PMADS

Id:	acc2180
Group:	2sens
Protein:	PKC
Gene Symbol:	PRKCA
Protein Id:	P17252
Protein Name:	KPCA_HUMAN
PTM:	phosphorylation
Site:	Ser660
Site Sequence:	SDFEGFSYVNPQFVHPILQSA
Disease Category:	Cancer
Disease:	Prostate Cancer
Disease Subtype:
Disease Cellline:	LNCaP
Disease Info:
Drug:	Ro-31-8220(PKC inhibitor)
Drug Info:	"Ro-31-8220 mesylate is a broad-spectrum protein kinase C (PKC) inhibitor with IC50 values of 5 nM, 24 nM, 14 nM, 27 nM, and 24 nM for PKC-alpha, PKC-betaI, PKC-betaII, PKC-gamma, and PKC-epsilon, respectively. "
Effect:	sensitize
Effect Info:	Elevated levels of protein phosphorylation result in Ro-31-8220 sensitivity to castration- and enzalutamide-resistant cells
Note:
Score:	5.0
Pubmed(PMID):	24352647
Sentence Index:	24352647_10-11
Sentence:	"Furthermore, PKC phosphorylation was elevated in castration-resistant and enzalutamide-resistant cells compared with their parental cells, leading to persistent sensitivity to Ro-31-8220 in castration- and enzalutamide-resistant cells. CONCLUSIONS: Taken together, these findings indicate that PKC/Twist1 signaling contributes to castration resistance as well as enzalutamide resistance in prostate cancer, and suggest that therapeutics targeting PKC/Twist1 signaling, such as PKC inhibitors, represent a promising novel therapeutic strategy for prostate cancer, especially castration-resistant prostate cancer, when combined with enzalutamide."

Sequence & Structure:

MADVFPGNDSTASQDVANRFARKGALRQKNVHEVKDHKFIARFFKQPTFCSHCTDFIWGFGKQGFQCQVCCFVVHKRCHEFVTFSCPGADKGPDTDDPRSKHKFKIHTYGSPTFCDHCGSLLYGLIHQGMKCDTCDMNVHKQCVINVPSLCGMDHTEKRGRIYLKAEVADEKLHVTVRDAKNLIPMDPNGLSDPYVKLKLIPDPKNESKQKTKTIRSTLNPQWNESFTFKLKPSDKDRRLSVEIWDWDRTTRNDFMGSLSFGVSELMKMPASGWYKLLNQEEGEYYNVPIPEGDEEGNMELRQKFEKAKLGPAGNKVISPSEDRKQPSNNLDRVKLTDFNFLMVLGKGSFGKVMLADRKGTEELYAIKILKKDVVIQDDDVECTMVEKRVLALLDKPPFLTQLHSCFQTVDRLYFVMEYVNGGDLMYHIQQVGKFKEPQAVFYAAEISIGLFFLHKRGIIYRDLKLDNVMLDSEGHIKIADFGMCKEHMMDGVTTRTFCGTPDYIAPEIIAYQPYGKSVDWWAYGVLLYEMLAGQPPFDGEDEDELFQSIMEHNVSYPKSLSKEAVSVCKGLMTKHPAKRLGCGPEGERDVREHAFFRRIDWEKLENREIQPPFKPKVCGKGAENFDKFFTRGQPVLTPPDQLVIANIDQSDFEGFSYVNPQFVHPILQSAV

