PRKCD (protein kinase C delta)

Gene

• Entrez ID: 5580
• Gene name: Protein kinase C delta
• Gene symbol: PRKCD
• Synonyms: ALPS3, CVID9, MAY1, PKCD, nPKC-delta
• Chromosome: 3
• Chromosome location: 3p21.1
• Summary: The protein encoded by this gene is a member of the protein kinase C family of serine- and threonine-specific protein kinases. The encoded protein is activated by diacylglycerol and is both a tumor suppressor and a positive regulator of cell cycle progression. Also, this protein can positively or negatively regulate apoptosis. Defects in this gene are a cause of autoimmune lymphoproliferative syndrome. [provided by RefSeq, Aug 2017]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs33911937	A>G	Conflicting-interpretations-of-pathogenicity	Intron variant, missense variant, coding sequence variant
rs398122958	G>A	Pathogenic	Splice donor variant
rs606231296	G>A	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs606231297	C>T	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs1295207359	A>G	Likely-pathogenic	Splice acceptor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT039609	hsa-miR-615-3p	CLASH	23622248
MIRT041814	hsa-miR-484	CLASH	23622248
MIRT053097	hsa-miR-26a-5p	Luciferase reporter assay, Western blot	23525216
MIRT053097	hsa-miR-26a-5p	HITS-CLIP	22473208
MIRT163253	hsa-miR-15a-5p	HITS-CLIP	22473208
MIRT163254	hsa-miR-16-5p	HITS-CLIP	22473208
MIRT163257	hsa-miR-15b-5p	HITS-CLIP	22473208
MIRT163261	hsa-miR-195-5p	HITS-CLIP	22473208
MIRT163340	hsa-miR-26b-5p	HITS-CLIP	22473208
MIRT163342	hsa-miR-181a-5p	HITS-CLIP	22473208
MIRT163342	hsa-miR-181a-5p	Luciferase reporter assay	24183997
MIRT163342	hsa-miR-181a-5p	Flow, Luciferase reporter assay, Microarray, qRT-PCR, Western blot	22847611
MIRT163342	hsa-miR-181a-5p	qRT-PCR, Luciferase reporter assay, Western blot	25174404
MIRT163343	hsa-miR-181b-5p	HITS-CLIP	22473208
MIRT163344	hsa-miR-181c-5p	HITS-CLIP	22473208
MIRT163344	hsa-miR-181c-5p	Luciferase reporter assay	26629004
MIRT163346	hsa-miR-190a-3p	PAR-CLIP	23446348
MIRT163346	hsa-miR-190a-3p	PAR-CLIP	21572407
MIRT163346	hsa-miR-190a-3p	HITS-CLIP	23824327
MIRT163348	hsa-miR-369-3p	PAR-CLIP	23446348
MIRT163348	hsa-miR-369-3p	PAR-CLIP	21572407
MIRT163349	hsa-miR-374a-5p	PAR-CLIP	23446348
MIRT163349	hsa-miR-374a-5p	PAR-CLIP	21572407
MIRT163350	hsa-miR-410-3p	PAR-CLIP	23446348
MIRT163350	hsa-miR-410-3p	PAR-CLIP	21572407
MIRT163351	hsa-miR-181d-5p	HITS-CLIP	22473208
MIRT163358	hsa-miR-374b-5p	PAR-CLIP	23446348
MIRT163358	hsa-miR-374b-5p	PAR-CLIP	21572407
MIRT163362	hsa-miR-1305	PAR-CLIP	23446348
MIRT163363	hsa-miR-1277-5p	PAR-CLIP	23446348
MIRT163363	hsa-miR-1277-5p	PAR-CLIP	21572407
MIRT163369	hsa-miR-3924	PAR-CLIP	23446348
MIRT163369	hsa-miR-3924	PAR-CLIP	21572407
MIRT163378	hsa-miR-5011-5p	PAR-CLIP	23446348
MIRT163378	hsa-miR-5011-5p	PAR-CLIP	21572407
MIRT163378	hsa-miR-5011-5p	HITS-CLIP	23824327
MIRT163379	hsa-miR-5692c	PAR-CLIP	23446348
MIRT163379	hsa-miR-5692c	PAR-CLIP	21572407
MIRT163380	hsa-miR-5692b	PAR-CLIP	23446348
MIRT163380	hsa-miR-5692b	PAR-CLIP	21572407
MIRT163384	hsa-miR-6856-3p	PAR-CLIP	21572407
MIRT515488	hsa-miR-4796-5p	PAR-CLIP	23446348
MIRT515488	hsa-miR-4796-5p	PAR-CLIP	21572407
MIRT515489	hsa-miR-654-3p	PAR-CLIP	23446348
MIRT515489	hsa-miR-654-3p	PAR-CLIP	21572407
MIRT613705	hsa-miR-129-5p	HITS-CLIP	23824327
MIRT613706	hsa-miR-6772-3p	HITS-CLIP	23824327
MIRT613707	hsa-miR-4448	HITS-CLIP	23824327
MIRT613708	hsa-miR-4268	HITS-CLIP	23824327
MIRT733094	hsa-miR-26a-1-3p	Luciferase reporter assay, qRT-PCR, Western blot	25961460
MIRT734493	hsa-miR-486-3p	Luciferase reporter assay, qRT-PCR, Western blot	28339053

