KPCE_RAT - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: KPCE_RAT
• UniProt AC: P09216
• Protein Name: Protein kinase C epsilon type
• Gene Name: Prkce
• Organism: Rattus norvegicus (Rat).
• Sequence Length: 737
• Subcellular Localization: Cytoplasm. Cytoplasm, cytoskeleton. Cell membrane. Cytoplasm, perinuclear region. Nucleus. Translocated to plasma membrane in epithelial cells stimulated by HGF. Associated with the Golgi at the perinuclear site in pre-passage fibroblasts. In passagi
• 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: MVVFNGLLKIKICEAVSLKPTAWSLRHAVGPRPQTFLLDPYIALNVDDSRIGQTATKQKTNSPAWHDEFVTDVCNGRKIELAVFHDAPIGYDDFVANCTIQFEELLQNGSRHFEDWIDLEPEGKVYVIIDLSGSSGEAPKDNEERVFRERMRPRKRQGAVRRRVHQVNGHKFMATYLRQPTYCSHCRDFIWGVIGKQGYQCQVCTCVVHKRCHELIITKCAGLKKQETPDEVGSQRFSVNMPHKFGIHNYKVPTFCDHCGSLLWGLLRQGLQCKVCKMNVHRRCETNVAPNCGVDARGIAKVLADLGVTPDKITNSGQRRKKLAAGAESPQPASGNSPSEDDRSKSAPTSPCDQELKELENNIRKALSFDNRGEEHRASSSTDGQLASPGENGEVRQGQAKRLGLDEFNFIKVLGKGSFGKVMLAELKGKDEVYAVKVLKKDVILQDDDVDCTMTEKRILALARKHPYLTQLYCCFQTKDRLFFVMEYVNGGDLMFQIQRSRKFDEPRSGFYAAEVTSALMFLHQHGVIYRDLKLDNILLDAEGHSKLADFGMCKEGILNGVTTTTFCGTPDYIAPEILQELEYGPSVDWWALGVLMYEMMAGQPPFEADNEDDLFESILHDDVLYPVWLSKEAVSILKAFMTKNPHKRLGCVAAQNGEDAIKQHPFFKEIDWVLLEQKKMKPPFKPRIKTKRDVNNFDQDFTREEPILTLVDEAIVKQINQEEFKGFSYFGEDLMP

