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Protein

Protein kinase C beta type

Gene

Prkcb

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).By similarity9 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Ca2+By similarityNote: Binds 3 Ca2+ ions per subunit. The ions are bound to the C2 domain.By similarity

Enzyme regulationi

Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-500 (activation loop of the kinase domain), Thr-642 (turn motif) and Ser-661 (hydrophobic region), need to be phosphorylated for its full activation. Specifically inhibited by enzastaurin (LY317615) (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi186Calcium 1; via carbonyl oxygenBy similarity1
Metal bindingi187Calcium 1By similarity1
Metal bindingi187Calcium 2By similarity1
Metal bindingi193Calcium 2By similarity1
Metal bindingi246Calcium 1By similarity1
Metal bindingi246Calcium 2By similarity1
Metal bindingi247Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi248Calcium 1By similarity1
Metal bindingi248Calcium 2By similarity1
Metal bindingi248Calcium 3By similarity1
Metal bindingi251Calcium 3By similarity1
Metal bindingi252Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi254Calcium 1By similarity1
Metal bindingi254Calcium 3By similarity1
Binding sitei371ATPPROSITE-ProRule annotation1
Active sitei466Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri36 – 86Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST51
Zinc fingeri101 – 151Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST51
Nucleotide bindingi348 – 356ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • apoptotic process Source: UniProtKB-KW
  • B cell activation Source: UniProtKB
  • B cell receptor signaling pathway Source: UniProtKB
  • calcium ion transport Source: MGI
  • cellular calcium ion homeostasis Source: MGI
  • cellular response to carbohydrate stimulus Source: MGI
  • histone H3-T6 phosphorylation Source: UniProtKB
  • intracellular signal transduction Source: InterPro
  • negative regulation of glucose transmembrane transport Source: UniProtKB
  • negative regulation of insulin receptor signaling pathway Source: UniProtKB
  • peptidyl-serine phosphorylation Source: GO_Central
  • positive regulation of angiogenesis Source: UniProtKB
  • positive regulation of B cell receptor signaling pathway Source: UniProtKB
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of vascular endothelial growth factor receptor signaling pathway Source: UniProtKB
  • protein phosphorylation Source: MGI
  • regulation of transcription by RNA polymerase II Source: UniProtKB
  • response to hypoxia Source: MGI
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionChromatin regulator, Kinase, Serine/threonine-protein kinase, Transferase
Biological processAdaptive immunity, Apoptosis, Immunity, Transcription, Transcription regulation
LigandATP-binding, Calcium, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi2.7.11.13 3474
ReactomeiR-MMU-114516 Disinhibition of SNARE formation
R-MMU-1169091 Activation of NF-kappaB in B cells
R-MMU-416993 Trafficking of GluR2-containing AMPA receptors
R-MMU-4419969 Depolymerisation of the Nuclear Lamina
R-MMU-5099900 WNT5A-dependent internalization of FZD4
R-MMU-5218921 VEGFR2 mediated cell proliferation
R-MMU-76005 Response to elevated platelet cytosolic Ca2+

Names & Taxonomyi

Protein namesi
Recommended name:
Protein kinase C beta type (EC:2.7.11.13)
Short name:
PKC-B
Short name:
PKC-beta
Gene namesi
Name:Prkcb
Synonyms:Pkcb, Prkcb1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:97596 Prkcb

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice develop an immunodeficiency characterized by impaired humoral immune responses and reduced cellular responses of B-cells similar to X-linked immunodeficiency (Xid). Mice are unable to activate NF-kappa-B and promote cell survival in B-cells upon BCR signaling, or even in mast cells. B-cells fail to recruit the I-kappa-B kinase (IKK) complex into lipid rafts, activate IKK, degrade I-kappa-B or up-regulate NF-kappa-B-dependent survival signals. Moreover, mutant animals are hyperphagic and exhibit higher food intake and reduced feed efficiency versus wild type. Mice are considerably leaner and display markedly decreased size of white fat depots. Triglyceride content in the liver and skeletal muscle is also significantly low.3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000556852 – 671Protein kinase C beta typeAdd BLAST670

