dbPTM

KPCG_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	KPCG_HUMAN
UniProt AC	P05129
Protein Name	Protein kinase C gamma type
Gene Name	PRKCG
Organism	Homo sapiens (Human).
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 contributes 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 (By similarity). 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 (By similarity)..
Protein Sequence	MAGLGPGVGDSEGGPRPLFCRKGALRQKVVHEVKSHKFTARFFKQPTFCSHCTDFIWGIGKQGLQCQVCSFVVHRRCHEFVTFECPGAGKGPQTDDPRNKHKFRLHSYSSPTFCDHCGSLLYGLVHQGMKCSCCEMNVHRRCVRSVPSLCGVDHTERRGRLQLEIRAPTADEIHVTVGEARNLIPMDPNGLSDPYVKLKLIPDPRNLTKQKTRTVKATLNPVWNETFVFNLKPGDVERRLSVEVWDWDRTSRNDFMGAMSFGVSELLKAPVDGWYKLLNQEEGEYYNVPVADADNCSLLQKFEACNYPLELYERVRMGPSSSPIPSPSPSPTDPKRCFFGASPGRLHISDFSFLMVLGKGSFGKVMLAERRGSDELYAIKILKKDVIVQDDDVDCTLVEKRVLALGGRGPGGRPHFLTQLHSTFQTPDRLYFVMEYVTGGDLMYHIQQLGKFKEPHAAFYAAEIAIGLFFLHNQGIIYRDLKLDNVMLDAEGHIKITDFGMCKENVFPGTTTRTFCGTPDYIAPEIIAYQPYGKSVDWWSFGVLLYEMLAGQPPFDGEDEEELFQAIMEQTVTYPKSLSREAVAICKGFLTKHPGKRLGSGPDGEPTIRAHGFFRWIDWERLERLEIPPPFRPRPCGRSGENFDKFFTRAAPALTPPDRLVLASIDQADFQGFTYVNPDFVHPDARSPTSPVPVPVM

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
11	Phosphorylation	LGPGVGDSEGGPRPL CCCCCCCCCCCCCCC	32.01	28188228
47	Phosphorylation	ARFFKQPTFCSHCTD HHHHCCCCCHHHHHH	34.48	20873877
50	Phosphorylation	FKQPTFCSHCTDFIW HCCCCCHHHHHHCHH	19.87	-
70	Phosphorylation	GLQCQVCSFVVHRRC CCCCCEEEEEEECCC	23.40	24076635
107	Phosphorylation	KHKFRLHSYSSPTFC CCEEEECCCCCCCCC	31.16	27080861
108	Phosphorylation	HKFRLHSYSSPTFCD CEEEECCCCCCCCCH	11.47	27080861
109	Phosphorylation	KFRLHSYSSPTFCDH EEEECCCCCCCCCHH	32.62	27080861
110	Phosphorylation	FRLHSYSSPTFCDHC EEECCCCCCCCCHHH	21.52	27080861
112	Phosphorylation	LHSYSSPTFCDHCGS ECCCCCCCCCHHHHH	38.55	27080861
119	Phosphorylation	TFCDHCGSLLYGLVH CCCHHHHHHHHHHHH	22.16	27080861
122	Phosphorylation	DHCGSLLYGLVHQGM HHHHHHHHHHHHCCC	17.44	27080861
145	Phosphorylation	VHRRCVRSVPSLCGV HHHHHHHHCHHHCCC	20.27	-
148	Phosphorylation	RCVRSVPSLCGVDHT HHHHHCHHHCCCCCC	33.85	25332170
155	Phosphorylation	SLCGVDHTERRGRLQ HHCCCCCCCCCCCEE	27.07	-
192	Phosphorylation	PMDPNGLSDPYVKLK CCCCCCCCCCCEEEE	37.63	28102081
195	Phosphorylation	PNGLSDPYVKLKLIP CCCCCCCCEEEEECC	18.40	25884760
197	Ubiquitination	GLSDPYVKLKLIPDP CCCCCCEEEEECCCC	33.78	-
197	Acetylation	GLSDPYVKLKLIPDP CCCCCCEEEEECCCC	33.78	23749302
250	Phosphorylation	EVWDWDRTSRNDFMG EEECCCCCCCCCHHH	29.57	-
264	Phosphorylation	GAMSFGVSELLKAPV HHHHHCHHHHHCCCC	23.94	24719451
312	Phosphorylation	CNYPLELYERVRMGP CCCCHHHHHHHHCCC	7.72	21082442
320	Phosphorylation	ERVRMGPSSSPIPSP HHHHCCCCCCCCCCC	37.41	24076635
321	Phosphorylation	RVRMGPSSSPIPSPS HHHCCCCCCCCCCCC	43.18	24076635
322	Phosphorylation	VRMGPSSSPIPSPSP HHCCCCCCCCCCCCC	31.05	24076635
326	Phosphorylation	PSSSPIPSPSPSPTD CCCCCCCCCCCCCCC	38.44	24076635
328	Phosphorylation	SSPIPSPSPSPTDPK CCCCCCCCCCCCCCC	42.20	24076635
330	Phosphorylation	PIPSPSPSPTDPKRC CCCCCCCCCCCCCCC	44.78	24076635
332	Phosphorylation	PSPSPSPTDPKRCFF CCCCCCCCCCCCCCC	70.08	25332170
342	Phosphorylation	KRCFFGASPGRLHIS CCCCCCCCCCCEEEC	28.41	23312004
359	Ubiquitination	SFLMVLGKGSFGKVM EEEEEECCCCHHHHE	47.42	-
359	Acetylation	SFLMVLGKGSFGKVM EEEEEECCCCHHHHE	47.42	19827463
361	Phosphorylation	LMVLGKGSFGKVMLA EEEECCCCHHHHEEE	34.02	27067055
373	Phosphorylation	MLAERRGSDELYAIK EEEECCCCCCEEEEE	26.54	25332170
503	Acetylation	ITDFGMCKENVFPGT ECCCCCCCCCCCCCC	43.35	12430661
510	Phosphorylation	KENVFPGTTTRTFCG CCCCCCCCCCEEECC	25.82	22322096
511	Phosphorylation	ENVFPGTTTRTFCGT CCCCCCCCCEEECCC	21.86	22322096
512	Phosphorylation	NVFPGTTTRTFCGTP CCCCCCCCEEECCCC	27.78	18669648
514	Phosphorylation	FPGTTTRTFCGTPDY CCCCCCEEECCCCCC	22.61	22322096
518	Phosphorylation	TTRTFCGTPDYIAPE CCEEECCCCCCCCCH	17.73	22167270
521	Phosphorylation	TFCGTPDYIAPEIIA EECCCCCCCCCHHHE	10.53	25463755
529	Phosphorylation	IAPEIIAYQPYGKSV CCCHHHEECCCCCCC	10.30	23663014
532	Phosphorylation	EIIAYQPYGKSVDWW HHHEECCCCCCCCHH	22.97	23403867
607	Phosphorylation	SGPDGEPTIRAHGFF CCCCCCCCEEEECCE	20.84	24719451
639	Phosphorylation	RPRPCGRSGENFDKF CCCCCCCCCCCHHHH	35.42	24076635
648	Phosphorylation	ENFDKFFTRAAPALT CCHHHHHHHCCCCCC	23.64	-
655	Phosphorylation	TRAAPALTPPDRLVL HHCCCCCCCCCCEEE	34.58	30266825
664	Phosphorylation	PDRLVLASIDQADFQ CCCEEEEECCHHHCC	23.65	27422710
674	Phosphorylation	QADFQGFTYVNPDFV HHHCCCCEEECCCCC	33.13	27422710
675	Phosphorylation	ADFQGFTYVNPDFVH HHCCCCEEECCCCCC	8.93	21082442
687	Phosphorylation	FVHPDARSPTSPVPV CCCCCCCCCCCCCCC	33.96	25332170
689	Phosphorylation	HPDARSPTSPVPVPV CCCCCCCCCCCCCCC	47.08	25332170
690	Phosphorylation	PDARSPTSPVPVPVM CCCCCCCCCCCCCCC	27.55	25332170

