dbPTM

KPCD_RAT - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	KPCD_RAT
UniProt AC	P09215
Protein Name	Protein kinase C delta type
Gene Name	Prkcd
Organism	Rattus norvegicus (Rat).
Sequence Length	673
Subcellular Localization	Cytoplasm . Nucleus . Cytoplasm, perinuclear region . 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. 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 (By similarity). 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).; Truncated isoform 2 is inactive..
Protein Sequence	MAPFLRISFNSYELGSLQAEDDASQPFCAVKMKEALTTDRGKTLVQKKPTMYPEWKSTFDAHIYEGRVIQIVLMRAAEDPMSEVTVGVSVLAERCKKNNGKAEFWLDLQPQAKVLMCVQYFLEDGDCKQSMRSEEEAMFPTMNRRGAIKQAKIHYIKNHEFIATFFGQPTFCSVCKEFVWGLNKQGYKCRQCNAAIHKKCIDKIIGRCTGTATNSRDTIFQKERFNIDMPHRFKVYNYMSPTFCDHCGTLLWGLVKQGLKCEDCGMNVHHKCREKVANLCGINQKLLAEALNQVTQKASRKPETPETVGIYQGFEKKTAVSGNDIPDNNGTYGKIWEGSNRCRLENFTFQKVLGKGSFGKVLLAELKGKERYFAIKYLKKDVVLIDDDVECTMVEKRVLALAWENPFLTHLICTFQTKDHLFFVMEFLNGGDLMFHIQDKGRFELYRATFYAAEIICGLQFLHGKGIIYRDLKLDNVMLDKDGHIKIADFGMCKENIFGENRASTFCGTPDYIAPEILQGLKYSFSVDWWSFGVLLYEMLIGQSPFHGDDEDELFESIRVDTPHYPRWITKESKDIMEKLFERDPAKRLGVTGNIRLHPFFKTINWNLLEKRKVEPPFKPKVKSPSDYSNFDPEFLNEKPQLSFSDKNLIDSMDQTAFKGFSFVNPKYEQFLE

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
37	Phosphorylation	VKMKEALTTDRGKTL EEHHHHHHCCCCCCH	33.43	23984901
38	Phosphorylation	KMKEALTTDRGKTLV EHHHHHHCCCCCCHH	25.25	23984901
43	Phosphorylation	LTTDRGKTLVQKKPT HHCCCCCCHHCCCCC	34.68	23984901
50	Phosphorylation	TLVQKKPTMYPEWKS CHHCCCCCCCCCHHH	37.91	-
64	Phosphorylation	STFDAHIYEGRVIQI HCEEEEEECCCEEEE	11.49	17562707
130	Phosphorylation	EDGDCKQSMRSEEEA HCCCHHHHHCCHHHH	11.14	22108457
141	Phosphorylation	EEEAMFPTMNRRGAI HHHHHCCCCCCCCHH	18.80	-
155	Phosphorylation	IKQAKIHYIKNHEFI HHHHEEEEEECCCEE	19.64	17562707
164	Phosphorylation	KNHEFIATFFGQPTF ECCCEEHHHHCCCCH	18.06	-
211	Phosphorylation	IIGRCTGTATNSRDT HHHHCCCCCCCCCCC	16.50	23984901
213	Phosphorylation	GRCTGTATNSRDTIF HHCCCCCCCCCCCCC	33.30	23984901
215	Phosphorylation	CTGTATNSRDTIFQK CCCCCCCCCCCCCEE	27.46	23984901
218	Phosphorylation	TATNSRDTIFQKERF CCCCCCCCCCEEHHC	23.68	22673903
295	O-linked_Glycosylation	AEALNQVTQKASRKP HHHHHHHHHHHHCCC	18.00	18295358
295	Phosphorylation	AEALNQVTQKASRKP HHHHHHHHHHHHCCC	18.00	23984901
297	Ubiquitination	ALNQVTQKASRKPET HHHHHHHHHHCCCCC	38.68	-
299	Phosphorylation	NQVTQKASRKPETPE HHHHHHHHCCCCCCC	48.12	-
304	Phosphorylation	KASRKPETPETVGIY HHHCCCCCCCCCEEE	34.65	28432305
307	Phosphorylation	RKPETPETVGIYQGF CCCCCCCCCEEECCC	25.82	28432305
311	Phosphorylation	TPETVGIYQGFEKKT CCCCCEEECCCEECC	9.17	19161989
331	Phosphorylation	DIPDNNGTYGKIWEG CCCCCCCCCCCCCCC	31.09	22276854
332	Phosphorylation	IPDNNGTYGKIWEGS CCCCCCCCCCCCCCC	20.16	17569658
348	O-linked_Glycosylation	RCRLENFTFQKVLGK CEEEECEEEEEECCC	36.42	12639201
357	Phosphorylation	QKVLGKGSFGKVLLA EEECCCCCCHHHHHH	34.02	18295358
357	O-linked_Glycosylation	QKVLGKGSFGKVLLA EEECCCCCCHHHHHH	34.02	18295358
372	Phosphorylation	ELKGKERYFAIKYLK HHCCCHHEEEEEHHC	9.84	10319993
449	Phosphorylation	RFELYRATFYAAEII CEEEHHHHHHHHHHH	14.26	-
504	Phosphorylation	IFGENRASTFCGTPD CCCCCCCHHCCCCCC	20.84	23991683
505	Phosphorylation	FGENRASTFCGTPDY CCCCCCHHCCCCCCC	23.20	23991683
509	Phosphorylation	RASTFCGTPDYIAPE CCHHCCCCCCCCCHH	17.73	27097102
512	Phosphorylation	TFCGTPDYIAPEILQ HCCCCCCCCCHHHHC	10.53	27097102
523	Phosphorylation	EILQGLKYSFSVDWW HHHCCCCCEEECCHH	21.71	9326592
565	Phosphorylation	IRVDTPHYPRWITKE HCCCCCCCCCCCCHH	8.83	10319993
592	O-linked_Glycosylation	PAKRLGVTGNIRLHP HHHHHCCCCCEEECH	23.78	182109
603	Phosphorylation	RLHPFFKTINWNLLE EECHHHCCCCHHHHH	17.87	23984901
628	Phosphorylation	KVKSPSDYSNFDPEF CCCCHHHHCCCCHHH	15.17	10319993
629	Phosphorylation	VKSPSDYSNFDPEFL CCCHHHHCCCCHHHH	35.69	25575281
643	Phosphorylation	LNEKPQLSFSDKNLI HCCCCCCCCCCCCHH	19.91	23712012
645	Phosphorylation	EKPQLSFSDKNLIDS CCCCCCCCCCCHHHH	44.28	27097102
652	Phosphorylation	SDKNLIDSMDQTAFK CCCCHHHHCCHHHHC	19.77	23984901
656	Phosphorylation	LIDSMDQTAFKGFSF HHHHCCHHHHCCCCC	29.78	25575281
662	Phosphorylation	QTAFKGFSFVNPKYE HHHHCCCCCCCHHHH	36.63	23991683

