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FLASH GENE

Symbol

DEK

contributors: mct/pgu - updated : 07-02-2018

HGNC name	DEK oncogene
HGNC id	2768

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	DEK myelodysplastic syndrome, refractory anemia with excess of blasts in transformation (MDS/RAEBT)
Location	6p22.3      Physical location : 18.224.399 - 18.264.799
Synonym name	DEK oncogene (DNA binding)
	protein DEK
Synonym symbol(s)	D6S231E

DNA

TYPE	functioning gene
STRUCTURE	40.40 kb     11 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001134709 10 - 2785 NP_001128181 - 341 - 2010 20040570 NM_003472 11 - 2879 NP_003463 43 375 - 2010 20040570

EXPRESSION

Type

widely

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 Cardiovascular vessel       highly Digestive esophagus       predominantly   intestine large intestine colon   moderately   intestine small intestine     moderately   salivary gland       highly Endocrine thyroid       moderately Hearing/Equilibrium ear       moderately Lymphoid/Immune thymus       moderately Reproductive female system uterus cervix   highly   male system prostate     moderately Urinary bladder       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly Connective bone     moderately

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES		acid
STRUCTURE

motifs/domains	a SAP putative DNA binding domain
	an acidic domain interacting with histone
	central and C-terminal regions are highly conserved

conjugated

PhosphoP

HOMOLOGY

interspecies	ortholog to rattus Dek (92.5 pc)
	ortholog to murine Dek (91.4 pc)

Homologene

FAMILY

DNA-binding SAP family

CATEGORY

chaperone/stress , protooncogene

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,nucleoplasm

basic FUNCTION	playing a role in viral genome replication
	inducing positive supercoils into closed circular DNA
	being also involved in splice site selection during mRNA processing
	nuclear phosphoprotein implicated in oncogenesis and autoimmunity
	promotes the repair of DNA lesions and protects cells from genotoxic agents that typically trigger poly(ADP-ribose) polymerase activation
	crucial role of poly(ADP-ribosyl)ation in shaping DEK autoantigenic properties and in its function as a promoter of cell survival
	suppresses cellular senescence, apoptosis, and differentiation, thus promoting cell growth and survival in monolayer and organotypic epithelial raft models
	required for intron removal
	exerting a potent inhibitory effect on both EP300 and PCAF-mediated histone acetyltransferase activity and transcription
	playing a role in the proliferation of hematopoietic cells
	DEK-NUP214 fusion protein appears defective, at least in part, in assisting transcriptional regulation of certain genes that might be essential for normal differentiation of hematopoietic cells
	may be a histone chaperone
	promotes leukemic cell survival and is downregulated by both Nutlin-3 and chlorambucil in B-chronic lymphocytic leukemic cells
	DEK positively regulates engrafting capability of self-renewing hematopoietic stem (HSCs)
	CEBPA and DEK coordinately activate myeloid gene expression and S21 phosphorylation on wild-type CEBPA mediates protein interactions that regulate the differentiation capacity of hematopoietic progenitors
	biochemically distinct, conserved nonhistone protein that is vital to global heterochromatin integrity
	paracrine loop involving DEK plays a role in chromatin biology
	identified as one of the most abundant proteins in human chromatin
	is a unique chromatin architectural factor which binds to non-B-form DNA structures, such as cruciform DNA or four-way junctions
	facilitates cellular proliferation under conditions of DNA replication stress by promoting replication fork progression
	plays an important role in cell processes and participates in a variety of cellular metabolic functions, and its altered expression is associated with several human malignancies
	critical role of DEK and its regulation in tumorigenesis and metastasis of hepatocellular carcinoma
	transcription factor, involved in mRNA splicing, transcriptional control, cell division and differentiation
	important for DNA double-strand break repair
	plays multiple roles to facilitate tumor growth and maintenance
	CELF1 and DEK were found to represent early-induced melanoma genes and adverse indicators of overall patient survival

CELLULAR PROCESS	nucleotide, transcription, regulation
	nucleotide, RNA splicing

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

found in a mRNA splicing-dependent exon junction complex (EJC) with DEK, RBM8A, RNPS1, SRRM1 and THOC4

INTERACTION

DNA	binding to cruciform and superhelical DNA

RNA

binding

small molecule	nucleotide,
	GTP

protein	histones H2A, H2B, H3, H4, acetylated histone H4
	non-phosporylated DAXX
	HDAC2
	interacting wth SET and PARP1 (constitute a network governing access to chromatin by the transcription machinery)
	molecular links between DEK and DNA damage response signaling pathways, suggesting that DEK contributes to DNA repair
	DEK emerges as an TERT repressor shared by various leukemia subtypes and seems involved in the deregulation of numerous genes associated with leukemogenesis
	is a critical factor that interacts with an essential upstream enhancer element of the KLF1 promoter and exerts a positive effect on KLF1 levels
	DEK is an unexpected target and downstream effector of CELF1

cell & other

the (pets) site of the HIV2 enhancer, autoantigen in patients with pauciarticular onset juvenile rheumatoid arthritis

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

DEK

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in hepatocellular carcinoma tumoral     --over   in many solid tumors such as colon cancer, larynx cancer, bladder cancer, and melanoma tumoral fusion translocation     t(6;9) chromosomal translocation associated with a subtype of acute myelogenous leukemia (AML), which results in the formation of a DEK-NUP214 fusion protein tumoral     --over gain of function in retinoblastoma tumoral     --over   overexpression in pancreatic ductal adenocarcinoma (PDAC) was correlated with tumor size, histological grade, tumor&8209;node&8209;metastasis (TNM) stage and overall survival (OS) rates

Susceptibility

Variant & Polymorphism

Candidate gene	detection of DEK protein expression should be useful for the diagnosis and prognosis of ovarian serous cancer
	may be a potential biomarker for poor prognostic evaluation in PDAC
Marker
Therapy target
	System Type Disorder Pubmed neurology ataxia   able to partially reverse the mutation-prone phenotype of cells from patients with ataxia telangiectasia cancer reproductive ovary might be a useful molecular target for ovarian cancer therapy cancer     targeted suppression of DEK may become a strategic approach to the treatment of cancer cancer brain   can be used as a potential target for astrocytic tumor gene therapy

ANIMAL & CELL MODELS