KPCG_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: KPCG_MOUSE
• UniProt AC: P63318
• Protein Name: Protein kinase C gamma type
• Gene Name: Prkcg
• Organism: Mus musculus (Mouse).
• Sequence Length: 697
• Subcellular Localization: Cytoplasm . Cytoplasm, perinuclear region. Cell membrane ; Peripheral membrane protein. Cell junction, synapse, synaptosome . Cell projection, dendrite . Translocates to synaptic membranes on stimulation.
• Protein Description: Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays diverse roles in neuronal cells and eye tissues, such as regulation of the neuronal receptors GRIA4/GLUR4 and GRIN1/NMDAR1, modulation of receptors and neuronal functions related to sensitivity to opiates, pain and alcohol, mediation of synaptic function and cell survival after ischemia, and inhibition of gap junction activity after oxidative stress. Binds and phosphorylates GRIA4/GLUR4 glutamate receptor and regulates its function by increasing plasma membrane-associated GRIA4 expression. In primary cerebellar neurons treated with the agonist 3,5-dihyidroxyphenylglycine, functions downstream of the metabotropic glutamate receptor GRM5/MGLUR5 and phosphorylates GRIN1/NMDAR1 receptor which plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. May be involved in the regulation of hippocampal long-term potentiation (LTP), but may be not necessary for the process of synaptic plasticity. May be involved in desensitization of mu-type opioid receptor-mediated G-protein activation in the spinal cord, and may be critical for the development and/or maintenance of morphine-induced reinforcing effects in the limbic forebrain. May modulate the functionality of mu-type-opioid receptors by participating in a signaling pathway which leads to the phosphorylation and degradation of opioid receptors. May also contribute to chronic morphine-induced changes in nociceptive processing. Plays a role in neuropathic pain mechanisms and contributes to the maintenance of the allodynia pain produced by peripheral inflammation. Plays an important role in initial sensitivity and tolerance to ethanol, by mediating the behavioral effects of ethanol as well as the effects of this drug on the GABA(A) receptors. During and after cerebral ischemia modulate neurotransmission and cell survival in synaptic membranes, and is involved in insulin-induced inhibition of necrosis, an important mechanism for minimizing ischemic injury. Required for the elimination of multiple climbing fibers during innervation of Purkinje cells in developing cerebellum. Is activated in lens epithelial cells upon hydrogen peroxide treatment, and phosphorylates connexin-43 (GJA1/CX43), resulting in disassembly of GJA1 gap junction plaques and inhibition of gap junction activity which could provide a protective effect against oxidative stress. Phosphorylates p53/TP53 and promotes p53/TP53-dependent apoptosis in response to DNA damage. Involved in the phase resetting of the cerebral cortex circadian clock during temporally restricted feeding. Stabilizes the core clock component ARNTL/BMAL1 by interfering with its ubiquitination, thus suppressing its degradation, resulting in phase resetting of the cerebral cortex clock. [PubMed: 23185022]
• Protein Sequence: MAGLGPGGGDSEGGPRPLFCRKGALRQKVVHEVKSHKFTARFFKQPTFCSHCTDFIWGIGKQGLQCQVCSFVVHRRCHEFVTFECPGAGKGPQTDDPRNKHKFRLHSYSSPTFCDHCGSLLYGLVHQGMKCSCCEMNVHRRCVRSVPSLCGVDHTERRGRLQLEIRAPTSDEIHITVGEARNLIPMDPNGLSDPYVKLKLIPDPRNLTKQKTKTVKATLNPVWNETFVFNLKPGDVERRLSVEVWDWDRTSRNDFMGAMSFGVSELLKAPVDGWYKLLNQEEGEYYNVPVADADNCSLLQKFEACNYPLELYERVRMGPSSSPIPSPSPSPTDSKRCFFGASPGRLHISDFSFLMVLGKGSFGKVMLAERRGSDELYAIKILKKDVIVQDDDVDCTLVEKRVLALGGRGPGGRPHFLTQLHSTFQTPDRLYFVMEYVTGGDLMYHIQQLGKFKEPHAAFYAAEIAIGLFFLHNQGIIYRDLKLDNVMLDAEGHIKITDFGMCKENVFPGSTTRTFCGTPDYIAPEIIAYQPYGKSVDWWSFGVLLYEMLAGQPPFDGEDEEELFQAIMEQTVTYPKSLSREAVAICKGFLTKHPGKRLGSGPDGEPTIRAHGFFRWIDWERLERLEIAPPFRPRPCGRSGENFDKFFTRAAPALTPPDRLVLASIDQADFQGFTYVNPDFVHPDARSPTSPVPVPVM

