PRKCI

Summary

PRKCI (protein kinase C iota, HGNC:9404) is a protein-coding gene on chromosome 3q26.2, encoding Protein kinase C iota type (P41743). Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics i….

This gene encodes a member of the protein kinase C (PKC) family of serine/threonine protein kinases. The PKC family comprises at least eight members, which are differentially expressed and are involved in a wide variety of cellular processes. This protein kinase is calcium-independent and phospholipid-dependent. It is not activated by phorbolesters or diacylglycerol. This kinase can be recruited to vesicle tubular clusters (VTCs) by direct interaction with the small GTPase RAB2, where this kinase phosphorylates glyceraldehyde-3-phosphate dehydrogenase (GAPD/GAPDH) and plays a role in microtubule dynamics in the early secretory pathway. This kinase is found to be necessary for BCL-ABL-mediated resistance to drug-induced apoptosis and therefore protects leukemia cells against drug-induced apoptosis. There is a single exon pseudogene mapped on chromosome X.

Source: NCBI Gene 5584 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 67 total
• Druggable target: yes — 20 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002740

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9404
Approved symbol	PRKCI
Name	protein kinase C iota
Location	3q26.2
Locus type	gene with protein product
Status	Approved
Aliases	PKCI
Ensembl gene	ENSG00000163558
Ensembl biotype	protein_coding
OMIM	600539
Entrez	5584

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 12 protein_coding, 6 retained_intron

ENST00000295797, ENST00000476635, ENST00000482353, ENST00000483697, ENST00000485837, ENST00000488541, ENST00000493761, ENST00000904925, ENST00000904926, ENST00000904927, ENST00000919187, ENST00000919188, ENST00000919189, ENST00000919190, ENST00000919191, ENST00000919192, ENST00000919193, ENST00000947708

RefSeq mRNA: 1 — MANE Select: NM_002740 NM_002740

CCDS: CCDS3212

Canonical transcript exons

ENST00000295797 — 18 exons

Exon	Start	End
ENSE00001075938	170273286	170273340
ENSE00001075940	170275229	170275287
ENSE00001075955	170291854	170291941
ENSE00001148433	170281882	170281968
ENSE00001148444	170281166	170281263
ENSE00001148448	170280227	170280403
ENSE00001148464	170270421	170270561
ENSE00001148468	170267915	170268000
ENSE00001148476	170263379	170263429
ENSE00001214886	170259969	170260058
ENSE00001214893	170235230	170235351
ENSE00001214914	170222424	170222770
ENSE00001868699	170303040	170305977
ENSE00003458686	170297304	170297393
ENSE00003472083	170293383	170293508
ENSE00003488305	170295911	170295990
ENSE00003595991	170284461	170284596
ENSE00003651957	170298995	170299110

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 97.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.2862 / max 119.5542, expressed in 1799 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39715	10.4094	1763
39713	5.3555	1686
39714	3.1501	1467
39711	1.0386	705
39712	0.3326	145

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.91	gold quality
pylorus	UBERON:0001166	96.79	gold quality
lower lobe of lung	UBERON:0008949	96.77	gold quality
corpus epididymis	UBERON:0004359	96.75	gold quality
cardia of stomach	UBERON:0001162	96.13	gold quality
oral cavity	UBERON:0000167	95.59	gold quality
renal medulla	UBERON:0000362	95.17	gold quality
pharyngeal mucosa	UBERON:0000355	94.96	gold quality
nipple	UBERON:0002030	94.67	gold quality
palpebral conjunctiva	UBERON:0001812	94.47	gold quality
jejunal mucosa	UBERON:0000399	94.39	gold quality
caput epididymis	UBERON:0004358	94.38	gold quality
cartilage tissue	UBERON:0002418	94.10	gold quality
cauda epididymis	UBERON:0004360	94.03	gold quality
colonic epithelium	UBERON:0000397	93.44	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.33	gold quality
skin of hip	UBERON:0001554	93.29	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.17	gold quality
eye	UBERON:0000970	93.16	gold quality
esophagus squamous epithelium	UBERON:0006920	93.09	gold quality
mammary duct	UBERON:0001765	93.02	gold quality
tongue squamous epithelium	UBERON:0006919	93.02	gold quality
colonic mucosa	UBERON:0000317	92.94	gold quality
choroid plexus epithelium	UBERON:0003911	92.91	gold quality
oviduct epithelium	UBERON:0004804	92.79	gold quality
Brodmann (1909) area 10	UBERON:0013541	92.75	gold quality
cerebellar vermis	UBERON:0004720	92.63	gold quality
bronchial epithelial cell	CL:0002328	92.62	gold quality
epithelium of mammary gland	UBERON:0003244	92.56	gold quality
mammalian vulva	UBERON:0000997	92.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ENAD-17	no	172.76
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ELK1

miRNA regulators (miRDB)

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

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-LET-7A-3P	100.00	74.03	3932
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-568	99.98	69.86	2084
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 40)

