receptor signaling
	Development EGFR signaling pathway
	Immune response Oncostatin M signaling via JAK-Stat in human cells
	Immune response IL-9 signaling pathway

5/43 BioSystems Pathways for STAT3 (see all 43)

	Oncostatin M Signaling Pathway
	AGE/RAGE pathway
	EPO Receptor Signaling
	Adipogenesis
	EGFR1 Signaling Pathway

5/20 Reactome Pathways for STAT3 (see all 20)

	Serine phosphorylation of STATs
	Signaling by FGFR1 mutants
	Disease
	Downstream signal transduction
	Signal Transduction

2 PharmGKB Pathways for STAT3

	Busulfan Pathway, Pharmacodynamics
	EGFR Inhibitor Pathway, Pharmacodynamics

5/9 Kegg Pathways (Kegg details for STAT3) (see all 9):

	Chemokine signaling pathway
	Jak-STAT signaling pathway
	Adipocytokine signaling pathway
	Toxoplasmosis
	Hepatitis C

STAT3 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for STAT3

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/795 Interacting proteins for STAT3 (P40763^{1, 2, 3} ENSP00000264657⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 795)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
GADD45GIP1	Q8TAE8²^,³, ENSP00000323065⁴	MINT-6492422 MINT-6492551 MINT-6492512 MINT-6492537 I2D: score=1 STRING: ENSP00000323065
CSF3R	Q99062²^,³	MINT-8037913 MINT-8037928 MINT-8035782 MINT-8035767 I2D: score=3
ERBB2	P04626²^,³, ENSP00000269571⁴	MINT-74756 MINT-8025768 MINT-8026372 I2D: score=2 STRING: ENSP00000269571
STAT1	P42224²^,³, ENSP00000354394⁴	MINT-8034934 MINT-8034919 I2D: score=5 STRING: ENSP00000354394
HDAC1	Q13547²^,³, ENSP00000362649⁴	MINT-8383061 MINT-7947479 I2D: score=4 STRING: ENSP00000362649

About this table

Gene Ontology (GO): 5/39 biological process terms (GO ID links to tree view) (see all 39): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000122	negative regulation of transcription from RNA polymerase II promoter	TAS	8675499
GO:0001659	temperature homeostasis	ISS	--
GO:0001754	eye photoreceptor cell differentiation	ISS	--
GO:0006355	regulation of transcription, DNA-dependent	IDA	15664994
GO:0006357	regulation of transcription from RNA polymerase II promoter	ISS	--

STAT3 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

STAT3 for compounds About GeneDecksing

EMD Millipore small molecules for STAT3:
Small Molecule - inhibitor

Enzo Life Sciences drugs & compounds for STAT3

Compounds for STAT3 available from Tocris Bioscience About this table

Compound	Action	CAS #
Cryptotanshinone	STAT3 inhibitor. Also displays multiple other activities	[35825-57-1]
Stattic	Selective STAT3 inhibitor	[19983-44-9]
Cucurbitacin I	Selective inhibitor of STAT3/JAK2 signaling	[2222-07-3]

10/122 Novoseek chemical compound relationships for STAT3 gene (see all 122) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
gp 130	92	215	19885008 (5), 18292512 (4), 7624343 (4), 10383440 (3) (see all 99)
tyrosine	83.7	741	11751994 (5), 17531096 (5), 12738762 (4), 9344858 (4) (see all 99)
cucurbitacin i	81.8	13	18200050 (3), 16707113 (3), 16939498 (1), 19843642 (1) (see all 9)
atiprimod	73.2	7	17237271 (3), 16828865 (2), 15970928 (1), 15844657 (1)
pd180970	67.5	3	10815799 (2), 12833138 (1)
pd 98,059	61.1	38	17370312 (5), 12913253 (2), 18786965 (2), 10727406 (1) (see all 18)
vegf	60.8	281	11960372 (7), 15312322 (7), 17937859 (7), 19020709 (6) (see all 87)
ly294002	59.6	13	17234779 (2), 8955182 (1), 15514005 (1), 17237271 (1) (see all 11)
phosphatidylinositol	56.9	39	9162009 (2), 17008315 (2), 15590660 (2), 12440226 (1) (see all 33)
cucurbitacins	56.3	1	16707113 (1)

Search CenterWatch for drugs/clinical trials and news about STAT3

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, Sirion Biotech, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for STAT3 gene (3 alternative transcripts):

NM_003150.3 NM_139276.2 NM_213662.1

Unigene Cluster for STAT3:

Signal transducer and activator of transcription 3 (acute-phase response factor)

Hs.463059 [show with all ESTs]

Unigene Representative Sequence: NM_139276

14 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000264657(uc002hzk.1 uc002hzl.1 uc002hzm.1 uc010wgh.1 uc002hzn.1)

