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PRKD1 (Protein Kinase D1)

Written2006-01C Du, M Jaggi, W Zhang, KC Balaji
Division of Urology, University of Massachusetts Memorial Medical Center, 55 Lake Avenue North, Worcester, MA 01605, USA

(Note : for Links provided by Atlas : click)

Identity

Other namesPKD1 (Protein Kinase D1)
PKCmu
PRKCM
HGNC (Hugo) PRKD1
LocusID (NCBI) 5587
Atlas_Id 41860
Location 14q12  [Link to chromosome band 14q12]
Location_base_pair Starts at 30045687 and ends at 30396899 bp from pter ( according to hg19-Feb_2009)  [Mapping PRKD1.png]
Fusion genes
(updated 2016)
ARID1A (1p36.11) / PRKD1 (14q12)DDX3X (Xp11.4) / PRKD1 (14q12)PRKD1 (14q12) / WAC (10p12.1)
PSMA6 (14q13.2) / PRKD1 (14q12)

DNA/RNA

Description The gene spans over 351 kb and the transcript consists of 18 exons
Transcription About 3.8 kb in length; Expressed in several organs with highest expression in kidney, heart and lungs.

Protein

 
Description 912 amino acids residues, 120 kDa on SDS-PAGE gel; contains an alanine and proline rich (AP), two cysteine-rich domains (CysI and CysII), acidic (AC), pleckstrin homology (PH) and kinase domain (KD). Several domain specific protein interactions and functions have been described (see figure below).
Localisation In rested cells, the majority of PKD1 are in the cytoplasm. When activated by phorbol ester, PKD1 rapidly moves to plasma membrane and nucleus.
Function Serine/threonine kinase; protein kinase C downstream effector; intracellular trafficking;
PKD1 has been shown to play a role in proliferation of keratinocytes in skin, B and T lymphocytes and mast cells signaling, possible role in development of central tolerance in thymus gland, proliferation of pancreatic cancer cells, cardiac myocyte contraction, endothelial cell proliferation, osteoblasts differentiation, and prostate cancer cells adhesion and invasion.
Homology Homologues present in mouse and rat.

Implicated in

Note
Entity Advanced prostate cancer
Disease PKD1 phosphorylates E-cadherin in prostate cancer cell lines. E-cadherin phosphorylation is associated with altered cellular aggregation and motility in prostate cancer. Inhibition of PKD1 activity by the selective inhibitor Go6976 in LNCaP cells resulted in decreased cellular aggregation and over expression of PKD1 in C4-2 prostate cancer cells increased cellular aggregation and decreased cellular motility.

  
Entity Cardiac hypertrophy
Disease Transcriptional regulation of gene expression is tightly coupled to histone deacetylases (HDAC) and histone acetyltransferase (HAT) that modify the access of transcription factors to DNA binding sites. PKD1 has been shown to participate in nuclear export of HDAC5. HDAC5 is phosphorylated by PKD1 in cardiac myocytes, which results in the binding of 14-3-3 protein to the phosphoserine motif on HDAC5, thus leading to nuclear export through a CRM1-dependent mechanism. This results in increased transcriptional activity of hypertrophy mediating genes in myocytes. Cardiac failure is usually preceded by cardiac hypertrophy that is mediated by altered gene expression involved in myocyte contraction, calcium handling and metabolism. PKD1 specific inhibitors may be of benefit in limiting cardiac hypertrophy.
  

Bibliography

An invasion-related complex of cortactin, paxillin and PKCmu associates with invadopodia at sites of extracellular matrix degradation.
Bowden ET, Barth M, Thomas D, Glazer RI, Mueller SC
Oncogene. 1999 ; 18 (31) : 4440-4449.
PMID 10442635
 
Structural requirements for localization and activation of protein kinase C mu (PKC mu) at the Golgi compartment.
Hausser A, Link G, Bamberg L, Burzlaff A, Lutz S, Pfizenmaier K, Johannes FJ
The Journal of cell biology. 2002 ; 156 (1) : 65-74.
PMID 11777941
 
Protein kinase C mu is negatively regulated by 14-3-3 signal transduction proteins.
Hausser A, Storz P, Link G, Stoll H, Liu YC, Altman A, Pfizenmaier K, Johannes FJ
The Journal of biological chemistry. 1999 ; 274 (14) : 9258-9264.
PMID 10092600
 
E-cadherin phosphorylation by protein kinase D1/protein kinase C{mu} is associated with altered cellular aggregation and motility in prostate cancer.
Jaggi M, Rao PS, Smith DJ, Wheelock MJ, Johnson KR, Hemstreet GP, Balaji KC
Cancer research. 2005 ; 65 (2) : 483-492.
PMID 15695390
 