• The assignment of PRKCI to bovine chromosome 1q34–>q36 by FISH suggests a new assignment to human chromosome 3. (PMID:11978974)
• PKC iota was the only isoform exclusively detected in tumour lysates, spontaneously transformed melanoma cells & cell lines, but not in normal melanocytes. It may therefore be associated with the transformed phenotype in human melanoma. (PMID:12140376)
• PKCiota has a role in regulating cell survival in tumor cells (PMID:12791393)
• Complete assignments for residues 2-14 and 21-118 except for 8 prolines have been obtained and deposited as BMRB-5661. (PMID:12815264)
• protein kinase C iota/lambda binds to Rab 2, which inhibits aPKCiota/lambda-dependent GADPH phosphorylation (PMID:14570876)
• Bcr-Abl-mediated transformation involves transcriptional activation of the PKCiota gene, which in turn is required for Bcr-Abl-mediated chemoresistance. (PMID:14670960)
• Data demonstrate that protein kinase C (PKC) iota is required for oncogenic Ras- and carcinogen-mediated colon carcinogenesis in vivo and define a procarcinogenic signaling axis consisting of Ras, PKCiota, and Rac1. (PMID:15024028)
• determined the three-dimensional structure of the PB1 domain of PKCiota by NMR and found that the PB1 domain adopts a ubiquitin fold (PMID:15143057)
• protein kinase C alpha, iota, and theta binding to L-selectin cytoplasmic domain is modulated by receptor phosphorylation (PMID:15192100)
• crystal structure of the complex of PKCiota and Par6alpha PB1 domains to a resolution of 1.5 A (PMID:15590654)
• Confocal microscopy revealed the co-localization of PKC-iota with CAK/cdk7 in both the cytoplasm and nucleus of U-373 MG glioma cells, supporting its role in cell signaling. (PMID:15695176)
• an NNK-activated physiological Bad kinase, can phosphorylate and inactivate BH3, enhancing survival of lung cancer cells (PMID:15705582)
• PKCI mediates opposing effects on Na(+)-K(+)-Exchanging ATPase activity in a breast neoplasm cell line. (PMID:15887250)
• Data demonstrate that protein kinase Ciota is a critical lung cancer gene that activates a Rac1–>Pak–>Mek1,2–>Erk1,2 signaling pathway required for transformed growth. (PMID:15994303)
• PKCiota as a potential oncogene in ovarian cancer regulating epithelial cell polarity and proliferation (PMID:16116079)
• Results describe the crystal structure of the catalytic domain of atypical protein kinase C iota in complex with bis(indolyl)maleimide at 3.0A resolution. (PMID:16125198)
• a novel role for PKCiota as a nicotine-activated, physiological calpain kinase that directly phosphorylates and activates calpains. (PMID:16361262)
• atypical PKCs are required for insulin-stimulated glucose transport in myocytes and adipocytes (PMID:16644736)
• High levels of endothelin-1 impair endothelial nitric oxide production via PKCLambda-mediated inhibition of eNOS expression. (PMID:16820593)
• These data indicate that the G-CSF-induced dynamic translocation and activation processes of PKCiota are important to neutrophilic proliferation. (PMID:17133348)
• evidence that PKC iota is a human oncogene is discussed; review of mechanisms controlling PKC iota expression in human cancers; description of the molecular details of PKC iota-mediated oncogenic signaling [review] (PMID:17570678)
• These data demonstrate that atypical PKCzeta/iota isotypes serve as direct downstream targets of PKCtheta in the signalling pathway leading to NF-kappaB activation in T lymphocytes. (PMID:17588663)
• The expression of aPKC-iota and E-cadherin may reflect the differentiation and invasive potential of cholangiocarcinoma. As a polar regulation-associated protein, aPKC-iota may play a role in the invasion and metastasis of cholangiocarcinoma. (PMID:17626746)
• a molecular marker for metastasis and occult advanced tumor stages in esophageal squamous cell carcinomas (PMID:17990328)
• presence of PKC-iota may be required for cell proliferation to take place (PMID:18211289)
• in glioblastoma, PKC iota and RhoB are mutually antagonistic, potentially creating a sensitive switch between invasive and non-invasive phenotypes (PMID:18212741)
• The expressions of aPKC-iota and E-cadherin may reflect the differentiation and invasive potential of cholangiocarcinoma (PMID:18234642)
• Apically localized phosphorylation by PKCiota is essential for the activation and normal distribution of ezrin at the early stages of intestinal epithelial cell differentiation. (PMID:18270268)
• data define a PKCiota-Par6alpha-Rac1 signaling axis that drives anchorage-independent growth and invasion of NSCLC cells through induction of MMP-10 expression (PMID:18427549)
• This is the first evidence to show aPKC lambda/iota overexpression in breast cancer and its localization associated with the trend of pathologic type of the tumor. (PMID:18538170)
• Neph1-Nephrin proteins bind the Par3-Par6-atypical protein kinase C (aPKC) complex to regulate podocyte cell polarity (PMID:18562307)
• Atypical protein kinase C (PKC-iota/-zeta) phosphorylates IKKalphabeta in transformed non-malignant and malignant prostate cell survival. (PMID:18571841)
• Atypical protein kinase C iota expression has a role in aurothiomalate sensitivity in lung cancer cells (PMID:18632643)
• ezrin is regulated during osteosarcoma metastasis by PKC (PMID:19060919)
• Differentiation degree and invasion of hepatoma are related to the expression of PKC-iota, which plays an important role in invasion and metastasis of hepatoma. (PMID:19101699)
• PKC-iota is required for cell survival in both transformed non-malignant prostate RWPE-1 cells and androgen-independent malignant prostate DU-145 cells. Suppressing PKC-iota lead to apoptosis in DU-145 prostate cells. (PMID:19243387)
• expression of aPKC-iota was closely related to pathological differentiation, tumor size, invasion, and metastasis of HCC. (PMID:19290490)
• Protein kinase C iota mediates lipid-induced apoptosis of human coronary artery endothelial cells. (PMID:19327373)
• Filamentous keratins and Hsp70 are required for the rescue rephosphorylation of mature atypical PKC, regulating the subcellular distribution and steady-state levels of active PKC iota. (PMID:19549684)
• Ect2 and PKCiota are genetically and functionally linked in NSCLC, acting to coordinately drive tumor cell proliferation and invasion through formation of an oncogenic PKCiota-Par6alpha-Ect2 complex. (PMID:19617897)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkci	ENSDARG00000021225
mus_musculus	Prkci	ENSMUSG00000037643
rattus_norvegicus	Prkci	ENSRNOG00000009652
drosophila_melanogaster	Pkc53E	FBGN0003091
drosophila_melanogaster	inaC	FBGN0004784
drosophila_melanogaster	Pkn	FBGN0020621
drosophila_melanogaster	Pkcdelta	FBGN0287828
caenorhabditis_elegans		WBGENE00004033
caenorhabditis_elegans		WBGENE00006599
caenorhabditis_elegans		WBGENE00009793

Paralogs (9): PRKCH (ENSG00000027075), PKN2 (ENSG00000065243), PRKCZ (ENSG00000067606), PKN1 (ENSG00000123143), PRKCG (ENSG00000126583), PRKCA (ENSG00000154229), PKN3 (ENSG00000160447), PRKCB (ENSG00000166501), PRKCE (ENSG00000171132)

Protein

Protein identifiers

Protein kinase C iota type — P41743 (reviewed: P41743)

Alternative names: Atypical protein kinase C-lambda/iota, nPKC-iota

All UniProt accessions (1): P41743

UniProt curated annotations — full annotation on UniProt →

Function. Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process at a very early step. In glioblastoma cells, may function downstream of phosphatidylinositol 3-kinase (PI(3)K) and PDPK1 in the promotion of cell survival by phosphorylating and inhibiting the pro-apoptotic factor BAD. Can form a protein complex in non-small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and regulate ECT2 oncogenic activity by phosphorylation, which in turn promotes transformed growth and invasion. In response to nerve growth factor (NGF), acts downstream of SRC to phosphorylate and activate IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal cell survival. Functions in the organization of the apical domain in epithelial cells by phosphorylating EZR. This step is crucial for activation and normal distribution of EZR at the early stages of intestinal epithelial cell differentiation. Forms a protein complex with LLGL1 and PARD6B independently of PARD3 to regulate epithelial cell polarity. Plays a role in microtubule dynamics in the early secretory pathway through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). In human coronary artery endothelial cells (HCAEC), is activated by saturated fatty acids and mediates lipid-induced apoptosis. Involved in early synaptic long term potentiation phase in CA1 hippocampal cells and short term memory formation.

