EKS-HOS-00174

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00174

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
AGC/PKC	479.5	1.4E-143	342	600	259

Status

Reviewed

Ensembl Protein

ENSP00000305355

UniProt Accession

P05771; C5IFJ8; D3DWF5; O43744; P05127; Q15138; Q93060; Q9UE49; Q9UE50; Q9UEH8; Q9UJ30; Q9UJ33;

Protein Name

Protein kinase C beta type

Protein Synonyms/Alias

PKC-B; PKC-beta;

Gene Name

PRKCB

Gene Synonyms/Alias

PRKCB; PKCB, PRKCB1;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000166501	ENSP00000457980	ENST00000472066
ENSG00000166501	ENSP00000458564	ENST00000466124
ENSG00000166501	ENSP00000305355	ENST00000303531
ENSG00000166501	ENSP00000459227	ENST00000498739
ENSG00000166501	ENSP00000454428	ENST00000498058
ENSG00000166501	ENSP00000318315	ENST00000321728

Organism

Homo sapiens

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).

Protein Length

673

Protein Sequence
(FASTA)

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

Nucleotide Sequence
(FASTA)

ATGGCTGACC CGGCTGCGGG GCCGCCGCCG AGCGAGGGCG AGGAGAGCAC CGTGCGCTTC 60

GCCCGCAAAG GCGCCCTCCG GCAGAAGAAC GTGCATGAGG TCAAGAACCA CAAATTCACC 120

GCCCGCTTCT TCAAGCAGCC CACCTTCTGC AGCCACTGCA CCGACTTCAT CTGGGGCTTC 180

GGGAAGCAGG GATTCCAGTG CCAAGTTTGC TGCTTTGTGG TGCACAAGCG GTGCCATGAA 240

TTTGTCACAT TCTCCTGCCC TGGCGCTGAC AAGGGTCCAG CCTCCGATGA CCCCCGCAGC 300

AAACACAAGT TTAAGATCCA CACGTACTCC AGCCCCACGT TTTGTGACCA CTGTGGGTCA 360

CTGCTGTATG GACTCATCCA CCAGGGGATG AAATGTGACA CCTGCATGAT GAATGTGCAC 420

AAGCGCTGCG TGATGAATGT TCCCAGCCTG TGTGGCACGG ACCACACGGA GCGCCGCGGC 480

CGCATCTACA TCCAGGCCCA CATCGACAGG GACGTCCTCA TTGTCCTCGT AAGAGATGCT 540

AAAAACCTTG TACCTATGGA CCCCAATGGC CTGTCAGATC CCTACGTAAA ACTGAAACTG 600

ATTCCCGATC CCAAAAGTGA GAGCAAACAG AAGACCAAAA CCATCAAATG CTCCCTCAAC 660

CCTGAGTGGA ATGAGACATT TAGATTTCAG CTGAAAGAAT CGGACAAAGA CAGAAGACTG 720

TCAGTAGAGA TTTGGGATTG GGATTTGACC AGCAGGAATG ACTTCATGGG ATCTTTGTCC 780

TTTGGGATTT CTGAACTTCA GAAAGCCAGT GTTGATGGCT GGTTTAAGTT ACTGAGCCAG 840

GAGGAAGGCG AGTACTTCAA TGTGCCTGTG CCACCAGAAG GAAGTGAGGC CAATGAAGAA 900

CTGCGGCAGA AATTTGAGAG GGCCAAGATC AGTCAGGGAA CCAAGGTCCC GGAAGAAAAG 960

ACGACCAACA CTGTCTCCAA ATTTGACAAC AATGGCAACA GAGACCGGAT GAAACTGACC 1020

GATTTTAACT TCCTAATGGT GCTGGGGAAA GGCAGCTTTG GCAAGGTCAT GCTTTCAGAA 1080

CGAAAAGGCA CAGATGAGCT CTATGCTGTG AAGATCCTGA AGAAGGACGT TGTGATCCAA 1140

