ID KPCB_RAT Reviewed; 671 AA. AC P68403; P04410; P04411; DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 02-SEP-2026, entry version 186. DE RecName: Full=Protein kinase C beta type; DE Short=PKC-B; DE Short=PKC-beta; DE EC=2.7.11.13 {ECO:0000250|UniProtKB:P05771}; GN Name=Prkcb; Synonyms=Pkcb, Prkcb1; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS BETA-I AND BETA-II). RX PubMed=3755379; DOI=10.1016/0092-8674(86)90874-3; RA Knopf J.L., Lee M.-H., Sultzman L.A., Kriz R.W., Loomis C.R., Hewick R.M., RA Bell R.M.; RT "Cloning and expression of multiple protein kinase C cDNAs."; RL Cell 46:491-502(1986). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS BETA-I AND BETA-II). RC TISSUE=Brain; RX PubMed=2428667; DOI=10.1016/0014-5793(86)81010-9; RA Ono Y., Kurokawa T., Fujii T., Kawahara K., Igarashi K., Kikkawa U., RA Ogita K., Nishizuka Y.; RT "Two types of complementary DNAs of rat brain protein kinase C. RT Heterogeneity determined by alternative splicing."; RL FEBS Lett. 206:347-352(1986). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-I). RC TISSUE=Fibroblast; RX PubMed=3345563; DOI=10.1016/s0092-8674(88)80027-8; RA Housey G.M., Johnson M.D., Hsiao W.L.W., O'Brian C.A., Murphy J.P., RA Kirschmeier P., Weinstein I.B.; RT "Overproduction of protein kinase C causes disordered growth control in rat RT fibroblasts."; RL Cell 52:343-354(1988). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 448-671 (ISOFORM BETA-I). RX PubMed=3755404; DOI=10.1016/0014-5793(86)80724-4; RA Ono Y., Kurokawa T., Kawahara K., Nishimura O., Marumoto R., Igarashi K., RA Sugino Y., Kikkawa U., Ogita K., Nishizuka Y.; RT "Cloning of rat brain protein kinase C complementary DNA."; RL FEBS Lett. 203:111-115(1986). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 448-671 (ISOFORM BETA-I). RX PubMed=3469647; DOI=10.1073/pnas.84.4.1065; RA Housey G.M., O'Brian C.A., Johnson M.D., Kirschmeier P., Weinstein I.B.; RT "Isolation of cDNA clones encoding protein kinase C: evidence for a protein RT kinase C-related gene family."; RL Proc. Natl. Acad. Sci. U.S.A. 84:1065-1069(1987). RN [6] RP PROTEIN SEQUENCE OF 500-520 AND 636-663 (ISOFORM BETA-II), AND RP PHOSPHORYLATION AT THR-500; THR-642 AND SER-661. RX PubMed=8749392; DOI=10.1016/s0960-9822(95)00277-6; RA Keranen L.M., Dutil E.M., Newton A.C.; RT "Protein kinase C is regulated in vivo by three functionally distinct RT phosphorylations."; RL Curr. Biol. 5:1394-1403(1995). RN [7] RP PHOSPHORYLATION AT SER-16; THR-17; THR-314; THR-324; THR-635 AND THR-642, RP AND MUTAGENESIS OF 16-SER-THR-17; THR-314; THR-324; THR-635 AND THR-642. RX PubMed=8327493; DOI=10.1073/pnas.90.13.6130; RA Zhang J., Wang L., Petrin J., Bishop W.R., Bond R.W.; RT "Characterization of site-specific mutants altered at protein kinase C beta RT 1 isozyme autophosphorylation sites."; RL Proc. Natl. Acad. Sci. U.S.A. 90:6130-6134(1993). RN [8] RP PHOSPHORYLATION AT THR-642 (ISOFORM BETA-I), AND MUTAGENESIS OF THR-635 AND RP THR-642. RX PubMed=8034726; DOI=10.1016/s0021-9258(17)32208-1; RA Zhang J., Wang L., Schwartz J., Bond R.W., Bishop W.R.; RT "Phosphorylation of Thr642 is an early event in the processing of newly RT synthesized protein kinase C beta 1 and is essential for its activation."; RL J. Biol. Chem. 269:19578-19584(1994). RN [9] RP PHOSPHORYLATION AT THR-500, AND MUTAGENESIS OF THR-500. RX PubMed=7961692; DOI=10.1016/s0021-9258(18)47044-5; RA Orr J.W., Newton A.C.; RT "Requirement for