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
62	Phosphorylation	ATKQKTNSPAWHDEF CCCCCCCCCCCCHHH	22.64	-
132	O-linked_Glycosylation	VYVIIDLSGSSGEAP EEEEEECCCCCCCCC	32.64	12639225
134	O-linked_Glycosylation	VIIDLSGSSGEAPKD EEEECCCCCCCCCCC	31.62	12639215
135	O-linked_Glycosylation	IIDLSGSSGEAPKDN EEECCCCCCCCCCCH	44.15	12639219
175	Phosphorylation	NGHKFMATYLRQPTY CCCCCHHHHHCCCCC	15.99	18295358
176	Phosphorylation	GHKFMATYLRQPTYC CCCCHHHHHCCCCCC	7.14	18295358
228	Phosphorylation	AGLKKQETPDEVGSQ CCCCCCCCCCCHHCC	33.28	25403869
234	Phosphorylation	ETPDEVGSQRFSVNM CCCCCHHCCCEEECC	24.29	-
250	Phosphorylation	HKFGIHNYKVPTFCD CCCCCCCCCCCCCCH	10.13	-
286	O-linked_Glycosylation	NVHRRCETNVAPNCG EEHHCCCCCCCCCCC	38.32	18295358
309	Phosphorylation	VLADLGVTPDKITNS HHHHHCCCHHHHCCH	24.79	27097102
312	Ubiquitination	DLGVTPDKITNSGQR HHCCCHHHHCCHHHH	53.27	-
314	Phosphorylation	GVTPDKITNSGQRRK CCCHHHHCCHHHHHH	29.13	27097102
316	Phosphorylation	TPDKITNSGQRRKKL CHHHHCCHHHHHHHH	27.87	27097102
329	Phosphorylation	KLAAGAESPQPASGN HHCCCCCCCCCCCCC	28.44	27097102
334	Phosphorylation	AESPQPASGNSPSED CCCCCCCCCCCCCCC	45.23	27097102
337	Phosphorylation	PQPASGNSPSEDDRS CCCCCCCCCCCCCCC	33.07	30411139
339	Phosphorylation	PASGNSPSEDDRSKS CCCCCCCCCCCCCCC	54.18	30240740
344	Phosphorylation	SPSEDDRSKSAPTSP CCCCCCCCCCCCCCH	37.65	28432305
346	O-linked_Glycosylation	SEDDRSKSAPTSPCD CCCCCCCCCCCCHHH	40.50	5615639
346	Phosphorylation	SEDDRSKSAPTSPCD CCCCCCCCCCCCHHH	40.50	30411139
349	O-linked_Glycosylation	DRSKSAPTSPCDQEL CCCCCCCCCHHHHHH	45.04	181981
349	Phosphorylation	DRSKSAPTSPCDQEL CCCCCCCCCHHHHHH	45.04	22108457
350	O-linked_Glycosylation	RSKSAPTSPCDQELK CCCCCCCCHHHHHHH	23.59	181983
350	Phosphorylation	RSKSAPTSPCDQELK CCCCCCCCHHHHHHH	23.59	30411139
368	O-linked_Glycosylation	NNIRKALSFDNRGEE HHHHHHHHCCCCCCC	35.10	4170007
368	Phosphorylation	NNIRKALSFDNRGEE HHHHHHHHCCCCCCC	35.10	30411139
380	Phosphorylation	GEEHRASSSTDGQLA CCCCCCCCCCCCCCC	35.95	18295358
388	Phosphorylation	STDGQLASPGENGEV CCCCCCCCCCCCCCC	41.87	30411139
418	Phosphorylation	IKVLGKGSFGKVMLA EEEECCCCCCCHHHH	34.02	23984901
418	O-linked_Glycosylation	IKVLGKGSFGKVMLA EEEECCCCCCCHHHH	34.02	12639235
453	O-linked_Glycosylation	QDDDVDCTMTEKRIL CCCCCCCCCCHHHHH	23.75	18295358
488	Phosphorylation	RLFFVMEYVNGGDLM EEEEEEEEECCCCEE	4.90	18295358
517	O-linked_Glycosylation	GFYAAEVTSALMFLH CCCHHHHHHHHHHHH	10.37	18295358
566	Phosphorylation	LNGVTTTTFCGTPDY CCCCCCCCCCCCCCC	18.16	-
573	Phosphorylation	TFCGTPDYIAPEILQ CCCCCCCCCCHHHHH	10.53	9326592
636	Phosphorylation	WLSKEAVSILKAFMT HCCHHHHHHHHHHHC	29.29	18295358
643	Phosphorylation	SILKAFMTKNPHKRL HHHHHHHCCCHHHCC	22.63	18295358
703	Phosphorylation	NNFDQDFTREEPILT CCCCCCCCCCCCHHH	45.52	23984901
710	Phosphorylation	TREEPILTLVDEAIV CCCCCHHHHHHHHHH	26.00	22108457
710	O-linked_Glycosylation	TREEPILTLVDEAIV CCCCCHHHHHHHHHH	26.00	19755
729	Phosphorylation	QEEFKGFSYFGEDLM HHHHCCCCCCCCCCC	28.37	18390563
730	Phosphorylation	EEFKGFSYFGEDLMP HHHCCCCCCCCCCCC	17.22	23984901

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
350	S	Phosphorylation	Kinase	MAPK14	P70618	Uniprot
350	S	Phosphorylation	Kinase	MAPK11	-	Uniprot
566	T	Phosphorylation	Kinase	PDPK1	O55173	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 (By similarity).	22673903
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 (By similarity).	-
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 (By similarity).	22673903
566	T	Phosphorylation	Phosphorylation on Thr-566 by PDPK1 triggers autophosphorylation on Ser-729.	-
729	S	Phosphorylation	Phosphorylation on Thr-566 by PDPK1 triggers autophosphorylation on Ser-729.	22673903

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_RAT !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
UBC_RAT	Ubc	physical	9447980
H11_RAT	Hist1h1a	physical	11118818

Drug and Disease Associations

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