Subunit / interactions. Forms a complex with SQSTM1 and MP2K5. Interacts directly with SQSTM1. Interacts with IKBKB. Interacts with PARD6A, PARD6B and PARD6G. Part of a quaternary complex containing aPKC, PARD3, a PARD6 protein (PARD6A, PARD6B or PARD6G) and a GTPase protein (CDC42 or RAC1). Part of a complex with LLGL1 and PARD6B. Interacts with ADAP1/CENTA1. Interaction with SMG1, through the ZN-finger domain, activates the kinase activity. Interacts with CDK7. Forms a complex with RAB2A and GAPDH involved in recruitment onto the membrane of vesicular tubular clusters (VTCs). Interacts with ECT2 (‘Thr-359’ phosphorylated form). Interacts with VAMP2. Interacts with WDFY2 (via WD repeats 1-3).

Subcellular location. Cytoplasm. Membrane. Endosome. Nucleus.

Tissue specificity. Predominantly expressed in lung and brain, but also expressed at lower levels in many tissues including pancreatic islets. Highly expressed in non-small cell lung cancers.

Post-translational modifications. Phosphorylation at Thr-412 in the activation loop is not mandatory for activation. Upon neuronal growth factor (NGF) stimulation, phosphorylated by SRC at Tyr-265, Tyr-280 and Tyr-334. Phosphorylation at Tyr-265 facilitates binding to KPNB1/importin-beta regulating entry of PRKCI into the nucleus. Phosphorylation on Tyr-334 is important for NF-kappa-B stimulation. Phosphorylated at Thr-564 during the initial phase of long term potentiation.

Activity regulation. Atypical PKCs (PRKCI and PRKCZ) exhibit an elevated basal enzymatic activity (that may be due to the interaction with SMG1 or SQSTM1) and are not regulated by diacylglycerol, phosphatidylserine, phorbol esters or calcium ions. Two specific sites, Thr-412 (activation loop of the kinase domain) and Thr-564 (turn motif), need to be phosphorylated for its full activation. Might also be a target for novel lipid activators that are elevated during nutrient-stimulated insulin secretion.

Domain organisation. The PB1 domain mediates interaction with SQSTM1. The C1 zinc finger does not bind diacylglycerol (DAG). The pseudosubstrate motif resembles the sequence around sites phosphorylated on target proteins, except the presence of a non-phosphorylatable residue in place of Ser, it modulates activity by competing with substrates.

Similarity. Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.

RefSeq proteins (1): NP_002731* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000270	PB1_dom	Domain
IPR000719	Prot_kinase_dom	Domain
IPR000961	AGC-kinase_C	Domain
IPR002219	PKC_DAG/PE	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR012233	PKC	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR017892	Pkinase_C	Domain
IPR020454	DAG/PE-bd	Domain
IPR034661	aPKC_iota	Domain
IPR034877	PB1_aPKC	Domain
IPR046349	C1-like_sf	Homologous_superfamily
IPR053793	PB1-like	Domain

Pfam: PF00069, PF00130, PF00433, PF00564

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.

Substrate	Km (mM)	Measurements
FKKQGSFAKKK	0.0166–0.0599	10
ATP	0.0001–0.0828	4
N6-PHENYL-ATP	0.0124	1
S6-(229-239) PEPTIDE	0.0036	1

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 (85 total): helix 22, strand 16, modified residue 10, mutagenesis site 9, turn 6, region of interest 5, domain 3, sequence conflict 3, compositionally biased region 2, binding site 2, sequence variant 2, initiator methionine 1, chain 1, short sequence motif 1, active site 1, zinc finger region 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
1WMH	X-RAY DIFFRACTION	1.5
5LI9	X-RAY DIFFRACTION	1.79
3A8X	X-RAY DIFFRACTION	2
5LI1	X-RAY DIFFRACTION	2
3A8W	X-RAY DIFFRACTION	2.1
8R3X	X-RAY DIFFRACTION	2.59
3ZH8	X-RAY DIFFRACTION	2.74
1ZRZ	X-RAY DIFFRACTION	3
9EJK	ELECTRON MICROSCOPY	3.08
5LIH	X-RAY DIFFRACTION	3.25
6ILZ	X-RAY DIFFRACTION	3.26
9EJM	ELECTRON MICROSCOPY	3.33
9EJL	ELECTRON MICROSCOPY	3.48
8R3Y	ELECTRON MICROSCOPY	3.68
1VD2	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P41743-F1	81.00	0.46

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): 378 (proton acceptor)

Ligand- & substrate-binding residues (2): 260–268; 283

Post-translational modifications (10): 2, 3, 7, 8, 9, 265, 280, 334, 412, 564

Mutagenesis-validated functional residues (9):

Position	Phenotype
29	no effect on interaction with sqstm1.
72	loss of interaction with ect2, pard6a and with sqstm1.
85	slight decrease of interaction with pard6a. loss of interaction with pard6a; when associated with a-91.
91	slight decrease of interaction with pard6a. loss of interaction with pard6a; when associated with a-85.
265	no effect on the src-mediated phosphorylation state. no effect on src-induced enzyme activity. little effect on traf6-me
274	no effect on activity.
274	abolishes activity.
280	no effect on the src-mediated phosphorylation state. no effect on src-induced enzyme activity. no effect on traf6-mediat
334	no effect on the src-mediated phosphorylation state. significant reduction of src-induced enzyme activity. greatly reduc

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-1912408	Pre-NOTCH Transcription and Translation
R-HSA-209543	p75NTR recruits signalling complexes
R-HSA-420029	Tight junction interactions
R-HSA-9755511	KEAP1-NFE2L2 pathway
R-HSA-1500931	Cell-Cell communication
R-HSA-157118	Signaling by NOTCH
R-HSA-162582	Signal Transduction
R-HSA-1912422	Pre-NOTCH Expression and Processing
R-HSA-193639	p75NTR signals via NF-kB
R-HSA-193704	p75 NTR receptor-mediated signalling
R-HSA-2262752	Cellular responses to stress
R-HSA-421270	Cell-cell junction organization
R-HSA-446728	Cell junction organization
R-HSA-73887	Death Receptor Signaling
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9711123	Cellular response to chemical stress

MSigDB gene sets: 423 (showing top): MODULE_97, REACTOME_SIGNALING_BY_NOTCH, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_MONOPOLAR_CELL_POLARITY, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_RESPONSE_TO_PEPTIDE, GOBP_VESICLE_ORGANIZATION, PID_IL1_PATHWAY, GOBP_POSITIVE_REGULATION_OF_NOTCH_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_PROTEIN_TARGETING, MODULE_182, GOBP_NEUROGENESIS

