KPCE_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: KPCE_MOUSE
• UniProt AC: P16054
• Protein Name: Protein kinase C epsilon type
• Gene Name: Prkce
• Organism: Mus musculus (Mouse).
• Sequence Length: 737
• Subcellular Localization: Cytoplasm. Cytoplasm, cytoskeleton. Cell membrane. Cytoplasm, perinuclear region . Nucleus . Translocated to plasma membrane in epithelial cells stimulated by HGF (By similarity). Associated with the Golgi at the perinuclear site in pre-passage fibro
• Protein Description: 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..
• Protein Sequence: MVVFNGLLKIKICEAVSLKPTAWSLRHAVGPRPQTFLLDPYIALNVDDSRIGQTATKQKTNSPAWHDEFVTDVCNGRKIELAVFHDAPIGYDDFVANCTIQFEELLQNGSRHFEDWIDLEPEGKVYVIIDLSGSSGEAPKDNEERVFRERMRPRKRQGAVRRRVHQVNGHKFMATYLRQPTYCSHCRDFIWGVIGKQGYQCQVCTCVVHKRCHELIITKCAGLKKQETPDEVGSQRFSVNMPHKFGIHNYKVPTFCDHCGSLLWGLLRQGLQCKVCKMNVHRRCETNVAPNCGVDARGIAKVLADLGVTPDKITNSGQRRKKLAAGAESPQPASGNSPSEDDRSKSAPTSPCDQELKELENNIRKALSFDNRGEEHRASSATDGQLASPGENGEVRPGQAKRLGLDEFNFIKVLGKGSFGKVMLAELKGKDEVYAVKVLKKDVILQDDDVDCTMTEKRILALARKHPYLTQLYCCFQTKDRLFFVMEYVNGGDLMFQIQRSRKFDEPRSRFYAAEVTSALMFLHQHGVIYRDLKLDNILLDAEGHCKLADFGMCKEGIMNGVTTTTFCGTPDYIAPEILQELEYGPSVDWWALGVLMYEMMAGQPPFEADNEDDLFESILHDDVLYPVWLSKEAVSILKAFMTKNPHKRLGCVAAQNGEDAIKQHPFFKEIDWVLLEQKKIKPPFKPRIKTKRDVNNFDQDFTREEPILTLVDEAIIKQINQEEFKGFSYFGEDLMP

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
13	S-palmitoylation	GLLKIKICEAVSLKP CEEEEEEEEECCCCC	2.03	28680068
24	Phosphorylation	SLKPTAWSLRHAVGP CCCCCHHHHHHCCCC	17.04	22817900
62	Phosphorylation	ATKQKTNSPAWHDEF CCCCCCCCCCCCHHH	22.64	25521595
228	Phosphorylation	AGLKKQETPDEVGSQ CCCCCCCCCCCHHCC	33.28	25521595
234	Phosphorylation	ETPDEVGSQRFSVNM CCCCCHHCCCEEECC	24.29	22817900
309	Phosphorylation	VLADLGVTPDKITNS HHHHHCCCHHHHCCH	24.79	24759943
312	Ubiquitination	DLGVTPDKITNSGQR HHCCCHHHHCCHHHH	53.27	-
314	Phosphorylation	GVTPDKITNSGQRRK CCCHHHHCCHHHHHH	29.13	24759943
316	Phosphorylation	TPDKITNSGQRRKKL CHHHHCCHHHHHHHH	27.87	22817900
329	Phosphorylation	KLAAGAESPQPASGN HHCCCCCCCCCCCCC	28.44	25521595
334	Phosphorylation	AESPQPASGNSPSED CCCCCCCCCCCCCCC	45.23	25521595
337	Phosphorylation	PQPASGNSPSEDDRS CCCCCCCCCCCCCCC	33.07	25521595
339	Phosphorylation	PASGNSPSEDDRSKS CCCCCCCCCCCCCCC	54.18	25521595
344	Phosphorylation	SPSEDDRSKSAPTSP CCCCCCCCCCCCCCH	37.65	22324799
346	Phosphorylation	SEDDRSKSAPTSPCD CCCCCCCCCCCCHHH	40.50	25521595
349	Phosphorylation	DRSKSAPTSPCDQEL CCCCCCCCCHHHHHH	45.04	25521595
350	Phosphorylation	RSKSAPTSPCDQELK CCCCCCCCHHHHHHH	23.59	25521595
368	Phosphorylation	NNIRKALSFDNRGEE HHHHHHHHCCCCCCC	35.10	25521595
379	Phosphorylation	RGEEHRASSATDGQL CCCCCCCCCCCCCCC	22.06	29899451
380	Phosphorylation	GEEHRASSATDGQLA CCCCCCCCCCCCCCC	33.91	30372032
382	Phosphorylation	EHRASSATDGQLASP CCCCCCCCCCCCCCC	42.48	29899451
388	Phosphorylation	ATDGQLASPGENGEV CCCCCCCCCCCCCCC	41.87	25521595
566	Phosphorylation	MNGVTTTTFCGTPDY CCCCCEECCCCCCCC	18.16	22817900
636	Phosphorylation	WLSKEAVSILKAFMT HCCHHHHHHHHHHHC	29.29	22006019
703	Phosphorylation	NNFDQDFTREEPILT CCCCCCCCCCCCHHH	45.52	22817900
710	Phosphorylation	TREEPILTLVDEAII CCCCCHHHHHHHHHH	26.00	26824392
729	Phosphorylation	QEEFKGFSYFGEDLM HHHHCCCCCCCCCCC	28.37	25521595
730	Phosphorylation	EEFKGFSYFGEDLMP HHHCCCCCCCCCCCC	17.22	22322096