GATGATGACG TGGAGTGCAC TATGGTGGAG AAGCGGGTGT TGGCCCTGCC TGGGAAGCCG 1200

CCCTTCCTGA CCCAGCTCCA CTCCTGCTTC CAGACCATGG ACCGCCTGTA CTTTGTGATG 1260

GAGTACGTGA ATGGGGGCGA CCTCATGTAT CACATCCAGC AAGTCGGCCG GTTCAAGGAG 1320

CCCCATGCTG TATTTTACGC TGCAGAAATT GCCATCGGTC TGTTCTTCTT ACAGAGTAAG 1380

GGCATCATTT ACCGTGACCT AAAACTTGAC AACGTGATGC TCGATTCTGA GGGACACATC 1440

AAGATTGCCG ATTTTGGCAT GTGTAAGGAA AACATCTGGG ATGGGGTGAC AACCAAGACA 1500

TTCTGTGGCA CTCCAGACTA CATCGCCCCC GAGATAATTG CTTATCAGCC CTATGGGAAG 1560

TCCGTGGATT GGTGGGCATT TGGAGTCCTG CTGTATGAAA TGTTGGCTGG GCAGGCACCC 1620

TTTGAAGGGG AGGATGAAGA TGAACTCTTC CAATCCATCA TGGAACACAA CGTAGCCTAT 1680

CCCAAGTCTA TGTCCAAGGA AGCTGTGGCC ATCTGCAAAG GGCTGATGAC CAAACACCCA 1740

GGCAAACGTC TGGGTTGTGG ACCTGAAGGC GAACGTGATA TCAAAGAGCA TGCATTTTTC 1800

CGGTATATTG ATTGGGAGAA ACTTGAACGC AAAGAGATCC AGCCCCCTTA TAAGCCAAAA 1860

GCTTGTGGGC GAAATGCTGA AAACTTCGAC CGATTTTTCA CCCGCCATCC ACCAGTCCTA 1920

ACACCTCCCG ACCAGGAAGT CATCAGGAAT ATTGACCAAT CAGAATTCGA AGGATTTTCC 1980

TTTGTTAACT CTGAATTTTT AAAACCCGAA GTCAAGAGCT AA 2022

Domain Profile

S: 1     fellkvlGkGsfgkvllaelkktdelyaikvlkkdvvlqdddveltlvekrvlalaskkp  60

         f++l+vlGkGsfgkv+l+e+k+tdelya+k+lkkdvv+qdddve+t+vekrvlal  k+p

Q: 342   FNFLMVLGKGSFGKVMLSERKGTDELYAVKILKKDVVIQDDDVECTMVEKRVLALPGKPP  401

         99**********************************************************

S: 61    flvqlfscfqtedrlffvleyvnGGdlmfhiqkarklkeerarfyaaeiilalkflhekg  120

         fl+ql+scfqt+drl+fv+eyvnGGdlm+hiq+++++ke++a+fyaaei+++l+fl++kg

Q: 402   FLTQLHSCFQTMDRLYFVMEYVNGGDLMYHIQQVGRFKEPHAVFYAAEIAIGLFFLQSKG  461

         ************************************************************

S: 121   iiyrdlkldnvlldaeGhikladfGlckeeilegkttstfcGtPdyiaPeilkeeeygks  180

         iiyrdlkldnv+ld+eGhik+adfG+cke+i++g tt+tfcGtPdyiaPei+++++ygks

Q: 462   IIYRDLKLDNVMLDSEGHIKIADFGMCKENIWDGVTTKTFCGTPDYIAPEIIAYQPYGKS  521

         ************************************************************

S: 181   vdwwalGvllyemlagqsPfegededelfesilekevlyPkslskeaveilkglltkdpe  240

         vdwwa+Gvllyemlagq+Pfegededelf+si+e++v+yPks+skeav+i+kgl+tk+p

Q: 522   VDWWAFGVLLYEMLAGQAPFEGEDEDELFQSIMEHNVAYPKSMSKEAVAICKGLMTKHPG  581

         ************************************************************

S: 241   krlGvkeegeedikehaff  259

         krlG+ +ege+dikehaff

Q: 582   KRLGCGPEGERDIKEHAFF  600

         ******************9

Domain Sequence
(FASTA)

