ID STAT4_HUMAN Reviewed; 748 AA. AC Q14765; Q96NZ6; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 27-MAR-2024, entry version 213. DE RecName: Full=Signal transducer and activator of transcription 4; GN Name=STAT4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Xu X., Sun Y.L., Hoey T.; RT "The STAT amino-terminal domain mediates cooperative DNA binding and RT confers selective sequence recognition."; RL Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 91-748. RG SeattleSNPs variation discovery resource; RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases. RN [4] RP FUNCTION, AND PHOSPHORYLATION. RX PubMed=7638186; DOI=10.1073/pnas.92.16.7307; RA Bacon C.M., Petricoin E.F. III, Ortaldo J.R., Rees R.C., Larner A.C., RA Johnston J.A., O'Shea J.J.; RT "Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in RT human lymphocytes."; RL Proc. Natl. Acad. Sci. U.S.A. 92:7307-7311(1995). RN [5] RP FUNCTION, AND PHOSPHORYLATION. RX PubMed=8943379; RA Cho S.S., Bacon C.M., Sudarshan C., Rees R.C., Finbloom D., Pine R., RA O'Shea J.J.; RT "Activation of STAT4 by IL-12 and IFN-alpha: evidence for the involvement RT of ligand-induced tyrosine and serine phosphorylation."; RL J. Immunol. 157:4781-4789(1996). RN [6] RP INTERACTION WITH IL12RB2, AND FUNCTION. RX PubMed=10415122; DOI=10.1006/abbi.1999.1302; RA Yao B.B., Niu P., Surowy C.S., Faltynek C.R.; RT "Direct interaction of STAT4 with the IL-12 receptor."; RL Arch. Biochem. Biophys. 368:147-155(1999). RN [7] RP INTERACTION WITH IL12RB2. RX PubMed=9890938; DOI=10.1074/jbc.274.4.1875; RA Naeger L.K., McKinney J., Salvekar A., Hoey T.; RT "Identification of a STAT4 binding site in the interleukin-12 receptor RT required for signaling."; RL J. Biol. Chem. 274:1875-1878(1999). RN [8] RP FUNCTION, PHOSPHORYLATION AT TYR-693 AND SER-721, AND MUTAGENESIS OF RP TYR-693 AND SER-721. RX PubMed=10961885; RA Visconti R., Gadina M., Chiariello M., Chen E.H., Stancato L.F., RA Gutkind J.S., O'Shea J.J.; RT "Importance of the MKK6/p38 pathway for interleukin-12-induced STAT4 serine RT phosphorylation and transcriptional activity."; RL Blood 96:1844-1852(2000). RN [9] RP FUNCTION. RX PubMed=11114383; DOI=10.1016/s1074-7613(00)00070-4; RA Oppmann B., Lesley R., Blom B., Timans J.C., Xu Y., Hunte B., Vega F., RA Yu N., Wang J., Singh K.P., Zonin F., Vaisberg E., Churakova T., Liu M.-R., RA Gorman D., Wagner J., Zurawski S., Liu Y.-J., Abrams J.S., Moore K.W., RA Rennick D.M., de Waal-Malefyt R., Hannum C., Bazan J.F., Kastelein R.A.; RT "Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with RT biological activities similar as well as distinct from IL-12."; RL Immunity 13:715-725(2000). RN [10] RP FUNCTION, AND PHOSPHORYLATION AT SER-721. RX PubMed=12213961; DOI=10.1073/pnas.182618999; RA Morinobu A., Gadina M., Strober W., Visconti R., Fornace A., Montagna C., RA Feldman G.M., Nishikomori R., O'Shea J.J.; RT "STAT4 serine phosphorylation is critical for IL-12-induced IFN-gamma RT production but not for cell proliferation."; RL Proc. Natl. Acad. Sci. U.S.A. 99:12281-12286(2002). RN [11] RP INVOLVEMENT IN SLEB11. RX PubMed=19109131; DOI=10.4049/jimmunol.182.1.34; RA Kariuki S.N., Kirou K.A., MacDermott E.J., Barillas-Arias L., Crow M.K., RA Niewold T.B.; RT "Cutting edge: autoimmune disease risk variant of STAT4 confers increased RT sensitivity to IFN-alpha in lupus patients in vivo."; RL J. Immunol. 