P16054 · KPCE_MOUSE
- ProteinProtein kinase C epsilon type
- GenePrkce
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids737 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. Mediates cell adhesion to the extracellular matrix via integrin-dependent signaling, by mediating angiotensin-2-induced activation of integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS, which phosphorylates and activates PTK2/FAK, leading to the spread of cardiomyocytes. Involved in the control of the directional transport of ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an intermediate filament (IF) protein. In epithelial cells, associates with and phosphorylates keratin-8 (KRT8), which induces targeting of desmoplakin at desmosomes and regulates cell-cell contact. Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-cell detachment prior to migration. During cytokinesis, forms a complex with YWHAB, which is crucial for daughter cell separation, and facilitates abscission by a mechanism which may implicate the regulation of RHOA. In cardiac myocytes, regulates myofilament function and excitation coupling at the Z-lines, where it is indirectly associated with F-actin via interaction with COPB1. During endothelin-induced cardiomyocyte hypertrophy, mediates activation of PTK2/FAK, which is critical for cardiomyocyte survival and regulation of sarcomere length. Plays a role in the pathogenesis of dilated cardiomyopathy via persistent phosphorylation of troponin I (TNNI3). Involved in nerve growth factor (NFG)-induced neurite outgrowth and neuron morphological change independently of its kinase activity, by inhibition of RHOA pathway, activation of CDC42 and cytoskeletal rearrangement. May be involved in presynaptic facilitation by mediating phorbol ester-induced synaptic potentiation. Phosphorylates gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), which reduces the response of GABA receptors to ethanol and benzodiazepines and may mediate acute tolerance to the intoxicating effects of ethanol. Upon PMA treatment, phosphorylates the capsaicin- and heat-activated cation channel TRPV1, which is required for bradykinin-induced sensitization of the heat response in nociceptive neurons. Is able to form a complex with PDLIM5 and N-type calcium channel, and may enhance channel activities and potentiates fast synaptic transmission by phosphorylating the pore-forming alpha subunit CACNA1B (CaV2.2). Downstream of TLR4, plays an important role in the lipopolysaccharide (LPS)-induced immune response by phosphorylating and activating TICAM2/TRAM, which in turn activates the transcription factor IRF3 and subsequent cytokines production. In differentiating erythroid progenitors, is regulated by EPO and controls the protection against the TNFSF10/TRAIL-mediated apoptosis, via BCL2. May be involved in the regulation of the insulin-induced phosphorylation and activation of AKT1. Phosphorylates NLRP5/MATER and may thereby modulate AKT pathway activation in cumulus cells (By similarity).
Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (By similarity).
Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (By similarity).
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Activity regulation
Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-566 (activation loop of the kinase domain), Thr-710 (turn motif) and Ser-729 (hydrophobic region), need to be phosphorylated for its full activation.
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProtein kinase C epsilon type
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP16054
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Translocated to plasma membrane in epithelial cells stimulated by HGF (By similarity).
Associated with the Golgi at the perinuclear site in pre-passage fibroblasts (PubMed:17611075).
In passaging cells, translocated to the cell periphery (PubMed:17611075).
Translocated to the nucleus in PMA-treated cells (PubMed:17611075).
Associated with the Golgi at the perinuclear site in pre-passage fibroblasts (PubMed:17611075).
In passaging cells, translocated to the cell periphery (PubMed:17611075).
Translocated to the nucleus in PMA-treated cells (PubMed:17611075).
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 346 | Loss of interaction with YWHAB and defects in the completion of cytokinesis. | ||||
Sequence: S → A | ||||||
Mutagenesis | 368 | Loss of interaction with YWHAB and defects in the completion of cytokinesis. | ||||
Sequence: S → A | ||||||
Mutagenesis | 729 | Loss of localization to the perinuclear region. Loss of translocation to the nucleus upon PMA stimulation. | ||||
Sequence: S → A, E, or T |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 26 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000055698 | 1-737 | Protein kinase C epsilon type | |||
Sequence: MVVFNGLLKIKICEAVSLKPTAWSLRHAVGPRPQTFLLDPYIALNVDDSRIGQTATKQKTNSPAWHDEFVTDVCNGRKIELAVFHDAPIGYDDFVANCTIQFEELLQNGSRHFEDWIDLEPEGKVYVIIDLSGSSGEAPKDNEERVFRERMRPRKRQGAVRRRVHQVNGHKFMATYLRQPTYCSHCRDFIWGVIGKQGYQCQVCTCVVHKRCHELIITKCAGLKKQETPDEVGSQRFSVNMPHKFGIHNYKVPTFCDHCGSLLWGLLRQGLQCKVCKMNVHRRCETNVAPNCGVDARGIAKVLADLGVTPDKITNSGQRRKKLAAGAESPQPASGNSPSEDDRSKSAPTSPCDQELKELENNIRKALSFDNRGEEHRASSATDGQLASPGENGEVRPGQAKRLGLDEFNFIKVLGKGSFGKVMLAELKGKDEVYAVKVLKKDVILQDDDVDCTMTEKRILALARKHPYLTQLYCCFQTKDRLFFVMEYVNGGDLMFQIQRSRKFDEPRSRFYAAEVTSALMFLHQHGVIYRDLKLDNILLDAEGHCKLADFGMCKEGIMNGVTTTTFCGTPDYIAPEILQELEYGPSVDWWALGVLMYEMMAGQPPFEADNEDDLFESILHDDVLYPVWLSKEAVSILKAFMTKNPHKRLGCVAAQNGEDAIKQHPFFKEIDWVLLEQKKIKPPFKPRIKTKRDVNNFDQDFTREEPILTLVDEAIIKQINQEEFKGFSYFGEDLMP | ||||||
Modified residue | 62 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 228 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 234 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 309 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 316 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 329 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 337 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 346 | Phosphoserine; by GSK3-beta | ||||
Sequence: S | ||||||
Modified residue | 349 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 350 | Phosphoserine; by MAPK11 and MAPK14 | ||||
Sequence: S | ||||||
Modified residue | 368 | Phosphoserine; by autocatalysis | ||||
Sequence: S | ||||||
Modified residue | 388 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 566 | Phosphothreonine; by PDPK1 | ||||
Sequence: T | ||||||
Modified residue | 703 | Phosphothreonine; by autocatalysis | ||||
Sequence: T | ||||||
Modified residue | 710 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 729 | Phosphoserine; by autocatalysis | ||||
Sequence: S |
Post-translational modification
Phosphorylation on Thr-566 by PDPK1 triggers autophosphorylation on Ser-729 (By similarity).