GO Biological Process (31): protein phosphorylation (GO:0006468), protein targeting to membrane (GO:0006612), cytoskeleton organization (GO:0007010), actin filament organization (GO:0007015), positive regulation of neuron projection development (GO:0010976), vesicle-mediated transport (GO:0016192), cell migration (GO:0016477), establishment of cell polarity (GO:0030010), cellular response to insulin stimulus (GO:0032869), negative regulation of glial cell apoptotic process (GO:0034351), establishment of apical/basal cell polarity (GO:0035089), intracellular signal transduction (GO:0035556), eye photoreceptor cell development (GO:0042462), negative regulation of apoptotic process (GO:0043066), negative regulation of neuron apoptotic process (GO:0043524), establishment or maintenance of epithelial cell apical/basal polarity (GO:0045197), cell-cell junction organization (GO:0045216), positive regulation of Notch signaling pathway (GO:0045747), positive regulation of D-glucose import across plasma membrane (GO:0046326), secretion (GO:0046903), Golgi vesicle budding (GO:0048194), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), positive regulation of glial cell proliferation (GO:0060252), membrane organization (GO:0061024), cellular response to chemical stress (GO:0062197), response to interleukin-1 (GO:0070555), protein localization to plasma membrane (GO:0072659), regulation of postsynaptic membrane neurotransmitter receptor levels (GO:0099072), positive regulation of protein localization to plasma membrane (GO:1903078), positive regulation of endothelial cell apoptotic process (GO:2000353), response to peptide hormone (GO:0043434)

GO Molecular Function (13): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), diacylglycerol-dependent serine/threonine kinase activity (GO:0004697), diacylglycerol-dependent, calcium-independent serine/threonine kinase activity (GO:0004699), ATP binding (GO:0005524), phospholipid binding (GO:0005543), 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 (22): Golgi membrane (GO:0000139), nucleus (GO:0005634), nucleoplasm (GO:0005654), endosome (GO:0005768), cytosol (GO:0005829), plasma membrane (GO:0005886), brush border (GO:0005903), bicellular tight junction (GO:0005923), cilium (GO:0005929), microtubule cytoskeleton (GO:0015630), apical plasma membrane (GO:0016324), cell leading edge (GO:0031252), Schmidt-Lanterman incisure (GO:0043220), intercellular bridge (GO:0045171), extracellular exosome (GO:0070062), tight junction (GO:0070160), Schaffer collateral - CA1 synapse (GO:0098685), glutamatergic synapse (GO:0098978), PAR polarity complex (GO:0120157), cytoplasm (GO:0005737), membrane (GO:0016020), apical part of cell (GO:0045177)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Signal Transduction	2
Pre-NOTCH Expression and Processing	1
p75NTR signals via NF-kB	1
Cell-cell junction organization	1
Cellular response to chemical stress	1
Signaling by NOTCH	1
p75 NTR receptor-mediated signalling	1
Death Receptor Signaling	1
Cellular responses to stimuli	1
Cell junction organization	1
Cell-Cell communication	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
transport	2
negative regulation of apoptotic process	2
establishment or maintenance of apical/basal cell polarity	2
intracellular anatomical structure	2
protein kinase activity	2
apical part of cell	2
synapse	2
phosphorylation	1
protein modification process	1
protein targeting	1
establishment of protein localization to membrane	1
organelle organization	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
cellular process	1
cell motility	1
establishment or maintenance of cell polarity	1
response to insulin	1
cellular response to peptide hormone stimulus	1
glial cell apoptotic process	1
regulation of glial cell apoptotic process	1
establishment of monopolar cell polarity	1
signal transduction	1
eye photoreceptor cell differentiation	1
photoreceptor cell development	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
cell junction organization	1
Notch signaling pathway	1
regulation of Notch signaling pathway	1
positive regulation of signal transduction	1
positive regulation of D-glucose transmembrane transport	1
regulation of D-glucose import across plasma membrane	1

Protein interactions and networks

STRING

2352 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKCI	PARD3	Q8TEW0	883
PRKCI	ECT2	Q9H8V3	774
PRKCI	PARD6A	Q9NPB6	729
PRKCI	SMG9	Q9H0W8	666
PRKCI	SMG8	Q8ND04	666
PRKCI	PPP1R1A	Q13522	649
PRKCI	ETF1	P46055	639
PRKCI	GSPT1	P15170	637
PRKCI	TP53	P04637	610
PRKCI	PARD6B	Q9BYG5	583
PRKCI	SKIL	P12756	562
PRKCI	SMG1	Q96Q15	558
PRKCI	UPF3A	Q9H1J1	550
PRKCI	UPF2	Q9HAU5	548
PRKCI	GAPDH	P00354	516

IntAct

206 interactions, top by confidence:

A	B	Type	Score
PARD6B	PRKCI	psi-mi:“MI:0915”(physical association)	0.960
PRKCI	PARD6B	psi-mi:“MI:0915”(physical association)	0.960
PARD6B	PRKCI	psi-mi:“MI:0914”(association)	0.960
PRKCI	PARD6A	psi-mi:“MI:0915”(physical association)	0.950
PARD6A	PRKCI	psi-mi:“MI:0915”(physical association)	0.950
PARD6A	PRKCI	psi-mi:“MI:0407”(direct interaction)	0.950
PARD6A	PRKCI	psi-mi:“MI:0914”(association)	0.950
PRKCZ	PRKCI	psi-mi:“MI:0914”(association)	0.890
PRKCI	SQSTM1	psi-mi:“MI:0915”(physical association)	0.890

BioGRID (459): PARD6A (Two-hybrid), PARD6B (Two-hybrid), PRKCI (Affinity Capture-MS), PRKCI (Affinity Capture-MS), PRKCI (Affinity Capture-MS), PRKCI (Affinity Capture-MS), PARD6A (Two-hybrid), PRKCI (Affinity Capture-MS), KIF23 (Co-fractionation), PPM1A (Co-fractionation), PPM1B (Co-fractionation), PRKCI (Co-fractionation), PRKCI (Proximity Label-MS), PRKCI (Proximity Label-MS), PRKCI (Two-hybrid)

ESM2 similar proteins: A1Z9X0, A8WUG4, A8XWC4, F1M7Y5, O13310, O19111, O74536, O97627, P00518, P07934, P09217, P13286, P23443, P26817, P26818, P26819, P31325, P34722, P35626, P41743, P54645, P54646, P67998, P67999, P83099, Q02111, Q02956, Q04759, Q05513, Q09137, Q12706, Q13131, Q16816, Q19266, Q21734, Q28948, Q2KJ16, Q3UYH7, Q5EG47, Q5R4K9

Diamond homologs: A0QQK3, A8WUG4, A8X5H5, A8X6H1, A8XJQ6, A8XW88, F1M7Y5, F4HYG2, F4J6F6, G4NH08, O02827, O76360, O88664, P00517, P0DPS8, P10421, P10830, P11799, P16054, P16912, P17612, P18431, P18654, P20911, P21137, P22216, P22694, P25321, P27636, P27791, P29294, P32490, P34099, P34103, P36887, P38070, P40376, P41743, P49673, P50613

SIGNOR signaling

21 interactions.

