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Database: UniProt
Entry: P05772
LinkDB: P05772
Original site: P05772 
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   01-OCT-2014, entry version 140.
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. Phosphorylates ATF2 which promotes
CC       cooperation between ATF2 and JUN, activating transcription (By
CC       similarity). {ECO:0000250}.
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). {ECO:0000250}.
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). {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   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus
CC       {ECO:0000250}. Membrane {ECO:0000250}; Peripheral membrane protein
CC       {ECO:0000250}.
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). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC       protein kinase family. PKC subfamily. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 1 AGC-kinase C-terminal domain.
CC       {ECO:0000305}.
CC   -!- SIMILARITY: Contains 1 C2 domain. {ECO:0000255|PROSITE-
CC       ProRule:PRU00041}.
CC   -!- SIMILARITY: Contains 2 phorbol-ester/DAG-type zinc fingers.
CC       {ECO:0000255|PROSITE-ProRule:PRU00226}.
CC   -!- SIMILARITY: Contains 1 protein kinase domain.
CC       {ECO:0000255|PROSITE-ProRule:PRU00159}.
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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. [P05772-2]
DR   RefSeq; NP_001095195.1; NM_001101725.1. [P05772-1]
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:UniProtKB-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:0035408; P:histone H3-T6 phosphorylation; 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 signaling; 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-templated; IEA:UniProtKB-KW.
DR   Gene3D; 2.60.40.150; -; 1.
DR   InterPro; IPR000961; AGC-kinase_C.
DR   InterPro; IPR000008; C2_dom.
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_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; SSF49562; 1.
DR   SUPFAM; SSF56112; SSF56112; 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. {ECO:0000250}.
FT   CHAIN         2    671       Protein kinase C beta type.
FT                                /FTId=PRO_0000055686.
FT   DOMAIN      173    260       C2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00041}.
FT   DOMAIN      342    600       Protein kinase. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159}.
FT   DOMAIN      601    671       AGC-kinase C-terminal.
FT   ZN_FING      36     86       Phorbol-ester/DAG-type 1.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00226}.
FT   ZN_FING     101    151       Phorbol-ester/DAG-type 2.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00226}.
FT   NP_BIND     348    356       ATP. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159}.
FT   ACT_SITE    466    466       Proton acceptor. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159, ECO:0000255|PROSITE-
FT                                ProRule:PRU10027}.
FT   METAL       186    186       Calcium 1; via carbonyl oxygen.
FT                                {ECO:0000250}.
FT   METAL       187    187       Calcium 1. {ECO:0000250}.
FT   METAL       187    187       Calcium 2. {ECO:0000250}.
FT   METAL       193    193       Calcium 2. {ECO:0000250}.
FT   METAL       246    246       Calcium 1. {ECO:0000250}.
FT   METAL       246    246       Calcium 2. {ECO:0000250}.
FT   METAL       247    247       Calcium 2; via carbonyl oxygen.
FT                                {ECO:0000250}.
FT   METAL       248    248       Calcium 1. {ECO:0000250}.
FT   METAL       248    248       Calcium 2. {ECO:0000250}.
FT   METAL       248    248       Calcium 3. {ECO:0000250}.
FT   METAL       251    251       Calcium 3. {ECO:0000250}.
FT   METAL       252    252       Calcium 3; via carbonyl oxygen.
FT                                {ECO:0000250}.
FT   METAL       254    254       Calcium 1. {ECO:0000250}.
FT   METAL       254    254       Calcium 3. {ECO:0000250}.
FT   BINDING     371    371       ATP. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159}.
FT   MOD_RES       2      2       N-acetylalanine. {ECO:0000250}.
FT   MOD_RES      16     16       Phosphoserine; by autocatalysis.
FT                                {ECO:0000255}.
FT   MOD_RES      17     17       Phosphothreonine; by autocatalysis.
FT                                {ECO:0000255}.
FT   MOD_RES     250    250       Phosphothreonine; by autocatalysis.
FT                                {ECO:0000250}.
FT   MOD_RES     314    314       Phosphothreonine; by autocatalysis.
FT                                {ECO:0000255}.
FT   MOD_RES     324    324       Phosphothreonine; by autocatalysis.
FT                                {ECO:0000255}.
FT   MOD_RES     500    500       Phosphothreonine; by PDPK1.
FT                                {ECO:0000250}.
FT   MOD_RES     504    504       Phosphothreonine. {ECO:0000250}.
FT   MOD_RES     635    635       Phosphothreonine; by autocatalysis.
FT                                {ECO:0000255}.
FT   MOD_RES     642    642       Phosphothreonine. {ECO:0000255}.
FT   MOD_RES     661    661       Phosphoserine; by autocatalysis.
FT                                {ECO:0000250}.
FT   MOD_RES     662    662       Phosphotyrosine; by SYK. {ECO:0000250}.
FT   VAR_SEQ     622    671       RDKRDTSNFDKEFTRQPVELTPTDKLFIMNLDQNEFAGFSY
FT                                TNPEFVINV -> CGRNAENFDRFFTRHPPVLTPPDQEVIR
FT                                NIDQSEFEGFSFVNSEFLKPEVKS (in isoform
FT                                Beta-II). {ECO:0000303|PubMed:3808073}.
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
//
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