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Q5PU49 (KPCD_CANFA) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 90. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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:

  1. Protein kinase C delta type regulatory subunit
  2. Protein kinase C delta type catalytic subunit
    Alternative name(s):
    Sphingosine-dependent protein kinase-1
    Short name=SDK1
Gene names
Name:PRKCD
OrganismCanis familiaris (Dog) (Canis lupus familiaris) [Reference proteome]
Taxonomic identifier9615 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis

Protein attributes

Sequence length674 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Enzyme regulation

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.

Subunit structure

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

Subcellular location

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

Domain

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.

Post-translational modification

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-terminus cleavage product of PKN2 By similarity.

Proteolytically cleaved into a catalytic subunit and a regulatory subunit by caspase-3 during apoptosis which results in kinase activation By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.

Contains 1 AGC-kinase C-terminal domain.

Contains 1 C2 domain.

Contains 2 phorbol-ester/DAG-type zinc fingers.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processApoptosis
Cell cycle
   Cellular componentCytoplasm
Endoplasmic reticulum
Membrane
Mitochondrion
Nucleus
   DiseaseTumor suppressor
   DomainRepeat
Zinc-finger
   LigandATP-binding
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

cell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

defense response to bacterium

Inferred from sequence or structural similarity. Source: UniProtKB

intracellular signal transduction

Inferred from electronic annotation. Source: InterPro

negative regulation of actin filament polymerization

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of filopodium assembly

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of glial cell apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of platelet aggregation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of superoxide anion generation

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentendoplasmic reticulum

Inferred from sequence or structural similarity. Source: UniProtKB

membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrion

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

non-membrane spanning protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein kinase C activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 674674Protein kinase C delta type
PRO_0000055693
Chain1 – 328328Protein kinase C delta type regulatory subunit By similarity
PRO_0000421665
Chain329 – 674346Protein kinase C delta type catalytic subunit By similarity
PRO_0000421666

Regions

Domain1 – 9090C2
Domain347 – 601255Protein kinase
Domain602 – 67372AGC-kinase C-terminal
Zinc finger158 – 20851Phorbol-ester/DAG-type 1
Zinc finger230 – 28051Phorbol-ester/DAG-type 2
Nucleotide binding353 – 3619ATP By similarity

Sites

Active site4711Proton acceptor By similarity
Binding site3761ATP By similarity
Site481Interaction with phosphotyrosine-containing peptide By similarity
Site621Interaction with phosphotyrosine-containing peptide By similarity
Site671Interaction with phosphotyrosine-containing peptide By similarity
Site1231Interaction with phosphotyrosine-containing peptide By similarity
Site328 – 3292Cleavage; by caspase-3 By similarity

Amino acid modifications

Modified residue431Phosphothreonine By similarity
Modified residue641Phosphotyrosine By similarity
Modified residue1301Phosphoserine By similarity
Modified residue1551Phosphotyrosine By similarity
Modified residue2181Phosphothreonine By similarity
Modified residue2991Phosphoserine; by autocatalysis By similarity
Modified residue3021Phosphoserine; by autocatalysis By similarity
Modified residue3101Phosphotyrosine; by SRC By similarity
Modified residue3321Phosphotyrosine; by SRC By similarity
Modified residue5051Phosphothreonine; by autocatalysis By similarity
Modified residue5651Phosphotyrosine By similarity
Modified residue6431Phosphoserine Probable
Modified residue6521Phosphoserine By similarity
Modified residue6621Phosphoserine By similarity

Sequences

Sequence LengthMass (Da)Tools
Q5PU49 [UniParc].

Last modified January 4, 2005. Version 1.
Checksum: 5A25DADDB7A364BA

FASTA67477,338
        10         20         30         40         50         60 
MAPFLRIAFT SYELGSLQAA DEASQPFCAV KMKEALSTER GKTLVQKKPT MYPEWKSTFD 

        70         80         90        100        110        120 
AHIYEGRVIQ IVLMRAAEEP MSEVTVGVSV LAERCKKNNX KAEFWLDLQP QAKVLMSVQY 

       130        140        150        160        170        180 
FLEDIDCRQS MHGEDEAKLP TMNRRGAIKQ AKIHYIKNHE FIATFFGQPT FCSVCKDFVW 

       190        200        210        220        230        240 
GLNKQGYKCR QCNAAIHKKC IDKIIGRCTG TAANSRDTIF QKERFNIDMP HRFKVYNYMS 

       250        260        270        280        290        300 
PTFCDHCGSL LWGLVKQGLK CEDCGMNVHH KCQKKVANLC GINQKLLAEA LNQVTQRSSR 

       310        320        330        340        350        360 
KSETESVGIY QNFERKPGVS GDIAPGEDNG TYGKIWEGST RCNIDNFIFH KVLGKGSFGK 

       370        380        390        400        410        420 
VLLVELKGKK EFFAIKALKK DVVLIDDDVE CTMVEKRVLA LAWENPFLTH LFCTFQTKDH 

       430        440        450        460        470        480 
LFFVMEFLNG GDLMYHIQDK GRFELYRATF YAAEIVCGLQ FLHNKGIIYR DLKLDNVMLD 

       490        500        510        520        530        540 
QDGHIKIADF GMCKENIFGE KQASTFCGTP DYIAPEILQG LKYSFSVDWW SFGVLLYEML 

       550        560        570        580        590        600 
IGQSPFHGDD EDELFESIRV DTPHYPRWIT KESKDILEKL LERDTTKRLG VTGNIKIHPF 

       610        620        630        640        650        660 
FKTINWTLLE KRAVEPPFKP KVKSPGDYSN FDQEFLNEKA RLSYTDKNLI DSMDQTAFAG 

       670 
FSFVNPKFER FLEK 

« Hide

References

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

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY825360 mRNA. Translation: AAV80465.1.
RefSeqNP_001008716.1. NM_001008716.1.
UniGeneCfa.16226.

3D structure databases

ProteinModelPortalQ5PU49.
SMRQ5PU49. Positions 149-218, 227-283, 344-666.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9615.ENSCAFP00000012799.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID494005.
KEGGcfa:494005.

Organism-specific databases

CTD5580.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233022.
HOVERGENHBG108317.
InParanoidQ5PU49.
KOK06068.

Family and domain databases

Gene3D2.60.40.150. 1 hit.
InterProIPR000961. AGC-kinase_C.
IPR000008. C2_dom.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR027436. PKC_delta.
IPR017892. Pkinase_C.
IPR014376. Prot_kin_PKC_delta.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00130. C1_1. 2 hits.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFPIRSF000551. PKC_delta. 1 hit.
PIRSF501104. Protein_kin_C_delta. 1 hit.
PRINTSPR00008. DAGPEDOMAIN.
SMARTSM00109. C1. 2 hits.
SM00239. C2. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF49562. SSF49562. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS51285. 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]
ProtoNetSearch...

Other

NextBio20865534.

Entry information

Entry nameKPCD_CANFA
AccessionPrimary (citable) accession number: Q5PU49
Entry history
Integrated into UniProtKB/Swiss-Prot: March 29, 2005
Last sequence update: January 4, 2005
Last modified: April 16, 2014
This is version 90 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families