dbPTM

KPCD_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	KPCD_MOUSE
UniProt AC	P28867
Protein Name	Protein kinase C delta type
Gene Name	Prkcd
Organism	Mus musculus (Mouse).
Sequence Length	674
Subcellular Localization	Cytoplasm . Cytoplasm, perinuclear region . Nucleus . Cell membrane Peripheral membrane protein .
Protein Description	Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses. Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction. Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis. In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53. In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53. In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation. Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1. Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-formyl-methionyl-leucyl-phenylalanine (fMLP)-treated cells, is required for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3 (ERK1/2) signaling pathways. May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA. In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation. Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion; acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release. Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin. The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion. Phosphorylates ELAVL1 in response to angiotensin-2 treatment (By similarity)..
Protein Sequence	MAPFLRISFNSYELGSLQVEDEASQPFCAVKMKEALSTERGKTLVQKKPTMYPEWKTTFDAHIYEGRVIQIVLMRAAEDPVSEVTVGVSVLAERCKKNNGKAEFWLDLQPQAKVLMCVQYFLEDGDCKQSMRSEEEAKFPTMNRRGAIKQAKIHYIKNHEFIATFFGQPTFCSVCKEFVWGLNKQGYKCRQCNAAIHKKCIDKIIGRCTGTATNSRDTIFQKERFNIDMPHRFKVYNYMSPTFCDHCGSLLWGLVKQGLKCEDCGMNVHHKCREKVANLCGINQKLLAEALNQVTQRSSRKLDTTESVGIYQGFEKKPEVSGSDILDNNGTYGKIWEGSTRCTLENFTFQKVLGKGSFGKVLLAELKGKDKYFAIKCLKKDVVLIDDDVECTMVEKRVLALAWESPFLTHLICTFQTKDHLFFVMEFLNGGDLMFHIQDKGRFELYRATFYAAEIICGLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGMCKENIFGEGRASTFCGTPDYIAPEILQGLKYSFSVDWWSFGVLLYEMLIGQSPFHGDDEDELFESIRVDTPHYPRWITKESKDIMEKLFERDPDKRLGVTGNIRIHPFFKTINWSLLEKRKVEPPFKPKVKSPSDYSNFDPEFLNEKPQLSFSDKNLIDSMDQEAFHGFSFVNPKFEQFLDI