182:34-38(2009). RN [12] RP FUNCTION. RX PubMed=26990433; DOI=10.1002/eji.201546050; RA Gonzales-van Horn S.R., Estrada L.D., van Oers N.S., Farrar J.D.; RT "STAT4-mediated transcriptional repression of the IL5 gene in human memory RT Th2 cells."; RL Eur. J. Immunol. 46:1504-1510(2016). RN [13] RP FUNCTION, AND INTERACTION WITH STAT1. RX PubMed=34508746; DOI=10.1016/j.yexcr.2021.112784; RA Li M., Liu Y., Fu Y., Gong R., Xia H., Huang X., Wu Y.; RT "Interleukin-35 inhibits lipopolysaccharide-induced endothelial cell RT activation by downregulating inflammation and apoptosis."; RL Exp. Cell Res. 407:112784-112784(2021). RN [14] RP FUNCTION, ACETYLATION AT LYS-667, AND SUBCELLULAR LOCATION. RX PubMed=35614130; DOI=10.1038/s41418-022-01017-9; RA Zhang Y.S., Xin D.E., Wang Z., Peng W., Zeng Y., Liang J., Xu M., Chen N., RA Zhang J., Yue J., Cao M., Zhang C., Wang Y., Chang Z., Lu X.M., Chang L., RA Chinn Y.E.; RT "Acetylation licenses Th1 cell polarization to constrain Listeria RT monocytogenes infection."; RL Cell Death Differ. 0:0-0(2022). RN [15] RP VARIANT [LARGE SCALE ANALYSIS] GLN-112. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [16] RP INVOLVEMENT IN SLEB11 AND RA. RX PubMed=17804842; DOI=10.1056/nejmoa073003; RA Remmers E.F., Plenge R.M., Lee A.T., Graham R.R., Hom G., Behrens T.W., RA de Bakker P.I.W., Le J.M., Lee H.-S., Batliwalla F., Li W., Masters S.L., RA Booty M.G., Carulli J.P., Padyukov L., Alfredsson L., Klareskog L., RA Chen W.V., Amos C.I., Criswell L.A., Seldin M.F., Kastner D.L., RA Gregersen P.K.; RT "STAT4 and the risk of rheumatoid arthritis and systemic lupus RT erythematosus."; RL N. Engl. J. Med. 357:977-986(2007). RN [17] RP INVOLVEMENT IN DPMC, VARIANTS DPMC TYR-623; VAL-635 AND ASP-650, RP CHARACTERIZATION OF VARIANTS DPMC TYR-623; VAL-635 AND ASP-650, MUTAGENESIS RP OF TYR-693, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=37256972; DOI=10.1056/nejmoa2202318; RA Baghdassarian H., Blackstone S.A., Clay O.S., Philips R., RA Matthiasardottir B., Nehrebecky M., Hua V.K., McVicar R., Liu Y., RA Tucker S.M., Randazzo D., Deuitch N., Rosenzweig S., Mark A., Sasik R., RA Fisch K.M., Pimpale Chavan P., Eren E., Watts N.R., Ma C.A., Gadina M., RA Schwartz D.M., Sanyal A., Werner G., Murdock D.R., Horita N., Chowdhury S., RA Dimmock D., Jepsen K., Remmers E.F., Goldbach-Mansky R., Gahl W.A., RA O'Shea J.J., Milner J.D., Lewis N.E., Chang J., Kastner D.L., Torok K., RA Oda H., Putnam C.D., Broderick L.; RT "Variant STAT4 and Response to Ruxolitinib in an Autoinflammatory RT Syndrome."; RL N. Engl. J. Med. 388:2241-2252(2023). CC -!- FUNCTION: Transcriptional regulator mainly expressed in hematopoietic CC cells that plays a critical role in cellular growth, differentiation CC and immune response (PubMed:8943379, PubMed:10961885, PubMed:37256972). CC Plays a key role in the differentiation of T-helper 1 cells and the CC production of interferon-gamma (PubMed:12213961, PubMed:35614130). CC Participates also in multiple neutrophil functions including chemotaxis CC and production of the neutrophil extracellular traps (By similarity). CC After IL12 binding to its receptor IL12RB2, STAT4 interacts with the CC intracellular domain of IL12RB2 and becomes tyrosine phosphorylated CC (PubMed:7638186, PubMed:10415122). Phosphorylated