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Protein

Protein kinase C delta type

Gene

PRKCD

Organism
Canis familiaris (Dog) (Canis lupus 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 (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)LengthDescriptionGraphical viewFeature identifierActions
Sitei48 – 481Interaction with phosphotyrosine-containing peptideBy similarity
Sitei62 – 621Interaction with phosphotyrosine-containing peptideBy similarity
Sitei67 – 671Interaction with phosphotyrosine-containing peptideBy similarity
Sitei123 – 1231Interaction with phosphotyrosine-containing peptideBy similarity
Sitei328 – 3292Cleavage; by caspase-3By similarity
Binding sitei376 – 3761ATPPROSITE-ProRule annotation
Active sitei471 – 4711Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri158 – 20851Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri230 – 28051Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd
BLAST
Nucleotide bindingi353 – 3619ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. metal ion binding Source: UniProtKB-KW
  3. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
  4. protein kinase C activity Source: UniProtKB

GO - Biological processi

  1. apoptotic process Source: UniProtKB-KW
  2. cell cycle Source: UniProtKB-KW
  3. defense response to bacterium Source: UniProtKB
  4. intracellular signal transduction Source: InterPro
  5. negative regulation of actin filament polymerization Source: UniProtKB
  6. negative regulation of filopodium assembly Source: UniProtKB
  7. negative regulation of glial cell apoptotic process Source: UniProtKB
  8. negative regulation of platelet aggregation Source: UniProtKB
  9. positive regulation of superoxide anion generation Source: UniProtKB
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 familiaris (Dog) (Canis lupus familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
ProteomesiUP000002254 Componenti: Unplaced

Subcellular locationi

Cytoplasm By similarity. Cytoplasmperinuclear region By similarity. Nucleus By similarity. Endoplasmic reticulum By similarity. Mitochondrion By similarity. Membrane By similarity; Peripheral membrane protein By similarity

GO - Cellular componenti

  1. endoplasmic reticulum Source: UniProtKB
  2. membrane Source: UniProtKB-SubCell
  3. mitochondrion Source: UniProtKB-SubCell
  4. nucleus Source: UniProtKB-SubCell
  5. perinuclear region of cytoplasm Source: UniProtKB-SubCell
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)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 674674Protein kinase C delta typePRO_0000055693Add
BLAST
Chaini1 – 328328Protein kinase C delta type regulatory subunitBy similarityPRO_0000421665Add
BLAST
Chaini329 – 674346Protein kinase C delta type catalytic subunitBy similarityPRO_0000421666Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei43 – 431PhosphothreonineBy similarity
Modified residuei64 – 641PhosphotyrosineBy similarity
Modified residuei130 – 1301PhosphoserineBy similarity
Modified residuei155 – 1551PhosphotyrosineBy similarity
Modified residuei218 – 2181PhosphothreonineBy similarity
Modified residuei299 – 2991Phosphoserine; by autocatalysisBy similarity
Modified residuei302 – 3021Phosphoserine; by autocatalysisBy similarity
Modified residuei310 – 3101Phosphotyrosine; by SRCBy similarity
Modified residuei332 – 3321Phosphotyrosine; by SRCBy similarity
Modified residuei505 – 5051Phosphothreonine; by autocatalysisBy similarity
Modified residuei565 – 5651PhosphotyrosineBy similarity
Modified residuei643 – 6431PhosphoserineCurated
Modified residuei652 – 6521PhosphoserineBy similarity
Modified residuei662 – 6621PhosphoserineBy similarity

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

Keywords - PTMi

Phosphoprotein

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000012799.

Structurei

3D structure databases

ProteinModelPortaliQ5PU49.
SMRiQ5PU49. Positions 149-218, 227-283, 344-666.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 9090C2Add
BLAST
Domaini347 – 601255Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini602 – 67372AGC-kinase C-terminalAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri158 – 20851Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri230 – 28051Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000233022.
HOVERGENiHBG108317.
InParanoidiQ5PU49.
KOiK06068.

Family and domain databases

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.
IPR002290. Ser/Thr_dual-sp_kinase.
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.
SM00239. C2. 1 hit.
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 3, 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.
SMRiQ5PU49. Positions 149-218, 227-283, 344-666.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000012799.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi494005.
KEGGicfa:494005.

Organism-specific databases

CTDi5580.

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000233022.
HOVERGENiHBG108317.
InParanoidiQ5PU49.
KOiK06068.

Miscellaneous databases

NextBioi20865534.

Family and domain databases

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.
IPR002290. Ser/Thr_dual-sp_kinase.
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.
SM00239. C2. 1 hit.
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...

Publicationsi

  1. "Canine protein kinase C delta."
    Hsieh Y.-T., Chen H.-C.
    Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Entry informationi

Entry nameiKPCD_CANFA
AccessioniPrimary (citable) accession number: Q5PU49
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 28, 2005
Last sequence update: January 3, 2005
Last modified: March 3, 2015
This is version 95 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

External Data

Dasty 3

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 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.