Human Gene STAT6 (uc009zpf.3) Description and Page Index
  Description: Homo sapiens signal transducer and activator of transcription 6, interleukin-4 induced (STAT6), transcript variant 1, mRNA.
RefSeq Summary (NM_001178078): The protein encoded by this gene is a member of the STAT family of transcription factors. 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 plays a central role in exerting IL4 mediated biological responses. It is found to induce the expression of BCL2L1/BCL-X(L), which is responsible for the anti-apoptotic activity of IL4. Knockout studies in mice suggested the roles of this gene in differentiation of T helper 2 (Th2) cells, expression of cell surface markers, and class switch of immunoglobulins. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010].
Transcript (Including UTRs)
   Position: hg19 chr12:57,489,187-57,505,196 Size: 16,010 Total Exon Count: 22 Strand: -
Coding Region
   Position: hg19 chr12:57,490,355-57,502,061 Size: 11,707 Coding Exon Count: 21 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-15

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr12:57,489,187-57,505,196)mRNA (may differ from genome)Protein (847 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
HGNCHPRDLynxMGIneXtProtOMIM
PubMedReactomeStanford SOURCETreefamUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: STAT6_HUMAN
DESCRIPTION: RecName: Full=Signal transducer and activator of transcription 6; AltName: Full=IL-4 Stat;
FUNCTION: Carries out a dual function: signal transduction and activation of transcription. Involved in interleukin-4 signalling.
SUBUNIT: Forms a homodimer or a heterodimer with a related family member (By similarity). Interacts with NCOA1 via its C-terminal LXXLL motif.
INTERACTION: Self; NbExp=2; IntAct=EBI-1186478, EBI-1186478; Q9UHD2:TBK1; NbExp=7; IntAct=EBI-1186478, EBI-356402; Q86WV6:TMEM173; NbExp=12; IntAct=EBI-1186478, EBI-2800345;
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Translocated into the nucleus in response to phosphorylation.
PTM: Tyrosine phosphorylated following stimulation by IL-4 and IL- 3 (By similarity).
SIMILARITY: Belongs to the transcription factor STAT family.
SIMILARITY: Contains 1 SH2 domain.
WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/stat6/";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): STAT6
CDC HuGE Published Literature: STAT6
Positive Disease Associations: allergic diseases , Allergic diseases (bronchial asthma. atopic dermatitis and/or food-related anaphylaxis) , asthma; dermatitis and eczema; anaphylaxis, food-related , atopy; IgE levels , Birth Weight|Leukemia|Leukemia, Myeloid, Acute|Precursor Cell Lymphoblastic Leukemia-Lymphoma , DRS , endometriosis , eosinophilia , eosinophilic esophagitis (pediatric) , Esophagitis , Graves' disease IgE , Immunoglobulin E , minimal change nephrotic syndrome , nut allergy , Total IgE , total serum IgE levels
Related Studies:
  1. allergic diseases
    Tamura K et al. 2003, Linkage and association studies of STAT6 gene polymorphisms and allergic diseases., International archives of allergy and immunology. 2003 May;131(1):33-8. [PubMed 12759487]
    Our findings indicate that in combination the dinucleotide repeat polymorphism of the STAT6 exon 1 gene and the 2964A variant may be useful markers for predicting allergic diseases in a Japanese population.
  2. Allergic diseases
    Tamura K 2001, , Clinical and experimental allergy. 2001 Oct;31(10):1509-14. [PubMed 11678849]
    This suggests that genetic variation in the STAT-6 gene may be associated with predisposition to allergic diseases.
  3. Allergic diseases (bronchial asthma. atopic dermatitis and/or food-related anaphylaxis)
    Tamura K 2001, , Clinical and experimental allergy. 2001 Oct;31(10):1509-14. [PubMed 11678849]
    This suggests that genetic variation in the STAT-6 gene may be associated with predisposition to allergic diseases.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: STAT6
Diseases sorted by gene-association score: hemangiopericytoma, malignant* (367), nut allergy (18), meninges hemangiopericytoma (16), allergic asthma (11), penicillin allergy (11), beta-lactam allergy (10), urinary schistosomiasis (8), inflammatory bowel disease 2 (8), primary mediastinal large b-cell lymphoma (7), jak3-deficient severe combined immunodeficiency (7), sclerosing liposarcoma (7), food allergy (6), primary amebic meningoencephalitis (6), allergic hypersensitivity disease (6), bronchial disease (5), ecthyma (5), inflammatory bowel disease (4), atopy (3), asthma (3), respiratory system disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 76.82 RPKM in Bladder
Total median expression: 2018.80 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -123.00325-0.378 Picture PostScript Text
3' UTR -430.601168-0.369 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011992 - EF-hand-like_dom
IPR008967 - p53-like_TF_DNA-bd
IPR000980 - SH2
IPR013800 - STAT_TF_alpha
IPR015988 - STAT_TF_coiled-coil
IPR001217 - STAT_TF_core
IPR013801 - STAT_TF_DNA-bd
IPR012345 - STAT_TF_DNA-bd_sub
IPR013799 - STAT_TF_prot_interaction