negative charge on 'activation loop' of protein kinase RT C."; RL J. Biol. Chem. 269:27715-27718(1994). RN [10] RP FUNCTION IN INSULIN SIGNALING. RX PubMed=10938109; DOI=10.1128/mcb.20.17.6323-6333.2000; RA Formisano P., Oriente F., Fiory F., Caruso M., Miele C., Maitan M.A., RA Andreozzi F., Vigliotta G., Condorelli G., Beguinot F.; RT "Insulin-activated protein kinase Cbeta bypasses Ras and stimulates RT mitogen-activated protein kinase activity and cell proliferation in muscle RT cells."; RL Mol. Cell. Biol. 20:6323-6333(2000). RN [11] RP FUNCTION IN INSULIN SIGNALING. RX PubMed=11714718; DOI=10.1074/jbc.m109647200; RA Kaneto H., Suzuma K., Sharma A., Bonner-Weir S., King G.L., Weir G.C.; RT "Involvement of protein kinase C beta 2 in c-myc induction by high glucose RT in pancreatic beta-cells."; RL J. Biol. Chem. 277:3680-3685(2002). RN [12] RP FUNCTION. RX PubMed=19176525; DOI=10.1074/jbc.m808719200; RA Yamasaki T., Takahashi A., Pan J., Yamaguchi N., Yokoyama K.K.; RT "Phosphorylation of activation transcription factor-2 at serine 121 by RT protein kinase c controls c-Jun-mediated activation of transcription."; RL J. Biol. Chem. 284:8567-8581(2009). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11 AND THR-642, RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-641; SER-654; SER-660 AND RP SER-664 (ISOFORM BETA-II), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE RP SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). RN [14] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 157-288 IN COMPLEX WITH CALCIUM RP IONS, AND COFACTOR. RX PubMed=9817842; DOI=10.1016/s0969-2126(98)00139-7; RA Sutton R.B., Sprang S.R.; RT "Structure of the protein kinase Cbeta phospholipid-binding C2 domain RT complexed with Ca2+."; RL Structure 6:1395-1405(1998). RN [15] RP X-RAY CRYSTALLOGRAPHY (4.00 ANGSTROMS) OF 1-661 IN COMPLEX WITH CALCIUM RP IONS, COFACTOR, AND PHOSPHORYLATION AT THR-500; THR-642 AND SER-661. RX PubMed=21215369; DOI=10.1016/j.cell.2010.12.013; RA Leonard T.A., Rozycki B., Saidi L.F., Hummer G., Hurley J.H.; RT "Crystal structure and allosteric activation of protein kinase C betaII."; RL Cell 144:55-66(2011). CC -!- FUNCTION: Calcium-activated, phospholipid- and diacylglycerol (DAG)- CC dependent serine/threonine-protein kinase involved in various cellular CC processes such as regulation of the B-cell receptor (BCR) signalosome, CC oxidative stress-induced apoptosis, androgen receptor-dependent CC transcription regulation, insulin signaling and endothelial cells CC proliferation. Plays a key role in B-cell activation by regulating BCR- CC induced NF-kappa-B activation. Mediates the activation of the canonical CC NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 CC at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CC CARD11/CARMA1 association with lipid rafts and recruitment of the CC BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK CC complex, resulting in nuclear translocation and activation of NFKB1. CC Plays a direct role in the negative feedback regulation of the BCR CC signaling, by down-modulating BTK function via direct phosphorylation CC of BTK at 'Ser-180', which results in the alteration of BTK plasma CC membrane localization and in turn inhibition of BTK activity. Involved CC in apoptosis following oxidative damage: in case of oxidative CC conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of CC SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc CC acts as a reactive oxygen species producer. Acts as a coactivator of CC androgen receptor (ANDR)-dependent transcription, by being recruited to CC ANDR target genes and specifically mediating phosphorylation of 'Thr-6' CC of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional CC activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) CC by LSD1/KDM1A. In insulin signaling, may function downstream of IRS1 in CC muscle cells and mediate insulin-dependent DNA synthesis through the CC RAF1-MAPK/ERK signaling cascade. Participates in the regulation of CC glucose transport in adipocytes by negatively modulating the insulin- CC stimulated translocation of the glucose transporter SLC2A4/GLUT4. CC Phosphorylates SLC2A1/GLUT1, promoting glucose uptake by SLC2A1/GLUT1. CC Under high glucose in pancreatic beta-cells, is probably involved in CC the inhibition of the insulin gene transcription, via regulation of MYC CC expression. In endothelial cells, activation of PRKCB induces increased CC phosphorylation of RB1, increased VEGFA-induced cell proliferation, and CC inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) CC regulation by insulin, which causes endothelial dysfunction. Also CC involved in triglyceride homeostasis (By similarity). Phosphorylates CC ATF2 which promotes cooperation between ATF2 and JUN, activating CC transcription. Phosphorylates KLHL3 in response to angiotensin II CC signaling, decreasing the interaction between KLHL3 and WNK4 (By CC similarity). Phosphorylates and activates LRRK1, which phosphorylates CC RAB proteins involved in intracellular trafficking (By similarity). CC Acts as a regulator of dopamine signaling by mediating constitutive CC phosphorylation of dopamine receptors DRD1 and DRD2, inhibiting G CC protein-coupled receptor signaling (By similarity). CC {ECO:0000250|UniProtKB:P05771, ECO:0000250|UniProtKB:P68404, CC ECO:0000269|PubMed:10938109, ECO:0000269|PubMed:11714718, CC ECO:0000269|PubMed:19176525}. CC -!- FUNCTION: [Isoform Beta-II]: Acts as an activator of ferroptosis by CC mediating phosphorylation and activation of ACSL4. Also stimulates CC ferroptosis propagation by catalyzing phosphorylation of FOXK1. CC {ECO:0000250|UniProtKB:P05771}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + CC H(+); Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.13; CC Evidence={ECO:0000250|UniProtKB:P05771}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.13; CC Evidence={ECO:0000250|UniProtKB:P05771}; CC -!- CATALYTIC ACTIVITY: [Isoform Beta-II]: CC Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + CC H(+); Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.13; CC Evidence={ECO:0000250|UniProtKB:P05771}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990; CC Evidence={ECO:0000250|UniProtKB:P05771}; CC -!- CATALYTIC ACTIVITY: [Isoform Beta-II]: CC Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.13; CC Evidence={ECO:0000250|UniProtKB:P05771}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609; CC Evidence={ECO:0000250|UniProtKB:P05771}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00041, ECO:0000269|PubMed:21215369, CC ECO:0000269|PubMed:9817842}; CC Note=Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 CC domain. {ECO:0000269|PubMed:21215369, ECO:0000269|PubMed:9817842}; CC -!