Gene/Proteome Database (LMPD)

LMPD ID
LMP000570
Gene ID
5587
Species
Homo sapiens (Human)
Gene Name
protein kinase D1
Gene Symbol
PRKD1
Synonyms
PKC-MU; PKCM; PKD; PRKCM
Alternate Names
serine/threonine-protein kinase D1; nPKC-D1; nPKC-mu; protein kinase D; protein kinase C, mu; protein kinase C mu type
Chromosome
14
Map Location
14q11
EC Number
2.7.11.13
Summary
PRKD1 is a serine/threonine kinase that regulates a variety of cellular functions, including membrane receptor signaling, transport at the Golgi, protection from oxidative stress at the mitochondria, gene transcription, and regulation of cell shape, motility, and adhesion (summary by Eiseler et al., 2009 [PubMed 19329994]).[supplied by OMIM, Nov 2010]
Orthologs
View orthologs and multiple alignments for PRKD1

Proteins

serine/threonine-protein kinase D1
Refseq ID NP_002733
Protein GI 115529463
UniProt ID Q15139
mRNA ID NM_002742
Length 912
RefSeq Status VALIDATED
MSAPPVLRPPSPLLPVAAAAAAAAAALVPGSGPGPAPFLAPVAAPVGGISFHLQIGLSREPVLLLQDSSGDYSLAHVREMACSIVDQKFPECGFYGMYDKILLFRHDPTSENILQLVKAASDIQEGDLIEVVLSASATFEDFQIRPHALFVHSYRAPAFCDHCGEMLWGLVRQGLKCEGCGLNYHKRCAFKIPNNCSGVRRRRLSNVSLTGVSTIRTSSAELSTSAPDEPLLQKSPSESFIGREKRSNSQSYIGRPIHLDKILMSKVKVPHTFVIHSYTRPTVCQYCKKLLKGLFRQGLQCKDCRFNCHKRCAPKVPNNCLGEVTINGDLLSPGAESDVVMEEGSDDNDSERNSGLMDDMEEAMVQDAEMAMAECQNDSGEMQDPDPDHEDANRTISPSTSNNIPLMRVVQSVKHTKRKSSTVMKEGWMVHYTSKDTLRKRHYWRLDSKCITLFQNDTGSRYYKEIPLSEILSLEPVKTSALIPNGANPHCFEITTANVVYYVGENVVNPSSPSPNNSVLTSGVGADVARMWEIAIQHALMPVIPKGSSVGTGTNLHRDISVSISVSNCQIQENVDISTVYQIFPDEVLGSGQFGIVYGGKHRKTGRDVAIKIIDKLRFPTKQESQLRNEVAILQNLHHPGVVNLECMFETPERVFVVMEKLHGDMLEMILSSEKGRLPEHITKFLITQILVALRHLHFKNIVHCDLKPENVLLASADPFPQVKLCDFGFARIIGEKSFRRSVVGTPAYLAPEVLRNKGYNRSLDMWSVGVIIYVSLSGTFPFNEDEDIHDQIQNAAFMYPPNPWKEISHEAIDLINNLLQVKMRKRYSVDKTLSHPWLQDYQTWLDLRELECKIGERYITHESDDLRWEKYAGEQGLQYPTHLINPSASHSDTPETEETEMKALGERVSIL

