Protein detail
KPCA
Protein kinase C alpha type (PKC-A) (PKC-alpha) (EC 2.7.11.13)
Entry name KPCA | UniProt ID | EVMP confidence score 0.38 |
Supporting publications (n) 5 | Transmembrane count | Protein classification Cancer-related genesEnzymesFDA approved drug targetsPlasma proteinsPredicted intracellular proteinsRAS pathway related proteins |
EVMP confidence score
Annotation confidence score; open for threshold definitions.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40Basic Information11
Protein Names
Protein kinase C alpha type (PKC-A) (PKC-alpha) (EC 2.7.11.13)
Protein Class (6)
Cancer-related genesEnzymesFDA approved drug targetsPlasma proteinsPredicted intracellular proteinsRAS pathway related proteins
Protein Function (7)
- Predicted intracellular proteins
- ENZYME proteins:Transferases
- RAS pathway related proteins
- Enzymes
- Cancer-related genes:Candidate cancer biomarkers
- Kinases:AGC Ser/Thr protein kinases
- FDA approved drug targets:Small molecule drugs
Ensembl
Entrez Gene Symbol
Gene Synonym (2)
PKCAPKCalpha
Gene Description
Protein kinase C alpha
Chromosome
17
Position
66302613-66810743
Supporting publications (n)
5
EVMP confidence score
0.38
Fluorescence & Localization2
Cell SpecificAstrocytesSingle-Nuclei Brain Specificastrocyte
Function & Pathway6
Protein Function (7)
- Predicted intracellular proteins
- ENZYME proteins:Transferases
- RAS pathway related proteins
- Enzymes
- Cancer-related genes:Candidate cancer biomarkers
- Kinases:AGC Ser/Thr protein kinases
- FDA approved drug targets:Small molecule drugs
Cellular Component (11)
- GO:0005654 nucleoplasm
- GO:0005737 cytoplasm
- GO:0005739 mitochondrion
- GO:0005783 endoplasmic reticulum
- GO:0005829 cytosol
- GO:0005886 plasma membrane
- GO:0031966 mitochondrial membrane
- GO:0035866 alphav-beta3 integrin-PKCalpha complex
- GO:0036064 ciliary basal body
- GO:0048471 perinuclear region of cytoplasm
Page 1 of 2
Molecular Function (12)
- GO:0004672 protein kinase activity
- GO:0004674 protein serine/threonine kinase activity
- GO:0004697 diacylglycerol-dependent serine/threonine kinase activity
- GO:0004698 calcium,diacylglycerol-dependent serine/threonine kinase activity
- GO:0005178 integrin binding
- GO:0005515 protein binding
- GO:0005524 ATP binding
- GO:0008270 zinc ion binding
- GO:0019899 enzyme binding
- GO:0019992 diacylglycerol binding
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KEGG (75)
- hsa01521 EGFR tyrosine kinase inhibitor resistance
- KEGG:hsa04010 MAPK signaling pathway
- KEGG:hsa04012 ErbB signaling pathway
- KEGG:hsa04014 Ras signaling pathway
- KEGG:hsa04015 Rap1 signaling pathway
- KEGG:hsa04020 Calcium signaling pathway
- KEGG:hsa04066 HIF-1 signaling pathway
- KEGG:hsa04070 Phosphatidylinositol signaling system
- KEGG:hsa04071 Sphingolipid signaling pathway
- KEGG:hsa04072 Phospholipase D signaling pathway
Page 1 of 8
Reactome (57)
- R-hsa-399997 acetylcholine regulates insulin secretion
- R-hsa-3858494 beta catenin independent wnt signaling
- R-hsa-4086398 ca2 pathway
- R-hsa-111996 ca dependent events
- R-hsa-1640170 cell cycle
- R-hsa-69278 cell cycle mitotic
- R-hsa-1489509 dag and ip3 signaling
- R-hsa-4419969 depolymerization of the nuclear lamina
- R-hsa-114516 disinhibition of snare formation
- R-hsa-2179392 egfr transactivation by gastrin
Page 1 of 6
Mediation Categories (6)
Adhesion and uptake mediationClinical-translation mediationFusion and delivery mediationImmune mediationMetabolism mediationReceptor-signaling mediation
Relations & Evidence347
