PRKCQ (protein kinase C theta)

Gene

• Entrez ID: 5588
• Gene name: Protein kinase C theta
• Gene symbol: PRKCQ
• Synonyms: PRKCT, nPKC-theta
• Chromosome: 10
• Chromosome location: 10p15.1
• Summary: Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role. The protein encoded by this gene is one of the PKC family members. It is a calcium-independent and phospholipid-dependent protein kinase. This kinase is important for T-cell activation. It is required for the activation of the transcription factors NF-kappaB and AP-1, and may link the T cell receptor (TCR) signaling complex to the activation of the transcription factors. [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs2236379	G>A,C	Pathogenic	Coding sequence variant, missense variant

Transcription factors

Transcription factor	Regulation	Reference
RUNX1	Unknown	21252065

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001558	Process	Regulation of cell growth	NAS	8444877
GO:0001772	Component	Immunological synapse	IEA
GO:0004672	Function	Protein kinase activity	TAS
GO:0004674	Function	Protein serine/threonine kinase activity	EXP	16356856
GO:0004674	Function	Protein serine/threonine kinase activity	IBA	21873635
GO:0004674	Function	Protein serine/threonine kinase activity	NAS	8444877
GO:0004698	Function	Calcium-dependent protein kinase C activity	IEA
GO:0005515	Function	Protein binding	IPI	10383400, 10636891, 11788586, 15254234, 17588663, 21964608, 21983831, 23352416, 23509302
GO:0005524	Function	ATP binding	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	TAS
GO:0006355	Process	Regulation of transcription, DNA-templated	ISS
GO:0006509	Process	Membrane protein ectodomain proteolysis	ISS
GO:0006954	Process	Inflammatory response	IEA
GO:0007411	Process	Axon guidance	TAS
GO:0016235	Component	Aggresome	IDA
GO:0018105	Process	Peptidyl-serine phosphorylation	IBA	21873635
GO:0030168	Process	Platelet activation	TAS
GO:0032212	Process	Positive regulation of telomere maintenance via telomerase	IMP	21531765
GO:0032740	Process	Positive regulation of interleukin-17 production	ISS
GO:0032743	Process	Positive regulation of interleukin-2 production	IEA
GO:0032753	Process	Positive regulation of interleukin-4 production	ISS
GO:0034451	Component	Centriolar satellite	IDA
GO:0035556	Process	Intracellular signal transduction	IBA	21873635
GO:0035556	Process	Intracellular signal transduction	NAS	7686153
GO:0038095	Process	Fc-epsilon receptor signaling pathway	TAS
GO:0042102	Process	Positive regulation of T cell proliferation	IEA
GO:0045652	Process	Regulation of megakaryocyte differentiation	TAS
GO:0046627	Process	Negative regulation of insulin receptor signaling pathway	IMP	15364919
GO:0046872	Function	Metal ion binding	IEA
GO:0050852	Process	T cell receptor signaling pathway	TAS
GO:0050870	Process	Positive regulation of T cell activation	ISS
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IDA	16356855
GO:0051973	Process	Positive regulation of telomerase activity	IMP	21531765
GO:0060326	Process	Cell chemotaxis	IMP	24008408
GO:0070233	Process	Negative regulation of T cell apoptotic process	IMP	11342610, 16709830
GO:0090330	Process	Regulation of platelet aggregation	ISS
GO:1904355	Process	Positive regulation of telomere capping	IMP	21531765
GO:2000318	Process	Positive regulation of T-helper 17 type immune response	ISS
GO:2000570	Process	Positive regulation of T-helper 2 cell activation	ISS

