dbPTM

KPCB_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	KPCB_MOUSE
UniProt AC	P68404
Protein Name	Protein kinase C beta type
Gene Name	Prkcb
Organism	Mus musculus (Mouse).
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. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription (By similarity)..
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	22817900
16	Phosphorylation	PPSEGEESTVRFARK CCCCCCHHHHHHHHH	28.09	-
17	Phosphorylation	PSEGEESTVRFARKG CCCCCHHHHHHHHHH	20.98	-
48	Phosphorylation	ARFFKQPTFCSHCTD HHHHCCCCCCCHHHH	34.48	-
50	S-palmitoylation	FFKQPTFCSHCTDFI HHCCCCCCCHHHHCH	2.74	28680068
68	Ubiquitination	GKQGFQCQVCCFVVH CCCCCEECEEEEEEE	22.09	27667366
70	Ubiquitination	QGFQCQVCCFVVHKR CCCEECEEEEEEECC	0.39	27667366
86	S-palmitoylation	HEFVTFSCPGADKGP CEEEEEECCCCCCCC	2.92	28680068
103	Ubiquitination	DDPRSKHKFKIHTYS CCCCCCCEEEEEECC	52.68	27667366
186	Ubiquitination	DAKNLVPMDPNGLSD CHHHCCCCCCCCCCC	11.88	27667366
195	Phosphorylation	PNGLSDPYVKLKLIP CCCCCCCCEEEEECC	18.40	25521595
197 (in isoform 2)	Ubiquitination	-	33.78	22790023
197	Ubiquitination	GLSDPYVKLKLIPDP CCCCCCEEEEECCCC	33.78	22790023
198	Ubiquitination	LSDPYVKLKLIPDPK CCCCCEEEEECCCCC	3.78	27667366
199 (in isoform 2)	Ubiquitination	-	38.36	22790023
199	Ubiquitination	SDPYVKLKLIPDPKS CCCCEEEEECCCCCC	38.36	22790023
205 (in isoform 2)	Ubiquitination	-	74.39	22790023
205	Ubiquitination	LKLIPDPKSESKQKT EEECCCCCCCCCCCC	74.39	22790023
206	Phosphorylation	KLIPDPKSESKQKTK EECCCCCCCCCCCCC	53.11	25521595
208	Phosphorylation	IPDPKSESKQKTKTI CCCCCCCCCCCCCEE	47.69	29899451
212	Phosphorylation	KSESKQKTKTIKCSL CCCCCCCCCEEEEEC	30.81	28059163
216 (in isoform 2)	Ubiquitination	-	24.01	22790023
216	Ubiquitination	KQKTKTIKCSLNPEW CCCCCEEEEECCCCC	24.01	22790023
217	S-nitrosocysteine	QKTKTIKCSLNPEWN CCCCEEEEECCCCCC	5.03	-
217	S-nitrosylation	QKTKTIKCSLNPEWN CCCCEEEEECCCCCC	5.03	24895380
232	Ubiquitination	ETFRFQLKESDKDRR CEEEEEECCCCCCCC	44.37	27667366
233	Ubiquitination	TFRFQLKESDKDRRL EEEEEECCCCCCCCE	73.15	27667366
242	Ubiquitination	DKDRRLSVEIWDWDL CCCCCEEEEEEECCC	7.97	27667366
250	Phosphorylation	EIWDWDLTSRNDFMG EEEECCCCCCCCHHH	24.14	-
279	Phosphorylation	DGWFKLLSQEEGEYF CHHHHHCCCCCCCCC	46.08	-
304	Ubiquitination	GNEELRQKFERAKIG CCHHHHHHHHHHHCC	42.64	22790023
304 (in isoform 2)	Ubiquitination	-	42.64	22790023
314	Phosphorylation	RAKIGQGTKAPEEKT HHHCCCCCCCCCHHC	19.02	-
315	Ubiquitination	AKIGQGTKAPEEKTA HHCCCCCCCCCHHCC	69.62	27667366
320	Ubiquitination	GTKAPEEKTANTISK CCCCCCHHCCCCHHC	51.80	22790023
320 (in isoform 2)	Ubiquitination	-	51.80	22790023
324	Phosphorylation	PEEKTANTISKFDNN CCHHCCCCHHCCCCC	24.94	-
327	Ubiquitination	KTANTISKFDNNGNR HCCCCHHCCCCCCCC	53.54	27667366
362 (in isoform 2)	Ubiquitination	-	63.21	22790023
362	Ubiquitination	KVMLSERKGTDELYA HHEECCCCCCCCEEE	63.21	22790023
371	Ubiquitination	TDELYAVKILKKDVV CCCEEEEEEECCCEE	33.86	27667366
449	Ubiquitination	HAVFYAAEIAIGLFF HHHHHHHHHHHHHHH	25.45	27667366
459	Phosphorylation	IGLFFLQSKGIIYRD HHHHHHHCCCEEEEE	34.69	-
465	Methylation	QSKGIIYRDLKLDNV HCCCEEEEEEEECCE	32.17	30988843
497	Phosphorylation	ENIWDGVTTKTFCGT CCCCCCCCCCCCCCC	28.27	20415495
498	Phosphorylation	NIWDGVTTKTFCGTP CCCCCCCCCCCCCCC	26.19	20415495
500	Phosphorylation	WDGVTTKTFCGTPDY CCCCCCCCCCCCCCC	23.28	24925903
504	Phosphorylation	TTKTFCGTPDYIAPE CCCCCCCCCCCCCCH	17.73	24925903
507	Phosphorylation	TFCGTPDYIAPEIIA CCCCCCCCCCCHHHC	10.53	25619855
515	Phosphorylation	IAPEIIAYQPYGKSV CCCHHHCCCCCCCCH	10.30	25619855
518	Phosphorylation	EIIAYQPYGKSVDWW HHHCCCCCCCCHHHH	22.97	20415495
578	Ubiquitination	ICKGLMTKHPGKRLG HHHHHHHCCCCCCCC	33.56	27667366
618	Ubiquitination	KEIQPPYKPKARDKR CCCCCCCCCCCCCCC	45.90	27667366
634 (in isoform 2)	Phosphorylation	-	9.33	29899451
635	Phosphorylation	SNFDKEFTRQPVELT CCCCHHHHCCCCEEC	29.50	22324799
641	Phosphorylation	FTRQPVELTPTDKLF HHCCCCEECCCCEEE	7.66	17114649
641 (in isoform 2)	Phosphorylation	-	7.66	25521595
642	Phosphorylation	TRQPVELTPTDKLFI HCCCCEECCCCEEEE	15.61	25521595
644	Phosphorylation	QPVELTPTDKLFIMN CCCEECCCCEEEEEE	40.30	25521595
654 (in isoform 2)	Phosphorylation	-	55.29	22324799
660 (in isoform 2)	Phosphorylation	-	4.53	25521595
661	Phosphorylation	QNEFAGFSYTNPEFV CCCCCCCCCCCCCCE	30.08	-
662	Phosphorylation	NEFAGFSYTNPEFVI CCCCCCCCCCCCCEE	14.31	12881490
664 (in isoform 2)	Phosphorylation	-	26.35	24453211
673 (in isoform 2)	Phosphorylation	-		21183079

