EKS-RAN-00172

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-RAN-00172

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
AGC/PKC	424.8	1.7E-127	347	600	254

Status

Reviewed

Ensembl Protein

ENSRNOP00000025858

UniProt Accession

P09215; Q6DG48; Q9JK29; Q9JL03;

Protein Name

Protein kinase C delta type

Protein Synonyms/Alias

nPKC-delta;

Gene Name

Prkcd

Gene Synonyms/Alias

Prkcd; Pkcd;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSRNOG00000016346	ENSRNOP00000061108	ENSRNOT00000067639
ENSRNOG00000016346	ENSRNOP00000025858	ENSRNOT00000025858

Organism

Rattus norvegicus

Functional Description

Calcium-independent, phospholipid- and diacylglycerol(DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor- initiated cell death, is involved in tumor suppression, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses. Upon DNA damage, activates the promoter of the death- promoting transcription factor BCLAF1/Btf to trigger BCLAF1- mediated p53/TP53 gene transcription and apoptosis. In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53. In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53. In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation. Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1. Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-formyl-methionyl- leucyl-phenylalanine (fMLP)-treated cells, is required for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3 (ERK1/2) signaling pathways. May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA. In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation. Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion; acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release. Phosphorylates MUC1 in the C- terminal and regulates the interaction between MUC1 and beta- catenin (By similarity). Truncated isoform 2 is inactive.

Protein Length

672

Protein Sequence
(FASTA)

MAPFLRISFN SYELGSLQAE DDASQPFCAV KMKEALTTDR GKTLVQKKPT MYPEWKSTFD 60

AHIYEGRVIQ IVLMRAAEDP MSEVTVGVSV LAERCKKNNG KAEFWLDLQP QAKVLMCVQY 120

FLEDGDCKQS MRSEEEAMFP TMNRRGAIKQ AKIHYIKNHE FIATFFGQPT FCSVCKEFVW 180

GLNKQGYKCR QCNAAIHKKC IDKIIGRCTG TATNSRDTIF QKERFNIDMP HRFKVYNYMS 240

PTFCDHCGSL LWGLVKQGLK CEDCGMNVHH KCREKVANLC GINQKLLAEA LNQVTQKASR 300

KPETPETVGI YQGFEKKTAV SGNDIPDNNG TYGKIWEGSN RCRLENFTFQ KVLGKGSFGK 360

VLLAELKGKE RYFAIKYLKK DVVLIDDDVE CTMVEKRVLA LAWENPFLTH LICTFQTKDH 420

LFFVMEFLNG GDLMFHIQDK GRFELYRATF YAAEIICGLQ FLHGKGIIYR DLKLDNVMLD 480

KDGHIKIADF GMCKENIFGE NRASTFCGTP DYIAPEILQG LKYSFSVDWW SFGVLLYEML 540

IGQSPFHGDD EDELFESIRV DTPHYPRWIT KDTAPVDQLF ERDPAKRLGV TGNIRLHPFF 600

KTINWNLLEK RKVEPPFKPK VKSPSDYSNF DPEFLNEKPQ LSFSDKNLID SMDQTAFKGF 660

SFVNPKYEQF LE 672

Nucleotide Sequence
(FASTA)

