KPCA_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: KPCA_MOUSE
• UniProt AC: P20444
• Protein Name: Protein kinase C alpha type
• Gene Name: Prkca
• Organism: Mus musculus (Mouse).
• Sequence Length: 672
• Subcellular Localization: Cytoplasm . Cell membrane ; Peripheral membrane protein . Mitochondrion membrane ; Peripheral membrane protein . Nucleus . Translocated to the cell periphery upon tetradecanoyl phorbol acetate (TPA) treatment.
• Protein Description: Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascades involving MAPK1/3 (ERK1/2) and RAP1GAP. Depending on the cell type, is involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation. In cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Depending on the cell type, exhibits anti-apoptotic function and protects cells from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, or mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42 (By similarity). Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF-kappa-B-induced genes, through IL1A-dependent induction of NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription..
• Protein Sequence: MADVYPANDSTASQDVANRFARKGALRQKNVHEVKDHKFIARFFKQPTFCSHCTDFIWGFGKQGFQCQVCCFVVHKRCHEFVTFSCPGADKGPDTDDPRSKHKFKIHTYGSPTFCDHCGSLLYGLIHQGMKCDTCDMNVHKQCVINDPSLCGMDHTEKRGRIYLKAEVTDEKLHVTVRDAKNLIPMDPNGLSDPYVKLKLIPDPKNESKQKTKTIRSNLNPQWNESFTFKLKPSDKDRRLSVEIWDWDRTTRNDFMGSLSFGVSELMKMPASGWYKAHNQEEGEYYNVPIPEGDEEGNMELRQKFEKAKLGPVGNKVISPSEDRKQPSNNLDRVKLTDFNFLMVLGKGSFGKVMLADRKGTEELYAIKILKKDVVIQDDDVECTMVEKRVLALLDKPPFLTQLHSCFQTVDRLYFVMEYVNGGDLMYHIQQVGKFKEPQAVFYAAEISIGLFFLHKRGIIYRDLKLNNVMLNSEGHIKIADFGMCKEHMMDGVTTRTFCGTPDYIAPEIIAYQPYGKSVDWWAYGVLLYEMLAGQPPFDGEDEDELFQSIMEHNVSYPKSLSKEAVSICKGLMTKQPAKRLGCGPEGERDVREHAFFRRIDWEKLENREIQPPFKPKVCGKGAENFDKFFTRGQPVLTPPDQLVIANIDQSDFEGFSYVNPQFVHPILQSAV