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
PRKCA	MIDOSTAURIN	Protein kinase C (PKC) inhibitor	4	-	acute myeloid leukemia	FDA
PRKCA	MIDOSTAURIN	Protein kinase C (PKC) inhibitor	4	-	neoplasm	ATC
PRKCA	MIDOSTAURIN	Protein kinase C (PKC) inhibitor	4	-	mast-cell leukemia	DailyMed FDA
PRKCA	MIDOSTAURIN	Protein kinase C (PKC) inhibitor	4	-	Mastocytosis	DailyMed
PRKCA	MIDOSTAURIN	Protein kinase C (PKC) inhibitor	4	-	systemic mastocytosis	FDA
PRKCA	MIDOSTAURIN	Protein kinase C (PKC) inhibitor	3	Completed	acute myeloid leukemia	ClinicalTrials ClinicalTrials
PRKCA	MIDOSTAURIN	Protein kinase C (PKC) inhibitor	3	Recruiting	acute myeloid leukemia	ClinicalTrials ClinicalTrials
PRKCA	MIDOSTAURIN	Protein kinase C (PKC) inhibitor	3	Unknown status	leukemia	ClinicalTrials
PRKCA	APRINOCARSEN	Protein kinase C alpha mRNA 3'UTR antisense inhibitor	3	Completed	non-small cell lung carcinoma	ClinicalTrials
PRKCA	MIDOSTAURIN	Protein kinase C (PKC) inhibitor	2	Active, not recruiting	acute myeloid leukemia	ClinicalTrials ClinicalTrials
PRKCA	MIDOSTAURIN	Protein kinase C (PKC) inhibitor	2	Completed	acute myeloid leukemia	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials
PRKCA	MIDOSTAURIN	Protein kinase C (PKC) inhibitor	2	Active, not recruiting	myelodysplastic syndrome	ClinicalTrials
PRKCA	MIDOSTAURIN	Protein kinase C (PKC) inhibitor	2	Recruiting	myelodysplastic syndrome	ClinicalTrials
PRKCA	MIDOSTAURIN	Protein kinase C (PKC) inhibitor	2	Recruiting	acute myeloid leukemia	ClinicalTrials ClinicalTrials
PRKCA	MIDOSTAURIN	Protein kinase C (PKC) inhibitor	2	Terminated	acute myeloid leukemia	ClinicalTrials
PRKCA	MIDOSTAURIN	Protein kinase C (PKC) inhibitor	2	Withdrawn	acute myeloid leukemia	ClinicalTrials ClinicalTrials
PRKCA	MIDOSTAURIN	Protein kinase C (PKC) inhibitor	2	Completed	leukemia	ClinicalTrials
PRKCA	UCN-01	Protein kinase C (PKC) inhibitor	2	Terminated	lymphoma	ClinicalTrials
PRKCA	SOTRASTAURIN	Protein kinase C (PKC) inhibitor	2	Completed	psoriasis	ClinicalTrials
PRKCA	UCN-01	Protein kinase C (PKC) inhibitor	2	Completed	small cell lung carcinoma	ClinicalTrials
PRKCA	SOTRASTAURIN	Protein kinase C (PKC) inhibitor	2	Completed	ulcerative colitis	ClinicalTrials
PRKCA	UCN-01	Protein kinase C (PKC) inhibitor	2	Terminated	melanoma	ClinicalTrials
PRKCA	UCN-01	Protein kinase C (PKC) inhibitor	2	Completed	pancreatic carcinoma	ClinicalTrials
PRKCA	APRINOCARSEN	Protein kinase C alpha mRNA 3'UTR antisense inhibitor	2	Completed	non-small cell lung carcinoma	ClinicalTrials
PRKCA	MIDOSTAURIN	Protein kinase C (PKC) inhibitor	2	Completed	mast-cell leukemia	ClinicalTrials

Note: Only show clinically investigational or approved drugs with protein targets.

Protein Tractability:

source: Open Targets

Small molecule

Antibody

PROTAC

Other modalities

Approved Drug

Advanced Clinical

Phase 1 Clinical

Structure with Ligand

High-Quality Ligand

High-Quality Pocket

Med-Quality Pocket

Druggable Family

Approved Drug

Advanced Clinical

Phase 1 Clinical

UniProt loc high conf

GO CC high conf

UniProt loc med conf

UniProt SigP or TMHMM

GO CC med conf

Human Protein Atlas loc

Approved Drug

Advanced Clinical

Phase 1 Clinical

Literature

UniProt Ubiquitination

Database Ubiquitination

Half-life Data

Small Molecule Binder

Approved Drug

Advanced Clinical

Phase 1 Clinical

PTM Intensity:

source: CPTAC

No intensity data of this site,
show all other sites!

