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STAT3 signal transducer and activator of transcription 3 (acute-phase response factor) [ Homo sapiens (human) ]

Gene ID: 6774, updated on 15-Sep-2014
Official Symbol
STAT3provided by HGNC
Official Full Name
signal transducer and activator of transcription 3 (acute-phase response factor)provided by HGNC
Primary source
HGNC:HGNC:11364
See related
Ensembl:ENSG00000168610; HPRD:00026; MIM:102582; Vega:OTTHUMG00000150645
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
APRF; HIES
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. Three alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]
See STAT3 in Epigenomics, MapViewer
Location:
17q21.31
Exon count:
24
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 17 NC_000017.11 (42313324..42388568, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (40465342..40540586, complement)

Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene signal transducer and activator of transcription 5B Neighboring gene signal transducer and activator of transcription 5A Neighboring gene polymerase I and transcript release factor Neighboring gene ATPase, H+ transporting, lysosomal V0 subunit a1 Neighboring gene microRNA 548at

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Associated conditions

Description Tests
Hyperimmunoglobulin E syndrome Compare labs

NHGRI GWAS Catalog

Description
A genome-wide association study identifies 2 susceptibility Loci for Crohn's disease in a Japanese population.
NHGRI GWA Catalog
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.
NHGRI GWA Catalog
Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease.
NHGRI GWA Catalog
Genome-wide association study in a high-risk isolate for multiple sclerosis reveals associated variants in STAT3 gene.
NHGRI GWA Catalog
Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci.
NHGRI GWA Catalog
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.
NHGRI GWA Catalog
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
NHGRI GWA Catalog

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120 recruits SOCS-3 through IL-10 activation for suppressing IL-6 and IL-6 dependent STAT3 in immature dentritic cells PubMed
env HIV-1 gp120-induced release of IL-10 inhibits STAT3 activation, leading to suppress HIV-1 Nef-induced IL-6 secretion in immature dentritic cells PubMed
env The transcription factors and kinases c-Jun, JNK, MEK, p38 MAPK, STAT-3, JAK-1, TFII D, TFII F, eIF-4E, and RNA polymerase II are induced by HIV-1 gp120 PubMed
Nef nef HIV-1 gp120-induced release of IL-10 inhibits STAT3 activation, leading to suppress HIV-1 Nef-induced IL-6 secretion in immature dentritic cells PubMed
nef Both myristoylation and acidic cluster of Nef are essential to induce the tyrosine phosphorylation of STAT3 PubMed
nef HIV-1 Nef induces phosphorylation of STAT3 in M2-type macrophages PubMed
nef HIV-1 Nef increases expression of both VEGF and its transcriptional regulator, hypoxia-inducible factor 2alpha (HIF-2alpha), in a Src kinase-and Stat3-dependent manner PubMed
nef HIV-1 Nef activates signal transducer and activator of transcription 3 (STAT3) in the granulocyte-macrophage colony-stimulating factor-independent myeloid cell line, TF-1, and in primary human macrophages PubMed
nef HIV-1 Nef specifically activates STAT3 in primary human monocyte-derived macrophages (MDM); Nef-dependent STAT3 activation is mediated by the release of soluble factor(s), including MIP-1alpha and IL-6 PubMed
nef HIV-1 Nef activates expression of phospho-Stat3, one of the downstream signaling pathways for cell proliferation PubMed
nef HIV-1 Nef, through its PxxP and RR106 motifs, upregulates Src kinase activity and signal transducer and activator of transcription 3 (Stat3) phosphorylation, and activates the Ras-c-Raf-MAPK1,2 pathway in podocytes PubMed
nef The expression of HIV-1 Nef in immature dendritic cells activates STAT3 PubMed
Tat tat Expression of HIV-1 Tat upregulates the abundance of signal transducer and activator of transcription 3 (STAT3) in the nucleoli of Jurkat T-cells PubMed
tat HIV-1 Tat in combination with KSHV kaposin A activates the MEK/ERK, STAT3, and PI3K/Akt signals in NIH3T3 cells PubMed
tat IL10 and STAT3 are required for HIV-1 Tat-mediated inhibition of autophagy in bystander macrophages/monocytic cells PubMed
tat Ectopic expression of HIV-1 Tat induces the production of human IL-6 (huIL-6) and its receptor (huIL-6Ra) and activates STAT3 signaling; these effects are involved in Tat-mediated activation of Kaposi's sarcoma-associated herpes virus (KSHV) replication PubMed
matrix gag Treatment of human stellate cells with HIV-1 MA induces phosphorylation of STAT1 and STAT3 proteins PubMed