Pfam Domains:
PF00017 - SH2 domain
PF01017 - STAT protein, all-alpha domain
PF02864 - STAT protein, DNA binding domain
PF02865 - STAT protein, protein interaction domain
PF14596 - STAT6 C-terminal

SCOP Domains:
47655 - STAT
48092 - Transcription factor STAT-4 N-domain
49417 - p53-like transcription factors
55550 - SH2 domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1OJ5
- X-ray


ModBase Predicted Comparative 3D Structure on P42226
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0003677 DNA binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0005515 protein binding
GO:0019903 protein phosphatase binding
GO:0042802 identical protein binding
GO:0043565 sequence-specific DNA binding

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0002296 T-helper 1 cell lineage commitment
GO:0002829 negative regulation of type 2 immune response
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0006366 transcription from RNA polymerase II promoter
GO:0007165 signal transduction
GO:0019221 cytokine-mediated signaling pathway
GO:0032481 positive regulation of type I interferon production
GO:0033598 mammary gland epithelial cell proliferation
GO:0034097 response to cytokine
GO:0035771 interleukin-4-mediated signaling pathway
GO:0042127 regulation of cell proliferation
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0048295 positive regulation of isotype switching to IgE isotypes
GO:0060443 mammary gland morphogenesis
GO:0070301 cellular response to hydrogen peroxide
GO:1902170 cellular response to reactive nitrogen species

Cellular Component:
GO:0000790 nuclear chromatin
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0031965 nuclear membrane
GO:0045121 membrane raft