ATGGCACCGT TCCTGCGCAT CTCCTTCAAT TCCTATGAGC TGGGCTCCCT GCAGGCGGAG 60

GACGACGCAA GCCAGCCTTT CTGTGCCGTG AAGATGAAGG AGGCACTCAC CACAGACCGA 120

GGGAAGACTC TGGTACAGAA GAAGCCCACC ATGTACCCTG AGTGGAAGTC AACATTCGAC 180

GCCCACATCT ATGAAGGCCG TGTCATCCAG ATCGTGCTGA TGCGGGCAGC TGAAGACCCC 240

ATGTCGGAGG TGACCGTGGG CGTGTCAGTG CTGGCTGAGC GCTGCAAGAA GAACAACGGC 300

AAGGCTGAGT TCTGGCTGGA CCTGCAGCCT CAGGCCAAGG TGCTGATGTG TGTGCAGTAT 360

TTCCTGGAGG ATGGGGATTG CAAACAGTCC ATGCGTAGTG AGGAGGAGGC CATGTTCCCA 420

ACTATGAACC GCCGTGGAGC CATTAAACAG GCCAAGATTC ACTACATCAA GAACCACGAG 480

TTCATCGCCA CCTTCTTTGG GCAGCCCACC TTCTGTTCTG TGTGCAAAGA GTTTGTCTGG 540

GGCCTCAACA AGCAAGGCTA CAAATGCAGG CAATGCAACG CTGCCATCCA TAAGAAATGC 600

ATCGACAAGA TTATCGGCCG CTGCACTGGC ACTGCTACCA ATAGCCGGGA CACCATCTTC 660

CAGAAAGAAC GCTTCAACAT CGACATGCCT CACCGATTCA AGGTCTATAA CTACATGAGC 720

CCCACCTTCT GTGACCACTG TGGCAGTTTG CTCTGGGGAT TGGTGAAACA GGGATTAAAG 780

TGTGAAGACT GCGGCATGAA TGTGCACCAC AAATGCCGGG AGAAGGTGGC CAACCTGTGT 840

GGTATCAACC AAAAGCTCTT GGCTGAGGCC TTGAACCAAG TGACCCAGAA AGCTTCCCGG 900

AAGCCAGAGA CACCAGAGAC TGTCGGAATA TACCAGGGAT TCGAGAAGAA GACAGCTGTC 960

TCTGGGAATG ACATCCCAGA CAACAACGGG ACCTATGGCA AGATCTGGGA GGGGAGCAAC 1020

CGGTGCCGCC TTGAGAACTT CACCTTCCAG AAAGTACTTG GCAAAGGCAG CTTTGGCAAG 1080

GTACTGCTTG CAGAACTGAA GGGCAAGGAA AGGTACTTTG CAATCAAGTA CCTGAAGAAG 1140

GACGTGGTGT TGATCGACGA TGACGTGGAG TGCACCATGG TGGAGAAGCG GGTGCTGGCG 1200

CTCGCCTGGG AGAATCCCTT CCTCACCCAT CTCATCTGTA CCTTCCAGAC CAAGGACCAC 1260

CTCTTCTTTG TGATGGAGTT CCTCAATGGG GGTGATCTGA TGTTCCACAT TCAGGACAAA 1320

GGCCGCTTCG AACTCTACCG GGCTACGTTT TATGCAGCTG AGATCATCTG CGGACTGCAG 1380

TTTCTACATG GCAAAGGCAT CATTTACAGG GACCTCAAGC TAGACAATGT AATGCTGGAC 1440

AAGGATGGCC ACATCAAGAT TGCTGACTTC GGGATGTGCA AAGAGAATAT ATTTGGGGAG 1500

AACCGGGCCA GCACATTCTG CGGCACTCCT GACTACATCG CCCCTGAGAT CCTGCAGGGC 1560

CTGAAGTACT CATTTTCCGT GGACTGGTGG TCTTTTGGGG TCCTCCTCTA TGAGATGCTC 1620

ATTGGCCAGT CCCCCTTCCA TGGTGATGAT GAGGACGAGC TCTTTGAGTC CATCCGGGTG 1680

GACACACCAC ACTACCCGCG CTGGATCACC AAGGACACGG CCCCTGTGGA TCAGCTCTTC 1740

GAGAGGGACC CTGCCAAGAG GCTGGGAGTA ACAGGAAACA TCAGGCTTCA CCCCTTTTTC 1800

AAGACTATCA ACTGGAACCT GCTGGAGAAG CGGAAGGTGG AGCCGCCCTT TAAGCCCAAA 1860

GTGAAATCCC CTTCAGACTA CAGCAACTTT GACCCAGAGT TCCTGAATGA GAAACCCCAA 1920

CTTTCCTTCA GTGACAAGAA CCTCATCGAC TCTATGGACC AGACAGCCTT CAAGGGCTTC 1980

TCCTTTGTGA ACCCCAAATA TGAGCAATTC CTGGAATAG 2019

Domain Profile

S: 1     fellkvlGkGsfgkvllaelkktdelyaikvlkkdvvlqdddveltlvekrvlalaskkp  60

         f++ kvlGkGsfgkvllaelk++++++aik lkkdvvl dddve+t+vekrvlala+++p

Q: 347   FTFQKVLGKGSFGKVLLAELKGKERYFAIKYLKKDVVLIDDDVECTMVEKRVLALAWENP  406

         89**********************************************************

S: 61    flvqlfscfqtedrlffvleyvnGGdlmfhiqkarklkeerarfyaaeiilalkflhekg  120

         fl++l+++fqt+d+lffv+e++nGGdlmfhiq++++++  ra+fyaaeii++l+flh kg

Q: 407   FLTHLICTFQTKDHLFFVMEFLNGGDLMFHIQDKGRFELYRATFYAAEIICGLQFLHGKG  466

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

S: 121   iiyrdlkldnvlldaeGhikladfGlckeeilegkttstfcGtPdyiaPeilkeeeygks  180

         iiyrdlkldnv+ld++Ghik+adfG+cke+i+ ++++stfcGtPdyiaPeil++ +y++s

Q: 467   IIYRDLKLDNVMLDKDGHIKIADFGMCKENIFGENRASTFCGTPDYIAPEILQGLKYSFS  526

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

S: 181   vdwwalGvllyemlagqsPfegededelfesilekevlyPkslskeaveilkglltkdpe  240

         vdww++Gvllyeml+gqsPf+g+dedelfesi+ ++++yP++++k+++ +  +l+++dp+

Q: 527   VDWWSFGVLLYEMLIGQSPFHGDDEDELFESIRVDTPHYPRWITKDTAPV-DQLFERDPA  585

         *********************************************98875.889******

