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Symbol DPYSL2 contributors: shn/npt - updated : 27-09-2018
HGNC name dihydropyrimidinase-like 2
HGNC id 3014
Location 8p21.2      Physical location : 26.435.420 - 26.515.693
Synonym name
  • collapsin response mediator protein hCRMP-2
  • dihydropyrimidinase-like 2 long form
  • unc-33-like phosphoprotein 2
  • Synonym symbol(s) CRMP2, ULIP2, DHPRP2, DRP-2, DRP2, CRMP-2, N2A3, ULIP-2,
    TYPE functioning gene
    STRUCTURE 143.98 kb     14 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    text structure
  • SP1, E2F, and GATA1/2 binding sites appeared to play some roles in regulation of expression
  • SMAD1 and -4 bind to the promoter in the neocortex, and overexpression of SMAD1 and 4 suppresses DPYSL2 expression
  • MAPPING cloned Y linked   status provisional
    Map qter - D8S1771 - D8S382 - DPYSL2 - D8S1839 - D8S1820 - cen
    Authors SCW8-3
    TRANSCRIPTS type messenger
    text derived from alternative splicing of their N-terminal region
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    14 - 4567 62 572 specifically localized in neuronal soma and/or axons but was absent from dendrites 2015 26555036
    also called CRMP2A
    - - - - - - 2015 26555036
  • increased expression of the nuclear short isoform of CRMP2B and decreased expression of full-length CRMP2B and ARPC5 in cortical neurons of rats with hypothyroidism
  • CRMP2B and ARPC5 may participate in CNS injury mediated by hypothyroidism by inducing neurite outgrowth inhibition and cytoskeletal protein disorganization
  • 14 - 4655 - 677 - 2015 26555036
    14 - 4297 - 536 - 2015 26555036
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Endocrinepancreas   lowly
    Nervousbrainforebraincerebral cortex highly Homo sapiensFetal
     brainhindbraincerebellum   Homo sapiens
     nerve   highly Homo sapiensFetal
    Reproductivefemale systemplacenta  lowly
    Respiratorylung   highly
    Urinarykidney   lowly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal lowly
    Nervouscentral    Homo sapiensFetal
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    at STAGE
    physiological period fetal, pregnancy
  • abundant in neuronal progenitors of the subependymal layer and in differentiating interneurons
  • onatal brain, in the developing neocortex
    an amidohydrolase motif
    interspecies ortholog to Dpysl2, Mus musculus
    ortholog to Dpysl2, Rattus norvegicus
    ortholog to dpysl2, danio rerio
    ortholog to DPYSL2, Pan troglodytes
    intraspecies homolog to dihydropyrimidinase protein 2
  • CRMP gene family
  • hydantoinase/dihydropyrimidinase subfamily
  • CATEGORY enzyme , signaling
    SUBCELLULAR LOCALIZATION     intracellular
  • located mainly in the dendrites of cerebellar granule neurons, in contrast to the axonal distribution in hippocampal neurons
  • basic FUNCTION
  • plays a role in axon guidance, neuronal growth cone collapse and cell migration
  • plays a critical role in the establishment of neuronal polarity
  • involved in the developmental process of the nervous system, oligodendroglia process extension
  • playing a critical role in axon outgrowth and axon-dendrite specification
  • critical for specifying axon/dendrite fate and axon growth in cultured hippocampal neurons
  • balance between cytoplasmic full-length CRMP2 and post-transcriptionally processed forms of CRMP2 translocated to the nuclear compartment may represent an important key in the regulation of neurite outgrowth during normal brain development
  • transports the Sra-1/WASF1 complex to axons in a kinesin-1-dependent manner and thereby regulates axon outgrowth and formation
  • involved in pathways that regulate the proliferation of non-neuronal cells through its phosphorylation by regulatory proteins
  • playing a role in signaling pathways that regulate the proliferation of non-neuronal cells
  • play a crucial role in neuronal differentiation and axonal outgrowth, and mediates axonal guidance by collapsing growth cones during development
  • may act as a regulator of other functions, such as migration and proliferation
  • complex of KLC1, KIF5C and CRMP2 is involved in transporting tubulin heterodimers and oligomers to the tip of the growing axon
  • promotes the assembly of tubulin subunits onto the ends of existing microtubules and is required for axon formation
  • binds to tubulin heterodimers to promote microtubule assembly
