======= HMGB1 =======
== Gene Information ==
* **Official Symbol**: HMGB1
* **Official Name**: high mobility group box 1
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=3146|3146]]
* **UniProt**: [[https://www.uniprot.org/uniprot/P09429|P09429]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=HMGB1&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20HMGB1|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/163905|Open OMIM]]
== Function Summary ==
* **Entrez Summary**: N/A
* **UniProt Summary**: 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 (PubMed:27362237). 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 (PubMed:23519706, PubMed:23446148, PubMed:23994764, PubMed:25048472). 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 (PubMed:23303669, PubMed:25549101). {ECO:0000250|UniProtKB:P10103, ECO:0000250|UniProtKB:P12682, ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:23303669, ECO:0000269|PubMed:25549101, ECO:0000269|PubMed:27362237, ECO:0000305|PubMed:23446148, ECO:0000305|PubMed:23519706, ECO:0000305|PubMed:23994764, ECO:0000305|PubMed:25048472}. In the cytoplasm proposed to dissociate the BECN1:BCL2 complex via competitive interaction with BECN1 leading to autophagy activation (PubMed:20819940). Involved in oxidative stress-mediated autophagy (PubMed:21395369). Can protect BECN1 and ATG5 from calpain-mediated cleavage and thus proposed to control their proautophagic and proapoptotic functions and to regulate the extent and severity of inflammation-associated cellular injury (By similarity). In myeloid cells has a protective role against endotoxemia and bacterial infection by promoting autophagy (By similarity). Involved in endosomal translocation and activation of TLR9 in response to CpG-DNA in macrophages (By similarity). {ECO:0000250|UniProtKB:P63158, ECO:0000269|PubMed:20819940, ECO:0000269|PubMed:21395369}.
|HMG box|
|regulation of restriction endodeoxyribonuclease activity|
|negative regulation of RNA polymerase II transcriptional preinitiation complex assembly|
|negative regulation of apoptotic cell clearance|
|regulation of T cell mediated immune response to tumor cell|
|T-helper 1 cell activation|
|alphav-beta3 integrin-HMGB1 complex|
|tumor necrosis factor secretion|
|positive regulation of mismatch repair|
|C-X-C chemokine binding|
|positive regulation of toll-like receptor 9 signaling pathway|
|regulation of mismatch repair|
|positive regulation of DNA ligation|
|neutrophil clearance|
|negative regulation of transcription initiation from RNA polymerase II promoter|
|positive regulation of dendritic cell differentiation|
|supercoiled DNA binding|
|regulation of DNA ligation|
|negative regulation of DNA-templated transcription, initiation|
|tumor necrosis factor production|
|regulation of endodeoxyribonuclease activity|
|bubble DNA binding|
|tumor necrosis factor superfamily cytokine production|
|T-helper 1 cell differentiation|
|regulation of toll-like receptor 9 signaling pathway|
|DNA ligation involved in DNA repair|
|DNA topological change|
|regulation of deoxyribonuclease activity|
|regulation of apoptotic cell clearance|
|regulation of interferon-alpha secretion|
|positive regulation of interferon-alpha secretion|
|neutrophil homeostasis|
|RAGE receptor binding|
|regulation of dendritic cell differentiation|
|DNA ligation|
|regulation of response to tumor cell|
|regulation of RNA polymerase II transcriptional preinitiation complex assembly|
|regulation of immune response to tumor cell|
|lyase activity|
|positive regulation of vascular endothelial cell proliferation|
|regulation of tolerance induction|
|four-way junction DNA binding|
|apoptotic DNA fragmentation|
|V(D)J recombination|
|dendritic cell chemotaxis|
|positive regulation of monocyte chemotaxis|
|T-helper 1 type immune response|
|DNA binding, bending|
|DNA polymerase binding|
|regulation of vascular endothelial cell proliferation|
|negative regulation of phagocytosis|
|negative regulation of CD4-positive, alpha-beta T cell differentiation|
|dendritic cell migration|
|positive regulation of activated T cell proliferation|
|myeloid dendritic cell activation|
|regulation of nuclease activity|
|positive regulation of interferon-alpha production|
|positive regulation of toll-like receptor signaling pathway|
|inflammatory response to antigenic stimulus|
|negative regulation of alpha-beta T cell differentiation|
|positive regulation of mononuclear cell migration|