-  Descriptions from all associated GenBank mRNAs
  KJ892217 - Synthetic construct Homo sapiens clone ccsbBroadEn_01611 STAT6 gene, encodes complete protein.
LF208944 - JP 2014500723-A/16447: Polycomb-Associated Non-Coding RNAs.
HH925529 - Sequence 145 from Patent WO2010107958.
BC075852 - Homo sapiens signal transducer and activator of transcription 6, interleukin-4 induced, mRNA (cDNA clone MGC:90177 IMAGE:5530399), complete cds.
BC004973 - Homo sapiens cDNA clone IMAGE:2958389, containing frame-shift errors.
BC005823 - Homo sapiens cDNA clone IMAGE:2958389, containing frame-shift errors.
JD475237 - Sequence 456261 from Patent EP1572962.
JD287478 - Sequence 268502 from Patent EP1572962.
JD162807 - Sequence 143831 from Patent EP1572962.
JD190822 - Sequence 171846 from Patent EP1572962.
LF324399 - JP 2014500723-A/131902: Polycomb-Associated Non-Coding RNAs.
JD226247 - Sequence 207271 from Patent EP1572962.
JD347404 - Sequence 328428 from Patent EP1572962.
JD272569 - Sequence 253593 from Patent EP1572962.
JD114801 - Sequence 95825 from Patent EP1572962.
JD565684 - Sequence 546708 from Patent EP1572962.
JD508937 - Sequence 489961 from Patent EP1572962.
LF324398 - JP 2014500723-A/131901: Polycomb-Associated Non-Coding RNAs.
JD548758 - Sequence 529782 from Patent EP1572962.
JD303938 - Sequence 284962 from Patent EP1572962.
AY615283 - Homo sapiens STAT6B (STAT6B) mRNA, complete cds.
AK316236 - Homo sapiens cDNA, FLJ79135 complete cds, highly similar to Signal transducer and activator of transcription 6.
LF324397 - JP 2014500723-A/131900: Polycomb-Associated Non-Coding RNAs.
JD454429 - Sequence 435453 from Patent EP1572962.
JD343688 - Sequence 324712 from Patent EP1572962.
AK298721 - Homo sapiens cDNA FLJ51956 complete cds, highly similar to Signal transducer and activator of transcription 6.
JD065274 - Sequence 46298 from Patent EP1572962.
U16031 - Human transcription factor IL-4 Stat mRNA, complete cds.
JD368617 - Sequence 349641 from Patent EP1572962.
AK291044 - Homo sapiens cDNA FLJ77755 complete cds, highly similar to Homo sapiens signal transducer and activator of transcription 6, interleukin-4 induced (STAT6), mRNA.
JD452247 - Sequence 433271 from Patent EP1572962.
JD056994 - Sequence 38018 from Patent EP1572962.
JD187418 - Sequence 168442 from Patent EP1572962.
JD190516 - Sequence 171540 from Patent EP1572962.
JD059265 - Sequence 40289 from Patent EP1572962.
AK308751 - Homo sapiens cDNA, FLJ98792.
AK316142 - Homo sapiens cDNA, FLJ79041 complete cds, highly similar to Signal transducer and activator of transcription 6.
JD164298 - Sequence 145322 from Patent EP1572962.
AK290431 - Homo sapiens cDNA FLJ77813 complete cds, highly similar to Homo sapiens signal transducer and activator of transcription 6, interleukin-4 induced (STAT6), mRNA.
LF324396 - JP 2014500723-A/131899: Polycomb-Associated Non-Coding RNAs.
JD146843 - Sequence 127867 from Patent EP1572962.
JD398375 - Sequence 379399 from Patent EP1572962.
AK299094 - Homo sapiens cDNA FLJ51958 complete cds, highly similar to Signal transducer and activator of transcription 6.
JD354245 - Sequence 335269 from Patent EP1572962.
JD121353 - Sequence 102377 from Patent EP1572962.
JD054575 - Sequence 35599 from Patent EP1572962.
JD411537 - Sequence 392561 from Patent EP1572962.
JD371943 - Sequence 352967 from Patent EP1572962.
JD215517 - Sequence 196541 from Patent EP1572962.
AB103089 - Homo sapiens STAT6 mRNA for signal transducer and activator of transcription 6 nirs variant 2, complete cds.
AK312471 - Homo sapiens cDNA, FLJ92827, highly similar to Homo sapiens signal transducer and activator of transcription 6, interleukin-4 induced (STAT6), mRNA.
AB385006 - Synthetic construct DNA, clone: pF1KB4980, Homo sapiens STAT6 gene for signal transducer and activator of transcription 6, complete cds, without stop codon, in Flexi system.
JD335904 - Sequence 316928 from Patent EP1572962.
JD423995 - Sequence 405019 from Patent EP1572962.
LF324395 - JP 2014500723-A/131898: Polycomb-Associated Non-Coding RNAs.
LF324394 - JP 2014500723-A/131897: Polycomb-Associated Non-Coding RNAs.
BT007380 - Homo sapiens signal transducer and activator of transcription 6, interleukin-4 induced mRNA, complete cds.
LF324393 - JP 2014500723-A/131896: Polycomb-Associated Non-Coding RNAs.
LF324391 - JP 2014500723-A/131894: Polycomb-Associated Non-Coding RNAs.
CU687302 - Synthetic construct Homo sapiens gateway clone IMAGE:100022835 5' read STAT6 mRNA.
AB103088 - Homo sapiens STAT6 mRNA for signal transducer and activator of transcription 6 nirs variant 1, complete cds.
JD140730 - Sequence 121754 from Patent EP1572962.
JD440202 - Sequence 421226 from Patent EP1572962.
JD147083 - Sequence 128107 from Patent EP1572962.
JD316780 - Sequence 297804 from Patent EP1572962.
JD539671 - Sequence 520695 from Patent EP1572962.
JD040076 - Sequence 21100 from Patent EP1572962.
MA559976 - JP 2018138019-A/131902: Polycomb-Associated Non-Coding RNAs.
MA559975 - JP 2018138019-A/131901: Polycomb-Associated Non-Coding RNAs.
MA559974 - JP 2018138019-A/131900: Polycomb-Associated Non-Coding RNAs.
MA559973 - JP 2018138019-A/131899: Polycomb-Associated Non-Coding RNAs.
MA559972 - JP 2018138019-A/131898: Polycomb-Associated Non-Coding RNAs.
MA559971 - JP 2018138019-A/131897: Polycomb-Associated Non-Coding RNAs.
MA559970 - JP 2018138019-A/131896: Polycomb-Associated Non-Coding RNAs.
MA559968 - JP 2018138019-A/131894: Polycomb-Associated Non-Coding RNAs.
MA444521 - JP 2018138019-A/16447: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04630 - Jak-STAT signaling pathway