Enzyme-Mediated Modification (18)
18 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| PRKCA | SYK | P43405 | Y | 658 | phosphorylation | Sparser_ProtMapperphosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperHPRDKEAphosphoELMSIGNOR_ProtMapper | ProtMapper:12881490HPRD:12881490KEA:12881490HPRD:20068231SIGNOR:12881490KEA:17192257phosphoELM:12881490 |
| PRKCA | PHLPP2 | Q6ZVD8 | S | 657 | dephosphorylation | SIGNORDEPOD | SIGNOR:18162466DEPOD:18162466 |
| PRKCA | PHLPP2 | Q6ZVD8 | S | 657 | phosphorylation | SIGNOR_ProtMapperProtMapper | ProtMapper:18162466 |
| PRKCA | PHLPP1 | O60346 | S | 657 | dephosphorylation | SIGNORDEPOD | SIGNOR:18162466DEPOD:18162466 |
| PRKCA | PHLPP1 | O60346 | S | 657 | phosphorylation | SIGNOR_ProtMapperProtMapper | ProtMapper:18162466 |
| PRKCA | PRKCZ | Q05513 | S | 657 | phosphorylation | phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPHPRDKEA | HPRD:12162751HPRD:10339425HPRD:20068231KEA:8856079KEA:12162751HPRD:18691976KEA:10339425HPRD:8856079 |
| PRKCA | STK3 | Q13188 | S | 226 | phosphorylation | Sparser_ProtMapperProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:26414765 |
| PRKCA | STK3 | Q13188 | T | 228 | phosphorylation | Sparser_ProtMapperProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:26414765 |
| PRKCA | MST1 | P26927 | S | 226 | phosphorylation | Sparser_ProtMapperProtMapper | ProtMapper:26414765 |
| PRKCA | MST1 | P26927 | T | 228 | phosphorylation | Sparser_ProtMapperProtMapper | ProtMapper:26414765 |
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Ligand-Receptor Signaling (10)
10 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| receptor | receptor | SignaLink_function | No | Yes | No | No | No |
| receptor | receptor | OmniPath | No | Yes | No | No | No |
| intracellular | intracellular | LOCATE | No | No | No | No | No |
| intracellular | intracellular | ComPPI | No | No | No | No | No |
| intracellular | intracellular | GO_Intercell | No | No | No | No | No |
| intracellular | intracellular | UniProt_location | No | No | No | No | No |
| intracellular | intracellular | OmniPath | No | No | No | No | No |
| plasma_membrane | plasma_membrane | UniProt_location | No | No | No | No | No |
| plasma_membrane | plasma_membrane | OmniPath | No | No | No | No | No |
| receptor | receptor | scConnect | No | Yes | No | No | No |
Regulatory Interaction Network (311)
311 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| KPCA | P17252 | RBP1 | Q15311 | Yes | Yes | No | Sparser_ProtMapperPhosphoSite_MIMPMIMPHPRD_MIMPPhosphoSite_norefPhosphoPointSIGNORProtMapperiPTMnetHPRDKEAHPRD_KEASIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapperSPIKE_LC | SIGNOR:16087181ProtMapper:21411502ProtMapper:16087181PhosphoSite:16087181HPRD:16087181SPIKE_LC:16087181KEA:16087181PhosphoSite:17706599 |
| KPCA | P17252 | C163A | Q86VB7 | Yes | No | No | PhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetPhosphoPointSIGNORProtMapperHPRDPhosphoSite_KEAKEAHPRD_KEASIGNOR_ProtMapperHPRD-phos | HPRD-phos:11298324HPRD:11298324SIGNOR:11298324ProtMapper:20166139KEA:11298324HPRD-phos:20166139ProtMapper:11298324 |
| KPCA | P17252 | GRM5 | P41594 | Yes | Yes | No | MIMPHPRD_MIMPiPTMnetPhosphoPointSIGNORProtMapperHPRDPhosphoSite_KEAKEAHPRD_KEASIGNOR_ProtMapper | HPRD:15894802KEA:9242710HPRD:9242710KEA:15894802ProtMapper:9242710SIGNOR:15894802ProtMapper:15894802 |