STAT4 then CC homodimerizes and migrates to the nucleus where it can recognize STAT CC target sequences present in IL12 responsive genes. Although IL12 CC appears to be the predominant activating signal, STAT4 can also be CC phosphorylated and activated in response to IFN-gamma stimulation via CC JAK1 and TYK2 and in response to different interleukins including IL23, CC IL2 and IL35 (PubMed:11114383, PubMed:34508746). Transcription CC activation of IFN-gamma gene is mediated by interaction with JUN that CC forms a complex that efficiently interacts with the AP-1-related CC sequence of the IFN-gamma promoter (By similarity). In response to IFN- CC alpha/beta signaling, acts as a transcriptional repressor and CC suppresses IL5 and IL13 mRNA expression during response to T-cell CC receptor (TCR) activation (PubMed:26990433). CC {ECO:0000250|UniProtKB:P42228, ECO:0000269|PubMed:10415122, CC ECO:0000269|PubMed:10961885, ECO:0000269|PubMed:11114383, CC ECO:0000269|PubMed:12213961, ECO:0000269|PubMed:26990433, CC ECO:0000269|PubMed:34508746, ECO:0000269|PubMed:35614130, CC ECO:0000269|PubMed:37256972, ECO:0000269|PubMed:7638186, CC ECO:0000269|PubMed:8943379}. CC -!- SUBUNIT: Forms a homodimer or a heterodimer with a related family CC member. Interacts with ARL2BP (By similarity). The SH2 domain CC interacts, in vitro, with IL12RB2 via a short cytoplasmic domain. CC Interacts with STAT1 (PubMed:34508746). Interacts with JUN; this CC complex efficiently interacts with the AP-1-related sequence of the CC IFN-gamma (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P42228, CC ECO:0000269|PubMed:10415122, ECO:0000269|PubMed:34508746, CC ECO:0000269|PubMed:9890938}. CC -!- INTERACTION: CC Q14765; O14901: KLF11; NbExp=3; IntAct=EBI-1186538, EBI-948266; CC Q14765; O43504: LAMTOR5; NbExp=2; IntAct=EBI-1186538, EBI-713382; CC Q14765; Q9BVL2: NUP58; NbExp=3; IntAct=EBI-1186538, EBI-2811583; CC Q14765; Q14765: STAT4; NbExp=2; IntAct=EBI-1186538, EBI-1186538; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000269|PubMed:35614130, CC ECO:0000269|PubMed:37256972}. Note=Translocated into the nucleus in CC response to phosphorylation. {ECO:0000269|PubMed:35614130}. CC -!- PTM: Acetylation at Lys-667 is required for JAK2-mediated CC phosphorylation and activation of STAT4. {ECO:0000269|PubMed:35614130}. CC -!- PTM: Tyrosine phosphorylated upon IL12 and IFN-alpha activation, but CC not by IFN-gamma in T-lymphocytes and NK cells (PubMed:8943379). Serine CC phosphorylation is required for maximal transcriptional activity but CC not for DNA binding (PubMed:8943379). Phosphorylation by MAP2K6 at Ser- CC 721 is required for full transcriptional activity induced by IL12 CC (PubMed:10961885). However this serine phosphorylation is not required CC for cell proliferation although critical for IFN-gamma production CC (PubMed:12213961). {ECO:0000269|PubMed:10961885, CC ECO:0000269|PubMed:12213961, ECO:0000269|PubMed:8943379}. CC -!- DISEASE: Systemic lupus erythematosus 11 (SLEB11) [MIM:612253]: A CC chronic, relapsing, inflammatory, and often febrile multisystemic CC disorder of connective tissue, characterized principally by involvement CC of the skin, joints, kidneys and serosal membranes. It is of unknown CC etiology, but is thought to represent a failure of the regulatory CC mechanisms of the autoimmune system. The disease is marked by a wide CC range of system dysfunctions, an elevated erythrocyte sedimentation CC rate, and the formation of LE cells in the blood or bone marrow. CC {ECO:0000269|PubMed:17804842, ECO:0000269|PubMed:19109131}. CC Note=Disease susceptibility is associated with variants affecting the CC gene represented in this entry. CC -!