PKCu is a novel, atypical member of the protein kinase C family.
Johannes FJ, Prestle J, Eis S, Oberhagemann P, Pfizenmaier K
The Journal of biological chemistry. 1994 ; 269 (8) : 6140-6148.
PMID 8119958
 
Getting to know protein kinase D.
Lint JV, Rykx A, Vantus T, Vandenheede JR
The international journal of biochemistry & cell biology. 2002 ; 34 (6) : 577-581.
PMID 11943587
 
Protein kinase D. A selective target for antigen receptors and a downstream target for protein kinase C in lymphocytes.
Matthews SA, Rozengurt E, Cantrell D
The Journal of experimental medicine. 2000 ; 191 (12) : 2075-2082.
PMID 10859332
 
Regulated nucleocytoplasmic transport of protein kinase D in response to G protein-coupled receptor activation.
Rey O, Sinnett-Smith J, Zhukova E, Rozengurt E
The Journal of biological chemistry. 2001 ; 276 (52) : 49228-49235.
PMID 11641411
 
Protein kinase D signaling.
Rozengurt E, Rey O, Waldron RT
The Journal of biological chemistry. 2005 ; 280 (14) : 13205-13208.
PMID 15701647
 
Protein kinase D: a family affair.
Rykx A, De Kimpe L, Mikhalap S, Vantus T, Seufferlein T, Vandenheede JR, Van Lint J
FEBS letters. 2003 ; 546 (1) : 81-86.
PMID 12829240
 
Protein kinase C mu (PKC mu) associates with the B cell antigen receptor complex and regulates lymphocyte signaling.
Sidorenko SP, Law CL, Klaus SJ, Chandran KA, Takata M, Kurosaki T, Clark EA
Immunity. 1996 ; 5 (4) : 353-363.
PMID 8885868
 
Molecular cloning and characterization of protein kinase D: a target for diacylglycerol and phorbol esters with a distinctive catalytic domain.
Valverde AM, Sinnett-Smith J, Van Lint J, Rozengurt E
Proceedings of the National Academy of Sciences of the United States of America. 1994 ; 91 (18) : 8572-8576.
PMID 8078925
 
Expression and characterization of PKD, a phorbol ester and diacylglycerol-stimulated serine protein kinase.
Van Lint JV, Sinnett-Smith J, Rozengurt E
The Journal of biological chemistry. 1995 ; 270 (3) : 1455-1461.
PMID 7836415
 
Regulation of protein kinase D by multisite phosphorylation. Identification of phosphorylation sites by mass spectrometry and characterization by site-directed mutagenesis.
Vertommen D, Rider M, Ni Y, Waelkens E, Merlevede W, Vandenheede JR, Van Lint J
The Journal of biological chemistry. 2000 ; 275 (26) : 19567-19576.
PMID 10867018
 
Protein kinase C phosphorylates protein kinase D activation loop Ser744 and Ser748 and releases autoinhibition by the pleckstrin homology domain.
Waldron RT, Rozengurt E
The Journal of biological chemistry. 2003 ; 278 (1) : 154-163.
PMID 12407104
 
Protein kinase D (PKD) activation in intact cells through a protein kinase C-dependent signal transduction pathway.
Zugaza JL, Sinnett-Smith J, Van Lint J, Rozengurt E
The EMBO journal. 1996 ; 15 (22) : 6220-6230.
PMID 8947045
 

Citation

This paper should be referenced as such :
Du, C ; Jaggi, M ; Zhang, W ; Balaji, KC
PKD1 (protein kinase D1)
Atlas Genet Cytogenet Oncol Haematol. 2006;10(3):159-160.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/PRKCMID41860ch14q11.html


