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FLASH GENE
Symbol HEXIM1 contributors: mct/pgu - updated : 06-03-2018
HGNC name hexamethylene bis-acetamide inducible 1
HGNC id 24953
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a central PYNT motif required to inhibit the cyclin-dependent kinase CDK9
  • C-terminal region critical for cardiovascular development, C-terminal coiled-coil domain that recognizes the Cyclin T subunit of CCNT1
  • mono polymer homomer , heteromer , dimer , oligo
    HOMOLOGY
    interspecies homolog to murine Hexim1 (86.0pc)
    Homologene
    FAMILY
  • HEXIM family
  • CATEGORY regulatory , RNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • sequestering CCNT1 into an inactive 7SK/HEXIM1/CCNT1 small nuclear ribonucleic acid particle for inhibition of transcription and, consequently, cell proliferation
  • dual roles in transcriptional regulation: inhibition of transcriptional elongation dependent on 7SK RNA and positive transcription elongation factor b and interference with the sequence-specific transcription factor GR via a direct protein-protein interaction
  • coregulator of ERalpha transcriptional activity
  • playing an inhibitory role in NF-kappa B dependent gene expression in vascular smooth muscle cells
  • possible role for HEXIM1 ubiquitination in the regulation of CCNT1 activity
  • involved in other nuclear and cytoplasmic processes besides controlling CDK9
  • may act as a gene-selective transcriptional regulator via direct interaction with certain transcriptional regulators including GR and contribute to fine-tuning of, for example, glucocorticoid-mediated biological responses
  • inhibits phosphorylation of RNA polymerase II by interacting with the positive transcription elongation factor CCNT1, regulating the transcription elongation
  • regulates estrogen-induced VEGF transcription through inhibition of estrogen receptor-alpha recruitment to the VEGF promoter
  • having a inhibitory role during angiogenesis and a role for HEXIM1 in cancer progression
  • potential for HEXIM1 to indirectly act on multiple cell types to suppress metastatic cancer
  • crucial role for the HEXIM1/CCNT1 pathway in the regulation of satellite cell–mediated muscle regeneration
  • plays a critical role in the inhibition of the androgen receptor by anti-androgens
  • might be a novel factor involved in maintaining whole-body energy balance
  • transcription elongation regulator, acting as a melanoma tumor suppressor that responds to nucleotide stress
  • plays an important role in inhibiting cancer cell-specific gene transcription while also facilitating anti-cancer gene expression, and in coupling nucleotide metabolism with transcriptional regulation in melanoma
  • acts as a tumor suppressor and is involved in the regulation of innate immunity
  • in addition to its action on CCNT1, plays a role in a variety of different mechanisms: it controls the stability of transcription factor components and assists binding of transcription factors to their targets
  • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    nucleotide, transcription, elongation
    nucleotide, transcription, regulation
    protein
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • part of CCNT1/HEXIM1/RN7SK complexes (RN7SK is released from CCNT1/HEXIM1/RN7SK complexes upon an arrest in transcription and physiological stimulations such as cardiac hypertrophy, leading to CCNT1 activation)
  • component of a distinct complex made of HEXIM1 and NR3C1
  • ribonuclear complex built around HEXIM1 and the long non-coding RNA NEAT1that regulates the innate immune response to DNA viruses
  • CCNT1 is stored in the 7SK ribonucleoprotein (RNP) that contains the three nuclear proteins HEXIM1, LARP7, and MEPCE
  • INTERACTION
    DNA
    RNA binding snRNA 7SK
    small molecule
    protein
  • associates with glucocorticoid receptor (NR3C1) to suppress glucocorticoid-inducible gene activation (the hinge region of NR3C1 is essential for its interaction with HEXIM1)
  • interacting with ERalpha via the cyclin T1
  • interacting with the p65 subunit of NF-kappa B
  • binding CCNT1 (positive transcriptional elongation factor b), and having regulated association with CCNT1
  • targets a repeated GAUC motif in the riboregulator of transcription RN7SK and promotes base pair rearrangements
  • BRD4 and HEXIM1 proteins interact with CCNT1 at or very near speckle domain
  • mechanism of release of CCNT1 and HEXIM1 from the RN7SK snRNP by viral and cellular activators includes a conformational change in RN7SK
  • interacts with two key TP53 regulators, nucleophosmin and double minute-2 protein (HDM2), implying a possible connection between HEXIM1 and the TP53 signaling pathway
  • role of HEXIM1 in regulating human pluripotent stem cells (hPSCs) fate through a CCNT1-independent pathway
  • HEXIM1 attenuated the interaction of HIF1A with HDAC1 (histone deacetylase 1), resulting in acetylation of HIF1A
  • binding of HEXIM1 protein triggers the inhibition of the kinase complex CCNT1, a key actor of the switch from paused transcription to elongation
  • PPM1G phosphatase directly binds RN7SK RNA and the kinase inhibitor HEXIM1 once CCNT1 has been released from the RN7SK snRNP
  • binds to the CDK9 catalytic site to inhibit CCNT1
  • inhibit androgen receptor transcriptional activity
  • cell & other
    REGULATION
    induced by by hexamethylene-bis-acetamide in vascular smooth muscle cells
    repressed by by estrogens
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    during the development and progression of prostate cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target might be a pharmacological target for drug development to modulate Glucocorticoid receptor function
    SystemTypeDisorderPubmed
    neuromuscular  
    1s a potential therapeutic target for degenerative muscular diseases
    ANIMAL & CELL MODELS