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Protein

Protein kinase C beta type

Gene

PRKCB

Organism
Homo sapiens (Human)
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 (By similarity). Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription.By similarity3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

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).1 Publication

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

  • androgen receptor binding Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • calcium-dependent protein kinase C activity Source: Reactome
  • chromatin binding Source: UniProtKB
  • histone binding Source: UniProtKB
  • histone kinase activity (H3-T6 specific) Source: UniProtKB
  • ligand-dependent nuclear receptor transcription coactivator activity Source: UniProtKB
  • protein kinase C activity Source: Reactome
  • protein kinase C binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: Reactome
  • zinc ion binding Source: InterPro

GO - Biological processi

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 2681
ReactomeiR-HSA-114516 Disinhibition of SNARE formation
R-HSA-1169091 Activation of NF-kappaB in B cells
R-HSA-416993 Trafficking of GluR2-containing AMPA receptors
R-HSA-418597 G alpha (z) signalling events
R-HSA-4419969 Depolymerisation of the Nuclear Lamina
R-HSA-5099900 WNT5A-dependent internalization of FZD4
R-HSA-5218921 VEGFR2 mediated cell proliferation
R-HSA-76005 Response to elevated platelet cytosolic Ca2+
R-HSA-8939246 RUNX1 regulates transcription of genes involved in differentiation of myeloid cells
SABIO-RKiP05771
SignaLinkiP05771
SIGNORiP05771

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000166501.12
HGNCiHGNC:9395 PRKCB
MIMi176970 gene
neXtProtiNX_P05771

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

Organism-specific databases

DisGeNETi5579
OpenTargetsiENSG00000166501
PharmGKBiPA33761

Chemistry databases

ChEMBLiCHEMBL3045
DrugBankiDB08846 Ellagic Acid
DB01738 O-Phosphoethanolamine
DB00675 Tamoxifen
DB00163 Vitamin E
GuidetoPHARMACOLOGYi1483

Polymorphism and mutation databases

BioMutaiPRKCB
DMDMi20141488

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000556842 – 671Protein kinase C beta typeAdd BLAST670

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanine1 Publication1
Modified residuei11PhosphoserineCombined sources1
Modified residuei16Phosphoserine; by autocatalysisSequence analysisBy similarity1
Modified residuei17PhosphothreonineCombined sources1
Modified residuei206PhosphoserineCombined sources1
Modified residuei250Phosphothreonine; by autocatalysisBy similarity1
Modified residuei311PhosphoserineCombined sources1
Modified residuei314PhosphothreonineCombined sources1
Modified residuei324Phosphothreonine; by autocatalysisSequence analysisBy similarity1
Modified residuei500Phosphothreonine; by PDPK11 Publication1
Modified residuei504PhosphothreonineCombined sources1
Modified residuei635Phosphothreonine; by autocatalysisBy similarity1
Modified residuei642PhosphothreonineCombined sources1 Publication1
Modified residuei661Phosphoserine; by autocatalysis1 Publication1
Modified residuei662Phosphotyrosine; by SYKBy similarity1
Isoform Beta-II (identifier: P05771-2)
Modified residuei641PhosphothreonineCombined sources1
Modified residuei660PhosphoserineCombined 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. Phosphorylation at Tyr-662 by SYK induces binding with GRB2 and contributes to the activation of MAPK/ERK signaling cascade (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP05771
MaxQBiP05771
PaxDbiP05771
PeptideAtlasiP05771
PRIDEiP05771
ProteomicsDBi51855
51856 [P05771-2]

PTM databases

iPTMnetiP05771
PhosphoSitePlusiP05771

Miscellaneous databases

PMAP-CutDBiP05771

Expressioni

Gene expression databases

BgeeiENSG00000166501
ExpressionAtlasiP05771 baseline and differential
GenevisibleiP05771 HS

Organism-specific databases

HPAiCAB003843
HPA048321
HPA054203

Interactioni

Subunit structurei

Interacts with PDK1 (By similarity). Interacts in vitro with PRKCBP1. Interacts with PHLPP1 and PHLPP2; both proteins mediate its dephosphorylation. Interacts with KDM1A/LSD1, PKN1 and ANDR.By similarity3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • androgen receptor binding Source: UniProtKB
  • histone binding Source: UniProtKB
  • protein kinase C binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111565, 65 interactors
DIPiDIP-34187N
IntActiP05771, 28 interactors
MINTiP05771
STRINGi9606.ENSP00000305355

Chemistry databases

BindingDBiP05771

Structurei

Secondary structure

1671
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi342 – 351Combined sources10
Beta strandi354 – 361Combined sources8
Beta strandi364 – 374Combined sources11
Helixi375 – 380Combined sources6
Helixi384 – 394Combined sources11
Beta strandi406 – 411Combined sources6
Beta strandi413 – 421Combined sources9
Helixi428 – 435Combined sources8
Helixi440 – 459Combined sources20
Helixi469 – 471Combined sources3
Beta strandi472 – 474Combined sources3
Beta strandi480 – 482Combined sources3
Helixi505 – 507Combined sources3
Helixi510 – 513Combined sources4
Helixi521 – 536Combined sources16
Helixi546 – 555Combined sources10
Helixi566 – 575Combined sources10
Helixi590 – 595Combined sources6
Helixi598 – 600Combined sources3
Helixi605 – 609Combined sources5
Helixi629 – 636Combined sources8
Helixi646 – 651Combined sources6
Turni654 – 657Combined sources4

3D structure databases

ProteinModelPortaliP05771
SMRiP05771
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05771

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
GeneTreeiENSGT00920000148938
HOVERGENiHBG108317
InParanoidiP05771
KOiK19662
OMAiQAHIDRE
OrthoDBiEOG091G0QRS
PhylomeDBiP05771
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: P05771-1) [UniParc]FASTAAdd to basket
Also known as: PRKCB1

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 DVLIVLVRDA KNLVPMDPNG LSDPYVKLKL
210 220 230 240 250
IPDPKSESKQ KTKTIKCSLN PEWNETFRFQ LKESDKDRRL SVEIWDWDLT
260 270 280 290 300
SRNDFMGSLS FGISELQKAS VDGWFKLLSQ EEGEYFNVPV PPEGSEANEE
310 320 330 340 350
LRQKFERAKI SQGTKVPEEK TTNTVSKFDN 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):76,869
Last modified:January 23, 2007 - v4
Checksum:i3937E7B667108C68
GO
Isoform Beta-II (identifier: P05771-2) [UniParc]FASTAAdd to basket
Also known as: PRKCB2

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

Show »
Length:673
Mass (Da):77,012
Checksum:i03D42B0E4164B48F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti69V → G in CAA44393 (PubMed:7880442).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_042304144V → M in a colorectal adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs764534677Ensembl.1
Natural variantiVAR_042305496V → M in a glioblastoma multiforme sample; somatic mutation. 1 Publication1
Natural variantiVAR_042306588P → H1 PublicationCorresponds to variant dbSNP:rs35631544Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004738622 – 671RDKRD…FVINV → CGRNAENFDRFFTRHPPVLT PPDQEVIRNIDQSEFEGFSF VNSEFLKPEVKS in isoform Beta-II. 2 PublicationsAdd BLAST50

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M13975 mRNA Translation: AAA60095.1
X06318 mRNA Translation: CAA29634.1
X07109 mRNA Translation: CAA30130.1
FJ907246 Genomic DNA Translation: ACS14045.1
AC130454 Genomic DNA No translation available.
AC002299 Genomic DNA Translation: AAB97933.1
AC002299 Genomic DNA Translation: AAB97934.1
CH471145 Genomic DNA Translation: EAW55797.1
CH471145 Genomic DNA Translation: EAW55798.1
BC036472 mRNA Translation: AAH36472.1
X62532 Genomic DNA Translation: CAA44393.1
S47311 Genomic DNA Translation: AAD13852.1
D10022 Genomic DNA Translation: BAA00912.1
AJ002799, AJ002800 Genomic DNA Translation: CAA05725.1
M18254 Genomic DNA Translation: AAA60096.1
M18255 Genomic DNA Translation: AAA60097.1
X05972 Genomic DNA Translation: CAA29396.1
X05971 Genomic DNA Translation: CAA29395.1
CCDSiCCDS10618.1 [P05771-1]
CCDS10619.1 [P05771-2]
PIRiB24664 KIHUC2
S00159 KIHUC1
RefSeqiNP_002729.2, NM_002738.6 [P05771-2]
NP_997700.1, NM_212535.2 [P05771-1]
UniGeneiHs.460355

Genome annotation databases

EnsembliENST00000303531; ENSP00000305355; ENSG00000166501 [P05771-2]
ENST00000321728; ENSP00000318315; ENSG00000166501 [P05771-1]
ENST00000643927; ENSP00000496129; ENSG00000166501 [P05771-2]
ENST00000646168; ENSP00000493817; ENSG00000166501 [P05771-1]
GeneIDi5579
KEGGihsa:5579
UCSCiuc002dmd.4 human [P05771-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKPCB_HUMAN
AccessioniPrimary (citable) accession number: P05771
Secondary accession number(s): C5IFJ8
, D3DWF5, O43744, P05127, Q15138, Q93060, Q9UE49, Q9UE50, Q9UEH8, Q9UJ30, Q9UJ33
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 23, 2007
Last modified: July 18, 2018
This is version 227 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

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