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
64	Y	Phosphorylation	Kinase	SRC	P12931	PSP
155	Y	Phosphorylation	Kinase	ABL1	P00519	GPS
311	Y	Phosphorylation	Kinase	SRC	P12931	PSP
311	Y	Phosphorylation	Kinase	SRC64	-	PhosphoELM
311	Y	Phosphorylation	Kinase	SRC	Q9WUD9	Uniprot
311	Y	Phosphorylation	Kinase	LCK	P06240	PSP
311	Y	Phosphorylation	Kinase	EGFR	P00533	PSP
332	Y	Phosphorylation	Kinase	SRC	P12931	PSP
332	Y	Phosphorylation	Kinase	EGFR	P00533	PSP
332	Y	Phosphorylation	Kinase	SRC	Q9WUD9	Uniprot
372	Y	Phosphorylation	Kinase	SRC	P12931	PSP
505	T	Phosphorylation	Kinase	PRKCE	P16054	GPS
505	T	Phosphorylation	Kinase	PDPK1	O15530	GPS
505	T	Phosphorylation	Kinase	PDK1	O55173	GPS
505	T	Phosphorylation	Kinase	PRKCD	P09215	GPS
565	Y	Phosphorylation	Kinase	SRC	P12931	PSP
628	Y	Phosphorylation	Kinase	SRC	P12931	PSP
662	S	Phosphorylation	Kinase	PRKCD	P09215	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
299	S	Phosphorylation	18550549
Autophosphorylated at Ser-299.
505	T	Phosphorylation	9677322
Autophosphorylated and/or phosphorylated at Thr-505, within the activation loop; phosphorylation at Thr-505 is not a prerequisite for enzymatic activity.
505	T	Phosphorylation	9677322
Phosphorylated at Tyr-311 and Tyr-332 by SRC; phosphorylation leads to enhanced autophosphorylation at Thr-505.

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_RAT !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
HMGB1_RAT	Hmgb1	physical	10617144
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.

Regulatory Network of KPCD_RAT

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Phosphoproteomic analysis of rat liver by high capacity IMAC and LC-MS/MS."; Moser K., White F.M.; J. Proteome Res. 5:98-104(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-662, AND MASSSPECTROMETRY.	16396499 [Abstract]
"Tyrosine phosphorylation modifies protein kinase C delta-dependentphosphorylation of cardiac troponin I."; Sumandea M.P., Rybin V.O., Hinken A.C., Wang C., Kobayashi T.,Harleton E., Sievert G., Balke C.W., Feinmark S.J., Solaro R.J.,Steinberg S.F.; J. Biol. Chem. 283:22680-22689(2008). Cited for: PHOSPHORYLATION AT TYR-311; TYR-332 AND THR-505.	18550549 [Abstract]
"Protein kinase Cepsilon (PKCepsilon) and Src control PKCdeltaactivation loop phosphorylation in cardiomyocytes."; Rybin V.O., Guo J., Gertsberg Z., Elouardighi H., Steinberg S.F.; J. Biol. Chem. 282:23631-23638(2007). Cited for: PHOSPHORYLATION AT THR-505.	17569658 [Abstract]
"The broad specificity of dominant inhibitory protein kinase C mutantsinfers a common step in phosphorylation."; Garcia-Paramio P., Cabrerizo Y., Bornancin F., Parker P.J.; Biochem. J. 333:631-636(1998). Cited for: MUTAGENESIS OF THR-505, AND PHOSPHORYLATION AT THR-505.	9677322 [Abstract]
"Induction of apoptosis is driven by nuclear retention of proteinkinase C delta."; DeVries-Seimon T.A., Ohm A.M., Humphries M.J., Reyland M.E.; J. Biol. Chem. 282:22307-22314(2007). Cited for: SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT TYR-64 AND TYR-155.	17562707 [Abstract]

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