- ACTIVITY REGULATION: Classical (or conventional) PKCs (PRKCA, PRKCB and CC PRKCG) are activated by calcium and diacylglycerol (DAG) in the CC presence of phosphatidylserine. Three specific sites; Thr-500 CC (activation loop of the kinase domain), Thr-642 (turn motif) and Ser- CC 661 (hydrophobic region), need to be phosphorylated for its full CC activation. Specifically inhibited by enzastaurin (LY317615) (By CC similarity). {ECO:0000250}. CC -!- SUBUNIT: Interacts with PDK1. Interacts in vitro with PRKCBP1. CC Interacts with PHLPP1 and PHLPP2; both proteins mediate its CC dephosphorylation. Interacts with KDM1A/LSD1, PKN1 and ANDR (By CC similarity). {ECO:0000250}. CC -!- INTERACTION: CC P68403; P18052: Ptpra; Xeno; NbExp=3; IntAct=EBI-397072, EBI-6597520; CC P68403-1; Q62920: Pdlim5; NbExp=5; IntAct=EBI-12559950, EBI-918433; CC P68403-2; Q8WV44-2: TRIM41; Xeno; NbExp=3; IntAct=EBI-397092, EBI-726015; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000250}. Membrane; CC Peripheral membrane protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Beta-I; CC IsoId=P68403-1, P04410-1; Sequence=Displayed; CC Name=Beta-II; CC IsoId=P68403-2, P04410-2; Sequence=VSP_004739; CC -!- PTM: Phosphorylation on Thr-500 of isoform beta-I, within the CC activation loop, renders it competent to autophosphorylate. Subsequent CC autophosphorylation of Thr-642 maintains catalytic competence, and CC autophosphorylation on Ser-661 appears to release the kinase into the CC cytosol. Similarly, isoform beta-II is autophosphorylated on 'Thr-641' CC and 'Ser-660', subsequent to phosphorylation on Thr-500. CC Autophosphorylated on other sites i.e. in the N-terminal and hinge CC regions have no effect on enzyme activity. Phosphorylation at Tyr-662 CC by SYK induces binding with GRB2 and contributes to the activation of CC MAPK/ERK signaling cascade. {ECO:0000269|PubMed:21215369, CC ECO:0000269|PubMed:7961692, ECO:0000269|PubMed:8327493, CC ECO:0000269|PubMed:8749392}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr CC protein kinase family. PKC subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M13706; AAA41875.1; -; mRNA. DR EMBL; K03485; AAA41864.1; -; mRNA. DR EMBL; K03486; AAA41865.1; -; mRNA. DR EMBL; X04439; CAA28035.1; -; Genomic_DNA. DR EMBL; X04440; CAA28036.1; -; mRNA. DR EMBL; M19007; AAA41868.1; -; mRNA. DR EMBL; X04139; CAA27756.1; -; mRNA. DR EMBL; M15522; AAA41876.1; -; mRNA. DR PIR; A00622; KIRTC1. DR RefSeq; NP_001165776.1; NM_001172305.1. DR RefSeq; XP_038957160.1; XM_039101232.2. [P68403-2] DR RefSeq; XP_038957162.1; XM_039101234.2. [P68403-1] DR PDB; 1A25; X-ray; 2.70 A; A/B=154-289. DR PDB; 3PFQ; X-ray; 4.00 A; A=1-668. DR AlphaFoldDB; P68403; -. DR SMR; P68403; -. DR BioGRID; 247103; 17. DR FunCoup; P68403; 1958. DR IntAct; P68403; 7. DR MINT; P68403; -. DR STRING; 10116.ENSRNOP00000016417; -. DR BindingDB; P68403; -. DR ChEMBL; CHEMBL3020; -. DR DrugCentral; P68403; -. DR GlyGen; P68403; 4 sites, 1 O-linked glycan (4 sites). DR iPTMnet; P68403; -. DR PhosphoSitePlus; P68403; -. DR jPOST; P68403; -. DR PaxDb; 10116-ENSRNOP00000016417; -. DR Ensembl; ENSRNOT00000016418.8; ENSRNOP00000016417.5; ENSRNOG00000012061.10. [P68403-1] DR Ensembl; ENSRNOT00000078705.3; ENSRNOP00000073511.2; ENSRNOG00000012061.10. [P68403-2] DR Ensembl; ENSRNOT00055013848; ENSRNOP00055011102; ENSRNOG00055008014. [P68403-1] DR Ensembl; ENSRNOT00060053332; ENSRNOP00060044337; ENSRNOG00060030161. [P68403-1] DR Ensembl; ENSRNOT00065021344; ENSRNOP00065016504; ENSRNOG00065013001. [P68403-1] DR GeneID; 25023; -. DR KEGG; rno:25023; -. DR UCSC; RGD:3396; rat. DR AGR; RGD:3396; -. DR