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Atlas / Gene / PRKD2

PRKD2

gene
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Also known as PKD2HSPC187DKFZP586E0820

Summary

PRKD2 (protein kinase D2, HGNC:17293) is a protein-coding gene on chromosome 19q13.32, encoding Serine/threonine-protein kinase D2 (Q9BZL6). 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, in….

The protein encoded by this gene belongs to the protein kinase D (PKD) family of serine/threonine protein kinases. This kinase can be activated by phorbol esters as well as by gastrin via the cholecystokinin B receptor (CCKBR) in gastric cancer cells. It can bind to diacylglycerol (DAG) in the trans-Golgi network (TGN) and may regulate basolateral membrane protein exit from TGN. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 25865 — RefSeq curated summary.

At a glance

  • GWAS associations: 15
  • Clinical variants (ClinVar): 101 total
  • Phenotypes (HPO): 44
  • Druggable target: yes — 63 molecules with ChEMBL bioactivity
  • Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
  • MANE Select transcript: NM_016457

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:17293
Approved symbolPRKD2
Nameprotein kinase D2
Location19q13.32
Locus typegene with protein product
StatusApproved
AliasesPKD2, HSPC187, DKFZP586E0820
Ensembl geneENSG00000105287
Ensembl biotypeprotein_coding
OMIM607074
Entrez25865

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 12 protein_coding, 5 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000291281, ENST00000433867, ENST00000593363, ENST00000593492, ENST00000595132, ENST00000595515, ENST00000597088, ENST00000597390, ENST00000597589, ENST00000597641, ENST00000598633, ENST00000599019, ENST00000599464, ENST00000600194, ENST00000601605, ENST00000601806, ENST00000602155, ENST00000869062, ENST00000869063, ENST00000940150

RefSeq mRNA: 4 — MANE Select: NM_016457 NM_001079880, NM_001079881, NM_001079882, NM_016457

CCDS: CCDS12689, CCDS59401

Canonical transcript exons

ENST00000291281 — 18 exons

ExonStartEnd
ENSE000007143194669715746697234
ENSE000007143204669773346697850
ENSE000008582984670079946700952
ENSE000011340984671613146717114
ENSE000012252554670103546701112
ENSE000022345354670416946704391
ENSE000031997184667431646674735
ENSE000035336404669173546691807
ENSE000035541994669060046690706
ENSE000035773764671386346714001
ENSE000035915284667839646678663
ENSE000035979154669387546694133
ENSE000036171694670449546704649
ENSE000036172704669193346691985
ENSE000036285284671090746711038
ENSE000036634214668165046681748
ENSE000036664664668953746689698
ENSE000036714104667503346675118

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 97.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.9031 / max 450.1909, expressed in 1803 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter IDTPM avgSamples expressed
18167020.17921792
2088721.3908857
1816671.1934456
1816691.0376559
1816680.6013236
1816650.4046107
1816660.096239

Top tissues by expression

298 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
vena cavaUBERON:000408797.93gold quality
superficial temporal arteryUBERON:000161496.98gold quality
skeletal muscle tissue of rectus abdominisUBERON:000451196.47gold quality
granulocyteCL:000009496.30gold quality
spleenUBERON:000210695.95gold quality
body of tongueUBERON:001187695.92gold quality
pylorusUBERON:000116695.69gold quality
mammary ductUBERON:000176595.60gold quality
cardia of stomachUBERON:000116295.54gold quality
skin of legUBERON:000151195.36gold quality
skin of abdomenUBERON:000141695.29gold quality
ponsUBERON:000098895.25gold quality
bloodUBERON:000017895.23gold quality
right uterine tubeUBERON:000130294.70gold quality
tendon of biceps brachiiUBERON:000818894.69gold quality
nippleUBERON:000203094.67gold quality
pharyngeal mucosaUBERON:000035594.49gold quality
lower esophagus mucosaUBERON:003583494.44gold quality
superior surface of tongueUBERON:000737194.03gold quality
mucosa of transverse colonUBERON:000499193.92gold quality
tongueUBERON:000172393.91gold quality
zone of skinUBERON:000001493.89gold quality
ventral tegmental areaUBERON:000269193.89gold quality
epithelium of mammary glandUBERON:000324493.78gold quality
nasal cavity epitheliumUBERON:000538493.78gold quality
lymph nodeUBERON:000002993.73gold quality
pericardiumUBERON:000240793.42gold quality
adenohypophysisUBERON:000219693.33gold quality
right lungUBERON:000216792.93gold quality
thymusUBERON:000237092.91gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes5.71
E-GEOD-93593no6.58

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIVEP3

miRNA regulators (miRDB)

12 targeting PRKD2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4713-3P100.0065.92505
HSA-MIR-4731-5P99.8967.232537
HSA-MIR-3922-5P98.7766.531059
HSA-MIR-1227-5P98.6565.321549
HSA-MIR-302F98.4469.021776
HSA-MIR-477398.3567.301710
HSA-MIR-1912-5P97.9467.98832
HSA-MIR-4640-5P97.4266.331543
HSA-MIR-4726-5P97.2465.671299
HSA-MIR-428697.2064.371587
HSA-MIR-6762-5P96.5564.62972
HSA-MIR-6845-5P96.5564.65969

Literature-anchored findings (GeneRIF, showing 40)

