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Q5PU49

- KPCD_CANFA

UniProt

Q5PU49 - KPCD_CANFA

Protein

Protein kinase C delta type

Gene

PRKCD

Organism
Canis familiaris (Dog) (Canis lupus familiaris)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 92 (01 Oct 2014)
      Sequence version 1 (04 Jan 2005)
      Previous versions | rss
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    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

    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: 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

    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.
    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]
    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

    MAPFLRIAFT SYELGSLQAA DEASQPFCAV KMKEALSTER GKTLVQKKPT    50
    MYPEWKSTFD AHIYEGRVIQ IVLMRAAEEP MSEVTVGVSV LAERCKKNNX 100
    KAEFWLDLQP QAKVLMSVQY FLEDIDCRQS MHGEDEAKLP TMNRRGAIKQ 150
    AKIHYIKNHE FIATFFGQPT FCSVCKDFVW GLNKQGYKCR QCNAAIHKKC 200
    IDKIIGRCTG TAANSRDTIF QKERFNIDMP HRFKVYNYMS PTFCDHCGSL 250
    LWGLVKQGLK CEDCGMNVHH KCQKKVANLC GINQKLLAEA LNQVTQRSSR 300
    KSETESVGIY QNFERKPGVS GDIAPGEDNG TYGKIWEGST RCNIDNFIFH 350
    KVLGKGSFGK VLLVELKGKK EFFAIKALKK DVVLIDDDVE CTMVEKRVLA 400
    LAWENPFLTH LFCTFQTKDH LFFVMEFLNG GDLMYHIQDK GRFELYRATF 450
    YAAEIVCGLQ FLHNKGIIYR DLKLDNVMLD QDGHIKIADF GMCKENIFGE 500
    KQASTFCGTP DYIAPEILQG LKYSFSVDWW SFGVLLYEML IGQSPFHGDD 550
    EDELFESIRV DTPHYPRWIT KESKDILEKL LERDTTKRLG VTGNIKIHPF 600
    FKTINWTLLE KRAVEPPFKP KVKSPGDYSN FDQEFLNEKA RLSYTDKNLI 650
    DSMDQTAFAG FSFVNPKFER FLEK 674
    Length:674
    Mass (Da):77,338
    Last modified:January 4, 2005 - v1
    Checksum:i5A25DADDB7A364BA
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY825360 mRNA. Translation: AAV80465.1 .
    RefSeqi NP_001008716.1. NM_001008716.1.
    UniGenei Cfa.16226.

    3D structure databases

    ProteinModelPortali Q5PU49.
    SMRi Q5PU49. Positions 149-218, 227-283, 344-666.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9615.ENSCAFP00000012799.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 494005.
    KEGGi cfa:494005.

    Organism-specific databases

    CTDi 5580.

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233022.
    HOVERGENi HBG108317.
    InParanoidi Q5PU49.
    KOi K06068.

    Miscellaneous databases

    NextBioi 20865534.

    Family and domain databases

    Gene3Di 2.60.40.150. 1 hit.
    InterProi IPR000961. 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 ]
    Pfami PF00130. C1_1. 2 hits.
    PF00069. Pkinase. 1 hit.
    PF00433. Pkinase_C. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF000551. PKC_delta. 1 hit.
    PIRSF501104. Protein_kin_C_delta. 1 hit.
    PRINTSi PR00008. DAGPEDOMAIN.
    SMARTi SM00109. C1. 2 hits.
    SM00239. C2. 1 hit.
    SM00133. S_TK_X. 1 hit.
    SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49562. SSF49562. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEi PS51285. 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 ]
    ProtoNeti Search...

    Publicationsi

    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].

    Entry informationi

    Entry nameiKPCD_CANFA
    AccessioniPrimary (citable) accession number: Q5PU49
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 29, 2005
    Last sequence update: January 4, 2005
    Last modified: October 1, 2014
    This is version 92 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