CTD; 5579; -. DR RGD; 3396; Prkcb. DR eggNOG; KOG0696; Eukaryota. DR GeneTree; ENSGT00940000155217; -. DR InParanoid; P68403; -. DR OMA; YYNINIS; -. DR PhylomeDB; P68403; -. DR BRENDA; 2.7.1.107; 5301. DR Reactome; R-RNO-114516; Disinhibition of SNARE formation. DR Reactome; R-RNO-1169091; Activation of NF-kappaB in B cells. DR Reactome; R-RNO-416993; Trafficking of GluR2-containing AMPA receptors. DR Reactome; R-RNO-4419969; Depolymerization of the Nuclear Lamina. DR Reactome; R-RNO-5099900; WNT5A-dependent internalization of FZD4. DR Reactome; R-RNO-5218921; VEGFR2 mediated cell proliferation. DR Reactome; R-RNO-5668599; RHO GTPases Activate NADPH Oxidases. DR Reactome; R-RNO-76005; Response to elevated platelet cytosolic Ca2+. DR EvolutionaryTrace; P68403; -. DR PRO; PR:P68403; -. DR Proteomes; UP000002494; Chromosome 1. DR ExpressionAtlas; P68403; baseline and differential. DR GO; GO:0031526; C:brush border membrane; IDA:RGD. DR GO; GO:0044305; C:calyx of Held; ISO:RGD. DR GO; GO:0005813; C:centrosome; IDA:RGD. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0005829; C:cytosol; IDA:RGD. DR GO; GO:0016020; C:membrane; ISO:RGD. DR GO; GO:0005654; C:nucleoplasm; ISO:RGD. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISO:RGD. DR GO; GO:0099523; C:presynaptic cytosol; ISO:RGD. DR GO; GO:0008091; C:spectrin; ISO:RGD. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0005246; F:calcium channel regulator activity; ISO:RGD. DR GO; GO:0004698; F:calcium,diacylglycerol-dependent serine/threonine kinase activity; ISO:RGD. DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB. DR GO; GO:0004697; F:diacylglycerol-dependent serine/threonine kinase activity; ISO:RGD. DR GO; GO:0042393; F:histone binding; ISS:UniProtKB. DR GO; GO:0035403; F:histone H3T6 kinase activity; ISS:UniProtKB. DR GO; GO:0050681; F:nuclear androgen receptor binding; ISS:UniProtKB. DR GO; GO:0005080; F:protein kinase C binding; ISO:RGD. DR GO; GO:0106310; F:protein serine kinase activity; ISS:UniProtKB. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0042113; P:B cell activation; ISS:UniProtKB. DR GO; GO:0050853; P:B cell receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0006816; P:calcium ion transport; ISO:RGD. DR GO; GO:0071322; P:cellular response to carbohydrate stimulus; ISO:RGD. DR GO; GO:0018894; P:dibenzo-p-dioxin metabolic process; IEP:RGD. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; ISO:RGD. DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central. DR GO; GO:0010829; P:negative regulation of D-glucose transmembrane transport; ISS:UniProtKB. DR GO; GO:0060160; P:negative regulation of dopamine receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0007207; P:phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway; ISO:RGD. DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; ISS:UniProtKB. DR GO; GO:0160020; P:positive regulation of ferroptosis; ISS:UniProtKB. DR GO; GO:0042488; P:positive regulation of odontogenesis of dentin-containing tooth; IEP:RGD. DR GO; GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0070528; P:protein kinase C signaling; ISS:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD. DR GO; GO:0010827; P:regulation of D-glucose transmembrane transport; ISS:UniProtKB. DR GO; GO:0014059; P:regulation of dopamine secretion; IMP:RGD. DR GO; GO:0040008; P:regulation of growth; IMP:RGD. DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; ISO:RGD. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:1990776; P:response to angiotensin; IDA:RGD. DR GO; GO:0045471; P:response to ethanol; IEP:RGD. DR GO; GO:0009749; P:response to glucose; IEP:RGD. DR GO; GO:0001666; P:response to hypoxia; ISO:RGD. DR GO; GO:0033280; P:response to vitamin D; IEP:RGD. DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:RGD. DR CDD; cd20833; C1_cPKC_rpt1; 1. DR CDD; cd20836; C1_cPKC_rpt2; 1. DR CDD; cd04026; C2_PKC_alpha_gamma; 1. DR CDD; cd05616; STKc_cPKC_beta; 1. DR FunFam; 2.60.40.150:FF:000012; Kinase C alpha type; 1. DR FunFam; 1.10.510.10:FF:000023; Protein kinase C; 1. DR FunFam; 3.30.200.20:FF:000080; Protein kinase C; 1. DR FunFam; 3.30.60.20:FF:000006; Protein kinase C; 1. DR FunFam; 3.30.60.20:FF:000031; Protein kinase C alpha; 1. DR Gene3D; 3.30.60.20; -; 2. DR Gene3D; 2.60.40.150; C2 domain; 1. DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 2. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR000961; AGC-kinase_C. DR InterPro; IPR046349; C1-like_sf. DR InterPro; IPR000008; C2_dom. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR034664; cPKC-beta. DR InterPro; IPR020454; DAG/PE-bd. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR002219; PKC_DAG/PE. DR InterPro; IPR017892; Pkinase_C. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR014375; Protein_kinase_C_a/b/g. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR24351; RIBOSOMAL PROTEIN S6 KINASE; 1. DR Pfam; PF00130; C1_1; 2. DR Pfam; PF00168; C2; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF00433; Pkinase_C; 1. DR PIRSF; PIRSF000550; PKC_alpha; 1. DR PRINTS; PR00360; C2DOMAIN. DR PRINTS; PR00008; DAGPEDOMAIN. DR SMART; SM00109; C1; 2. DR SMART; SM00239; C2; 1. DR SMART; SM00133; S_TK_X; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF57889; Cysteine-rich domain; 2. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS51285; AGC_KINASE_CTER; 1. DR PROSITE; PS50004; C2; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR PROSITE; PS00479; ZF_DAG_PE_1; 2. DR PROSITE; PS50081; ZF_DAG_PE_2; 2. DR PDBsum; 1A25; -. DR PDBsum; 3PFQ; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Adaptive immunity; Alternative splicing; KW Apoptosis; ATP-binding; Calcium; Chromatin regulator; Cytoplasm; KW Direct protein sequencing; Immunity; Kinase; Membrane; Metal-binding; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat; KW Serine/threonine-protein kinase; Transcription; Transcription regulation; KW Transferase; Zinc; Zinc-finger. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P05771" FT CHAIN 2..671 FT /note="Protein kinase C beta type" FT /id="PRO_0000055687" FT DOMAIN 158..275 FT /note="C2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT DOMAIN 342..600 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 601..671 FT /note="AGC-kinase C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618" FT ZN_FING 36..86 FT /note="Phorbol-ester/DAG-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226" FT ZN_FING 101..151 FT /note="Phorbol-ester/DAG-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226" FT REGION 614..635 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 623..635 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 466 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 186 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:21215369, FT ECO:0000269|PubMed:9817842" FT BINDING 187 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:21215369, FT