PRKCA-Ser100
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	-0.707
HNSC
LUAD
LUSC
non_ccRCC	0.707
PDAC
UCEC

PRKCA-Ser149
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	-0.033
GBM	-1.615
HNSC
LUAD	1.109
LUSC
non_ccRCC	0.355
PDAC
UCEC	0.185

PRKCA-Ser226
Cancer	Intensity
BRCA	0.522
COAD	-0.419
HGSC	0.884
ccRCC	0.091
GBM	-0.108
HNSC	0.149
LUAD	1.192
LUSC	0.487
non_ccRCC	-0.241
PDAC	0.091
UCEC	-2.647

PRKCA-Ser234
Cancer	Intensity
BRCA
COAD	-1.154
HGSC
ccRCC
GBM
HNSC
LUAD	0.549
LUSC	0.605
non_ccRCC
PDAC
UCEC

PRKCA-Ser319
Cancer	Intensity
BRCA	-1.653
COAD	0.449
HGSC	1.387
ccRCC	0.074
GBM	-0.865
HNSC	1.178
LUAD	1.219
LUSC	-0.643
non_ccRCC	-0.84
PDAC	0.264
UCEC	-0.57

PRKCA-Ser321
Cancer	Intensity
BRCA
COAD	0.569
HGSC	1.343
ccRCC	-0.933
GBM	0.606
HNSC
LUAD	-0.358
LUSC
non_ccRCC
PDAC
UCEC	-1.227

PRKCA-Ser567
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	-0.707
HNSC
LUAD
LUSC
non_ccRCC	0.707
PDAC
UCEC

PRKCA-Ser651
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	-0.707
GBM	0.707
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

PRKCA-Ser657
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	-0.707
GBM	0.707
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

PRKCA-Thr218
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	0.477
GBM
HNSC	-1.149
LUAD	0.672
LUSC
non_ccRCC
PDAC
UCEC

PRKCA-Thr228
Cancer	Intensity
BRCA
COAD	-0.387
HGSC	1.136
ccRCC
GBM	-0.749
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

PRKCA-Thr48
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	-0.707
HNSC
LUAD
LUSC
non_ccRCC	0.707
PDAC
UCEC

PRKCA-Thr497
Cancer	Intensity
BRCA
COAD	0.795
HGSC	0.515
ccRCC
GBM	-0.932
HNSC
LUAD
LUSC
non_ccRCC
PDAC	0.851
UCEC	-1.229

PRKCA-Thr501
Cancer	Intensity
BRCA	1.347
COAD
HGSC	-0.937
ccRCC
GBM	-0.54
HNSC
LUAD
LUSC	0.13
non_ccRCC
PDAC
UCEC

PRKCA-Thr54
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	0.707
GBM
HNSC
LUAD	-0.707
LUSC
non_ccRCC
PDAC
UCEC

PRKCA-Thr638
Cancer	Intensity
BRCA
COAD	-0.582
HGSC	2
ccRCC	-0.504
GBM	-0.595
HNSC	-0.15
LUAD
LUSC
non_ccRCC
PDAC
UCEC	-0.169

PRKCA-Tyr195
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	0.472
GBM	-0.908
HNSC
LUAD	-0.101
LUSC	1.523
non_ccRCC	0.262
PDAC
UCEC	-1.247

PRKCA-Tyr504
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	-0.707
GBM
HNSC
LUAD	0.707
LUSC
non_ccRCC
PDAC
UCEC

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
-	-	P	Acute myelomonocytic leukemia	Phosphorylation	24334295

State Note: Based on the distinct PTM states in diseases, PTMD classified all disease-associated PTMs into six classes, including whether the up-regulation (U) or down-regulation (D) of PTM levels, the absence (A) or presence (P) of PTMs, and the creation (C) or disruption (N) of PTM sites are associated with diseases.

PTM-Drug Perturbation Response:

source: DecryptM

No data.

Function score:

source: funscoR

No data.

Cross Links:

CTD
DMRdb