DegronMD - Q9BZL6(PRKD2)

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:15604256, PubMed:14743217, PubMed:17077180, PubMed:16928771, PubMed:17962809, PubMed:17951978, PubMed:18262756, PubMed:19192391, PubMed:19001381, 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}. View more >>

GO - Biological processes (BP): adaptive immune response [GO:0002250]; angiogenesis [GO:0001525]; cell adhesion [GO:0007155]; cell death [GO:0008219]; cellular response to vascular endothelial growth factor stimulus [GO:0035924]; endothelial tube morphogenesis [GO:0061154]; intracellular signal transduction [GO:0035556]; peptidyl-serine phosphorylation [GO:0018105]; peptidyl-threonine phosphorylation [GO:0018107]; positive regulation of angiogenesis [GO:0045766]; positive regulation of blood vessel endothelial cell migration [GO:0043536]; positive regulation of cell adhesion [GO:0045785]; positive regulation of CREB transcription factor activity [GO:0032793]; positive regulation of DNA-binding transcription factor activity [GO:0051091]; positive regulation of DNA biosynthetic process [GO:2000573]; positive regulation of endothelial cell chemotaxis [GO:2001028]; positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway [GO:0038033]; positive regulation of endothelial cell migration [GO:0010595]; positive regulation of endothelial cell proliferation [GO:0001938]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]; positive regulation of fibroblast growth factor receptor signaling pathway [GO:0045743]; positive regulation of histone deacetylase activity [GO:1901727]; positive regulation of interleukin-2 production [GO:0032743]; positive regulation of interleukin-8 production [GO:0032757]; positive regulation of intracellular signal transduction [GO:1902533]; positive regulation of NF-kappaB transcription factor activity [GO:0051092]; positive regulation of peptidyl-serine phosphorylation [GO:0033138]; positive regulation of T cell receptor signaling pathway [GO:0050862]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of vascular endothelial growth factor receptor signaling pathway [GO:0030949]; protein autophosphorylation [GO:0046777]; protein kinase D signaling [GO:0089700]; protein phosphorylation [GO:0006468]; sphingolipid biosynthetic process [GO:0030148]; T cell receptor signaling pathway [GO:0050852]; vascular endothelial growth factor receptor signaling pathway [GO:0048010] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.A497T	TCGA-A5-A0G2	UCEC	TCGA	IRQALMPVI	DEG_APCC_DBOX_1	504:512	Mutation rewiring degron network	0.1389
p.R232H	TCGA-AA-3864	COAD	TCGA	PPSSS	DEG_SPOP_SBC_1	234:238	Mutation rewiring degron network	0.2778
p.R224H	TCGA-BR-8059	STAD	TCGA	PPSSS	DEG_SPOP_SBC_1	234:238	Mutation rewiring degron network	0.0556
p.E228K	TCGA-BR-8361	STAD	TCGA	PPSSS	DEG_SPOP_SBC_1	234:238	Mutation rewiring degron network	0.1667
p.E228K	TCGA-FI-A2D5	UCEC	TCGA	PPSSS	DEG_SPOP_SBC_1	234:238	Mutation rewiring degron network	0.1667
p.A516T	TCGA-CG-5726	STAD	TCGA	IRQALMPVI	DEG_APCC_DBOX_1	504:512	Mutation rewiring degron network	0.2222
