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FLASH GENE

Symbol

PRKCD

contributors: mct - updated : 10-12-2017

HGNC name	protein kinase C, delta
HGNC id	9399

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	CVID9 immunodeficiency, common variable, 9
Location	3p21.1      Physical location : 53.195.222 - 53.226.731
Synonym name	serine/threonine protein kinase
Synonym symbol(s)	PKCD, MAY1, nPKC-delta
EC.number	2.7.11.13

DNA

TYPE	functioning gene
STRUCTURE	31.53 kb     19 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site   transcription factor
text structure	multiple putative tranription binding sites involved in spermatogenesis, embryogenesis, development

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_006254 19 - 2850 NP_006245 77 676 - 2003 12809676 encoding for the same product as variant 2 NM_212539 18 splicing 2738 NP_997704 77 676 - 2003 12809676 lacking exon 2 encoding for the same product as variant 1

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 Digestive intestine large intestine colon   moderately Endocrine pancreas       lowly   parathyroid       moderately Lymphoid/Immune spleen       lowly Nervous brain       lowly   nerve       moderately Reproductive female system ovary     moderately   female system breast mammary gland   moderately   male system prostate     moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic platelet Homo sapiens

cell lineage
cell lines
fluid/secretion	lymph

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an N-terminal regulatory domain with an inhibitory pseudosubstrate sequence and two cysteine-rich zinc-finger-like sequences (C1A and C1B)
	two zinc-dependent phorbol-ester and DAG binding domains
	one c2 domain
	a C-terminal catalytic domain with two conserved regions, an ATP-binding region (C3) and a catalytically active substrate-binding region (C4), with a putative nuclear localization signal in the catalytic domain

HOMOLOGY

interspecies	homolog to rattus Prkcd (89.90 pc)
	homolog to murine Prkcd (90.79 pc)

Homologene

FAMILY	Ser/Thr protein kinases family
	PKC subfamily

CATEGORY

signaling , receptor membrane tyrosine

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus
text	translocates into the nucleus after exposure of cells to 1-beta-d-arabinofuranosylcytosine (ara-C)

basic FUNCTION	involved in proheparin-binding EGF-like growth factor (HBEGF) ectodomain shedding upon TPA stimulation
	may be playing a role in antigen-dependent control of B-cell function
	required for mitochondrial apoptosis induction by genotoxic stress
	plays an essential role in the genotoxic stress response leading to apoptotic cell death in various cell types
	plays a role in the development of hypertension-induced encephalopathy
	plays an essential role in the regulation of apoptosis in response to a large and diverse array of apoptotic stimuli
	directly transduces TCR signals leading to polarized granule secretion
	plays a key role in the inflammatory effect of IL6 in adipose cells
	differentially regulates platelet functional responses
	function in telomerase reverse transcriptase (TERT) gene repression and plays a key role in cellular senescence program
	acts both upstream and downstream of caspase-3 for apoptosis of vascular smooth muscle cells
	with PRKCH, differently regulate the expression of loricrin and Jun family proteins in keratinocytes
	plays a role in alanine aminotransferase release, the ER stress signal, and cell death
	regulates palmitic acid-induced lipotoxicity
	plays a role not only in the propagation of the ER stress signal but also in cell death

CELLULAR PROCESS	cell life, differentiation
	cell life, proliferation/growth
	cell life, cell death/apoptosis
	protein, post translation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

PRKCD-MARK2-EIF2A cascade that may play a critical role in cellular proteotoxic stress responses and human diseases

a component

PRMT5/WDR77-dependent methylation is an epigenetic mechanism that assists in silencing of IVL expression, and PRKCD signaling activates gene expression by directly activating transcription and by suppressing PRMT5/WDR77-dependent arginine dimethylation of promoter-associated histones

INTERACTION

DNA

RNA

small molecule

protein	PDK1, NFKB (involved in the expression of PRKCD)
	RAD9A
	interacting with VHL
	interaction between PRKCD and PRKDC participates in apoptosis induced by DNA damage
	apoptotic lamin kinase (efficient nuclear lamina disassembly at apoptosis requires lamin B phosphorylation followed by its caspase-6-mediated proteolytic degradation)
	interacted with and phosphorylated phospholipid scramblase 3 (PLSCR3) after UV irradiation
	IFNA1-induced the expression of IFIT3 and STAT1 in THP-1 cells, and this process was significantly antagonized by the specific inhibitors of both PRKCD and MAPK8
	interacting with TRO (Trophinin-mediated cell adhesion induces apoptosis of human endometrial epithelial cells through PRKCD)
	cathepsin K exocytosis is controlled by PRKCD through modulation of the actin bundling protein myristoylated alanine-rich C-kinase substrate (MARCKS)
	BTK was involved in close contact with Tyr86 and Tyr106 of MAL whereas PKRKCD may phosphorylate Tyr106 only
	PRKCD-mediated MARCKS phosphorylation as a key step in the inflammatory response of neutrophils

cell & other

REGULATION

activated by

a variety of stimuli, including ionizing radiation, anticancer agents, reactive oxygen species (ROS), ultraviolet radiation, growth factors and cytokines

ASSOCIATED DISORDERS

corresponding disease(s)

CVID9

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       gain of function its activation plays a role in progression of steatosis to non-alcoholic steatohepatitis

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed immunology inflammatory   may be a suitable target for novel anti-inflammatory agents neurology leukoencephalopathy   may be a therapeutic target for the prevention of blood-brain barrier disruption

ANIMAL & CELL MODELS