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
37	Phosphorylation	VKMKEALSTERGKTL EEHHHHHCCCCCCCH	34.96	29514104
43	Phosphorylation	LSTERGKTLVQKKPT HCCCCCCCHHCCCCC	34.68	19144319
47	Acetylation	RGKTLVQKKPTMYPE CCCCHHCCCCCCCCC	53.92	15620999
50	Phosphorylation	TLVQKKPTMYPEWKT CHHCCCCCCCCCCCE	37.91	-
52	Phosphorylation	VQKKPTMYPEWKTTF HCCCCCCCCCCCEEE	10.65	15774464
64	Phosphorylation	TTFDAHIYEGRVIQI EEEEEEEECCCEEEE	11.49	30635358
127	Glutathionylation	YFLEDGDCKQSMRSE HHHHCCCHHHHCCCH	5.44	24333276
130	Phosphorylation	EDGDCKQSMRSEEEA HCCCHHHHCCCHHHH	11.14	19060867
133	Phosphorylation	DCKQSMRSEEEAKFP CHHHHCCCHHHHCCC	40.49	23375375
141	Phosphorylation	EEEAKFPTMNRRGAI HHHHCCCCCCCCCHH	30.15	25159016
155	Phosphorylation	IKQAKIHYIKNHEFI HHHHEEEEEECCCEE	19.64	10783308
184	Ubiquitination	EFVWGLNKQGYKCRQ HHHHCCCCCCCCCCC	50.58	22790023
184 (in isoform 2)	Ubiquitination	-	50.58	22790023
187	Phosphorylation	WGLNKQGYKCRQCNA HCCCCCCCCCCCCCH	12.38	8824297
209	Phosphorylation	DKIIGRCTGTATNSR HHHHHHCCCCCCCCC	35.89	23375375
211	Phosphorylation	IIGRCTGTATNSRDT HHHHCCCCCCCCCCC	16.50	29550500
213	Phosphorylation	GRCTGTATNSRDTIF HHCCCCCCCCCCCCC	33.30	23375375
215	Phosphorylation	CTGTATNSRDTIFQK CCCCCCCCCCCCCEE	27.46	25159016
218	Phosphorylation	TATNSRDTIFQKERF CCCCCCCCCCEEHHC	23.68	30352176
222	Ubiquitination	SRDTIFQKERFNIDM CCCCCCEEHHCCCCC	39.86	-
236	Phosphorylation	MPHRFKVYNYMSPTF CCCCEEEECCCCHHH	10.93	-
295	Phosphorylation	AEALNQVTQRSSRKL HHHHHHHHHHHHCCC	14.43	27600695
298	Phosphorylation	LNQVTQRSSRKLDTT HHHHHHHHHCCCCCC	25.36	25266776
299	Phosphorylation	NQVTQRSSRKLDTTE HHHHHHHHCCCCCCC	35.31	27600695
301 (in isoform 2)	Ubiquitination	-	53.30	22790023
301	Ubiquitination	VTQRSSRKLDTTESV HHHHHHCCCCCCCCC	53.30	22790023
304	Phosphorylation	RSSRKLDTTESVGIY HHHCCCCCCCCCCCC	42.79	28833060
305	Phosphorylation	SSRKLDTTESVGIYQ HHCCCCCCCCCCCCC	26.40	28833060
307	Phosphorylation	RKLDTTESVGIYQGF CCCCCCCCCCCCCCC	24.45	28833060
311	Phosphorylation	TTESVGIYQGFEKKP CCCCCCCCCCCCCCC	9.17	28725479
321 (in isoform 2)	Phosphorylation	-	30.80	25159016
321	Phosphorylation	FEKKPEVSGSDILDN CCCCCCCCCCCCCCC	30.80	25367039
323 (in isoform 2)	Phosphorylation	-	17.61	26643407
323	Phosphorylation	KKPEVSGSDILDNNG CCCCCCCCCCCCCCC	17.61	25367039
331 (in isoform 2)	Phosphorylation	-	31.09	26643407
331	Phosphorylation	DILDNNGTYGKIWEG CCCCCCCCCCCCCCC	31.09	30635358
332	Phosphorylation	ILDNNGTYGKIWEGS CCCCCCCCCCCCCCC	20.16	25159016
334 (in isoform 2)	Phosphorylation	-	33.94	25159016
372	Phosphorylation	ELKGKDKYFAIKCLK HHCCCCCEEEEEECC	14.37	-
449	Phosphorylation	RFELYRATFYAAEII CEEEHHHHHHHHHHH	14.26	-
464	Phosphorylation	CGLQFLHSKGIIYRD HHHHHHCCCCCEECC	34.42	28507225
470	Methylation	HSKGIIYRDLKLDNV CCCCCEECCCCCCCE	32.17	30988847
504	Phosphorylation	IFGEGRASTFCGTPD CCCCCCHHHCCCCCC	22.21	22322096
505	Phosphorylation	FGEGRASTFCGTPDY CCCCCHHHCCCCCCC	23.20	25521595
507	Glutathionylation	EGRASTFCGTPDYIA CCCHHHCCCCCCCCC	6.34	24333276
509	Phosphorylation	RASTFCGTPDYIAPE CHHHCCCCCCCCCHH	17.73	24925903
512	Phosphorylation	TFCGTPDYIAPEILQ HCCCCCCCCCHHHHC	10.53	25521595
523	Phosphorylation	EILQGLKYSFSVDWW HHHCCCCCEEECCHH	21.71	-
565	Phosphorylation	IRVDTPHYPRWITKE HCCCCCCCCCCCCHH	8.83	11812791
607	Phosphorylation	FFKTINWSLLEKRKV HHCCCCHHHHHHCCC	20.70	29514104
624	Phosphorylation	PFKPKVKSPSDYSNF CCCCCCCCHHHHCCC	32.40	25619855
626	Phosphorylation	KPKVKSPSDYSNFDP CCCCCCHHHHCCCCH	57.16	25619855
628	Phosphorylation	KVKSPSDYSNFDPEF CCCCHHHHCCCCHHH	15.17	25619855
629	Phosphorylation	VKSPSDYSNFDPEFL CCCHHHHCCCCHHHH	35.69	25619855
643	Phosphorylation	LNEKPQLSFSDKNLI HCCCCCCCCCCCCCC	19.91	24925903
645	Phosphorylation	EKPQLSFSDKNLIDS CCCCCCCCCCCCCCC	44.28	25521595
652	Phosphorylation	SDKNLIDSMDQEAFH CCCCCCCCCCHHHHH	19.77	26824392
662	Phosphorylation	QEAFHGFSFVNPKFE HHHHHCCCCCCHHHH	32.64	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
52	Y	Phosphorylation	Kinase	LYN	P25911	PhosphoELM
52	Y	Phosphorylation	Kinase	LYN	P07948	PSP
155	Y	Phosphorylation	Kinase	SRC64	-	PhosphoELM
155	Y	Phosphorylation	Kinase	SRC	P05480	PSP
155	Y	Phosphorylation	Kinase	LYN	P25911	PhosphoELM
155	Y	Phosphorylation	Kinase	LYN	P07948	PSP
187	Y	Phosphorylation	Kinase	SRC	P05480	PSP
311	Y	Phosphorylation	Kinase	LYN	P25911	PSP
311	Y	Phosphorylation	Kinase	YES1	Q04736	GPS
311	Y	Phosphorylation	Kinase	SRC	P05480	Uniprot
311	Y	Phosphorylation	Kinase	PDGFRB	P05622	PSP
311	Y	Phosphorylation	Kinase	ABL1	P00520	GPS
311	Y	Phosphorylation	Kinase	LCK	P06240	PhosphoELM
311	Y	Phosphorylation	Kinase	HCK	P08103	PSP
311	Y	Phosphorylation	Kinase	FYN	P39688	PSP
332	Y	Phosphorylation	Kinase	LYN	P25911	PSP
332	Y	Phosphorylation	Kinase	PDGFRB	P05622	PSP
332	Y	Phosphorylation	Kinase	SRC	P05480	Uniprot
332	Y	Phosphorylation	Kinase	YES1	Q04736	GPS
332	Y	Phosphorylation	Kinase	FYN	P39688	PSP
505	T	Phosphorylation	Kinase	PRKCD	P28867	GPS
523	Y	Phosphorylation	Kinase	HCK	P08103	PSP
565	Y	Phosphorylation	Kinase	LYN	P25911	PhosphoELM
565	Y	Phosphorylation	Kinase	LYN	P07948	PSP
643	S	Phosphorylation	Kinase	PRKCD	P28867	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
299	S	Phosphorylation	-
Autophosphorylated at Ser-299.
505	T	Phosphorylation	9748166
Autophosphorylated and/or phosphorylated at Thr-505, within the activation loop; phosphorylation at Thr-505 is not a prerequisite for enzymatic activity.