ENST00000585517 ENST00000462286 ENST00000389272 ENST00000588969 ENST00000491272

ENST00000404395 ENST00000462269 ENST00000471989 ENST00000498330 ENST00000478276

ENST00000585360 ENST00000588065 ENST00000590776

miRNA Products:		OriGene 3'-UTR Clone (see all 3): STAT3 Browse OriGene MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat STAT3
		8/80 QIAGEN miScript miRNA Assays for microRNAs that regulate STAT3 (see all 80):
		hsa-miR-548j hsa-miR-3938 hsa-miR-106a hsa-miR-138-2* hsa-miR-519a hsa-miR-629* hsa-miR-93 hsa-miR-298

		SwitchGear 3'UTR luciferase reporter plasmid: STAT3 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for STAT3 (see all 7) OriGene shRNA RFP: STAT3 OriGene siRNA: STAT3
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		Sirion Biotech Custom design and validation of potent shRNA sequences against STAT3

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		GenScript: all cDNA clones in your preferred vector (see all 3): STAT3 (NM_139276)
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		Search QIAGEN QuantiFast Probe-based Assays in human, mouse, rat STAT3

Additional cDNA sequence:

AB451232.1 AF029311.1 AJ012463.1 AK024535.1 AK291933.1 AK297994.1 AK301200.1 AK316139.1

BC000627.2 BC008044.2 BC014482.1 BC067119.1 BC107775.1

24/29 DOTS entries (see all 29):

DT.211127 DT.100031562 DT.95165134 DT.95165127 DT.100662067 DT.97810673 DT.95165131 DT.101963163

DT.40106148 DT.75112737 DT.91921971 DT.95376389 DT.121008645 DT.91700570 DT.95165138 DT.100655225

DT.100801462 DT.100831275 DT.121008511 DT.121008515 DT.121008542 DT.40295982 DT.75122302 DT.92010195

24/522 AceView cDNA sequences (see all 522):

BX441253 BQ881070 AW152057 BM746435 CB216860 BQ889550 CA396565 BE908460

AI276576 BM550353 BQ670453 AA255469 BM912742 CB122210 BQ672301 AA374078

BG617189 AA057655 AI571562 CB215513 NM_139276 BX096773 CA394550 AA383745

GeneLoc Exon Structure

5/9 Alternative Splicing Database (ASD) splice patterns (SP) for STAT3 (see all 9) About this scheme

ExUns:	1a	·	1b	·	1c	^	2a	·	2b	^	3	^	4a	·	4b	^	5	^	6	^	7	^	8	^	9	^	10	^	11	^	12	^	13	^	14	^	15	^	16a	·	16b	^	17	^	18	^	19a	·	19b	^	20a	·
SP1:							-																																-
SP2:																																							-
SP3:
SP4:
SP5:

ExUns:	20b	·	20c	^	21	^	22a	·	22b	^	23a	·	23b	^	24a	·	24b	·	24c	·	24d	·	24e
SP1:							-
SP2:							-
SP3:
SP4:							-				-
SP5:

ECgene alternative splicing isoforms for STAT3

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

STAT3 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: TATCTGGTCT

About this image

STAT3 expression in embryonic tissues and stem cells
Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

10 LifeMap In Vivo Development Anatomical Compartments/Cells

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Spinal Cord

Spinal Dorsal Columns

Dorsal Spinal Cord Progenitor Cells

Spinal Cord

Spinal Ventral Columns

Ventral Spinal Cord Progenitor Cells

Motor Neurons

Bone

Brain

Brain

Limb

Neural Tube

Neural Tube

Spinal Dorsal Columns

Spinal Cord

Spinal Ventral Columns

Spinal Cord

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

Stem Cell Differentiation: 1 LifeMap Cell

Name

Category

HSF-1 (UC01) (Embryonic Stem Cell)

Early Embryo, Inner Cell Mass

See STAT3 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for STAT3

SOURCE GeneReport for Unigene cluster: Hs.463059

UniProtKB/Swiss-Prot: STAT3_HUMAN, P40763

Tissue specificity: Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas

SABiosciences Expression via Pathway-Focused PCR Arrays including STAT3 (see all 26):

Neurogenesis in human mouse rat

HIV Host Response in human mouse rat

Stem Cell Transcription Factors in human mouse rat

Multiple Sclerosis in human mouse rat

Wound Healing in human mouse rat

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for STAT3 Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat STAT3
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		Search QIAGEN QuantiFast Probe-based Assays in human, mouse, rat STAT3

In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for STAT3

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of animals.

