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FLASH GENE
Symbol HMGA2 contributors: mct/npt/pgu - updated : 03-02-2016
HGNC name high mobility group AT-hook 2
HGNC id 5009
Corresponding disease
DEL12Q14 chromosome12q14 deletions
Location 12q14.3      Physical location : 66.218.239 - 66.360.068
Synonym name
  • high-mobility group (nonhistone chromosomal) protein isoform I-C
  • high-mobility group protein HMGI-C
  • Synonym symbol(s) BABL, LIPO, HMGIC, LIPO, STQTL9, HMGI-C
    DNA
    TYPE functioning gene
    STRUCTURE 141.83 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    text structure three DNA binding domains
    MAPPING cloned Y linked N status confirmed
    Map cen - D12S1476 - D12S131 - D12S1620 - GPD1 - D12S1585 - D12S159 - D12S1649 - D12S1426 - D12S1491 - D12S1489 - HMGA2 - D12S1556 - D12S1557 - D12S288 - D12S1461 - D12S868 - D12S1601 - qter
    Authors UCSC (2009)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 4150 - 109 - 1995 7501444
    4 - 1539 - 106 - 1995 7501444
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver    
    Hearing/Equilibriumearinnercochlea   Mus musculusAdult
     earinnercochlea   Mus musculusFetal
    Respiratorylung    
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularsmouthuterusmyometrium 
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Hearing / Equilibriumhair cell receptor Mus musculus
    cell lineage
    cell lines in transformed cells
    fluid/secretion
    at STAGE
    physiological period embryo
    Text early embryogenesis, embryonic stem cells
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • three AT-hooks that enable these proteins to bind to A/T-rich sequences in the minor groove of DNA
  • a C terminal acidic domain
  • HOMOLOGY
    Homologene
    FAMILY
  • HMGA family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome,telomere
    text
  • localizes to mammalian telomeres and enhances telomere stability in cancer cells
  • basic FUNCTION
  • architectural transcription factor
  • organizing the framework of nucleoprotein-DNA transcriptional complex
  • regulates expression of many important repressors of E-cadherin (CDH1)
  • playing a role in leukemogenesis
  • involved in regulation of cell proliferation
  • playing a role in adipogenesis, osteogenesis, and general growth control
  • having a critical function in cardiogenesis
  • acts in a gene-specific manner to orchestrate the transcriptional network necessary for the epithelial-mesenchymal transition program
  • chaperoning HMGA2 protein protects stalled replication forks in stem and cancer cells
  • tissue-specific expression and transcription level of HMGA2 during inner ear development, suggesting its potential dual role in early differentiation and maintenance of both hair and supporting cell phenotypes
  • directly regulates GATA6 and thereby modulates FZD2 expression
  • critical role for HMGA2 in promoting EMT, migration, invasion, and proliferation of colon cancer cells
  • HMGA2-induced apoptosis was likely dependent on the pathway of DNA damage
  • played an important role in the progression of bladder cancer
  • non-histone chromatin binding protein that plays important roles in the repair and protection of genomic DNA in embryonic stem cells and cancer cells
  • novel role of HMGA2 in telomere protection and promoting telomere stability in cancer cells
  • CELLULAR PROCESS nucleotide, chromatin organization
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • HMGA2-IGF2BP2 axis functions as a key regulator of satellite cell activation and therefore skeletal muscle development
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • directly binds to the SNAI1 promoter and acts as a transcriptional regulator of SNAI1 expression
  • LUM, a tumor suppressor that inhibits epithelial-to-mesenchymal transition(EMT), is transcriptionally repressed by HMGA2 and frequently lost in human high-grade serous papillary carcinoma
  • PEBP1 inhibits syndecan-2 (SDC2), which is aberrantly expressed in breast cancer, via downregulation of HMGA2
  • HMGA2-mediated direct regulation of GATA6 is crucial for fine-tuning the activity of WNT signaling in the airway epithelium
  • HMGA2 positively regulates the SNAI2 expression by directly binding to the regulatory region in SNAI2 promoter
  • interaction of HMGA2 with the key shelterin protein TERF2
  • FGF2, a growth factor commonly used to promote self-renewal in Mesenchymal stem cells (MSCs), rapidly induces HMGA2 expression in a time- and concentration-dependent manner
  • cell & other
    REGULATION
    activated by OTX2 and HMGA2 protein binds to the enhancers targeted by OTX2, thus facilitating the engagement and/or the stable association of OTX2
    ASSOCIATED DISORDERS
    corresponding disease(s) DEL12Q14
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    RAD51L/HMGIC fusion, HEI1/HMGIC t(14;12)in uterine leiomyoma
    tumoral   translocation    
    t(3;12),t(12;3),t(12;4),t(8;12) in benign mesenchymal tumors (see RATT, MAR, ERV5, ALDH2, ULCR12, LPP, LHFP, COX6C), see also TSG12A)
    tumoral   amplification    
    in well differentiated liposarcoma
    tumoral     --over  
    in myelofibrosis with myeloid metaplasia and in uterine leiomyoma (associated with loss of TSC2 function)
    tumoral     --over  
    in thyroid carcinomas
    tumoral     --over  
    increased HMGA2 expression in uterine leiomyomas with 12q14-15 rearrangements
    tumoral     --over  
    in polycythemia vera with t(12;21)(q14;q22)
    constitutional     --other  
    rearrangement of HMGA1 and HMGA2 genes likely contributes to endometriosis
    tumoral     --over  
    in human ovarian carcinomas
    tumoral     --over  
    common in both early and late-stage high-grade ovarian serous papillary carcinoma
    tumoral     --over  
    through its relationship to epithelial-mesenchymal transition (EMT), thus seems to aggravate invasion and metastasis in gastric cancer
    Susceptibility
  • to variation of adult and childhood height in the general population
  • to uterine leyomyomatosis (UL) and decreased height
  • to type 2 diabetes
  • Variant & Polymorphism SNP , other
  • common variant is associated with adult and childhood height in the general population
  • a specific TC dinucleotide repeat (TC227) in the 5 UTR of HMGA2 with both predisposition to UL with decreased height
  • increasing the risk of type 2 diabetes
  • Candidate gene for growth restriction in del 12q14 syndrome
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveovary
    represents a promising target for gene silencing therapy in ovarian cancer
    cancerurinary 
    target for therapy in human bladder cancer
    cancerdigestivecolon
    a potential molecular target to prevent colon cancer progression
    ANIMAL & CELL MODELS
  • diet induced obsity in (-/-) mice
  • Hmga2 knockout mice exhibit impaired muscle development and reduced myoblast proliferation, while overexpression of Hmga2 promotes myoblast growth