KPCB_RABIT
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-AUG-2022, entry version 183.
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; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; 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 (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. Phosphorylates ATF2 which
CC promotes cooperation between ATF2 and JUN, activating transcription.
CC {ECO:0000250|UniProtKB:P05771, ECO:0000250|UniProtKB:P68404}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; 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 -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.13;
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC Note=Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2
CC domain. {ECO:0000250|UniProtKB:P68403};
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 -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Membrane {ECO:0000250}; Peripheral membrane protein {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. 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-640'
CC and 'Ser-659', 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 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. PKC subfamily. {ECO:0000305}.
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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 AlphaFoldDB; P05772; -.
DR SMR; P05772; -.
DR STRING; 9986.ENSOCUP00000016353; -.
DR PRIDE; P05772; -.
DR GeneID; 100037719; -.
DR KEGG; ocu:100037719; -.
DR CTD; 5579; -.
DR eggNOG; KOG0696; Eukaryota.
DR InParanoid; P05772; -.
DR OrthoDB; 614710at2759; -.
DR BRENDA; 2.7.11.13; 1749.
DR Proteomes; UP000001811; Unplaced.
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:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004698; F:calcium-dependent protein kinase C activity; IEA:UniProtKB-EC.
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:0050681; F:nuclear androgen receptor binding; ISS:UniProtKB.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; ISS:UniProtKB.
DR GO; GO:0004697; F:protein kinase C activity; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
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:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0010829; P:negative regulation of glucose transmembrane 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:0043687; P:post-translational protein modification; ISS:UniProtKB.
DR GO; GO:0010827; P:regulation of glucose transmembrane transport; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR CDD; cd00029; C1; 2.
DR CDD; cd05616; STKc_cPKC_beta; 1.
DR Gene3D; 2.60.40.150; -; 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; PE/DAG-bd.
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 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 SUPFAM; SSF57889; SSF57889; 2.
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; Cytoplasm; Immunity; Kinase;
KW Membrane; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; Transcription;
KW Transcription regulation; 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_0000055686"
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 313..332
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 614..635
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 315..330
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 614..633
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:0000250|UniProtKB:P68403"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P68403"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P68403"
FT BINDING 193
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P68403"
FT BINDING 246
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P68403"
FT BINDING 246
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P68403"
FT BINDING 247
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P68403"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P68403"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P68403"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P68403"
FT BINDING 251
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P68403"
FT BINDING 252
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P68403"
FT BINDING 254
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P68403"
FT BINDING 254
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P68403"
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:0000250|UniProtKB:P05771"
FT MOD_RES 16
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P68403, ECO:0000255"
FT MOD_RES 17
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P68403, ECO:0000255"
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:0000250|UniProtKB:P68403, ECO:0000255"
FT MOD_RES 324
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P68403, ECO:0000255"
FT MOD_RES 500
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000250|UniProtKB:P05771"
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:0000250|UniProtKB:P68403"
FT MOD_RES 642
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P68403, ECO:0000255"
FT MOD_RES 661
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P05771"
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:3808073"
FT /id="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
