PRKD2
entrez
25865
canonical
uniprot
Q9BZL6
canonical
ensembl
ENSG00000105287
resolver
ensp
ENSP00000291281
resolver
ensp
ENSP00000393978
resolver
ensp
ENSP00000470804
resolver
ensp
ENSP00000472744
resolver
genesymbol
PRKD2
resolver
genesymbol_syn
PKD2
resolver
hgnc
HGNC:17293
resolver
uniprot
B4DTS2
resolver
uniprot
M0QZW1
resolver
uniprot
M0R2R2
resolver
uniprot
Q8NCK8
resolver
uniprot
Q8TB08
resolver
uniprot
Q9P0T6
resolver
uniprot
Q9Y3X8
resolver
uniprot_entry
KPCD2_HUMAN
resolver
uniprot_sec
B4DTS2
resolver
uniprot_sec
M0QZW1
resolver
uniprot_sec
M0R2R2
resolver
uniprot_sec
Q8NCK8
resolver
uniprot_sec
Q8TB08
resolver
uniprot_sec
Q9P0T6
resolver
uniprot_sec
Q9Y3X8
resolver
activity_regulation
ACTIVITY REGULATION: Activated by DAG and phorbol esters (PubMed:12058027, PubMed:17962809, PubMed:28428613). Phorbol-ester/DAG-type domains bind DAG, mediating translocation to membranes (PubMed:17962809). Autophosphorylation of Ser-710 and phosphorylation of Ser-706 by PKC relieves auto-inhibition by the PH domain (PubMed:17962809). Catalytic activity is further increased by phosphorylation at Tyr-717 in response to oxidative stress (PubMed:28428613). {ECO:0000269|PubMed:12058027, ECO:0000269|PubMed:17962809, ECO:0000269|PubMed:28428613}.
uniprot
proteins
amino_acid_sequence
MATAPSYPAGLPGSPGPGSPPPPGGLELQSPPPLLPQIPAPGSGVSFHIQIGLTREFVLLPAASELAHVKQLACSIVDQKFPECGFYGLYDKILLFKHDPTSANLLQLVRSSGDIQEGDLVEVVLSASATFEDFQIRPHALTVHSYRAPAFCDHCGEMLFGLVRQGLKCDGCGLNYHKRCAFSIPNNCSGARKRRLSSTSLASGHSVRLGTSESLPCTAEELSRSTTELLPRRPPSSSSSSSASSYTGRPIELDKMLLSKVKVPHTFLIHSYTRPTVCQACKKLLKGLFRQGLQCKDCKFNCHKRCATRVPNDCLGEALINGDVPMEEATDFSEADKSALMDESEDSGVIPGSHSENALHASEEEEGEGGKAQSSLGYIPLMRVVQSVRHTTRKSSTTLREGWVVHYSNKDTLRKRHYWRLDCKCITLFQNNTTNRYYKEIPLSEILTVESAQNFSLVPPGTNPHCFEIVTANATYFVGEMPGGTPGGPSGQGAEAARGWETAIRQALMPVILQDAPSAPGHAPHRQASLSISVSNSQIQENVDIATVYQIFPDEVLGSGQFGVVYGGKHRKTGRDVAVKVIDKLRFPTKQESQLRNEVAILQSLRHPGIVNLECMFETPEKVFVVMEKLHGDMLEMILSSEKGRLPERLTKFLITQILVALRHLHFKNIVHCDLKPENVLLASADPFPQVKLCDFGFARIIGEKSFRRSVVGTPAYLAPEVLLNQGYNRSLDMWSVGVIMYVSLSGTFPFNEDEDINDQIQNAAFMYPASPWSHISAGAIDLINNLLQVKMRKRYSVDKSLSHPWLQEYQTWLDLRELEGKMGERYITHESDDARWEQFAAEHPLPGSGLPTDRDLGGACPPQDHDMQGLAERISVL
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 cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion (PubMed:14743217, PubMed:15604256, PubMed:16928771, PubMed:17077180, PubMed:17951978, PubMed:17962809, PubMed:18262756, PubMed:19001381, PubMed:19192391, PubMed:23503467, PubMed:28428613). May potentiate mitogenesis induced by the neuropeptide bombesin 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 (By similarity). In response to oxidative stress, is phosphorylated at Tyr-438 and Tyr-717 by ABL1, which leads to the activation of PRKD2 without increasing its catalytic activity, and mediates activation of NF-kappa-B (PubMed:15604256, PubMed:28428613). In response to the activation of the gastrin receptor CCKBR, is phosphorylated at Ser-244 by CSNK1D and CSNK1E, translocates to the nucleus, phosphorylates HDAC7, leading to nuclear export of HDAC7 and inhibition of HDAC7 transcriptional repression of NR4A1/NUR77 (PubMed:17962809). Upon TCR stimulation, is activated independently of ZAP70, translocates from the cytoplasm to the nucleus and is required for interleukin-2 (IL2) promoter up-regulation (PubMed:17077180). During adaptive immune responses, is required in peripheral T-lymphocytes for the