Search Results

Overview

Uniprot IDP42224
Protein NameSignal transducer and activator of transcription 1-alpha/beta
Gene NameSTAT1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
110 MIIYSCLKEERKILE
138 QSTVMLDKQKELDSK
152 KVRNVKDKVMCIEHE
193 GVAKSDQKQEQLLLK
201 QEQLLLKKMYLMLDN
296 YEHDPITKNKQVLWD
379 NTVKGFRKFNILGTH
410 EFRHLQLKEQKNAGT
413 HLQLKEQKNAGTRTN
637 AVEPYTKKELSAVTF
652 PDIIRNYKVMAAENI
685 GKYYSRPKEAPEPME
697 PMELDGPKGTGYIKT
703 PKGTGYIKTELISVS

Function

Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors (PubMed:12764129, PubMed:12855578, PubMed:15322115, PubMed:23940278, PubMed:34508746, PubMed:35568036, PubMed:9724754, PubMed:32814877). Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors, signaling via protein kinases leads to activation of Jak kinases (TYK2 and JAK1) and to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize and associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus (PubMed:28753426, PubMed:35568036). ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of IFN-stimulated genes (ISG), which drive the cell in an antiviral state (PubMed:28753426, PubMed:35568036). In response to type II IFN (IFN-gamma), STAT1 is tyrosine- and serine-phosphorylated (PubMed:26479788). It then forms a homodimer termed IFN-gamma-activated factor (GAF), migrates into the nucleus and binds to the IFN gamma activated sequence (GAS) to drive the expression of the target genes, inducing a cellular antiviral state (PubMed:8156998). Becomes activated in response to KITLG/SCF and KIT signaling (PubMed:15526160). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:19088846). Following bacterial lipopolysaccharide (LPS)-induced TLR4 endocytosis, phosphorylated at Thr-749 by IKBKB which promotes binding of STAT1 to the 5'-TTTGAGGC-3' sequence in the ARID5A promoter, resulting in transcriptional activation of ARID5A and subsequent ARID5A-mediated stabilization of IL6 (PubMed:32209697). Phosphorylation at Thr-749 also promotes binding of STAT1 to the 5'-TTTGAGTC-3' sequence in the IL12B promoter and activation of IL12B transcription (PubMed:32209697). Involved in food tolerance in small intestine: associates with the Gasdermin-D, p13 cleavage product (13 kDa GSDMD) and promotes transcription of CIITA, inducing type 1 regulatory T (Tr1) cells in upper small intestine (By similarity)

Protein Sequence

10 MSQWYELQQL 20 DSKFLEQVHQ 30 LYDDSFPMEI 40 RQYLAQWLEK 50 QDWEHAANDV 60 SFATIRFHDL 70 LSQLDDQYSR 80 FSLENNFLLQ 90 HNIRKSKRNL 100 QDNFQEDPIQ 110 MSMIIYSCLK 120 EERKILENAQ 130 RFNQAQSGNI 140 QSTVMLDKQK 150 ELDSKVRNVK 160 DKVMCIEHEI 170 KSLEDLQDEY 180 DFKCKTLQNR 190 EHETNGVAKS 200 DQKQEQLLLK 210 KMYLMLDNKR 220 KEVVHKIIEL 230 LNVTELTQNA 240 LINDELVEWK 250 RRQQSACIGG 260 PPNACLDQLQ 270 NWFTIVAESL 280 QQVRQQLKKL 290 EELEQKYTYE 300 HDPITKNKQV 310 LWDRTFSLFQ 320 QLIQSSFVVE 330 RQPCMPTHPQ 340 RPLVLKTGVQ 350 FTVKLRLLVK 360 LQELNYNLKV 370 KVLFDKDVNE 380 RNTVKGFRKF 390 NILGTHTKVM 400 NMEESTNGSL 410 AAEFRHLQLK 420 EQKNAGTRTN 430 EGPLIVTEEL 440 HSLSFETQLC 450 QPGLVIDLET 460 TSLPVVVISN 470 VSQLPSGWAS 480 ILWYNMLVAE 490 PRNLSFFLTP 500 PCARWAQLSE 510 VLSWQFSSVT 520 KRGLNVDQLN 530 MLGEKLLGPN 540 ASPDGLIPWT 550 RFCKENINDK 560 NFPFWLWIES 570 ILELIKKHLL 580 PLWNDGCIMG 590 FISKERERAL 600 LKDQQPGTFL 610 LRFSESSREG 620 AITFTWVERS 630 QNGGEPDFHA 640 VEPYTKKELS 650 AVTFPDIIRN 660 YKVMAAENIP 670 ENPLKYLYPN 680 IDKDHAFGKY 690 YSRPKEAPEP 700 MELDGPKGTG 710 YIKTELISVS 720 EVHPSRLQTT 730 DNLLPMSPEE 740 FDEVSRIVGS 750 VEFDSMMNTV