p.A516T	TCGA-VQ-A8PB	STAD	TCGA	IRQALMPVI	DEG_APCC_DBOX_1	504:512	Mutation rewiring degron network	0.2222
p.A516T	SIDM01432	Kidney Carcinoma	GDSC	IRQALMPVI	DEG_APCC_DBOX_1	504:512	Mutation rewiring degron network	0.2222
p.A516T	ACH-000495	Kidney Cancer	CCLE	IRQALMPVI	DEG_APCC_DBOX_1	504:512	Mutation rewiring degron network	0.2222
p.R505C	TCGA-CM-4746	COAD	TCGA	IRQALMPVI	DEG_APCC_DBOX_1	504:512	Mutation altering degron motif	0.8301
p.R505H	TCGA-FI-A2D5	UCEC	TCGA	IRQALMPVI	DEG_APCC_DBOX_1	504:512	Mutation altering degron motif	0.8244
p.A503T	TCGA-IB-7651	PAAD	TCGA	IRQALMPVI	DEG_APCC_DBOX_1	504:512	Mutation rewiring degron network	0.3056
p.A519S	TCGA-QR-A70R	PCPG	TCGA	IRQALMPVI	DEG_APCC_DBOX_1	504:512	Mutation rewiring degron network	0.1389
p.T502I	TCGA-UY-A78O	BLCA	TCGA	IRQALMPVI	DEG_APCC_DBOX_1	504:512	Mutation rewiring degron network	0.2778
p.A494D	TCGA-X6-A7WA	SARC	TCGA	IRQALMPVI	DEG_APCC_DBOX_1	504:512	Mutation rewiring degron network	0.0556
p.K511N	DO2401	BRCA	ICGC	IRQALMPVI	DEG_APCC_DBOX_1	504:512	Mutation altering degron motif	0.6918
p.L242P	DO227802	COCA	ICGC	PPSSS	DEG_SPOP_SBC_1	234:238	Mutation blocking phosphorylation signal	0.6667
p.L508I	DO233903	GACA	ICGC	IRQALMPVI	DEG_APCC_DBOX_1	504:512	Mutation altering degron motif	0.7174
p.Q229K	DO220312	SARC	ICGC	PPSSS	DEG_SPOP_SBC_1	234:238	Mutation rewiring degron network	0.1944
p.M225T	DO48020	STAD	ICGC	PPSSS	DEG_SPOP_SBC_1	234:238	Mutation blocking phosphorylation signal	0.5278
p.R236W	DO47973	STAD	ICGC	PPSSS	DEG_SPOP_SBC_1	234:238	Mutation altering degron motif	0.8634
p.I498V	DO38296	STAD	ICGC	IRQALMPVI	DEG_APCC_DBOX_1	504:512	Mutation rewiring degron network	0.1667
p.L518F	DO229240	THCA	ICGC	IRQALMPVI	DEG_APCC_DBOX_1	504:512	Mutation blocking phosphorylation signal	0.6111
p.T240N	DO41752	UCEC	ICGC	PPSSS	DEG_SPOP_SBC_1	234:238	Mutation rewiring degron network	0.2778
p.V514A	DO41331	UCEC	ICGC	IRQALMPVI	DEG_APCC_DBOX_1	504:512	Mutation rewiring degron network	0.2778
p.S245T	SIDM00889	Cervical Carcinoma	GDSC	PPSSS	DEG_SPOP_SBC_1	234:238	Mutation blocking phosphorylation signal	0.5833
p.S245T	ACH-001333	Cervical Cancer	CCLE	PPSSS	DEG_SPOP_SBC_1	234:238	Mutation blocking phosphorylation signal	0.5833
p.S245T	C-33-A	cervix	COSMIC	PPSSS	DEG_SPOP_SBC_1	234:238	Mutation blocking phosphorylation signal	0.5833
p.W500S	ACH-001097	Lymphoma	CCLE	IRQALMPVI	DEG_APCC_DBOX_1	504:512	Mutation rewiring degron network	0.2222
p.P510H	ACH-001669	Leukemia	CCLE	IRQALMPVI	DEG_APCC_DBOX_1	504:512	Mutation altering degron motif	0.6583
p.T494I	GEO	large intestine	COSMIC	IRQALMPVI	DEG_APCC_DBOX_1	504:512	Mutation rewiring degron network	0.0556
p.R243Q	MOLT-16	haematopoietic and lymphoid tissue	COSMIC	PPSSS	DEG_SPOP_SBC_1	234:238	Mutation rewiring degron network	0.1944

Kaplan plot for PRKD2 in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

PRKD2

UniProt ID: Q9BZL6

Entrez ID: 25865

Protein name: Serine/threonine-protein kinase D2 (EC 2.7.11.13) (nPKC-D2)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for PRKD2 in