ID KPCB_RABIT Reviewed; 671 AA.
AC P05772; P05773;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-APR-2013, entry version 133.
DE RecName: Full=Protein kinase C beta type;
DE Short=PKC-B;
DE Short=PKC-beta;
DE EC=2.7.11.13;
GN Name=PRKCB; Synonyms=PRKCB1;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae;
OC Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS BETA-I AND BETA-II).
RC TISSUE=Brain;
RX PubMed=3808073; DOI=10.1038/325161a0;
RA Ohno S., Kawasaki H., Imajoh S., Suzuki K., Inagaki M., Yokokura H.,
RA Sakoh T., Hidaka H.;
RT "Tissue-specific expression of three distinct types of rabbit protein
RT kinase C.";
RL Nature 325:161-166(1987).
CC -!- FUNCTION: Calcium-activated, phospholipid- and diacylglycerol
CC (DAG)-dependent serine/threonine-protein kinase involved in
CC various cellular processes such as regulation of the B-cell
CC receptor (BCR) signalosome, oxidative stress-induced apoptosis,
CC androgen receptor-dependent transcription regulation, insulin
CC signaling and endothelial cells proliferation. Plays a key role in
CC B-cell activation by regulating BCR-induced NF-kappa-B activation.
CC Mediates the activation of the canonical NF-kappa-B pathway
CC (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559',
CC 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1
CC association with lipid rafts and recruitment of the BCL10-MALT1
CC complex as well as MAP3K7/TAK1, which then activates IKK complex,
CC resulting in nuclear translocation and activation of NFKB1. Plays
CC a direct role in the negative feedback regulation of the BCR
CC signaling, by down-modulating BTK function via direct
CC phosphorylation of BTK at 'Ser-180', which results in the
CC alteration of BTK plasma membrane localization and in turn
CC inhibition of BTK activity. Involved in apoptosis following
CC oxidative damage: in case of oxidative conditions, specifically
CC phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to
CC mitochondrial accumulation of p66Shc, where p66Shc acts as a
CC reactive oxygen species producer. Acts as a coactivator of
CC androgen receptor (ANDR)-dependent transcription, by being
CC recruited to ANDR target genes and specifically mediating
CC phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag
CC for epigenetic transcriptional activation that prevents
CC demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A. In
CC insulin signaling, may function downstream of IRS1 in muscle cells
CC and mediate insulin-dependent DNA synthesis through the RAF1-
CC MAPK/ERK signaling cascade. May participate in the regulation of
CC glucose transport in adipocytes by negatively modulating the
CC insulin-stimulated translocation of the glucose transporter
CC SLC2A4/GLUT4. Under high glucose in pancreatic beta-cells, is
CC probably involved in the inhibition of the insulin gene
CC transcription, via regulation of MYC expression. In endothelial
CC cells, activation of PRKCB induces increased phosphorylation of
CC RB1, increased VEGFA-induced cell proliferation, and inhibits
CC PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by
CC insulin, which causes endothelial dysfunction. Also involved in
CC triglyceride homeostasis (By similarity).
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- COFACTOR: Binds 3 calcium ions per subunit. The ions are bound to
CC the C2 domain (By similarity).
CC -!- ENZYME REGULATION: Classical (or conventional) PKCs (PRKCA, PRKCB
CC and PRKCG) are activated by calcium and diacylglycerol (DAG) in
CC the presence of phosphatidylserine. Three specific sites; Thr-500
CC (activation loop of the kinase domain), Thr-642 (turn motif) and
CC Ser-661 (hydrophobic region), need to be phosphorylated for its
CC full activation. Specifically inhibited by enzastaurin (LY317615)
CC (By similarity).
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).
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By
CC similarity). Membrane; Peripheral membrane protein (By
CC similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Beta-I;
CC IsoId=P05772-1; Sequence=Displayed;
CC Name=Beta-II;
CC IsoId=P05772-2; Sequence=VSP_004740;
CC -!- PTM: Phosphorylation on 'Thr-499' of isoform beta-I, within the
CC activation loop, renders it competent to autophosphorylate.
CC Subsequent autophosphorylation of Thr-642 maintains catalytic
CC competence, and autophosphorylation on Ser-661 appears to release
CC the kinase into the cytosol. Similarly, isoform beta-II is
CC autophosphorylated on 'Thr-640' and 'Ser-659', subsequent to
CC phosphorylation on Thr-500. Autophosphorylated on other sites i.e.
CC in the N-terminal and hinge regions have no effect on enzyme
CC activity. Phosphorylation at Tyr-662 by SYK induces binding with
CC GRB2 and contributes to the activation of MAPK/ERK signaling
CC cascade (By similarity).
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. PKC subfamily.
CC -!- SIMILARITY: Contains 1 AGC-kinase C-terminal domain.
CC -!- SIMILARITY: Contains 1 C2 domain.
CC -!- SIMILARITY: Contains 2 phorbol-ester/DAG-type zinc fingers.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
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DR EMBL; X04795; CAA28482.1; -; mRNA.
DR EMBL; X04793; CAA28480.1; -; mRNA.
DR PIR; A26037; KIRBC2.
DR PIR; B26037; KIRBC1.
DR RefSeq; NP_001095193.1; NM_001101723.1.
DR RefSeq; NP_001095195.1; NM_001101725.1.
DR UniGene; Ocu.3267; -.