External links

Nomenclature
HGNC (Hugo)PRKD1   9407
Cards
AtlasPRKCMID41860ch14q11
Entrez_Gene (NCBI)PRKD1  5587  protein kinase D1
AliasesPKC-MU; PKCM; PKD; PRKCM
GeneCards (Weizmann)PRKD1
Ensembl hg19 (Hinxton)ENSG00000184304 [Gene_View]  chr14:30045687-30396899 [Contig_View]  PRKD1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000184304 [Gene_View]  chr14:30045687-30396899 [Contig_View]  PRKD1 [Vega]
ICGC DataPortalENSG00000184304
TCGA cBioPortalPRKD1
AceView (NCBI)PRKD1
Genatlas (Paris)PRKD1
WikiGenes5587
SOURCE (Princeton)PRKD1
Genomic and cartography
GoldenPath hg19 (UCSC)PRKD1  -     chr14:30045687-30396899 -  14q11   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)PRKD1  -     14q11   [Description]    (hg38-Dec_2013)
EnsemblPRKD1 - 14q11 [CytoView hg19]  PRKD1 - 14q11 [CytoView hg38]
Mapping of homologs : NCBIPRKD1 [Mapview hg19]  PRKD1 [Mapview hg38]
OMIM605435   
Gene and transcription
Genbank (Entrez)AK314170 BC160015 BX645735 CN412379 X75756
RefSeq transcript (Entrez)NM_002742
RefSeq genomic (Entrez)NC_000014 NC_018925 NT_026437 NW_004929393
Consensus coding sequences : CCDS (NCBI)PRKD1
Cluster EST : UnigeneHs.508999 [ NCBI ]
CGAP (NCI)Hs.508999
Alternative Splicing GalleryENSG00000184304
Gene ExpressionPRKD1 [ NCBI-GEO ]   PRKD1 [ EBI - ARRAY_EXPRESS ]   PRKD1 [ SEEK ]   PRKD1 [ MEM ]
Gene Expression Viewer (FireBrowse)PRKD1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5587
GTEX Portal (Tissue expression)PRKD1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ15139 (Uniprot)
NextProtQ15139  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ15139
Splice isoforms : SwissVarQ15139 (Swissvar)
Catalytic activity : Enzyme2.7.11.13 [ Enzyme-Expasy ]   2.7.11.132.7.11.13 [ IntEnz-EBI ]   2.7.11.13 [ BRENDA ]   2.7.11.13 [ KEGG ]   
PhosPhoSitePlusQ15139
Domaine pattern : Prosite (Expaxy)PH_DOMAIN (PS50003)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)    ZF_DAG_PE_1 (PS00479)    ZF_DAG_PE_2 (PS50081)   
Domains : Interpro (EBI)DAG/PE-bd    Kinase-like_dom    PE/DAG-bd    PH_dom-like    PH_domain    Prot_kinase_dom    Protein_kinase_ATP_BS    Protein_Kinase_C_mu-related    Ser/Thr_dual-sp_kinase    Ser/Thr_kinase_AS   
Domain families : Pfam (Sanger)C1_1 (PF00130)    PH (PF00169)    Pkinase (PF00069)   
Domain families : Pfam (NCBI)pfam00130    pfam00169    pfam00069   
Domain families : Smart (EMBL)C1 (SM00109)  PH (SM00233)  S_TKc (SM00220)  
DMDM Disease mutations5587
Blocks (Seattle)PRKD1
SuperfamilyQ15139
Human Protein AtlasENSG00000184304
Peptide AtlasQ15139
HPRD05668
IPIIPI00782950   IPI00646409   IPI01020780   IPI01021830   IPI01021550   IPI00953419   
Protein Interaction databases
DIP (DOE-UCLA)Q15139
IntAct (EBI)Q15139
FunCoupENSG00000184304
BioGRIDPRKD1
STRING (EMBL)PRKD1
ZODIACPRKD1
Ontologies - Pathways
QuickGOQ15139
Ontology : AmiGOangiogenesis  positive regulation of endothelial cell proliferation  protein serine/threonine kinase activity  protein serine/threonine kinase activity  protein kinase C activity  protein binding  ATP binding  nucleus  cytoplasm  Golgi apparatus  trans-Golgi network  cytosol  cytosol  plasma membrane  integral component of plasma membrane  cell-cell junction  cell cortex  protein phosphorylation  apoptotic process  inflammatory response  Golgi organization  signal transduction  integrin-mediated signaling pathway  Ras protein signal transduction  cell proliferation  positive regulation of endothelial cell migration  regulation of keratinocyte proliferation  positive regulation of neuron projection development  kinase activity  peptidyl-serine phosphorylation  sphingolipid biosynthetic process  regulation of protein stability  positive regulation of CREB transcription factor activity  positive regulation of peptidyl-serine phosphorylation  cellular response to oxidative stress  intracellular signal transduction  cellular response to vascular endothelial growth factor stimulus  cellular response to vascular endothelial growth factor stimulus  positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway  positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway  identical protein binding  positive regulation of I-kappaB kinase/NF-kappaB signaling  positive regulation of blood vessel endothelial cell migration  positive regulation of blood vessel endothelial cell migration  innate immune response  positive regulation of osteoblast differentiation  positive regulation of angiogenesis  positive regulation of angiogenesis  negative regulation of endocytosis  positive regulation of transcription from RNA polymerase II promoter  protein autophosphorylation  protein autophosphorylation  metal ion binding  vascular endothelial growth factor receptor signaling pathway  Golgi vesicle transport  positive regulation of NF-kappaB transcription factor activity  regulation of release of sequestered calcium ion into cytosol  negative regulation of cell death  protein kinase D signaling  positive regulation of histone deacetylase activity  positive regulation of endothelial cell chemotaxis  regulation of integrin-mediated signaling pathway  