BioCarta from NCI Cancer Genome Anatomy Project
h_il4Pathway - IL 4 signaling pathway

Reactome (by CSHL, EBI, and GO)

Protein P42226 (Reactome details) participates in the following event(s):

R-HSA-3249378 STING recruits TBK1 and STAT6
R-HSA-3249379 p-S407-STAT6 is phosphorylated at Tyr641
R-HSA-3249371 TBK1 phosphorylates STAT6 at Ser407
R-HSA-3249372 p-S407,Y641-STAT6 is dimerized
R-HSA-3249390 TBK1 is phosphorylated within STING:TBK1:STAT6 complex
R-HSA-380782 STAT binds to the active receptor
R-HSA-6786124 STAT3,STAT6 bind p-Y-IL4R
R-HSA-6788571 STAT1,STAT3,STAT6 bind IL13:IL13R type II
R-HSA-3249370 p-S407,Y641-STAT6 dimer migrates to the nucleus
R-HSA-6786095 JAK1 phosphorylates STAT3,STAT6
R-HSA-6788582 STAT1,STAT3,STAT6 phosphorylation
R-HSA-3249367 STAT6-mediated induction of chemokines
R-HSA-186763 Downstream signal transduction
R-HSA-6785807 Interleukin-4 and 13 signaling
R-HSA-1834941 STING mediated induction of host immune responses
R-HSA-186797 Signaling by PDGF
R-HSA-449147 Signaling by Interleukins
R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-168249 Innate Immune System
R-HSA-162582 Signal Transduction
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: A8K316, NM_001178078, NP_001171552, P42226, Q5FBW5, Q71UP4, STAT6_HUMAN
UCSC ID: uc009zpf.3
RefSeq Accession: NM_001178078
Protein: P42226 (aka STAT6_HUMAN or STA6_HUMAN)
CCDS: CCDS8931.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_001178078.1
exon count: 22CDS single in 3' UTR: no RNA size: 4050
ORF size: 2544CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 5175.50frame shift in genome: no % Coverage: 99.68
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.