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	PDPK1	O15530	Uniprot
675	Y	Phosphorylation	Kinase	SYK	P43405	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	SMURF1	Q9HCE7	PMID:20804422

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.

Disease-associated PTM Sites based on SAP

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

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of KPCG_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
1433G_HUMAN	YWHAG	physical	10433554
GRIA4_HUMAN	GRIA4	physical	12471040
RGS2_HUMAN	RGS2	physical	11063746
TIAM1_HUMAN	TIAM1	physical	10212259
GBRA4_HUMAN	GABRA4	physical	12091471
NF2L2_HUMAN	NFE2L2	physical	19920073
KPCG_HUMAN	PRKCG	physical	19920073
DDX58_HUMAN	DDX58	physical	22114345
IBTK_HUMAN	IBTK	physical	21482705
PICK1_HUMAN	PICK1	physical	16713569
NOXA1_HUMAN	NOXA1	physical	16713569
EXOC5_HUMAN	EXOC5	physical	16713569
CCHCR_HUMAN	CCHCR1	physical	16713569
TOP2A_HUMAN	TOP2A	physical	7499337
A4_HUMAN	APP	physical	21832049
MARCS_MOUSE	Marcks	physical	7588787
SDC2_HUMAN	SDC2	physical	9244383
ITB2_HUMAN	ITGB2	physical	11700305
GSK3A_HUMAN	GSK3A	physical	11884598
CASR_HUMAN	CASR	physical	9694886
ARHGP_HUMAN	ARHGEF25	physical	20395553
RBP10_HUMAN	RANBP10	physical	20395553
GFAP_HUMAN	GFAP	physical	20395553
HSP74_HUMAN	HSPA4	physical	20395553
EPHB1_HUMAN	EPHB1	physical	20395553
SCN3A_HUMAN	SCN3A	physical	20395553
TRIM5_HUMAN	TRIM5	physical	20395553
RANB9_HUMAN	RANBP9	physical	20395553
DAB2_HUMAN	DAB2	physical	10542228
CTNB1_HUMAN	CTNNB1	physical	25639486
UBE2T_HUMAN	UBE2T	physical	28162934

Drug and Disease Associations

Kegg Disease
H00063	Spinocerebellar ataxia (SCA); Machado-Joseph disease (SCA3)
OMIM Disease
605361	Spinocerebellar ataxia 14 (SCA14)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
DB00675	Tamoxifen

Regulatory Network of KPCG_HUMAN

Related Literatures of Post-Translational Modification

Acetylation
Reference	PubMed
"Lysine acetylation targets protein complexes and co-regulates majorcellular functions."; Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.; Science 325:834-840(2009). Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-197, AND MASS SPECTROMETRY.	19608861 [Abstract]
Phosphorylation
Reference	PubMed
"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer."; Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.; Cell 131:1190-1203(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-195, AND MASSSPECTROMETRY.	18083107 [Abstract]

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