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002223	Process	Stimulatory C-type lectin receptor signaling pathway	TAS
GO:0004672	Function	Protein kinase activity	IDA	24008408
GO:0004674	Function	Protein serine/threonine kinase activity	EXP	12391145, 18285462
GO:0004674	Function	Protein serine/threonine kinase activity	IBA	21873635
GO:0004674	Function	Protein serine/threonine kinase activity	IDA	10770950, 18285462, 19059439
GO:0004697	Function	Protein kinase C activity	ISS
GO:0004698	Function	Calcium-dependent protein kinase C activity	IEA
GO:0004699	Function	Calcium-independent protein kinase C activity	TAS	14583092
GO:0004715	Function	Non-membrane spanning protein tyrosine kinase activity	IEA
GO:0005515	Function	Protein binding	IPI	9139733, 10383400, 10948194, 12628935, 12649167, 12721299, 15591124, 16377624, 16611985, 16940418, 22465666, 22528498, 23814099, 24396867, 24996056, 25241761, 26112605, 32814053
GO:0005524	Function	ATP binding	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005634	Component	Nucleus	IDA	15632189, 15774464, 16611985, 18285462
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IDA	15632189, 16611985, 18285462
GO:0005739	Component	Mitochondrion	IEA
GO:0005783	Component	Endoplasmic reticulum	IDA	15774464, 18556656
GO:0005829	Component	Cytosol	IDA	10770950, 15774464, 17303575
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA	10770950, 15632189, 17303575
GO:0005886	Component	Plasma membrane	TAS
GO:0005911	Component	Cell-cell junction	IEA
GO:0006468	Process	Protein phosphorylation	IDA	10713049, 12649167, 16611985
GO:0006915	Process	Apoptotic process	IDA	10770950, 12649167
GO:0007049	Process	Cell cycle	IEA
GO:0007165	Process	Signal transduction	TAS	8357834
GO:0008047	Function	Enzyme activator activity	IDA	16611985
GO:0008631	Process	Intrinsic apoptotic signaling pathway in response to oxidative stress	TAS	24522549
GO:0010469	Process	Regulation of signaling receptor activity	TAS	14583092
GO:0016064	Process	Immunoglobulin mediated immune response	IEA
GO:0016363	Component	Nuclear matrix	IEA
GO:0016572	Process	Histone phosphorylation	IDA	19059439
GO:0018105	Process	Peptidyl-serine phosphorylation	IBA	21873635
GO:0018105	Process	Peptidyl-serine phosphorylation	IDA	18285462
GO:0018107	Process	Peptidyl-threonine phosphorylation	IDA	10770950
GO:0018108	Process	Peptidyl-tyrosine phosphorylation	IEA
GO:0019899	Function	Enzyme binding	IDA	18556656
GO:0019899	Function	Enzyme binding	IPI	16611985, 19059439
GO:0019900	Function	Kinase binding	IPI	19059439
GO:0019901	Function	Protein kinase binding	IPI	10713049, 28428613
GO:0023021	Process	Termination of signal transduction	IMP	19279008
GO:0030168	Process	Platelet activation	TAS
GO:0030837	Process	Negative regulation of actin filament polymerization	ISS
GO:0032079	Process	Positive regulation of endodeoxyribonuclease activity	IMP	19059439
GO:0032091	Process	Negative regulation of protein binding	TAS	14583092
