PRKD1 (Protein Kinase D1)

2006-01-01 C Du , M Jaggi , W Zhang , KC Balaji Affiliation

Division of Urology, University of Massachusetts Memorial Medical Center, 55 Lake Avenue North, Worcester, MA 01605, USA

Identity

HGNC

PRKD1

LOCATION

14q12

LOCUSID

5587

ALIAS

CHDED,PKC-MU,PKCM,PKD,PRKCM

FUSION GENES

Show Gene Fusions

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.

Proteins

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

Entity name

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 name

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

Pubmed ID	Last Year	Title	Authors

Other Information

Locus ID:

NCBI: 5587
MIM: 605435
HGNC: 9407
Ensembl: ENSG00000184304

Variants:

dbSNP: 5587
ClinVar: 5587
TCGA: ENSG00000184304
COSMIC: PRKD1

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000184304	ENST00000331968	Q15139
ENSG00000184304	ENST00000415220	F8WBA3
ENSG00000184304	ENST00000490795	H0YHS9
ENSG00000184304	ENST00000546371	H0YHL5
ENSG00000184304	ENST00000549503	F8VZ98
ENSG00000184304	ENST00000616995	Q15139
ENSG00000184304	ENST00000651571	A0A494C196
ENSG00000184304	ENST00000651616	A0A494C0Q1

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Rap1 signaling pathway	KEGG	hsa04015
Rap1 signaling pathway	KEGG	ko04015
Metabolism	REACTOME	R-HSA-1430728
Metabolism of lipids and lipoproteins	REACTOME	R-HSA-556833
Sphingolipid metabolism	REACTOME	R-HSA-428157
Sphingolipid de novo biosynthesis	REACTOME	R-HSA-1660661
Aldosterone synthesis and secretion	KEGG	hsa04925
Aldosterone synthesis and secretion	KEGG	ko04925

Protein levels (Protein atlas)

Not detected

Low

Medium

High

PharmGKB

Entity ID	Name	Type	Evidence	Association
PA128394595	PLCH1	Gene	Pathway	associated
PA134875646	PLCZ1	Gene	Pathway	associated
PA134914471	PLCH2	Gene	Pathway	associated
PA33384	PLCB1	Gene	Pathway	associated
PA33385	PLCB2	Gene	Pathway	associated
PA33386	PLCB3	Gene	Pathway	associated
PA33387	PLCB4	Gene	Pathway	associated
PA33388	PLCD1	Gene	Pathway	associated
PA33389	PLCD3	Gene	Pathway	associated
PA33390	PLCD4	Gene	Pathway	associated
PA33391	PLCE1	Gene	Pathway	associated
PA33392	PLCG1	Gene	Pathway	associated
PA33393	PLCG2	Gene	Pathway	associated
PA33394	PLCL1	Gene	Pathway	associated
PA33395	PLCL2	Gene	Pathway	associated

References

Pubmed ID	Year	Title	Citations
19329994	2009	Protein kinase D1 regulates cofilin-mediated F-actin reorganization and cell motility through slingshot.	116
15024053	2004	Protein kinase Cdelta selectively regulates protein kinase D-dependent activation of NF-kappaB in oxidative stress signaling.	95
14743217	2004	Protein kinase D regulates basolateral membrane protein exit from trans-Golgi network.	94
16166634	2005	Protein kinase D mediates mitochondrion-to-nucleus signaling and detoxification from mitochondrial reactive oxygen species.	90
18332134	2008	Protein kinase D-dependent phosphorylation and nuclear export of histone deacetylase 5 mediates vascular endothelial growth factor-induced gene expression and angiogenesis.	78
17591919	2007	Regulation of secretory transport by protein kinase D-mediated phosphorylation of the ceramide transfer protein.	77
15728188	2005	A phosphorylation state-specific antibody recognizes Hsp27, a novel substrate of protein kinase D.	75
18829454	2008	Potent and selective disruption of protein kinase D functionality by a benzoxoloazepinolone.	73
27479907	2016	Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing.	73
11978539	2002	Protein kinase D: an intracellular traffic regulator on the move.	66

Citation

C Du ; M Jaggi ; W Zhang ; KC Balaji

PRKD1 (Protein Kinase D1)

Atlas Genet Cytogenet Oncol Haematol. 2006-01-01

Online version: http://atlasgeneticsoncology.org/gene/41860/prkd1