Prkcd
entrez
18753
canonical
uniprot
P28867
canonical
ensembl
ENSMUSG00000021948
resolver
ensp
ENSMUSP00000022521
resolver
ensp
ENSMUSP00000107821
resolver
ensp
ENSMUSP00000107829
resolver
ensp
ENSMUSP00000107830
resolver
ensp
ENSMUSP00000276635
resolver
ensp
ENSMUSP00000276656
resolver
genesymbol
Prkcd
resolver
genesymbol_syn
Pkcd
resolver
uniprot
Q3TGE4
resolver
uniprot
Q53YN4
resolver
uniprot
Q91V85
resolver
uniprot
Q9Z333
resolver
uniprot_entry
KPCD_MOUSE
resolver
uniprot_entry
Q3TGE4_MOUSE
resolver
uniprot_entry
Q53YN4_MOUSE
resolver
uniprot_sec
Q91V85
resolver
uniprot_sec
Q9Z333
resolver
activity_regulation
ACTIVITY REGULATION: Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-505 (activation loop of the kinase domain), Ser-643 (turn motif) and Ser-662 (hydrophobic region), need to be phosphorylated for its full activation. Activated by caspase-3 (CASP3) cleavage during apoptosis. After cleavage, the pseudosubstrate motif in the regulatory subunit is released from the substrate recognition site of the catalytic subunit, which enables PRKCD to become constitutively activated. The catalytic subunit which displays properties of a sphingosine-dependent protein kinase is activated by D-erythro-sphingosine (Sph) or N,N-dimethyl-D-erythrosphingosine (DMS) or N,N,N-trimethyl-D-erythrosphingosine (TMS), but not by ceramide or Sph-1-P and is strongly inhibited by phosphatidylserine (By similarity). {ECO:0000250|UniProtKB:Q05655}.
uniprot
proteins
amino_acid_sequence
MAPFLRISFNSYELGSLQVEDEASQPFCAVKMKEALSTERGKTLVQKKPTMYPEWKTTFDAHIYEGRVIQIVLMRAAEDPVSEVTVGVSVLAERCKKNNGKAEFWLDLQPQAKVLMCVQYFLEDGDCKQSMRSEEEAKFPTMNRRGAIKQAKIHYIKNHEFIATFFGQPTFCSVCKEFVWGLNKQGYKCRQCNAAIHKKCIDKIIGRCTGTATNSRDTIFQKERFNIDMPHRFKVYNYMSPTFCDHCGSLLWGLVKQGLKCEDCGMNVHHKCREKVANLCGINQKLLAEALNQVTQRSSRKLDTTESVGIYQGFEKKPEVSGSDILDNNGTYGKIWEGSTRCTLENFTFQKVLGKGSFGKVLLAELKGKDKYFAIKCLKKDVVLIDDDVECTMVEKRVLALAWESPFLTHLICTFQTKDHLFFVMEFLNGGDLMFHIQDKGRFELYRATFYAAEIICGLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGMCKENIFGEGRASTFCGTPDYIAPEILQGLKYSFSVDWWSFGVLLYEMLIGQSPFHGDDEDELFESIRVDTPHYPRWITKESKDIMEKLFERDPDKRLGVTGNIRIHPFFKTINWSLLEKRKVEPPFKPKVKSPSDYSNFDPEFLNEKPQLSFSDKNLIDSMDQEAFHGFSFVNPKFEQFLDI
uniprot
proteins
ec_number
2.7.10.2
uniprot
proteins
ec_number
2.7.11.13
uniprot
proteins
function
FUNCTION: Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression, is required for oxygen radical production by NADPH oxidase and acts as a positive or negative regulator in platelet functional responses. Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction (PubMed:11976686, PubMed:11976687). Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis. In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53. In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53. In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation (PubMed:19917613). Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1. Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA (By similarity). In N-formyl-methionyl-leucyl-phenylalanine (fMLP)-treated cells, is required for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3 (ERK1/2) signaling pathways (PubMed:18025218). Involved in antifungal immunity by mediating phosphorylation and activation of CARD9 downstream of C-type lectin receptors activation, promoting interaction between CARD9 and BCL10, followed by activation of NF-kappa-B and MAP kinase p38 pathways (PubMed:22265677). May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA. In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation. Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion; acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release. Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin. The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion (PubMed:9705322). Phosphorylates ELAVL1 in response to angiotensin-2 treatment (By similarity). Phosphorylates mitochondrial phospholipid scramblase 3 (PLSCR3), resulting in increased cardiolipin expression on the mitochondrial outer membrane which facilitates apoptosis (By similarity). Phosphorylates SMPD1 which induces SMPD1 secretion (By similarity). Acts as a negative regulator of smoothened signaling by mediating phosphorylation of GLI1, preventing its localization to the nucleus (PubMed:19015273). Acts as a regulator of dopamine signaling by mediating constitutive phosphorylation of dopamine receptor DRD1, inhibiting G protein-coupled receptor signaling (By similarity). {ECO:0000250|UniProtKB:Q05655, ECO:0000269|PubMed:11976686, ECO:0000269|PubMed:11976687, ECO:0000269|PubMed:18025218, ECO:0000269|PubMed:19015273, ECO:0000269|PubMed:19917613, ECO:0000269|PubMed:9705322}.
uniprot
proteins
mass_dalton
77547
uniprot
proteins
mutagenesis
MUTAGEN 376; /note="K->R: Abolished serine/threonine kinase activity."; /evidence="ECO:0000269|PubMed:19015273
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated and/or phosphorylated at Thr-505, within the activation loop; phosphorylation at Thr-505 is not a prerequisite for enzymatic activity (By similarity). Autophosphorylated at Ser-299 (By similarity). Upon TNFSF10/TRAIL treatment, phosphorylated at Tyr-155; phosphorylation is required for its translocation to the endoplasmic reticulum and cleavage by caspase-3 (By similarity). Phosphorylated at Tyr-311, Tyr-332 and Tyr-565; phosphorylation of Tyr-311 and Tyr-565 following thrombin or zymosan stimulation potentiates its kinase activity (By similarity). Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminal cleavage product of PKN2 (By similarity). Phosphorylated at Tyr-311 through a SYK and SRC mechanism downstream of C-type lectin receptors activation, promoting its activation (PubMed:22265677). {ECO:0000250|UniProtKB:Q05655, ECO:0000269|PubMed:22265677}.; PTM: Proteolytically cleaved into a catalytic subunit and a regulatory subunit by caspase-3 during apoptosis which results in kinase activation. {ECO:0000250}.
uniprot
proteins
protein_family
AGC Ser/Thr protein kinase family
uniprot
proteins
protein_family
PKC subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
11558579
uniprot
proteins
pubmed
11976686
uniprot
proteins
pubmed
11976687
uniprot
proteins
pubmed
1765103
uniprot
proteins
pubmed
17947660
uniprot
proteins
pubmed
18025218
uniprot
proteins
pubmed
18034455
uniprot
proteins
pubmed
1868068
uniprot
proteins
pubmed
19015273
uniprot
proteins
pubmed
19131326
uniprot
proteins
pubmed
19144319
uniprot
proteins
pubmed
19917613
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22265677
uniprot
proteins
pubmed
7781068
uniprot
proteins
pubmed
9054438
uniprot
proteins
pubmed
9705322
uniprot
proteins
pubmed
9748166
uniprot
proteins
sequence_length
674
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q05655}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q05655}. Nucleus {ECO:0000250|UniProtKB:Q05655}. Cell membrane {ECO:0000250|UniProtKB:Q05655}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q05655}. Mitochondrion {ECO:0000250|UniProtKB:Q05655}. Endomembrane system {ECO:0000250|UniProtKB:Q05655}. Note=Translocates to the mitochondria upon apoptotic stimulation. Upon activation, translocates to the plasma membrane followed by partial location to the endolysosomes. {ECO:0000250|UniProtKB:Q05655}.
uniprot
proteins