Gene Ontology

Classification GO ID Description
Cellular Component GO:0000785 chromatin
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0070721 ISGF3 complex
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0048471 perinuclear region of cytoplasm
Cellular Component GO:0032991 protein-containing complex
Molecular Function GO:0045296 cadherin binding
Molecular Function GO:0003700 DNA-binding transcription factor activity
Molecular Function GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
Molecular Function GO:0003690 double-stranded DNA binding
Molecular Function GO:0019899 enzyme binding
Molecular Function GO:0035035 histone acetyltransferase binding
Molecular Function GO:0042393 histone binding
Molecular Function GO:0042802 identical protein binding
Molecular Function GO:1990841 promoter-specific chromatin binding
Molecular Function GO:0042803 protein homodimerization activity
Molecular Function GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
Molecular Function GO:0000979 RNA polymerase II core promoter sequence-specific DNA binding
Molecular Function GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding
Molecular Function GO:0001223 transcription coactivator binding
Molecular Function GO:0001222 transcription corepressor binding
Molecular Function GO:0005164 tumor necrosis factor receptor binding
Molecular Function GO:0044389 ubiquitin-like protein ligase binding
Biological Process GO:0007259 cell surface receptor signaling pathway via JAK-STAT
Biological Process GO:0097696 cell surface receptor signaling pathway via STAT
Biological Process GO:0035458 cellular response to interferon-beta
Biological Process GO:0071346 cellular response to type II interferon
Biological Process GO:0006952 defense response
Biological Process GO:0051607 defense response to virus
Biological Process GO:0006351 DNA-templated transcription
Biological Process GO:0070106 interleukin-27-mediated signaling pathway
Biological Process GO:0038111 interleukin-7-mediated signaling pathway
Biological Process GO:0038113 interleukin-9-mediated signaling pathway
Biological Process GO:0072162 metanephric mesenchymal cell differentiation
Biological Process GO:0072136 metanephric mesenchymal cell proliferation involved in metanephros development
Biological Process GO:0046725 negative regulation by virus of viral protein levels in host cell
Biological Process GO:0016525 negative regulation of angiogenesis
Biological Process GO:0043124 negative regulation of canonical NF-kappaB signal transduction
Biological Process GO:0001937 negative regulation of endothelial cell proliferation
Biological Process GO:0003340 negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis
Biological Process GO:0072308 negative regulation of metanephric nephron tubule epithelial cell differentiation
Biological Process GO:0000122 negative regulation of transcription by RNA polymerase II
Biological Process GO:0002230 positive regulation of defense response to virus by host
Biological Process GO:0045893 positive regulation of DNA-templated transcription
Biological Process GO:0045648 positive regulation of erythrocyte differentiation
Biological Process GO:0032727 positive regulation of interferon-alpha production
Biological Process GO:0002053 positive regulation of mesenchymal cell proliferation
Biological Process GO:0045944 positive regulation of transcription by RNA polymerase II
Biological Process GO:0042981 regulation of apoptotic process
Biological Process GO:0042127 regulation of cell population proliferation
Biological Process GO:0006357 regulation of transcription by RNA polymerase II
Biological Process GO:0061326 renal tubule development
Biological Process GO:0035456 response to interferon-beta
Biological Process GO:0043434 response to peptide hormone
Biological Process GO:0034341 response to type II interferon
Biological Process GO:0033209 tumor necrosis factor-mediated signaling pathway
Biological Process GO:0060337 type I interferon-mediated signaling pathway
Biological Process GO:0060333 type II interferon-mediated signaling pathway

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[3] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[4] Lin Y, Chen M, Wang D, Yu Y, Chen R et al.. Multi-Proteomic Analysis Reveals the Effect of Protein Lactylation on Matrix and Cholesterol Metabolism in Tendinopathy.. J Proteome Res 22(6):1712-1722. 2023 Jun 2. PMID: 37159428.

[5] Yang YH, Wang QC, Kong J, Yang JT, Liu JF. Global profiling of lysine lactylation in human lungs.. Proteomics 23(15):e2200437. 2023 Aug. PMID: 37170646.

[6] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[7] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.

[8] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[9] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.