|DNA catabolic process, endonucleolytic|
|apoptotic nuclear changes|
|regulation of monocyte chemotaxis|
|regulation of transcription initiation from RNA polymerase II promoter|
|condensed chromosome|
|cellular component disassembly involved in execution phase of apoptosis|
|T-helper cell differentiation|
|CD4-positive, alpha-beta T cell differentiation involved in immune response|
|alpha-beta T cell activation involved in immune response|
|alpha-beta T cell differentiation involved in immune response|
|DNA catabolic process|
|negative regulation of CD4-positive, alpha-beta T cell activation|
|regulation of interferon-alpha production|
|positive regulation of interleukin-6 secretion|
|negative regulation of blood vessel endothelial cell migration|
|T cell differentiation involved in immune response|
|positive regulation of interleukin-1 beta secretion|
|negative regulation of interferon-gamma production|
|CD4-positive, alpha-beta T cell differentiation|
|lipopolysaccharide binding|
|positive regulation of interleukin-12 production|
|somatic diversification of immune receptors via germline recombination within a single locus|
|somatic cell DNA recombination|
|regulation of activated T cell proliferation|
|chemoattractant activity|
|regulation of DNA-templated transcription, initiation|
|positive regulation of interleukin-10 production|
|negative regulation of alpha-beta T cell activation|
|positive regulation of interleukin-1 secretion|
|apoptotic cell clearance|
|CD4-positive, alpha-beta T cell activation|
|repressing transcription factor binding|
|negative regulation of T cell differentiation|
|regulation of mononuclear cell migration|
|regulation of CD4-positive, alpha-beta T cell differentiation|
|regulation of interleukin-1 beta secretion|
|positive chemotaxis|
|cytokine secretion|
|negative regulation of endothelial cell migration|
|somatic diversification of immune receptors|
|alpha-beta T cell differentiation|
|positive regulation of interleukin-1 beta production|
|regulation of interleukin-10 production|
|negative regulation of lymphocyte differentiation|
|execution phase of apoptosis|
|regulation of interleukin-1 secretion|
|regulation of interleukin-12 production|
|positive regulation of blood vessel endothelial cell migration|
|damaged DNA binding|
|positive regulation of DNA binding|
|transcriptional repressor complex|
|positive regulation of interleukin-1 production|
|phosphatidylserine binding|
|chromatin organization involved in negative regulation of transcription|
|chromatin silencing|
|regulation of CD4-positive, alpha-beta T cell activation|
|alpha-beta T cell activation|
|regulation of alpha-beta T cell differentiation|
|T cell activation involved in immune response|
|negative regulation of epithelial cell migration|
|positive regulation of DNA repair|
|regulation of toll-like receptor signaling pathway|
|leukocyte homeostasis|
|regulation of T cell mediated immunity|
|chromatin organization involved in regulation of transcription|
|endoplasmic reticulum-Golgi intermediate compartment|
|positive regulation of NIK/NF-kappaB signaling|
|positive regulation of type I interferon production|
|negative regulation of gene expression, epigenetic|
|regulation of interleukin-1 beta production|
|positive regulation of tumor necrosis factor production|
|positive regulation of tumor necrosis factor superfamily cytokine production|
|positive regulation of leukocyte chemotaxis|
|regulation of blood vessel endothelial cell migration|
|regulation of alpha-beta T cell activation|
|positive regulation of endothelial cell proliferation|
|positive regulation of interleukin-6 production|
|regulation of interleukin-1 production|
|positive regulation of T cell proliferation|
|regulation of phagocytosis|
|positive regulation of response to DNA damage stimulus|
|positive regulation of endothelial cell migration|
|regulation of interferon-gamma production|
|toll-like receptor signaling pathway|
|negative regulation of leukocyte differentiation|
|tissue remodeling|
|double-stranded DNA binding|
|myeloid cell homeostasis|
|single-stranded DNA binding|
|regulation of NIK/NF-kappaB signaling|
|lymphocyte activation involved in immune response|
|negative regulation of T cell activation|
|regulation of leukocyte chemotaxis|
|secretory granule lumen|
|DNA geometric change|
|positive regulation of autophagy|
|negative regulation of leukocyte cell-cell adhesion|
|ficolin-1-rich granule lumen|
|regulation of DNA repair|