DR ProteinModelPortal; P05772; -.
DR SMR; P05772; 37-288, 339-668.
DR STRING; 9986.ENSOCUP00000016353; -.
DR GeneID; 100037719; -.
DR CTD; 5579; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000233022; -.
DR HOVERGEN; HBG108317; -.
DR BRENDA; 2.7.11.13; 1749.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0050681; F:androgen receptor binding; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0042393; F:histone binding; ISS:UniProtKB.
DR GO; GO:0035403; F:histone kinase activity (H3-T6 specific); ISS:UniProtKB.
DR GO; GO:0030374; F:ligand-dependent nuclear receptor transcription coactivator activity; ISS:UniProtKB.
DR GO; GO:0004697; F:protein kinase C activity; IEA:EC.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
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:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0010829; P:negative regulation of glucose transport; ISS:UniProtKB.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0050861; P:positive regulation of B cell receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; ISS:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR000008; C2_Ca-dep.
DR InterPro; IPR008973; C2_Ca/lipid-bd_dom_CaLB.
DR InterPro; IPR020477; C2_dom.
DR InterPro; IPR018029; C2_membr_targeting.
DR InterPro; IPR020454; DAG/PE-bd.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR002219; Prot_Kinase_C-like_PE/DAG-bd.
DR InterPro; IPR000719; Prot_kinase_cat_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR014375; Protein_kinase_C_a/b/g.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
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_CaLB; 1.
DR SUPFAM; SSF56112; Kinase_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.
PE 2: Evidence at transcript level;
KW Acetylation; Adaptive immunity; Alternative splicing; Apoptosis;
KW ATP-binding; Calcium; Chromatin regulator; Complete proteome;
KW Cytoplasm; Immunity; Kinase; Membrane; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Serine/threonine-protein kinase; Transcription;
KW Transcription regulation; Transferase; Zinc; Zinc-finger.
FT INIT_MET 1 1 Removed (By similarity).
FT CHAIN 2 671 Protein kinase C beta type.
FT /FTId=PRO_0000055686.
FT DOMAIN 173 260 C2.
FT DOMAIN 342 600 Protein kinase.
FT DOMAIN 601 671 AGC-kinase C-terminal.
FT ZN_FING 36 86 Phorbol-ester/DAG-type 1.
FT ZN_FING 101 151 Phorbol-ester/DAG-type 2.
FT NP_BIND 348 356 ATP (By similarity).
FT ACT_SITE 466 466 Proton acceptor (By similarity).
FT METAL 186 186 Calcium 1; via carbonyl oxygen (By
FT similarity).
FT METAL 187 187 Calcium 1 (By similarity).
FT METAL 187 187 Calcium 2 (By similarity).
FT METAL 193 193 Calcium 2 (By similarity).
FT METAL 246 246 Calcium 1 (By similarity).
FT METAL 246 246 Calcium 2 (By similarity).
FT METAL 247 247 Calcium 2; via carbonyl oxygen (By
FT similarity).
FT METAL 248 248 Calcium 1 (By similarity).
FT METAL 248 248 Calcium 2 (By similarity).
FT METAL 248 248 Calcium 3 (By similarity).
FT METAL 251 251 Calcium 3 (By similarity).
FT METAL 252 252 Calcium 3; via carbonyl oxygen (By
FT similarity).
FT METAL 254 254 Calcium 1 (By similarity).
FT METAL 254 254 Calcium 3 (By similarity).
FT BINDING 371 371 ATP (By similarity).
FT MOD_RES 2 2 N-acetylalanine (By similarity).
FT MOD_RES 16 16 Phosphoserine; by autocatalysis
FT (Potential).
FT MOD_RES 17 17 Phosphothreonine; by autocatalysis
FT (Potential).
FT MOD_RES 195 195 Phosphotyrosine (By similarity).
FT MOD_RES 250 250 Phosphothreonine; by autocatalysis (By
FT similarity).
FT MOD_RES 314 314 Phosphothreonine; by autocatalysis
FT (Potential).
FT MOD_RES 324 324 Phosphothreonine; by autocatalysis
FT (Potential).
FT MOD_RES 500 500 Phosphothreonine; by PDPK1 (By
FT similarity).
FT MOD_RES 504 504 Phosphothreonine (By similarity).
FT MOD_RES 635 635 Phosphothreonine; by autocatalysis
FT (Potential).
FT MOD_RES 642 642 Phosphothreonine (Potential).
FT MOD_RES 661 661 Phosphoserine; by autocatalysis (By
FT similarity).
FT MOD_RES 662 662 Phosphotyrosine; by SYK (By similarity).
FT VAR_SEQ 622 671 RDKRDTSNFDKEFTRQPVELTPTDKLFIMNLDQNEFAGFSY
FT TNPEFVINV -> CGRNAENFDRFFTRHPPVLTPPDQEVIR
FT NIDQSEFEGFSFVNSEFLKPEVKS (in isoform
FT Beta-II).
FT /FTId=VSP_004740.
SQ SEQUENCE 671 AA; 76828 MW; DFBF22EEB3D41861 CRC64;
MADPAAGQPP 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 GQGTKTPEEK TTNTISKFDN 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 ERDIKDHAFF
RYIDWEKLER KEIQPPYKPK ARDKRDTSNF DKEFTRQPVE LTPTDKLFIM NLDQNEFAGF
SYTNPEFVIN V
//
