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FLASH GENE

Symbol

PRKD1

contributors: mct/ - updated : 15-06-2016

HGNC name	protein kinase D1
HGNC id	9407

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002742 18 - 3679 NP_002733 - 912 - 2009 19581308

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 Endocrine neuroendocrine pituitary     highly   thyroid       highly Hearing/Equilibrium ear inner cochlea   highly Nervous brain         Reproductive female system breast mammary gland     Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone       Muscular striatum skeletal   predominantly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Muscular myocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a cysteine-rich domain that comprises 2 domains, C1a and C1b
	a pleckstrin homology domain
	a kinase domain at the carboxy terminus, PDZ-binding motifs that can target the kinases to distinct subcellular scaffolds through interactions with PDZ domain-containing proteins

HOMOLOGY

Homologene

FAMILY	protein kinase superfamily
	CAMK Ser/Thr protein kinase family
	Ca2+/Calmodulin-dependent kinase superfamily

CATEGORY

signaling , receptor membrane serine/threonine

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus
text	predominantly expressed in type I myofibers

basic FUNCTION	cytosolic serine-threonine kinase binding to the trans-Golgi network and regulating the fission of transport carriers specifically destined to the cell surface
	inducing pre-T cell proliferation
	implicated in the regulation of cell shape, adhesion, and migration
	playing a role in actin remodelling
	having a negative regulatory function in cell migration
	regulates the dynamics of actin turnover through phosphorylation of proteins of the actin polymerization machinery, such as cortactin
	key regulator of the cofilin signaling pathway thereby controlling actin remodeling and polarized cell motility in cervix carcinoma, breast cancer, and pancreatic cancer cells
	role in contraction-induced SLC2A4 translocation and the combined actions of PRKD1 on TNNI3 phosphorylation and on SLC2A4 translocation would efficiently link accelerated contraction mechanics to increased energy production when the heart is forced to increase its contractile activity
	highly effective class II HDAC kinase, and key regulator of skeletal muscle function
	plays a role in numerous processes including cell proliferation, cell survival, immune cell signaling, gene expression, vesicle trafficking, and neuronal development
	role in cardiomyocyte signal transduction through effects on class IIa HDACs
	upstream regulator of cortactin (CTTN) and function in actin organization as well as cell migration
	potentially important role in controlling cancer progression and metastasis
	unlike PRKD1, PRKD2 catalytic activity is dispensable for normal embryogenesis
	PRKD1-mediated phosphorylation of DLC1 on serine 807 negatively regulates DLC1 cellular function
	key signaling enzyme that mediate a range of physiologically important cellular responses
	novel role of PRKD1, PRKD2 as a regulator of RHOA activity and actin stress fiber formation through phosphorylation of rhotekin
	PRKD1 signaling promotes the migration of intestinal epithelial cells
	major regulator of anchorage-dependent and -independent growth of cancer cells controlled via the transcription factor SNAI1
	involved in Golgi-to-cell surface transport by controlling the biogenesis of specific transport carriers
	is crucial for the cleavage of the noncompact zones of Golgi membranes in G2 phase
	controls interstack Golgi connections in a RAF1/MAP2K1-dependent manner, a process required for entry of the cells into mitosis
	tight spatio-temporal control of PRKD1 activity is likely critical for the coordination of directed cell migration
	is a downstream effector of ROS signaling to regulate IL6/IL8 induction via modulation of NFKB1 activity
	could potentially act as a tumor suppressor at early stage of tumor development in certain types of cancers
	is an upstream regulatory kinase of MTA1 status and its associated metastatic activity

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

	novel PRKD1 signaling pathway through RIN1 and Abl kinases that is involved in the regulation of actin remodeling and cell migration
	AKAP13-mediated PRKD1 signaling regulates the transcriptional response to cardiac hypertrophy

a component

INTERACTION

DNA

RNA

small molecule

protein	directly interacts with F-actin, phosphorylates cortactin and negatively regulates cell migration
	interacts and phosphorylates HSPB1
	interaction with MYD88 (is essential for MYD88-dependent proinflammatory immune responses)
	OSBP is a substrate of PRKD1 at the Golgi
	serine 1884 is essential for the regulation of CACNA1C by PRKD1
	efficiently interacts with SNAI1 in nuclei
	VASP is a novel substrate for PRKD1(PRKD1 directly phosphorylates VASP at two serine residues, Ser-157 and Ser-322)
	FHL1 and FHL2 are novel cardiac PRKD1 partners, which differentially facilitate PRKD1 activation and HDAC5 phosphorylation by distinct neurohormonal stimuli, but are unlikely to regulate MEF2A-driven transcriptional reprogramming
	PRKD1 specifically phosphorylates NOS1 in the activatory residue Ser 1412, and this phosphorylation increases NOS1 activity and ·NO production in living cells
	PRKD1 is an upstream regulatory kinase of MTA1

cell & other

REGULATION

activated by

activated in an agonist-specific manner in cardiomyocytes

Other

canonical pathway for PRKD1 activation by growth factor receptors involves diacylglycerol binding to the C1 domain and protein kinase C-dependent phosphorylation at the activation loop

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       gain of function PRKD1 activation impicated in the pathogenesis of cardiac hypertrophy and the evolution of heart failure syndromes constitutional   deletion     in Rett syndrome variant. probably with misregulation of the FOXG1 gene rather than a primary abnormality of PRKD1 tumoral     --low   aberrantly methylated and silenced in its expression in invasive breast cancer cells and during breast tumor progression, increasing with the aggressiveness of tumors

Susceptibility

to muscular fatigue

Variant & Polymorphism other	genetic deletion in type I myofibers increases susceptibility to fatigue

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer reproductive breast targeted upregulation of PKD1 expression may be used as a therapeutic approach to reverse the invasive phenotype of breast cancer cells

ANIMAL & CELL MODELS