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FLASH GENE

Symbol

DAPK1

contributors: mct/pgu - updated : 15-11-2019

HGNC name	death-associated protein kinase 1
HGNC id	2674

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	9q21.33      Physical location : 90.112.755 - 90.323.548
Synonym name	DAP kinase 1
Synonym symbol(s)	DAPK, DAPK-1, DKFZp781I035
EC.number	2.7.11.1

DNA

TYPE	functioning gene
STRUCTURE	210.80 kb     26 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence

cytosine-phosphate-guanine/HTF

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_004938 26 - 5942 NP_004929 - 1430 - 2001 11579085

EXPRESSION

Type

widely

constitutive of

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 Endocrine parathyroid       highly Lymphoid/Immune thymus       highly Reproductive female system placenta     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal   highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N terminal protein-kinase domain followed by a conserved calmodulin binding domain
	eight ankyrin repeats
	two P-loops
	a death domain
	a functional ROC (Ras of complex proteins) domain that mediates homo-oligomerization and GTP binding through a defined P-loop motif (GTP binding regulates its function through intramolecular signalling)

HOMOLOGY

Homologene

FAMILY	protein kinase superfamily
	serine/threonine protein kinase family
	ROCO family of proteins

CATEGORY

enzyme , signaling

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytoskeleton,microfilament

basic FUNCTION	adhesion inhibitory effect, inducing death coupling the control of apoptosis to metastasis
	calcium/calmodulin serine/threonine kinase, which positively mediates programmed cell death in a variety of systems
	involved in Fas-induced extrinsic apoptosis in lymphoid cells
	phosphorylates BECN1 on Thr 119 located at a crucial position within its BH3 domain, and thus promotes the dissociation of BECN1 from BCL2L1 and the induction of autophagy
	phosphorylates tropomyosin-1 in response to ERK activation by hydrogen peroxide (H(2)O(2), and regulates the formation of stress fibers in response to oxidative stress
	modulation of DAPK1 activities is critical for regulation of apoptosis and cellular homeostasis
	phosphorylating GRIN2B and in turn enhancing the NR1/NR2B receptor channel conductance
	promotes cell death partly through its effect on regulating actin cytoskeletons (
	molecular link of DAPK to tau phosphorylation, an event associated with Alzheimer disease pathology
	inhibits the ability of PIN1 to induce centrosome amplification and cell transformation
	calmodulin-dependent protein kinases that are regulated by oligomerization, calmodulin binding, and autophosphorylation
	new functions and regulation for both DAPK1 and DDX20 in carcinogenesis

CELLULAR PROCESS	cell life, cell death/apoptosis

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

constituent of the actin microfilament network

INTERACTION

DNA

RNA

small molecule

protein	suppressing integrin activity and disrupting matrix survival signals thereby activating a p53 dependent apoptotic pathway
	interaction with GRIN2B mediating brain damage in stroke
	KLHL20-CUL3-RBX1 E3 ligase complex promotes DAPK1 polyubiquitination, thereby inducing the proteasomal degradation of DAPK1, and controling interferon response
	interacting with PIN1 (phosphorylates PIN1 and inhibits its prolyl isomerase activity and cellular function)
	interacting with UNC5B (triggers cell death through the activation of the serine-threonine protein kinase DAPK1)
	ATF6 in association with the transcription factor CEBPB, regulates IFNG-induced expression of DAPK1
	ITPRIP binds directly to DAPK1 and inhibits DAPK1 catalytic activity

cell & other

REGULATION

repressed by

HOXB7

Other	calcium Ca2+/calmodulin-regulated
	triggered by IFNG
	regulated by CEBPB (CEBPB binds to the promoter of DAPK1 and is required for the regulation of DAPK1)
	regulated by RGM/neogenin that regulates cell fate by controlling the DAPK1 activity

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral         by hypermethylation in head and neck carcinomas tumoral     --low   by promoter methylation in B cell chronic lymphocytic leukemia and chronic myeloid leukemia (promoter methylation might play a significant role in the progression of CML)

Susceptibility

to late-onset Alzheimer's disease to chronic lymphocytic leukemia

Variant & Polymorphism SNP	significantly associated with late-onset Alzheimer's disease
	downregulation in familial chronic lymphocytic leukemia

Candidate gene	for sensitive detection in plasma or serum of cancer gastric, lung cancer, head and neck cancer, by DNA methylation markers
Marker
Therapy target
	System Type Disorder Pubmed cancer hemopathy   for the development of novel treatment regimens in chronic lymphocytic leukemia involving epigenetic therapies for gene reactivation cancer digestive liver potential therapeutic targets for HCC

ANIMAL & CELL MODELS