GO:0032147	Process	Activation of protein kinase activity	IDA	10713049
GO:0032930	Process	Positive regulation of superoxide anion generation	IMP	19801500
GO:0032956	Process	Regulation of actin cytoskeleton organization	IMP	22554282
GO:0034351	Process	Negative regulation of glial cell apoptotic process	IMP	15774464
GO:0034644	Process	Cellular response to UV	IDA	17303575
GO:0035307	Process	Positive regulation of protein dephosphorylation	IMP	19279008
GO:0035556	Process	Intracellular signal transduction	IBA	21873635
GO:0035578	Component	Azurophil granule lumen	TAS
GO:0036019	Component	Endolysosome	IDA	17303575
GO:0038096	Process	Fc-gamma receptor signaling pathway involved in phagocytosis	TAS
GO:0042100	Process	B cell proliferation	IEA
GO:0042119	Process	Neutrophil activation	IDA	10770950
GO:0042307	Process	Positive regulation of protein import into nucleus	IMP	19059439
GO:0042742	Process	Defense response to bacterium	ISS
GO:0043312	Process	Neutrophil degranulation	TAS
GO:0043407	Process	Negative regulation of MAP kinase activity	IMP	19279008
GO:0043488	Process	Regulation of mRNA stability	TAS
GO:0043560	Function	Insulin receptor substrate binding	ISS
GO:0046627	Process	Negative regulation of insulin receptor signaling pathway	ISS
GO:0046627	Process	Negative regulation of insulin receptor signaling pathway	TAS	14583092
GO:0046872	Function	Metal ion binding	IEA
GO:0048471	Component	Perinuclear region of cytoplasm	IEA
GO:0050728	Process	Negative regulation of inflammatory response	IC	19279008
GO:0050732	Process	Negative regulation of peptidyl-tyrosine phosphorylation	ISS	14583092
GO:0050821	Process	Protein stabilization	NAS	16611985
GO:0051490	Process	Negative regulation of filopodium assembly	ISS
GO:0060326	Process	Cell chemotaxis	IMP	24008408
GO:0060333	Process	Interferon-gamma-mediated signaling pathway	TAS
GO:0070062	Component	Extracellular exosome	HDA	19056867
GO:0070301	Process	Cellular response to hydrogen peroxide	IDA	10713049
GO:0071447	Process	Cellular response to hydroperoxide	IDA	19059439
GO:0090331	Process	Negative regulation of platelet aggregation	ISS
GO:0090398	Process	Cellular senescence	IMP	15282327
GO:0106310	Function	Protein serine kinase activity	IDA	17303575
GO:1900163	Process	Positive regulation of phospholipid scramblase activity	IMP	10770950
GO:1904385	Process	Cellular response to angiotensin	IDA	18285462
GO:2000303	Process	Regulation of ceramide biosynthetic process	IDA	17303575
GO:2000304	Process	Positive regulation of ceramide biosynthetic process	IMP	19279011
GO:2000753	Process	Positive regulation of glucosylceramide catabolic process	IMP	19279011
GO:2000755	Process	Positive regulation of sphingomyelin catabolic process	IMP	19279011
GO:2001022	Process	Positive regulation of response to DNA damage stimulus	IMP	17938203
GO:2001235	Process	Positive regulation of apoptotic signaling pathway	IEA

