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FLASH GENE

Symbol

DPYSL5

contributors: mct/pgu - updated : 21-03-2019

HGNC name	dihydropyrimidinase-like 5
HGNC id	20637

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	102.25 kb     13 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_020134 13 - 5225 NP_064519 - 564 - 2015 26122847 NM_001253724 13 - 5145 NP_001240653 - 564 - 2015 26122847 NM_001253723 13 - 5142 NP_001240652 - 564 - 2015 26122847 CRMP5T - - - - - - 2013 23298946 new short isoform, derived from C-terminal processing of DPYSL5, presenting a nuclear localization both in glioblastoma, and in cancer cell lines

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain midbrain     highly Homo sapiens Fetal   brain hindbrain     moderately Homo sapiens Adult   ganglia sensory ganglia dorsal root     Homo sapiens   spinal cord         Homo sapiens Reproductive male system testis       Respiratory lung       lowly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central     highly Homo sapiens Fetal Nervous peripherous     highly Homo sapiens Fetal

cells

System Cell Pubmed Species Stage Rna symbol Nervous oligodendrocyte Nervous Purkinje cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal, perinatal

Text	abundant in neuronal progenitors of the subependymal layer and in differentiating interneurons
	abundantly in the developing brain

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cancer bone   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