Other IDs

• MIM: 600448
• HGNC: 9410
• e!Ensembl: ENSG00000065675

Protein

• UniProt ID: Q04759
• Protein name: Protein kinase C theta type (EC 2.7.11.13) (nPKC-theta)
• Protein function: Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non-redundant functions in T-cell receptor (TCR) signaling, including T-cells activation, proliferation, differentiation and survival, by mediating activation of multiple transcription factors such as NF-kappa-B, JUN, NFATC1 and NFATC2. In TCR-CD3/CD28-co-stimulated T-cells, is required for the activation of NF-kappa-B and JUN, which in turn are essential for IL2 production, and participates in the calcium-dependent NFATC1 and NFATC2 transactivation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11 on several serine residues, inducing CARD11 association with lipid rafts and recruitment of the BCL10-MALT1 complex, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. May also play an indirect role in activation of the non-canonical NF-kappa-B (NFKB2) pathway. In the signaling pathway leading to JUN activation, acts by phosphorylating the mediator STK39/SPAK and may not act through MAP kinases signaling. Plays a critical role in TCR/CD28-induced NFATC1 and NFATC2 transactivation by participating in the regulation of reduced inositol 1,4,5-trisphosphate generation and intracellular calcium mobilization. After costimulation of T-cells through CD28 can phosphorylate CBLB and is required for the ubiquitination and subsequent degradation of CBLB, which is a prerequisite for the activation of TCR. During T-cells differentiation, plays an important role in the development of T-helper 2 (Th2) cells following immune and inflammatory responses, and, in the development of inflammatory autoimmune diseases, is necessary for the activation of IL17-producing Th17 cells. May play a minor role in Th1 response. Upon TCR stimulation, mediates T-cell protective survival signal by phosphorylating BAD, thus protecting T-cells from BAD-induced apoptosis, and by up-regulating BCL-X(L)/BCL2L1 levels through NF-kappa-B and JUN pathways. In platelets, regulates signal transduction downstream of the ITGA2B, CD36/GP4, F2R/PAR1 and F2RL3/PAR4 receptors, playing a positive role in 'outside-in' signaling and granule secretion signal transduction. May relay signals from the activated ITGA2B receptor by regulating the uncoupling of WASP and WIPF1, thereby permitting the regulation of actin filament nucleation and branching activity of the Arp2/3 complex. May mediate inhibitory effects of free fatty acids on insulin signaling by phosphorylating IRS1, which in turn blocks IRS1 tyrosine phosphorylation and downstream activation of the PI3K/AKT pathway. Phosphorylates MSN (moesin) in the presence of phosphatidylglycerol or phosphatidylinositol. Phosphorylates PDPK1 at 'Ser-504' and 'Ser-532' and negatively regulates its ability to phosphorylate PKB/AKT1. Phosphorylates CCDC88A/GIV and inhibits its guanine nucleotide exchange factor activity (PubMed:23509302).
• PDB: 1XJD, 2ENJ, 2ENN, 2ENZ, 2JED, 4Q9Z, 4RA5, 5F9E
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00130	C1_1	160 → 212	Phorbol esters/diacylglycerol binding domain (C1 domain)	Domain
  PF00130	C1_1	232 → 284	Phorbol esters/diacylglycerol binding domain (C1 domain)	Domain
  PF00069	Pkinase	380 → 634	Protein kinase domain	Domain
  PF00433	Pkinase_C	655 → 696	Protein kinase C terminal domain	Family

• Sequence:

  MSPFLRIGLSNFDCGSCQSCQGEAVNPYCAVLVKEYVESENGQMYIQKKPTMYPPWDSTF
  DAHINKGRVMQIIVKGKNVDLISETTVELYSLAERCRKNNGKTEIWLELKPQGRMLMNAR
  YFLEMSDTKDMNEFETEGFFALHQRRGAIKQAKVHHVKCHEFTATFFPQPTFCSVCHEFV
  WGLNKQGYQCRQCNAAIHKKCIDKVIAKCTGSAINSRETMFHKERFKIDMPHRFKVYNYK
  SPTFCEHCGTLLWGLARQGLKCDACGMNVHHRCQTKVANLCGINQKLMAEALAMIESTQQ
  ARCLRDTEQIFREGPVEIGLPCSIKNEARPPCLPTPGKREPQGISWESPLDEVDKMCHLP
  EPELNKERPSLQIKLKIEDFILHKMLGKGSFGKVFLAEFKKTNQFFAIKALKKDVVLMDD
  DVECTMVEKRVLSLAWEHPFLTHMFCTFQTKENLFFVMEYLNGGDLMYHIQSCHKFDLSR
  ATFYAAEIILGLQFLHSKGIVYRDLKLDNILLDKDGHIKIADFGMCKENMLGDAKTNTFC
  GTPDYIAPEILLGQKYNHSVDWWSFGVLLYEMLIGQSPFHGQDEEELFHSIRMDNPFYPR
  WLEKEAKDLLVKLFVREPEKRLGVRGDIRQHPLFREINWEELERKEIDPPFRPKVKSPFD
  CSNFDKEFLNEKPRLSFADRALINSMDQNMFRNFSFMNPGMERLIS

• Sequence length: 706