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FLASH GENE
Symbol HMGB1 contributors: mct/shn - updated : 13-06-2016
HGNC name high-mobility group box 1
HGNC id 4983
Location 13q12.3      Physical location : 31.032.880 - 31.040.081
Synonym name
  • high-mobility group (non histone chromosomal) protein 1
  • amphoterin
  • sulfoglucuronyl carbohydrate binding protein
  • high-mobility group box 1
  • high mobility group box 1
  • high mobility group protein 1
  • Synonym symbol(s) HMG1, HMG3, SBP-1, DKFZp686A04236
    DNA
    TYPE functioning gene
    STRUCTURE 7.20 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   enhancer   silencer
    MAPPING cloned Y linked N status provisional
    Map cen - D13S217 - D13S1299 - HMGB1 - D13S1246 - D13S289 - qter
    Physical map
    GSH1 13q12.13 GS homeobox 1 IPF1 13q12.1 insulin promoter factor 1, homeodomain transcription factor LOC387915 13 hypothetical gene supported by AK000246 CDX2 13q12-q13 caudal type homeo box transcription factor 2 FLT3 13q12 fms-related tyrosine kinase 3 LOC390390 13 similar to chromosome 7 open reading frame 17 protein; 16.7kD protein LOC390391 13 similar to Elongation factor 1-alpha 1 (EF-1-alpha-1) (Elongation factor 1 A-1) (eEF1A-1) (Elongation factor Tu) (EF-Tu) PAN3 13q12.2 PABP1-dependent poly A-specific ribonuclease subunit PAN3 FLT1 13q12 fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor) LOC341784 13q12.3 similar to eukaryotic translation initiation factor 4A1; initiation factor eIF-4A long form C13orf12 13q12.13 chromosome 13 open reading frame 12 LOC283537 13q12.3 hypothetical protein LOC283537 CYP51P2 13 hypothetical protein LOC283537 KIAA0774 13q12.13-q12.2 hypothetical protein LOC283537 SLC7A1 13q12.3 solute carrier family 7 (cationic amino acid transporter, y+ system), member 1 UBL3 13q12-q13 ubiquitin-like 3 MGC2599 13q12.3 hypothetical protein MGC2599 similar to katanin p60 subunit A 1 2599 PRDX2P1 13p12 peroxiredoxin 2 pseudogene 1 UBCH7N2 13q12.3 ubiquitin-conjugating enzyme-like HMGB1 13q12 high-mobility group box 1 LOC390392 13 similar to Protein-tyrosine phosphatase, non-receptor type 2 (T-cell protein-tyrosine phosphatase) (TCPTP) D13S106E 13q12-q14 highly charged protein ALOX5AP 13q12 arachidonate 5-lipoxygenase-activating protein LOC387917 13 LOC387917 FLJ14834 13q12.3 hypothetical protein FLJ14834 MGC40178 13q12.3 hypothetical protein MGC40178 HSPH1 13q12.3 heat shock 105kDa/110kDa protein 1 B3GTL 13q12.3 beta 3-glycosyltransferase-like GREAT 13q12.3 beta 3-glycosyltransferase-like LOC196549 13q12.3 similar to hypothetical protein FLJ20897 13CDNA73 13q12.3 hypothetical protein CG003 BRCA2 13q12.3 breast cancer 2, early onset IFIT1P 13q12-q13 interferon-induced protein with tetratricopeptide repeats 1, pseudogene CG018 13q12-q13 hypothetical gene CG018 PRO0297 13q12-q13 hypothetical gene CG018 LOC88523 13q12.3 CG016 CG005 APRIN 13q12.3 androgen-induced proliferation inhibitor LOC122038 13q13.1 similar to Mitochondrial import receptor subunit TOM22 homolog (Translocase of outer membrane 22 kDa subunit homolog) (hTom22) (1C9-2) KL 13q12 klotho
    RNA
    TRANSCRIPTS type messenger
    text a number of different transcription start sites and numerous alternatively spliced exons (PMID: 8414980)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 3428 24.9 215 - 2007 17958791
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly
    Endocrineparathyroid   highly
    Lymphoid/Immunetonsils   highly
    Urinarybladder   highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skin/Tegumentmelanocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    Text expressed by term placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two basic DNA binding domains of the HMG box type
  • three cysteines, Cys23, 45, and 106 (in mild oxidative conditions, Cys23 and Cys45 readily form an intramolecular disulfide bridge, whereas Cys106 remains in the reduced form)
  • a C terminal stretch of negatively charged aminoacids
  • secondary structure disulfide bond between Cys23 and Cys45 is a target of glutathione-dependent reduction by glutaredoxin
    HOMOLOGY
    interspecies ortholog to Hmgb1, Mus musculus
    ortholog to Hmgb1, Rattus norvegicus
    ortholog to HMGB1, Pan troglodytes
    Homologene
    FAMILY
  • HMGB family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,nucleus,chromatin/chromosome,nucleosome
    text
  • in mitotic cells, free and associated with the condensed chromatin
  • associated with chromosomes in mitosis and due to its extreme mobility in the cell the protein is continuously exchanged between nucleus and cytoplasm
  • basic FUNCTION
  • non-histone chromatin-associated protein,
  • which functions in a number of fundamental cellular processes such as transcription, replication, DNA repair and recombination
  • binding the double helix significantly through the minor groove predominantly the linker DNA at the entry and exit of nucleosomes
  • stimulating the catalytic activity of the enzyme TOP2A via enhancement of DNA cleavage
  • DNA-binding protein, regulating gene transcription and stabilizing nucleosome formation
  • also recruited to DNA by interactions with proteins required for basal regulated transcription and V(D)J recombination
  • functions as a chromatin-binding factor that bends DNA and promotes access to transcriptional protein assemblies on specific DNA targets
  • requiring at a step prior to the excision of mispaired nucleotide in mismatch repair
  • a potent regulator of melanoma inhibitory activity expression (
