DEPOD - human DEPhOsphorylation Database

Basic Information
Phosphatases
Pathway
Interacting Proteins
Phosphorylating Kinases

Gene Name	PRKD1 (QuickGO)	Interactive visualization of PRKD1 structures (A quick tutorial to explore the interctive visulaization) Representative structure: NA
Synonyms	PRKD1, PKD, PKD1, PRKCM
Protein Name	PRKD1
Alternative Name(s)	Serine/threonine-protein kinase D1;2.7.11.13;Protein kinase C mu type;Protein kinase D;nPKC-D1;nPKC-mu;
Protein Family	Belongs to the protein kinase superfamily CAMKSer/Thr protein kinase family PKD subfamily
EntrezGene ID	5587 (Comparitive Toxicogenomics)
UniProt AC (Human)	Q15139 (protein sequence)
Enzyme Class	2.7.11.13 (BRENDA )
Molecular Weight	101704 Dalton
Protein Length	912 amino acids (AA)
Genome Browsers	NCBI \| ENSG00000184304 (Ensembl) \| UCSC
Crosslinking annotations	Query our ID-mapping table
Orthologues	Quest For Orthologues (QFO) \| GeneTree \| eggNOG - KOG4236 \| eggNOG - ENOG410XQZ3
Phosphorylation Network	Visualize

Domain organization, Expression, Diseases

(show / hide)

Localization, Function, Catalytic activity and Sequence

(show / hide)

Localization (UniProt annotation)
Cytoplasm Cell membrane Golgi apparatus,trans-Golgi network Note=Translocation to the cell membrane is required for kinaseactivation
Function (UniProt annotation)
Serine/threonine-protein kinase that converts transientdiacylglycerol (DAG) signals into prolonged physiological effectsdownstream of PKC, and is involved in the regulation of MAPK8/JNK1and Ras signaling, Golgi membrane integrity and trafficking, cellsurvival through NF-kappa-B activation, cell migration, celldifferentiation by mediating HDAC7 nuclear export, cellproliferation via MAPK1/3 (ERK1/2) signaling, and plays a role incardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-inducedapoptosis and flagellin-stimulated inflammatory responsePhosphorylates the epidermal growth factor receptor (EGFR) on dualthreonine residues, which leads to the suppression of epidermalgrowth factor (EGF)-induced MAPK8/JNK1 activation and subsequentJUN phosphorylation Phosphorylates RIN1, inducing RIN1 binding to14-3-3 proteins YWHAB, YWHAE and YWHAZ and increased competitionwith RAF1 for binding to GTP-bound form of Ras proteins (NRAS,HRAS and KRAS) Acts downstream of the heterotrimeric G-proteinbeta/gamma-subunit complex to maintain the structural integrity ofthe Golgi membranes, and is required for protein transport alongthe secretory pathway In the trans-Golgi network (TGN), regulatesthe fission of transport vesicles that are on their way to theplasma membrane May act by activating the lipid kinasephosphatidylinositol 4-kinase beta (PI4KB) at the TGN for thelocal synthesis of phosphorylated inositol lipids, which induces asequential production of DAG, phosphatidic acid (PA) and lyso-PA(LPA) that are necessary for membrane fission and generation ofspecific transport carriers to the cell surface Under oxidativestress, is phosphorylated at Tyr-463 via SRC-ABL1 and contributesto cell survival by activating IKK complex and subsequent nucleartranslocation and activation of NFKB1 Involved in cell migrationby regulating integrin alpha-5/beta-3 recycling and promoting itsrecruitment in newly forming focal adhesion In osteoblastdifferentiation, mediates the bone morphogenetic protein 2 (BMP2)-induced nuclear export of HDAC7, which results in the inhibitionof HDAC7 transcriptional repression of RUNX2 In neurons, plays animportant role in neuronal polarity by regulating the biogenesisof TGN-derived dendritic vesicles, and is involved in themaintenance of dendritic arborization and Golgi structure inhippocampal cells May potentiate mitogenesis induced by theneuropeptide bombesin or vasopressin by mediating an increase inthe duration of MAPK1/3 (ERK1/2) signaling, which leads toaccumulation of immediate-early gene products including FOS thatstimulate cell cycle progression Plays an important role in theproliferative response induced by low calcium in keratinocytes,through sustained activation of MAPK1/3 (ERK1/2) pathwayDownstream of novel PKC signaling, plays a role in cardiachypertrophy by phosphorylating HDAC5, which in turn triggersXPO1/CRM1-dependent nuclear export of HDAC5, MEF2A transcriptionalactivation and induction of downstream target genes that promotemyocyte hypertrophy and pathological cardiac remodeling Mediatescardiac troponin I (TNNI3) phosphorylation at the PKA sites, whichresults in reduced myofilament calcium sensitivity, andaccelerated crossbridge cycling kinetics The PRKD1-HDAC5 pathwayis also involved in angiogenesis by mediating VEGFA-inducedspecific subset of gene expression, cell migration, and tubeformation In response to VEGFA, is necessary and required forHDAC7 phosphorylation which induces HDAC7 nuclear export andendothelial cell proliferation and migration During apoptosisinduced by cytarabine and other genotoxic agents, PRKD1 is cleavedby caspase-3 at Asp-378, resulting in activation of its kinasefunction and increased sensitivity of cells to the cytotoxiceffects of genotoxic agents In epithelial cells, is required fortransducing flagellin-stimulated inflammatory responses by bindingand phosphorylating TLR5, which contributes to MAPK14/p38activation and production of inflammatory cytokines May play arole in inflammatory response by mediating activation of NF-kappa-B May be involved in pain transmission by directly modulatingTRPV1 receptor Plays a role in activated KRAS-mediatedstabilization of ZNF304 in colorectal cancer (CRC) cells(PubMed:24623306) Regulates nuclear translocation oftranscription factor TFEB in macrophages upon live Sentericainfection (By similarity)
Catalytic Activity (UniProt annotation)
ATP + a protein = ADP + a phosphoprotein
Protein Sequence
MSAPPVLRPPSPLLPVAAAAAAAAAALVPGSGPGPAPFLAPVAAPVGGISFHLQIGLSREPVLLLQDSSGDYSLAHVREM ACSIVDQKFPECGFYGMYDKILLFRHDPTSENILQLVKAASDIQEGDLIEVVLSASATFEDFQIRPHALFVHSYRAPAFC DHCGEMLWGLVRQGLKCEGCGLNYHKRCAFKIPNNCSGVRRRRLSNVSLTGVSTIRTSSAELSTSAPDEPLLQKSPSESF IGREKRSNSQSYIGRPIHLDKILMSKVKVPHTFVIHSYTRPTVCQYCKKLLKGLFRQGLQCKDCRFNCHKRCAPKVPNNC LGEVTINGDLLSPGAESDVVMEEGSDDNDSERNSGLMDDMEEAMVQDAEMAMAECQNDSGEMQDPDPDHEDANRTISPST SNNIPLMRVVQSVKHTKRKSSTVMKEGWMVHYTSKDTLRKRHYWRLDSKCITLFQNDTGSRYYKEIPLSEILSLEPVKTS ALIPNGANPHCFEITTANVVYYVGENVVNPSSPSPNNSVLTSGVGADVARMWEIAIQHALMPVIPKGSSVGTGTNLHRDI SVSISVSNCQIQENVDISTVYQIFPDEVLGSGQFGIVYGGKHRKTGRDVAIKIIDKLRFPTKQESQLRNEVAILQNLHHP GVVNLECMFETPERVFVVMEKLHGDMLEMILSSEKGRLPEHITKFLITQILVALRHLHFKNIVHCDLKPENVLLASADPF PQVKLCDFGFARIIGEKSFRRSVVGTPAYLAPEVLRNKGYNRSLDMWSVGVIIYVSLSGTFPFNEDEDIHDQIQNAAFMY PPNPWKEISHEAIDLINNLLQVKMRKRYSVDKTLSHPWLQDYQTWLDLRELECKIGERYITHESDDLRWEKYAGEQGLQY PTHLINPSASHSDTPETEETEMKALGERVSIL