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
11	Phosphorylation	LGPGGGDSEGGPRPL CCCCCCCCCCCCCCC	41.22	18056256
47	Phosphorylation	ARFFKQPTFCSHCTD HHHHCCCCCHHHHHH	34.48	-
70	Phosphorylation	GLQCQVCSFVVHRRC CCCCCEEEEEEECCC	23.40	25521595
132	Phosphorylation	VHQGMKCSCCEMNVH HHCCCCCCCHHCHHH	19.11	29899451
148	Phosphorylation	RCVRSVPSLCGVDHT HHHHHCHHHCCCCCC	33.85	18056256
169	Phosphorylation	QLEIRAPTSDEIHIT EEEEECCCCCEEEEE	48.07	19060867
170	Phosphorylation	LEIRAPTSDEIHITV EEEECCCCCEEEEEE	31.99	22817900
176	Phosphorylation	TSDEIHITVGEARNL CCCEEEEEEECHHCC	14.32	-
195	Phosphorylation	PNGLSDPYVKLKLIP CCCCCCCCEEEEECC	18.40	20415495
197	Ubiquitination	GLSDPYVKLKLIPDP CCCCCCEEEEECCCC	33.78	22790023
199	Ubiquitination	SDPYVKLKLIPDPRN CCCCEEEEECCCCCC	38.36	22790023
250	Phosphorylation	EVWDWDRTSRNDFMG EEECCCCCCCCCHHH	29.57	-
296	S-nitrosylation	PVADADNCSLLQKFE CCCCCCCCCHHHHHH	2.89	22178444
296	S-nitrosocysteine	PVADADNCSLLQKFE CCCCCCCCCHHHHHH	2.89	-
297	Phosphorylation	VADADNCSLLQKFEA CCCCCCCCHHHHHHH	38.07	25521595
305	S-nitrosylation	LLQKFEACNYPLELY HHHHHHHCCCCHHHH	3.84	24895380
312	Phosphorylation	CNYPLELYERVRMGP CCCCHHHHHHHHCCC	7.72	18034455
320	Phosphorylation	ERVRMGPSSSPIPSP HHHHCCCCCCCCCCC	37.41	24925903
321	Phosphorylation	RVRMGPSSSPIPSPS HHHCCCCCCCCCCCC	43.18	24925903
322	Phosphorylation	VRMGPSSSPIPSPSP HHCCCCCCCCCCCCC	31.05	25521595
326	Phosphorylation	PSSSPIPSPSPSPTD CCCCCCCCCCCCCCC	38.44	25521595
328	Phosphorylation	SSPIPSPSPSPTDSK CCCCCCCCCCCCCCC	42.20	25521595
330	Phosphorylation	PIPSPSPSPTDSKRC CCCCCCCCCCCCCCC	44.78	25521595
332	Phosphorylation	PSPSPSPTDSKRCFF CCCCCCCCCCCCCCC	58.19	25521595
334	Phosphorylation	PSPSPTDSKRCFFGA CCCCCCCCCCCCCCC	25.20	22324799
335	Ubiquitination	SPSPTDSKRCFFGAS CCCCCCCCCCCCCCC	56.87	22790023
342	Phosphorylation	KRCFFGASPGRLHIS CCCCCCCCCCCEEEC	28.41	22817900
364	Ubiquitination	LGKGSFGKVMLAERR ECCCCHHHHEEEECC	23.59	22790023
373	Phosphorylation	MLAERRGSDELYAIK EEEECCCCCCEEEEE	26.54	22817900
380	Acetylation	SDELYAIKILKKDVI CCCEEEEEEECCCEE	33.54	19860959
479	Methylation	HNQGIIYRDLKLDNV CCCCEEECCCCCCCE	32.17	30988853
503	Ubiquitination	ITDFGMCKENVFPGS ECCCCCCCCCCCCCC	43.35	22790023
510	Phosphorylation	KENVFPGSTTRTFCG CCCCCCCCCCEEECC	27.18	29899451
511	Phosphorylation	ENVFPGSTTRTFCGT CCCCCCCCCEEECCC	26.64	24925903
512	Phosphorylation	NVFPGSTTRTFCGTP CCCCCCCCEEECCCC	29.43	24925903
514	Phosphorylation	FPGSTTRTFCGTPDY CCCCCCEEECCCCCC	22.61	25521595
518	Phosphorylation	TTRTFCGTPDYIAPE CCEEECCCCCCCCCH	17.73	25521595
521	Phosphorylation	TFCGTPDYIAPEIIA EECCCCCCCCCHHHE	10.53	25619855
529	Phosphorylation	IAPEIIAYQPYGKSV CCCHHHEECCCCCCC	10.30	25619855
532	Phosphorylation	EIIAYQPYGKSVDWW HHHEECCCCCCCCHH	22.97	24925903
587	Ubiquitination	REAVAICKGFLTKHP HHHHHHHHHHHHCCC	46.73	22790023
592	Ubiquitination	ICKGFLTKHPGKRLG HHHHHHHCCCCCCCC	50.37	22790023
639	Phosphorylation	RPRPCGRSGENFDKF CCCCCCCCCCCHHHH	35.42	25521595
645	Ubiquitination	RSGENFDKFFTRAAP CCCCCHHHHHHHCCC	37.94	22790023
648	Phosphorylation	ENFDKFFTRAAPALT CCHHHHHHHCCCCCC	23.64	-
655	Phosphorylation	TRAAPALTPPDRLVL HHCCCCCCCCCCEEE	34.58	25521595
664	Phosphorylation	PDRLVLASIDQADFQ CCCEEEEECCHHHCC	23.65	29899451
674	Phosphorylation	QADFQGFTYVNPDFV HHHCCCCEEECCCCC	33.13	17904530
675	Phosphorylation	ADFQGFTYVNPDFVH HHCCCCEEECCCCCC	8.93	20415495
687	Phosphorylation	FVHPDARSPTSPVPV CCCCCCCCCCCCCCC	33.96	25521595
689	Phosphorylation	HPDARSPTSPVPVPV CCCCCCCCCCCCCCC	47.08	25521595
690	Phosphorylation	PDARSPTSPVPVPVM CCCCCCCCCCCCCCC	27.55	25521595

