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FLASH GENE
Symbol ING2 contributors: mct - updated : 11-04-2018
HGNC name inhibitor of growth family, member 2
HGNC id 6063
Location 4q35.1      Physical location : 184.426.219 - 184.432.249
Synonym name
  • inhibitor of growth family, member 1-like
  • inhibitor of growth protein 2
    • Synonym symbol(s) P33ING2, ING1L, ING1Lp, p32
    DNA
    TYPE functioning gene
    STRUCTURE 6.03 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure promoter has two TP53 binding sites through which TP53 down-regulates expression of ING2
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 1135 32 280 testis, muscle, pancreas, ovary, fetal brain 2008 18951897
    also called ING2a
    2 - 783 28 240 testis 2008 18951897
  • also called ING2b
  • shares exon 2 with ING2a, but lacks the N-terminal TP53 binding region
  • exon 1b
  • a HSF1 and HSF2 binding site, a C-Rel binding site, a SP1 binding site, five MZF1 binding sites, and a p300 binding site were predicted in the promoter region
    		•
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Hearing/Equilibriumearinnercochlea highly
    Lymphoid/Immunelymph node   moderately
    Reproductivefemale systemuterus  moderately
     female systemovary  lowly
     male systemprostate  highly
    Respiratoryrespiratory tractlarynx  moderately
    cell lineage
    cell lines colon tumor cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N-terminal leucine zipper-like motif, and an intact coiled-coil domain, involved in TP53 binding
  • a central NLS sequence
  • two nucleolar-targeting sequences, a RRQR motif and a KKKK motif in their first and third NLS, respectively
  • a polybasic region (PBR) adjacent to the PHDs that binds stress-inducible phosphatidylinositol monophosphate (PtIn-MP) signaling lipids to activate ING2
  • a PHD (CH4-H-C3) zinc finger motif at the C terminus, required for SMURF1-mediated degradation
    • mono polymer complex
    HOMOLOGY
    interspecies homolog to rattus Ing1 (96.77 pc)
    homolog to murine Ing2 (96.79 pc)
    intraspecies homolog to ING1
    Homologene
    FAMILY
  • inhibitor of growth (ING) protein family
    • CATEGORY regulatory , DNA associated , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    intracellular,nucleus,nucleolus
    text
  • upon reduced PtdIns(5)P levels seems to be released from chromatin and, at least partially, translocated to the cytoplasm
  • sumoylation of ING2 is not required for the targeting of ING2 to the nucleus or to the chromatin
    • basic FUNCTION
  • inhibitor of cell growth (through the induction of G1 phase cell cycle arrest and apoptosis)
  • enhancing the transcriptional transactivation activity of TP53
  • can act as a cofactor of p300 for p53 acetylation and thereby plays a positive regulatory role during p53-mediated replicative senescence
  • upregulating Fas expression and activating caspase 8
  • modulating cellular responses to genotoxic insults
  • promoting TGF-beta-induced transcription
  • mediating responses by the transforming growth factor (TGF)-beta-Smad signaling pathway
  • have compensatory roles that protect cells from cell cycle arrest and apoptosis and may be involved in development of chemotherapeutic resistance
  • seems to have crucial roles in transcriptional regulation of various genes
  • might function as a tumor suppressor gene by directly maintaining DNA integrity
  • regulate cell growth, apoptosis, DNA repair, chromatin remodeling and gene expression through association with various proteins including SIN3A–HDAC complex, EP300
  • its sumoylation is required for the presence of both ING2 and SIN3A on its promoter to allow its expression (mechanism of ING2 regulation by a post-translational modification)
  • acts as a cell proliferation inhibitor by regulating cell cycle progression, apoptosis and senescence
    • CELLULAR PROCESS cell life, proliferation/growth
    cell life, cell death/apoptosis
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of a SIN3A histone deacetylase complex
  • forming a complex with SKIL and SMAD2
  • ING1 and ING2 are stoichiometric members of histone deacetylase complexes
    • INTERACTION
    DNA binding
    RNA
    small molecule metal binding,
  • Zn2+
    • protein
  • H3K4me3
  • interacting with SKIL
  • interacting with proliferating cell nuclear antigen and regulating its amount to the chromatin fraction
  • able to activate TP53 and cooperates with TP53 to induce cellular growth arrest and apoptosis
  • can bind to the promoter of genes to mediate their expression and that sumoylation of ING2 is required for this binding to some of these genes
  • interacting with TMEM71 (must be sumoylated to bind to the promoter of TMEM71 and to recruit the SIN3A chromatin-modifying complex to this promoter, in order to regulate TMEM71 transcription)
  • ING2 interacts with AR and hampers the AR transcriptional activation, causes growth arrest, and induces cellular senescence
  • potential crosstalk between ING1 and ING2 tumor suppressors to inhibit AR signaling and induce cellular senescence in PCa cells
    • cell & other
    REGULATION
    induced by the DNA-damaging agents etoposide and neocarzinostatin
    Other modulated by binding to phosphoinositides
    stability of ING2 could be regulated by ubiquitin-mediated degradation
    ING2 sumoylation enhances its association with SIN3A
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    loss of heterozygozity in basal cell carcinoma (BCC)
    tumoral     --low  
    in melanomas and reduced ING2 may be an important molecular event in the initiation of melanoma development
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target possibility of ING2 siRNA as a new generation of cancer therapeutic agent
    ANIMAL & CELL MODELS