- DISEASE: Rheumatoid arthritis (RA) [MIM:180300]: An inflammatory CC disease with autoimmune features and a complex genetic component. It CC primarily affects the joints and is characterized by inflammatory CC changes in the synovial membranes and articular structures, widespread CC fibrinoid degeneration of the collagen fibers in mesenchymal tissues, CC and by atrophy and rarefaction of bony structures. CC {ECO:0000269|PubMed:17804842}. Note=Disease susceptibility is CC associated with variants affecting the gene represented in this entry. CC -!- DISEASE: Disabling pansclerotic morphea of childhood (DPMC) CC [MIM:620443]: An autosomal dominant, severe systemic inflammatory CC disorder that is part of the juvenile localized scleroderma spectrum. CC DPMC is characterized by poor wound healing with rapidly progressive CC deep fibrosis involving the mucous membranes, dermis, subcutaneous fat, CC fascia, muscles, and bone, leading to contractures, musculoskeletal CC atrophy, and articular ankylosis. Systemic manifestations include CC cytopenias and hypogammaglobulinemia, but scleroderma-associated CC autoantibodies are usually not present. The disorder is associated with CC high morbidity and mortality due to squamous-cell carcinoma, CC restrictive pulmonary disease, sepsis, and gangrene. CC {ECO:0000269|PubMed:37256972}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the transcription factor STAT family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/stat4/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L78440; AAB05605.1; -; mRNA. DR EMBL; BC031212; AAH31212.1; -; mRNA. DR EMBL; AF423072; AAL12164.1; -; Genomic_DNA. DR CCDS; CCDS2310.1; -. DR RefSeq; NP_001230764.1; NM_001243835.1. DR RefSeq; NP_003142.1; NM_003151.3. DR RefSeq; XP_006712782.1; XM_006712719.3. DR RefSeq; XP_011510007.1; XM_011511705.2. DR AlphaFoldDB; Q14765; -. DR BMRB; Q14765; -. DR SMR; Q14765; -. DR BioGRID; 112652; 30. DR ComplexPortal; CPX-6042; STAT1/STAT4 complex. DR ComplexPortal; CPX-6046; STAT3/STAT4 complex. DR ComplexPortal; CPX-6050; STAT4 homodimer. DR DIP; DIP-39854N; -. DR IntAct; Q14765; 41. DR MINT; Q14765; -. DR STRING; 9606.ENSP00000351255; -. DR BindingDB; Q14765; -. DR ChEMBL; CHEMBL4523296; -. DR GlyCosmos; Q14765; 3 sites, 1 glycan. DR GlyGen; Q14765; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; Q14765; -. DR PhosphoSitePlus; Q14765; -. DR BioMuta; STAT4; -. DR DMDM; 6226158; -. DR CPTAC; CPTAC-1277; -. DR EPD; Q14765; -. DR jPOST; Q14765; -. DR MassIVE; Q14765; -. DR PaxDb; 9606-ENSP00000376134; -. DR PeptideAtlas; Q14765; -. DR ProteomicsDB; 60158; -. DR Antibodypedia; 661; 1314 antibodies from 47 providers. DR DNASU; 6775; -. DR Ensembl; ENST00000358470.8; ENSP00000351255.4; ENSG00000138378.19. DR Ensembl; ENST00000392320.7; ENSP00000376134.2; ENSG00000138378.19. DR GeneID; 6775; -. DR KEGG; hsa:6775; -. DR MANE-Select; ENST00000392320.7; ENSP00000376134.2; NM_003151.4; NP_003142.1. DR UCSC; uc002usm.3; human. DR AGR; HGNC:11365; -. DR