dbPTM

KPCB_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	KPCB_HUMAN
UniProt AC	P05771
Protein Name	Protein kinase C beta type
Gene Name	PRKCB
Organism	Homo sapiens (Human).
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	MADPAAGPPPSEGEESTVRFARKGALRQKNVHEVKNHKFTARFFKQPTFCSHCTDFIWGFGKQGFQCQVCCFVVHKRCHEFVTFSCPGADKGPASDDPRSKHKFKIHTYSSPTFCDHCGSLLYGLIHQGMKCDTCMMNVHKRCVMNVPSLCGTDHTERRGRIYIQAHIDRDVLIVLVRDAKNLVPMDPNGLSDPYVKLKLIPDPKSESKQKTKTIKCSLNPEWNETFRFQLKESDKDRRLSVEIWDWDLTSRNDFMGSLSFGISELQKASVDGWFKLLSQEEGEYFNVPVPPEGSEANEELRQKFERAKISQGTKVPEEKTTNTVSKFDNNGNRDRMKLTDFNFLMVLGKGSFGKVMLSERKGTDELYAVKILKKDVVIQDDDVECTMVEKRVLALPGKPPFLTQLHSCFQTMDRLYFVMEYVNGGDLMYHIQQVGRFKEPHAVFYAAEIAIGLFFLQSKGIIYRDLKLDNVMLDSEGHIKIADFGMCKENIWDGVTTKTFCGTPDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQAPFEGEDEDELFQSIMEHNVAYPKSMSKEAVAICKGLMTKHPGKRLGCGPEGERDIKEHAFFRYIDWEKLERKEIQPPYKPKARDKRDTSNFDKEFTRQPVELTPTDKLFIMNLDQNEFAGFSYTNPEFVINV