  • mechanism of activation by CCK(B)/gastrin receptor (PMID:12058027)
  • specificity of different PKD isoforms in regulating protein trafficking from the trans-Golgi network (PMID:14743217)
  • Data show that Bcr-Abl-induced activation of the nuclear factor kappaB cascade in myeloid leukemia cells is largely mediated by tyrosine-phosphorylated PKD2. (PMID:15604256)
  • Critical components of the PKD2 regulatory domain control phorbol ester binding, catalytic activity, and nucleocytoplasmic shuttling and reveal similarities but also striking differences compared to the published data for this domain in PKD1. (PMID:15975900)
  • PKD2 plays an important role in carcinoid tumor progression. (PMID:16899224)
  • PKD2 is involved in the production of IL-8, a potent proinflammatory chemokine, by epithelial cells. (PMID:16928771)
  • The data suggest that PKD2 is involved in IL-2 promoter regulation and cell death depending on its activity upon TCR stimulation in Jurkat cells. (PMID:17077180)
  • Neurotensin induces a striking increase in Hsp27 phosphorylation on Ser-82 in PANC-1 cells through convergent p38 MAPK, PKD, and PKD2 signaling. (PMID:17570131)
  • stimulation of P-selectin surface expression via PKCalpha-dependent PKD2 activation could be an important mechanism in the early onset of AII-initiated endothelial adhesiveness (PMID:17951978)
  • Signal transduction pathway is defined downstream of CCK2 receptor showing that CK1 delta and epsilon phosphorylate PKD2 at 3 sites, resulting in nuclear accumulation of PKD2 and phosphorylation of nuclear PKD2 substrates in human gastric cancer cells. (PMID:17962809)
  • expression and catalytic activity of PKD2 are required for the release of chromogranin A containing secretory vesicles (PMID:18262756)
  • PKD2 plays a pivotal role in endothelial cell proliferation and migration necessary for angiogenesis at least in part through modulation of the expression of vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1 (PMID:19001381)
  • Lck regulated the activity of PKD2 by tyrosine phosphorylation, which in turn may have modulated the physiological functions of PKD2 during T cell receptor-induced T cell activation. (PMID:19192391)
  • Lysophosphatidylcholine activates a novel PKD2-mediated signaling pathway that controls monocyte migration. (PMID:19520973)
  • a transient association of PKD1 and PKD2 with NHERF-1 in live cells that is triggered by phorbol ester stimulation and, importantly, differs strikingly from the sustained translocation to plasma membrane. (PMID:19581308)
  • PKD2 regulates hypoxia-induced VEGF-A expression/secretion by tumour cells and VEGF-A stimulated blood vessel formation and a essential mediator of tumour cell-endothelial cell communication and a target to inhibit angiogenesis in gastrointestinal cancers (PMID:20732914)
  • Expression and kinase activity of PKD2 are required for the ligand-inducible stimulation of IFNAR1 ubiquitination and endocytosis and for accelerated proteolytic turnover of IFNAR1. (PMID:21173164)
  • PKD2 is a common signaling target downstream of various agonist receptors in platelets and G(q)-mediated signals along with calcium and novel PKC isoforms, in particular, PKCdelta activate PKD2 in platelets. (PMID:21736870)
  • Tyrosine phosphorylation of PKD2 is required for IFNalpha-stimulated activation of this kinase as well as for efficient serine phosphorylation and degradation of IFNAR1 and ensuing restriction of the extent of cellular responses to IFNalpha. (PMID:21865166)
  • upregulation of PKD2 expression may determine the behavior of gastric tumor cells, which promotes invasive phenotype and could result in general poor prognosis. (PMID:22217708)
  • found that AMAP1 had the ability to bind directly to PRKD2 and hence to make a complex with the cytoplasmic tail of the beta1 subunit (PMID:22734003)
  • results suggest that PKD2 is involved in the regulation of PP2A activity in activated T cells through phosphorylation of Ser171 of SET (PMID:23251465)
  • We have identified PKD2 and PKD3, especially PKD3, as novel cell growth regulators in HCC1806 triple-negative breast cancer cells (PMID:23393329)
  • PRKD2 mediates BAZF gene expression by VEGF-A stimulation. (PMID:23515950)
  • PRKD2 is a potential target to interfere with glioblastoma cell migration and invasion, two major determinants contributing to recurrence of glioblastoma after multimodality treatment. (PMID:23562655)
  • PKD2 controls secretion of MMP7 and 9 in an isoform-specific manner (PMID:24336522)
  • PRKD2 silencing induces glioma cell senescence via p53-dependent and -independent pathways. (PMID:24463355)
  • Activation of PKD2 and further increase of PKD3 activity leads to additional phosphorylation and inhibition of endogenous phosphatase slingshot 1L. (PMID:24840177)
  • Both PKD2 and GOLPH3 play important roles in the progression of human gliomas by promoting cell proliferation. (PMID:25218347)
  • Loss of PKD2 enhanced KC proliferative potential while loss of PKD3 resulted in a progressive proliferation defect, loss of clonogenicity and diminished tissue regenerative ability. (PMID:25802335)
  • The results implied that PKD2 silencing might inhibit migration of MCF7/DOX cells without affecting chemoresistance significantly (PMID:25874490)
  • the knockdown of PKD2 reduces cell death and promotes polyploidization induced by PMA. PMA/PKD2-mediated necrosis via PARP cleavage involves both SOD1-dependent and -independent pathways. (PMID:26241492)
  • Studies indicate that the loss of protein kinase D PKD1 is thought to promote invasion and metastasis, while PKD2 and upregulated PKD3 to be positive regulators of proliferation. (PMID:26253275)
  • None of the Polymorphous low-grade adenocarcinoma (PLGA) lacking PRKD1 somatic mutations or PRKD gene family rearrangements harboured somatic mutations in the kinase domains of the PRKD2 or PRKD3 genes. (PMID:26426580)
  • This study discovered and characterized a novel, highly conserved N-terminal domain, comprising 92 amino acids, which mediates dimerization of Protein Kinase D (PKD) isoforms, PKD1, PKD2, and PKD3 monomers. (PMID:27662904)
  • This review discusses the versatile functions of PKD2 from the perspective of cancer hallmarks as described by Hanahan and Weinberg. The PKD2 status, signaling pathways affected in different tumor types and the molecular mechanisms that lead to tumorigenesis and tumor progression are presented. [review] (PMID:29259300)
  • Study identified, for the first time, a functional crosstalk between protein kinase D2 (PKD2) and Aurora A kinase in cancer cells. The data demonstrate that PKD2 is catalytically active during the G2-M phases of the cell cycle, and inactivation or depletion of PKD2 causes delay in mitotic entry due to downregulation of Aurora A, an effect that can be rescued by overexpression of Aurora A. (PMID:30018032)
  • PKD2 and PKD3 were the two major isoforms of PKD overexpressed in breast cancer. Suppressing either PKD2 or PKD3 was able to reduce breast cancer cell proliferation and metastasis. (PMID:30652415)
  • High PKD2 predicts poor prognosis in lung adenocarcinoma via promoting Epithelial-mesenchymal Transition. (PMID:30718593)
  • exogenous SCF, CCL5 and CCL11 reversed the effect on MCs migration inhibited by PKD2/3 silencing. Mechanistically, PKD2/3 interacted with Erk1/2 and activated Erk1/2 or NF-kappaB signaling pathway, leading to AP-1 or NF-kappaB binding to the promoter of scf, ccl5 and ccl11. (PMID:30841931)

Cross-species orthologs

7 orthologs

OrganismSymbolGene ID
danio_rerioENSDARG00000087018
danio_rerioprkd2ENSDARG00000104676
mus_musculusPrkd2ENSMUSG00000041187
rattus_norvegicusPrkd2ENSRNOG00000016434
drosophila_melanogasterPKDFBGN0038603
caenorhabditis_elegansWBGENE00012019
caenorhabditis_elegansdkf-1WBGENE00012352

Paralogs (2): PRKD3 (ENSG00000115825), PRKD1 (ENSG00000184304)

Protein

Protein identifiers

Serine/threonine-protein kinase D2 — Q9BZL6 (reviewed: Q9BZL6)

Alternative names: nPKC-D2

All UniProt accessions (7): Q9BZL6, M0QXC6, M0QZ82, M0QZC2, M0R012, M0R2Z8, M0R346

UniProt curated annotations — full annotation on UniProt →

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. In secretory pathway, is required for the release of chromogranin-A (CHGA)-containing secretory granules from the TGN. Downstream of PRKCA, plays important roles in angiotensin-2-induced monocyte adhesion to endothelial cells. 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.