CTD; 6775; -. DR DisGeNET; 6775; -. DR GeneCards; STAT4; -. DR HGNC; HGNC:11365; STAT4. DR HPA; ENSG00000138378; Tissue enhanced (testis). DR MalaCards; STAT4; -. DR MIM; 180300; phenotype. DR MIM; 600558; gene. DR MIM; 612253; phenotype. DR MIM; 620443; phenotype. DR neXtProt; NX_Q14765; -. DR OpenTargets; ENSG00000138378; -. DR Orphanet; 117; Behcet disease. DR Orphanet; 85410; Oligoarticular juvenile idiopathic arthritis. DR Orphanet; 93552; Pediatric systemic lupus erythematosus. DR Orphanet; 85408; Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis. DR Orphanet; 536; Systemic lupus erythematosus. DR PharmGKB; PA36185; -. DR VEuPathDB; HostDB:ENSG00000138378; -. DR eggNOG; KOG3667; Eukaryota. DR GeneTree; ENSGT01050000244905; -. DR HOGENOM; CLU_014189_3_0_1; -. DR InParanoid; Q14765; -. DR OMA; EGSHMVT; -. DR OrthoDB; 7823at2759; -. DR PhylomeDB; Q14765; -. DR TreeFam; TF318648; -. DR PathwayCommons; Q14765; -. DR Reactome; R-HSA-8854691; Interleukin-20 family signaling. DR Reactome; R-HSA-8950505; Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation. DR Reactome; R-HSA-8984722; Interleukin-35 Signalling. DR Reactome; R-HSA-9020591; Interleukin-12 signaling. DR Reactome; R-HSA-9020933; Interleukin-23 signaling. DR Reactome; R-HSA-9020958; Interleukin-21 signaling. DR SignaLink; Q14765; -. DR SIGNOR; Q14765; -. DR BioGRID-ORCS; 6775; 12 hits in 1179 CRISPR screens. DR ChiTaRS; STAT4; human. DR GeneWiki; STAT4; -. DR GenomeRNAi; 6775; -. DR Pharos; Q14765; Tchem. DR PRO; PR:Q14765; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q14765; Protein. DR Bgee; ENSG00000138378; Expressed in granulocyte and 123 other cell types or tissues. DR ExpressionAtlas; Q14765; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProt. DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IPI:ComplexPortal. DR GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:ProtInc. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central. DR GO; GO:0006952; P:defense response; IBA:GO_Central. DR GO; GO:0035722; P:interleukin-12-mediated signaling pathway; IDA:UniProt. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IBA:GO_Central. DR GO; GO:0042127; P:regulation of cell population proliferation; IBA:GO_Central. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0043434; P:response to peptide hormone; IBA:GO_Central. DR GO; GO:0045063; P:T-helper 1 cell differentiation; IDA:UniProt. DR CDD; cd10375; SH2_STAT4; 1. DR CDD; cd16854; STAT4_CCD; 1. DR CDD; cd16848; STAT4_DBD; 1. DR Gene3D; 1.10.238.10; EF-hand; 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR Gene3D; 1.20.1050.20; STAT transcription factor, all-alpha domain; 1. DR Gene3D; 2.60.40.630; STAT transcription factor, DNA-binding domain; 1. DR Gene3D; 1.10.532.10; STAT transcription factor, N-terminal domain; 1. DR InterPro; IPR008967; p53-like_TF_DNA-bd_sf. