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FLASH GENE
Symbol DHX9 contributors: mct/ - updated : 05-09-2023
HGNC name DEAH (Asp-Glu-Ala-His) box polypeptide 9
HGNC id 2750
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • seven conserved core motifs, including two copies of a double-stranded RNA-binding domain at the N-terminus
  • a RGG box, forming a protein-protein interaction surface that contacts the exonuclease domain of WRN
  • nuclear localization signal(RHA-NLS) consisting of 19 AAs is highly conserved through species
  • a bidirectional nuclear transport domain (NTD) located in its C- terminus and a RGG rich region
  • HOMOLOGY
    interspecies homolog to Drosophila maleless (MLE)
    intraspecies paralog to DHX30
    paralog to DDX3X
    Homologene
    FAMILY
  • DEAD box helicase family
  • DEXH family of helicase superfamily 2
  • CATEGORY structural protein
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic,granule
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,nucleoplasm,nuclear bodies
    intracellular,nucleus,nucleolus
    text
  • its translocation from the nucleolus to the nucleus found with IMPDH inhibition does not mediate the inhibition of rRNA synthesis
  • shuttles rapidly between the nucleus and the cytoplasm by virtue of a bidirectional nuclear transport domain (NTD) located in its carboxyl terminus
  • basic FUNCTION
  • forming a matrix of keratin intermediate filaments which contribute to the structure of hair fibers
  • involved in transcription and RNA processing
  • plays a role in promoting the DNA processing function of WRN, which in turn might be necessary for maintaining genomic stability
  • involved in multiple cellular processes and the life cycles of many viruses
  • essential for survival of cultured hepatoma cells and the ATPase activity appears to be important for this critical role
  • acting as a bridging factor linking nuclear beta-actin with Pol II
  • substrate for EIF2AK2, with phosphorylation perturbing the association of the helicase with double-stranded RNA (dsRNA)
  • cooperative functions for WRN and DHX9 at both migrating and stalled replication forks, where they seem to be involved in the removal of primer RNA-containing Okazaki fragments
  • role in maintaining genome integrity by unwinding mutagenic triplex DNA structures
  • possesses strand displacement activity on triplex DNA structures containing a 3prime-single-stranded overhang, but undetectable activity on the blunt-end duplex DNA structures
  • having ability to preferentially resolve mutagenic triplex DNA structures in an ATP-dependent fashion
  • DDX3X, DDX1 and DHX9 are among the helicases that are required for the replication of a diverse range of viruses
  • is involved in preventing genomic instability induced by alternatively structured DNA in human cells
  • key participant in a number of gene regulatory steps, including transcriptional, translational, and microRNA-mediated control, DNA replication and maintenance of genomic stabilit
  • its functions include regulation of DNA replication, transcription, translation, microRNA biogenesis, RNA processing and transport, and maintenance of genomic stability
  • promotes R-loop formation in cells with impaired RNA splicing
  • nuclear matrix associated protein that facilitates a number of nuclear functions including initiation of DNA replication, epigenetic maintenance and associates with the inactive X-chromosome
  • DHX9 plays an integral role in repairing DNA breaks through homologous recombination (HR) via its recruitment of BRCA1 to DSBs
  • critical role for DHX9, a RNA helicase involved in the processing of pre-mRNA during transcription, in the initiation of HR
  • role for DHX9 in the DNA Damage Response that provides a critical link between RNA, RNA Pol II and the repair of DNA damage by homologous recombination
  • transcriptional regulator, which is consistent with its mostly nucleic localization, and is also involved in recognizing RNA viruses in the cytoplasm
  • is crucial for host resistance to RNA virus infections, and plays an important role in antiviral immunity
  • is a critical regulator of mammalian neurodevelopment and neuronal homeostasis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of the triplex DNA-protein complex in mammalian cells
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binds MBD2, HRMT1L2/PRMT1, and RELA
  • interact with XRCC5 and with TOP2A in an RNA dependent
  • manner
  • interacts with the Werner syndrome helicase WRN, an enzyme associated with premature aging and predisposition to tumorigenesis, DNA helicase (WRN) that can engage in direct protein–protein interactions with DHX9, an essential enzyme involved in transcription and DNA repair
  • actin-interacting protein in pre-initiation complexes
  • DHX9 suppression elicits an apoptotic or senescence response by activating TP53 signaling
  • DHX9 shares common functions with CIZ1, including interaction with XIST long-non-coding RNA, epigenetic maintenance and regulation of DNA replication
  • DHX9-CIZ1 are required for efficient cell cycle progression at the G1/S transition and that nucleolar recruitment is integral to their mechanism of action
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) CMT2EE , DIMBE
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • DHX9 may be a promising and valuable biomarker for Pancreatic ductal adenocarcinoma (PDAC)
  • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivepancreas
    potential target for treating Pancreatic ductal adenocarcinoma (PDAC)
    cancer  
    targeting of DHX9 as an effective and specific chemotherapeutic approach
    ANIMAL & CELL MODELS
  • Dhx9-/- mice exhibited decreased locomotor activity (both forward and vertical) and locomotor speed