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei11PhosphoserineBy similarity1
Modified residuei16Phosphoserine; by autocatalysisBy similarity1
Modified residuei17Phosphothreonine; by autocatalysisBy similarity1
Modified residuei206PhosphoserineBy similarity1
Modified residuei250Phosphothreonine; by autocatalysisBy similarity1
Modified residuei314Phosphothreonine; by autocatalysisBy similarity1
Modified residuei324Phosphothreonine; by autocatalysisBy similarity1
Modified residuei500Phosphothreonine; by PDPK1By similarity1
Modified residuei504PhosphothreonineBy similarity1
Modified residuei635Phosphothreonine; by autocatalysisBy similarity1
Modified residuei642Phosphothreonine; by autocatalysisBy similarity1
Modified residuei661PhosphoserineBy similarity1
Modified residuei662Phosphotyrosine; by SYK1 Publication1
Isoform Beta-II (identifier: P68404-2)
Modified residuei641PhosphothreonineCombined sources1
Modified residuei654PhosphoserineCombined sources1
Modified residuei660PhosphoserineCombined sources1
Modified residuei664PhosphoserineCombined sources1
Modified residuei673PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation on Thr-500 within the activation loop renders it competent to autophosphorylate. Subsequent autophosphorylation of Thr-642 maintains catalytic competence, and autophosphorylation on Ser-661 appears to release the kinase into the cytosol. Autophosphorylation on other sites i.e. in the N-terminal and hinge regions have no effect on enzyme activity (By similarity). Phosphorylation at Tyr-662 by SYK induces binding with GRB2 and contributes to the activation of MAPK/ERK signaling cascade.By similarity1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP68404
MaxQBiP68404
PaxDbiP68404
PeptideAtlasiP68404
PRIDEiP68404

PTM databases

iPTMnetiP68404
PhosphoSitePlusiP68404
SwissPalmiP68404

Expressioni

Gene expression databases

BgeeiENSMUSG00000052889
GenevisibleiP68404 MM

Interactioni

Subunit structurei

Interacts with PDK1. Interacts in vitro with PRKCBP1. Interacts with PHLPP1 and PHLPP2; both proteins mediate its dephosphorylation. Interacts with KDM1A/LSD1, PKN1 and ANDR (By similarity).By similarity

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202195, 21 interactors
DIPiDIP-31583N
IntActiP68404, 16 interactors
MINTiP68404
STRINGi10090.ENSMUSP00000070019

Structurei

3D structure databases

ProteinModelPortaliP68404
SMRiP68404
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini173 – 260C2PROSITE-ProRule annotationAdd BLAST88
Domaini342 – 600Protein kinasePROSITE-ProRule annotationAdd BLAST259
Domaini601 – 671AGC-kinase C-terminalAdd BLAST71

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri36 – 86Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST51
Zinc fingeri101 – 151Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST51

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG0694 Eukaryota
ENOG410XNPH LUCA
GeneTreeiENSGT00820000126964
HOGENOMiHOG000233022
HOVERGENiHBG108317
InParanoidiP68404
KOiK19662
OMAiQAHIDRE
OrthoDBiEOG091G0QRS
TreeFamiTF351133

Family and domain databases

CDDicd00029 C1, 2 hits
cd05616 STKc_cPKC_beta, 1 hit
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR034664 cPKC_beta
IPR020454 DAG/PE-bd
IPR011009 Kinase-like_dom_sf
IPR002219 PE/DAG-bd
IPR017892 Pkinase_C
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR014375 Protein_kinase_C_a/b/g
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00130 C1_1, 2 hits
PF00168 C2, 1 hit
PF00069 Pkinase, 1 hit
PF00433 Pkinase_C, 1 hit
PIRSFiPIRSF000550 PKC_alpha, 1 hit
PRINTSiPR00360 C2DOMAIN
PR00008 DAGPEDOMAIN
SMARTiView protein in SMART
SM00109 C1, 2 hits
SM00239 C2, 1 hit
SM00133 S_TK_X, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51285 AGC_KINASE_CTER, 1 hit
PS50004 C2, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
PS00479 ZF_DAG_PE_1, 2 hits
PS50081 ZF_DAG_PE_2, 2 hits

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Beta-I (identifier: P68404-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MADPAAGPPP SEGEESTVRF ARKGALRQKN VHEVKNHKFT ARFFKQPTFC
60 70 80 90 100
SHCTDFIWGF GKQGFQCQVC CFVVHKRCHE FVTFSCPGAD KGPASDDPRS
110 120 130 140 150
KHKFKIHTYS SPTFCDHCGS LLYGLIHQGM KCDTCMMNVH KRCVMNVPSL
160 170 180 190 200
CGTDHTERRG RIYIQAHIDR EVLIVVVRDA KNLVPMDPNG LSDPYVKLKL
210 220 230 240 250
IPDPKSESKQ KTKTIKCSLN PEWNETFRFQ LKESDKDRRL SVEIWDWDLT
260 270 280 290 300
SRNDFMGSLS FGISELQKAG VDGWFKLLSQ EEGEYFNVPV PPEGSEGNEE
310 320 330 340 350
LRQKFERAKI GQGTKAPEEK TANTISKFDN NGNRDRMKLT DFNFLMVLGK
360 370 380 390 400
GSFGKVMLSE RKGTDELYAV KILKKDVVIQ DDDVECTMVE KRVLALPGKP
410 420 430 440 450
PFLTQLHSCF QTMDRLYFVM EYVNGGDLMY HIQQVGRFKE PHAVFYAAEI
460 470 480 490 500
AIGLFFLQSK GIIYRDLKLD NVMLDSEGHI KIADFGMCKE NIWDGVTTKT
510 520 530 540 550
FCGTPDYIAP EIIAYQPYGK SVDWWAFGVL LYEMLAGQAP FEGEDEDELF
560 570 580 590 600
QSIMEHNVAY PKSMSKEAVA ICKGLMTKHP GKRLGCGPEG ERDIKEHAFF
610 620 630 640 650
RYIDWEKLER KEIQPPYKPK ARDKRDTSNF DKEFTRQPVE LTPTDKLFIM
660 670
NLDQNEFAGF SYTNPEFVIN V
Length:671
Mass (Da):76,751
Last modified:September 21, 2011 - v4
Checksum:iA1935030F758513C
GO
Isoform Beta-II (identifier: P68404-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     622-671: RDKRDTSNFD...YTNPEFVINV → CGRNAENFDR...SEFLKPEVKS

Show »
Length:673
Mass (Da):76,894
Checksum:iA65573AAF6E224C7
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041812622 – 671RDKRD…FVINV → CGRNAENFDRFFTRHPPVLT PPDQEVIRNIDQSEFEGFSF VNSEFLKPEVKS in isoform Beta-II. 1 PublicationAdd BLAST50

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X53532 mRNA Translation: CAA37611.1
X59274 mRNA No translation available.
AC016522 Genomic DNA No translation available.
AC122232 Genomic DNA No translation available.
AC123837 Genomic DNA No translation available.
AC151986 Genomic DNA No translation available.
BC127083 mRNA Translation: AAI27084.1
CCDSiCCDS21815.1 [P68404-2]
CCDS85402.1 [P68404-1]
PIRiS11213
RefSeqiNP_001303601.1, NM_001316672.1 [P68404-1]
NP_032881.1, NM_008855.2 [P68404-2]
UniGeneiMm.207496
Mm.446371

Genome annotation databases

EnsembliENSMUST00000064921; ENSMUSP00000064812; ENSMUSG00000052889 [P68404-1]
ENSMUST00000064989; ENSMUSP00000070019; ENSMUSG00000052889 [P68404-2]
ENSMUST00000143692; ENSMUSP00000138788; ENSMUSG00000052889 [P68404-2]
GeneIDi18751
KEGGimmu:18751
UCSCiuc009jot.1 mouse [P68404-1]
uc009jou.1 mouse [P68404-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiKPCB_MOUSE
AccessioniPrimary (citable) accession number: P68404
Secondary accession number(s): A0JNZ5
, F2Z441, P04410, P04411
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: September 21, 2011
Last modified: April 25, 2018
This is version 156 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health