KPCD_CANLF
ID KPCD_CANLF Reviewed; 674 AA.
AC Q5PU49;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Protein kinase C delta type;
DE EC=2.7.11.13 {ECO:0000250|UniProtKB:Q05655};
DE AltName: Full=Tyrosine-protein kinase PRKCD;
DE EC=2.7.10.2;
DE AltName: Full=nPKC-delta;
DE Contains:
DE RecName: Full=Protein kinase C delta type regulatory subunit;
DE Contains:
DE RecName: Full=Protein kinase C delta type catalytic subunit;
DE AltName: Full=Sphingosine-dependent protein kinase-1;
DE Short=SDK1;
GN Name=PRKCD;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Hsieh Y.-T., Chen H.-C.;
RT "Canine protein kinase C delta.";
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Calcium-independent, phospholipid- and diacylglycerol (DAG)-
CC dependent serine/threonine-protein kinase that plays contrasting roles
CC in cell death and cell survival by functioning as a pro-apoptotic
CC protein during DNA damage-induced apoptosis, but acting as an anti-
CC apoptotic protein during cytokine receptor-initiated cell death, is
CC involved in tumor suppression, is required for oxygen radical
CC production by NADPH oxidase and acts as positive or negative regulator
CC in platelet functional responses. Upon DNA damage, activates the
CC promoter of the death-promoting transcription factor BCLAF1/Btf to
CC trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis. In
CC response to oxidative stress, interact with and activate CHUK/IKKA in
CC the nucleus, causing the phosphorylation of p53/TP53. In the case of ER
CC stress or DNA damage-induced apoptosis, can form a complex with the
CC tyrosine-protein kinase ABL1 which trigger apoptosis independently of
CC p53/TP53. In cytosol can trigger apoptosis by activating MAPK11 or
CC MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor
CC of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via
CC the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is
CC required for the activation of the apoptosis regulators BAX and BAK,
CC which trigger the mitochondrial cell death pathway. Can phosphorylate
CC MCL1 and target it for degradation which is sufficient to trigger for
CC BAX activation and apoptosis. Is required for the control of cell cycle
CC progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate
CC 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S
CC phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the
CC cyclin CCNA2 promoter activity. In response to UV irradiation can
CC phosphorylate CDK1, which is important for the G2/M DNA damage
CC checkpoint activation. Can protect glioma cells from the apoptosis
CC induced by TNFSF10/TRAIL, probably by inducing increased
CC phosphorylation and subsequent activation of AKT1. Can also act as
CC tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-
CC formyl-methionyl-leucyl-phenylalanine (fMLP)-treated cells, is required
CC for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase
CC activity, and regulates TNF-elicited superoxide anion production in
CC neutrophils, by direct phosphorylation and activation of NCF1 or
CC indirectly through MAPK1/3 (ERK1/2) signaling pathways. Involved in
CC antifungal immunity by mediating phosphorylation and activation of
CC CARD9 downstream of C-type lectin receptors activation, promoting
CC interaction between CARD9 and BCL10, followed by activation of NF-
CC kappa-B and MAP kinase p38 pathways (By similarity). May also play a
CC role in the regulation of NADPH oxidase activity in eosinophil after
CC stimulation with IL5, leukotriene B4 or PMA. In collagen-induced
CC platelet aggregation, acts a negative regulator of filopodia formation
CC and actin polymerization by interacting with and negatively regulating
CC VASP phosphorylation. Downstream of PAR1, PAR4 and CD36/GP4 receptors,
CC regulates differentially platelet dense granule secretion; acts as a
CC positive regulator in PAR-mediated granule secretion, whereas it
CC negatively regulates CD36/GP4-mediated granule release. Phosphorylates
CC MUC1 in the C-terminal and regulates the interaction between MUC1 and
CC beta-catenin (By similarity). The catalytic subunit phosphorylates 14-
CC 3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent
CC fashion. Phosphorylates ELAVL1 in response to angiotensin-2 treatment
CC (By similarity). Phosphorylates mitochondrial phospholipid scramblase 3
CC (PLSCR3), resulting in increased cardiolipin expression on the
CC mitochondrial outer membrane which facilitates apoptosis (By
CC similarity). Phosphorylates SMPD1 which induces SMPD1 secretion (By
CC similarity). {ECO:0000250|UniProtKB:P28867,
CC ECO:0000250|UniProtKB:Q05655}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.13;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.13; Evidence={ECO:0000250|UniProtKB:Q05655};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10027};
CC -!- ACTIVITY REGULATION: Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are
CC calcium-insensitive, but activated by diacylglycerol (DAG) and
CC phosphatidylserine. Three specific sites; Thr-505 (activation loop of
CC the kinase domain), Ser-643 (turn motif) and Ser-662 (hydrophobic
CC region), need to be phosphorylated for its full activation. Activated
CC by caspase-3 (CASP3) cleavage during apoptosis. After cleavage, the
CC pseudosubstrate motif in the regulatory subunit is released from the
CC substrate recognition site of the catalytic subunit, which enables
CC PRKCD to become constitutively activated. The catalytic subunit which
CC displays properties of a sphingosine-dependent protein kinase is
CC activated by D-erythro-sphingosine (Sph) or N,N-dimethyl-D-
CC erythrosphingosine (DMS) or N,N,N-trimethyl-D-erythrosphingosine (TMS),
CC but not by ceramide or Sph-1-P and is strongly inhibited by
CC phosphatidylserine (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with PDPK1 (via N-terminal region). Interacts with
CC RAD9A (By similarity). Interacts with CDCP1. Interacts with MUC1.