Gene Information

Entrez Gene ID
5587
Gene Name
protein kinase D1
Gene Symbol
PRKD1
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005938 IEA:Ensembl C cell cortex
GO:0005911 IEA:Ensembl C cell-cell junction
GO:0005737 IDA:HPA C cytoplasm
GO:0005829 ISS:UniProtKB C cytosol
GO:0005887 TAS:ProtInc C integral component of plasma membrane
GO:0005634 IEA:Ensembl C nucleus
GO:0005886 IDA:HPA C plasma membrane
GO:0005802 IDA:UniProtKB C trans-Golgi network
GO:0005524 IEA:UniProtKB-KW F ATP binding
GO:0042802 IPI:IntAct F identical protein binding
GO:0046872 IEA:UniProtKB-KW F metal ion binding
GO:0004697 IEA:UniProtKB-EC F protein kinase C activity
GO:0004674 TAS:UniProtKB F protein serine/threonine kinase activity
GO:0007030 IMP:UniProtKB P Golgi organization
GO:0048193 ISS:UniProtKB P Golgi vesicle transport
GO:0001525 IEA:UniProtKB-KW P angiogenesis
GO:0006915 IEA:UniProtKB-KW P apoptotic process
GO:0008283 TAS:ProtInc P cell proliferation
GO:0034599 IDA:UniProtKB P cellular response to oxidative stress
GO:0035924 IMP:UniProtKB P cellular response to vascular endothelial growth factor stimulus
GO:0006954 IEA:UniProtKB-KW P inflammatory response
GO:0045087 IEA:UniProtKB-KW P innate immune response
GO:0007229 TAS:BHF-UCL P integrin-mediated signaling pathway
GO:0035556 IMP:BHF-UCL P intracellular signal transduction
GO:0060548 IMP:UniProtKB P negative regulation of cell death
GO:0045806 TAS:BHF-UCL P negative regulation of endocytosis
GO:0018105 IDA:BHF-UCL P peptidyl-serine phosphorylation
GO:0032793 IGI:BHF-UCL P positive regulation of CREB transcription factor activity
GO:0043123 IMP:UniProtKB P positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0051092 IMP:UniProtKB P positive regulation of NF-kappaB transcription factor activity
GO:0045766 IMP:UniProtKB P positive regulation of angiogenesis
GO:0043536 IMP:BHF-UCL P positive regulation of blood vessel endothelial cell migration
GO:2001028 IMP:BHF-UCL P positive regulation of endothelial cell chemotaxis
GO:0038033 IMP:BHF-UCL P positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway
GO:0010595 IMP:UniProtKB P positive regulation of endothelial cell migration
GO:0001938 IGI:BHF-UCL P positive regulation of endothelial cell proliferation
GO:1901727 IGI:BHF-UCL P positive regulation of histone deacetylase activity
GO:0010976 IMP:UniProtKB P positive regulation of neuron projection development
GO:0045669 ISS:UniProtKB P positive regulation of osteoblast differentiation
GO:0033138 IGI:BHF-UCL P positive regulation of peptidyl-serine phosphorylation
GO:0045944 IMP:BHF-UCL P positive regulation of transcription from RNA polymerase II promoter
GO:0046777 TAS:BHF-UCL P protein autophosphorylation
GO:2001044 TAS:BHF-UCL P regulation of integrin-mediated signaling pathway
GO:0010837 ISS:UniProtKB P regulation of keratinocyte proliferation
GO:0007165 TAS:ProtInc P signal transduction
GO:0044281 TAS:Reactome P small molecule metabolic process
GO:0030148 TAS:Reactome P sphingolipid biosynthetic process
GO:0006665 TAS:Reactome P sphingolipid metabolic process
GO:0048010 IMP:BHF-UCL P vascular endothelial growth factor receptor signaling pathway

KEGG Pathway Links

KEGG Pathway ID Description
hsa04015 Rap1 signaling pathway

Domain Information

InterPro Annotations

Accession Description
IPR020454 Diacylglycerol/phorbol-ester binding
IPR001849 Pleckstrin homology domain
IPR011993 Pleckstrin homology-like domain
IPR002219 Protein kinase C-like, phorbol ester/diacylglycerol-binding domain
IPR000719 Protein kinase domain
IPR017441 Protein kinase, ATP binding site
IPR011009 Protein kinase-like domain
IPR015727 Protein_Kinase_C_mu-related
IPR008271 Serine/threonine-protein kinase, active site
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain

UniProt Annotations

Entry Information

Gene Name
protein kinase D1
Protein Entry
KPCD1_HUMAN
UniProt ID
Q15139
Species
Human