production of the effector cytokines IL2 and IFNG after TCR engagement and for optimal induction of antibody responses to antigens (By similarity). In epithelial cells stimulated with lysophosphatidic acid (LPA), is activated through a PKC-dependent pathway and mediates LPA-stimulated interleukin-8 (IL8) secretion via a NF-kappa-B-dependent pathway (PubMed:16928771). During TCR-induced T-cell activation, interacts with and is activated by the tyrosine kinase LCK, which results in the activation of the NFAT transcription factors (PubMed:19192391). In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane and in polarized cells is involved in the transport of proteins from the TGN to the basolateral membrane (PubMed:14743217). Plays an important role in endothelial cell proliferation and migration prior to angiogenesis, partly through modulation of the expression of KDR/VEGFR2 and FGFR1, two key growth factor receptors involved in angiogenesis (PubMed:19001381). In secretory pathway, is required for the release of chromogranin-A (CHGA)-containing secretory granules from the TGN (PubMed:18262756). Downstream of PRKCA, plays important roles in angiotensin-2-induced monocyte adhesion to endothelial cells (PubMed:17951978). Plays a regulatory role in angiogenesis and tumor growth by phosphorylating a downstream mediator CIB1 isoform 2, resulting in vascular endothelial growth factor A (VEGFA) secretion (PubMed:23503467). {ECO:0000250|UniProtKB:Q8BZ03, ECO:0000269|PubMed:14743217, ECO:0000269|PubMed:15604256, ECO:0000269|PubMed:16928771, ECO:0000269|PubMed:17077180, ECO:0000269|PubMed:17951978, ECO:0000269|PubMed:17962809, ECO:0000269|PubMed:18262756, ECO:0000269|PubMed:19001381, ECO:0000269|PubMed:19192391, ECO:0000269|PubMed:23503467, ECO:0000269|PubMed:28428613}.
uniprot
proteins
mass_dalton
96722
uniprot
proteins
mutagenesis
MUTAGEN 87; /note="Y->F: Loss of phosphorylation. No effect on the interaction with PRKCD. No effect on Ser-706 or/and Ser-710 phosphorylation."; /evidence="ECO:0000269|PubMed:28428613"; MUTAGEN 244; /note="S->E: Constitutive kinase activity; when associated with E-706 and E-710."; /evidence="ECO:0000269|PubMed:23503467"; MUTAGEN 275; /note="P->G: Increase in ability to bind phorbol ester, slight increase in ability to bind DAG."; /evidence="ECO:0000269|PubMed:18076381"; MUTAGEN 438; /note="Y->D: Slight increase in Tyr-717 phosphorylation. No effect on Ser-706 or/and Ser-710 phosphorylation. Increase in Tyr-717 phosphorylation; when associated with E-706 and E-710."; /evidence="ECO:0000269|PubMed:28428613"; MUTAGEN 438; /note="Y->F: Loss of phosphorylation. No effect on phosphorylation of Tyr-717 and on Ser-706 or/and Ser-710 phosphorylation."; /evidence="ECO:0000269|PubMed:15604256, ECO:0000269|PubMed:28428613"; MUTAGEN 695; /note="D->A: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:23503467"; MUTAGEN 706; /note="S->A: Abolishes phosphorylation. Loss of Tyr-717 phosphorylation and any other tyrosine phosphorylation, and increases NF-kappa-B activation in response to oxidative stress; when associated with A-710."; /evidence="ECO:0000269|PubMed:28428613"; MUTAGEN 706; /note="S->E: Constitutive kinase activity; when associated with E-710 or with E-244 and E-710. Increases Tyr-717 phosphorylation; when associated with E-710 or with E-710 and D-438."; /evidence="ECO:0000269|PubMed:23503467, ECO:0000269|PubMed:28428613"; MUTAGEN 