CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-002291
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Protein kinase C beta type 
Protein Synonyms/Alias
 PKC-B; PKC-beta 
Gene Name
 PRKCB 
Gene Synonyms/Alias
 PKCB; PRKCB1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
141TCMMNVHKRCVMNVPubiquitination[1]
197GLSDPYVKLKLIPDPubiquitination[1]
199SDPYVKLKLIPDPKSubiquitination[1]
362KVMLSERKGTDELYAubiquitination[1]
489IADFGMCKENIWDGVubiquitination[1]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 
Functional Description
 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). 
Sequence Annotation
 DOMAIN 173 260 C2.
 DOMAIN 342 600 Protein kinase.
 DOMAIN 601 671 AGC-kinase C-terminal.
 ZN_FING 36 86 Phorbol-ester/DAG-type 1.
 ZN_FING 101 151 Phorbol-ester/DAG-type 2.
 NP_BIND 348 356 ATP (By similarity).
 ACT_SITE 466 466 Proton acceptor (By similarity).
 METAL 186 186 Calcium 1; via carbonyl oxygen (By
 METAL 187 187 Calcium 1 (By similarity).
 METAL 187 187 Calcium 2 (By similarity).
 METAL 193 193 Calcium 2 (By similarity).
 METAL 246 246 Calcium 1 (By similarity).
 METAL 246 246 Calcium 2 (By similarity).
 METAL 247 247 Calcium 2; via carbonyl oxygen (By
 METAL 248 248 Calcium 1 (By similarity).
 METAL 248 248 Calcium 2 (By similarity).
 METAL 248 248 Calcium 3 (By similarity).
 METAL 251 251 Calcium 3 (By similarity).
 METAL 252 252 Calcium 3; via carbonyl oxygen (By
 METAL 254 254 Calcium 1 (By similarity).
 METAL 254 254 Calcium 3 (By similarity).
 BINDING 371 371 ATP (By similarity).
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 16 16 Phosphoserine; by autocatalysis
 MOD_RES 17 17 Phosphothreonine; by autocatalysis
 MOD_RES 195 195 Phosphotyrosine (By similarity).
 MOD_RES 250 250 Phosphothreonine; by autocatalysis (By
 MOD_RES 314 314 Phosphothreonine; by autocatalysis
 MOD_RES 324 324 Phosphothreonine; by autocatalysis
 MOD_RES 500 500 Phosphothreonine; by PDPK1 (Probable).
 MOD_RES 504 504 Phosphothreonine.
 MOD_RES 635 635 Phosphothreonine; by autocatalysis.
 MOD_RES 642 642 Phosphothreonine.
 MOD_RES 661 661 Phosphoserine; by autocatalysis.
 MOD_RES 662 662 Phosphotyrosine; by SYK (By similarity).  
Keyword
 3D-structure; Acetylation; Adaptive immunity; Alternative splicing; Apoptosis; ATP-binding; Calcium; Chromatin regulator; Complete proteome; Cytoplasm; Direct protein sequencing; Immunity; Kinase; Membrane; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Serine/threonine-protein kinase; Transcription; Transcription regulation; Transferase; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 671 AA 
Protein Sequence
MADPAAGPPP SEGEESTVRF ARKGALRQKN VHEVKNHKFT ARFFKQPTFC SHCTDFIWGF 60
GKQGFQCQVC CFVVHKRCHE FVTFSCPGAD KGPASDDPRS KHKFKIHTYS SPTFCDHCGS 120
LLYGLIHQGM KCDTCMMNVH KRCVMNVPSL CGTDHTERRG RIYIQAHIDR DVLIVLVRDA 180
KNLVPMDPNG LSDPYVKLKL IPDPKSESKQ KTKTIKCSLN PEWNETFRFQ LKESDKDRRL 240
SVEIWDWDLT SRNDFMGSLS FGISELQKAS VDGWFKLLSQ EEGEYFNVPV PPEGSEANEE 300
LRQKFERAKI SQGTKVPEEK TTNTVSKFDN NGNRDRMKLT DFNFLMVLGK GSFGKVMLSE 360
RKGTDELYAV KILKKDVVIQ DDDVECTMVE KRVLALPGKP PFLTQLHSCF QTMDRLYFVM 420
EYVNGGDLMY HIQQVGRFKE PHAVFYAAEI AIGLFFLQSK GIIYRDLKLD NVMLDSEGHI 480
KIADFGMCKE NIWDGVTTKT FCGTPDYIAP EIIAYQPYGK SVDWWAFGVL LYEMLAGQAP 540
FEGEDEDELF QSIMEHNVAY PKSMSKEAVA ICKGLMTKHP GKRLGCGPEG ERDIKEHAFF 600
RYIDWEKLER KEIQPPYKPK ACGRNAENFD RFFTRHPPVL TPPDQEVIRN IDQSEFEGFS 660
FVNSEFLKPE VKS 673 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0005886; C:plasma membrane; IDA:UniProtKB.
 GO:0050681; F:androgen receptor binding; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0005246; F:calcium channel regulator activity; IEA:Compara.
 GO:0003682; F:chromatin binding; IDA:UniProtKB.
 GO:0042393; F:histone binding; IDA:UniProtKB.
 GO:0035403; F:histone kinase activity (H3-T6 specific); IDA:UniProtKB.
 GO:0030374; F:ligand-dependent nuclear receptor transcription coactivator activity; IMP:UniProtKB.
 GO:0004697; F:protein kinase C activity; TAS:ProtInc.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0042113; P:B cell activation; ISS:UniProtKB.
 GO:0050853; P:B cell receptor signaling pathway; ISS:UniProtKB.
 GO:0006816; P:calcium ion transport; IEA:Compara.
 GO:0006874; P:cellular calcium ion homeostasis; IEA:Compara.
 GO:0071322; P:cellular response to carbohydrate stimulus; IEA:Compara.
 GO:0035556; P:intracellular signal transduction; IEA:InterPro.
 GO:0042953; P:lipoprotein transport; TAS:BHF-UCL.
 GO:0010829; P:negative regulation of glucose transport; ISS:UniProtKB.
 GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISS:UniProtKB.
 GO:0030168; P:platelet activation; TAS:Reactome.
 GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
 GO:0050861; P:positive regulation of B cell receptor signaling pathway; ISS:UniProtKB.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; ISS:UniProtKB.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
 GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; ISS:UniProtKB.
 GO:0006357; P:regulation of transcription from RNA polymerase II promoter; IMP:UniProtKB.
 GO:0007268; P:synaptic transmission; TAS:Reactome.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 
Interpro
 IPR000961; AGC-kinase_C.
 IPR000008; C2_Ca-dep.
 IPR008973; C2_Ca/lipid-bd_dom_CaLB.
 IPR020477; C2_dom.
 IPR018029; C2_membr_targeting.
 IPR020454; DAG/PE-bd.
 IPR011009; Kinase-like_dom.
 IPR017892; Pkinase_C.
 IPR002219; Prot_Kinase_C-like_PE/DAG-bd.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR014375; Protein_kinase_C_a/b/g.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 
Pfam
 PF00130; C1_1
 PF00168; C2
 PF00069; Pkinase
 PF00433; Pkinase_C 
SMART
 SM00109; C1
 SM00239; C2
 SM00133; S_TK_X
 SM00220; S_TKc 
PROSITE
 PS51285; AGC_KINASE_CTER
 PS50004; C2
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST
 PS00479; ZF_DAG_PE_1
 PS50081; ZF_DAG_PE_2 
PRINTS
 PR00360; C2DOMAIN.
 PR00008; DAGPEDOMAIN.