PRKCZ (protein kinase C zeta)

Gene

• Entrez ID: 5590
• Gene name: Protein kinase C zeta
• Gene symbol: PRKCZ
• Synonyms: PKC-ZETA, PKC2
• Chromosome: 1
• Chromosome location: 1p36.33
• Summary: Protein kinase C (PKC) zeta is a member of the PKC family of serine/threonine kinases which are involved in a variety of cellular processes such as proliferation, differentiation and secretion. Unlike the classical PKC isoenzymes which are calcium-dependent, PKC zeta exhibits a kinase activity which is independent of calcium and diacylglycerol but not of phosphatidylserine. Furthermore, it is insensitive to typical PKC inhibitors and cannot be activated by phorbol ester. Unlike the classical PKC isoenzymes, it has only a single zinc finger module. These structural and biochemical properties indicate that the zeta subspecies is related to, but distinct from other isoenzymes of PKC. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT732637	hsa-miR-200c-3p	Immunoblot, Immunohistochemistry, Luciferase reporter assay, Microarray	28218902
MIRT733776	hsa-miR-25-5p	qRT-PCR, Western blot	27911275

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000226	Process	Microtubule cytoskeleton organization	IEA
GO:0001725	Component	Stress fiber	IEA
GO:0001954	Process	Positive regulation of cell-matrix adhesion	IEA
GO:0004672	Function	Protein kinase activity	IDA	10770950
GO:0004674	Function	Protein serine/threonine kinase activity	EXP	12391145
GO:0004674	Function	Protein serine/threonine kinase activity	IBA	21873635
GO:0004674	Function	Protein serine/threonine kinase activity	IDA	15069075
GO:0004698	Function	Calcium-dependent protein kinase C activity	IEA
GO:0005515	Function	Protein binding	IPI	10831594, 11260256, 11755531, 12893243, 14676191, 15707389, 16189514, 16792529, 17057644, 17203073, 17313651, 17350623, 17588663, 18190796, 18650932, 21829704, 22939624, 24375676, 25011391, 25241761, 25852190, 26583432, 27040869, 27107012, 28514442, 31980649, 32296183
GO:0005524	Function	ATP binding	IEA
GO:0005635	Component	Nuclear envelope	IEA
GO:0005737	Component	Cytoplasm	TAS	7925449
GO:0005768	Component	Endosome	IEA
GO:0005815	Component	Microtubule organizing center	IEA
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA
GO:0005911	Component	Cell-cell junction	IDA	20332120
GO:0005923	Component	Bicellular tight junction	IEA
GO:0006468	Process	Protein phosphorylation	IDA	10770950, 17313651
GO:0006954	Process	Inflammatory response	IEA
GO:0007165	Process	Signal transduction	TAS	8224878
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	TAS
GO:0007616	Process	Long-term memory	IEA
GO:0008284	Process	Positive regulation of cell population proliferation	IEA
GO:0014069	Component	Postsynaptic density	IEA
GO:0015459	Function	Potassium channel regulator activity	IEA
GO:0016020	Component	Membrane	TAS	7925449
GO:0016324	Component	Apical plasma membrane	IEA
GO:0016363	Component	Nuclear matrix	IEA
GO:0016477	Process	Cell migration	IEA
GO:0018105	Process	Peptidyl-serine phosphorylation	IBA	21873635
GO:0018105	Process	Peptidyl-serine phosphorylation	IDA	15069075
GO:0019901	Function	Protein kinase binding	IEA
GO:0030010	Process	Establishment of cell polarity	ISS
GO:0030054	Component	Cell junction	TAS
GO:0031252	Component	Cell leading edge	IEA
GO:0031333	Process	Negative regulation of protein-containing complex assembly	IMP	15069075
GO:0031584	Process	Activation of phospholipase D activity	IEA
GO:0031982	Component	Vesicle	IDA	17313651
GO:0032148	Process	Activation of protein kinase B activity	IEA
GO:0032733	Process	Positive regulation of interleukin-10 production	ISS
GO:0032736	Process	Positive regulation of interleukin-13 production	ISS
GO:0032753	Process	Positive regulation of interleukin-4 production	ISS
GO:0032754	Process	Positive regulation of interleukin-5 production	ISS
GO:0032869	Process	Cellular response to insulin stimulus	IEA
GO:0035556	Process	Intracellular signal transduction	IBA	21873635
GO:0035748	Component	Myelin sheath abaxonal region	IEA
GO:0043066	Process	Negative regulation of apoptotic process	IEA
GO:0043203	Component	Axon hillock	IEA
GO:0043274	Function	Phospholipase binding	IEA
GO:0043560	Function	Insulin receptor substrate binding	IC	15069075
GO:0044877	Function	Protein-containing complex binding	IEA
GO:0045121	Component	Membrane raft	IEA
GO:0045179	Component	Apical cortex	IEA
GO:0045630	Process	Positive regulation of T-helper 2 cell differentiation	ISS
GO:0046627	Process	Negative regulation of insulin receptor signaling pathway	IMP	15069075
GO:0046628	Process	Positive regulation of insulin receptor signaling pathway	ISS
GO:0046872	Function	Metal ion binding	IEA
GO:0047496	Process	Vesicle transport along microtubule	IEA
GO:0048471	Component	Perinuclear region of cytoplasm	IEA
GO:0050732	Process	Negative regulation of peptidyl-tyrosine phosphorylation	IMP	15069075
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	ISS
GO:0051222	Process	Positive regulation of protein transport	IEA
GO:0051346	Process	Negative regulation of hydrolase activity	IEA
GO:0051899	Process	Membrane depolarization	IEA
GO:0060081	Process	Membrane hyperpolarization	IEA
GO:0060291	Process	Long-term synaptic potentiation	ISS
GO:0070062	Component	Extracellular exosome	HDA	19056867
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	IMP	11035106
GO:0070528	Process	Protein kinase C signaling	IEA
GO:0071889	Function	14-3-3 protein binding	IEA
GO:0072659	Process	Protein localization to plasma membrane	IEA
GO:0098685	Component	Schaffer collateral - CA1 synapse	IEA
GO:0098696	Process	Regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	IEA
GO:0098978	Component	Glutamatergic synapse	IEA
GO:1990138	Process	Neuron projection extension	IEA
GO:2000463	Process	Positive regulation of excitatory postsynaptic potential	ISS
GO:2000553	Process	Positive regulation of T-helper 2 cell cytokine production	ISS

