STAT6

Protein identityUniProt · HPA

UniProt accession

P42226

Gene

STAT6

Ensembl

ENSG00000166888

Chromosome

12

Canonical length

847 aa

Protein class

Cancer-related genes, Predicted intracellular proteins, Transcription factors

Subcellular location

Nucleoplasm,Cytosol,Connecting piece

Quaternary structure

Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

847 residues, UniProt reviewed canonical sequence.

>P42226|STAT6
     1  MSLWGLVSKM PPEKVQRLYV DFPQHLRHLL GDWLESQPWE FLVGSDAFCC NLASALLSDT
    61  VQHLQASVGE QGEGSTILQH ISTLESIYQR DPLKLVATFR QILQGEKKAV MEQFRHLPMP
   121  FHWKQEELKF KTGLRRLQHR VGEIHLLREA LQKGAEAGQV SLHSLIETPA NGTGPSEALA
   181  MLLQETTGEL EAAKALVLKR IQIWKRQQQL AGNGAPFEES LAPLQERCES LVDIYSQLQQ
   241  EVGAAGGELE PKTRASLTGR LDEVLRTLVT SCFLVEKQPP QVLKTQTKFQ AGVRFLLGLR
   301  FLGAPAKPPL VRADMVTEKQ ARELSVPQGP GAGAESTGEI INNTVPLENS IPGNCCSALF
   361  KNLLLKKIKR CERKGTESVT EEKCAVLFSA SFTLGPGKLP IQLQALSLPL VVIVHGNQDN
   421  NAKATILWDN AFSEMDRVPF VVAERVPWEK MCETLNLKFM AEVGTNRGLL PEHFLFLAQK
   481  IFNDNSLSME AFQHRSVSWS QFNKEILLGR GFTFWQWFDG VLDLTKRCLR SYWSDRLIIG
   541  FISKQYVTSL LLNEPDGTFL LRFSDSEIGG ITIAHVIRGQ DGSPQIENIQ PFSAKDLSIR
   601  SLGDRIRDLA QLKNLYPKKP KDEAFRSHYK PEQMGKDGRG YVPATIKMTV ERDQPLPTPE
   661  LQMPTMVPSY DLGMAPDSSM SMQLGPDMVP QVYPPHSHSI PPYQGLSPEE SVNVLSAFQE
   721  PHLQMPPSLG QMSLPFDQPH PQGLLPCQPQ EHAVSSPDPL LCSDVTMVED SCLSQPVTAF
   781  PQGTWIGEDI FPPLLPPTEQ DLTKLLLEGQ GESGGGSLGA QPLLQPSHYG QSGISMSHMD
   841  LRANPSW

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against STAT6 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.38

Highest tissue expression

107 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about STAT6.

Disease | AllUniProt

Conditions STAT6 is implicated in, by any mechanism.

• Hyper-IgE syndrome 6, autosomal dominant, with recurrent infections (HIES6) MIM:620532

Disease | GeneticClinVar

6 pathogenic / likely-pathogenic of 143 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hyper-IgE syndrome 6, autosomal dominant, with recurrent infections
• Neoplasm

Disease | ImmuneIEDB

Conditions an epitope on STAT6 was assayed in.

• type 1 diabetes mellitus T cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.3

gnomAD pLI

0.99

gnomAD missense Z

2.41

DepMap mean gene effect

-0.14

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell surface receptor signaling pathway via JAK-STAT
• cytokine-mediated signaling pathway
• defense response
• growth hormone receptor signaling pathway via JAK-STAT
• interleukin-4-mediated signaling pathway
• isotype switching to IgE isotypes
• mammary gland epithelial cell proliferation
• mammary gland morphogenesis
• negative regulation of transcription by RNA polymerase II
• negative regulation of type 2 immune response
• positive regulation of cold-induced thermogenesis
• positive regulation of isotype switching to IgE isotypes
• positive regulation of transcription by RNA polymerase II
• regulation of cell population proliferation
• regulation of transcription by RNA polymerase II
• response to peptide hormone
• T-helper 1 cell lineage commitment
• regulation of mast cell proliferation

Molecular functions

• DNA-binding transcription activator activity, RNA polymerase II-specific
• DNA-binding transcription factor activity
• DNA-binding transcription factor activity, RNA polymerase II-specific
• identical protein binding
• protein phosphatase binding
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• RNA polymerase II transcription regulatory region sequence-specific DNA binding
• transcription coactivator binding

Cellular components

• chromatin
• cytoplasm
• cytosol
• nucleoplasm
• nucleus
• RNA polymerase II transcription regulator complex
• sperm head-tail coupling apparatus

Protein domainsUniProt · Pfam · InterPro

• SH2 domain
• Transcription factor STAT
• p53-like transcription factor, DNA-binding domain superfamily
• STAT transcription factor, DNA-binding, N-terminal
• STAT transcription factor, protein interaction
• STAT transcription factor, all-alpha domain
• STAT transcription factor, DNA-binding
• STAT transcription factor, coiled coil
• STAT transcription factor, N-terminal domain superfamily
• SH2 domain superfamily
• Signal transducer and activator of transcription, linker domain
• SH2 domain
• STAT transcription factor, coiled-coil domain
• STAT protein, DNA binding domain
• STAT protein, protein interaction domain
• Signal transducer and activator of transcription, linker domain
• STAT6, C-terminal
• STAT6, SH2 domain
• STAT6 C-terminal

KeywordsUniProt

• Acetylation
• Activator
• ADP-ribosylation
• Cytoplasm
• DNA-binding
• Nucleus
• Phosphoprotein
• SH2 domain
• Transcription
• Transcription regulation

InteractionsUniProt · HPA

Protein binding partners of STAT6 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• NCOA1
• PARP14
• LITAF