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
2	Acetylation	------MADVYPAND ------CCCCCCCCC	18.25	-
5	Phosphorylation	---MADVYPANDSTA ---CCCCCCCCCCCC	9.36	22345495
10	Phosphorylation	DVYPANDSTASQDVA CCCCCCCCCCCHHHH	26.19	20415495
11	Phosphorylation	VYPANDSTASQDVAN CCCCCCCCCCHHHHH	32.94	23375375
13	Phosphorylation	PANDSTASQDVANRF CCCCCCCCHHHHHHH	27.31	30352176
48	Phosphorylation	ARFFKQPTFCSHCTD HHHHCCCCCCHHHHH	34.48	22817900
50	S-palmitoylation	FFKQPTFCSHCTDFI HHCCCCCCHHHHHCH	2.74	28680068
86	S-palmitoylation	HEFVTFSCPGADKGP CEEEEEECCCCCCCC	2.92	28680068
195	Phosphorylation	PNGLSDPYVKLKLIP CCCCCCCCEEEEECC	18.40	22322096
197	Ubiquitination	GLSDPYVKLKLIPDP CCCCCCEEEEECCCC	33.78	-
199	Ubiquitination	SDPYVKLKLIPDPKN CCCCEEEEECCCCCC	38.36	-
226	Phosphorylation	LNPQWNESFTFKLKP CCCCCCCCEEEECCC	26.77	21659605
228	Phosphorylation	PQWNESFTFKLKPSD CCCCCCEEEECCCCC	29.19	-
285	Phosphorylation	HNQEEGEYYNVPIPE CCCCCCCEEECCCCC	15.93	-
319	Phosphorylation	PVGNKVISPSEDRKQ CCCCEECCCCCCCCC	25.92	25521595
321	Phosphorylation	GNKVISPSEDRKQPS CCEECCCCCCCCCCC	45.39	25521595
462	Methylation	HKRGIIYRDLKLNNV HHCCEEEEECCCCCE	32.17	30988835
494	Phosphorylation	EHMMDGVTTRTFCGT HHCCCCCCHHCCCCC	18.98	25521595
495	Phosphorylation	HMMDGVTTRTFCGTP HCCCCCCHHCCCCCC	25.88	22322096
497	Phosphorylation	MDGVTTRTFCGTPDY CCCCCHHCCCCCCCC	22.61	25521595
501	Phosphorylation	TTRTFCGTPDYIAPE CHHCCCCCCCCCCCH	17.73	25521595
504	Phosphorylation	TFCGTPDYIAPEIIA CCCCCCCCCCCHHHE	10.53	25521595
512	Phosphorylation	IAPEIIAYQPYGKSV CCCHHHEECCCCCCH	10.30	25619855
515	Phosphorylation	EIIAYQPYGKSVDWW HHHEECCCCCCHHHH	22.97	25777480
567	Phosphorylation	SLSKEAVSICKGLMT CCCHHHHHHHHHHCC	29.35	-
574	Phosphorylation	SICKGLMTKQPAKRL HHHHHHCCCCCHHHC	31.41	28059163
628	Acetylation	KGAENFDKFFTRGQP CCCCCHHHHHCCCCC	37.94	-
631	Phosphorylation	ENFDKFFTRGQPVLT CCHHHHHCCCCCCCC	36.70	-
638	Phosphorylation	TRGQPVLTPPDQLVI CCCCCCCCCCCCEEE	32.77	26824392
651	Phosphorylation	VIANIDQSDFEGFSY EEEECCHHHCCCCCC	40.28	23737553
657	Phosphorylation	QSDFEGFSYVNPQFV HHHCCCCCCCCHHHH	38.74	26824392
658	Phosphorylation	SDFEGFSYVNPQFVH HHCCCCCCCCHHHHH	11.28	23649490
670	Phosphorylation	FVHPILQSAV----- HHHHHHHHCC-----	27.79	23737553

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
497	T	Phosphorylation	Kinase	PRKCA	P20444	GPS
497	T	Phosphorylation	Kinase	PRKCB	P68404	GPS
497	T	Phosphorylation	Kinase	PDPK1	Q9Z2A0	Uniprot
638	T	Phosphorylation	Kinase	MAPK1	P63085	GPS
638	T	Phosphorylation	Kinase	MAPK3	Q63844	GPS
657	S	Phosphorylation	Kinase	PRKCA	P20444	GPS
658	Y	Phosphorylation	Kinase	SYK	P48025	Uniprot
658	Y	Phosphorylation	Kinase	SYK	Q99MN1	PhosphoELM

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of KPCA_MOUSE !!

Disease-associated PTM Sites based on SAP

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

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

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
PDLI2_MOUSE	Pdlim2	physical	20889505
ITB3_MOUSE	Itgb3	physical	16014375
GRM5_MOUSE	Grm5	physical	9242710

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"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-319, AND MASSSPECTROMETRY.
PubMed: 17114649

"A Ras activation pathway dependent on Syk phosphorylation of proteinkinase C.";
Kawakami Y., Kitaura J., Yao L., McHenry R.W., Kawakami Y.,Newton A.C., Kang S., Kato R.M., Leitges M., Rawlings D.J.,Kawakami T.;
Proc. Natl. Acad. Sci. U.S.A. 100:9470-9475(2003).
Cited for: PHOSPHORYLATION AT TYR-658.
PubMed: 12881490