STAT4

 Signal transducer and activator of transcription 4 (STAT4) is a transcription factor belonging to the STAT protein family.^[5] It is required for the development of Th1 cells from naive CD4+ T cells^[6] and IFN-γ production in response to IL-12.^[7]

STAT4
Identifiers
Aliases	STAT4, SLEB11, signal transducer and activator of transcription 4
External IDs	OMIM: 600558 MGI: 103062 HomoloGene: 20679 GeneCards: STAT4
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q32.2-q32.3 Start 191,029,576 bp[1] End 191,151,596 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1 C1.1|1 26.67 cM Start 51,987,148 bp[2] End 52,107,189 bp[2]
Gene ontology Molecular function • GO:0001948 protein binding • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • DNA binding • identical protein binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific Cellular component • cytoplasm • cell nucleus • nucleoplasm • cytosol Biological process • transcription, DNA-templated • regulation of transcription, DNA-templated • JAK-STAT cascade • signal transduction • positive regulation of transcription from RNA polymerase II promoter • interleukin-12-mediated signaling pathway • cytokine-mediated signaling pathway • interleukin-21-mediated signaling pathway • interleukin-23-mediated signaling pathway • interleukin-35-mediated signaling pathway • defense response • regulation of cell proliferation • response to peptide hormone Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	6775	20849
Ensembl	ENSG00000138378	ENSMUSG00000062939
UniProt	Q14765	P42228
RefSeq (mRNA)	NM_001243835 NM_003151	NM_011487 NM_001308266
RefSeq (protein)	NP_001230764 NP_003142	NP_001295195 NP_035617
Location (UCSC)	Chr 2: 191.03 – 191.15 Mb	Chr 1: 51.99 – 52.11 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

StructureEdit

Human as well murine STAT4 genes lie next to STAT1 gene locus suggesting that the genes arose by gene duplication.^[5] STAT proteins have several functional domains, including an N-terminal interaction domain, a central DNA-binding domain, an SH2 domain, and the C-terminal transactivation domain.^[8] The length of the protein is 748 amino acids, and the molecular weight is 85 941 Dalton.^[9]

ExpressionEdit

Distribution of STAT4 is restricted to myeloid cells, thymus and testis.^[5] In resting human T cells it is expressed at very low levels, but its production is amplified by PHA stimulation.^[7]

ActivationEdit

Two chains of IL-12 receptor form heterodimer after IL-12 binding and activate the receptor associated JAK kinases, termed JAK2 and TYK2. Stat4 is phosphorylated by these tyrosine kinases, homodimerizes via its SH2 domain and translocates into nucleus to activate gene transcription.^[10]

Target genesEdit

STAT4 binds to hundreds of sites in the genome,^[11] among others to the promoters of genes for cytokines (IFN-γ, TNF), receptors (IL18R1, IL12rβ2, IL18RAP), and signaling factors (MYD88).^[11]

DiseaseEdit

STAT4 is involved in several autoimmune and cancer diseases in animal models humans, significantly in the disease progression and pathology. STAT4 were significantly increased in patients with colitis ulcerative^[12] and skin T cells of psoriatic patients.^[13] Moreover, STAT4 -/- mice developed less severe experimental autoimmune encephalo-myelitis (EAE) than the wild type mice.^[14]

Intronic single nucleotide polymorphism (SNP) mostly in third intron of the STAT4 has shown to be associated with immune dysregulation and autoimmunity including systemic lupus erythematosus (SLE)^[15] and rheumatoid arthritis ^[16] as well as Sjögren's disease (SD),^[17] systemic sclerosis,^[18] psoriasis^[19] and also type-1 diabetes.^[20] High incident of STAT4 genetic polymorphisms and susceptibility to autoimmune diseases is a reason to consider the STAT4 as general autoimmune disease susceptibility locus.^[21]

This article uses material from the Wikipedia article  Metasyntactic variable, which is released under the  Creative Commons Attribution-ShareAlike 3.0 Unported License.