Subunit / interactions. Interacts (via C-terminus) with LCK. Interacts (via N-terminal AP-rich region) with CIB1 isoform 2. Interacts (via N-terminus and zing-finger domain 1 and 2) with PRKCD in response to oxidative stress; the interaction is independent of PRKD2 tyrosine phosphorylation.

Subcellular location. Cytoplasm. Cell membrane. Nucleus. Golgi apparatus. trans-Golgi network.

Tissue specificity. Widely expressed.

Post-translational modifications. Phosphorylation of Ser-876 correlates with the activation status of the kinase. Ser-706 or/and Ser-710 are probably phosphorylated by PKC. Phosphorylation at Ser-244 by CSNK1D and CSNK1E promotes nuclear localization and substrate targeting. Phosphorylation at Ser-244, Ser-706 and Ser-710 is required for nuclear localization. Phosphorylated at Tyr-438 by ABL1 in response to oxidative stress. Phosphorylated at Tyr-717 by ABL1 specifically in response to oxidative stress; requires prior phosphorylation at Ser-706 or/and Ser-710.

Activity regulation. Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domains bind DAG, mediating translocation to membranes. Autophosphorylation of Ser-710 and phosphorylation of Ser-706 by PKC relieves auto-inhibition by the PH domain. Catalytic activity is further increased by phosphorylation at Tyr-717 in response to oxidative stress.

Similarity. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PKD subfamily.

Isoforms (3)

UniProt IDNamesCanonical?
Q9BZL6-11yes
Q9BZL6-22
Q9BZL6-33

RefSeq proteins (4): NP_001073349, NP_001073350, NP_001073351, NP_057541* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000719Prot_kinase_domDomain
IPR001849PH_domainDomain
IPR002219PKC_DAG/PEDomain
IPR008271Ser/Thr_kinase_ASActive_site
IPR011009Kinase-like_dom_sfHomologous_superfamily
IPR011993PH-like_dom_sfHomologous_superfamily
IPR015727Protein_Kinase_C_mu-relatedFamily
IPR017441Protein_kinase_ATP_BSBinding_site
IPR020454DAG/PE-bdDomain
IPR046349C1-like_sfHomologous_superfamily
IPR057764Ubiquitin_PRKD1-3_NDomain

Pfam: PF00069, PF00130, PF00169, PF25525

Enzyme classification (BRENDA):

  • EC 2.7.11.13 — protein kinase C (BRENDA: 25 organisms, 203 substrates, 258 inhibitors, 20 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
FKKQGSFAKKK0.0166–0.059910
ATP0.0001–0.08284
N6-PHENYL-ATP0.01241
S6-(229-239) PEPTIDE0.00361

Catalyzed reactions (Rhea), 2 shown:

  • L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
  • L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (66 total): modified residue 17, mutagenesis site 12, strand 9, sequence variant 7, region of interest 4, compositionally biased region 3, domain 2, binding site 2, zinc finger region 2, splice variant 2, chain 1, active site 1, sequence conflict 1, turn 1, helix 1, short sequence motif 1

Structure

Experimental structures (PDB)

4 structures.

PDBMethodResolution (Å)
3BGMX-RAY DIFFRACTION1.6
4NNYX-RAY DIFFRACTION1.9
4NNXX-RAY DIFFRACTION2.1
2COASOLUTION NMR

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9BZL6-F169.850.24

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 674 (proton acceptor)

Ligand- & substrate-binding residues (2): 557–565; 580

Post-translational modifications (17): 30, 87, 197, 198, 200, 203, 206, 212, 214, 244, 407, 438, 518, 706, 710, 717, 876

Mutagenesis-validated functional residues (12):

PositionPhenotype
87loss of phosphorylation. no effect on the interaction with prkcd. no effect on ser-706 or/and ser-710 phosphorylation.
244constitutive kinase activity; when associated with e-706 and e-710.
275increase in ability to bind phorbol ester, slight increase in ability to bind dag.
438slight increase in tyr-717 phosphorylation. no effect on ser-706 or/and ser-710 phosphorylation. increase in tyr-717 pho
438loss of phosphorylation. no effect on phosphorylation of tyr-717 and on ser-706 or/and ser-710 phosphorylation.
695loss of kinase activity.
706abolishes phosphorylation. loss of tyr-717 phosphorylation and any other tyrosine phosphorylation, and increases nf-kapp
706constitutive kinase activity; when associated with e-710 or with e-244 and e-710. increases tyr-717 phosphorylation; whe
710abolishes phosphorylation. loss of tyr-717 phosphorylation and any other tyrosine phosphorylation, and increases nf-kapp
710constitutive kinase activity; when associated with e-706 or with e-244 and e-706. when associated with e-710 or with e-2
717abolishes phosphorylation. decreases substrate affinity and increases catalytic efficiency. increases ser-706 or/and ser
724–726reduced catalytic activity. severe reduction in tyr-717 phosphorylation by abl1 in response to oxidative stress. no effe

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

IDPathway
R-HSA-1660661Sphingolipid de novo biosynthesis
R-HSA-1430728Metabolism
R-HSA-428157Sphingolipid metabolism
R-HSA-556833Metabolism of lipids

MSigDB gene sets: 863 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_POTASSIUM_ION_TRANSPORT, GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_METANEPHRIC_NEPHRON_MORPHOGENESIS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, YAGI_AML_WITH_INV_16_TRANSLOCATION

GO Biological Process (29): angiogenesis (GO:0001525), positive regulation of endothelial cell proliferation (GO:0001938), adaptive immune response (GO:0002250), protein phosphorylation (GO:0006468), cell adhesion (GO:0007155), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of endothelial cell migration (GO:0010595), sphingolipid biosynthetic process (GO:0030148), positive regulation of vascular endothelial growth factor receptor signaling pathway (GO:0030949), positive regulation of interleukin-2 production (GO:0032743), positive regulation of interleukin-8 production (GO:0032757), intracellular signal transduction (GO:0035556), cellular response to vascular endothelial growth factor stimulus (GO:0035924), positive regulation of blood vessel endothelial cell migration (GO:0043536), positive regulation of fibroblast growth factor receptor signaling pathway (GO:0045743), positive regulation of angiogenesis (GO:0045766), positive regulation of cell adhesion (GO:0045785), positive regulation of transcription by RNA polymerase II (GO:0045944), vascular endothelial growth factor receptor signaling pathway (GO:0048010), T cell receptor signaling pathway (GO:0050852), positive regulation of T cell receptor signaling pathway (GO:0050862), obsolete positive regulation of DNA-binding transcription factor activity (GO:0051091), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), endothelial tube morphogenesis (GO:0061154), regulation of T cell apoptotic process (GO:0070232), positive regulation of ERK1 and ERK2 cascade (GO:0070374), positive regulation of DNA biosynthetic process (GO:2000573), positive regulation of endothelial cell chemotaxis (GO:2001028), immune system process (GO:0002376)

