dbPTM

KPCB_RAT - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	KPCB_RAT
UniProt AC	P68403
Protein Name	Protein kinase C beta type
Gene Name	Prkcb
Organism	Rattus norvegicus (Rat).
Sequence Length	671
Subcellular Localization	Cytoplasm. Nucleus. Membrane Peripheral membrane protein.
Protein Description	Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity. Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A. In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. May participate in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis (By similarity). Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription..
Protein Sequence	MADPAAGPPPSEGEESTVRFARKGALRQKNVHEVKNHKFTARFFKQPTFCSHCTDFIWGFGKQGFQCQVCCFVVHKRCHEFVTFSCPGADKGPASDDPRSKHKFKIHTYSSPTFCDHCGSLLYGLIHQGMKCDTCMMNVHKRCVMNVPSLCGTDHTERRGRIYIQAHIDREVLIVVVRDAKNLVPMDPNGLSDPYVKLKLIPDPKSESKQKTKTIKCSLNPEWNETFRFQLKESDKDRRLSVEIWDWDLTSRNDFMGSLSFGISELQKAGVDGWFKLLSQEEGEYFNVPVPPEGSEGNEELRQKFERAKIGQGTKAPEEKTANTISKFDNNGNRDRMKLTDFNFLMVLGKGSFGKVMLSERKGTDELYAVKILKKDVVIQDDDVECTMVEKRVLALPGKPPFLTQLHSCFQTMDRLYFVMEYVNGGDLMYHIQQVGRFKEPHAVFYAAEIAIGLFFLQSKGIIYRDLKLDNVMLDSEGHIKIADFGMCKENIWDGVTTKTFCGTPDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQAPFEGEDEDELFQSIMEHNVAYPKSMSKEAVAICKGLMTKHPGKRLGCGPEGERDIKEHAFFRYIDWEKLERKEIQPPYKPKARDKRDTSNFDKEFTRQPVELTPTDKLFIMNLDQNEFAGFSYTNPEFVINV

