Gene/Proteome Database (LMPD)
LMPD ID
LMP001177
Gene ID
Species
Mus musculus (Mouse)
Gene Name
protein kinase C, beta
Gene Symbol
Synonyms
A130082F03Rik; PKC-Beta; Pkcb; Prkcb1; Prkcb2
Alternate Names
protein kinase C beta type; PKC-B; protein kinase C beta-II; protein kinase C, beta 1
Chromosome
7
Map Location
7 F3|7 65.75 cM
EC Number
2.7.11.13
Proteins
| protein kinase C beta type | |
|---|---|
| Refseq ID | NP_032881 |
| Protein GI | 6679345 |
| UniProt ID | P68404 |
| mRNA ID | NM_008855 |
| Length | 673 |
| RefSeq Status | VALIDATED |
| MADPAAGPPPSEGEESTVRFARKGALRQKNVHEVKNHKFTARFFKQPTFCSHCTDFIWGFGKQGFQCQVCCFVVHKRCHEFVTFSCPGADKGPASDDPRSKHKFKIHTYSSPTFCDHCGSLLYGLIHQGMKCDTCMMNVHKRCVMNVPSLCGTDHTERRGRIYIQAHIDREVLIVVVRDAKNLVPMDPNGLSDPYVKLKLIPDPKSESKQKTKTIKCSLNPEWNETFRFQLKESDKDRRLSVEIWDWDLTSRNDFMGSLSFGISELQKAGVDGWFKLLSQEEGEYFNVPVPPEGSEGNEELRQKFERAKIGQGTKAPEEKTANTISKFDNNGNRDRMKLTDFNFLMVLGKGSFGKVMLSERKGTDELYAVKILKKDVVIQDDDVECTMVEKRVLALPGKPPFLTQLHSCFQTMDRLYFVMEYVNGGDLMYHIQQVGRFKEPHAVFYAAEIAIGLFFLQSKGIIYRDLKLDNVMLDSEGHIKIADFGMCKENIWDGVTTKTFCGTPDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQAPFEGEDEDELFQSIMEHNVAYPKSMSKEAVAICKGLMTKHPGKRLGCGPEGERDIKEHAFFRYIDWEKLERKEIQPPYKPKACGRNAENFDRFFTRHPPVLTPPDQEVIRNIDQSEFEGFSFVNSEFLKPEVKS | |
Gene Information
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0005737 | IDA:MGI | C | cytoplasm |
| GO:0070062 | IEA:Ensembl | C | extracellular vesicular exosome |
| GO:0005634 | ISS:UniProtKB | C | nucleus |
| GO:0005886 | IEA:Ensembl | C | plasma membrane |
| GO:0005524 | IEA:UniProtKB-KW | F | ATP binding |
| GO:0050681 | ISS:UniProtKB | F | androgen receptor binding |
| GO:0005246 | IDA:MGI | F | calcium channel regulator activity |
| GO:0003682 | ISS:UniProtKB | F | chromatin binding |
| GO:0042393 | ISS:UniProtKB | F | histone binding |
| GO:0035403 | ISS:UniProtKB | F | histone kinase activity (H3-T6 specific) |
| GO:0030374 | ISS:UniProtKB | F | ligand-dependent nuclear receptor transcription coactivator activity |
| GO:0004697 | IDA:MGI | F | protein kinase C activity |
| GO:0008270 | IEA:InterPro | F | zinc ion binding |
| GO:0042113 | IMP:UniProtKB | P | B cell activation |
| GO:0050853 | IMP:UniProtKB | P | B cell receptor signaling pathway |
| GO:0006915 | IEA:UniProtKB-KW | P | apoptotic process |
| GO:0006816 | IDA:MGI | P | calcium ion transport |
| GO:0006874 | IDA:MGI | P | cellular calcium ion homeostasis |
| GO:0071322 | IDA:MGI | P | cellular response to carbohydrate stimulus |
| GO:0035408 | ISS:UniProtKB | P | histone H3-T6 phosphorylation |
| GO:0035556 | IEA:InterPro | P | intracellular signal transduction |
| GO:0010829 | IMP:UniProtKB | P | negative regulation of glucose transport |
| GO:0046627 | ISS:UniProtKB | P | negative regulation of insulin receptor signaling pathway |
| GO:0050861 | IMP:UniProtKB | P | positive regulation of B cell receptor signaling pathway |
| GO:0043123 | IMP:UniProtKB | P | positive regulation of I-kappaB kinase/NF-kappaB signaling |
| GO:0051092 | IMP:UniProtKB | P | positive regulation of NF-kappaB transcription factor activity |
| GO:0045766 | IMP:UniProtKB | P | positive regulation of angiogenesis |
| GO:0030949 | IMP:UniProtKB | P | positive regulation of vascular endothelial growth factor receptor signaling pathway |
| GO:0006468 | IDA:MGI | P | protein phosphorylation |
| GO:0006357 | ISS:UniProtKB | P | regulation of transcription from RNA polymerase II promoter |
| 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 |
| IPR014375 | Protein kinase C, alpha/beta/gamma types |
| IPR002219 | Protein kinase C-like, phorbol ester/diacylglycerol-binding domain |