GO Molecular Function (12): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), diacylglycerol-dependent serine/threonine kinase activity (GO:0004697), protein kinase C binding (GO:0005080), ATP binding (GO:0005524), zinc ion binding (GO:0008270), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

CategoryPathways
Sphingolipid metabolism1
Metabolism of lipids1
Metabolism1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure4
positive regulation of signal transduction2
positive regulation of cytokine production2
intracellular anatomical structure2
protein kinase activity2
intracellular membrane-bounded organelle2
cytoplasm2
blood vessel morphogenesis1
anatomical structure formation involved in morphogenesis1
endothelial cell proliferation1
regulation of endothelial cell proliferation1
positive regulation of epithelial cell proliferation1
immune response1
phosphorylation1
protein modification process1
cellular process1
G protein-coupled receptor signaling pathway1
phospholipase C activator activity1
regulation of endothelial cell migration1
positive regulation of cell migration1
endothelial cell migration1
sphingolipid metabolic process1
lipid biosynthetic process1
regulation of vascular endothelial growth factor receptor signaling pathway1
vascular endothelial growth factor receptor signaling pathway1
interleukin-2 production1
regulation of interleukin-2 production1
interleukin-8 production1
regulation of interleukin-8 production1
signal transduction1
cellular response to growth factor stimulus1
positive regulation of endothelial cell migration1
blood vessel endothelial cell migration1
regulation of blood vessel endothelial cell migration1
fibroblast growth factor receptor signaling pathway1
regulation of fibroblast growth factor receptor signaling pathway1
angiogenesis1
regulation of angiogenesis1
positive regulation of vasculature development1
cell adhesion1

Protein interactions and networks

STRING

1202 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
PRKD2ARF1P10947834
PRKD2AKAP13Q12802766
PRKD2PLEK2Q9NYT0669
PRKD2PLEKP08567667
PRKD2PI4KBP78405617
PRKD2HDAC5Q9UQL6602
PRKD2CERT1Q9Y5P4595
PRKD2TCAPO15273588
PRKD2KIDINS220Q9ULH0575
PRKD2RYR2Q92736547
PRKD2OSBPP22059543
PRKD2MTORP42345540
PRKD2ANK2Q01484530
PRKD2ANK1P16157529
PRKD2ANK3Q12955529

IntAct

240 interactions, top by confidence:

ABTypeScore
NHERF2PODXLpsi-mi:“MI:0914”(association)0.770
ARPC5ARPC3psi-mi:“MI:0914”(association)0.730
PRKD2PRKD3psi-mi:“MI:0914”(association)0.730
CFTRESYT2psi-mi:“MI:0914”(association)0.710
PRKD2NHERF2psi-mi:“MI:0407”(direct interaction)0.690
SOCS7NCK2psi-mi:“MI:0914”(association)0.670
PRKD3PRKD1psi-mi:“MI:0914”(association)0.640
PPP2R2BMYO9Apsi-mi:“MI:0914”(association)0.640
TSC22D4TSC22D2psi-mi:“MI:0914”(association)0.640
YWHAHPLEKHG3psi-mi:“MI:0914”(association)0.610
APBA1LIN7Apsi-mi:“MI:0914”(association)0.590
PRKD2PTPN3psi-mi:“MI:0407”(direct interaction)0.590
PRKD2GORASP1psi-mi:“MI:0407”(direct interaction)0.590
PRKD2APBA1psi-mi:“MI:0407”(direct interaction)0.590
PRKD2GRIP1psi-mi:“MI:0407”(direct interaction)0.590
GRIP1PRKD2psi-mi:“MI:0407”(direct interaction)0.590
PRKD2CASKpsi-mi:“MI:0407”(direct interaction)0.590
IL13RA2METTL15psi-mi:“MI:0914”(association)0.530
SKP2DPYSL4psi-mi:“MI:0914”(association)0.530
PLA2G10CHEK1psi-mi:“MI:0914”(association)0.530
PHYHIPTRIP6psi-mi:“MI:0914”(association)0.530
YWHAZBLTP3Bpsi-mi:“MI:0914”(association)0.530

BioGRID (284): PRKD2 (Affinity Capture-MS), PRKD2 (Affinity Capture-MS), PRKD2 (Affinity Capture-MS), PRKD2 (Affinity Capture-MS), PRKD2 (Affinity Capture-MS), CDK10 (Affinity Capture-MS), YWHAQ (Affinity Capture-MS), SEC23IP (Affinity Capture-MS), PRKD3 (Affinity Capture-MS), NGDN (Affinity Capture-MS), NGRN (Affinity Capture-MS), PRKD2 (Affinity Capture-MS), PRKD2 (Affinity Capture-MS), PRKD2 (Affinity Capture-MS), PRKD2 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C0TYJ0, A0A8I5ZNK2, A5D7H2, O55047, O88506, O94806, O95747, P00535, P11273, P32298, P34947, P43249, P49137, Q08CW1, Q12959, Q13033, Q15139, Q15700, Q16644, Q1ECX4, Q28C55, Q3SYZ2, Q3UMW7, Q5PYH5, Q5PYH6, Q5R372, Q5R495, Q5RCW6, Q5XIS9, Q62101, Q62696, Q62833, Q63622, Q66H84, Q6P9R2, Q811D0, Q863I2, Q86UE8, Q8BZ03, Q8C0V0

Diamond homologs: A2ASS6, A2CG49, A4IFM7, A8C984, A8WXF6, E9PT87, F1M0Z1, G4SLH0, O02827, O08875, O43293, O44997, O54784, O60229, O62305, O70150, O75962, O88764, O94768, O94806, P07313, P08414, P10911, P13234, P18652, P18653, P18654, P20689, P22216, P25323, P29294, P51812, P53355, P97924, Q00168, Q0KHT7, Q0KL02, Q14012, Q15139, Q15418

SIGNOR signaling

32 interactions.