FNFLMVLGKG SFGKVMLSER KGTDELYAVK ILKKDVVIQD DDVECTMVEK RVLALPGKPP 60

FLTQLHSCFQ TMDRLYFVME YVNGGDLMYH IQQVGRFKEP HAVFYAAEIA IGLFFLQSKG 120

IIYRDLKLDN VMLDSEGHIK IADFGMCKEN IWDGVTTKTF CGTPDYIAPE IIAYQPYGKS 180

VDWWAFGVLL YEMLAGQAPF EGEDEDELFQ SIMEHNVAYP KSMSKEAVAI CKGLMTKHPG 240

KRLGCGPEGE RDIKEHAFF 259

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

Ensembl

Orthology

Ortholog group

Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Danio rerio"; ?>Equus caballus"; ?>Felis catus"; ?>Gadus morhua"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Macaca mulatta"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Ochotona princeps"; ?>Oreochromis niloticus"; ?>Oryctolagus cuniculus"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Pongo abelii"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Tetraodon nigroviridis"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005829	; C:cytosol
GO:0005634	; C:nucleus
GO:0005886	; C:plasma membrane
GO:0050681	; F:androgen receptor binding
GO:0005524	; F:ATP binding
GO:0005246	; F:calcium channel regulator activity
GO:0003682	; F:chromatin binding
GO:0042393	; F:histone binding
GO:0035403	; F:histone kinase activity (H3-T6 specific)
GO:0030374	; F:ligand-dependent nuclear receptor transcription coactivator activity
GO:0004697	; F:protein kinase C activity
GO:0008270	; F:zinc ion binding
GO:0006915	; P:apoptotic process
GO:0042113	; P:B cell activation
GO:0050853	; P:B cell receptor signaling pathway
GO:0006816	; P:calcium ion transport
GO:0006874	; P:cellular calcium ion homeostasis
GO:0071322	; P:cellular response to carbohydrate stimulus
GO:0035556	; P:intracellular signal transduction
GO:0042953	; P:lipoprotein transport
GO:0010829	; P:negative regulation of glucose transport
GO:0046627	; P:negative regulation of insulin receptor signaling pathway
GO:0030168	; P:platelet activation
GO:0045766	; P:positive regulation of angiogenesis
GO:0050861	; P:positive regulation of B cell receptor signaling pathway
GO:0043123	; P:positive regulation of I-kappaB kinase/NF-kappaB cascade
GO:0051092	; P:positive regulation of NF-kappaB transcription factor activity
GO:0030949	; P:positive regulation of vascular endothelial growth factor receptor signaling pathway
GO:0006357	; P:regulation of transcription from RNA polymerase II promoter
GO:0007268	; P:synaptic transmission
GO:0006351	; P:transcription, DNA-dependent

KEGG

hsa:5579

;

InterPros

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; 2.
PF00168	; C2; 1.
PF00069	; Pkinase; 1.
PF00433	; Pkinase_C; 1.

SMARTs

SM00109	; C1; 2.
SM00239	; C2; 1.
SM00133	; S_TK_X; 1.
SM00220	; S_TKc; 1.

Prosites

PS51285	; AGC_KINASE_CTER; 1.
PS50004	; C2; 1.
PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00108	; PROTEIN_KINASE_ST; 1.
PS00479	; ZF_DAG_PE_1; 2.
PS50081	; ZF_DAG_PE_2; 2.

Prints

PR00360	; C2DOMAIN.
PR00008	; DAGPEDOMAIN.

Created Date

20-Feb-2013