Overview
| Uniprot ID | P05771 |
|---|
| Protein Name | Protein kinase C beta type |
|---|
| Gene Name | PRKCB |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 199 |
SDPYVKLKLIPDPKS |
| 315 |
AKISQGTKVPEEKTT |
| 327 |
KTTNTVSKFDNNGNR |
Function
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 (PubMed:11598012). 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 (AR)-dependent transcription, by being recruited to AR 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 (PubMed:20228790). In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. Participates in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Phosphorylates SLC2A1/GLUT1, promoting glucose uptake by SLC2A1/GLUT1 (PubMed:25982116). 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 (PubMed:19176525). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (PubMed:25313067). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231)
Protein Sequence
10
MADPAAGPPP
20
SEGEESTVRF
30
ARKGALRQKN
40
VHEVKNHKFT
50
ARFFKQPTFC
60
SHCTDFIWGF
70
GKQGFQCQVC
80
CFVVHKRCHE
90
FVTFSCPGAD
100
KGPASDDPRS
110
KHKFKIHTYS
120
SPTFCDHCGS
130
LLYGLIHQGM
140
KCDTCMMNVH
150
KRCVMNVPSL
160
CGTDHTERRG
170
RIYIQAHIDR
180
DVLIVLVRDA
190
KNLVPMDPNG
200
LSDPYVKLKL
210
IPDPKSESKQ
220
KTKTIKCSLN
230
PEWNETFRFQ
240
LKESDKDRRL
250
SVEIWDWDLT
260
SRNDFMGSLS
270
FGISELQKAS
280
VDGWFKLLSQ
290
EEGEYFNVPV
300
PPEGSEANEE
310
LRQKFERAKI
320
SQGTKVPEEK
330
TTNTVSKFDN
340
NGNRDRMKLT
350
DFNFLMVLGK
360
GSFGKVMLSE
370
RKGTDELYAV
380
KILKKDVVIQ
390
DDDVECTMVE
400
KRVLALPGKP
410
PFLTQLHSCF
420
QTMDRLYFVM
430
EYVNGGDLMY
440
HIQQVGRFKE
450
PHAVFYAAEI
460
AIGLFFLQSK
470
GIIYRDLKLD
480
NVMLDSEGHI
490
KIADFGMCKE
500
NIWDGVTTKT
510
FCGTPDYIAP
520
EIIAYQPYGK
530
SVDWWAFGVL
540
LYEMLAGQAP
550
FEGEDEDELF
560
QSIMEHNVAY
570
PKSMSKEAVA
580
ICKGLMTKHP
590
GKRLGCGPEG
600
ERDIKEHAFF
610
RYIDWEKLER
620
KEIQPPYKPK
630
ARDKRDTSNF
640
DKEFTRQPVE
650
LTPTDKLFIM
660
NLDQNEFAGF
670
SYTNPEFVIN
V
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0044305 |
calyx of Held |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0070062 |
extracellular exosome |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:0005886 |
plasma membrane |
| Cellular Component |
GO:0099523 |
presynaptic cytosol |
| Cellular Component |
GO:0008091 |
spectrin |
| Molecular Function |
GO:0005524 |
ATP binding |
| Molecular Function |
GO:0005246 |
calcium channel regulator activity |
| Molecular Function |
GO:0004698 |
calcium,diacylglycerol-dependent serine/threonine kinase activity |
| Molecular Function |
GO:0003682 |
chromatin binding |
| Molecular Function |
GO:0004697 |
diacylglycerol-dependent serine/threonine kinase activity |
| Molecular Function |
GO:0042393 |
histone binding |
| Molecular Function |
GO:0035403 |
histone H3T6 kinase activity |
| Molecular Function |
GO:0050681 |
nuclear androgen receptor binding |
| Molecular Function |
GO:0005080 |
protein kinase C binding |
| Molecular Function |
GO:0106310 |
protein serine kinase activity |
| Molecular Function |
GO:0004674 |
protein serine/threonine kinase activity |
| Molecular Function |
GO:0003713 |
transcription coactivator activity |
| Molecular Function |
GO:0008270 |
zinc ion binding |
| Biological Process |
GO:0002250 |
adaptive immune response |
| Biological Process |
GO:0006915 |
apoptotic process |
| Biological Process |
GO:0042113 |
B cell activation |
| Biological Process |
GO:0050853 |
B cell receptor signaling pathway |
| Biological Process |
GO:0006351 |
DNA-templated transcription |
| Biological Process |
GO:0035556 |
intracellular signal transduction |
| Biological Process |
GO:0042953 |
lipoprotein transport |
| Biological Process |
GO:0007077 |
mitotic nuclear membrane disassembly |
| Biological Process |
GO:0010829 |
negative regulation of D-glucose transmembrane transport |
| Biological Process |
GO:0046627 |
negative regulation of insulin receptor signaling pathway |
| Biological Process |
GO:0007207 |
phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway |
| Biological Process |
GO:0045766 |
positive regulation of angiogenesis |
| Biological Process |
GO:0043123 |
positive regulation of canonical NF-kappaB signal transduction |
| Biological Process |
GO:0160020 |
positive regulation of ferroptosis |
| Biological Process |
GO:0030949 |
positive regulation of vascular endothelial growth factor receptor signaling pathway |
| Biological Process |
GO:0070528 |
protein kinase C signaling |
| Biological Process |
GO:0006468 |
protein phosphorylation |
| Biological Process |
GO:0010827 |
regulation of D-glucose transmembrane transport |
| Biological Process |
GO:2000300 |
regulation of synaptic vesicle exocytosis |
| Biological Process |
GO:0006357 |
regulation of transcription by RNA polymerase II |
| Biological Process |
GO:0007165 |
signal transduction |
Reference
[1] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.