|regulation of DNA binding|
|regulation of type I interferon production|
|pattern recognition receptor signaling pathway|
|regulation of endothelial cell proliferation|
|positive regulation of leukocyte migration|
|positive regulation of lymphocyte proliferation|
|positive regulation of mononuclear cell proliferation|
|integrin binding|
|negative regulation of protein complex assembly|
|positive regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|T cell differentiation|
|positive regulation of chemotaxis|
|negative regulation of hemopoiesis|
|positive regulation of leukocyte proliferation|
|regulation of T cell differentiation|
|positive regulation of cytokine secretion|
|positive regulation of JNK cascade|
|regulation of interleukin-6 production|
|positive regulation of epithelial cell migration|
|negative regulation of lymphocyte activation|
|regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|leukocyte chemotaxis|
|positive regulation of leukocyte differentiation|
|regulation of tumor necrosis factor production|
|cytokine production|
|regulation of lymphocyte mediated immunity|
|positive regulation of cysteine-type endopeptidase activity|
|gene silencing|
|regulation of tumor necrosis factor superfamily cytokine production|
|regulation of T cell proliferation|
|regulation of endothelial cell migration|
|protein secretion|
|establishment of protein localization to extracellular region|
|regulation of adaptive immune response|
|chromatin remodeling|
|protein localization to extracellular region|
|positive regulation of stress-activated MAPK cascade|
|positive regulation of stress-activated protein kinase signaling cascade|
|regulation of lymphocyte differentiation|
|positive regulation of endopeptidase activity|
|regulation of signaling receptor activity|
|peptide secretion|
|cytokine activity|
|negative regulation of cell-cell adhesion|
|negative regulation of leukocyte activation|
|positive regulation of binding|
|cellular response to lipopolysaccharide|
|regulation of JNK cascade|
|positive regulation of hemopoiesis|
|positive regulation of epithelial cell proliferation|
|positive regulation of peptidase activity|
|cellular response to molecule of bacterial origin|
|positive regulation of DNA metabolic process|
|regulation of leukocyte migration|
|negative regulation of cell activation|
|homeostasis of number of cells|
|positive regulation of T cell activation|
|regulation of cytokine secretion|
|regulation of leukocyte mediated immunity|
|regulation of lymphocyte proliferation|
|regulation of mononuclear cell proliferation|
|cell chemotaxis|
|positive regulation of ERK1 and ERK2 cascade|
|regulation of chemotaxis|
|cellular response to biotic stimulus|
|regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|positive regulation of leukocyte cell-cell adhesion|
|regulation of response to DNA damage stimulus|
|transcription regulatory region DNA binding|
|regulation of epithelial cell migration|
|DNA recombination|
|regulation of leukocyte proliferation|
|regulation of stress-activated MAPK cascade|
|innate immune response-activating signal transduction|
|T cell activation|
|regulation of stress-activated protein kinase signaling cascade|
|regulation of gene expression, epigenetic|
|nuclear chromatin|
|lymphocyte differentiation|
|regulation of cysteine-type endopeptidase activity|
|positive regulation of cell-cell adhesion|
|activation of innate immune response|
|negative regulation of cell migration|
|autophagy|
|process utilizing autophagic mechanism|
|positive regulation of protein secretion|
|endosome|
|negative regulation of cell adhesion|
|regulation of leukocyte differentiation|
|negative regulation of cell motility|
|negative regulation of cytokine production|
|adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|positive regulation of cytosolic calcium ion concentration|
|transcription coactivator activity|
|positive regulation of peptide secretion|
|regulation of ERK1 and ERK2 cascade|
|regulation of leukocyte cell-cell adhesion|
|DNA conformation change|
|nucleic acid phosphodiester bond hydrolysis|
|negative regulation of cellular component movement|
|response to lipopolysaccharide|
|regulation of T cell activation|
|negative regulation of locomotion|
|response to molecule of bacterial origin|
|regulation of cytosolic calcium ion concentration|
|phagocytosis|
|leukocyte differentiation|
|regulation of autophagy|
|transcription factor binding|
|regulation of epithelial cell proliferation|