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 KPCD_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference	Domain-Domain Interactions
HSPB1_MOUSE	Hspb1	physical	15731106
NEUM_RAT	Gap43	physical	8694767

Drug and Disease Associations

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

Regulatory Network of KPCD_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"The phagosomal proteome in interferon-gamma-activated macrophages."; Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,Thibault P.; Immunity 30:143-154(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-43; TYR-311 AND SER-662,AND MASS SPECTROMETRY.	19144319 [Abstract]
"Solid tumor proteome and phosphoproteome analysis by high resolutionmass spectrometry."; Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J.,Faessler R., Mann M.; J. Proteome Res. 7:5314-5326(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-662, AND MASSSPECTROMETRY.	19367708 [Abstract]
"A critical role of protein kinase C delta activation loopphosphorylation in formyl-methionyl-leucyl-phenylalanine-inducedphosphorylation of p47(phox) and rapid activation of nicotinamideadenine dinucleotide phosphate oxidase."; Cheng N., He R., Tian J., Dinauer M.C., Ye R.D.; J. Immunol. 179:7720-7728(2007). Cited for: FUNCTION, AND PHOSPHORYLATION AT THR-505.	18025218 [Abstract]
"Protein kinase C isotypes controlled by phosphoinositide 3-kinasethrough the protein kinase PDK1."; Le Good J.A., Ziegler W.H., Parekh D.B., Alessi D.R., Cohen P.,Parker P.J.; Science 281:2042-2045(1998). Cited for: PHOSPHORYLATION AT THR-505.	9748166 [Abstract]

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