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Protein

Protein kinase C delta type

Gene

PRKCD

Organism
Canis lupus familiaris (Dog) (Canis familiaris)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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). The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion. Phosphorylates ELAVL1 in response to angiotensin-2 treatment (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Enzyme regulationi

Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-505 (activation loop of the kinase domain), Ser-643 (turn motif) and Ser-662 (hydrophobic region), need to be phosphorylated for its full activation. Activated by caspase-3 (CASP3) cleavage during apoptosis. After cleavage, the pseudosubstrate motif in the regulatory subunit is released from the substrate recognition site of the catalytic subunit, which enables PRKCD to become constitutively activated. The catalytic subunit which displays properties of a sphingosine-dependent protein kinase is activated by D-erythro-sphingosine (Sph) or N,N-dimethyl-D-erythrosphingosine (DMS) or N,N,N-trimethyl-D-erythrosphingosine (TMS), but not by ceramide or Sph-1-P and is strongly inhibited by phosphatidylserine (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei376ATPPROSITE-ProRule annotation1
Active sitei471Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri158 – 208Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST51
Zinc fingeri230 – 280Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST51
Nucleotide bindingi353 – 361ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Cell cycle

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Protein kinase C delta type (EC:2.7.11.13)
Alternative name(s):
Tyrosine-protein kinase PRKCD (EC:2.7.10.2)
nPKC-delta
Cleaved into the following 2 chains:
Alternative name(s):
Sphingosine-dependent protein kinase-1
Short name:
SDK1
Gene namesi
Name:PRKCD
OrganismiCanis lupus familiaris (Dog) (Canis familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
Proteomesi
  • UP000002254 Componenti: Unplaced

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Membrane, Mitochondrion, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000556931 – 674Protein kinase C delta typeAdd BLAST674
ChainiPRO_00004216651 – 328Protein kinase C delta type regulatory subunitBy similarityAdd BLAST328
ChainiPRO_0000421666329 – 674Protein kinase C delta type catalytic subunitBy similarityAdd BLAST346

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei43PhosphothreonineBy similarity1
Modified residuei50PhosphothreonineBy similarity1
Modified residuei64PhosphotyrosineBy similarity1
Modified residuei130PhosphoserineBy similarity1
Modified residuei141PhosphothreonineBy similarity1
Modified residuei155PhosphotyrosineBy similarity1
Modified residuei218PhosphothreonineBy similarity1
Modified residuei299Phosphoserine; by autocatalysisBy similarity1
Modified residuei302Phosphoserine; by autocatalysisBy similarity1
Modified residuei310Phosphotyrosine; by SRCBy similarity1
Modified residuei332Phosphotyrosine; by SRCBy similarity1
Modified residuei449PhosphothreonineBy similarity1
Modified residuei504PhosphoserineBy similarity1
Modified residuei505Phosphothreonine; by autocatalysisBy similarity1
Modified residuei565PhosphotyrosineBy similarity1
Modified residuei643PhosphoserineCurated1
Modified residuei652PhosphoserineBy similarity1
Modified residuei662PhosphoserineBy similarity1

Post-translational modificationi

Autophosphorylated and/or phosphorylated at Thr-505, within the activation loop; phosphorylation at Thr-505 is not a prerequisite for enzymatic activity. Autophosphorylated at Ser-299 and Ser-302. Upon TNFSF10/TRAIL treatment, phosphorylated at Tyr-155; phosphorylation is required for its translocation to the endoplasmic reticulum and cleavage by caspase-3. Phosphorylated at Tyr-310, Tyr-332 and Tyr-565; phosphorylation of Tyr-310 and Tyr-565 following thrombin stimulation potentiates its kinase activity. Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminal cleavage product of PKN2 (By similarity).By similarity
Proteolytically cleaved into a catalytic subunit and a regulatory subunit by caspase-3 during apoptosis which results in kinase activation.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei328 – 329Cleavage; by caspase-3By similarity2

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ5PU49.

Interactioni

Subunit structurei

Interacts with PDPK1 (via N-terminal region), RAD9A, CDCP1, MUC1 and VASP.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei48Interaction with phosphotyrosine-containing peptideBy similarity1
Sitei62Interaction with phosphotyrosine-containing peptideBy similarity1
Sitei67Interaction with phosphotyrosine-containing peptideBy similarity1
Sitei123Interaction with phosphotyrosine-containing peptideBy similarity1

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000012799.

Structurei

3D structure databases

ProteinModelPortaliQ5PU49.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 90C2Add BLAST90
Domaini347 – 601Protein kinasePROSITE-ProRule annotationAdd BLAST255
Domaini602 – 673AGC-kinase C-terminalAdd BLAST72

Domaini

The C1 domain, containing the phorbol ester/DAG-type region 1 (C1A) and 2 (C1B), is the diacylglycerol sensor.
The C2 domain is a non-calcium binding domain. It binds proteins containing phosphotyrosine in a sequence-specific manner (By similarity).By similarity

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 C2 domain.Curated
Contains 2 phorbol-ester/DAG-type zinc fingers.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri158 – 208Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST51
Zinc fingeri230 – 280Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST51

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG0694. Eukaryota.
ENOG410XNPH. LUCA.
HOGENOMiHOG000233022.
HOVERGENiHBG108317.
InParanoidiQ5PU49.
KOiK06068.