A	Effect	B	Mechanism
SRC	up-regulates	PRKCI	phosphorylation
PRKCI	down-regulates	NUMB	phosphorylation
PRKCI	up-regulates	EZR	phosphorylation
PRKCI	up-regulates	ECT2	phosphorylation
PRKCI	down-regulates	BAD	phosphorylation
1,2-diacyl-sn-glycerol	“up-regulates activity”	PRKCI	binding
PRKCI	“down-regulates activity”	NOS3	phosphorylation
RAB2A	“down-regulates activity”	PRKCI	binding
VCB-Cul2	“down-regulates quantity by destabilization”	PRKCI	polyubiquitination
PRKCI	“up-regulates quantity by stabilization”	PARD6A	phosphorylation
PRKCI	“down-regulates activity”	FBXW7	phosphorylation
PRKCI	“up-regulates activity”	VIM	phosphorylation
PRKCI	“up-regulates activity”	GLI1	phosphorylation
PRKCI	“up-regulates activity”	CDK7	phosphorylation
PRKCI	“up-regulates activity”	LLGL1	phosphorylation
PRKCI	“up-regulates activity”	LLGL2	phosphorylation
PRKCI	“down-regulates activity”	MAPT	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 143 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:

Pathway	Partners	Fold	FDR
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	8	51.2×	4e-10
Activation of BAD and translocation to mitochondria	7	50.8×	8e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	44.8×	2e-08
Activation of BH3-only proteins	7	33.1×	1e-07
Chaperone Mediated Autophagy	6	28.4×	4e-06
RHO GTPases activate PKNs	8	24.2×	1e-07
Intrinsic Pathway for Apoptosis	8	22.3×	2e-07
GPVI-mediated activation cascade	7	20.6×	3e-06

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	8	35.8×	5e-08
establishment or maintenance of cell polarity	7	21.6×	1e-05
establishment of cell polarity	7	20.6×	1e-05
mitophagy	7	17.1×	4e-05
protein targeting	6	16.9×	2e-04
autophagosome maturation	5	13.5×	2e-03
ephrin receptor signaling pathway	5	13.2×	2e-03
mitotic spindle organization	6	12.5×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3454 predictions. Top by Δscore:

Variant	Effect	Δscore
3:170222767:GCGG:G	donor_gain	1.0000
3:170222769:GG:G	donor_gain	1.0000
3:170222769:GGGT:G	donor_loss	1.0000
3:170222770:GG:G	donor_gain	1.0000
3:170222770:GGT:G	donor_loss	1.0000
3:170222771:G:GG	donor_gain	1.0000
3:170222771:GTGA:G	donor_loss	1.0000
3:170222772:T:G	donor_loss	1.0000
3:170222773:GAGT:G	donor_loss	1.0000
3:170235228:A:AC	acceptor_loss	1.0000
3:170235228:A:AG	acceptor_gain	1.0000
3:170235228:AG:A	acceptor_gain	1.0000
3:170235228:AGG:A	acceptor_gain	1.0000
3:170235229:G:GT	acceptor_gain	1.0000
3:170235229:GG:G	acceptor_gain	1.0000
3:170235229:GGG:G	acceptor_gain	1.0000
3:170235229:GGGAT:G	acceptor_gain	1.0000
3:170235347:GGAAG:G	donor_gain	1.0000
3:170235348:G:GT	donor_gain	1.0000
3:170235348:GAAG:G	donor_gain	1.0000
3:170235349:A:T	donor_gain	1.0000
3:170235352:G:GG	donor_gain	1.0000
3:170235353:T:A	donor_loss	1.0000
3:170259965:TTAG:T	acceptor_loss	1.0000
3:170259966:TA:T	acceptor_loss	1.0000
3:170259967:A:AG	acceptor_gain	1.0000
3:170259967:AG:A	acceptor_gain	1.0000
3:170259968:G:GT	acceptor_gain	1.0000
3:170259968:GG:G	acceptor_gain	1.0000
3:170259968:GGA:G	acceptor_gain	1.0000

AlphaMissense

3998 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:170235336:T:A	W70R	1.000
3:170235336:T:C	W70R	1.000
3:170260010:G:C	A89P	1.000
3:170267926:C:A	R126S	1.000
3:170267971:C:G	H141D	1.000
3:170267973:C:A	H141Q	1.000
3:170267973:C:G	H141Q	1.000
3:170267977:T:C	F143L	1.000
3:170267978:T:C	F143S	1.000
3:170267979:C:A	F143L	1.000
3:170267979:C:G	F143L	1.000
3:170267984:C:A	A145D	1.000
3:170267986:A:G	K146E	1.000
3:170267988:G:C	K146N	1.000
3:170267988:G:T	K146N	1.000
3:170267993:T:C	F148S	1.000
3:170270430:T:A	C154S	1.000
3:170270430:T:C	C154R	1.000
3:170270430:T:G	C154G	1.000
3:170270431:G:A	C154Y	1.000
3:170270431:G:C	C154S	1.000
3:170270431:G:T	C154F	1.000
3:170270432:T:G	C154W	1.000
3:170270439:T:A	C157S	1.000
3:170270439:T:C	C157R	1.000
3:170270440:G:A	C157Y	1.000
3:170270440:G:C	C157S	1.000
3:170270440:G:T	C157F	1.000
3:170270441:C:G	C157W	1.000
3:170270452:T:A	I161K	1.000

dbSNP variants (sampled 300 via entrez): RS1000053010 (3:170258384 C>T), RS1000054831 (3:170262645 AT>A,ATT), RS1000123876 (3:170261070 C>T), RS1000124670 (3:170258091 A>G), RS1000132903 (3:170262914 T>C), RS1000160823 (3:170240337 A>C,G), RS1000213015 (3:170288218 C>T), RS1000215236 (3:170246505 G>C), RS1000241721 (3:170268724 T>C), RS1000261847 (3:170224910 C>T), RS1000317783 (3:170240610 A>C), RS1000335759 (3:170224650 A>G), RS1000369319 (3:170287548 T>C), RS1000447417 (3:170230505 T>C,G), RS1000474707 (3:170305962 A>G)