| IPR000719 | Protein kinase domain |
| IPR017441 | Protein kinase, ATP binding site |
| IPR017892 | Protein kinase, C-terminal |
| IPR011009 | Protein kinase-like domain |
| IPR008271 | Serine/threonine-protein kinase, active site |
| IPR002290 | Serine/threonine/dual specificity protein kinase, catalytic domain |
UniProt Annotations
Entry Information
Comments
| Comment Type | Description |
|---|---|
| Alternative Products | Event=Alternative splicing; Named isoforms=2; Name=Beta-I; IsoId=P68404-1; Sequence=Displayed; Name=Beta-II; IsoId=P68404-2; Sequence=VSP_041812; Note=Contains a phosphothreonine at position 641.; |
| Catalytic Activity | ATP + a protein = ADP + a phosphoprotein. |
| Cofactor | Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250}; Note=Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domain. {ECO:0000250}; |
| Disruption Phenotype | 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. {ECO:0000269|PubMed:12118249, ECO:0000269|PubMed:17962198, ECO:0000269|PubMed:8670417}. |
| 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) (By similarity). {ECO:0000250}. |
| 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. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription (By similarity). {ECO:0000250}. |
| Interaction | Q13873:BMPR2 (xeno); NbExp=4; IntAct=EBI-397048, EBI-527196; P56537:EIF6 (xeno); NbExp=2; IntAct=EBI-397048, EBI-372243; |
| 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 (By similarity). Phosphorylation at Tyr-662 by SYK induces binding with GRB2 and contributes to the activation of MAPK/ERK signaling cascade. {ECO:0000250, ECO:0000269|PubMed:12881490}. |
| Similarity | Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily. {ECO:0000305}. |
| Similarity | Contains 1 AGC-kinase C-terminal domain. {ECO:0000305}. |
| Similarity | Contains 1 C2 domain. {ECO:0000255|PROSITE- ProRule:PRU00041}. |
| Similarity | Contains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}. |
| Similarity | Contains 2 phorbol-ester/DAG-type zinc fingers. {ECO:0000255|PROSITE-ProRule:PRU00226}. |
| Subcellular Location | Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. Membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. |
| Subunit | 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). {ECO:0000250}. |
Identical and Related Proteins
Unique RefSeq proteins for LMP001177 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 6679345 | RefSeq | NP_032881 | 673 | protein kinase C beta type |
Identical Sequences to LMP001177 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:6679345 | EMBL | CAA37611.1 | 673 | unnamed protein product [Mus musculus] |
| GI:6679345 | GenBank | AAI27084.1 | 673 | Protein kinase C, beta [Mus musculus] |
| GI:6679345 | GenBank | ABK42345.1 | 673 | protein kinase C beta2 [synthetic construct] |
Related Sequences to LMP001177 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:6679345 | EMBL | CAA28036.1 | 673 | unnamed protein product [Rattus norvegicus] |
| GI:6679345 | PIR | - | 673 | protein kinase C (EC 2.7.1.-) beta-II - rat [Rattus norvegicus] |
| GI:6679345 | RefSeq | XP_003795783.1 | 673 | PREDICTED: protein kinase C beta type isoform 2 [Otolemur garnettii] |
| GI:6679345 | RefSeq | XP_004268631.1 | 673 | PREDICTED: protein kinase C beta type isoform 1 [Orcinus orca] |
| GI:6679345 | RefSeq | XP_004670252.1 | 673 | PREDICTED: protein kinase C beta type isoform X1 [Jaculus jaculus] |
| GI:6679345 | RefSeq | XP_006980411.1 | 673 | PREDICTED: protein kinase C beta type isoform X1 [Peromyscus maniculatus bairdii] |