  • essential for axon-dendrite specification, axon outgrowth, and elongation
  • can regulate microtubule assembly, reorganization of actin filaments, and protein trafficking during neurite elongation and axon specification
  • may be required for multipolar to bipolar transition for directional neuronal migration and neurite outgrowth
  • plays essential roles at multiple stages of neuronal development
  • INPP5J and DPYSL2 exert opposing roles in promoting axon selection and neurite elongation and the complex between these proteins serves to regulate the localization of effectors that promote neurite extension
  • modulates Ca2+ channel activity via alterations in surface expression
  • not only involved in glutamate-mediated neurotoxicity but may be effectively targeted to prevent excitotoxicity-mediated neuronal death
  • plays a pivotal role in promoting axon formation, neurite outgrowth and elongation in neuronal cells
  • is a protein critically involved in primary cilia formation
  • ARPC5 and DPYSL2 are closely associated with neurite outgrowth in brain development
  • novel role for SUMO modification in DPYSL2/CACNA1B signaling pathway
  • tethers kainate receptor activity to cytoskeleton dynamics during neuronal maturation
  • is traditionally viewed as an axonal growth protein involved in axon/dendrite specification
  • DPYSL2 and DPYSL3 interacted with one another coordinately to promote growth cone development and axonal elongation
  • DPYSL2 and DPYSL3 form likely complexes to bridge microtubules and actin and thus work cooperatively to regulate growth cone development and axonal elongation
  • plays a key role in axon guidance, dendritic morphogenesis and cell polarization, and is implicated in various neurological and psychiatric disorders
    text neurogenesis
  • novel GSK3A, GSK3B/DPYSL2 pathway that connects neuronal activity to dendritic growth
  • a component
  • DPYSL22·INPP5J complex is likely to dynamically regulate both neurite outgrowth and axon polarity in the normal brain
    small molecule
  • phosphorylated by glycogen synthase kinase-3beta (GSK-3beta)
  • protein
  • DYSPSL5, SEMA3A in oligodendroglia mediating SEMA3A signaling pathway in developing neuron
  • binds to tubulin heterodimers to promote microtubule assembly
  • Rac1-associated protein 1 (Sra-1)/WASP family verprolin-homologous protein 1 (WASF1) complex
  • kinesin light chain 1 (KLC1) and kinesin family member 5C (KIF5C)
  • Collapsin response mediator protein 1 (CRMP1)
  • tubulin
  • numb homolog (Drosophila) (NUMB)
  • DPYSL5 binding to tubulin modulates DPYSL2 regulation of neurite outgrowth and neuronal polarity during brain development
  • BMP-SMAD signaling pathway controls neuronal migration and neurite outgrowth by suppressing the transcription of DPYSL2
  • association between INPP5J and DPYSL2 does not require DPYSL2 phosphorylation, rather this complex significantly reduces when GSK3B is active, conditions under which PI3K/Akt signaling is not activated
  • CHN1 regulates bipolar transition and neuronal migration through modulating the activity of DPYSL2, a microtubule-associated protein
  • DPYSL2 protein SUMOylation modulates SCN9A channel trafficking
  • DPYSL2 interacts with NMDAR and SLC8A1 and regulates their functional activity
  • GDI1, PACSIN1, and DPYSL2 interact with not only phosphatidic acid (PA) but also with other phospholipids
  • diverse modifications of DPYSL2 cross-talk to control SCN9A activity
  • cell & other
    induced by GDNF but increased expression of DPYSL2 alone is not sufficient for neuritogenesis
    repressed by BMP-SMAD signaling pathway in brain development (this pathway can suppress the transcription of DPYSL2
    Other inhibition of DPYSL2 phosphorylation repairs CNS by regulating neurotrophic and inhibitory responses
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in Down syndrome
    constitutional     --other  
    dysregulation of DPYSL2 may be involved in pathophysiology of neuropsychiatric disorders
    Susceptibility to schizophrenia
    Variant & Polymorphism other polymorphism 2236T>C increasing the risk of schizophrenia
    Candidate gene
    Therapy target
    may be effectively targeted to prevent excitotoxicity-mediated neuronal death, in traumatic brain injury
  • Crmp2-/- mice showed altered expression of proteins involved in GABAergic synapse, glutamatergic synapse and neurotrophin signaling pathways