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
514	T	Phosphorylation	Kinase	PKCD	P28867	PSP
514	T	Phosphorylation	Kinase	PDPK1	Q9Z2A0	Uniprot
655	T	Phosphorylation	Kinase	PRKCG	P63318	GPS
674	T	Phosphorylation	Kinase	PRKCG	P63318	GPS
675	Y	Phosphorylation	Kinase	SYK	P48025	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
674	T	Phosphorylation	Autophosphorylation on Thr-674 appears to regulate motor functions of junctophilins, JPH3 and JPH4.	17904530

Disease-associated PTM Sites based on SAP

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

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

Protein-Protein Interaction

Oops, there are no PPI records of KPCG_MOUSE !!

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-322; SER-330; THR-514;THR-518; THR-655 AND SER-687, SUBCELLULAR LOCATION, TISSUESPECIFICITY, AND MASS SPECTROMETRY.
PubMed: 17114649

"Abnormal features in mutant cerebellar Purkinje cells lackingjunctophilins.";
Ikeda A., Miyazaki T., Kakizawa S., Okuno Y., Tsuchiya S., Myomoto A.,Saito S.Y., Yamamoto T., Yamazaki T., Iino M., Tsujimoto G.,Watanabe M., Takeshima H.;
Biochem. Biophys. Res. Commun. 363:835-839(2007).
Cited for: PHOSPHORYLATION AT THR-514; THR-655 AND THR-674, SUBCELLULAR LOCATION,FUNCTION, AND TISSUE SPECIFICITY.
PubMed: 17904530

"Large-scale identification and evolution indexing of tyrosinephosphorylation sites from murine brain.";
Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
J. Proteome Res. 7:311-318(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-195 AND TYR-312, ANDMASS SPECTROMETRY.
PubMed: 18034455