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR001217; STAT. DR InterPro; IPR046991; STAT4_CCD. DR InterPro; IPR029839; STAT4_DBD. DR InterPro; IPR035856; STAT4_SH2. DR InterPro; IPR048988; STAT_linker. DR InterPro; IPR036535; STAT_N_sf. DR InterPro; IPR013800; STAT_TF_alpha. DR InterPro; IPR015988; STAT_TF_coiled-coil. DR InterPro; IPR013801; STAT_TF_DNA-bd. DR InterPro; IPR012345; STAT_TF_DNA-bd_N. DR InterPro; IPR013799; STAT_TF_prot_interaction. DR PANTHER; PTHR11801; SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION; 1. DR PANTHER; PTHR11801:SF19; SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 4; 1. DR Pfam; PF00017; SH2; 1. DR Pfam; PF01017; STAT_alpha; 1. DR Pfam; PF02864; STAT_bind; 1. DR Pfam; PF02865; STAT_int; 1. DR Pfam; PF21354; STAT_linker; 1. DR SMART; SM00964; STAT_int; 1. DR SUPFAM; SSF49417; p53-like transcription factors; 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR SUPFAM; SSF47655; STAT; 1. DR SUPFAM; SSF48092; Transcription factor STAT-4 N-domain; 1. DR PROSITE; PS50001; SH2; 1. DR Genevisible; Q14765; HS. PE 1: Evidence at protein level; KW Acetylation; Activator; Cytoplasm; Disease variant; DNA-binding; Nucleus; KW Phosphoprotein; Reference proteome; SH2 domain; KW Systemic lupus erythematosus; Transcription; Transcription regulation. FT CHAIN 1..748 FT /note="Signal transducer and activator of transcription 4" FT /id="PRO_0000182420" FT DOMAIN 569..664 FT /note="SH2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT MOD_RES 667 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:35614130" FT MOD_RES 693 FT /note="Phosphotyrosine; by JAK" FT /evidence="ECO:0000269|PubMed:10961885" FT MOD_RES 721 FT /note="Phosphoserine; by MAP2K6" FT /evidence="ECO:0000269|PubMed:10961885" FT VARIANT 112 FT /note="E -> Q (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036002" FT VARIANT 115 FT /note="I -> V (in dbSNP:rs3024839)" FT /id="VAR_020190" FT VARIANT 584 FT /note="R -> W (in dbSNP:rs3024933)" FT /id="VAR_047939" FT VARIANT 623 FT /note="H -> Y (in DPMC; likely pathogenic; increased FT function in receptor signaling pathway via JAK-STAT)" FT /evidence="ECO:0000269|PubMed:37256972" FT /id="VAR_088806" FT VARIANT 635 FT /note="A -> V (in DPMC; likely pathogenic; increased FT function in receptor signaling pathway via JAK-STAT)" FT /evidence="ECO:0000269|PubMed:37256972" FT /id="VAR_088807" FT VARIANT 650 FT /note="A -> D (in DPMC; likely pathogenic; increased FT function in receptor signaling pathway via JAK-STAT)" FT /evidence="ECO:0000269|PubMed:37256972" FT /id="VAR_088808" FT MUTAGEN 693 FT /note="Y->A: Abrogates phosphorylation and transcriptional FT activity." FT /evidence="ECO:0000269|PubMed:10961885, FT ECO:0000269|PubMed:37256972" FT MUTAGEN 721 FT /note="S->A: About 50% loss of transcriptional activity." FT /evidence="ECO:0000269|PubMed:10961885" FT CONFLICT 365..371 FT /note="KNVSTLS -> N (in Ref. 3; AAL12164)" FT /evidence="ECO:0000305" SQ SEQUENCE 748 AA; 85941 MW; 11E43803A9AF4FFA CRC64; MSQWNQVQQL EIKFLEQVDQ FYDDNFPMEI RHLLAQWIEN QDWEAASNNE TMATILLQNL LIQLDEQLGR VSKEKNLLLI HNLKRIRKVL QGKFHGNPMH VAVVISNCLR EERRILAAAN MPVQGPLEKS LQSSSVSERQ RNVEHKVAAI KNSVQMTEQD TKYLEDLQDE FDYRYKTIQT MDQSDKNSAM VNQEVLTLQE MLNSLDFKRK EALSKMTQII HETDLLMNTM LIEELQDWKR RQQIACIGGP LHNGLDQLQN CFTLLAESLF QLRRQLEKLE EQSTKMTYEG DPIPMQRTHM LERVTFLIYN LFKNSFVVER QPCMPTHPQR PLVLKTLIQF TVKLRLLIKL PELNYQVKVK ASIDKNVSTL SNRRFVLCGT NVKAMSIEES SNGSLSVEFR HLQPKEMKSS AGGKGNEGCH MVTEELHSIT FETQICLYGL TIDLETSSLP VVMISNVSQL PNAWASIIWY NVSTNDSQNL VFFNNPPPAT LSQLLEVMSW QFSSYVGRGL NSDQLHMLAE KLTVQSSYSD GHLTWAKFCK EHLPGKSFTF WTWLEAILDL IKKHILPLWI DGYVMGFVSK EKERLLLKDK MPGTFLLRFS ESHLGGITFT WVDHSESGEV RFHSVEPYNK GRLSALPFAD ILRDYKVIMA ENIPENPLKY LYPDIPKDKA FGKHYSSQPC EVSRPTERGD KGYVPSVFIP ISTIRSDSTE PHSPSDLLPM SPSVYAVLRE NLSPTTIETA MKSPYSAE //