S: 241   krlGvkeegeedikehaff  259

         krlGv  +g  +i+ h+ff

Q: 586   KRLGV--TG--NIRLHPFF  600

         *****..56..79999998

Domain Sequence
(FASTA)

FTFQKVLGKG SFGKVLLAEL KGKERYFAIK YLKKDVVLID DDVECTMVEK RVLALAWENP 60

FLTHLICTFQ TKDHLFFVME FLNGGDLMFH IQDKGRFELY RATFYAAEII CGLQFLHGKG 120

IIYRDLKLDN VMLDKDGHIK IADFGMCKEN IFGENRASTF CGTPDYIAPE ILQGLKYSFS 180

VDWWSFGVLL YEMLIGQSPF HGDDEDELFE SIRVDTPHYP RWITKDTAPV DQLFERDPAK 240

RLGVTGNIRL HPFF 254

Keyword

3D-structure; Alternative splicing; Apoptosis; ATP-binding; Cell cycle; Complete proteome; Cytoplasm; Direct protein sequencing; Endoplasmic reticulum; Kinase; Membrane; Metal-binding; Mitochondrion; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase; Tumor suppressor; Zinc; Zinc-finger.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Caenorhabditis elegans"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Ciona savignyi"; ?>Danio rerio"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Felis catus"; ?>Gadus morhua"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Homo sapiens"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Ochotona princeps"; ?>Oreochromis niloticus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pelodiscus sinensis"; ?>Pongo abelii"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005829	; C:cytosol
GO:0005783	; C:endoplasmic reticulum
GO:0005739	; C:mitochondrion
GO:0005634	; C:nucleus
GO:0048471	; C:perinuclear region of cytoplasm
GO:0005886	; C:plasma membrane
GO:0005524	; F:ATP binding
GO:0004699	; F:calcium-independent protein kinase C activity
GO:0046872	; F:metal ion binding
GO:0007568	; P:aging
GO:0006915	; P:apoptotic process
GO:0015810	; P:aspartate transport
GO:0007049	; P:cell cycle
GO:0042149	; P:cellular response to glucose starvation
GO:0032869	; P:cellular response to insulin stimulus
GO:0032963	; P:collagen metabolic process
GO:0042742	; P:defense response to bacterium
GO:0006917	; P:induction of apoptosis
GO:0035556	; P:intracellular signal transduction
GO:0030837	; P:negative regulation of actin filament polymerization
GO:0051490	; P:negative regulation of filopodium assembly
GO:0034351	; P:negative regulation of glial cell apoptotic process
GO:0090331	; P:negative regulation of platelet aggregation
GO:0046326	; P:positive regulation of glucose import
GO:0043406	; P:positive regulation of MAP kinase activity
GO:0043410	; P:positive regulation of MAPK cascade
GO:0032930	; P:positive regulation of superoxide anion generation
GO:0046777	; P:protein autophosphorylation
GO:0043200	; P:response to amino acid stimulus
GO:0042493	; P:response to drug
GO:0045471	; P:response to ethanol
GO:0009749	; P:response to glucose stimulus
GO:0009408	; P:response to heat
GO:0042542	; P:response to hydrogen peroxide
GO:0001666	; P:response to hypoxia
GO:0009612	; P:response to mechanical stimulus
GO:0014070	; P:response to organic cyclic compound

KEGG

rno:170538

;

InterPros

IPR000961	; AGC-kinase_C.
IPR000008	; C2_Ca-dep.
IPR008973	; C2_Ca/lipid-bd_dom_CaLB.
IPR020454	; DAG/PE-bd.
IPR011009	; Kinase-like_dom.
IPR017892	; Pkinase_C.
IPR014376	; Prot_kin_PKC_delta.
IPR002219	; Prot_Kinase_C-like_PE/DAG-bd.
IPR000719	; Prot_kinase_cat_dom.
IPR017441	; Protein_kinase_ATP_BS.
IPR002290	; Ser/Thr_dual-sp_kinase_dom.
IPR008271	; Ser/Thr_kinase_AS.

Pfam

PF00130	; C1_1; 2.
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; FALSE_NEG.
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

PR00008

; DAGPEDOMAIN.

Created Date

20-Feb-2013