|positive regulation of innate immune response|
|regulation of DNA metabolic process|
|positive regulation of proteolysis|
|positive regulation of lymphocyte activation|
|positive regulation of response to biotic stimulus|
|positive regulation of cellular catabolic process|
|nucleobase-containing compound catabolic process|
|regulation of binding|
|leukocyte migration|
|lymphocyte activation|
|regulation of cell-cell adhesion|
|cellular component disassembly|
|positive regulation of secretion by cell|
|positive regulation of cell adhesion|
|positive regulation of leukocyte activation|
|positive regulation of cell activation|
|regulation of endopeptidase activity|
|positive regulation of protein transport|
|positive regulation of catabolic process|
|heterocycle catabolic process|
|cellular nitrogen compound catabolic process|
|positive regulation of secretion|
|cellular calcium ion homeostasis|
|negative regulation of immune system process|
|aromatic compound catabolic process|
|regulation of peptidase activity|
|calcium ion homeostasis|
|positive regulation of cytokine production|
|regulation of protein complex assembly|
|regulation of hemopoiesis|
|regulation of innate immune response|
|positive regulation of establishment of protein localization|
|regulation of protein secretion|
|regulation of immune effector process|
|cellular divalent inorganic cation homeostasis|
|positive regulation of defense response|
|organic cyclic compound catabolic process|
|negative regulation of transport|
|neutrophil degranulation|
|divalent inorganic cation homeostasis|
|neutrophil activation involved in immune response|
|regulation of peptide secretion|
|neutrophil mediated immunity|
|inflammatory response|
|positive regulation of cell migration|
|neutrophil activation|
|granulocyte activation|
|positive regulation of multi-organism process|
|DNA repair|
|leukocyte degranulation|
|regulation of lymphocyte activation|
|myeloid leukocyte mediated immunity|
|cellular response to lipid|
|positive regulation of cell motility|
|myeloid cell activation involved in immune response|
|regulation of response to biotic stimulus|
|positive regulation of cellular component movement|
|positive regulation of MAPK cascade|
|chemotaxis|
|regulation of vesicle-mediated transport|
|positive regulation of locomotion|
|taxis|
|hemopoiesis|
|cellular metal ion homeostasis|
|immune response-activating signal transduction|
|myeloid leukocyte activation|
|immune response-regulating signaling pathway|
|positive regulation of response to external stimulus|
|regulation of leukocyte activation|
|hematopoietic or lymphoid organ development|
|adaptive immune response|
|cell surface|
|leukocyte activation involved in immune response|
|metal ion homeostasis|
|cell activation involved in immune response|
|activation of immune response|
|cellular cation homeostasis|
|regulation of cell activation|
|positive regulation of apoptotic process|
|cellular ion homeostasis|
|positive regulation of programmed cell death|
|immune system development|
|neuron projection development|
|regulation of cell adhesion|
|response to bacterium|
|regulation of cytokine production|
|positive regulation of cell death|
|chromatin organization|
|regulated exocytosis|
|negative regulation of cellular component organization|
|regulation of protein transport|
|cation homeostasis|
|negative regulation of cell differentiation|
|inorganic ion homeostasis|
|regulation of proteolysis|
|regulation of cellular response to stress|
|regulation of peptide transport|
|cellular chemical homeostasis|
|DNA metabolic process|
|regulation of establishment of protein localization|
|regulation of secretion by cell|
|regulation of MAPK cascade|
|regulation of defense response|
|leukocyte mediated immunity|
|innate immune response|
|positive regulation of hydrolase activity|
|regulation of multi-organism process|
|cellular response to DNA damage stimulus|
|ion homeostasis|
|exocytosis|
|regulation of secretion|
|neuron development|
|regulation of cellular catabolic process|
|regulation of cell migration|
|response to lipid|
|negative regulation of transcription by RNA polymerase II|
|positive regulation of immune response|
|cellular homeostasis|
|cellular macromolecule catabolic process|
|regulation of cell motility|
|positive regulation of cell population proliferation|
|apoptotic process|
|leukocyte activation|
|negative regulation of developmental process|
