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Details on Person UniProt:P42228 Stat4

Class:Id	ReferenceGeneProduct:102395
_chainChangeLog	chain:1-749 added on Fri February 6 2015;chain:1-749 removed on Tue November 3 2015;initiator methionine:1 added on Tue November 3 2015;chain:2-749 added on Tue November 3 2015;initiator methionine:1 removed on Fri May 6 2016;chain:2-749 removed on Fri May 6 2016;chain:1-749 added on Fri May 6 2016
_displayName	UniProt:P42228 Stat4
_timestamp	2025-05-21 21:39:44
chain	chain:1-749
checksum	A88B837E49FCFEBC
comment	FUNCTION Transcriptional regulator mainly expressed in hematopoietic cells that plays a critical role in cellular growth, differentiation and immune response. Plays a key role in the differentiation of T-helper 1 cells and the production of interferon-gamma (PubMed:8700209). Also participates in multiple neutrophil functions including chemotaxis and production of the neutrophil extracellular traps (PubMed:34138758). After IL12 binding to its receptor IL12RB2, STAT4 interacts with the intracellular domain of IL12RB2 and becomes tyrosine phosphorylated. Phosphorylated STAT4 then homodimerizes and migrates to the nucleus where it can recognize STAT target sequences present in IL12 responsive genes. Although IL12 appears to be the predominant activating signal, STAT4 can also be phosphorylated and activated in response to IFN-gamma stimulation via JAK1 and TYK2 and in response to different interleukins including IL23, IL2 and IL35 (By similarity). Transcription activation of IFN-gamma gene is mediated by interaction with JUN that forms a complex that efficiently interacts with the AP-1-related sequence of the IFN-gamma promoter (PubMed:14734615). In response to IFN-alpha/beta signaling, acts as a transcriptional repressor and suppresses IL5 and IL13 mRNA expression during response to T-cell receptor (TCR) activation (By similarity).SUBUNIT Forms a homodimer or a heterodimer with a related family member (By similarity). Interacts with ARL2BP. Interacts with STAT1 (By similarity). Interacts with JUN; this complex efficiently interacts with the AP-1-related sequence of the IFN-gamma promoter (PubMed:14734615).INTERACTION Translocated into the nucleus in response to phosphorylation.TISSUE SPECIFICITY Expression is restricted to testis, thymus, and spleen.PTM Acetylation at Lys-668 is required for JAK2-mediated phosphorylation and activation of STAT4.PTM Tyrosine phosphorylated upon IL12 and IFN-alpha activation, but not by IFN-gamma in T-lymphocytes and NK cells. Serine phosphorylation is required for maximal transcriptional activity but not for DNA binding. Phosphorylation by MAP2K6 at Ser-722 is required for full transcriptional activity induced by IL12. However this serine phosphorylation is not required for cell proliferation although critical for IFN-gamma production.DISRUPTION PHENOTYPE STAT4-deficient mice are grossly indistinguishable from wild-type mice. However, the development of T-helper 1 cells in response to either IL12 or Listeria monocytogenes is strongly impaired (PubMed:8700209). In addition, mice are acutely sensitive to methicillin-resistant Staphylococcus aureus (MRSA) infection (PubMed:34138758).SIMILARITY Belongs to the transcription factor STAT family.
description	recommendedName: Signal transducer and activator of transcription 4
geneName	Stat4
identifier	P42228
isSequenceChanged	FALSE
keyword	3D-structure Acetylation Activator Cytoplasm DNA-binding Nucleus Phosphoprotein Reference proteome SH2 domain Transcription Transcription regulation
modified	[InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:6807888] Weiser, JD [InstanceEdit:8869714] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9657908] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9819394] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21
name	Stat4
referenceDatabase	[ReferenceDatabase:2] UniProt
secondaryIdentifier	STAT4_MOUSE
sequenceLength	749
species	[Species:48892] Mus musculus
(referenceEntity)	[EntityWithAccessionedSequence:9006462] Stat4 [cytosol] [Mus musculus] [EntityWithAccessionedSequence:9006464] p-Y693-Stat4 [cytosol] [Mus musculus] [EntityWithAccessionedSequence:9943453] p-Y694-Stat4 [nucleoplasm] [Mus musculus]
(referenceSequence)	[ModifiedResidue:9006467] O4'-phospho-L-tyrosine at 693 [ModifiedResidue:9943444] O4'-phospho-L-tyrosine at 694
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No pathways have been reviewed or authored by UniProt:P42228 Stat4 (102395)