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
346	S	Phosphorylation	Kinase	GSK3B	Q9WV60	GPS
350	S	Phosphorylation	Kinase	MAPK11	Q9WUI1	Uniprot
350	S	Phosphorylation	Kinase	MAPK14	P47811	Uniprot
368	S	Phosphorylation	Kinase	PRKCA	P17252	GPS
368	S	Phosphorylation	Kinase	PRKCE	P16054	GPS
566	T	Phosphorylation	Kinase	PDPK1	Q9Z2A0	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
346	S	Phosphorylation	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.	18604201
350	S	Phosphorylation	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.	18604201
368	S	Phosphorylation	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.	18237277
566	T	Phosphorylation	Phosphorylation on Thr-566 by PDPK1 triggers autophosphorylation on Ser-729 (By similarity).	18237277
729	S	Phosphorylation	Phosphorylation on Thr-566 by PDPK1 triggers autophosphorylation on Ser-729 (By similarity).	17611075

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of KPCE_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SRC_MOUSE	Src	physical	11834516
NEUM_RAT	Gap43	physical	8694767
FBXW7_MOUSE	Fbxw7	physical	20815813

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Phosphorylation

"The regulated assembly of a PKCepsilon complex controls thecompletion of cytokinesis.";
Saurin A.T., Durgan J., Cameron A.J., Faisal A., Marber M.S.,Parker P.J.;
Nat. Cell Biol. 10:891-901(2008).
Cited for: FUNCTION, INTERACTION WITH YWHAB, PHOSPHORYLATION AT SER-346; SER-350AND SER-368, AND MUTAGENESIS OF SER-346 AND SER-368.
PubMed: 18604201

"The identification and characterization of novel PKCepsilonphosphorylation sites provide evidence for functional cross-talkwithin the PKC superfamily.";
Durgan J., Cameron A.J., Saurin A.T., Hanrahan S., Totty N.,Messing R.O., Parker P.J.;
Biochem. J. 411:319-331(2008).
Cited for: PHOSPHORYLATION AT SER-234; SER-316 AND SER-368.
PubMed: 18237277

"Qualitative and quantitative analyses of protein phosphorylation innaive and stimulated mouse synaptosomal preparations.";
Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D.,Gerrits B., Panse C., Schlapbach R., Mansuy I.M.;
Mol. Cell. Proteomics 6:283-293(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-337 AND THR-349, ANDMASS SPECTROMETRY.
PubMed: 17114649