CC Interacts with VASP. Interacts with CAVIN3. Interacts with PRKD2 (via
CC N-terminus and zing-finger domain 1 and 2) in response to oxidative
CC stress; the interaction is independent of PRKD2 tyrosine
CC phosphorylation (By similarity). Interacts with PLSC3; interaction is
CC enhanced by UV irradiation (By similarity).
CC {ECO:0000250|UniProtKB:P28867, ECO:0000250|UniProtKB:Q05655}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q05655}.
CC Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q05655}. Nucleus
CC {ECO:0000250|UniProtKB:Q05655}. Cell membrane
CC {ECO:0000250|UniProtKB:Q05655}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q05655}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q05655}. Endomembrane system
CC {ECO:0000250|UniProtKB:Q05655}. Note=Translocates to the mitochondria
CC upon apoptotic stimulation. Upon activation, translocates to the plasma
CC membrane followed by partial location to the endolysosomes.
CC {ECO:0000250|UniProtKB:Q05655}.
CC -!- DOMAIN: The C1 domain, containing the phorbol ester/DAG-type region 1
CC (C1A) and 2 (C1B), is the diacylglycerol sensor.
CC -!- DOMAIN: The C2 domain is a non-calcium binding domain. It binds
CC proteins containing phosphotyrosine in a sequence-specific manner (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Autophosphorylated and/or phosphorylated at Thr-505, within the
CC activation loop; phosphorylation at Thr-505 is not a prerequisite for
CC enzymatic activity. Autophosphorylated at Ser-299 and Ser-302. Upon
CC TNFSF10/TRAIL treatment, phosphorylated at Tyr-155; phosphorylation is
CC required for its translocation to the endoplasmic reticulum and
CC cleavage by caspase-3. Phosphorylated at Tyr-310, Tyr-332 and Tyr-565;
CC phosphorylation of Tyr-310 and Tyr-565 following thrombin or zymosan
CC stimulation potentiates its kinase activity. Phosphorylated by protein
CC kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminal
CC cleavage product of PKN2. Phosphorylated at Tyr-310 through a SYK and
CC SRC mechanism downstream of C-type lectin receptors activation,
CC promoting its activation (By similarity).
CC {ECO:0000250|UniProtKB:P28867, ECO:0000250|UniProtKB:Q05655}.
CC -!- PTM: Proteolytically cleaved into a catalytic subunit and a regulatory
CC subunit by caspase-3 during apoptosis which results in kinase
CC activation. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. PKC subfamily. {ECO:0000305}.
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DR EMBL; AY825360; AAV80465.1; -; mRNA.
DR RefSeq; NP_001008716.1; NM_001008716.1.
DR STRING; 9615.ENSCAFP00000012799; -.
DR PaxDb; Q5PU49; -.
DR PRIDE; Q5PU49; -.
DR GeneID; 494005; -.
DR KEGG; cfa:494005; -.
DR CTD; 5580; -.
DR eggNOG; KOG0694; Eukaryota.
DR InParanoid; Q5PU49; -.
DR OrthoDB; 222529at2759; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0036019; C:endolysosome; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004698; F:calcium-dependent protein kinase C activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004697; F:protein kinase C activity; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; ISS:UniProtKB.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; ISS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:1904385; P:cellular response to angiotensin; ISS:UniProtKB.
DR GO; GO:0034644; P:cellular response to UV; ISS:UniProtKB.