|defense response to other organism|
|regulation of cellular component biogenesis|
|cell migration|
|positive regulation of cell differentiation|
|regulation of locomotion|
|positive regulation of transport|
|regulation of catabolic process|
|regulation of cellular component movement|
|secretion by cell|
|neuron differentiation|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|regulation of protein localization|
|export from cell|
|macromolecule catabolic process|
|programmed cell death|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|chromosome organization|
|cell activation|
|cell motility|
|localization of cell|
|immune effector process|
|cell death|
|regulation of response to external stimulus|
|chemical homeostasis|
|plasma membrane bounded cell projection organization|
|secretion|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|positive regulation of immune system process|
|regulation of immune response|
|cell projection organization|
|negative regulation of transcription, DNA-templated|
|negative regulation of multicellular organismal process|
|positive regulation of transcription by RNA polymerase II|
|positive regulation of protein modification process|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|regulation of hydrolase activity|
|response to other organism|
|response to external biotic stimulus|
|locomotion|
|response to biotic stimulus|
|negative regulation of RNA metabolic process|
|defense response|
|positive regulation of developmental process|
|negative regulation of cellular macromolecule biosynthetic process|
|RNA binding|
|positive regulation of catalytic activity|
|negative regulation of nucleobase-containing compound metabolic process|
|regulation of protein phosphorylation|
|negative regulation of macromolecule biosynthetic process|
|regulation of response to stress|
|protein transport|
|negative regulation of cellular biosynthetic process|
|generation of neurons|
|peptide transport|
|positive regulation of transcription, DNA-templated|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|movement of cell or subcellular component|
|response to oxygen-containing compound|
|regulation of programmed cell death|
|amide transport|
|regulation of phosphorylation|
|extracellular space|
|positive regulation of cellular protein metabolic process|
|establishment of protein localization|
|regulation of cell population proliferation|
|neurogenesis|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|homeostatic process|
|cell development|
|regulation of immune system process|
|positive regulation of signal transduction|
|regulation of cell death|
|cellular response to stress|
|positive regulation of protein metabolic process|
|negative regulation of gene expression|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|organic substance catabolic process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|cellular catabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|nitrogen compound transport|
|regulation of protein modification process|
|regulation of transport|
|immune response|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|extracellular region|
|vesicle-mediated transport|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|positive regulation of biosynthetic process|
\\
=== CRISPR Data ===
^Screen^Score^
|[[:results:exp68|Clomiphene 4.4μM R02 exp68]]|-1.99|
|[[:results:exp66|BI-D1870 3.15μM R02 exp66]]|-1.9|
|[[:results:exp89|Vemurafenib 6.6μM R02 exp89]]|-1.7|
|[[:results:exp504|MK2206 4μM R08 exp504]]|1.74|
|[[:results:exp326|CCT251545 20μM R07 exp326]]|1.76|
|[[:results:exp514|Phorbol-12-myristate-13-acetate 0.57μM R08 exp514]]|1.78|
|[[:results:exp54|Taxol 0.002μM R01 exp54]]|1.8|
|[[:results:exp505|ML-792 0.2μM R08 exp505]]|1.82|
|[[:results:exp97|BI-6727 0.0125μM R03 exp97]]|1.84|
|[[:results:exp227|Cryptotanshinone 12μM R05 exp227]]|1.9|
|[[:results:exp219|A-395N 10μM R05 exp219]]|2.25|
No correlation found to any other genes in chemogenomics.
Global Fraction of Cell Lines Where Essential: 12/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|1/28|
|bone|0/25|
|breast|1/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|1/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|0/21|
|liver|1/20|
|lung|1/75|
|lymphocyte|0/14|
|ovary|1/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|1/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 1034
* **Expression level (log2 read counts)**: 10.38
{{:chemogenomics:nalm6 dist.png?nolink |}}