Ontology : EGO-EBIangiogenesis  positive regulation of endothelial cell proliferation  protein serine/threonine kinase activity  protein serine/threonine kinase activity  protein kinase C activity  protein binding  ATP binding  nucleus  cytoplasm  Golgi apparatus  trans-Golgi network  cytosol  cytosol  plasma membrane  integral component of plasma membrane  cell-cell junction  cell cortex  protein phosphorylation  apoptotic process  inflammatory response  Golgi organization  signal transduction  integrin-mediated signaling pathway  Ras protein signal transduction  cell proliferation  positive regulation of endothelial cell migration  regulation of keratinocyte proliferation  positive regulation of neuron projection development  kinase activity  peptidyl-serine phosphorylation  sphingolipid biosynthetic process  regulation of protein stability  positive regulation of CREB transcription factor activity  positive regulation of peptidyl-serine phosphorylation  cellular response to oxidative stress  intracellular signal transduction  cellular response to vascular endothelial growth factor stimulus  cellular response to vascular endothelial growth factor stimulus  positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway  positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway  identical protein binding  positive regulation of I-kappaB kinase/NF-kappaB signaling  positive regulation of blood vessel endothelial cell migration  positive regulation of blood vessel endothelial cell migration  innate immune response  positive regulation of osteoblast differentiation  positive regulation of angiogenesis  positive regulation of angiogenesis  negative regulation of endocytosis  positive regulation of transcription from RNA polymerase II promoter  protein autophosphorylation  protein autophosphorylation  metal ion binding  vascular endothelial growth factor receptor signaling pathway  Golgi vesicle transport  positive regulation of NF-kappaB transcription factor activity  regulation of release of sequestered calcium ion into cytosol  negative regulation of cell death  protein kinase D signaling  positive regulation of histone deacetylase activity  positive regulation of endothelial cell chemotaxis  regulation of integrin-mediated signaling pathway  
Pathways : KEGGRap1 signaling pathway   
REACTOMEQ15139 [protein]
REACTOME PathwaysR-HSA-1660661 Sphingolipid de novo biosynthesis [pathway]
NDEx NetworkPRKD1
Atlas of Cancer Signalling NetworkPRKD1
Wikipedia pathwaysPRKD1
Orthology - Evolution
OrthoDB5587
GeneTree (enSembl)ENSG00000184304
Phylogenetic Trees/Animal Genes : TreeFamPRKD1
Homologs : HomoloGenePRKD1
Homology/Alignments : Family Browser (UCSC)PRKD1
Gene fusions - Rearrangements
Fusion : MitelmanARID1A/PRKD1 [1p36.11/14q12]  [t(1;14)(p36;q12)]  
Fusion : MitelmanDDX3X/PRKD1 [Xp11.4/14q12]  [t(X;14)(p11;q12)]  
Fusion : MitelmanPSMA6/PRKD1 [14q13.2/14q12]  [t(14;14)(q12;q13)]  
Fusion: TCGAPSMA6 14q13.2 PRKD1 14q12 LGG
Polymorphisms : SNP, variants
NCBI Variation ViewerPRKD1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PRKD1
dbVarPRKD1
ClinVarPRKD1
1000_GenomesPRKD1 
Exome Variant ServerPRKD1
ExAC (Exome Aggregation Consortium)PRKD1 (select the gene name)
Genetic variants : HAPMAP5587
Genomic Variants (DGV)PRKD1 [DGVbeta]
Mutations
ICGC Data PortalPRKD1 
TCGA Data PortalPRKD1 
Broad Tumor PortalPRKD1
OASIS PortalPRKD1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPRKD1 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch PRKD1
DgiDB (Drug Gene Interaction Database)PRKD1
DoCM (Curated mutations)PRKD1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PRKD1 (select a term)
intoGenPRKD1
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)14:30045687-30396899  ENSG00000184304
CONAN: Copy Number AnalysisPRKD1 
Mutations and Diseases : HGMDPRKD1
OMIM605435   
MedgenPRKD1
Genetic Testing Registry PRKD1
NextProtQ15139 [Medical]
TSGene5587
GENETestsPRKD1
Huge Navigator PRKD1 [HugePedia]
snp3D : Map Gene to Disease5587
BioCentury BCIQPRKD1
ClinGenPRKD1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5587
Chemical/Pharm GKB GenePA33771
Clinical trialPRKD1
Miscellaneous
canSAR (ICR)PRKD1 (select the gene name)
Probes
Litterature
PubMed172 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePRKD1
EVEXPRKD1
GoPubMedPRKD1
iHOPPRKD1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Sep 28 15:58:00 CEST 2016

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