Protein: High mobility group protein B1 (High mobility group protein 1) (HMG-1) (P09429)
Organism: Homo sapiens (Human)
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 proangiogdenic activity (By similarity). May be involved in platelet activation (By similarity). Binds to phosphatidylserine and phosphatidylethanolamide (By similarity). Bound to RAGE mediates signaling for neuronal outgrowth (By similarity). May play a role in accumulation of expanded polyglutamine (polyQ) proteins such as huntingtin (HTT) or TBP.
Subcellular location: Nucleus {ECO:0000269|PubMed:12231511, ECO:0000269|PubMed:17114460, ECO:0000269|PubMed:20819940, ECO:0000269|PubMed:22696656, ECO:0000269|PubMed:22869893, ECO:0000269|PubMed:27362237, ECO:0000269|PubMed:29618516, ECO:0000269|PubMed:33147444}. Chromosome {ECO:0000250|UniProtKB:P10103, ECO:0000250|UniProtKB:P63159, ECO:0000305}. Cytoplasm {ECO:0000269|PubMed:11154118, ECO:0000269|PubMed:12231511, ECO:0000269|PubMed:17114460, ECO:0000269|PubMed:20819940, ECO:0000269|PubMed:22869893, ECO:0000269|PubMed:29618516, ECO:0000269|PubMed:33147444, ECO:0000269|PubMed:34971702}. Secreted {ECO:0000250|UniProtKB:P63158, ECO:0000269|PubMed:12231511, ECO:0000269|PubMed:14532127, ECO:0000269|PubMed:15944249, ECO:0000269|PubMed:19811284, ECO:0000269|PubMed:22869893, ECO:0000269|PubMed:33147444}. Cell membrane {ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:11154118}; Peripheral membrane protein {ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:11154118}; Extracellular side {ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:11154118}. 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 (PubMed:12231511, PubMed:17114460). Translocates from the nucleus to the cytoplasm upon autophagy stimulation (PubMed:20819940). 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 HGMB1 which subsequently gets oxidized (PubMed:19811284). Also released from apoptotic cells (PubMed:16855214, PubMed:18631454). Active secretion 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 such as LPS and cytokines involves a nonconventional secretory process via secretory lysosomes (PubMed:12231511, PubMed:14532127, PubMed:15944249). Secreted by plasma cells in response to LPS (By similarity). Found on the surface of activated platelets (PubMed:11154118). An increased chromatin association is observed when associated with the adenovirus protein pVII (PubMed:27362237). {ECO:0000250|UniProtKB:P63158, ECO:0000269|PubMed:11154118, ECO:0000269|PubMed:12231511, ECO:0000269|PubMed:14532127, ECO:0000269|PubMed:15944249, ECO:0000269|PubMed:16855214, ECO:0000269|PubMed:17114460, ECO:0000269|PubMed:18631454, ECO:0000269|PubMed:19811284, ECO:0000269|PubMed:20819940, ECO:0000269|PubMed:27362237, ECO:0000305|PubMed:20123072}.; SUBCELLULAR LOCATION: Endoplasmic reticulum {ECO:0000269|PubMed:35239449}. Note=(Microbial infection) SARS-COV-2 ORF3A promotes HMGB1 translocation from the nucleus to the cytoplasm where it is recruited by and colocalizes with ORF3A at the endoplasmic reticulum. {ECO:0000269|PubMed:35239449}.
Interaction partners:
- Advanced glycosylation end product-specific receptor
- Toll-like receptor 4
- Beclin-1
- Toll-like receptor 2
- Toll-like receptor 9
- Cellular tumor antigen p53
- Signal transducer CD24
- Hepatitis A virus cellular receptor 2
- Stromal cell-derived factor 1
- High mobility group protein B2
Sequence:
MGKGDPKKPRGKMSSYAFFVQTCREEHKKKHPDASVNFSEFSKKCSERWKTMSAKEKGKFEDMAKADKARYEREMKTYIPPKGETKKKFKDPNAPKRPPSAFFLFCSEYRPKIKGEHPGLSIGDVAKKLGEMWNNTAADDKQPYEKKAAKLKEKYEKDIAAYRAKGKPDAAKKGVVKAEKSKKKKEEEEDEEDEEDEEEEEDEEDEDEEEDDDDE