Protein: High mobility group protein B1 (Amphoterin) (Heparin-binding protein p30) (High mobility group protein 1) (HMG-1) (P63159)
Organism: Rattus norvegicus (Rat)
Function: Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone involved in replication, transcription, chromatin remodeling, V(D)J recombination, DNA repair and genome stability. Proposed to be an universal biosensor for nucleic acids. Promotes host inflammatory response to sterile and infectious signals and is involved in the coordination and integration of innate and adaptive immune responses. In the cytoplasm functions as sensor and/or chaperone for immunogenic nucleic acids implicating the activation of TLR9-mediated immune responses, and mediates autophagy. Acts as danger associated molecular pattern (DAMP) molecule that amplifies immune responses during tissue injury. Released to the extracellular environment can bind DNA, nucleosomes, IL-1 beta, CXCL12, AGER isoform 2/sRAGE, lipopolysaccharide (LPS) and lipoteichoic acid (LTA), and activates cells through engagement of multiple surface receptors. In the extracellular compartment fully reduced HMGB1 (released by necrosis) acts as a chemokine, disulfide HMGB1 (actively secreted) as a cytokine, and sulfonyl HMGB1 (released from apoptotic cells) promotes immunological tolerance. Has proangiogenic activity. May be involved in platelet activation. Binds to phosphatidylserine and phosphatidylethanolamide. Bound to RAGE mediates signaling for neuronal outgrowth. May play a role in accumulation of expanded polyglutamine (polyQ) proteins.
Subcellular location: Nucleus {ECO:0000269|PubMed:22869893}. Cytoplasm {ECO:0000269|PubMed:22869893}. Secreted {ECO:0000269|PubMed:1885601, ECO:0000269|PubMed:22869893}. Chromosome {ECO:0000269|PubMed:12110890, ECO:0000269|PubMed:15808513}. Cell membrane {ECO:0000269|PubMed:1885601, ECO:0000269|PubMed:2461949}; Peripheral membrane protein {ECO:0000269|PubMed:1885601, ECO:0000269|PubMed:2461949}; Extracellular side {ECO:0000269|PubMed:2461949}. Endosome {ECO:0000250|UniProtKB:P63158}. Endoplasmic reticulum-Golgi intermediate compartment {ECO:0000250|UniProtKB:P63158}. Note=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). {ECO:0000250|UniProtKB:P63158, ECO:0000269|PubMed:14532127, ECO:0000269|PubMed:15808513, ECO:0000269|PubMed:1885601, ECO:0000269|PubMed:22869893}.
Sequence: MGKGDPKKPRGKMSSYAFFVQTCREEHKKKHPDASVNFSEFSKKCSERWKTMSAKEKGKFEDMAKADKARYEREMKTYIPPKGETKKKFKDPNAPKRPPSAFFLFCSEYRPKIKGEHPGLSIGDVAKKLGEMWNNTAADDKQPYEKKAAKLKEKYEKDIAAYRAKGKPDAAKKGVVKAEKSKKKKEEEDDEEDEEDEEEEEEEEDEDEEEDDDDE
InterPro domains: - IPR050342: High Mobility Group Box (HMGB) (family) [2-208]
- IPR036910: High mobility group box domain superfamily (homologous_superfamily) [1-166]
- IPR017967: HMG box A DNA-binding domain, conserved site (conserved_site) [41-52]
- IPR009071: High mobility group box domain (domain) [6-164]
Interaction partners: - Toll-like receptor 4
- Toll-like receptor 2
- Toll-like receptor 9
- Beclin-1
- Advanced glycosylation end product-specific receptor
- High mobility group box 1 like 5
- Signal transducer CD24
- Hepatitis A virus cellular receptor 2 homolog
- Toll-like receptor 5
- Sialic acid binding Ig-like lectin 10
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0097159 (organic cyclic compound binding), GO:1901363 (heterocyclic compound binding), GO:0008289 (lipid binding), GO:0003676 (nucleic acid binding), GO:0003677 (DNA binding), GO:0003690 (double-stranded DNA binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0032502 (developmental process), GO:0032501 (multicellular organismal process), GO:0048856 (anatomical structure development), GO:0007275 (multicellular organism development), GO:0048522 (positive regulation of cellular process), GO:0019222 (regulation of metabolic process), GO:0050794 (regulation of cellular process), GO:0009893 (positive regulation of metabolic process), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0031325 (positive regulation of cellular metabolic process), GO:0048731 (system development), GO:0048513 (animal organ development), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0080090 (regulation of primary metabolic process), GO:0031099 (regeneration), GO:0009891 (positive regulation of biosynthetic process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0031100 (animal organ regeneration), GO:0010557 (positive regulation of macromolecule biosynthetic process), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0051254 (positive regulation of RNA metabolic process), GO:0007399 (nervous system development), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0051054 (positive regulation of DNA metabolic process), GO:0051052 (regulation of DNA metabolic process), GO:0031326 (regulation of cellular biosynthetic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0051252 (regulation of RNA metabolic process), GO:0031328 (positive regulation of cellular biosynthetic process), GO:0010468 (regulation of gene expression), GO:1902680 (positive regulation of RNA biosynthetic process), GO:2001141 (regulation of RNA biosynthetic process), GO:0006355 (regulation of DNA-templated transcription), GO:0045893 (positive regulation of DNA-templated transcription), GO:1903508 (positive regulation of nucleic acid-templated transcription), GO:1903506 (regulation of nucleic acid-templated transcription)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0042995 (cell projection), GO:0044297 (cell body), GO:0005615 (extracellular space), GO:0036477 (somatodendritic compartment), GO:0048471 (perinuclear region of cytoplasm), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0005576 (extracellular region), GO:0043025 (neuronal cell body), GO:0030141 (secretory granule), GO:0120025 (plasma membrane bounded cell projection), GO:0031410 (cytoplasmic vesicle), GO:0097447 (dendritic tree), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043005 (neuron projection), GO:0099503 (secretory vesicle), GO:0043231 (intracellular membrane-bounded organelle), GO:0031982 (vesicle), GO:0030425 (dendrite), GO:0097708 (intracellular vesicle), GO:0005634 (nucleus)