Go to the HIV-1, Human Protein Interaction Database

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    Signaling events mediated by Stem cell factor receptor (c-Kit), organism-specific biosystem
    Signaling events mediated by Stem cell factor receptor (c-Kit)
  • Signaling events mediated by TCPTP, organism-specific biosystem (from Pathway Interaction Database)
    Signaling events mediated by TCPTP, organism-specific biosystem
    Signaling events mediated by TCPTP
  • Signaling of Hepatocyte Growth Factor Receptor, organism-specific biosystem (from WikiPathways)
    Signaling of Hepatocyte Growth Factor Receptor, organism-specific biosystem
    Signaling of Hepatocyte Growth Factor Receptor
  • Signaling pathways regulating pluripotency of stem cells, organism-specific biosystem (from KEGG)
    Signaling pathways regulating pluripotency of stem cells, organism-specific biosystemPluripotent stem cells (PSCs) are basic cells with an indefinite self-renewal capacity and the potential to generate all the cell types of the three germinal layers. The types of PSCs known to date i...
  • Signaling pathways regulating pluripotency of stem cells, conserved biosystem (from KEGG)
    Signaling pathways regulating pluripotency of stem cells, conserved biosystemPluripotent stem cells (PSCs) are basic cells with an indefinite self-renewal capacity and the potential to generate all the cell types of the three germinal layers. The types of PSCs known to date i...
  • Signalling by NGF, organism-specific biosystem (from REACTOME)
    Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...
  • Signalling to STAT3, organism-specific biosystem (from REACTOME)
    Signalling to STAT3, organism-specific biosystemNeurotrophin-induced increase in Signal transducer and activator of transcription 3 (STAT3; acute-phase response factor) activation appears to underly several downstream functions of neurotrophin sig...
  • TFs Regulate miRNAs related to cardiac hypertrophy, organism-specific biosystem (from WikiPathways)
    TFs Regulate miRNAs related to cardiac hypertrophy, organism-specific biosystemTranscription Factors that possibly regulate the expression of microRNAs related to cardiac hypertrophy. Interactions found by using TransMir. MicroRNAs are represented by a purple color and a rounde...
  • TGF Beta Signaling Pathway, organism-specific biosystem (from WikiPathways)
    TGF Beta Signaling Pathway, organism-specific biosystemThe Transforming growth factor beta (TGFβ) signaling pathway is involved in many cellular processes in both the adult organism and the developing embryo including cell growth, cell differentiat...
  • TSH signaling pathway, organism-specific biosystem (from WikiPathways)
    TSH signaling pathway, organism-specific biosystemHuman thyroid stimulating hormone (TSH) is a glycoprotein secreted by the anterior part of the pituitary gland (1). TSH plays an important physiological role in the regulation of the hypothalamic-pit...
  • TSLP Signaling Pathway, organism-specific biosystem (from WikiPathways)
    TSLP Signaling Pathway, organism-specific biosystemThymic stromal lymphopoietin (TSLP) is a type I cytokine member of interleukin-2 cytokine family. TSLP signals through interleukin-7 receptor a chain (IL-7Ra) and the TSLP receptor subunit (TSLPR), h...
  • Toxoplasmosis, organism-specific biosystem (from KEGG)
    Toxoplasmosis, organism-specific biosystemToxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechan...
  • Toxoplasmosis, conserved biosystem (from KEGG)
    Toxoplasmosis, conserved biosystemToxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechan...
  • Transcriptional regulation of pluripotent stem cells, organism-specific biosystem (from REACTOME)
    Transcriptional regulation of pluripotent stem cells, organism-specific biosystemPluripotent stem cells are undifferentiated cells posessing an abbreviated cell cycle (reviewed in Stein et al. 2012), a characteristic profile of gene expression (Rao et al. 2004, Kim et al. 2006, P...
  • Viral carcinogenesis, organism-specific biosystem (from KEGG)
    Viral carcinogenesis, organism-specific biosystemThere is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C vi...
  • Viral carcinogenesis, conserved biosystem (from KEGG)
    Viral carcinogenesis, conserved biosystemThere is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C vi...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • FLJ20882, MGC16063

Gene Ontology Provided by GOA

Function Evidence Code Pubs
CCR5 chemokine receptor binding IEA
Inferred from Electronic Annotation
more info
 