ECO:0000269|PubMed:9817842" FT BINDING 187 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:21215369, FT ECO:0000269|PubMed:9817842" FT BINDING 193 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:21215369, FT ECO:0000269|PubMed:9817842" FT BINDING 246 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:21215369, FT ECO:0000269|PubMed:9817842" FT BINDING 246 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:21215369, FT ECO:0000269|PubMed:9817842" FT BINDING 247 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:21215369, FT ECO:0000269|PubMed:9817842" FT BINDING 248 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:21215369, FT ECO:0000269|PubMed:9817842" FT BINDING 248 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:21215369, FT ECO:0000269|PubMed:9817842" FT BINDING 248 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:21215369, FT ECO:0000269|PubMed:9817842" FT BINDING 251 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:21215369, FT ECO:0000269|PubMed:9817842" FT BINDING 252 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:21215369, FT ECO:0000269|PubMed:9817842" FT BINDING 254 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:21215369, FT ECO:0000269|PubMed:9817842" FT BINDING 254 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:21215369, FT ECO:0000269|PubMed:9817842" FT BINDING 348..356 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 371 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000250|UniProtKB:P05771" FT MOD_RES 11 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 16 FT /note="Phosphoserine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:8327493" FT MOD_RES 17 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:8327493" FT MOD_RES 206 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P05771" FT MOD_RES 250 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000250" FT MOD_RES 314 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:8327493" FT MOD_RES 324 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:8327493" FT MOD_RES 500 FT /note="Phosphothreonine; by PDPK1" FT /evidence="ECO:0000305|PubMed:21215369, FT ECO:0000305|PubMed:7961692, ECO:0000305|PubMed:8749392" FT MOD_RES 504 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P05771" FT MOD_RES 635 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:8327493" FT MOD_RES 642 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:21215369, FT ECO:0000269|PubMed:8327493, ECO:0000269|PubMed:8749392, FT ECO:0007744|PubMed:22673903" FT MOD_RES 661 FT /note="Phosphoserine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:21215369, FT ECO:0000269|PubMed:8749392" FT MOD_RES 662 FT /note="Phosphotyrosine; by SYK" FT /evidence="ECO:0000250|UniProtKB:P68404" FT VAR_SEQ 622..671 FT /note="RDKRDTSNFDKEFTRQPVELTPTDKLFIMNLDQNEFAGFSYTNPEFVINV FT -> CGRNAENFDRFFTRHPPVLTPPDQEVIRNIDQSEFEGFSFVNSEFLKPEVKS (in FT isoform Beta-II)" FT /evidence="ECO:0000303|PubMed:2428667, FT ECO:0000303|PubMed:3755379" FT /id="VSP_004739" FT MUTAGEN 16..17 FT /note="ST->AA: No effect." FT /evidence="ECO:0000269|PubMed:8327493" FT MUTAGEN 314 FT /note="T->A: No effect; when associated with A-323." FT /evidence="ECO:0000269|PubMed:8327493" FT MUTAGEN 324 FT /note="T->A: No effect; when associated with A-313." FT /evidence="ECO:0000269|PubMed:8327493" FT MUTAGEN 500 FT /note="T->E: 50% increase of enzymatic activity." FT /evidence="ECO:0000269|PubMed:7961692" FT MUTAGEN 500 FT /note="T->S: 