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Acetylation	------MADPAAGPP ------CCCCCCCCC	31.34	-
11	Phosphorylation	PAAGPPPSEGEESTV CCCCCCCCCCCHHHH	65.10	27097102
16	Phosphorylation	PPSEGEESTVRFARK CCCCCCHHHHHHHHH	28.09	8327493
17	Phosphorylation	PSEGEESTVRFARKG CCCCCHHHHHHHHHH	20.98	8327493
38	Acetylation	VHEVKNHKFTARFFK HHHHHCCCEEHHHHC	54.53	22902405
48	Phosphorylation	ARFFKQPTFCSHCTD HHHHCCCCCCCHHHH	34.48	23984901
51	Phosphorylation	FKQPTFCSHCTDFIW HCCCCCCCHHHHCHH	19.87	23984901
54	Phosphorylation	PTFCSHCTDFIWGFG CCCCCHHHHCHHCCC	28.64	23984901
108	Phosphorylation	KHKFKIHTYSSPTFC CCEEEEEECCCCCCH	28.68	27097102
109	Phosphorylation	HKFKIHTYSSPTFCD CEEEEEECCCCCCHH	7.93	27097102
110	Phosphorylation	KFKIHTYSSPTFCDH EEEEEECCCCCCHHH	30.88	27097102
111	Phosphorylation	FKIHTYSSPTFCDHC EEEEECCCCCCHHHH	19.97	27097102
113	Phosphorylation	IHTYSSPTFCDHCGS EEECCCCCCHHHHHH	38.55	27097102
120	Phosphorylation	TFCDHCGSLLYGLIH CCHHHHHHHHHHHHH	22.16	27097102
123	Phosphorylation	DHCGSLLYGLIHQGM HHHHHHHHHHHHCCC	18.38	27097102
192	Phosphorylation	PMDPNGLSDPYVKLK CCCCCCCCCCCEEEE	37.63	-
195	Phosphorylation	PNGLSDPYVKLKLIP CCCCCCCCEEEEECC	18.40	-
205	Acetylation	LKLIPDPKSESKQKT EEECCCCCCCCCCCC	74.39	22902405
206	Phosphorylation	KLIPDPKSESKQKTK EECCCCCCCCCCCCC	53.11	25403869
241	Phosphorylation	SDKDRRLSVEIWDWD CCCCCCEEEEEEECC	18.85	-
250	Phosphorylation	EIWDWDLTSRNDFMG EEEECCCCCCCCHHH	24.14	-
279	Phosphorylation	DGWFKLLSQEEGEYF CHHHHHCCCCCCCCC	46.08	-
285	Phosphorylation	LSQEEGEYFNVPVPP CCCCCCCCCCCCCCC	16.00	-
295	Phosphorylation	VPVPPEGSEGNEELR CCCCCCCCCCCHHHH	40.44	-
314	Phosphorylation	RAKIGQGTKAPEEKT HHHCCCCCCCCCHHC	19.02	8327493
320	Ubiquitination	GTKAPEEKTANTISK CCCCCCHHCCCCHHC	51.80	-
324	Phosphorylation	PEEKTANTISKFDNN CCHHCCCCHHCCCCC	24.94	8327493
352	Phosphorylation	LMVLGKGSFGKVMLS EEEECCCCCCHHEEC	34.02	23984901
362	Ubiquitination	KVMLSERKGTDELYA HHEECCCCCCCCEEE	63.21	-
368	Phosphorylation	RKGTDELYAVKILKK CCCCCCEEEEEEECC	13.80	-
387	O-linked_Glycosylation	QDDDVECTMVEKRVL CCCCEEEEEEEEEEE	15.67	18295358
408	Phosphorylation	PFLTQLHSCFQTMDR CHHHHHHHHHHHHHH	25.81	-
412	Phosphorylation	QLHSCFQTMDRLYFV HHHHHHHHHHHHHHE	10.78	-
500	Phosphorylation	WDGVTTKTFCGTPDY CCCCCCCCCCCCCCC	23.28	23991683
504	Phosphorylation	TTKTFCGTPDYIAPE CCCCCCCCCCCCCCH	17.73	27097102
507	Phosphorylation	TFCGTPDYIAPEIIA CCCCCCCCCCCHHHC	10.53	27097102
515	Phosphorylation	IAPEIIAYQPYGKSV CCCHHHCCCCCCCCH	10.30	23991683
518	Phosphorylation	EIIAYQPYGKSVDWW HHHCCCCCCCCHHHH	22.97	-
628	Phosphorylation	ARDKRDTSNFDKEFT CCCCCCCCCCCHHHH	39.53	-
634 (in isoform 2)	Phosphorylation	-	9.33	-
635	Phosphorylation	SNFDKEFTRQPVELT CCCCHHHHCCCCEEC	29.50	8327493
641 (in isoform 2)	Phosphorylation	-	7.66	28689409
642	Phosphorylation	TRQPVELTPTDKLFI HCCCCEECCCCEEEE	15.61	8327493
644	Phosphorylation	QPVELTPTDKLFIMN CCCEECCCCEEEEEE	40.30	27097102
654 (in isoform 2)	Phosphorylation	-	55.29	27097102
660 (in isoform 2)	Phosphorylation	-	4.53	21738781
661	Phosphorylation	QNEFAGFSYTNPEFV CCCCCCCCCCCCCCE	30.08	8749392
662	Phosphorylation	NEFAGFSYTNPEFVI CCCCCCCCCCCCCEE	14.31	-
664 (in isoform 2)	Phosphorylation	-	26.35	27097102