| KPCA | P17252 | HMGN1 | P05114 | Yes | No | Yes | phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetPhosphoPointSIGNORProtMapperHPRDHINTPhosphoSite_KEAKEAHPRD_KEASIGNOR_ProtMapperHPRD-phos | KEA:11438671KEA:10739259HINT:12773393HPRD:10739259SIGNOR:10739259ProtMapper:17924679KEA:12773393HPRD-phos:20068231ProtMapper:10739259HINT:10739259HPRD-phos:12773393ProtMapper:12773393HPRD-phos:11438671HINT:11438671HPRD-phos:10739259ProtMapper:11438671HPRD-phos:17924679ProtMapper:20166139ProtMapper:20068231HPRD-phos:20166139HPRD:12773393HPRD:11438671 |
| KPCA | P17252 | CDN1A | P38936 | Yes | Yes | No | PhosphoNetworksphosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetSIGNORProtMapperPhosphoSite_KEAKEAKinexus_KEAphosphoELM_KEAphosphoELMSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper | KEA:11756412KEA:10753973PhosphoSite:15851482KEA:16055744phosphoELM:10753973SIGNOR:16055744PhosphoSite:16055744KEA:17855660phosphoELM:15001356ProtMapper:16055744 |
| KPCA | P17252 | URP2 | Q86UX7 | Yes | Yes | No | iPTMnetSIGNORProtMapperSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:25609252SIGNOR:25609252PhosphoSite:25609252PhosphoSite:32730588 |
| KPCA | P17252 | MYOD1 | P15172 | Yes | No | Yes | phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetPhosphoPointSIGNORProtMapperHPRDPhosphoSite_KEAKEAHPRD_KEASIGNOR_ProtMapperNetworKIN_KEA | KEA:1335366KEA:11025438HPRD:1335366ProtMapper:1335366KEA:17570479SIGNOR:1335366 |
| KPCA | P17252 | PP16B | Q96T49 | Yes | No | Yes | SIGNORPhosphoSitePhosphoSite_ProtMapperProtMapper | PhosphoSite:27939168SIGNOR:27939168 |
| KPCA | P17252 | KCNE1 | P15382 | Yes | No | Yes | PhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetPhosphoPointSIGNORProtMapperHPRDPhosphoSite_KEAKEAHPRD_KEASIGNOR_ProtMapperNetworKIN_KEA | ProtMapper:1553557KEA:17570479SIGNOR:1553557KEA:1553557HPRD:1553557 |
| COMPLEX:Q96EP0_Q9BYM8 | KPCA | P17252 | Yes | No | Yes | SIGNOR | SIGNOR:17069764 |
Protein Complex Composition (7)
7 records.
| Component Name | Component Gene Symbols | Component UniProt ID | Stoichiometry | Database | Database IDs | References |
|---|---|---|---|---|---|---|
| PRKCAPRKCBPRKCGPRKCH | C0HM02P05129P05771P17252 | 0:0:0:0 | hu.MAP2 | |||
| PRKCAPRKCBPRKCGPRKCH | P05129P05771P17252P24723 | 0:0:0:0 | hu.MAP2 | |||
| GRIA4PICK1PRKCAPRKCG | P05129P17252P48058Q9NRD5 | 1:1:1:1 | CompleatCFinder | Compleat:HC8969 | ||
| CDK1HSPA4NCF1PRKCAPRKCBTOP2A | P05771P06493P11388P14598P17252P34932 | 1:1:1:1:1:1 | NetworkBlastCompleat | Compleat:HC7043 | ||
| PRKCA | P17252 | 3 | PDB | PDB:3iw4 | ||
| ATP6V1B2H4C4HMGCS1IGBP1JMJD6MLST8MORF4L1NRGNPRKCASCPEP1 | P17252P21281P62805P78318Q01581Q6NYC1Q92686Q9BVC4Q9HB40Q9UBU8 | 1:1:1:1:1:1:1:1:1:1 | NetworkBlastCompleat | Compleat:HC3946 | ||
| CBX8NCAPHPCGF2PHC2PRKCATOP2B | P17252P35227Q02880Q15003Q8IXK0Q9HC52 | 1:1:1:1:1:1 | NetworkBlastCompleat | Compleat:HC4640 |
Sequence, Structure & Domains11
Sequences
Length
672
Mass
76,750
Sequence
MADVFPGNDSTASQDVANRFARKGALRQKNVHEVKDHKFIARFFKQPTFCSHCTDFIWGFGKQGFQCQVCCFVVHKRCHEFVTFSCPGADKGPDTDDPRSKHKFKIHTYGSPTFCDHCGSLLYGLIHQGMKCDTCDMNVHKQCVINVPSLCGMDHTEKRGRIYLKAEVADEKLHVTVRDAKNLIPMDPNGLSDPYVKLKLIPDPKNESKQKTKTIRSTLNPQWNESFTFKLKPSDKDRRLSVEIWDWDRTTRNDFMGSLSFGVSELMKMPASGWYKLLNQEEGEYYNVPIPEGDEEGNMELRQKFEKAKLGPAGNKVISPSEDRKQPSNNLDRVKLTDFNFLMVLGKGSFGKVMLADRKGTEELYAIKILKKDVVIQDDDVECTMVEKRVLALLDKPPFLTQLHSCFQTVDRLYFVMEYVNGGDLMYHIQQVGKFKEPQAVFYAAEISIGLFFLHKRGIIYRDLKLDNVMLDSEGHIKIADFGMCKEHMMDGVTTRTFCGTPDYIAPEIIAYQPYGKSVDWWAYGVLLYEMLAGQPPFDGEDEDELFQSIMEHNVSYPKSLSKEAVSVCKGLMTKHPAKRLGCGPEGERDVREHAFFRRIDWEKLENREIQPPFKPKVCGKGAENFDKFFTRGQPVLTPPDQLVIANIDQSDFEGFSYVNPQFVHPILQSAV
3D Structural Models
Turn
98..100; 141..146
Helix