DR GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0030837; P:negative regulation of actin filament polymerization; ISS:UniProtKB.
DR GO; GO:0051490; P:negative regulation of filopodium assembly; ISS:UniProtKB.
DR GO; GO:0034351; P:negative regulation of glial cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0090331; P:negative regulation of platelet aggregation; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:0032930; P:positive regulation of superoxide anion generation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:2000303; P:regulation of ceramide biosynthetic process; ISS:UniProtKB.
DR CDD; cd00029; C1; 2.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR020454; DAG/PE-bd.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR027436; PKC_delta.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR014376; Prot_kin_PKC_delta.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00130; C1_1; 2.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR PIRSF; PIRSF000551; PKC_delta; 1.
DR PIRSF; PIRSF501104; Protein_kin_C_delta; 1.
DR PRINTS; PR00008; DAGPEDOMAIN.
DR SMART; SM00109; C1; 2.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57889; SSF57889; 2.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 2.
DR PROSITE; PS50081; ZF_DAG_PE_2; 2.
PE 2: Evidence at transcript level;
KW Apoptosis; ATP-binding; Cell cycle; Cell membrane; Cytoplasm; Kinase;
KW Membrane; Metal-binding; Mitochondrion; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase; Tumor suppressor; Zinc;
KW Zinc-finger.
FT CHAIN 1..674
FT /note="Protein kinase C delta type"
FT /id="PRO_0000055693"
FT CHAIN 1..328
FT /note="Protein kinase C delta type regulatory subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000421665"
FT CHAIN 329..674
FT /note="Protein kinase C delta type catalytic subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000421666"
FT DOMAIN 1..106
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 347..601
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 602..673
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT ZN_FING 158..208
FT /note="Phorbol-ester/DAG-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ZN_FING 230..280
FT /note="Phorbol-ester/DAG-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ACT_SITE 471
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 353..361
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 376
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 48
FT /note="Interaction with phosphotyrosine-containing peptide"
FT /evidence="ECO:0000250"
FT SITE 62
FT /note="Interaction with phosphotyrosine-containing peptide"
FT /evidence="ECO:0000250"
FT SITE 67
FT /note="Interaction with phosphotyrosine-containing peptide"
FT /evidence="ECO:0000250"
FT SITE 123
FT /note="Interaction with phosphotyrosine-containing peptide"
FT /evidence="ECO:0000250"
FT SITE 328..329
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250"
FT MOD_RES 43
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P28867"
FT MOD_RES 50
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 64
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P09215"
FT MOD_RES 130
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 141
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 155
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 218
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 299
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 302
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 310
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P28867"
FT MOD_RES 332
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P09215"
FT MOD_RES 449
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 504
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 505
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 565
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 643
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 652
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 662
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
SQ SEQUENCE 674 AA; 77338 MW; 5A25DADDB7A364BA CRC64;
MAPFLRIAFT SYELGSLQAA DEASQPFCAV KMKEALSTER GKTLVQKKPT MYPEWKSTFD
AHIYEGRVIQ IVLMRAAEEP MSEVTVGVSV LAERCKKNNX KAEFWLDLQP QAKVLMSVQY
FLEDIDCRQS MHGEDEAKLP TMNRRGAIKQ AKIHYIKNHE FIATFFGQPT FCSVCKDFVW
GLNKQGYKCR QCNAAIHKKC IDKIIGRCTG TAANSRDTIF QKERFNIDMP HRFKVYNYMS
PTFCDHCGSL LWGLVKQGLK CEDCGMNVHH KCQKKVANLC GINQKLLAEA LNQVTQRSSR
KSETESVGIY QNFERKPGVS GDIAPGEDNG TYGKIWEGST RCNIDNFIFH KVLGKGSFGK
VLLVELKGKK EFFAIKALKK DVVLIDDDVE CTMVEKRVLA LAWENPFLTH LFCTFQTKDH
LFFVMEFLNG GDLMYHIQDK GRFELYRATF YAAEIVCGLQ FLHNKGIIYR DLKLDNVMLD
QDGHIKIADF GMCKENIFGE KQASTFCGTP DYIAPEILQG LKYSFSVDWW SFGVLLYEML
IGQSPFHGDD EDELFESIRV DTPHYPRWIT KESKDILEKL LERDTTKRLG VTGNIKIHPF
FKTINWTLLE KRAVEPPFKP KVKSPGDYSN FDQEFLNEKA RLSYTDKNLI DSMDQTAFAG
FSFVNPKFER FLEK
