Q5PU49 (KPCD_CANFA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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:

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

Organism

Canis familiaris (Dog) (Canis lupus familiaris) [Reference proteome]

Taxonomic identifier

9615 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Carnivora › Caniformia › Canidae › Canis › Canis lupus

Protein attributes

Sequence length	674 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. Cytoplasm › perinuclear 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 process	Apoptosis Cell cycle
Cellular component	Cytoplasm Endoplasmic reticulum Membrane Mitochondrion Nucleus
Disease	Tumor suppressor
Domain	Repeat Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic 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_component	endoplasmic 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_function	ATP 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: EC protein kinase C activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 674	674	Protein kinase C delta type		PRO_0000055693
	Chain	1 – 328	328	Protein kinase C delta type regulatory subunit By similarity		PRO_0000421665
	Chain	329 – 674	346	Protein kinase C delta type catalytic subunit By similarity		PRO_0000421666
Regions
	Domain	1 – 90	90	C2
	Domain	347 – 601	255	Protein kinase
	Domain	602 – 673	72	AGC-kinase C-terminal
	Zinc finger	158 – 208	51	Phorbol-ester/DAG-type 1
	Zinc finger	230 – 280	51	Phorbol-ester/DAG-type 2
	Nucleotide binding	353 – 361	9	ATP By similarity
Sites
	Active site	471	1	Proton acceptor By similarity
	Binding site	376	1	ATP By similarity
	Site	48	1	Interaction with phosphotyrosine-containing peptide By similarity
	Site	62	1	Interaction with phosphotyrosine-containing peptide By similarity
	Site	67	1	Interaction with phosphotyrosine-containing peptide By similarity
	Site	123	1	Interaction with phosphotyrosine-containing peptide By similarity
	Site	328 – 329	2	Cleavage; by caspase-3 By similarity
Amino acid modifications
	Modified residue	43	1	Phosphothreonine By similarity
	Modified residue	64	1	Phosphotyrosine By similarity
	Modified residue	130	1	Phosphoserine By similarity
	Modified residue	155	1	Phosphotyrosine By similarity
	Modified residue	218	1	Phosphothreonine By similarity
	Modified residue	299	1	Phosphoserine; by autocatalysis By similarity
	Modified residue	302	1	Phosphoserine; by autocatalysis By similarity
	Modified residue	310	1	Phosphotyrosine; by SRC By similarity
	Modified residue	332	1	Phosphotyrosine; by SRC By similarity
	Modified residue	505	1	Phosphothreonine; by autocatalysis By similarity
	Modified residue	565	1	Phosphotyrosine By similarity
	Modified residue	643	1	Phosphoserine Probable
	Modified residue	652	1	Phosphoserine By similarity
	Modified residue	662	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q5PU49 [UniParc]. Last modified January 4, 2005. Version 1. Checksum: 5A25DADDB7A364BA	FASTA	674	77,338
	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

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.
RefSeq	NP_001008716.1. NM_001008716.1.
UniGene	Cfa.16226.
3D structure databases
ProteinModelPortal	Q5PU49.
SMR	Q5PU49. Positions 149-218, 227-283, 344-666.
ModBase	Search...
Protein-protein interaction databases
STRING	9615.ENSCAFP00000012799.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	494005.
KEGG	cfa:494005.
Organism-specific databases
CTD	5580.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000233022.
HOVERGEN	HBG108317.
InParanoid	Q5PU49.
KO	K06068.
OrthoDB	EOG4M91QX.
Family and domain databases
InterPro	IPR000961. AGC-kinase_C. IPR000008. C2_Ca-dep. IPR008973. C2_Ca/lipid-bd_dom_CaLB. IPR020454. DAG/PE-bd. IPR011009. Kinase-like_dom. IPR017892. Pkinase_C. IPR014376. Prot_kin_PKC_delta. IPR002219. Prot_Kinase_C-like_PE/DAG-bd. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00130. C1_1. 2 hits. PF00069. Pkinase. 1 hit. PF00433. Pkinase_C. 1 hit. [Graphical view]
PIRSF	PIRSF000551. PKC_delta. 1 hit.
PRINTS	PR00008. DAGPEDOMAIN.
SMART	SM00109. C1. 2 hits. SM00239. C2. 1 hit. SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF49562. C2_CaLB. 1 hit. SSF56112. Kinase_like. 1 hit.
PROSITE	PS51285. AGC_KINASE_CTER. 1 hit. PS50004. C2. False negative. 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]
ProtoNet	Search...
Other
NextBio	20865534.

Entry information

Entry name

KPCD_CANFA

Accession

Primary (citable) accession number: Q5PU49

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 29, 2005
Last sequence update:	January 4, 2005
Last modified:	April 3, 2013
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program