Disease associations

OMIM: gene MIM:600539 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002890_8	Prostate cancer	8.000000e-14
GCST006586_10	Urinary albumin excretion	3.000000e-12
GCST008790_17	Urinary albumin-to-creatinine ratio	7.000000e-14
GCST008791_25	Microalbuminuria	5.000000e-08
GCST008794_55	Urinary albumin-to-creatinine ratio	2.000000e-13
GCST009640_18	Urinary albumin-to-creatinine ratio	1.000000e-12
GCST90011899_114	Aspartate aminotransferase levels	1.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004285	albuminuria
EFO:0007778	urinary albumin to creatinine ratio
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2093867 (PROTEIN FAMILY), CHEMBL2598 (SINGLE PROTEIN), CHEMBL3885627 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

20 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 279,759 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1863513	INGENOL MEBUTATE	4	1,475
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL83	TAMOXIFEN	4	171,635
CHEMBL265502	SURAMIN	3	36,848
CHEMBL38380	FASUDIL	3	11,953
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL279115	PHORBOL MYRISTATE ACETATE	2	1,362
CHEMBL28509	EDELFOSINE	2	10,540
CHEMBL3137336	UPROSERTIB	2	1,624
CHEMBL574737	UCN-01	2	2,217
CHEMBL1967878	CENISERTIB	2	358
CHEMBL1980297	ILORASERTIB	2	581
CHEMBL2386889	SCH-900776	2	740
CHEMBL3545396	BMS-690514	2	567
CHEMBL565612	SOTRASTAURIN	2	1,355
CHEMBL1908394	GSK-461364	1	1,093
CHEMBL3128043	PF-03758309	1	233
CHEMBL494089	GSK-690693	1	2,061

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Iota subfamily

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
staurosporine	Inhibition	6.46	pIC50

Binding affinities (BindingDB)

11 measured of 37 human assays (37 total across all organisms); most potent 11 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4442196	IC50	0.09 nM
CHEMBL3741746	IC50	0.13 nM
CHEMBL4528495	IC50	0.15 nM
CHEMBL4538431	IC50	0.17 nM
CHEMBL4443190	IC50	0.18 nM
CHEMBL4435580	IC50	0.22 nM
CHEMBL4587471	IC50	0.36 nM
CHEMBL4575056	EC50	0.6 nM
CHEMBL411351	IC50	15000 nM
CHEMBL3215313	IC50	17000 nM
CHEMBL81478	IC50	30000 nM

ChEMBL bioactivities

830 potent at pChembl≥5 of 952 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.10	IC50	0.08	nM	STAUROSPORINE
10.05	IC50	0.09	nM	CHEMBL4442196
9.89	IC50	0.13	nM	CHEMBL3741746
9.85	IC50	0.14	nM	CHEMBL4575056
9.82	IC50	0.15	nM	CHEMBL4528495
9.77	IC50	0.17	nM	CHEMBL4538431
9.74	IC50	0.18	nM	CHEMBL4443190
9.72	EC50	0.19	nM	CHEMBL3741746
9.66	IC50	0.22	nM	CHEMBL4435580
9.44	IC50	0.36	nM	CHEMBL4587471
9.26	EC50	0.55	nM	CHEMBL4587471
9.22	EC50	0.6	nM	CHEMBL4575056
9.22	IC50	0.6	nM	STAUROSPORINE
9.00	IC50	1	nM	STAUROSPORINE
8.77	IC50	1.7	nM	CHEMBL291126
8.70	IC50	2	nM	CHEMBL162621
8.70	IC50	2	nM	STAUROSPORINE
8.66	IC50	2.2	nM	CHEMBL83790
8.57	IC50	2.7	nM	STAUROSPORINE
8.57	IC50	2.7	nM	CHEMBL4212424
8.55	IC50	2.8	nM	CHEMBL4202753
8.52	IC50	3	nM	STAUROSPORINE
8.50	Ki	3.162	nM	CHEMBL592030
8.42	IC50	3.8	nM	CHEMBL4208685
8.39	IC50	4.1	nM	UCN-01
8.30	IC50	5	nM	CHEMBL4206065
8.30	IC50	5	nM	CHEMBL538718
8.28	Ki	5.3	nM	BALANOL
8.22	Kd	6	nM	CHEMBL27768
8.22	IC50	6	nM	STAUROSPORINE
8.19	IC50	6.5	nM	CHEMBL4216507
8.19	IC50	6.5	nM	STAUROSPORINE
8.15	IC50	7	nM	STAUROSPORINE
8.12	IC50	7.5	nM	STAUROSPORINE
8.10	IC50	8	nM	STAUROSPORINE
8.10	IC50	7.9	nM	STAUROSPORINE
8.10	IC50	8	nM	CHEMBL538718
8.05	IC50	9	nM	CHEMBL337026
8.02	EC50	9.5	nM	PHORBOL MYRISTATE ACETATE
8.00	IC50	10	nM	CHEMBL444864
8.00	IC50	10	nM	CHEMBL162903
8.00	IC50	10	nM	BISINDOLYLMALEIMIDE IX
8.00	IC50	10	nM	CHEMBL163269
8.00	IC50	10	nM	CHEMBL329274
8.00	IC50	10	nM	STAUROSPORINE
7.89	IC50	13	nM	CHEMBL338049
7.85	IC50	14	nM	CHEMBL338935
7.85	IC50	14	nM	CHEMBL340611
7.80	IC50	16	nM	CHEMBL4441825
7.78	IC50	16.7	nM	STAUROSPORINE

PubChem BioAssay actives

180 with measured affinity, of 1910 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.