710; /note="S->A: Abolishes phosphorylation. Loss of Tyr-717 phosphorylation and any other tyrosine phosphorylation, and increases NF-kappa-B activation in response to oxidative stress; when associated with A-706."; /evidence="ECO:0000269|PubMed:28428613"; MUTAGEN 710; /note="S->E: Constitutive kinase activity; when associated with E-706 or with E-244 and E-706. when associated with E-710 or with E-244 and E-710. Increases Tyr-717 phosphorylation; when associated with E-710 or with E-710 and D-438."; /evidence="ECO:0000269|PubMed:23503467, ECO:0000269|PubMed:28428613"; MUTAGEN 717; /note="Y->F: Abolishes phosphorylation. Decreases substrate affinity and increases catalytic efficiency. Increases Ser-706 or/and Ser-710 phosphorylation. Increases NF-kappa-B activation in response to oxidative stress."; /evidence="ECO:0000269|PubMed:28428613"; MUTAGEN 724..726; /note="LNQ->RNK: Reduced catalytic activity. Severe reduction in Tyr-717 phosphorylation by ABL1 in response to oxidative stress. No effect on Ser-706 or/and Ser-710 phosphorylation and on NF-kappa-B activation in response to oxidative stress."; /evidence="ECO:0000269|PubMed:28428613
uniprot
proteins
post_translational_modification
PTM: Phosphorylation of Ser-876 correlates with the activation status of the kinase (PubMed:11062248). Ser-706 or/and Ser-710 are probably phosphorylated by PKC (PubMed:12058027, PubMed:28428613). Phosphorylation at Ser-244 by CSNK1D and CSNK1E promotes nuclear localization and substrate targeting (PubMed:17962809). Phosphorylation at Ser-244, Ser-706 and Ser-710 is required for nuclear localization (PubMed:17962809). Phosphorylated at Tyr-438 by ABL1 in response to oxidative stress (PubMed:15604256). Phosphorylated at Tyr-717 by ABL1 specifically in response to oxidative stress; requires prior phosphorylation at Ser-706 or/and Ser-710 (PubMed:28428613). {ECO:0000269|PubMed:11062248, ECO:0000269|PubMed:12058027, ECO:0000269|PubMed:15604256, ECO:0000269|PubMed:17962809, ECO:0000269|PubMed:28428613}.
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
11042152
uniprot
proteins
pubmed
11062248
uniprot
proteins
pubmed
12058027
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14743217
uniprot
proteins
pubmed
15057824
uniprot
proteins
pubmed
15604256
uniprot
proteins
pubmed
16928771
uniprot
proteins
pubmed
17077180
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17951978
uniprot
proteins
pubmed
17962809
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18076381
uniprot
proteins
pubmed
18262756
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18836451
uniprot
proteins
pubmed
19001381
uniprot
proteins
pubmed
19192391
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23503467
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
28428613
uniprot
proteins
sequence_length
878
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17962809}. Cell membrane {ECO:0000250|UniProtKB:Q15139}. Nucleus {ECO:0000269|PubMed:17962809}. Golgi apparatus, trans-Golgi network {ECO:0000269|PubMed:18262756}. Note=Translocation to the cell membrane is required for kinase activation. Accumulates in the nucleus upon CK1-mediated phosphorylation after activation of G protein-coupled receptors. Nuclear accumulation is regulated by blocking nuclear export of active PRKD2 rather than by increasing import. {ECO:0000269|PubMed:17962809}.
uniprot
proteins