DNA binding ISS
Inferred from Sequence or Structural Similarity
more info
 
RNA polymerase II repressing transcription factor binding IPI
Inferred from Physical Interaction
more info
 
calcium ion binding IEA
Inferred from Electronic Annotation
more info
 
glucocorticoid receptor binding IEA
Inferred from Electronic Annotation
more info
 
ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein dimerization activity ISS
Inferred from Sequence or Structural Similarity
more info
 
protein kinase binding ISS
Inferred from Sequence or Structural Similarity
more info
 
protein phosphatase binding IPI
Inferred from Physical Interaction
more info
PubMed 
sequence-specific DNA binding IEA
Inferred from Electronic Annotation
more info
 
sequence-specific DNA binding transcription factor activity TAS
Traceable Author Statement
more info
PubMed 
signal transducer activity IEA
Inferred from Electronic Annotation
more info
 
transcription factor binding IPI
Inferred from Physical Interaction
more info
PubMed 
transcription regulatory region DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
JAK-STAT cascade TAS
Traceable Author Statement
more info
PubMed 
JAK-STAT cascade involved in growth hormone signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
JAK-STAT cascade involved in growth hormone signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
 
JAK-STAT cascade involved in growth hormone signaling pathway TAS
Traceable Author Statement
more info
 
acute-phase response IEA
Inferred from Electronic Annotation
more info
 
astrocyte differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
cell proliferation IEA
Inferred from Electronic Annotation
more info
 
cellular component movement TAS
Traceable Author Statement
more info
PubMed 
cellular response to hormone stimulus IDA
Inferred from Direct Assay
more info
PubMed 
cytokine-mediated signaling pathway NAS
Non-traceable Author Statement
more info
PubMed 
eating behavior ISS
Inferred from Sequence or Structural Similarity
more info
 
eye photoreceptor cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
glucose homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
 
growth hormone receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
interleukin-6-mediated signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
intracellular receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cell death IEA
Inferred from Electronic Annotation
more info
 
negative regulation of cell proliferation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of glycolytic process IEA
Inferred from Electronic Annotation
more info
 
negative regulation of neuron migration IEA
Inferred from Electronic Annotation
more info
 
negative regulation of transcription from RNA polymerase II promoter TAS
Traceable Author Statement
more info
PubMed 
nervous system development TAS
Traceable Author Statement
more info
PubMed 
neurotrophin TRK receptor signaling pathway TAS
Traceable Author Statement
more info
 
phosphorylation ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of Notch signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of transcription from RNA polymerase II promoter IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription, DNA-templated ISS
Inferred from Sequence or Structural Similarity
more info
 
protein import into nucleus IDA
Inferred from Direct Assay
more info
PubMed 
radial glial cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of multicellular organism growth IEA
Inferred from Electronic Annotation
more info
 
regulation of transcription from RNA polymerase II promoter ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
PubMed 
response to drug IEA
Inferred from Electronic Annotation
more info
 
response to estradiol IDA
Inferred from Direct Assay
more info
PubMed 
response to ethanol IEA
Inferred from Electronic Annotation
more info
 
sexual reproduction ISS
Inferred from Sequence or Structural Similarity
more info
 
signal transduction TAS
Traceable Author Statement
more info
PubMed 
stem cell maintenance IEA
Inferred from Electronic Annotation
more info
 
temperature homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
 
transcription from RNA polymerase II promoter IEA
Inferred from Electronic Annotation
more info
 
viral process IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cytoplasm IDA
Inferred from Direct Assay
more info
 
cytoplasm ISS
Inferred from Sequence or Structural Similarity
more info
 
cytosol TAS
Traceable Author Statement
more info
 
NOT nucleolus IDA
Inferred from Direct Assay
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IDA
Inferred from Direct Assay
more info
 
nucleus ISS
Inferred from Sequence or Structural Similarity
more info
 
plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
 
Preferred Names
signal transducer and activator of transcription 3
Names
signal transducer and activator of transcription 3
DNA-binding protein APRF
acute-phase response factor

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_007370.1 

    Range
    5001..80171
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_112

mRNA and Protein(s)