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	PRKCA	P20444	GPS
500	T	Phosphorylation	Kinase	PRKCB	P68404	GPS
500	T	Phosphorylation	Kinase	PDPK1	Q9Z2A0	Uniprot
660	S	Phosphorylation	Kinase	PRKCB	P68404	GPS
661	S	Phosphorylation	Kinase	PRKCB	P68404	GPS
662	Y	Phosphorylation	Kinase	SYK	P48025	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
500	T	Phosphorylation	12881490
Phosphorylation on Thr-500 within the activation loop renders it competent to autophosphorylate.
642	T	Phosphorylation	12881490
Subsequent autophosphorylation of Thr-642 maintains catalytic competence, and autophosphorylation on Ser-661 appears to release the kinase into the cytosol.
661	S	Phosphorylation	12881490
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_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
NEUM_RAT	Gap43	physical	8694767
RB_MOUSE	Rb1	physical	11805327
USP9X_MOUSE	Usp9x	physical	26936881

Drug and Disease Associations

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

Regulatory Network of KPCB_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Large-scale identification and evolution indexing of tyrosinephosphorylation sites from murine brain."; Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.; J. Proteome Res. 7:311-318(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-195, AND MASSSPECTROMETRY.	18034455 [Abstract]
"A Ras activation pathway dependent on Syk phosphorylation of proteinkinase C."; Kawakami Y., Kitaura J., Yao L., McHenry R.W., Kawakami Y.,Newton A.C., Kang S., Kato R.M., Leitges M., Rawlings D.J.,Kawakami T.; Proc. Natl. Acad. Sci. U.S.A. 100:9470-9475(2003). Cited for: PHOSPHORYLATION AT TYR-662.	12881490 [Abstract]

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