Motif information from Eukaryotic Linear Motif atlas (ELM)

(show / hide)

Gene Ontology (P: Process; F: Function and C: Component terms)

(show / hide)

GO:0000421	C:autophagosome membrane
GO:0001525	P:angiogenesis
GO:0001938	P:positive regulation of endothelial cell proliferation
GO:0004674	F:protein serine/threonine kinase activity
GO:0004697	F:protein kinase C activity
GO:0005524	F:ATP binding
GO:0005794	C:Golgi apparatus
GO:0005802	C:trans-Golgi network
GO:0005829	C:cytosol
GO:0005886	C:plasma membrane
GO:0006468	P:protein phosphorylation
GO:0006915	P:apoptotic process
GO:0006954	P:inflammatory response
GO:0007030	P:Golgi organization
GO:0007165	P:signal transduction
GO:0007229	P:integrin-mediated signaling pathway
GO:0007265	P:Ras protein signal transduction
GO:0008283	P:cell proliferation
GO:0010508	P:positive regulation of autophagy
GO:0010595	P:positive regulation of endothelial cell migration
GO:0010837	P:regulation of keratinocyte proliferation
GO:0010976	P:positive regulation of neuron projection development
GO:0016301	F:kinase activity
GO:0018105	P:peptidyl-serine phosphorylation
GO:0018107	P:peptidyl-threonine phosphorylation
GO:0030148	P:sphingolipid biosynthetic process
GO:0031647	P:regulation of protein stability
GO:0032793	P:positive regulation of CREB transcription factor activity
GO:0033138	P:positive regulation of peptidyl-serine phosphorylation
GO:0034198	P:cellular response to amino acid starvation
GO:0034599	P:cellular response to oxidative stress
GO:0035556	P:intracellular signal transduction
GO:0035924	P:cellular response to vascular endothelial growth factor stimulus
GO:0038033	P:positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway
GO:0042802	F:identical protein binding
GO:0043123	P:positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043536	P:positive regulation of blood vessel endothelial cell migration
GO:0043552	P:positive regulation of phosphatidylinositol 3-kinase activity
GO:0045087	P:innate immune response
GO:0045669	P:positive regulation of osteoblast differentiation
GO:0045766	P:positive regulation of angiogenesis
GO:0045806	P:negative regulation of endocytosis
GO:0045944	P:positive regulation of transcription by RNA polymerase II
GO:0046777	P:protein autophosphorylation
GO:0046872	F:metal ion binding
GO:0048010	P:vascular endothelial growth factor receptor signaling pathway
GO:0048193	P:Golgi vesicle transport
GO:0051092	P:positive regulation of NF-kappaB transcription factor activity
GO:0060548	P:negative regulation of cell death
GO:0071447	P:cellular response to hydroperoxide
GO:0089700	P:protein kinase D signaling
GO:1901727	P:positive regulation of histone deacetylase activity
GO:2001028	P:positive regulation of endothelial cell chemotaxis
GO:2001044	P:regulation of integrin-mediated signaling pathway

KEGG Pathway
Reactome Pathway

Top

PRKD1