  1. NM_003150.3NP_003141.2  signal transducer and activator of transcription 3 isoform 2

    See proteins identical to NP_003141.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks a segment in the 5' UTR and 3 nt within the CDS, as compared to variant 1. The resulting isoform (2) lacks an amino acid compared to isoform 1.
    Source sequence(s)
    AI631896, AK092965, BC000627, BC008044, BI461226, CB216860, CF454565
    Consensus CDS
    CCDS32657.1
    UniProtKB/Swiss-Prot
    P40763
    Conserved Domains (4) summary
    pfam02864
    Location:321574
    Blast Score: 1128
    STAT_bind; STAT protein, DNA binding domain
    cd10374
    Location:554714
    Blast Score: 928
    SH2_STAT3; Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 3 proteins
    smart00964
    Location:2120
    Blast Score: 467
    STAT_int; STAT protein, protein interaction domain
    pfam01017
    Location:139319
    Blast Score: 587
    STAT_alpha; STAT protein, all-alpha domain
  2. NM_139276.2NP_644805.1  signal transducer and activator of transcription 3 isoform 1

    See proteins identical to NP_644805.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript, and encodes the longest isoform (1).
    Source sequence(s)
    AI631896, AK092965, BC008044, BC014482, BI461226, CB216860, CF454565
    Consensus CDS
    CCDS32656.1
    UniProtKB/Swiss-Prot
    P40763
    Related
    ENSP00000264657, OTTHUMP00000198123, ENST00000264657, OTTHUMT00000319353
    Conserved Domains (4) summary
    pfam02864
    Location:321574
    Blast Score: 1128
    STAT_bind; STAT protein, DNA binding domain
    cd10374
    Location:554715
    Blast Score: 943
    SH2_STAT3; Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 3 proteins
    smart00964
    Location:2120
    Blast Score: 467
    STAT_int; STAT protein, protein interaction domain
    pfam01017
    Location:139319
    Blast Score: 588
    STAT_alpha; STAT protein, all-alpha domain
  3. NM_213662.1NP_998827.1  signal transducer and activator of transcription 3 isoform 3

    See proteins identical to NP_998827.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3), also called STAT3B or STAT3beta, lacks a segment in the coding region resulting in an early termination codon, compared to variant 1. Variant 3 encodes isoform 3, which has a shorter and distinct C-terminus compared to isoform 1.
    Source sequence(s)
    AI631896, AK092965, BC008044, BC014482, CB216860, CB321646, CF454565
    Consensus CDS
    CCDS59288.1
    UniProtKB/TrEMBL
    K7ENL3
    UniProtKB/Swiss-Prot
    P40763
    Conserved Domains (4) summary
    pfam02864
    Location:321574
    Blast Score: 1126
    STAT_bind; STAT protein, DNA binding domain
    cd10374
    Location:554715
    Blast Score: 943
    SH2_STAT3; Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 3 proteins
    smart00964
    Location:2120
    Blast Score: 463
    STAT_int; STAT protein, protein interaction domain
    pfam01017
    Location:139319
    Blast Score: 583
    STAT_alpha; STAT protein, all-alpha domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000017.11 

    Range
    42313324..42388568
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005257618.1XP_005257675.1  

    Conserved Domains (4) summary
    pfam02864
    Location:415668
    Blast Score: 1137
    STAT_bind; STAT protein, DNA binding domain
    cd10374
    Location:648808
    Blast Score: 928
    SH2_STAT3; Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 3 proteins
    smart00964
    Location:96214
    Blast Score: 473
    STAT_int; STAT protein, protein interaction domain
    pfam01017
    Location:233413
    Blast Score: 596
    STAT_alpha; STAT protein, all-alpha domain
  2. XM_005257617.1XP_005257674.1  

    Conserved Domains (4) summary
    pfam02864
    Location:415668
    Blast Score: 1137
    STAT_bind; STAT protein, DNA binding domain
    cd10374
    Location:648809
    Blast Score: 943
    SH2_STAT3; Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 3 proteins
    smart00964
    Location:96214
    Blast Score: 473
    STAT_int; STAT protein, protein interaction domain
    pfam01017
    Location:233413
    Blast Score: 596
    STAT_alpha; STAT protein, all-alpha domain
  3. XM_005257616.1XP_005257673.1  

    Conserved Domains (4) summary
    pfam02864
    Location:416669
    Blast Score: 1137
    STAT_bind; STAT protein, DNA binding domain
    cd10374
    Location:649809
    Blast Score: 928
    SH2_STAT3; Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 3 proteins
    smart00964
    Location:97215
    Blast Score: 473
    STAT_int; STAT protein, protein interaction domain
    pfam01017
    Location:234414
    Blast Score: 596
    STAT_alpha; STAT protein, all-alpha domain

Alternate HuRef

Genomic

  1. AC_000149.1 

    Range
    36230024..36304785
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018928.2 

    Range
    40701045..40776137
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)