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FLASH GENE
Symbol ING4 contributors: mct/pgu - updated : 21-06-2017
HGNC name inhibitor of growth family, member 4
HGNC id 19423
Location 12p13.31      Physical location : 6.759.704 - 6.772.308
Synonym name
  • brain my036 protein
  • candidate tumor suppressor p33 ING1 homolog
  • inhibitor of growth protein 4
  • Synonym symbol(s) p29ING4, my036, MGC12557
    DNA
    TYPE functioning gene
    STRUCTURE 12.87 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 1458 28.4 248 - PMID: 17325660, PMID: 16973615
    encodes the longer isoform
    - - 1993 - 47 - Gunduz
  • contains an additional exon within the coding region, which leads to a frameshift
  • has a distinct and shorter C-terminus
  • 8 - 1461 28.5 249 - PMID: 17325660
    8 - 1452 28.2 246 - PMID: 17325660, PMID: 16973615
    lack the full NLS, resulting in increased cytoplasmic localization
    7 - 1389 25.6 225 - PMID: 17325660
    7 - 1313 - 179 - PMID: 17325660
    8 - 1449 28.1 245 - PMID: 17325660, PMID: 16973615
  • lack the full NLS, resulting in increased cytoplasmic localization
  • played dominant-negative roles in the induction of p21(WAF1) promoter activation
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    digestivemouthgingiva   
    Endocrineneuroendocrinepituitary  highly
    Lymphoid/Immunetonsils   highly
    Nervousbrainforebraincerebral lobefrontal 
     nerve   highly
    Reproductivefemale systemovary  highly
    Respiratorylung    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervousperipherous   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a conserved C-terminal plant homeodomain-like zinc finger
  • in the middle region, a potential bipartite nuclear localization signal (NLS), could be involved in the binding to TP53
  • HOMOLOGY
    interspecies ortholog to rattus ing4_predicted
    ortholog to murine Ing4
    Homologene
    FAMILY
  • inhibitor of growth (ING) family of chromatin-modifying proteins
  • CATEGORY tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,nucleus,nucleolus
    text nucleolar accumulation of ING4 prolongs its half-life, but lack of nucleolar targeting potentially increases ING4 degradation
    basic FUNCTION
  • involved in regulating brain tumour growth and angiogenesis
  • involved in negative regulation of transcription, DNA-dependent
  • play an important role in cell cycle, transcription and oncogenesis
  • potential role in lung fibrogenesis because its down-regulation may facilitate aberrant vascular remodelling and fibroblast proliferation and migration leading to progressive disease
  • may specifically regulate the activity of NF-kappaB molecules that are bound to target gene promoters
  • may regulate a wide variety of cellular processes, including DNA repair, apoptosis, cell-cycle regulation, metastasis, angiogenesis, and tumor suppression
  • role in regulating NF-KB–mediated innate immunity
  • play important roles in regulating apoptosis, cell cycle progress, cell migration, and invasion
  • non-histone protein whose citrullination impacts regulation of gene expression
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • subunit of the MYST2-PHF17-MEAF6 histone acetyltransferase complex responsible for most nucleosomal histone H4 acetylation
  • INTERACTION
    DNA binding
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • NFKB1 to repress NFKB1 responsive genes
  • with TP53 and enhancing its activity as a trancription factor (the binding of ING4 to TP53 is necessary for the function of ING4)
  • interacts with methylated histone H3 and with the MYST2-PHF17-MEAF6 histone acetyltransferase complex
  • ING4-MYST2 association is required for cells to progress properly through the DNA synthesis (S) phase of the cell cycle
  • downstream target of BRMS1 in regulating tumor angiogenesis
  • Epstein-Barr virus (EBV)-encoded EBNA3C significantly suppresses both the ING4- and ING5-mediated regulation of TP53 transcriptional activity in a dose-dependent manner
  • binding of PADI4 to ING4 stabilizes ING4 and protects it from rapid degradation (protein binding occurs through the IgG-like domains of PADI4 and the PHD finger of ING4)
  • ING4 acts as an E3 ubiquitin ligase to induce ubiquitination of RELA and degradation, which is critical to terminate NFKB activation
  • RAS downregulated thymine-DNA glycosylase (TDG), a DNA demethylation enzyme, by inhibiting the interaction of transcription activator ING4 with TDG promoter
  • ZBTB17 is a newly identified ING4-induced target gene which can drive prostate luminal epithelial cell differentiation
  • cell & other
    REGULATION
    induced by BRMS1 (its expression was induced by BRMS1, a metastasis suppressor that inhibits melanoma angiogenesis through inhibiting NFKB activity and IL6 level as well)(
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    in breast cancer
    tumoral     --low  
    in glioma tissues, and the extent of reduction correlated with the progression from lower to higher grades of tumors
    tumoral     --low  
    in head and neck squamous cell carcinomas
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerskin 
    restoration of ING4 function offers a potential new strategy for the treatment of human melanoma
    ANIMAL & CELL MODELS