AEffectBMechanism
PRKD2up-regulatesPI4KBphosphorylation
PRKD2down-regulatesSSH1phosphorylation
PRKD2“down-regulates activity”SETphosphorylation
PRKD2“down-regulates activity”BCL6phosphorylation
PRKD2up-regulatesPRKD2phosphorylation
PRKCEup-regulatesPRKD2phosphorylation
PRKCHup-regulatesPRKD2phosphorylation
PRKD2“up-regulates activity”HDAC5phosphorylation
PRKD2“up-regulates activity”HDAC7phosphorylation
PRKD2“down-regulates activity”SSH1phosphorylation
PRKD2“up-regulates activity”MFFphosphorylation
PKA“up-regulates activity”PRKD2phosphorylation
PRKCA“up-regulates activity”PRKD2phosphorylation
PRKCH“up-regulates activity”PRKD2phosphorylation
PRKCE“up-regulates activity”PRKD2phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 193 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

PathwayPartnersFoldFDR
Assembly and cell surface presentation of NMDA receptors1225.2×1e-11
Ras activation upon Ca2+ influx through NMDA receptor523.6×1e-04
Unblocking of NMDA receptors, glutamate binding and activation522.5×1e-04
Negative regulation of NMDA receptor-mediated neuronal transmission522.5×1e-04
Dopamine Neurotransmitter Release Cycle520.5×2e-04
Long-term potentiation519.7×2e-04
Neurexins and neuroligins1117.9×5e-09
Protein-protein interactions at synapses715.4×3e-05

GO biological processes:

GO termPartnersFoldFDR
establishment or maintenance of epithelial cell apical/basal polarity928.9×1e-08
protein localization to synapse625.4×3e-05
receptor clustering724.1×6e-06
regulation of postsynaptic membrane neurotransmitter receptor levels616.4×2e-04
regulation of small GTPase mediated signal transduction86.4×4e-03
protein-containing complex assembly95.7×3e-03
cell-cell adhesion105.6×2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — PCM.

Clinical variants and AI predictions

ClinVar

101 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance77
Likely benign4
Benign5

Top pathogenic / likely-pathogenic (0)

SpliceAI

5424 predictions. Top by Δscore:

VariantEffectΔscore
19:46674733:CTC:Cacceptor_gain1.0000
19:46675029:TCAC:Tdonor_loss1.0000
19:46675030:CACC:Cdonor_loss1.0000
19:46675031:A:Cdonor_loss1.0000
19:46675032:CCTG:Cdonor_gain1.0000
19:46675034:TGTA:Tdonor_gain1.0000
19:46675114:AATGG:Aacceptor_gain1.0000
19:46675115:ATGG:Aacceptor_gain1.0000
19:46675116:TGG:Tacceptor_gain1.0000
19:46675116:TGGC:Tacceptor_loss1.0000
19:46675117:GG:Gacceptor_gain1.0000
19:46675119:C:CCacceptor_gain1.0000
19:46675122:C:CTacceptor_gain1.0000
19:46675124:C:CTacceptor_gain1.0000
19:46675125:A:Tacceptor_gain1.0000
19:46678391:GGCAC:Gdonor_loss1.0000
19:46678392:GCAC:Gdonor_loss1.0000
19:46678393:CACC:Cdonor_loss1.0000
19:46678394:AC:Adonor_loss1.0000
19:46678395:C:CTdonor_loss1.0000
19:46678397:T:TAdonor_gain1.0000
19:46678660:TCAC:Tacceptor_gain1.0000
19:46678661:CACC:Cacceptor_gain1.0000
19:46678665:T:Cacceptor_loss1.0000
19:46678667:C:CTacceptor_gain1.0000
19:46681645:CTGA:Cdonor_loss1.0000
19:46681646:TGA:Tdonor_loss1.0000
19:46681647:GACCT:Gdonor_loss1.0000
19:46681649:C:CTdonor_loss1.0000
19:46681745:GGAT:Gacceptor_gain1.0000

AlphaMissense

5726 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
19:46675074:G:TR795S1.000
19:46675094:A:GL788P1.000
19:46675097:A:GL787P1.000
19:46675109:A:GL783P1.000
19:46678417:A:GW773R1.000
19:46678417:A:TW773R1.000
19:46678436:G:CF766L1.000
19:46678436:G:TF766L1.000
19:46678438:A:GF766L1.000
19:46678481:G:CF751L1.000
19:46678481:G:TF751L1.000
19:46678482:A:GF751S1.000
19:46678483:A:GF751L1.000
19:46678483:A:TF751I1.000
19:46678485:G:CP750R1.000
19:46678485:G:TP750H1.000
19:46678486:G:AP750S1.000
19:46678486:G:TP750T1.000
19:46678487:G:CF749L1.000
19:46678487:G:TF749L1.000
19:46678488:A:CF749C1.000
19:46678488:A:GF749S1.000
19:46678489:A:GF749L1.000
19:46678494:C:AG747V1.000
19:46678494:C:TG747D1.000
19:46678500:A:GL745P1.000
19:46678502:G:CS744R1.000
19:46678502:G:TS744R1.000
19:46678504:T:GS744R1.000
19:46678506:A:TV743D1.000

dbSNP variants (sampled 300 via entrez): RS1000060494 (19:46699512 G>A), RS1000121112 (19:46692433 C>T), RS1000121965 (19:46709636 C>G,T), RS1000283991 (19:46686278 G>A), RS1000341239 (19:46686331 T>C), RS1000374156 (19:46697690 C>A,T), RS1000431760 (19:46699143 G>A,C), RS1000501997 (19:46717116 C>T), RS1000506948 (19:46693819 C>A,T), RS1000554045 (19:46717333 A>G), RS1000722204 (19:46693416 T>C), RS1000738157 (19:46680094 T>G), RS1000770627 (19:46680342 C>T), RS1000854469 (19:46705644 G>A,T), RS1000923606 (19:46715564 A>C)

Disease associations

OMIM: gene MIM:607074 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

44 total (30 of 44 shown, HPO-id order):

HPOTerm
HP:0000006Autosomal dominant inheritance
HP:0000010Recurrent urinary tract infections
HP:0000083Renal insufficiency
HP:0000105Enlarged kidney
HP:0000107Renal cyst
HP:0000113Polycystic kidney dysplasia
HP:0000324Facial asymmetry
HP:0000790Hematuria
HP:0000791Uric acid nephrolithiasis
HP:0000822Hypertension
HP:0000952Jaundice
HP:0001407Hepatic cysts
HP:0001634Mitral valve prolapse
HP:0001651Dextrocardia
HP:0001696Situs inversus totalis
HP:0001737Pancreatic cysts
HP:0002240Hepatomegaly
HP:0002616Aortic root aneurysm
HP:0002900Hypokalemia
HP:0003155Elevated circulating alkaline phosphatase concentration
HP:0003259Elevated circulating creatinine concentration
HP:0003596Middle age onset
HP:0003621Juvenile onset
HP:0003676Progressive
HP:0003774Stage 5 chronic kidney disease
HP:0003829Typified by incomplete penetrance
HP:0004944Dilatation of the cerebral artery
HP:0005562Multiple renal cysts
HP:0006254Elevated circulating alpha-fetoprotein concentration
HP:0006557Polycystic liver disease

