Prkd1
entrez
18760
canonical
uniprot
Q62101
canonical
ensembl
ENSMUSG00000002688
resolver
ensp
ENSMUSP00000002765
resolver
ensp
ENSMUSP00000191441
resolver
ensp
ENSMUSP00000191443
resolver
ensp
ENSMUSP00000191446
resolver
enst
ENSMUST00000002765
resolver
genesymbol
Prkd1
resolver
genesymbol_syn
Pkcm
resolver
genesymbol_syn
Pkd
resolver
genesymbol_syn
Prkcm
resolver
uniprot
E9QNA3
resolver
uniprot_entry
KPCD1_MOUSE
resolver
uniprot_sec
E9QNA3
resolver
activity_regulation
ACTIVITY 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-748 and phosphorylation of Ser-744 by PKC relieves auto-inhibition by the PH domain. Phosphorylation on Tyr-469 by the SRC-ABL1 pathway in response to oxidative stress, is also required for activation. Activated by DAPK1 under oxidative stress (By similarity). {ECO:0000250|UniProtKB:Q15139}.
uniprot
proteins
amino_acid_sequence
MSVPPLLRPPSPLLPAAAAVAAAAAALVPGSGPAPFPAPGAAPAGGISFHLQIGLSREPVLLLQDSSGDYSLAHVREMACSIVDQKFPECGFYGLYDKILLFRHDPASDNILQLVKIASDIQEGDLIEVVLSASATFEDFQIRPHALFVHSYRAPAFCDHCGEMLWGLVRQGLKCEGCGLNYHKRCAFKIPNNCSGVRRRRLSNVSLTGLGTVRTASAEFSTSVPDEPLLSPVSPGFEQKSPSESFIGREKRSNSQSYIGRPIQLDKLLMSKVKVPHTFVIHSYTRPTVCQFCKKLLKGLFRQGLQCKDCRFNCHKRCAPKVPNNCLGEVTINGELLSPGAESDVVMEEGSDDNDSERNSGLMDDMDEAMVQDTEMALAEGQSGGAEMQDPDADQEDSNRTISPSTSNNIPLMRVVQSVKHTKRRSSTVMKEGWMVHYTSKDTLRKRHYWRLDSKCITLFQNDTGSRYYKEIPLSEILCLEPAKPSALTPVGATPHCFEITTANVVYYVGENVVNPSSSPPNNSVLPSGIGPDVARMWEVAIQHALMPVIPKGSSVGSGSNSHKDISVSISVSNCQIQENVDISTVYQIFPDEVLGSGQFGIVYGGKHRKTGRDVAIKIIDKLRFPTKQESQLRNEVAILQNLHHPGVVNLECMFETPERVFVVMEKLHGDMLEMILSSEKGRLPEHITKFLITQILVALRHLHFKNIVHCDLKPENVLLASADPFPQVKLCDFGFARIIGEKSFRRSVVGTPAYLAPEVLRNKGYNRSLDMWSVGVIIYVSLSGTFPFNEDEDIHDQIQNAAFMYPPNPWKEISHEAIDLINNLLQVKMRKRYSVDKTLSHPWLQDYQTWLDLRELECRIGERYITHESDDSRWEQYAGEQGLQYPAHLISLSASHSDSPEAEEREMKALSERVSIL
uniprot
proteins
ec_number
2.7.11.13
uniprot
proteins
function
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 (PubMed:12407104, PubMed:14963034, PubMed:15192707, PubMed:20463010, PubMed:24161911, PubMed:28716882). 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) (PubMed:11784866). 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 (PubMed:11239398). 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-469 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 (PubMed:15192707). In osteoblast differentiation, mediates the bone morphogenetic protein 2 (BMP2)-induced nuclear export of HDAC7, which results in the inhibition of HDAC7 transcriptional repression of RUNX2 (PubMed:19029091). 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 (PubMed:14963034, PubMed:20463010). 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 (PubMed:24161911). 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. Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (PubMed:28716882). 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. Plays a role in activated KRAS-mediated stabilization of ZNF304 in colorectal cancer (CRC) cells (By similarity). Regulates nuclear translocation of transcription factor TFEB in macrophages upon live S.enterica infection (PubMed:27184844). Acts as a regulator of social behavior by mediating phosphorylation of OXTR, enhancing G(q)-dependent G protein-coupled receptor signaling (PubMed:35104164). {ECO:0000250|UniProtKB:Q15139, ECO:0000269|PubMed:11239398, ECO:0000269|PubMed:11784866, ECO:0000269|PubMed:12407104, ECO:0000269|PubMed:14963034, ECO:0000269|PubMed:15192707, ECO:0000269|PubMed:19029091, ECO:0000269|PubMed:20463010, ECO:0000269|PubMed:24161911, ECO:0000269|PubMed:27184844, ECO:0000269|PubMed:35104164}.
uniprot
proteins
mass_dalton
102037
uniprot
proteins
mutagenesis
MUTAGEN 744; /note="S->A: Loss of basal kinase activity and phorbol ester-stimulated kinase activity; when associated with A-748."; /evidence="ECO:0000269|PubMed:12407104"; MUTAGEN 744; /note="S->D: High basal kinase activity, loss of phorbol ester-stimulated kinase activity; when associated with D-748."; /evidence="ECO:0000269|PubMed:12407104"; MUTAGEN 748; /note="S->A: Loss of basal kinase activity and phorbol ester-stimulated kinase activity; when associated with A-744."; /evidence="ECO:0000269|PubMed:12407104"; MUTAGEN 748; /note="S->D: High basal kinase activity, loss of phorbol ester-stimulated kinase activity; when associated with D-744."; /evidence="ECO:0000269|PubMed:12407104
uniprot
proteins
post_translational_modification
PTM: Phosphorylated at Ser-403 and Ser-407 by MAPK13 during regulation of insulin secretion in pancreatic beta cells (By similarity). Phosphorylated by DAPK1 (By similarity). Phosphorylated at Tyr-93 and by ABL at Tyr-469, which primes the kinase in response to oxidative stress, and promotes a second step activating phosphorylation at Ser-744/Ser-748 by PKRD (By similarity). Phosphorylated at Ser-916 upon S.enterica infection in macrophages (PubMed:27184844). {ECO:0000250|UniProtKB:Q15139, ECO:0000269|PubMed:27184844}.
uniprot
proteins
protein_family
CAMK Ser/Thr protein kinase family
uniprot
proteins
protein_family
PKD subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
10473617
uniprot
proteins
pubmed
11239398
uniprot
proteins
pubmed
11410586
uniprot
proteins
pubmed
11784866
uniprot
proteins
pubmed
12407104
uniprot
proteins
pubmed
14963034
uniprot
proteins
pubmed
15192707
uniprot
proteins
pubmed
19029091
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
20463010
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
24161911
uniprot
proteins
pubmed
27184844
uniprot
proteins
pubmed
28716882
uniprot
proteins
pubmed
35104164
uniprot
proteins
pubmed
8078925
uniprot
proteins
sequence_length
918
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q15139}. Cell membrane {ECO:0000250|UniProtKB:Q15139}. Golgi apparatus, trans-Golgi network {ECO:0000269|PubMed:11239398}. Note=Translocation to the cell membrane is required for kinase activation. {ECO:0000250|UniProtKB:Q15139}.
uniprot
proteins