Orthologs for STAT3 gene from 5/15 species (see all 15) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	STAT3¹	signal transducer and activator of transcription 3 more	83.53(n) 97.4(a)		420027 NM_001030931.1 NP_001026102.1
lizard (Anolis carolinensis)	Reptilia	STAT3⁶	--	96(a)	1 ↔ 1	6(72499188-72521804)
African clawed frog (Xenopus laevis)	Amphibia	stat3-A²	signal transducer and activator of transcription 3 more	78.25(n)		AB017701.1
zebrafish (Danio rerio)	Actinopterygii	stat3²	signal transduction and activation of transcription more	77.75(n)		30767 AJ005693.1
worm (Caenorhabditis elegans)	Secernentea	sta-1⁶ sta-2⁶	Signal transducer and activator of transcription 1... Signal transducer and activator of transcription b...	22(a) 16(a)	1 ↔ many possible ortholog	IV(16664287-16671437) V(9741198-9744206)

ENSEMBL Gene Tree for STAT3 (if available)
TreeFam Gene Tree for STAT3 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for STAT3 gene

STAT5B² STAT1² STAT4² STAT2² STAT6² STAT5A²

8 SIMAP similar genes for STAT3 using alignment to 6 protein entries: STAT3_HUMAN (see all proteins):

STAT1 Stat2 STAT4 STAT6 STAT2 DKFZp686H05229

STAT5B STAT5A

STAT3 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 17 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs17882069^1,2	C,F,H	non-pathogenic	38073195(-)	`ACGGAC/TGAGGA`	6	D	syn¹ ese³		15		NS NA EU	7071
rs17882035^1,2	C,F	non-pathogenic	38087385(-)	`TTACTC/GTTTTC`	3	--	int¹ trp³		4		NS WA	270
rs113994135^1,2	C	pathogenic	38081107(-)	`GATCCC/TGGAAA`	6	R W	mis¹		0	--	--	--	--
rs113994136^1,2	C	pathogenic	38081108(-)	`ATCCCA/G/TGAAAT`	9	Q R L	mis¹		0	--	--	--	--
rs113994137^1,2	C	pathogenic	38081327(-)	`GGGCCA/GAGCCA`	6	Q R	mis¹		0	--	--	--	--
rs113994138^1,2	C	pathogenic	38085712(-)	`TTGTG-/GTGATCTC`	3	--	cds¹		0	--	--	--	--
rs113994139^1,2	C	pathogenic	38088276(-)	`AGTCCA/GTGGAA`	6	M V	mis¹		0	--	--	--	--
rs80350541^1,2	F	--	36229544(+)	`TAGCTG/CAGGTT`	3	--	ds500¹		1		WA	118
rs200029754^1,2	C	--	36230101(-)	`TTTGTC/TTNNNN`	3	--	ut3¹		0	--	--	--	--
rs10775^1,2	C	--	36230610(+)	`CTCCCC/ACTTAA`	3	--	ut3¹		1		MN	184

HapMap Linkage Disequilibrium report for STAT3 (40465342 - 40540586 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 3 variations for STAT3
1 CNV: 102460
2 Indels: 25843 67201
Human Gene Mutation Database (HGMD): STAT3

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing STAT3

DNA2.0 Custom Variant and Variant Library Synthesis for STAT3

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

STAT3 for disorders           About GeneDecksing

OMIM gene information: 102582
OMIM disorders: 147060
UniProtKB/Swiss-Prot: STAT3_HUMAN, P40763

Defects in STAT3 are the cause of hyperimmunoglobulin E recurrent infection syndrome autosomal dominant

(AD-HIES) [MIM:147060]; also known as hyper-IgE syndrome or Job syndrome. AD-HIES is a rare disorder of immunity and

connective tissue characterized by immunodeficiency, chronic eczema, recurrent Staphylococcal infections, increased

serum IgE, eosinophilia, distinctive coarse facial appearance, abnormal dentition, hyperextensibility of the joints,

and bone fractures

20/210 diseases for STAT3 (see all 210): About MalaCards

hyper-ige syndrome estrogen-receptor positive breast cancer chronic inflammatory demyelinating polyradiculoneuropathy eccrine porocarcinoma

anaplastic large cell lymphoma diffuse large b-cell lymphoma cleft lip/palate polycythemia vera

gastrointestinal stromal tumor mycosis fungoides squamous cell carcinoma non-small cell lung carcinoma

actinic cheilitis b-cell lymphomas salivary gland cancer cleft lip

chronic myeloproliferative disease familial medullary thyroid carcinoma primitive neuroectodermal tumor non-hodgkin lymphoma

4 diseases from the University of Copenhagen DISEASES database for STAT3:

Cancer Job's syndrome Vascular disease Inflammatory bowel disease

10/93 Novoseek disease relationships for STAT3 gene (see all 93) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
hyper-ige syndrome	74.6	23	17881745 (4), 20093388 (3), 19648655 (2), 18841165 (2) (see all 16)
tumors	67.9	693	17824789 (5), 16536977 (5), 17015686 (5), 19244102 (5) (see all 99)
response acute phase	66.5	51	7876144 (2), 17461989 (2), 7678052 (2), 8164674 (2) (see all 32)
cancer	65.7	392	20072652 (5), 14659041 (5), 20026083 (5), 17311011 (5) (see all 99)
leukemia	64.8	74	19074878 (5), 20133729 (4), 11337018 (3), 18047677 (2) (see all 57)
hnscc	59.7	73	12782602 (7), 19638453 (7), 18172861 (5), 16642480 (4) (see all 22)
myeloma	58.6	37	15958645 (3), 10023775 (3), 12953802 (3), 18824601 (2) (see all 21)
anaplastic large cell lymphoma	53.5	13	17439836 (2), 14506160 (2), 15161657 (1), 18509351 (1) (see all 10)
prostate cancer	51.3	167	18483213 (7), 20167868 (6), 10728680 (5), 12438264 (5) (see all 60)
carcinoma squamous cell	47.4	66	12873986 (3), 17822622 (3), 17013800 (3), 18813829 (3) (see all 41)

Genetic Association Database (GAD): STAT3
Human Genome Epidemiology (HuGE) Navigator: STAT3 (76 documents)

Export disorders for STAT3 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for STAT3 gene, integrated from 9 sources (see all 2648):
(articles sorted by number of sources associating them with STAT3)

Utopia: connect your pdf to the dynamic
world of online information

Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91- related transcription factor involved in the gp130-mediated signaling pathway. (PubMed id 7512451)^{1, 2, 3, 9} Akira S.... Kishimoto T. (1994)
Erythropoietin-induced serine 727 phosphorylation of STAT3 in erythroid cells is mediated by a MEK-, ERK-, and MSK1-dependent pathway. (PubMed id 12763138)^{1, 2, 9} Wierenga A.T....Vellenga E. (2003)
Identification and characterization of signal transducer and activator of transcription 3 recruitment sites within the epidermal growth factor receptor. (PubMed id 12873986)^{1, 2, 9} Shao H....Tweardy D.J. (2003)
Suppressor of cytokine signaling 7 inhibits prolactin, growth hormone, and leptin signaling by interacting with STAT5 or STAT3 and attenuating their nuclear translocation. (PubMed id 15677474)^{1, 2, 9} Martens N....Gertler A. (2005)
STAT3 mutations in the hyper-IgE syndrome. (PubMed id 17881745)^{1, 2, 9} Holland S.M.... Grimbacher B. (2007)
The Fer tyrosine kinase cooperates with interleukin-6 to activate signal transducer and activator of transcription 3 and promote human prostate cancer cell growth. (PubMed id 19147545)^{1, 2, 9} Zoubeidi A....Chevalier S. (2009)
The functional role of an interleukin 6-inducible CDK9.STAT3 complex in human gamma-fibrinogen gene expression. (PubMed id 17956865)^{1, 2, 9} Hou T....Brasier A.R. (2007)
Etk, a Btk family tyrosine kinase, mediates cellular transformation by linking Src to STAT3 activation. (PubMed id 10688651)^{1, 2, 9} Tsai Y.T....Chen R.H. (2000)
Protein kinase Cepsilon interacts with signal transducers and activators of transcription 3 (Stat3), phosphorylates Stat3Ser727, and regulates its constitutive activation in prostate cancer. (PubMed id 17875724)^{1, 2, 9} Aziz M.H....Verma A.K. (2007)
Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. (PubMed id 17676033)^{1, 2, 9} Minegishi Y....Karasuyama H. (2007)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 6774	HGNC: 11364	AceView: STAT3	Ensembl:ENSG00000168610	euGenes: HUgn6774
ECgene: STAT3	Kegg: 6774	H-InvDB: STAT3

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for STAT3	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for STAT3	Genetics and Cytogenetics in Oncology and Haematology
Wikipedia	http://en.wikipedia.org/wiki/STAT3
STAT3base	http://bioinf.uta.fi/STAT3base/
SeattleSNPs	http://pga.gs.washington.edu/data/stat3/

Intellectual Property for STAT3 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

About This Section

Patent Information for STAT3 gene:
Search GeneIP for patents involving STAT3

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Uscn, Thermo Fisher Scientific, Gene Editing from DNA2.0 and Sirion Biotech, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, LifeMap BioReagents, and Sirion Biotech, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences, In Situ Hybridization Assays from
Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory)
About This Section

	EMD Millipore small molecules (inhibitor) for STAT3
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Tocris compounds for STAT3

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Sirion Biotech Customized:

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latent infection
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for STAT3 gene

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for STAT3 gene

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for STAT3 gene

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for STAT3 gene

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for STAT3 gene

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for STAT3 gene

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for STAT3 gene

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for STAT3 gene

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for STAT3 gene

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for STAT3 gene

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for STAT3 gene

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for STAT3 gene

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for STAT3 gene

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for STAT3 gene