别名:Amphoterin,Heparin-binding protein p30,High mobility group protein 1,HMG-1,Hmg-1,Hmg1
序列号:P63159
来源:E.coli
种属:Rat
标签:His
序列:1-120aa
预估分子量:13.2 kDa (monomer)
纯度:Greater than 90% by SDS-PAGE
浓度:Reconstitution Dependent
研究领域:RNA Binding Protein(RBP)
形态:Liquid
应用:ELISA、Western Blot、Antigen Protein
存储缓冲液:50mM NaH2PO4, 500mM NaCl Buffer with 500mM Imidazole, 10%glycerol(PH8.0)
存储:Store at -20°C. (Avoid repeated freezing and thawing.)
研究领域:RNA Binding Protein(RBP)
通用注释
亚单元:Interacts (fully reduced HMGB1) with CXCL12; probably in a 1:2 ratio involving two molecules of CXCL12, each interacting with one HMG box of HMGB1; inhibited by glycyrrhizin (PubMed:22869893). Associates with the TLR4:LY96 receptor complex (PubMed:20547845). Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2 (By similarity). Interacts (in cytoplasm upon starvation) with BECN1; inhibits the interaction of BECN1 and BCL2 leading to promotion of autophagy (PubMed:20819940). Interacts with KPNA1; involved in nuclear import (By similarity). Interacts with AGER (PubMed:12183440). Interacts with PTPRZ1 isoform 3/phosphacan (PubMed:9507007). Interacts with SREBF1, TLR2, TLR4, TLR9, APEX1, FEN1, POLB, TERT, IL1B, MSH2, XPA, XPC, HNF1A, TP53 (By similarity). Interacts with CD24; the probable CD24:SIGLEC10 complex is proposed to inhibit HGMB1-mediated tissue damage immune response. Interacts with THBD; prevents HGMB1 interaction with ACER/RAGE and inhibits HGMB1 proinflammatory activity. Interacts with HAVCR2; impairs HMGB1 binding to B-DNA and likely HMGB1-mediated innate immume response (By similarity). Interacts with XPO1; mediating nuclear export (PubMed:14532127).
功能:In the extracellular compartment (following either active secretion or passive release) involved in regulation of the inflammatory response. Fully reduced HGMB1 (which subsequently gets oxidized after release) in association with CXCL12 mediates the recruitment of inflammatory cells during the initial phase of tissue injury; the CXCL12:HMGB1 complex triggers CXCR4 homodimerization (PubMed:22869893). Induces the migration of monocyte-derived immature dendritic cells and seems to regulate adhesive and migratory functions of neutrophils implicating AGER/RAGE and ITGAM (By similarity). Can bind to various types of DNA and RNA including microbial unmethylated CpG-DNA to enhance the innate immune response to nucleic acids. Proposed to act in promiscuous DNA/RNA sensing which cooperates with subsequent discriminative sensing by specific pattern recognition receptors. Promotes extracellular DNA-induced AIM2 inflammasome activation implicating AGER/RAGE (By similarity). Disulfide HMGB1 binds to transmembrane receptors, such as AGER/RAGE, TLR2, TLR4 and probably TREM1, thus activating their signal transduction pathways. Mediates the release of cytokines/chemokines such as TNF, IL-1, IL-6, IL-8, CCL2, CCL3, CCL4 and CXCL10 (PubMed:10952726, PubMed:20547845, PubMed:22869893). Promotes secretion of interferon-gamma by macrophage-stimulated natural killer (NK) cells in concert with other cytokines like IL-2 or IL-12. TLR4 is proposed to be the primary receptor promoting macrophage activation and signaling through TLR4 seems to implicate LY96/MD-2 (By similarity). In bacterial LPS- or LTA-mediated inflammatory responses binds to the endotoxins and transfers them to CD14 for signaling to the respective TLR4:LY96 and TLR2 complexes (PubMed:23508573). Contributes to tumor proliferation by association with ACER/RAGE (PubMed:10830965). Can bind to IL1-beta and signals through the IL1R1:IL1RAP receptor complex (By similarity). Binding to class A CpG activates cytokine production in plasmacytoid dendritic cells implicating TLR9, MYD88 and AGER/RAGE and can activate autoreactive B cells (By similarity). Via HMGB1-containing chromatin immune complexes may also promote B cell responses to endogenous TLR9 ligands through a B-cell receptor (BCR)-dependent and ACER/RAGE-independent mechanism (By similarity). Inhibits phagocytosis of apoptotic cells by macrophages; the function is dependent on poly-ADP-ribosylation and involves binding to phosphatidylserine on the cell surface of apoptotic cells (By similarity). In adaptive immunity may be involved in enhancing immunity through activation of effector T-cells and suppression of regulatory T (TReg) cells (By similarity). In contrast, without implicating effector or regulatory T-cells, required for tumor infiltration and activation of T-cells expressing the lymphotoxin LTA:LTB heterotrimer thus promoting tumor malignant progression (By similarity). Also reported to limit proliferation of T-cells (PubMed:18277947). Released HMGB1:nucleosome complexes formed during apoptosis can signal through TLR2 to induce cytokine production. Involved in induction of immunological tolerance by apoptotic cells; its pro-inflammatory activities when released by apoptotic cells are neutralized by reactive oxygen species (ROS)-dependent oxidation specifically on Cys-106 (By similarity). During macrophage activation by activated lymphocyte-derived self apoptotic DNA (ALD-DNA) promotes recruitment of ALD-DNA to endosomes.
亚细胞位置: Nucleus Cytoplasm Secreted Chromosome Cell membrane Peripheral membrane protein Extracellular side Endosome Endoplasmic reticulum-Golgi intermediate compartment In basal state predominantly nuclear. Shuttles between the cytoplasm and the nucleus. Nuclear export is in part XPO1-dependent implicating NES contained in both HMG boxes 1 and 2 (PubMed:14532127). Release from macrophages in the extracellular milieu requires the activation of NLRC4 or NLRP3 inflammasomes (By similarity). Passively released to the extracellular milieu from necrotic cells by diffusion, involving the fully reduced form which subsequently gets oxidized (PubMed:22869893). Actively secreted from a variety of immune and non-immune cells such as macrophages, monocytes, neutrophils, dendritic cells and natural killer cells in response to various stimuli, involving a nonconventional secretory process via secretory lysosomes. Secreted by plasma cells in response to LPS (By similarity). Associated with the plasma membrane of filipodia in process-growing cells, and also deposited into the substrate-attached material (PubMed:1885601).
文献
1. Ethyl pyruvate protects against experimental acute-on-chronic liver failure in rats
Auth: Lu-Wen Wang, Li-Kun Wang, Hui Chen, Cheng Fan, Xun Li, Can-Ming He, and Zuo-Jiong Gong
From: World J Gastroenterol
2. Ethyl pyruvate prevents inflammatory factors release and decreases intestinal permeability in rats with D-galactosamine-induced acute liver failure
Auth: LK Wang, LW Wang, X Li, et al.
From: Hepatobiliary & Pancreatic Diseases International
3. Severity of sepsis correlated with the elevation of serum high-mobility group box 1 in rats
Auth: LC Hou, MZ Qin, LN Zheng, et al.
From: Chinese Medical Journal
4. High mobility group box 1 protein released in the course of aseptic necrosis of tissues sensitizes rats to pyrogenic effects of lipopolysaccharide
Auth: J Piotrowski, M Pawlikowska, S Wrotek, et al.
From: Journal of Thermal Biology