GWAS associations

15 associations (top):

StudyTraitp-value
GCST000224_3Chronic lymphocytic leukemia4.000000e-09
GCST003262_579Post bronchodilator FEV11.000000e-06
GCST003262_581Post bronchodilator FEV11.000000e-06
GCST003262_582Post bronchodilator FEV11.000000e-06
GCST003262_583Post bronchodilator FEV11.000000e-06
GCST003262_584Post bronchodilator FEV11.000000e-06
GCST003262_585Post bronchodilator FEV11.000000e-06
GCST003262_586Post bronchodilator FEV17.000000e-07
GCST004030_10Primary sclerosing cholangitis2.000000e-12
GCST004146_22Chronic lymphocytic leukemia3.000000e-08
GCST005196_241Coronary artery disease8.000000e-06
GCST006670_2Primary sclerosing cholangitis7.000000e-10
GCST006979_685Heel bone mineral density1.000000e-14
GCST90002381_351Eosinophil count3.000000e-10
GCST90011899_125Aspartate aminotransferase levels6.000000e-13

EFO canonical traits (4, from GWAS)

EFO IDTrait name
EFO:0004314forced expiratory volume
EFO:0009270heel bone mineral density
EFO:0004842eosinophil count
EFO:0004736aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4900 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

63 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 454,790 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL1078178MOMELOTINIB43,481
CHEMBL1173055RUCAPARIB47,009
CHEMBL180022NERATINIB49,404
CHEMBL189963PALBOCICLIB413,102
CHEMBL2028663DABRAFENIB412,430
CHEMBL2325741CAPIVASERTIB42,157
CHEMBL3301610ABEMACICLIB47,045
CHEMBL3545110RIBOCICLIB48,018
CHEMBL3545311BRIGATINIB45,634
CHEMBL502835NINTEDANIB48,545
CHEMBL535SUNITINIB479,020
CHEMBL553ERLOTINIB4108,300
CHEMBL601719CRIZOTINIB414,403
CHEMBL608533MIDOSTAURIN47,259
CHEMBL939GEFITINIB4117,814
CHEMBL2219422AFURESERTIB31,467
CHEMBL3426621RIPASUDIL3870
CHEMBL38380FASUDIL311,953
CHEMBL428690ALVOCIDIB327,781
CHEMBL491473CEDIRANIB39,098
CHEMBL522892DOVITINIB3
CHEMBL603469LESTAURTINIB3
CHEMBL91829RUBOXISTAURIN3
CHEMBL103667DORAMAPIMOD2
CHEMBL1090090VX-7022
CHEMBL1614713CC-4012
CHEMBL1721885SU-0148132
CHEMBL1944698ZOTIRACICLIB2
CHEMBL1967878CENISERTIB2
CHEMBL1980297ILORASERTIB2

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

VariantTypeLevelDrugsPhenotypes
rs2725215Efficacy3allopurinol

PharmGKB variants

1 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs2725215PKD230.001allopurinol

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Protein kinase D (PKD) family

Most potent curated ligand interactions (2 total), top 2:

LigandActionAffinityParameter
CRT 0066101Inhibition8.6pIC50
BPKDiInhibition8.05pIC50

Binding affinities (BindingDB)

13 measured of 14 human assays (14 total across all organisms); most potent 13 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValue
StaurosporineKD1.7 nM
kb-NB142-70IC5028.3 nM
PD-146626IC5082.5 nM
kb-NB165-92IC50111 nM
kb-NB165-31IC50114 nM
PKC-412KD190 nM
kb-NB184-02IC50193 nM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.1^{7,14}.0^{2,6}.0^{8,13}.0^{22,27}]nonacosa-1(28),2(6),7(29),8(13),9,11,22(27),23,25-nonaene-3,5-dioneKD700 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]ureaKD1400 nM
BMS-387072KD1800 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamideKD2600 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamideKD3500 nM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S)-3-hydroxy-1-methyl-4-piperidinyl]-1-benzopyran-4-oneKD5300 nM

ChEMBL bioactivities

517 potent at pChembl≥5 of 521 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
9.00IC501nMCHEMBL1215000
9.00IC501nMCHEMBL1215151
8.88IC501.33nMSTAUROSPORINE
8.83IC501.48nMSTAUROSPORINE
8.78IC501.65nMSTAUROSPORINE
8.71IC501.93nMCHEMBL5897911
8.70IC502nMCHEMBL5419827
8.70IC502nMCHEMBL1214998
8.70IC502nMCHEMBL1215153
8.70IC502nMCHEMBL1215219
8.60IC502.5nMCHEMBL5428541
8.60Ki2.512nMCHEMBL1980995
8.52Kd3nMCHEMBL400402
8.27IC505.43nMCHEMBL5969973
8.20Ki6.31nMCHEMBL1990496
8.18IC506.54nMCHEMBL5980821
8.18IC506.54nMCHEMBL5926047
8.15IC507nMCHEMBL1215074
8.10IC507.97nMCHEMBL5879939
8.10IC508nMCHEMBL1215002
8.10IC508nMCHEMBL1215075
8.10Ki7.943nMCHEMBL437747
8.10Ki7.943nMCHEMBL1997129
8.09Kd8.1nMLESTAURTINIB
8.05IC509nMCHEMBL4515390
8.05IC509nMCHEMBL5440043
8.05IC509nMCHEMBL1214999
8.05IC509nMCHEMBL1215001
7.90Ki12.59nMCHEMBL1986263
7.90Ki12.59nMCHEMBL1982874
7.80IC5016nMCHEMBL1214857
7.80Ki15.85nMCHEMBL2001751
7.80Ki15.85nMGO-6976
7.77IC5017nMCHEMBL4644939
7.75IC5018nMCHEMBL1215220
7.70Ki19.95nMCHEMBL1986943
7.70Ki19.95nMCHEMBL1965423
7.68Ki21nMPF-03758309
7.60Ki25.12nMCHEMBL1966628
7.60Ki25.12nMCHEMBL2003657
7.58IC5026nMPF-03758309
7.52Kd30nMK-252A
7.51Kd30.86nMCHEMBL5653589
7.51IC5031nMCHEMBL1215077
7.50Ki31.62nMCHEMBL1970903
7.50Ki31.62nMCENISERTIB
7.50Ki31.62nMCHEMBL1991063
7.47Kd34nMDABRAFENIB
7.46IC5035nMCHEMBL4787572
7.46IC5035nMCHEMBL1215149