Compound	Assay	Type	Value	Unit
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-12-benzoyloxy-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-22-acetyloxy-12-benzoyloxy-10,11-dihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] naphthalene-2-carboxylate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,25R)-12-benzoyloxy-10,11-dihydroxy-9-(hydroxymethyl)-13,15-dimethyl-22-oxo-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
(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-one	165147: Inhibition Protein kinase C (PKC)	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] 4-nitrobenzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0002	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-12-benzoyloxy-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-propan-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0002	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] 4-methoxybenzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0002	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] pyridine-4-carboxylate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0004	uM
(15R,16R,18S)-16-(hydroxymethyl)-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-3,5-dione	155717: In vitro inhibition of protein kinase C (PKC)	ic50	0.0017	uM
3-(fluoromethyl)-6-methoxy-7-[5-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrazolo[1,5-a]pyridin-3-yl]-1,2,3,4-tetrahydroisoquinoline	1375384: Inhibition of full-length N-terminal GST-fused human PKC-iota expressed in baculovirus expression system using (5FAM) RFARKGSLRQKNV as substrate after 60 mins by caliper assay	ic50	0.0027	uM
6-methoxy-7-[5-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrazolo[1,5-a]pyridin-3-yl]-1,2,3,4-tetrahydroisoquinoline	1375384: Inhibition of full-length N-terminal GST-fused human PKC-iota expressed in baculovirus expression system using (5FAM) RFARKGSLRQKNV as substrate after 60 mins by caliper assay	ic50	0.0028	uM
6-methoxy-3-methyl-7-[5-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrazolo[1,5-a]pyridin-3-yl]-1,2,3,4-tetrahydroisoquinoline	1375384: Inhibition of full-length N-terminal GST-fused human PKC-iota expressed in baculovirus expression system using (5FAM) RFARKGSLRQKNV as substrate after 60 mins by caliper assay	ic50	0.0038	uM
3-(6-methoxy-2-methyl-1,3-dihydroisoindol-5-yl)-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrazolo[1,5-a]pyridine	1375384: Inhibition of full-length N-terminal GST-fused human PKC-iota expressed in baculovirus expression system using (5FAM) RFARKGSLRQKNV as substrate after 60 mins by caliper assay	ic50	0.0050	uM
2-[2,6-dihydroxy-4-[(3R,4R)-3-[(4-hydroxybenzoyl)amino]azepan-4-yl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	254306: Inhibitory constant against protein kinase C	ki	0.0053	uM
[(1S,2S,6R,10S,11R,13S,14R,15R)-13-butanoyloxy-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] butanoate	2150891: Binding affinity to PKC (unknown origin) assessed as dissociation constant	kd	0.0060	uM
3-(6-methoxy-2,3-dihydro-1H-isoindol-5-yl)-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrazolo[1,5-a]pyridine	1375384: Inhibition of full-length N-terminal GST-fused human PKC-iota expressed in baculovirus expression system using (5FAM) RFARKGSLRQKNV as substrate after 60 mins by caliper assay	ic50	0.0065	uM
[(1S,2S,6R,10S,11R,13S,14R,15R)-13-acetyloxy-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] tetradecanoate	1459482: Activation of PKC in human platelet assessed as induction of platelet aggregation measured within 15 mins by tribidimetric method	ec50	0.0095	uM
5-chloro-4-(4-chloro-1-methylpyrazol-5-yl)-N-[(3S,4S,6S)-4-(3,4-difluorophenyl)-6-(2-hydroxyethyl)piperidin-3-yl]furan-2-carboxamide	1608042: Inhibition of PKC (unknown origin)	ic50	0.0160	uM
(2S,5S)-9-decyl-5-(hydroxymethyl)-1-methyl-2-propan-2-yl-2,4,5,6-tetrahydro-1,4-benzodiazocin-3-one	2163933: Activation of PKC in human ACH-2 cells infected with latent HIV-1 assessed as reversal of HIV-1 latency by measuring increase in p24 antigen level incubated for 48 hrs by chemiluminescent enzyme immunoassay	ec50	0.0250	uM
1-(6-methoxy-2,3-dihydro-1H-isoindol-5-yl)-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)imidazo[4,5-c]pyridine	1375384: Inhibition of full-length N-terminal GST-fused human PKC-iota expressed in baculovirus expression system using (5FAM) RFARKGSLRQKNV as substrate after 60 mins by caliper assay	ic50	0.0300	uM
4-[[[6-methoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]quinolin-8-yl]amino]methyl]phenol	1180278: Inhibition of PKC (unknown origin) using C1 peptide substrate	ic50	0.0350	uM
N-[(1R,2S)-2-aminocyclohexyl]-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637126: Inhibition of full-length recombinant human His-tagged PRKCI expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0370	uM
(10S,13S)-13-(hydroxymethyl)-9-methyl-10-propan-2-yl-3,9,12-triazatricyclo[6.6.1.04,15]pentadeca-1,4(15),5,7-tetraen-11-one	2163933: Activation of PKC in human ACH-2 cells infected with latent HIV-1 assessed as reversal of HIV-1 latency by measuring increase in p24 antigen level incubated for 48 hrs by chemiluminescent enzyme immunoassay	ec50	0.0470	uM
1-(6-methoxy-2,3-dihydro-1H-isoindol-5-yl)-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzimidazole	1375384: Inhibition of full-length N-terminal GST-fused human PKC-iota expressed in baculovirus expression system using (5FAM) RFARKGSLRQKNV as substrate after 60 mins by caliper assay	ic50	0.0480	uM
3-(6-methoxy-2,3-dihydro-1H-isoindol-5-yl)-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)imidazo[4,5-b]pyridine	1375384: Inhibition of full-length N-terminal GST-fused human PKC-iota expressed in baculovirus expression system using (5FAM) RFARKGSLRQKNV as substrate after 60 mins by caliper assay	ic50	0.0650	uM
[1-(2-pyridin-4-yl-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl]methanamine	1662460: Inhibition of recombinant full-length human aPKCiota using CREBtide as substrate incubated for 3 hrs in presence of ATP by kinase Glo luminescent assay	ic50	0.0700	uM
[(1S,4S,5S,6R,9S,10R,12R,14R)-5,6-dihydroxy-7-(hydroxymethyl)-3,11,11,14-tetramethyl-15-oxo-4-tetracyclo[7.5.1.01,5.010,12]pentadeca-2,7-dienyl] (Z)-2-methylbut-2-enoate	1459482: Activation of PKC in human platelet assessed as induction of platelet aggregation measured within 15 mins by tribidimetric method	ec50	0.0725	uM
bis(3,3-bis[4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]-2-phenylprop-2-enenitrile);pentahydrochloride	1323681: Inhibition of PKC in human SH-SY5Y cells assessed as inhibition of PMA-stimulated MARCKS phosphorylation preincubated for 1 hr followed by PMA-stimulation for 15 mins by Western blot analysis	ic50	0.0800	uM
3-hydroxy-2-[4-[(3R,4R)-3-[(4-hydroxybenzoyl)amino]azepan-4-yl]oxycarbonylbenzoyl]benzoic acid	254303: Inhibitory activity against protein kinase C	ki	0.0800	uM
3,13-diazahexacyclo[14.8.0.02,10.04,9.011,15.017,22]tetracosa-1(16),2(10),4,6,8,11(15),17,19,21-nonaene-12,14-dione	277640: Inhibition of PKC	ic50	0.0830	uM
5-chloro-4-(4-chloro-1-methylpyrazol-5-yl)-N-[(3S,4S,6S)-4-(3,4-difluorophenyl)-6-[2-(methylamino)-2-oxoethyl]piperidin-3-yl]furan-2-carboxamide	1608042: Inhibition of PKC (unknown origin)	ic50	0.0940	uM
(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-3-hydroxy-2-[3-[2-(isoquinolin-5-ylsulfonylamino)ethylamino]propanoylamino]propanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoic acid	164148: Displacement of ATP from protein kinase C (PKC)	ki	0.1000	uM
3-(6-methoxy-2,3-dihydro-1H-isoindol-5-yl)-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrazolo[1,5-a]pyrimidine	1375384: Inhibition of full-length N-terminal GST-fused human PKC-iota expressed in baculovirus expression system using (5FAM) RFARKGSLRQKNV as substrate after 60 mins by caliper assay	ic50	0.1100	uM
methyl (15S,16S,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-carboxylate	165267: Inhibition of protein kinase C (PKC)	ic50	0.1140	uM
[3-methoxy-4-[6-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzimidazol-1-yl]phenyl]methanamine	1375384: Inhibition of full-length N-terminal GST-fused human PKC-iota expressed in baculovirus expression system using (5FAM) RFARKGSLRQKNV as substrate after 60 mins by caliper assay	ic50	0.1200	uM
N’-[5-[2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]-2-pyridinyl]ethane-1,2-diamine	165284: Inhibition of protein kinase C (PKC)	ic50	0.1500	uM
5-chloro-4-(4-chloro-1-methylpyrazol-5-yl)-N-[(3S,4S)-4-(3,4-difluorophenyl)piperidin-3-yl]furan-2-carboxamide;(2R,3R)-2,3-dihydroxybutanedioic acid	1608042: Inhibition of PKC (unknown origin)	ic50	0.1560	uM
8-[(4-hydroxyphenyl)methylamino]-4-methyl-5-[3-(trifluoromethyl)phenoxy]quinolin-6-ol	1180278: Inhibition of PKC (unknown origin) using C1 peptide substrate	ic50	0.1580	uM
3-(23-methyl-14-oxo-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4,6,8,10,15,17,19,21-nonaen-3-yl)propanenitrile	2197074: Inhibition of PKC in human bortezomib-resistant ANBL6 cells assessed as reduction of cell growth incubated for 72 hrs by CellTiter 96 aqueous one solution cell proliferation assay	ic50	0.1632	uM
5-(1H-benzimidazol-2-yl)-2-chloro-4-(piperidin-3-ylamino)-7H-thieno[2,3-b]pyridin-6-one	1184488: Inhibition of PKC (unknown origin) by Z’-LYTETM kinase assay	ic50	0.1689	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149080: Binding affinity to human PRKCI incubated for 45 mins by Kinobead based pull down assay	kd	0.1736	uM
3-[1-[3-(dimethylamino)propyl]indol-3-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	2150852: Inhibition of PKC in human platelet assessed as inhibition of diC8-induced p47 phosphorylation pre-incubated for 1 min followed by diC8 stimulation and measured after 30 sec by autoradiographic analysis	ic50	0.1900	uM
3,4-bis(1H-indol-3-yl)pyrrole-2,5-dione	155709: Inhibitory activity was determined against protein kinase C (PKC) from porcine brain	ic50	0.1900	uM
2-chloro-5-(6-methoxy-1H-benzimidazol-2-yl)-4-[[(3S)-piperidin-3-yl]amino]-7H-thieno[2,3-b]pyridin-6-one	1184488: Inhibition of PKC (unknown origin) by Z’-LYTETM kinase assay	ic50	0.2045	uM
3,13-diazahexacyclo[14.8.0.02,10.04,9.011,15.017,22]tetracosa-1(16),2(10),4,6,8,11(15),17,19,21-nonaen-12-one	277640: Inhibition of PKC	ic50	0.2050	uM
3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4,6,8,10,15,17,19,21-nonaen-12-one	2150895: Inhibition of PKC (unknown origin) incubated for 30 mins in presence of ATP by Pep-Tag reagent based UV-laser densitometer analysis	ic50	0.2140	uM
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[[(3S)-piperidin-3-yl]methoxy]imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	624883: Binding constant for PRKCI kinase domain	kd	0.2500	uM
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-carboxylate	165267: Inhibition of protein kinase C (PKC)	ic50	0.2500	uM
methyl (15R,16S,18S)-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-carboxylate	277640: Inhibition of PKC	ic50	0.2500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
perfluorooctane sulfonic acid	decreases expression	2
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Tretinoin	affects expression, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
TL8-506	affects cotreatment, increases expression	1
oxybenzone	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
beta-lapachone	increases expression	1
arsenite	decreases reaction, affects binding	1
sodium arsenite	decreases expression, increases abundance	1
cobaltous chloride	increases expression	1
coumarin	decreases phosphorylation	1
tamibarotene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
wogonin	decreases reaction, increases localization	1
ON 01910	increases expression	1
jinfukang	decreases expression	1
Irinotecan	increases phosphorylation	1
Acetaminophen	affects response to substance	1
Arsenic	decreases expression, increases abundance	1
Caffeine	increases phosphorylation	1
Carbamazepine	affects expression	1
Cisplatin	affects response to substance	1
Diclofenac	affects expression	1
Doxorubicin	affects response to substance	1
Fluorouracil	affects reaction, decreases expression	1
Indomethacin	decreases expression	1
Ivermectin	decreases expression	1