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Acetylation	------MADPAAGPP ------CCCCCCCCC	31.34	12665801
11	Phosphorylation	PAAGPPPSEGEESTV CCCCCCCCCCCHHHH	65.10	23401153
16	Phosphorylation	PPSEGEESTVRFARK CCCCCCHHHHHHHHH	28.09	8327493
17	Phosphorylation	PSEGEESTVRFARKG CCCCCHHHHHHHHHH	20.98	30108239
23	Ubiquitination	STVRFARKGALRQKN HHHHHHHHHHHHCCC	45.14	29967540
29	Ubiquitination	RKGALRQKNVHEVKN HHHHHHCCCHHHHHC	55.28	24816145
40	Phosphorylation	EVKNHKFTARFFKQP HHHCCCEEHHHHCCC	23.02	27080861
48	Phosphorylation	ARFFKQPTFCSHCTD HHHHCCCCCCCHHHH	34.48	30108239
51	Phosphorylation	FKQPTFCSHCTDFIW HCCCCCCCHHHHCHH	19.87	30108239
54	Phosphorylation	PTFCSHCTDFIWGFG CCCCCHHHHCHHCCC	28.64	28450419
76	Ubiquitination	VCCFVVHKRCHEFVT EEEEEEECCCCEEEE	45.14	-
76	Acetylation	VCCFVVHKRCHEFVT EEEEEEECCCCEEEE	45.14	25953088
83	Phosphorylation	KRCHEFVTFSCPGAD CCCCEEEEEECCCCC	18.36	27080861
91	Ubiquitination	FSCPGADKGPASDDP EECCCCCCCCCCCCC	67.28	29967540
108	Phosphorylation	KHKFKIHTYSSPTFC CCEEEEEECCCCCCH	28.68	27080861
109	Phosphorylation	HKFKIHTYSSPTFCD CEEEEEECCCCCCHH	7.93	27080861
110	Phosphorylation	KFKIHTYSSPTFCDH EEEEEECCCCCCHHH	30.88	27080861
111	Phosphorylation	FKIHTYSSPTFCDHC EEEEECCCCCCHHHH	19.97	27080861
113	Phosphorylation	IHTYSSPTFCDHCGS EEECCCCCCHHHHHH	38.55	27080861
120	Phosphorylation	TFCDHCGSLLYGLIH CCHHHHHHHHHHHHH	22.16	30108239
123	Phosphorylation	DHCGSLLYGLIHQGM HHHHHHHHHHHHCCC	18.38	30108239
134	Phosphorylation	HQGMKCDTCMMNVHK HCCCCCCCCCCCCHH	16.27	28857561
141 (in isoform 2)	Ubiquitination	-	43.12	-
141	Ubiquitination	TCMMNVHKRCVMNVP CCCCCCHHHHHHCCC	43.12	30230243
149	Phosphorylation	RCVMNVPSLCGTDHT HHHHCCCHHCCCCCC	31.82	30108239
153	Phosphorylation	NVPSLCGTDHTERRG CCCHHCCCCCCCCCC	24.50	27080861
181	Ubiquitination	IVLVRDAKNLVPMDP EEEEECHHHCCCCCC	55.92	30230243
195	Phosphorylation	PNGLSDPYVKLKLIP CCCCCCCCEEEEECC	18.40	19060867
197	Ubiquitination	GLSDPYVKLKLIPDP CCCCCCEEEEECCCC	33.78	32015554
197 (in isoform 2)	Ubiquitination	-	33.78	-
197	Acetylation	GLSDPYVKLKLIPDP CCCCCCEEEEECCCC	33.78	25953088
199 (in isoform 2)	Ubiquitination	-	38.36	-
199	Acetylation	SDPYVKLKLIPDPKS CCCCEEEEECCCCCC	38.36	25953088
199	Ubiquitination	SDPYVKLKLIPDPKS CCCCEEEEECCCCCC	38.36	29967540
206	Phosphorylation	KLIPDPKSESKQKTK EECCCCCCCCCCCCC	53.11	25307156
208	Phosphorylation	IPDPKSESKQKTKTI CCCCCCCCCCCCCEE	47.69	28060719
216	Ubiquitination	KQKTKTIKCSLNPEW CCCCCEEEEECCCCC	24.01	29967540
216	Acetylation	KQKTKTIKCSLNPEW CCCCCEEEEECCCCC	24.01	25953088
226	Phosphorylation	LNPEWNETFRFQLKE CCCCCCCEEEEEECC	19.52	30108239
232	Ubiquitination	ETFRFQLKESDKDRR CEEEEEECCCCCCCC	44.37	24816145
234	Phosphorylation	FRFQLKESDKDRRLS EEEEECCCCCCCCEE	48.66	27067055
236	Ubiquitination	FQLKESDKDRRLSVE EEECCCCCCCCEEEE	63.51	24816145
241	Phosphorylation	SDKDRRLSVEIWDWD CCCCCCEEEEEEECC	18.85	-
250	Phosphorylation	EIWDWDLTSRNDFMG EEEECCCCCCCCHHC	24.14	21082442
311	Phosphorylation	KFERAKISQGTKVPE HHHHHHHCCCCCCCC	23.11	29978859
314	Phosphorylation	RAKISQGTKVPEEKT HHHHCCCCCCCCHHC	22.64	23401153
315	Ubiquitination	AKISQGTKVPEEKTT HHHCCCCCCCCHHCC	63.72	-
320	Ubiquitination	GTKVPEEKTTNTVSK CCCCCCHHCCCCCCC	60.01	25015289
