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FLASH GENE
Symbol PRKD1 contributors: mct/ - updated : 15-06-2016
HGNC name protein kinase D1
HGNC id 9407
Location 14q12      Physical location : 30.045.688 - 30.396.899
Synonym name
  • protein kinase C, mu
  • protein kinase D
  • serine/threonine-protein kinase D1
    • Synonym symbol(s) PKD, PKCM, PRKCM, PKC-MU, PKD1
    EC.number 2.7.11.13
    DNA
    TYPE functioning gene
    STRUCTURE 351.21 kb     18 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    18 - 3679 - 912 - 2009 19581308
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineneuroendocrinepituitary  highly
     thyroid   highly
    Hearing/Equilibriumearinnercochlea highly
    Nervousbrain    
    Reproductivefemale systembreastmammary gland   Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    Muscularstriatumskeletal predominantly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Muscularmyocyte 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)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    targeted upregulation of PKD1 expression may be used as a therapeutic approach to reverse the invasive phenotype of breast cancer cells
    ANIMAL & CELL MODELS