  • having a prominent role in a number of processes of specific interest for the placenta
  • chromatin protein that has a dual function as a nuclear factor and as an extracellular factor
  • functioning as a chemoattractant for osteoclasts and osteoblasts, as well as for endothelial cells and is a regulator of endochondral ossification during osteogenesis
  • base excision repair (BER) cofactor capable of modulating BER capacity in cells
  • function in a number of fundamental cellular processes such as transcription, replication, DNA repair and recombination
  • potential HMGB1-induced apoptosis of macrophages in a dose- and time-dependent manner
  • involved in the pathogenesis of inflammatory and autoimmune diseases
  • undergoes reversible oxidative modifications at cysteine residues during cell death, which may modulate its biological properties
  • with HMGB2, HMGB3, function as universal sentinels for nucleic acid
  • also exhibits an important extracellular function in mediation of inflammation mechanisms, tumor growth and metastasis
  • plays an important role in promoting genomic stability
  • important role of HMGB1 in modulating genome stability
  • involved in ictogenesis (
  • redox-sensitive regulator of the balance between autophagy and apoptosis
  • in tumor cells treated with various cytotoxic agents, HMGB1 release is a widespread phenomenon regardless of the type of tumor cell death
  • promotes kidney damage after schemia-reperfusion injury, possibly through the TLR4 pathway
  • mediates ischemia-reperfusion injury by TICAM2-adaptor independent Toll-like receptor 4 signaling
  • HMGB1 and HMGB2 have critical roles in cellular processes, including transcription and DNA modification
  • induces MUC8 expression in a JNK and PI3K/Akt signaling pathway-dependent manner but HMGB1 acts in an ROS-independent manner
  • mediates chronic inflammatory responses in endothelial cells, which play a critical role in atherosclerosis
  • ER stress plays a critical role in HMGB1-induced inflammatory responses in endothelial cells
  • HMGB1 can trigger apoptosis of T lymphocytes through mitochondrial death pathway associated with [Ca2+] elevation
  • cardiac HMGB1 increases HSPB1 expression in cardiomyocytes in a heat shock factor 2-dependent manner
  • CELLULAR PROCESS nucleotide, chromatin organization
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA linear DNA moderately
    double helix significantly
    RNA
    small molecule
    protein
  • plasminogen and tissue plasminogen activator (
  • homeobox D9, HOXD9 (
  • TP53 (
  • core domain of human TATA box-binding protein (
  • recombination activating gene 1, RAG1 (
  • transcriptional activators like the heterogeneous nuclear ribonucleoprotein K (hnRNP K), methyl-CpG binding protein 2 (MeCP2), retinoblastoma susceptibility protein (pRb) and Groucho-related gene proteins 1 (Grg1) and 5 (Grg5) (
  • P73 (
  • Casein kinase Ialpha, CKIalpha (
  • p50 subunit (
  • MSH2, MSH6
  • TLR2 and TLR4 (
  • specifically interacting with the base excision repair (BER) intermediate
  • could significantly up-regulate TOP2A gene promoter only in cells lacking functional retinoblastoma protein pRb
  • TLR4
  • AGER
  • bound to microglial Mac1 (macrophage antigen complex 1) and activated nuclear factor-kB pathway and NADPH oxidase to stimulate production of multiple inflammatory and neurotoxic factors (
  • HMGB1 is one of the important AGER ligands
  • promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4
  • activates inflammatory pathways and triggers a cascade of pro-inflammatory cytokines, including ICAM1 and P-selectin, in endothelial cells
  • HMGB1 markedly increased MUC8 expression, and the expression of other MUC genes was also regulated by HMGB1
  • HMGB1 hyperacetylation and release, and inflammasome activation, are regulated by EIF2AK2
  • HMGB1 promotes an inflammatory response by inducing the expression of ICAM1 and P-selectin via AGER-mediated stimulation of the endoplasmic reticulum stress pathway
  • induces the inflammatory response in endothelial cells in a manner that is mediated by AGER activation
  • overexpression of MFN2 ameliorates the apoptosis of T cells induced by HMGB1
  • TLR4 adaptor, myeloid differentiation factor 2 (LY96), binds specifically to the cytokine-inducing disulfide isoform of HMGB1, to the exclusion of other isoforms
  • cardiac HMGB1 increases HSPB1 expression and attenuates cardiomyocyte apoptosis associated with doxorubicin-induced cardiomyopathy
  • involvement of BBC3 in cold preservation/rewarming-mediated pancreatic islet injury, possibly through modulating HMGB1- and oxidative stress-mediated injury to islets
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in estrogen stimulated breast cancer cells
    tumoral     --over  
    in colorectal cancer tissue compared with normal colorectal mucosa
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    novel therapeutic approach to potentiate cancer treatment efficacy by inhibiting HMGB1 release and the resultant autophagy or by enhancing the aerobic denaturation of HMGB1
    diabete  
    blockage of HMGB1 might represent a therapeutic strategy to reduce post-ischemic remodeling in diabetes mellitus
    cardiovascularaquired 
    HMGB1-antagonizing gene therapy represents a new therapeutic strategy in inflammatory cardiomyopathy
    ANIMAL & CELL MODELS
  • Hmg1-/- pups are born alive, but die within 24 hours due to hypoglycaemia (
  • Hmg1-deficient mice survive for several days if given glucose parenterally, then waste away with pleiotropic defects (