Phosphorylation in the hinge domain at Ser-350 by MAPK11 or MAPK14, Ser-346 by GSK3B and Ser-368 by autophosphorylation is required for interaction with YWHAB
Phosphorylation in the hinge domain at Ser-350 by MAPK11 or MAPK14, Ser-346 by GSK3B and Ser-368 by autophosphorylation is required for interaction with YWHAB
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
Forms a ternary complex with TRIM63 and RACK1/GN2BL1 (By similarity).
Can form a complex with PDLIM5 and N-type calcium channel (By similarity).
Interacts with COPB1 (By similarity).
Interacts with DGKQ (By similarity).
Interacts with STAT3 (By similarity).
Interacts with YWHAB (PubMed:18604201).
Interacts with HSP90AB1; promotes functional activation in a heat shock-dependent manner (By similarity).
Interacts (via phorbol-ester/DAG-type 2 domain) with PRPH and VIM (By similarity).
Interacts with NLRP5/MATER (By similarity).
Can form a complex with PDLIM5 and N-type calcium channel (By similarity).
Interacts with COPB1 (By similarity).
Interacts with DGKQ (By similarity).
Interacts with STAT3 (By similarity).
Interacts with YWHAB (PubMed:18604201).
Interacts with HSP90AB1; promotes functional activation in a heat shock-dependent manner (By similarity).
Interacts (via phorbol-ester/DAG-type 2 domain) with PRPH and VIM (By similarity).
Interacts with NLRP5/MATER (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P16054 | Gja1 P23242 | 3 | EBI-298451, EBI-298630 | |
BINARY | P16054 | Ywhab Q9CQV8 | 5 | EBI-298451, EBI-771608 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, zinc finger, motif, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 1-117 | C2 | ||||
Sequence: MVVFNGLLKIKICEAVSLKPTAWSLRHAVGPRPQTFLLDPYIALNVDDSRIGQTATKQKTNSPAWHDEFVTDVCNGRKIELAVFHDAPIGYDDFVANCTIQFEELLQNGSRHFEDWI | ||||||
Zinc finger | 169-220 | Phorbol-ester/DAG-type 1 | ||||
Sequence: GHKFMATYLRQPTYCSHCRDFIWGVIGKQGYQCQVCTCVVHKRCHELIITKC | ||||||
Motif | 223-228 | Interaction with actin | ||||
Sequence: LKKQET | ||||||
Zinc finger | 242-292 | Phorbol-ester/DAG-type 2 | ||||
Sequence: PHKFGIHNYKVPTFCDHCGSLLWGLLRQGLQCKVCKMNVHRRCETNVAPNC | ||||||
Region | 310-356 | Disordered | ||||
Sequence: PDKITNSGQRRKKLAAGAESPQPASGNSPSEDDRSKSAPTSPCDQEL | ||||||
Compositional bias | 330-351 | Polar residues | ||||
Sequence: PQPASGNSPSEDDRSKSAPTSP | ||||||
Region | 370-398 | Disordered | ||||
Sequence: DNRGEEHRASSATDGQLASPGENGEVRPG | ||||||
Domain | 408-668 | Protein kinase | ||||
Sequence: FNFIKVLGKGSFGKVMLAELKGKDEVYAVKVLKKDVILQDDDVDCTMTEKRILALARKHPYLTQLYCCFQTKDRLFFVMEYVNGGDLMFQIQRSRKFDEPRSRFYAAEVTSALMFLHQHGVIYRDLKLDNILLDAEGHCKLADFGMCKEGIMNGVTTTTFCGTPDYIAPEILQELEYGPSVDWWALGVLMYEMMAGQPPFEADNEDDLFESILHDDVLYPVWLSKEAVSILKAFMTKNPHKRLGCVAAQNGEDAIKQHPFF | ||||||
Domain | 669-737 | AGC-kinase C-terminal | ||||
Sequence: KEIDWVLLEQKKIKPPFKPRIKTKRDVNNFDQDFTREEPILTLVDEAIIKQINQEEFKGFSYFGEDLMP |
Domain
The C1 domain, containing the phorbol ester/DAG-type region 1 (C1A) and 2 (C1B), is the diacylglycerol sensor and the C2 domain is a non-calcium binding domain.
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length737
- Mass (Da)83,561
- Last updated1990-04-01 v1
- Checksum7AEBB8CC10C99F57
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
Q8C944 | Q8C944_MOUSE | Prkce | 125 |
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 330-351 | Polar residues | ||||
Sequence: PQPASGNSPSEDDRSKSAPTSP |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF028009 EMBL· GenBank· DDBJ | AAB84189.1 EMBL· GenBank· DDBJ | mRNA | ||
AF325507 EMBL· GenBank· DDBJ | AAG53692.1 EMBL· GenBank· DDBJ | mRNA |