Comments

Comment Type Description
Catalytic Activity ATP + a protein = ADP + a phosphoprotein.
Cofactor Name=Mg(2+); Xref=ChEBI
Enzyme Regulation Activated by DAG and phorbol esters. Phorbol- ester/DAG-type domain 1 binds DAG with high affinity and appears to play the dominant role in mediating translocation to the cell membrane and trans-Golgi network. Phorbol-ester/DAG-type domain 2 binds phorbol ester with higher affinity. Autophosphorylation of Ser-742 and phosphorylation of Ser-738 by PKC relieves auto- inhibition by the PH domain. Phosphorylation on Tyr-463 by the SRC-ABL1 pathway in response to oxidative stress, is also required for activation. Activated by DAPK1 under oxidative stress. {ECO
Function Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response. Phosphorylates the epidermal growth factor receptor (EGFR) on dual threonine residues, which leads to the suppression of epidermal growth factor (EGF)-induced MAPK8/JNK1 activation and subsequent JUN phosphorylation. Phosphorylates RIN1, inducing RIN1 binding to 14-3-3 proteins YWHAB, YWHAE and YWHAZ and increased competition with RAF1 for binding to GTP-bound form of Ras proteins (NRAS, HRAS and KRAS). Acts downstream of the heterotrimeric G-protein beta/gamma-subunit complex to maintain the structural integrity of the Golgi membranes, and is required for protein transport along the secretory pathway. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane. May act by activating the lipid kinase phosphatidylinositol 4-kinase beta (PI4KB) at the TGN for the local synthesis of phosphorylated inositol lipids, which induces a sequential production of DAG, phosphatidic acid (PA) and lyso-PA (LPA) that are necessary for membrane fission and generation of specific transport carriers to the cell surface. Under oxidative stress, is phosphorylated at Tyr-463 via SRC-ABL1 and contributes to cell survival by activating IKK complex and subsequent nuclear translocation and activation of NFKB1. Involved in cell migration by regulating integrin alpha-5/beta-3 recycling and promoting its recruitment in newly forming focal adhesion. In osteoblast differentiation, mediates the bone morphogenic protein 2 (BMP2)- induced nuclear export of HDAC7, which results in the inhibition of HDAC7 transcriptional repression of RUNX2. In neurons, plays an important role in neuronal polarity by regulating the biogenesis of TGN-derived dendritic vesicles, and is involved in the maintenance of dendritic arborization and Golgi structure in hippocampal cells. May potentiate mitogenesis induced by the neuropeptide bombesin or vasopressin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression. Plays an important role in the proliferative response induced by low calcium in keratinocytes, through sustained activation of MAPK1/3 (ERK1/2) pathway. Downstream of novel PKC signaling, plays a role in cardiac hypertrophy by phosphorylating HDAC5, which in turn triggers XPO1/CRM1-dependent nuclear export of HDAC5, MEF2A transcriptional activation and induction of downstream target genes that promote myocyte hypertrophy and pathological cardiac remodeling. Mediates cardiac troponin I (TNNI3) phosphorylation at the PKA sites, which results in reduced myofilament calcium sensitivity, and accelerated crossbridge cycling kinetics. The PRKD1-HDAC5 pathway is also involved in angiogenesis by mediating VEGFA-induced specific subset of gene expression, cell migration, and tube formation. In response to VEGFA, is necessary and required for HDAC7 phosphorylation which induces HDAC7 nuclear export and endothelial cell proliferation and migration. During apoptosis induced by cytarabine and other genotoxic agents, PRKD1 is cleaved by caspase-3 at Asp-378, resulting in activation of its kinase function and increased sensitivity of cells to the cytotoxic effects of genotoxic agents. In epithelial cells, is required for transducing flagellin-stimulated inflammatory responses by binding and phosphorylating TLR5, which contributes to MAPK14/p38 activation and production of inflammatory cytokines. May play a role in inflammatory response by mediating activation of NF-kappa- B. May be involved in pain transmission by directly modulating TRPV1 receptor. {ECO
Interaction Self; NbExp=2; IntAct=EBI-1181072, EBI-1181072; Q07021:C1QBP; NbExp=9; IntAct=EBI-1181072, EBI-347528; P12830:CDH1; NbExp=7; IntAct=EBI-1181072, EBI-727477; P08238:HSP90AB1; NbExp=2; IntAct=EBI-1181072, EBI-352572; O15264:MAPK13; NbExp=6; IntAct=EBI-1181072, EBI-2116951; P02795:MT2A; NbExp=7; IntAct=EBI-1181072, EBI-996616;
Ptm Phosphorylated at Ser-397 and Ser-401 by MAPK13 during regulation of insulin secretion in pancreatic beta cells. Phosphorylated by DAPK1. Phosphorylated by ABL at Tyr-463, which primes the kinase in response to oxidative stress, and promotes a second step activating phosphorylation at Ser-738/Ser-742 by PKRD. {ECO
Similarity Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PKD subfamily.
Similarity Contains 1 PH domain. {ECO
Similarity Contains 1 protein kinase domain.
Similarity Contains 2 phorbol-ester/DAG-type zinc fingers.
Subcellular Location Cytoplasm . Cell membrane . Golgi apparatus, trans-Golgi network . Note=Translocation to the cell membrane is required for kinase activation.
Subunit Interacts (via N-terminus) with ADAP1/CENTA1. Interacts with MAPK13 and SRC. Interacts with DAPK1 in an oxidative stress- regulated manner. {ECO
Web Resource Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PRKCMID41860ch14q11.html";

Identical and Related Proteins

Unique RefSeq proteins for LMP000570 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
115529463 RefSeq NP_002733 912 serine/threonine-protein kinase D1

Identical Sequences to LMP000570 proteins

Reference Database Accession Length Protein Name
GI:115529463 DBBJ BAG36853.1 912 unnamed protein product [Homo sapiens]
GI:115529463 GenBank EAW65971.1 912 protein kinase D1, isoform CRA_b [Homo sapiens]
GI:115529463 GenBank AAI60015.1 912 Protein kinase D1 [synthetic construct]
GI:115529463 GenBank ADS87452.1 912 Sequence 328 from patent US 7820380
GI:115529463 GenBank AEW40447.1 912 Sequence 328 from patent US 8071302
GI:115529463 SwissProt Q15139.2 912 RecName: Full=Serine/threonine-protein kinase D1; AltName: Full=Protein kinase C mu type; AltName: Full=Protein kinase D; AltName: Full=nPKC-D1; AltName: Full=nPKC-mu [Homo sapiens]

Related Sequences to LMP000570 proteins

Reference Database Accession Length Protein Name
GI:115529463 EMBL CAA53384.1 912 protein kinase C mu [Homo sapiens]
GI:115529463 GenBank ABW49139.1 912 Sequence 173 from patent US 7265092
GI:115529463 GenBank ADA36099.1 912 Sequence 240 from patent US 7615626
GI:115529463 GenBank ADM03578.1 912 Sequence 173 from patent US 7727958
GI:115529463 GenBank AGA37720.1 912 Sequence 240 from patent US 8318137
GI:115529463 GenBank AGV86236.1 912 Sequence 173 from patent US 8524673