233..237; 263..268; 282..284; 336..338; 372..378; 381..392; 425..430; 437..456; 466..468; 502..504; 507..510; 518..533; 543..552; 563..572; 577..579; 587..592; 595..597; 602..606; 642..645; 650..653
Beta Strand
105..107; 116..118; 125..127; 129..131; 133..135; 138..140; 161..169; 172..182; 194..202; 222..230; 239..246; 249..251; 254..262; 271..276; 339..348; 351..358; 364..371; 403..408; 410..418; 422..424; 469..471; 477..479
3D Structure
NMR spectroscopy (1); X-ray crystallography (5)
Domain & Motif Annotations
Zinc Finger
36..86; Phorbol-ester/DAG-type 1; 101..151; Phorbol-ester/DAG-type 2
Domain (FT)
158..275; C2; 339..597; Protein kinase; 598..668; AGC-kinase C-terminal
Protein Families (3)
- Protein kinase superfamily
- AGC Ser/Thr protein kinase family
- PKC subfamily
Sequence Similarities
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.
Clinical Relevance9
Disease Involvement (3)
Cancer-related genesFDA approved drug targetsProto-oncogene
Related Diseases (4)
Biomarker
Investigative; Approved; Terminated; Phase 2
Drug Targets
FDA approved drug targets
Drugs (25)
CI-1040NULL4-PHENYLBUTYRIC ACIDTRISMETHOXYRESVERATROLAPRINOCARSENGSK-690693UCN-01ENZASTAURINPHORBOL 12-MYRISTATE 13-ACETATEBEVACIZUMAB-AWWBDIURETICINGENOL MEBUTATESOTRASTAURINBRYOSTATINMIDOSTAURINBRYOSTATIN 1ENOXOLONEREDIOCIDE ACEP-2563DIMETHYLSPINGOSINEHYDROCHLOROTHIAZIDESOTRASTAURIN ACETATERESVERATROLCHEMBL:CHEMBL27768QUERCETIN
Interaction Protein (2)
ENSG00000126583ENSG00000146648
Interaction Count
2
Interaction Dataset
intact_biogrid
Supporting Publications5
| PMID | Title | Abstract |
|---|---|---|
| 18490724 | Human tumor-derived exosomes down-modulate NKG2D expression. | Exosomes produced by various cancer cell lines in vitro, or isolated from pleural effusions of mesothelioma patients triggered down-regulation of surface NKG2D expression by NK cells and CD8(+) T cells. In this study, we show that exosomes derived from cancer cells express ligands for NKG2D and express TGFbeta1, and we investigate the impact of such exosomes on CD8(+) T and NK cell NKG2D expression and on NKG2D-dependent functions. This decrease was rapid, sustained, and resulted from direct interactions between exosomes and NK cells or CD8(+) T cells. |
| 36335434 | NKG2D-mediated cytotoxicity improves after primary surgery for high-grade serous ovarian cancer. | HGSC exosomes from patients' sera downregulated NKG2D-mediated cytotoxicity in NK cells of healthy donors. |
| 36374819 | NKG2D Ligands in Liquid Biopsy: The Importance of Soluble and Vesicle-Bound Proteins for Immune Modulation. | The biology of NKG2D and its ligands comprises a complex network of cellular pathways leading to the expression of these tumor-associated ligands on the cell surface or to their release either as soluble proteins, or in extracellular vesicles that potently inhibit NKG2D-mediated responses. |
| 36499501 | miR-221-5p and miR-186-5p Are the Critical Bladder Cancer Derived Exosomal miRNAs in Natural Killer Cell Dysfunction. | Meanwhile, T24 cell-derived exosomes inhibited the expression of the important functional receptors NKG2D, NKp30, and CD226 on NK cells as well as the secretion of perforin and granzyme-B. |
| 36931723 | NKG2A and circulating extracellular vesicles are key regulators of natural killer cell activity in prostate cancer after prostatectomy. | With the decrease in NKG2A levels on NK cells and the increase in total NKG2D ligands on circulating EVs, which was increased postoperatively, both NKG2A on NK cells and NKG2D ligands on circulating exosomes are main regulators of NKA restoration after prostatectomy. |