PubChem BioAssay actives

157 with measured affinity, of 2036 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
2-(2-anilino-4-pyridinyl)-6-piperazin-1-ylpyridine-4-carboxamide500135: Inhibition of PKD2 by TR-FRET assayic500.0010uM
N-cyclohexyl-4-[6-piperazin-1-yl-4-(1H-pyrazol-4-yl)-2-pyridinyl]pyridin-2-amine500135: Inhibition of PKD2 by TR-FRET assayic500.0010uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one1531848: Inhibition of human PKD2 using KKLNRTLSVA as substrate by [gamma-33P]-ATP assayic500.0013uM
N-cyclohexyl-4-(1-piperazin-1-yl-2,6-naphthyridin-3-yl)pyridin-2-amine500091: Inhibition of PKD2 ( assessed as residual activity at 1 uM ) by TR-FRET assayic500.0020uM
4-[6-piperazin-1-yl-4-(1H-pyrazol-4-yl)-2-pyridinyl]-N-propan-2-ylpyridin-2-amine500135: Inhibition of PKD2 by TR-FRET assayic500.0020uM
N-(oxan-4-yl)-4-[6-piperazin-1-yl-4-(1H-pyrazol-4-yl)-2-pyridinyl]pyridin-2-amine500135: Inhibition of PKD2 by TR-FRET assayic500.0020uM
3-[6-amino-5-(6-ethoxynaphthalen-2-yl)-3-pyridinyl]-N-[2-(dimethylamino)ethyl]benzamide1964577: Inhibition of PKD2 (unknown origin)ic500.0020uM
2-[4-[[(2S)-2-aminobutyl]amino]pyrimidin-2-yl]-4-(1-methylpyrazol-4-yl)phenol1964577: Inhibition of PKD2 (unknown origin)ic500.0025uM
4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol1425136: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.kd0.0030uM
2-[2-[(1-methylpyrazol-3-yl)amino]-4-pyridinyl]-6-piperazin-1-ylpyridine-4-carboxamide500135: Inhibition of PKD2 by TR-FRET assayic500.0070uM
2-piperazin-1-yl-6-[2-(propan-2-ylamino)-4-pyridinyl]pyridine-4-carboxamide500135: Inhibition of PKD2 by TR-FRET assayic500.0080uM
2-[2-(2-chloroanilino)-4-pyridinyl]-6-piperazin-1-ylpyridine-4-carboxamide500135: Inhibition of PKD2 by TR-FRET assayic500.0080uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one508048: Binding affinity to PRKD2kd0.0081uM
2-[4-[[(2R)-2-aminobutyl]amino]pyrimidin-2-yl]-4-(1-methylpyrazol-4-yl)phenol1742910: Inhibition of recombinant FLAG-tagged PKD2 (unknown origin) expressed in HEK293T cells using Syntide-2 as substrate measured after 15 mins by ADP-Glo assayic500.0090uM
2-piperazin-1-yl-6-(2-piperidin-1-yl-4-pyridinyl)pyridine-4-carboxamide1964577: Inhibition of PKD2 (unknown origin)ic500.0090uM
2-[2-(cyclohexylamino)-4-pyridinyl]-6-piperazin-1-ylpyridine-4-carboxamide500135: Inhibition of PKD2 by TR-FRET assayic500.0090uM
2-[2-(oxan-4-ylamino)-4-pyridinyl]-6-piperazin-1-ylpyridine-4-carboxamide500135: Inhibition of PKD2 by TR-FRET assayic500.0090uM
1-[3-[2-(oxan-4-ylamino)-4-pyridinyl]-2,6-naphthyridin-1-yl]-N-propan-2-ylpiperidine-4-carboxamide500091: Inhibition of PKD2 ( assessed as residual activity at 1 uM ) by TR-FRET assayic500.0160uM
4-[5-(piperidin-3-ylamino)isoquinolin-7-yl]phenol1658853: Inhibition of PKD2 (unknown origin)ic500.0170uM
2-[2-(cyclohexylamino)-4-pyridinyl]-6-[[(3R)-pyrrolidin-3-yl]amino]pyridine-4-carboxamide500135: Inhibition of PKD2 by TR-FRET assayic500.0180uM
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide2167987: Inhibition of human PKD2 (PRKD2) assessed as inhibition constant in presence of ATPki0.0210uM
methyl (15S,16R,18R)-16-hydroxy-15-methyl-3-oxo-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaene-16-carboxylate1425136: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.kd0.0300uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2149083: Binding affinity to human PRKD2 incubated for 45 mins by Kinobead based pull down assaykd0.0309uM
2-[2-(ethylamino)-4-pyridinyl]-6-piperazin-1-ylpyridine-4-carboxamide500135: Inhibition of PKD2 by TR-FRET assayic500.0310uM
Dabrafenib1425136: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.kd0.0340uM
3-(1H-indol-3-yl)-1-(piperidin-4-ylmethyl)pyrazolo[3,4-d]pyrimidin-4-amine1742910: Inhibition of recombinant FLAG-tagged PKD2 (unknown origin) expressed in HEK293T cells using Syntide-2 as substrate measured after 15 mins by ADP-Glo assayic500.0350uM
2-(2-anilino-4-pyridinyl)-6-piperazin-1-ylpyridine-4-carbonitrile500135: Inhibition of PKD2 by TR-FRET assayic500.0350uM
3-[4-amino-3-(1H-indol-3-yl)pyrazolo[3,4-d]pyrimidin-1-yl]-2,2-dimethylpropan-1-ol1742910: Inhibition of recombinant FLAG-tagged PKD2 (unknown origin) expressed in HEK293T cells using Syntide-2 as substrate measured after 15 mins by ADP-Glo assayic500.0430uM
3-(2-ethoxyquinolin-6-yl)-1-[(1-methylpiperidin-4-yl)methyl]pyrazolo[3,4-d]pyrimidin-4-amine1742910: Inhibition of recombinant FLAG-tagged PKD2 (unknown origin) expressed in HEK293T cells using Syntide-2 as substrate measured after 15 mins by ADP-Glo assayic500.0480uM
N-[(1R)-1-cyanoethyl]-3-[5-[4-[(oxan-4-ylamino)methyl]phenyl]-1,2-oxazol-3-yl]benzamide580271: Inhibition of human PKD2ic500.0480uM
4-methoxy-8,14-dithia-3,5,11-triazatricyclo[7.5.0.02,7]tetradeca-1(9),2,4,6-tetraen-10-one570426: Inhibition of human recombinant PKD2 after 10 mins by radiometric assayic500.0500uM
3-naphthalen-1-yl-1-(piperidin-4-ylmethyl)pyrazolo[3,4-d]pyrimidin-4-amine1742910: Inhibition of recombinant FLAG-tagged PKD2 (unknown origin) expressed in HEK293T cells using Syntide-2 as substrate measured after 15 mins by ADP-Glo assayic500.0550uM
3-[3-(2-piperidin-1-ylethoxy)phenyl]-5-(1H-1,2,4-triazol-5-yl)-1H-indazole1425136: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.kd0.0560uM
9-hydroxy-3,4-dihydro-2H-[1]benzothiolo[2,3-f][1,4]thiazepin-5-one1799562: In Vitro Radiometric Kinase Assay from Article 10.1186/1472-6769-10-5: “Novel protein kinase D inhibitors cause potent arrest in prostate cancer cell growth and motility.”ic500.0587uM
2-[2-(cyclopentylamino)-4-pyridinyl]-6-piperazin-1-ylpyridine-4-carboxamide500135: Inhibition of PKD2 by TR-FRET assayic500.0590uM
2-[2-(cyclohexylamino)-4-pyridinyl]-6-[(3R)-3-methylpiperazin-1-yl]pyridine-4-carboxamide500135: Inhibition of PKD2 by TR-FRET assayic500.0600uM
N-cyclohexyl-4-[6-piperazin-1-yl-4-(1H-pyrazol-5-yl)-2-pyridinyl]pyridin-2-amine500135: Inhibition of PKD2 by TR-FRET assayic500.0620uM
2-[2-[(1-methylpyrazol-3-yl)amino]-4-pyridinyl]-6-piperazin-1-ylpyridine-4-carbonitrile500135: Inhibition of PKD2 by TR-FRET assayic500.0680uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone1425136: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.kd0.0690uM
N-cyclohexyl-4-[4-(difluoromethyl)-6-piperazin-1-yl-2-pyridinyl]pyridin-2-amine500135: Inhibition of PKD2 by TR-FRET assayic500.0760uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide1526174: Binding affinity to recombinant full-length N-terminal His-FLAG-tagged PRKD2 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assaykd0.0790uM
2-[2-(cyclohexylamino)-4-pyridinyl]-6-[(3S)-3-methylpiperazin-1-yl]pyridine-4-carboxamide500135: Inhibition of PKD2 by TR-FRET assayic500.0860uM
2-(5-chloro-2-fluorophenyl)-N-pyridin-4-ylpteridin-4-amine1964577: Inhibition of PKD2 (unknown origin)ic500.0940uM
1-tert-butyl-3-(1H-indol-3-yl)pyrazolo[3,4-d]pyrimidin-4-amine1742910: Inhibition of recombinant FLAG-tagged PKD2 (unknown origin) expressed in HEK293T cells using Syntide-2 as substrate measured after 15 mins by ADP-Glo assayic500.0940uM
10-hydroxy-2,3,4,5-tetrahydro-[1]benzothiolo[3,2-b][1,5]thiazocin-6-one1799562: In Vitro Radiometric Kinase Assay from Article 10.1186/1472-6769-10-5: “Novel protein kinase D inhibitors cause potent arrest in prostate cancer cell growth and motility.”ic500.1007uM
N-cyclohexyl-4-[6-piperazin-1-yl-4-(trifluoromethyl)-2-pyridinyl]pyridin-2-amine500135: Inhibition of PKD2 by TR-FRET assayic500.1010uM
7-(3-aminophenyl)-N-piperidin-3-ylisoquinolin-5-amine1658853: Inhibition of PKD2 (unknown origin)ic500.1020uM
N-[6,6-dimethyl-5-(1-methylpiperidine-4-carbonyl)-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-3-methylbutanamide1425136: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.kd0.1030uM
2-[2-(cyclohexylamino)-4-pyridinyl]-6-piperazin-1-ylpyridine-4-carbonitrile500135: Inhibition of PKD2 by TR-FRET assayic500.1300uM
1-tert-butyl-3-naphthalen-1-ylpyrazolo[3,4-d]pyrimidin-4-amine1964577: Inhibition of PKD2 (unknown origin)ic500.1330uM