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
16	S	Phosphorylation	Kinase	PRKCB	P68403	GPS
17	T	Phosphorylation	Kinase	PRKCB	P68403	GPS
314	T	Phosphorylation	Kinase	PRKCB	P68403	GPS
324	T	Phosphorylation	Kinase	PRKCB	P68403	GPS
500	T	Phosphorylation	Kinase	PDPK1	O55173	Uniprot
635	T	Phosphorylation	Kinase	PRKCB	P68403	GPS
642	T	Phosphorylation	Kinase	PRKCB	P68403	GPS
661	S	Phosphorylation	Kinase	PRKCB	P68403	GPS
662	Y	Phosphorylation	Kinase	SYK	Q64725	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
500	T	Phosphorylation	8749392
Phosphorylation on Thr-500 of isoform beta-I, within the activation loop, renders it competent to autophosphorylate.
500	T	Phosphorylation	8749392
Similarly, isoform beta-II is autophosphorylated on 'Thr-641' and 'Ser-660', subsequent to phosphorylation on Thr-500.
641	T	Phosphorylation	22673903
Similarly, isoform beta-II is autophosphorylated on 'Thr-641' and 'Ser-660', subsequent to phosphorylation on Thr-500.
642	T	Phosphorylation	8749392
Subsequent autophosphorylation of Thr-642 maintains catalytic competence, and autophosphorylation on Ser-661 appears to release the kinase into the cytosol.
660	S	Phosphorylation	22673903
Similarly, isoform beta-II is autophosphorylated on 'Thr-641' and 'Ser-660', subsequent to phosphorylation on Thr-500.
661	S	Phosphorylation	8749392
Subsequent autophosphorylation of Thr-642 maintains catalytic competence, and autophosphorylation on Ser-661 appears to release the kinase into the cytosol.

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 KPCB_RAT !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
HMGB1_RAT	Hmgb1	physical	10617144
HOIL1_RAT	Rbck1	physical	9514928
H11_RAT	Hist1h1a	physical	11118818
STXB1_RAT	Stxbp1	physical	8631738
PEBP1_RAT	Pebp1	physical	12551925
CD5_HUMAN	CD5	physical	11123317
CXA1_RAT	Gja1	physical	10871288
NMDE2_MOUSE	Grin2b	physical	11306676
ANXA7_HUMAN	ANXA7	physical	11278415
BCL2_MOUSE	Bcl2	physical	7929424

Drug and Disease Associations

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

Regulatory Network of KPCB_RAT

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Crystal structure and allosteric activation of protein kinase CbetaII."; Leonard T.A., Rozycki B., Saidi L.F., Hummer G., Hurley J.H.; Cell 144:55-66(2011). Cited for: X-RAY CRYSTALLOGRAPHY (4.00 ANGSTROMS) OF 1-661 IN COMPLEX WITHCALCIUM IONS, AND PHOSPHORYLATION AT THR-500; THR-642 AND SER-661.	21215369 [Abstract]
"Characterization of site-specific mutants altered at protein kinase Cbeta 1 isozyme autophosphorylation sites."; Zhang J., Wang L., Petrin J., Bishop W.R., Bond R.W.; Proc. Natl. Acad. Sci. U.S.A. 90:6130-6134(1993). Cited for: PHOSPHORYLATION AT SER-16; THR-17; THR-314; THR-324; THR-635 ANDTHR-642, AND MUTAGENESIS OF 16-SER-THR-17; THR-314; THR-324; THR-635AND THR-642.	8327493 [Abstract]
"Protein kinase C is regulated in vivo by three functionally distinctphosphorylations."; Keranen L.M., Dutil E.M., Newton A.C.; Curr. Biol. 5:1394-1403(1995). Cited for: PROTEIN SEQUENCE OF 500-520 AND 636-663 (ISOFORM BETA-II), ANDPHOSPHORYLATION AT THR-500; THR-642 AND SER-661.	8749392 [Abstract]
"Phosphorylation of Thr642 is an early event in the processing ofnewly synthesized protein kinase C beta 1 and is essential for itsactivation."; Zhang J., Wang L., Schwartz J., Bond R.W., Bishop W.R.; J. Biol. Chem. 269:19578-19584(1994). Cited for: PHOSPHORYLATION AT THR-642 (ISOFORM BETA-I), AND MUTAGENESIS OFTHR-635 AND THR-642.	8034726 [Abstract]

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