321	Phosphorylation	TKVPEEKTTNTVSKF CCCCCHHCCCCCCCC	28.67	23403867
322	Phosphorylation	KVPEEKTTNTVSKFD CCCCHHCCCCCCCCC	39.70	23403867
324	Phosphorylation	PEEKTTNTVSKFDNN CCHHCCCCCCCCCCC	24.86	23403867
326	Phosphorylation	EKTTNTVSKFDNNGN HHCCCCCCCCCCCCC	26.10	23403867
327	Ubiquitination	KTTNTVSKFDNNGNR HCCCCCCCCCCCCCC	53.02	24816145
350	Ubiquitination	NFLMVLGKGSFGKVM CEEEEECCCCCCHHE	47.42	-
352	Phosphorylation	LMVLGKGSFGKVMLS EEEECCCCCCHHEEC	34.02	28348404
362 (in isoform 2)	Ubiquitination	-	63.21	-
362	Ubiquitination	KVMLSERKGTDELYA HHEECCCCCCCCEEE	63.21	30230243
364	Phosphorylation	MLSERKGTDELYAVK EECCCCCCCCEEEEE	29.36	-
368	Phosphorylation	RKGTDELYAVKILKK CCCCCCEEEEEEECC	13.80	-
391	Ubiquitination	VECTMVEKRVLALPG EEEEEEEEEEECCCC	36.07	29901268
408	Phosphorylation	PFLTQLHSCFQTMDR CHHHHHHHHHHHHHH	25.81	25921289
412	Phosphorylation	QLHSCFQTMDRLYFV HHHHHHHHHHHHHHE	10.78	25921289
430	Phosphorylation	VNGGDLMYHIQQVGR CCCCCHHHEEEECCC	11.76	25921289
468	Ubiquitination	GIIYRDLKLDNVMLD CEEEEEEEECCEEEC	59.07	-
473	Sulfoxidation	DLKLDNVMLDSEGHI EEEECCEEECCCCCE	4.28	21406390
476	Phosphorylation	LDNVMLDSEGHIKIA ECCEEECCCCCEEEC	41.33	-
481	Ubiquitination	LDSEGHIKIADFGMC ECCCCCEEECCCCCC	26.60	-
487	Sulfoxidation	IKIADFGMCKENIWD EEECCCCCCCCCCCC	2.73	21406390
489 (in isoform 2)	Ubiquitination	-	44.92	-
489	Ubiquitination	IADFGMCKENIWDGV ECCCCCCCCCCCCCC	44.92	30230243
497	Phosphorylation	ENIWDGVTTKTFCGT CCCCCCCCCCCCCCC	28.27	28464451
498	Phosphorylation	NIWDGVTTKTFCGTP CCCCCCCCCCCCCCC	26.19	22322096
499	Ubiquitination	IWDGVTTKTFCGTPD CCCCCCCCCCCCCCC	30.18	30230243
500	Phosphorylation	WDGVTTKTFCGTPDY CCCCCCCCCCCCCCC	23.28	22322096
504	Phosphorylation	TTKTFCGTPDYIAPE CCCCCCCCCCCCCCH	17.73	22167270
507	Phosphorylation	TFCGTPDYIAPEIIA CCCCCCCCCCCHHHC	10.53	30631047
515	Phosphorylation	IAPEIIAYQPYGKSV CCCHHHCCCCCCCCH	10.30	23663014
518	Phosphorylation	EIIAYQPYGKSVDWW HHHCCCCCCCCHHHH	22.97	23403867
563	Phosphorylation	HNVAYPKSMSKEAVA CCCCCCCCCCHHHHH	24.63	23898821
565	Phosphorylation	VAYPKSMSKEAVAIC CCCCCCCCHHHHHHH	34.14	23898821
566	Ubiquitination	AYPKSMSKEAVAICK CCCCCCCHHHHHHHH	40.84	29967540
573	Acetylation	KEAVAICKGLMTKHP HHHHHHHHHHHHCCC	49.30	25953088
595	Ubiquitination	PEGERDIKEHAFFRY CCCCCCHHHHHHHEE	47.97	29967540
611	Ubiquitination	DWEKLERKEIQPPYK CHHHHHHCCCCCCCC	50.20	30230243
620	Ubiquitination	IQPPYKPKARDKRDT CCCCCCCCCCCCCCC	52.48	29967540
632	Ubiquitination	RDTSNFDKEFTRQPV CCCCCCCHHHHCCCC	51.06	30230243
634 (in isoform 2)	Phosphorylation	-	9.33	28634298
635	Phosphorylation	SNFDKEFTRQPVELT CCCCHHHHCCCCEEC	29.50	8327493
641 (in isoform 2)	Phosphorylation	-	7.66	24670416
642	Phosphorylation	TRQPVELTPTDKLFI HCCCCEECCCCEEEE	15.61	23401153
644	Phosphorylation	QPVELTPTDKLFIMN CCCEECCCCEEEEEE	40.30	23898821
654 (in isoform 2)	Phosphorylation	-	55.29	26657352
660 (in isoform 2)	Phosphorylation	-	4.53	26307563
661	Phosphorylation	QNEFAGFSYTNPEFV CCCCCCCCCCCCCCE	30.08	17504762
662	Phosphorylation	NEFAGFSYTNPEFVI CCCCCCCCCCCCCEE	14.31	-
664 (in isoform 2)	Phosphorylation	-	26.35	26657352
668	Ubiquitination	SYTNPEFVINV---- CCCCCCCEEEC----	2.72	29967540
672	Ubiquitination	PEFVINV-------- CCCEEEC--------		30230243
673 (in isoform 2)	Phosphorylation	-		-

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
500	T	Phosphorylation	Kinase	BLVRA	P53004	GPS
500	T	Phosphorylation	Kinase	PDPK1	O15530	Uniprot
660	S	Phosphorylation	Kinase	PRKCB	P05771	GPS
660	S	Phosphorylation	Kinase	PKCB ISO2	P05771-2	PSP
662	Y	Phosphorylation	Kinase	SYK	P43405	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	RNF31	Q96EP0	PMID:17069764
-	K	Ubiquitination	E3 ubiquitin ligase	TRIM41	Q8WV44	PMID:17893151

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
500	T	Phosphorylation	17115692
Phosphorylation on Thr-500 within the activation loop renders it competent to autophosphorylate.
642	T	Phosphorylation	23186163
Subsequent autophosphorylation of Thr-642 maintains catalytic competence, and autophosphorylation on Ser-661 appears to release the kinase into the cytosol.
661	S	Phosphorylation	17115692
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_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
GRP3_HUMAN	RASGRP3	physical	15213298
RACK1_HUMAN	GNB2L1	physical	10480917
1433G_HUMAN	YWHAG	physical	10433554
GNA12_HUMAN	GNA12	physical	8824244
GNA13_HUMAN	GNA13	physical	8824244
RGS2_HUMAN	RGS2	physical	11063746
TIAM1_HUMAN	TIAM1	physical	10212259
PDLI5_HUMAN	PDLIM5	physical	8940095
LMNB1_HUMAN	LMNB1	physical	11901153
CDK1_HUMAN	CDK1	physical	11901153
HOIL1_HUMAN	RBCK1	physical	18303026
HSP74_HUMAN	HSPA4	physical	16954220
H31_HUMAN	HIST1H3A	physical	20228790
KPCB_HUMAN	PRKCB	physical	19920073
DDX58_HUMAN	DDX58	physical	22114345
TRI41_HUMAN	TRIM41	physical	17893151
EGFR_HUMAN	EGFR	physical	9815893
HOIL1_HUMAN	RBCK1	physical	17121852
RNF31_HUMAN	RNF31	physical	17069764
HOIL1_HUMAN	RBCK1	physical	17069764
IBTK_HUMAN	IBTK	physical	21482705
TOP2A_HUMAN	TOP2A	physical	7499337
NCF1_HUMAN	NCF1	physical	12056906
H11_HUMAN	HIST1H1A	physical	12056906
LSP1_HUMAN	LSP1	physical	15090600
LMNB1_HUMAN	LMNB1	physical	8034666
KPCB_HUMAN	PRKCB	physical	8034666
H10_HUMAN	H1F0	physical	8034666
CAR11_HUMAN	CARD11	physical	16356855
MARCS_MOUSE	Marcks	physical	7588787
SDC2_HUMAN	SDC2	physical	9244383
GRP3_HUMAN	RASGRP3	physical	12730099
ITB2_HUMAN	ITGB2	physical	11700305
KPCB_HUMAN	PRKCB	physical	8749392
GSK3A_HUMAN	GSK3A	physical	11884598
CASR_HUMAN	CASR	physical	9694886
RB_HUMAN	RB1	physical	11805327
SYT6_HUMAN	SYT6	physical	16111671
KPCB_HUMAN	PRKCB	physical	16111671
H15_HUMAN	HIST1H1B	physical	8663071
MARCS_HUMAN	MARCKS	physical	8557118
NUMB_HUMAN	NUMB	physical	17203073
RACK1_HUMAN	GNB2L1	physical	24681954
MBP_HUMAN	MBP	physical	24681954
EP300_HUMAN	EP300	physical	11020388
SHCBP_HUMAN	SHCBP1	physical	25852190
DAB2_HUMAN	DAB2	physical	10542228
IKKB_HUMAN	IKBKB	physical	25241761
IKKA_HUMAN	CHUK	physical	25241761
GSK3B_HUMAN	GSK3B	physical	25241761
ARRB2_HUMAN	ARRB2	physical	26545496
AKT1_HUMAN	AKT1	physical	19605547

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
D04014	Enzastaurin hydrochloride (JAN/USAN)
DrugBank
DB00675	Tamoxifen
DB00163	Vitamin E

Regulatory Network of KPCB_HUMAN

Related Literatures of Post-Translational Modification

Acetylation
Reference	PubMed
"Exploring proteomes and analyzing protein processing by massspectrometric identification of sorted N-terminal peptides."; Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,Thomas G.R., Vandekerckhove J.; Nat. Biotechnol. 21:566-569(2003). Cited for: PROTEIN SEQUENCE OF 2-19, AND ACETYLATION AT ALA-2.	12665801 [Abstract]
Phosphorylation
Reference	PubMed
"Structure of the catalytic domain of human protein kinase C beta IIcomplexed with a bisindolylmaleimide inhibitor."; Grodsky N., Li Y., Bouzida D., Love R., Jensen J., Nodes B.,Nonomiya J., Grant S.; Biochemistry 45:13970-13981(2006). Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 321-660 IN COMPLEX WITHINHIBITOR, AND PHOSPHORYLATION AT THR-500; THR-642 AND SER-661.	17115692 [Abstract]
"Large-scale proteomics analysis of the human kinome."; Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.; Mol. Cell. Proteomics 8:1751-1764(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-500 AND THR-504,PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-641 AND SER-660 (ISOFORMBETA-II), AND MASS SPECTROMETRY.	19369195 [Abstract]
"Phosphoproteome of resting human platelets."; Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,Schuetz C., Walter U., Gambaryan S., Sickmann A.; J. Proteome Res. 7:526-534(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-642, AND MASSSPECTROMETRY.	18088087 [Abstract]
"Proteomics analysis of protein kinases by target class-selectiveprefractionation and tandem mass spectrometry."; Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R.,Keri G., Wehland J., Daub H.; Mol. Cell. Proteomics 6:537-547(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-500 AND THR-504, ANDMASS SPECTROMETRY.	17192257 [Abstract]

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