CTD chemical–gene interactions

52 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
CRT 0066101increases phosphorylation, decreases expression, decreases phosphorylation, decreases reaction, increases expression4
Valproic Acidincreases expression, increases methylation3
Benzo(a)pyreneaffects methylation, increases expression2
Cisplatinaffects cotreatment, increases expression, decreases expression2
Tetradecanoylphorbol Acetateincreases phosphorylation, decreases reaction2
aristolochic acid Iincreases expression1
FR900359decreases phosphorylation1
dicrotophosincreases expression1
triphenyl phosphateaffects expression1
sodium arseniteincreases expression1
perfluorooctanoic aciddecreases expression1
coumarindecreases phosphorylation1
bafilomycin A1affects expression, affects reaction, affects response to substance, affects cotreatment, affects abundance1
beta-methylcholineaffects expression1
perfluorooctane sulfonic aciddecreases expression1
U 0126decreases expression, decreases reaction, decreases phosphorylation1
motexafin gadoliniumdecreases expression1
erastinaffects reaction, affects response to substance, affects cotreatment, affects abundance, affects expression1
bisphenol Sdecreases methylation1
jinfukangaffects cotreatment, increases expression1
(+)-JQ1 compounddecreases expression1
PCI 5002affects cotreatment, increases expression1
kb-NB142-70increases phosphorylation, decreases reaction1
Vorinostatincreases expression1
Air Pollutantsaffects expression, increases abundance1
Arsenicaffects expression1
Vehicle Emissionsincreases abundance, increases expression1
Caffeineaffects phosphorylation1
Carbamazepineaffects expression1
Chloroquineaffects expression, affects reaction, affects response to substance1

ChEMBL screening assays

360 unique, capped per target: 359 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1011943BindingInhibition of PKD2 at 100 nM relative to controlStructural analysis of ARC-type inhibitor (ARC-1034) binding to protein kinase A catalytic subunit and rational design of bisubstrate analogue inhibitors of basophilic protein kinases. — J Med Chem
CHEMBL1963707FunctionalPUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PRKD2PubChem BioAssay data set

Cellosaurus cell lines

8 cell lines: 7 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_D1YKAbcam A-549 PRKD2 KOCancer cell lineMale
CVCL_D2CPAbcam HCT 116 PRKD2 KOCancer cell lineMale
CVCL_D7YNUbigene A-549 PRKD2 KOCancer cell lineMale
CVCL_D8U1Ubigene HCT 116 PRKD2 KOCancer cell lineMale
CVCL_D9PSUbigene HEK293 PRKD2 KOTransformed cell lineFemale
CVCL_E0LZUbigene HeLa PRKD2 KOCancer cell lineFemale
CVCL_TG98HAP1 PRKD2 (-) 1Cancer cell lineMale
CVCL_TG99HAP1 PRKD2 (-) 2Cancer cell lineMale

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
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Sources 80

This page pulls from 80 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot