Gene/Proteome Database (LMPD)
LMPD ID
LMP002174
Gene ID
Species
Homo sapiens (Human)
Gene Name
protein kinase C, beta
Gene Symbol
Synonyms
PKC-beta; PKCB; PRKCB1; PRKCB2
Alternate Names
protein kinase C beta type; PKC-B; protein kinase C, beta 1 polypeptide
Chromosome
16
Map Location
16p11.2
EC Number
2.7.11.13
Summary
Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This protein kinase has been reported to be involved in many different cellular functions, such as B cell activation, apoptosis induction, endothelial cell proliferation, and intestinal sugar absorption. Studies in mice also suggest that this kinase may also regulate neuronal functions and correlate fear-induced conflict behavior after stress. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]
Orthologs
Proteins
| protein kinase C beta type isoform 1 | |
|---|---|
| Refseq ID | NP_997700 |
| Protein GI | 47157322 |
| UniProt ID | P05771 |
| mRNA ID | NM_212535 |
| Length | 671 |
| RefSeq Status | REVIEWED |
| MADPAAGPPPSEGEESTVRFARKGALRQKNVHEVKNHKFTARFFKQPTFCSHCTDFIWGFGKQGFQCQVCCFVVHKRCHEFVTFSCPGADKGPASDDPRSKHKFKIHTYSSPTFCDHCGSLLYGLIHQGMKCDTCMMNVHKRCVMNVPSLCGTDHTERRGRIYIQAHIDRDVLIVLVRDAKNLVPMDPNGLSDPYVKLKLIPDPKSESKQKTKTIKCSLNPEWNETFRFQLKESDKDRRLSVEIWDWDLTSRNDFMGSLSFGISELQKASVDGWFKLLSQEEGEYFNVPVPPEGSEANEELRQKFERAKISQGTKVPEEKTTNTVSKFDNNGNRDRMKLTDFNFLMVLGKGSFGKVMLSERKGTDELYAVKILKKDVVIQDDDVECTMVEKRVLALPGKPPFLTQLHSCFQTMDRLYFVMEYVNGGDLMYHIQQVGRFKEPHAVFYAAEIAIGLFFLQSKGIIYRDLKLDNVMLDSEGHIKIADFGMCKENIWDGVTTKTFCGTPDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQAPFEGEDEDELFQSIMEHNVAYPKSMSKEAVAICKGLMTKHPGKRLGCGPEGERDIKEHAFFRYIDWEKLERKEIQPPYKPKARDKRDTSNFDKEFTRQPVELTPTDKLFIMNLDQNEFAGFSYTNPEFVINV | |
| protein kinase C beta type isoform 2 | |
|---|---|
| Refseq ID | NP_002729 |
| Protein GI | 20127450 |
| UniProt ID | P05771 |
| mRNA ID | NM_002738 |
| Length | 673 |
| RefSeq Status | REVIEWED |
| MADPAAGPPPSEGEESTVRFARKGALRQKNVHEVKNHKFTARFFKQPTFCSHCTDFIWGFGKQGFQCQVCCFVVHKRCHEFVTFSCPGADKGPASDDPRSKHKFKIHTYSSPTFCDHCGSLLYGLIHQGMKCDTCMMNVHKRCVMNVPSLCGTDHTERRGRIYIQAHIDRDVLIVLVRDAKNLVPMDPNGLSDPYVKLKLIPDPKSESKQKTKTIKCSLNPEWNETFRFQLKESDKDRRLSVEIWDWDLTSRNDFMGSLSFGISELQKASVDGWFKLLSQEEGEYFNVPVPPEGSEANEELRQKFERAKISQGTKVPEEKTTNTVSKFDNNGNRDRMKLTDFNFLMVLGKGSFGKVMLSERKGTDELYAVKILKKDVVIQDDDVECTMVEKRVLALPGKPPFLTQLHSCFQTMDRLYFVMEYVNGGDLMYHIQQVGRFKEPHAVFYAAEIAIGLFFLQSKGIIYRDLKLDNVMLDSEGHIKIADFGMCKENIWDGVTTKTFCGTPDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQAPFEGEDEDELFQSIMEHNVAYPKSMSKEAVAICKGLMTKHPGKRLGCGPEGERDIKEHAFFRYIDWEKLERKEIQPPYKPKACGRNAENFDRFFTRHPPVLTPPDQEVIRNIDQSEFEGFSFVNSEFLKPEVKS | |
Gene Information
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0005737 | IDA:UniProtKB | C | cytoplasm |
| GO:0005829 | TAS:Reactome | C | cytosol |
| GO:0070062 | IDA:UniProt | C | extracellular vesicular exosome |
| GO:0005634 | IDA:UniProtKB | C | nucleus |
| GO:0005886 | IDA:UniProtKB | C | plasma membrane |
| GO:0050681 | IDA:UniProtKB | F | androgen receptor binding |
| GO:0005524 | IEA:UniProtKB-KW | F | ATP binding |
| GO:0005246 | IEA:Ensembl | F | calcium channel regulator activity |
| GO:0003682 | IDA:UniProtKB | F | chromatin binding |
| GO:0042393 | IDA:UniProtKB | F | histone binding |
| GO:0035403 | IDA:UniProtKB | F | histone kinase activity (H3-T6 specific) |
| GO:0030374 | IMP:UniProtKB | F | ligand-dependent nuclear receptor transcription coactivator activity |
| GO:0004697 | TAS:ProtInc | F | protein kinase C activity |
| GO:0005080 | IPI:UniProtKB | F | protein kinase C binding |
| GO:0004674 | TAS:Reactome | F | protein serine/threonine kinase activity |
| GO:0008270 | IEA:InterPro | F | zinc ion binding |
| GO:0006915 | IEA:UniProtKB-KW | P | apoptotic process |
| GO:0042113 | ISS:UniProtKB | P | B cell activation |
| GO:0050853 | ISS:UniProtKB | P | B cell receptor signaling pathway |
| GO:0007596 | TAS:Reactome | P | blood coagulation |
| GO:0006816 | IEA:Ensembl | P | calcium ion transport |
| GO:0006874 | IEA:Ensembl | P | cellular calcium ion homeostasis |
| GO:0071322 | IEA:Ensembl | P | cellular response to carbohydrate stimulus |
| GO:0035408 | IDA:UniProtKB | P | histone H3-T6 phosphorylation |
| GO:0035556 | IEA:InterPro | P | intracellular signal transduction |
| GO:0042953 | TAS:BHF-UCL | P | lipoprotein transport |
| GO:0010829 | ISS:UniProtKB | P | negative regulation of glucose transport |
| GO:0046627 | ISS:UniProtKB | P | negative regulation of insulin receptor signaling pathway |
| GO:0030168 | TAS:Reactome | P | platelet activation |
| GO:0045766 | ISS:UniProtKB | P | positive regulation of angiogenesis |
| GO:0050861 | ISS:UniProtKB | P | positive regulation of B cell receptor signaling pathway |
| GO:0043123 | ISS:UniProtKB | P | positive regulation of I-kappaB kinase/NF-kappaB signaling |
| GO:0051092 | ISS:UniProtKB | P | positive regulation of NF-kappaB transcription factor activity |
| GO:0030949 | ISS:UniProtKB | P | positive regulation of vascular endothelial growth factor receptor signaling pathway |
| GO:0006468 | TAS:ProtInc | P | protein phosphorylation |
| GO:0006357 | IMP:UniProtKB | P | regulation of transcription from RNA polymerase II promoter |
| GO:0007165 | NAS:ProtInc | P | signal transduction |
| GO:0007268 | TAS:Reactome | P | synaptic transmission |
| GO:0006351 | IEA:UniProtKB-KW | P | transcription, DNA-templated |
KEGG Pathway Links
Domain Information
InterPro Annotations
| Accession | Description |
|---|---|
| IPR000961 | AGC-kinase, C-terminal |
| IPR000008 | C2 domain |
| IPR020454 | Diacylglycerol/phorbol-ester binding |
| IPR017441 | Protein kinase, ATP binding site |
| IPR014375 | Protein kinase C, alpha/beta/gamma types |
| IPR002219 | Protein kinase C-like, phorbol ester/diacylglycerol-binding domain |
| IPR017892 | Protein kinase, C-terminal |
| IPR000719 | Protein kinase domain |
| IPR011009 | Protein kinase-like domain |
| IPR002290 | Serine/threonine/dual specificity protein kinase, catalytic domain |
| IPR008271 | Serine/threonine-protein kinase, active site |
UniProt Annotations
Entry Information
Comments
| Comment Type | Description |
|---|---|
| Alternative Products | Event=Alternative splicing; Named isoforms=2; Name=Beta-I; Synonyms=PRKCB1; IsoId=P05771-1; Sequence=Displayed; Name=Beta-II; Synonyms=PRKCB2; IsoId=P05771-2; Sequence=VSP_004738; Note=Contains a phosphoserine at position 660. Contains a phosphothreonine at position 641.; |
| Catalytic Activity | ATP + a protein = ADP + a phosphoprotein. |
| Cofactor | Name=Ca(2+); Xref=ChEBI |
| Enzyme Regulation | 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). |
| 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. 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. {ECO |
| Interaction | O60346:PHLPP1; NbExp=5; IntAct=EBI-5774511, EBI-2511516; |
| Ptm | 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). |
| Similarity | Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily. |
| Similarity | Contains 1 AGC-kinase C-terminal domain. |
| Similarity | Contains 1 C2 domain. {ECO |
| Similarity | Contains 1 protein kinase domain. |
| Similarity | Contains 2 phorbol-ester/DAG-type zinc fingers. |
| Subcellular Location | Cytoplasm . Nucleus {ECO |
| Subunit | 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. {ECO |
| Web Resource | Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/prkcb1/"; |
Identical and Related Proteins
Unique RefSeq proteins for LMP002174 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 47157322 | RefSeq | NP_997700 | 671 | protein kinase C beta type isoform 1 |
| 20127450 | RefSeq | NP_002729 | 673 | protein kinase C beta type isoform 2 |
Identical Sequences to LMP002174 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:20127450 | DBBJ | BAJ17874.1 | 673 | protein kinase C, beta, partial [synthetic construct] |
| GI:47157322 | GenBank | EAW55796.1 | 671 | protein kinase C, beta 1, isoform CRA_a [Homo sapiens] |
| GI:47157322 | GenBank | ABW49131.1 | 671 | Sequence 165 from patent US 7265092 |
| GI:47157322 | GenBank | ADM03570.1 | 671 | Sequence 165 from patent US 7727958 |
| GI:47157322 | GenBank | ADS40178.1 | 671 | Sequence 121 from patent US 7792665 |
| GI:20127450 | GenBank | ADS40179.1 | 673 | Sequence 122 from patent US 7792665 |
| GI:47157322 | GenBank | AGV86228.1 | 671 | Sequence 165 from patent US 8524673 |
| GI:20127450 | GenBank | AGV86229.1 | 673 | Sequence 166 from patent US 8524673 |
| GI:20127450 | GenBank | AHD71836.1 | 673 | Sequence 6530 from patent US 8586006 |
| GI:47157322 | GenBank | AHD71837.1 | 671 | Sequence 6531 from patent US 8586006 |
| GI:20127450 | GenBank | AIC49475.1 | 673 | PRKCB, partial [synthetic construct] |
| GI:20127450 | GenBank | AIC62575.1 | 673 | PRKCB, partial [synthetic construct] |
Related Sequences to LMP002174 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:47157322 | GenBank | AFE63508.1 | 671 | protein kinase C beta type isoform 1 [Macaca mulatta] |
| GI:20127450 | GenBank | AFE79187.1 | 673 | protein kinase C beta type isoform 2 [Macaca mulatta] |
| GI:47157322 | GenBank | AFH27613.1 | 671 | protein kinase C beta type isoform 1 [Macaca mulatta] |
| GI:20127450 | GenBank | JAB22720.1 | 673 | protein kinase C beta type isoform 2 [Callithrix jacchus] |
| GI:47157322 | GenBank | JAB22721.1 | 671 | protein kinase C beta type isoform 1 [Callithrix jacchus] |
| GI:20127450 | GenBank | JAB31456.1 | 673 | protein kinase C beta type isoform 2 [Callithrix jacchus] |
| GI:20127450 | GenBank | JAB31457.1 | 673 | protein kinase C beta type isoform 2 [Callithrix jacchus] |
| GI:20127450 | GenBank | JAB31458.1 | 673 | protein kinase C beta type isoform 2 [Callithrix jacchus] |
| GI:20127450 | GenBank | JAB31459.1 | 673 | protein kinase C beta type isoform 2 [Callithrix jacchus] |
| GI:47157322 | RefSeq | XP_002756047.1 | 671 | PREDICTED: protein kinase C beta type [Callithrix jacchus] |
| GI:47157322 | RefSeq | XP_003261718.1 | 671 | PREDICTED: protein kinase C beta type isoform 2 [Nomascus leucogenys] |
| GI:47157322 | RefSeq | XP_003930254.1 | 671 | PREDICTED: protein kinase C beta type isoform X2 [Saimiri boliviensis boliviensis] |