Family and domain databases

CDDicd00029. C1. 2 hits.
Gene3Di2.60.40.150. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR000008. C2_dom.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR002219. PE/DAG-bd.
IPR027436. PKC_delta.
IPR017892. Pkinase_C.
IPR014376. Prot_kin_PKC_delta.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00130. C1_1. 2 hits.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFiPIRSF000551. PKC_delta. 1 hit.
PIRSF501104. Protein_kin_C_delta. 1 hit.
PRINTSiPR00008. DAGPEDOMAIN.
SMARTiSM00109. C1. 2 hits.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS00479. ZF_DAG_PE_1. 2 hits.
PS50081. ZF_DAG_PE_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q5PU49-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPFLRIAFT SYELGSLQAA DEASQPFCAV KMKEALSTER GKTLVQKKPT
60 70 80 90 100
MYPEWKSTFD AHIYEGRVIQ IVLMRAAEEP MSEVTVGVSV LAERCKKNNX
110 120 130 140 150
KAEFWLDLQP QAKVLMSVQY FLEDIDCRQS MHGEDEAKLP TMNRRGAIKQ
160 170 180 190 200
AKIHYIKNHE FIATFFGQPT FCSVCKDFVW GLNKQGYKCR QCNAAIHKKC
210 220 230 240 250
IDKIIGRCTG TAANSRDTIF QKERFNIDMP HRFKVYNYMS PTFCDHCGSL
260 270 280 290 300
LWGLVKQGLK CEDCGMNVHH KCQKKVANLC GINQKLLAEA LNQVTQRSSR
310 320 330 340 350
KSETESVGIY QNFERKPGVS GDIAPGEDNG TYGKIWEGST RCNIDNFIFH
360 370 380 390 400
KVLGKGSFGK VLLVELKGKK EFFAIKALKK DVVLIDDDVE CTMVEKRVLA
410 420 430 440 450
LAWENPFLTH LFCTFQTKDH LFFVMEFLNG GDLMYHIQDK GRFELYRATF
460 470 480 490 500
YAAEIVCGLQ FLHNKGIIYR DLKLDNVMLD QDGHIKIADF GMCKENIFGE
510 520 530 540 550
KQASTFCGTP DYIAPEILQG LKYSFSVDWW SFGVLLYEML IGQSPFHGDD
560 570 580 590 600
EDELFESIRV DTPHYPRWIT KESKDILEKL LERDTTKRLG VTGNIKIHPF
610 620 630 640 650
FKTINWTLLE KRAVEPPFKP KVKSPGDYSN FDQEFLNEKA RLSYTDKNLI
660 670
DSMDQTAFAG FSFVNPKFER FLEK
Length:674
Mass (Da):77,338
Last modified:January 4, 2005 - v1
Checksum:i5A25DADDB7A364BA
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY825360 mRNA. Translation: AAV80465.1.
RefSeqiNP_001008716.1. NM_001008716.1.
UniGeneiCfa.16226.

Genome annotation databases

GeneIDi494005.
KEGGicfa:494005.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY825360 mRNA. Translation: AAV80465.1.
RefSeqiNP_001008716.1. NM_001008716.1.
UniGeneiCfa.16226.

3D structure databases

ProteinModelPortaliQ5PU49.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000012799.

Proteomic databases

PaxDbiQ5PU49.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi494005.
KEGGicfa:494005.

Organism-specific databases

CTDi5580.

Phylogenomic databases

eggNOGiKOG0694. Eukaryota.
ENOG410XNPH. LUCA.
HOGENOMiHOG000233022.
HOVERGENiHBG108317.
InParanoidiQ5PU49.
KOiK06068.

Family and domain databases

CDDicd00029. C1. 2 hits.
Gene3Di2.60.40.150. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR000008. C2_dom.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR002219. PE/DAG-bd.
IPR027436. PKC_delta.
IPR017892. Pkinase_C.
IPR014376. Prot_kin_PKC_delta.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00130. C1_1. 2 hits.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFiPIRSF000551. PKC_delta. 1 hit.
PIRSF501104. Protein_kin_C_delta. 1 hit.
PRINTSiPR00008. DAGPEDOMAIN.
SMARTiSM00109. C1. 2 hits.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS00479. ZF_DAG_PE_1. 2 hits.
PS50081. ZF_DAG_PE_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKPCD_CANLF
AccessioniPrimary (citable) accession number: Q5PU49
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 29, 2005
Last sequence update: January 4, 2005
Last modified: November 30, 2016
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.