ChEMBL screening assays

513 unique, capped per target: 504 binding, 9 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000235	Binding	Activation of PKC in PMA-stimulated human LNCAP cells assessed as ERK phosphorylation at 1 nM to 10 uM by Western blot relative to PMA	Conformationally constrained analogues of diacylglycerol (DAG). 31. Modulation of the biological properties of diacylgycerol lactones (DAG-lactones) containing rigid-rod acyl groups separated from the core lactone by spacer units of different lengths. — J Med Chem
CHEMBL688555	Functional	Retained protein kinase C activity in the presence of 1.25 uM compound	Synthesis and biological activity of novel quaternary ammonium derivatives of alkylglycerols as potent inhibitors of protein kinase C. — J Med Chem

Cellosaurus cell lines

7 cell lines: 6 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2C6	Abcam HeLa PRKCI KO	Cancer cell line	Female
CVCL_D7YJ	Ubigene A-549 PRKCI KO	Cancer cell line	Male
CVCL_D8TZ	Ubigene HCT 116 PRKCI KO	Cancer cell line	Male
CVCL_D9PN	Ubigene HEK293 PRKCI KO	Transformed cell line	Female
CVCL_E0LX	Ubigene HeLa PRKCI KO	Cancer cell line	Female
CVCL_TG90	HAP1 PRKCI (-) 1	Cancer cell line	Male
CVCL_TG91	HAP1 PRKCI (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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