Other IDs

• MIM: 176977
• HGNC: 9399
• e!Ensembl: ENSG00000163932

Protein

• UniProt ID: Q05655
• Protein name: Protein kinase C delta type (EC 2.7.11.13) (Tyrosine-protein kinase PRKCD) (EC 2.7.10.2) (nPKC-delta) [Cleaved into: Protein kinase C delta type regulatory subunit; Protein kinase C delta type catalytic subunit (Sphingosine-dependent protein kinase-1) (SDK1)]
• Protein 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 as well as survival of several cancers, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses (PubMed:21810427, PubMed:21406692). Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction (By similarity). Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis (PubMed:21810427, PubMed:21406692). In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53 (PubMed:21810427, PubMed:21406692). 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 (PubMed:21810427, PubMed:21406692). 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 (By similarity). Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1 (PubMed:15774464). Is highly expressed in a number of cancer cells and promotes cell survival and resistance against chemotherapeutic drugs by inducing cyclin D1 (CCND1) and hyperphosphorylation of RB1, and via several pro-survival pathways, including NF-kappa-B, AKT1 and MAPK1/3 (ERK1/2). Involved in antifungal immunity by mediating phosphorylation and activation of CARD9 downstream of C-type lectin receptors activation, promoting interaction between CARD9 and BCL10, followed by activation of NF-kappa-B and MAP kinase p38 pathways (By similarity). 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 (PubMed:19801500). May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA (PubMed:11748588). In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation (PubMed:16940418). 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 (PubMed:19587372). Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin (PubMed:11877440). The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion (By similarity). Phosphorylates ELAVL1 in response to angiotensin-2 treatment (PubMed:18285462). Phosphorylates mitochondrial phospolipid scramblase 3 (PLSCR3), resulting in increased cardiolipin expression on the mitochondrial outer membrane which facilitates apoptosis (PubMed:12649167). Phosphorylates SMPD1 which induces SMPD1 secretion (PubMed:17303575).
• PDB: 1YRK, 2YUU
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00130	C1_1	159 → 211	Phorbol esters/diacylglycerol binding domain (C1 domain)	Domain
  PF00130	C1_1	231 → 283	Phorbol esters/diacylglycerol binding domain (C1 domain)	Domain
  PF00069	Pkinase	349 → 603	Protein kinase domain	Domain
  PF00433	Pkinase_C	624 → 665	Protein kinase C terminal domain	Family

• Sequence:

  MAPFLRIAFNSYELGSLQAEDEANQPFCAVKMKEALSTERGKTLVQKKPTMYPEWKSTFD
  AHIYEGRVIQIVLMRAAEEPVSEVTVGVSVLAERCKKNNGKAEFWLDLQPQAKVLMSVQY
  FLEDVDCKQSMRSEDEAKFPTMNRRGAIKQAKIHYIKNHEFIATFFGQPTFCSVCKDFVW
  GLNKQGYKCRQCNAAIHKKCIDKIIGRCTGTAANSRDTIFQKERFNIDMPHRFKVHNYMS
  PTFCDHCGSLLWGLVKQGLKCEDCGMNVHHKCREKVANLCGINQKLLAEALNQVTQRASR
  RSDSASSEPVGIYQGFEKKTGVAGEDMQDNSGTYGKIWEGSSKCNINNFIFHKVLGKGSF
  GKVLLGELKGRGEYFAIKALKKDVVLIDDDVECTMVEKRVLTLAAENPFLTHLICTFQTK
  DHLFFVMEFLNGGDLMYHIQDKGRFELYRATFYAAEIMCGLQFLHSKGIIYRDLKLDNVL
  LDRDGHIKIADFGMCKENIFGESRASTFCGTPDYIAPEILQGLKYTFSVDWWSFGVLLYE
  MLIGQSPFHGDDEDELFESIRVDTPHYPRWITKESKDILEKLFEREPTKRLGVTGNIKIH
  PFFKTINWTLLEKRRLEPPFRPKVKSPRDYSNFDQEFLNEKARLSYSDKNLIDSMDQSAF
  AGFSFVNPKFEHLLED

• Sequence length: 676