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FLASH GENE
Symbol DPYSL5 contributors: mct/pgu - updated : 21-03-2019
HGNC name dihydropyrimidinase-like 5
HGNC id 20637
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • an amidohydrolase motif
  • two central WD repeats, as well as several consensus phosphorylation sites
    • conjugated PhosphoP
    mono polymer heteromer , tetramer
    HOMOLOGY
    interspecies homolog to C.elegans unl-33
    intraspecies homolog to dihydropyrimidinase
    Homologene
    FAMILY
  • DHOase family
  • hydantoinase/dihydropyrimidinase subfamily
  • Collapsin Response Mediator Protein (CRMP) family
    • CATEGORY regulatory , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,inner
    intracellular,cytoplasm,cytosolic
    text
  • present in brain mitochondria and is targeted to the inner mitochondrial membrane
  • strongly expressed during postnatal development and regeneration and decreased with myelination
    • basic FUNCTION
  • mediating signals involved in the guidance and outgrowth of axons
  • neural growth cone collapse
  • involved in signaling of axon guidance and neurite outgrowth during neural development and regeneration
  • inhibits tubulin polymerization and neurite outgrowth
  • potentially involved in the development, maintenance and synaptic plasticity of Purkinje cells
  • importance of DPYSL5 in axon-Schwann cell cooperation during development and regeneration
  • plays an important role in the regulation of neuronal polarity by inhibiting dendrite outgrowth at early developmental stages
  • novel regulatory mechanism that utilizes DPYSL5-induced mitophagy to orchestrate proper dendrite outgrowth and neuronal function
  • cytosolic protein that play a major role in nervous system development
  • plays a critical role in the regulation of osteosarcoma
  • plays a significant role in neuronal migration, axonal guidance, dendrite outgrowth, and synapse formation by interacting with microtubules
  • is likely an inhibitory regulator of both neurite outgrowth and axonal guidance contributing to neuronal polarity, as well as dendrite development at early developmental stages
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    text oligodendroglia process extension
    PATHWAY
    metabolism
    signaling
    a component form a large complex composed of DPYSL4 and other unidentified proteins
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • dihydropyrimidinase and all the CRMP with the exception of CRMP1
  • DPYSL2 mediating SEMA3A signaling pathway in oligodendrocytes
  • interacts with DPYSL4 and protein-tyrosine kinase(s), and is a new member of an emerging family of molecules that potentially mediate signals involved in the guidance and outgrowth of axons
  • DPYSL5 binding to tubulin modulates DPYSL2 regulation of neurite outgrowth and neuronal polarity during brain development
  • DPYSL5 serves as a major mediator of NOTCH1 signaling and AKT1 activation by controlling the degradation of the NOTCH1 receptor
  • is able to interact with the actin cytoskeleton network in the growth cone and affect growth cone development and neurite outgrowth via this interaction in developing hippocampal neurons
  • SOX5 increases DPYSL5 promoter activity, but not if the putative SOX5 binding site is mutated
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) NDDCCA
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    CRMP-5-IgG found in paraneoplastic ophthalmological entity of combined optic neuritis and retinitis with vitreous inflammatory cells
    tumoral     --other  
    paraneoplastic immunoglobulin G (IgG) autoantibody expressed in thymoma, lung carcinoma
    tumoral     --over  
    in 98.6p 100 of high-grade neuroendocrine lung tumors, including small cell lung carcinoma and large cell lung neuroendocrine carcinoma, but not in any of the squamous cell carcinomas or lung adenocarcinomas
    tumoral     --over  
    in osteosarcoma cell lines and associated with increased migration and invasion
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • novel marker for routine pathologic evaluation of lung tumors surgical samples in distinguishing between highly aggressive neuroendocrine carcinoma and the other lung cancers
  • prognostic factor in osteosarcoma
    • Therapy target
    SystemTypeDisorderPubmed
    cancerbone 
    could be a potential therapeutic target in osteosarcoma
    ANIMAL & CELL MODELS
  • collapsin response mediator protein 5-deficient mice showed abnormal Schwann process extension resulting in abnormal cell-axon segregation