STAT4
entrez
6775
canonical
uniprot
Q14765
canonical
ensembl
ENSG00000138378
resolver
ensp
ENSP00000351255
resolver
ensp
ENSP00000376134
resolver
ensp
ENSP00000412397
resolver
ensp
ENSP00000414322
resolver
ensp
ENSP00000630272
resolver
enst
ENST00000358470
resolver
enst
ENST00000392320
resolver
enst
ENST00000432798
resolver
enst
ENST00000450994
resolver
enst
ENST00000960213
resolver
genesymbol
STAT4
resolver
hgnc
HGNC:11365
resolver
uniprot
Q96NZ6
resolver
uniprot_entry
STAT4_HUMAN
resolver
uniprot_sec
Q96NZ6
resolver
amino_acid_sequence
MSQWNQVQQLEIKFLEQVDQFYDDNFPMEIRHLLAQWIENQDWEAASNNETMATILLQNLLIQLDEQLGRVSKEKNLLLIHNLKRIRKVLQGKFHGNPMHVAVVISNCLREERRILAAANMPVQGPLEKSLQSSSVSERQRNVEHKVAAIKNSVQMTEQDTKYLEDLQDEFDYRYKTIQTMDQSDKNSAMVNQEVLTLQEMLNSLDFKRKEALSKMTQIIHETDLLMNTMLIEELQDWKRRQQIACIGGPLHNGLDQLQNCFTLLAESLFQLRRQLEKLEEQSTKMTYEGDPIPMQRTHMLERVTFLIYNLFKNSFVVERQPCMPTHPQRPLVLKTLIQFTVKLRLLIKLPELNYQVKVKASIDKNVSTLSNRRFVLCGTNVKAMSIEESSNGSLSVEFRHLQPKEMKSSAGGKGNEGCHMVTEELHSITFETQICLYGLTIDLETSSLPVVMISNVSQLPNAWASIIWYNVSTNDSQNLVFFNNPPPATLSQLLEVMSWQFSSYVGRGLNSDQLHMLAEKLTVQSSYSDGHLTWAKFCKEHLPGKSFTFWTWLEAILDLIKKHILPLWIDGYVMGFVSKEKERLLLKDKMPGTFLLRFSESHLGGITFTWVDHSESGEVRFHSVEPYNKGRLSALPFADILRDYKVIMAENIPENPLKYLYPDIPKDKAFGKHYSSQPCEVSRPTERGDKGYVPSVFIPISTIRSDSTEPHSPSDLLPMSPSVYAVLRENLSPTTIETAMKSPYSAE
uniprot
proteins
disease_involvement
DISEASE: Systemic lupus erythematosus 11 (SLEB11) [MIM:612253]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. {ECO:0000269|PubMed:17804842, ECO:0000269|PubMed:19109131}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Rheumatoid arthritis (RA) [MIM:180300]: An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. {ECO:0000269|PubMed:17804842}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Disabling pansclerotic morphea of childhood (DPMC) [MIM:620443]: An autosomal dominant, severe systemic inflammatory disorder that is part of the juvenile localized scleroderma spectrum. DPMC is characterized by poor wound healing with rapidly progressive deep fibrosis involving the mucous membranes, dermis, subcutaneous fat, fascia, muscles, and bone, leading to contractures, musculoskeletal atrophy, and articular ankylosis. Systemic manifestations include cytopenias and hypogammaglobulinemia, but scleroderma-associated autoantibodies are usually not present. The disorder is associated with high morbidity and mortality due to squamous-cell carcinoma, restrictive pulmonary disease, sepsis, and gangrene. {ECO:0000269|PubMed:37256972}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Transcriptional regulator mainly expressed in hematopoietic cells that plays a critical role in cellular growth, differentiation and immune response (PubMed:10961885, PubMed:37256972, PubMed:8943379). Plays a key role in the differentiation of T-helper 1 cells and the production of interferon-gamma (PubMed:12213961, PubMed:35614130). Also participates in multiple neutrophil functions including chemotaxis and production of the neutrophil extracellular traps (By similarity). After IL12 binding to its receptor IL12RB2, STAT4 interacts with the intracellular domain of IL12RB2 and becomes tyrosine phosphorylated (PubMed:10415122, PubMed:7638186). 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 (PubMed:11114383, PubMed:34508746). 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 (By similarity). 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 (PubMed:26990433). {ECO:0000250|UniProtKB:P42228, ECO:0000269|PubMed:10415122, ECO:0000269|PubMed:10961885, ECO:0000269|PubMed:11114383, ECO:0000269|PubMed:12213961, ECO:0000269|PubMed:26990433, ECO:0000269|PubMed:34508746, ECO:0000269|PubMed:35614130, ECO:0000269|PubMed:37256972, ECO:0000269|PubMed:7638186, ECO:0000269|PubMed:8943379}.
uniprot
proteins
mass_dalton
85941
uniprot
proteins
mutagenesis
MUTAGEN 693; /note="Y->A: Abrogates phosphorylation and transcriptional activity."; /evidence="ECO:0000269|PubMed:10961885, ECO:0000269|PubMed:37256972"; MUTAGEN 721; /note="S->A: About 50% loss of transcriptional activity."; /evidence="ECO:0000269|PubMed:10961885
uniprot
proteins
post_translational_modification
PTM: Acetylation at Lys-667 is required for JAK2-mediated phosphorylation and activation of STAT4. {ECO:0000269|PubMed:35614130}.; PTM: Tyrosine phosphorylated upon IL12 and IFN-alpha activation, but not by IFN-gamma in T-lymphocytes and NK cells (PubMed:8943379). Serine phosphorylation is required for maximal transcriptional activity but not for DNA binding (PubMed:8943379). Phosphorylation by MAP2K6 at Ser-721 is required for full transcriptional activity induced by IL12 (PubMed:10961885). However this serine phosphorylation is not required for cell proliferation although critical for IFN-gamma production (PubMed:12213961). {ECO:0000269|PubMed:10961885, ECO:0000269|PubMed:12213961, ECO:0000269|PubMed:8943379}.
uniprot
proteins
protein_family
Transcription factor STAT family
uniprot
proteins
pubmed
10415122
uniprot
proteins
pubmed
10961885
uniprot
proteins
pubmed
11114383
uniprot
proteins
pubmed
12213961
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17804842
uniprot
proteins
pubmed
19109131
uniprot
proteins
pubmed
26990433
uniprot
proteins
pubmed
34508746
uniprot
proteins
pubmed
35614130
uniprot
proteins
pubmed
37256972
uniprot
proteins
pubmed
7638186
uniprot
proteins
pubmed
8943379
uniprot
proteins
pubmed
9890938
uniprot
proteins
sequence_length
748
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000269|PubMed:35614130, ECO:0000269|PubMed:37256972}. Note=Translocated into the nucleus in response to phosphorylation. {ECO:0000269|PubMed:35614130}.
uniprot
proteins