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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
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
  • CKAP4 is required for stabilizing DICER1 protein and for optimal regulation of a reporter gene coupled to the 3prime untranslated region of HMGA2 mRNA in human cells
  • 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