50% decrease of enzymatic activity." FT /evidence="ECO:0000269|PubMed:7961692" FT MUTAGEN 500 FT /note="T->V,D: Loss of enzymatic activity." FT /evidence="ECO:0000269|PubMed:7961692" FT MUTAGEN 635 FT /note="T->A: Loss of enzymatic activity; when associated FT with T-643 change in subcellular location, loss of FT PMA-induced down-regulation and loss of enzymatic FT activity." FT /evidence="ECO:0000269|PubMed:8034726, FT ECO:0000269|PubMed:8327493" FT MUTAGEN 642 FT /note="T->A: Loss of enzymatic activity; when associated FT with T-636 change in subcellular location, loss of FT PMA-induced down-regulation and loss of enzymatic FT activity." FT /evidence="ECO:0000269|PubMed:8034726, FT ECO:0000269|PubMed:8327493" FT CONFLICT 25 FT /note="A -> P (in Ref. 3; AAA41868)" FT /evidence="ECO:0000305" FT CONFLICT 126 FT /note="I -> V (in Ref. 1; AAA41875)" FT /evidence="ECO:0000305" FT CONFLICT 138 FT /note="N -> S (in Ref. 1; AAA41875)" FT /evidence="ECO:0000305" FT CONFLICT 141 FT /note="K -> R (in Ref. 1; AAA41875)" FT /evidence="ECO:0000305" FT CONFLICT 149 FT /note="S -> G (in Ref. 1; AAA41875)" FT /evidence="ECO:0000305" FT CONFLICT 164 FT /note="I -> V (in Ref. 1; AAA41875)" FT /evidence="ECO:0000305" FT CONFLICT 170..171 FT /note="RE -> GG (in Ref. 1; AAA41875)" FT /evidence="ECO:0000305" FT CONFLICT 174 FT /note="I -> V (in Ref. 1; AAA41875)" FT /evidence="ECO:0000305" FT CONFLICT 294 FT /note="G -> E (in Ref. 3; AAA41868)" FT /evidence="ECO:0000305" FT CONFLICT 419 FT /note="V -> M (in Ref. 2; CAA28035/CAA28036)" FT /evidence="ECO:0000305" FT CONFLICT 628 FT /note="Missing (in Ref. 1; AAA41865)" FT /evidence="ECO:0000305" FT CONFLICT 640 FT /note="Missing (in Ref. 1; AAA41865)" FT /evidence="ECO:0000305" FT STRAND 161..182 FT /evidence="ECO:0007829|PDB:1A25" FT HELIX 183..185 FT /evidence="ECO:0007829|PDB:1A25" FT STRAND 194..202 FT /evidence="ECO:0007829|PDB:1A25" FT HELIX 213..215 FT /evidence="ECO:0007829|PDB:1A25" FT STRAND 222..230 FT /evidence="ECO:0007829|PDB:1A25" FT HELIX 234..237 FT /evidence="ECO:0007829|PDB:1A25" FT STRAND 239..246 FT /evidence="ECO:0007829|PDB:1A25" FT STRAND 249..251 FT /evidence="ECO:0007829|PDB:1A25" FT STRAND 254..262 FT /evidence="ECO:0007829|PDB:1A25" FT HELIX 263..266 FT /evidence="ECO:0007829|PDB:1A25" FT STRAND 271..276 FT /evidence="ECO:0007829|PDB:1A25" FT HELIX 280..283 FT /evidence="ECO:0007829|PDB:1A25" FT MOD_RES P68403-2:641 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES P68403-2:654 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES P68403-2:660 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES P68403-2:664 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" SQ SEQUENCE 671 AA; 76751 MW; A1935030F758513C CRC64; MADPAAGPPP SEGEESTVRF ARKGALRQKN VHEVKNHKFT ARFFKQPTFC SHCTDFIWGF GKQGFQCQVC CFVVHKRCHE FVTFSCPGAD KGPASDDPRS KHKFKIHTYS SPTFCDHCGS LLYGLIHQGM KCDTCMMNVH KRCVMNVPSL CGTDHTERRG RIYIQAHIDR EVLIVVVRDA KNLVPMDPNG LSDPYVKLKL IPDPKSESKQ KTKTIKCSLN PEWNETFRFQ LKESDKDRRL SVEIWDWDLT SRNDFMGSLS FGISELQKAG VDGWFKLLSQ EEGEYFNVPV PPEGSEGNEE LRQKFERAKI GQGTKAPEEK TANTISKFDN NGNRDRMKLT DFNFLMVLGK GSFGKVMLSE RKGTDELYAV KILKKDVVIQ DDDVECTMVE KRVLALPGKP PFLTQLHSCF QTMDRLYFVM EYVNGGDLMY HIQQVGRFKE PHAVFYAAEI AIGLFFLQSK GIIYRDLKLD NVMLDSEGHI KIADFGMCKE NIWDGVTTKT FCGTPDYIAP EIIAYQPYGK SVDWWAFGVL LYEMLAGQAP FEGEDEDELF QSIMEHNVAY PKSMSKEAVA ICKGLMTKHP GKRLGCGPEG ERDIKEHAFF RYIDWEKLER KEIQPPYKPK ARDKRDTSNF DKEFTRQPVE LTPTDKLFIM NLDQNEFAGF SYTNPEFVIN V //