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FLASH GENE
Symbol DDX5 contributors: mct - updated : 19-10-2015
HGNC name DEAD (Asp-Glu-Ala-Asp) box polypeptide 5
HGNC id 2746
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • one helicase ATP-binding domain
  • one helicase C-terminal domain
  • conjugated PhosphoP
    mono polymer heteromer , dimer
    HOMOLOGY
    interspecies homolog to murine Ddx5 (99.2pc)
    homolog to rattus Ddx5 (99.3pc)
    Homologene
    FAMILY
  • DEAD box helicase family
  • DDX5/DBP2 subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleolus
    text
  • can localize to the nuclear matrix during interphase by binding AKAP95
  • basic FUNCTION
  • RNA helicase with RNA dependent ATPase activity
  • involved in translation initiation, nuclear and mitochondrial splicing and ribosome and spliceosome assembly
  • important transcriptional regulator, functioning as a coactivator or corepressor, depending on the context of the promoter and the transcriptional complex
  • may act as a tumor cosuppressor in governing p53 transcriptional activity
  • proliferation-associated nuclear antigen, reacting with the simian virus 40 tumor antigen
  • playing a critical role with DDX17 in promoting the assembly of proteins required for formation of the transcription initiation complex and chromatin remodeling
  • coactivator of MYOD1
  • may be involved in pre-mRNA splicing
  • may also confer apoptosis resistance by upregulation of X-chromosome-linked inhibitor apoptosis protein-associated factor 1
  • phosphorylated DDX5 protects cells from programmed cell death by preventing procaspase-8 from proteolytic cleavage
  • androgen receptor transcriptional coactivator
  • involved in multiple myeloma tumorigenesis
  • DDX5 and DDX17 have been shown to act as transcriptional co-activators for a diverse range of transcription factors, including oestrogen receptor-alpha (ESR1)
  • crucial role for DDX17 in ESR1 co-activation and oestrogen-dependent cell growth and likely distinct but important roles for both DDX5 and DDX17 in regulating ESR1 activity in breast cancer
  • repressor of fibrogenic genes in hepatic stellate cells through interaction with transcriptional complexes
  • is a key TP53-independent target of the CDKN2A and is a novel non-oncogene participant in ribosome biogenesis
  • DDX5 and DDX17 have a dual role in the control of the pro-migratory NFAT5 transcription factor
  • DDX5 and DDX17 are members of a large family of highly conserved proteins that are involved in gene-expression regulation
  • RNA helicases DDX5 and DDX17 dynamically orchestrate transcription, miRNA, and splicing programs in cell differentiation
  • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • identified in the spliceosome C complex
  • DDX5/SRA1 stabilizes the interaction of cohesin with CTCF by binding to both, and is required for proper insulator function
  • INTERACTION
    DNA
    RNA
  • binding
  • small molecule nucleotide,
  • ATP binding
  • protein
  • substrate of TLK1 (phosphorylates immunoprecipitated DDX5)
  • phosphorylated DDX5 interacts with nuclear beta catenin and is thus involved in cell proliferation
  • interacting with fibrillarin in nascent nucleoli during late telophase
  • interacting with SARS coronavirus helicase
  • CDKN2A inhibited the interaction between DDX5 and nucleophosmin (NPM), preventing association of DDX5 with the rDNA promoter and nuclear pre-ribosomes
  • DDX5 and DDX17 act are transcriptional coactivators of NFAT5 and are required for activating NFAT5 target genes involved in tumor cell migration
  • ATP-dependent DEAD-box RNA helicase, is a component of the MAML1 protein complex
  • DDX5 interacts with MAML1 and is associated with the endogenous NOTCH1 transcription activation complex in human T-ALL leukemic cells
  • ARVCF interacts with different proteins involved in mRNA-processing: SRSF1 (SF2/ASF), DDX5, and HNRNPH2
  • cell & other
    REGULATION
    Other sumoylation on lys53 modulates its transcriptional activity and promotes its interaction with HDAC1
    PDGF-dependent phosphorylation by c-Abl kinase in the nyucleus
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    increased expression and polyubiquitylated in colorectal tumors, may contribute to colon cancer formation by directly upregulating proto-oncogenes
    tumoral     --over  
    overexpressed in prostate cancer with a possible role in progression to hormone refractory disease
    tumoral fusion      
    gene fused in frame with ETV4 in prostate cancer, leading to the expression of a DDX5-ETV4 fusion protein
    Susceptibility
    Variant & Polymorphism SNP
  • SNP S480A is linked to a reduced repressive function of DDX5 and thus an enhanced fibrogenic activity
  • DDX5 minor allele is associated with increased risk of developing advanced fibrosis in patients with chronic hepatitis C
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    potential new target for modulating the Notch signaling in leukemia
    ANIMAL & CELL MODELS