Other IDs

• MIM: 176982
• HGNC: 9412
• e!Ensembl: ENSG00000067606

Protein

• UniProt ID: Q05513
• Protein name: Protein kinase C zeta type (EC 2.7.11.13) (nPKC-zeta)
• Protein function: Calcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Required for insulin-dependent activation of AKT3, but may function as an adapter rather than a direct activator. Upon insulin treatment may act as a downstream effector of PI3K and contribute to the activation of translocation of the glucose transporter SLC2A4/GLUT4 and subsequent glucose transport in adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-MAPK7/ERK5 independently of its kinase activity and can activate JUN promoter through MEF2C. Through binding with SQSTM1/p62, functions in interleukin-1 signaling and activation of NF-kappa-B with the specific adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in turn leads to the degradation of NF-kappa-B inhibitors. In migrating astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by CDC42 to function in the establishment of cell polarity along with the microtubule motor and dynein. In association with FEZ1, stimulates neuronal differentiation in PC12 cells. In the inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukin production, efficient activation of JAK1 and the subsequent phosphorylation and nuclear translocation of STAT6. May be involved in development of allergic airway inflammation (asthma), a process dependent on Th2 immune response. In the NF-kappa-B-mediated inflammatory response, can relieve SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. Phosphorylates VAMP2 in vitro (PubMed:17313651). ; [Isoform 2]: Involved in late synaptic long term potention phase in CA1 hippocampal cells and long term memory maintenance.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00564	PB1	15 → 98	PB1 domain	Domain
  PF00130	C1_1	131 → 183	Phorbol esters/diacylglycerol binding domain (C1 domain)	Domain
  PF00069	Pkinase	252 → 518	Protein kinase domain	Domain
  PF00433	Pkinase_C	539 → 580	Protein kinase C terminal domain	Family

• Sequence:

  MPSRTGPKMEGSGGRVRLKAHYGGDIFITSVDAATTFEELCEEVRDMCRLHQQHPLTLKW
  VDSEGDPCTVSSQMELEEAFRLARQCRDEGLIIHVFPSTPEQPGLPCPGEDKSIYRRGAR
  RWRKLYRANGHLFQAKRFNRRAYCGQCSERIWGLARQGYRCINCKLLVHKRCHGLVPLTC
  RKHMDSVMPSQEPPVDDKNEDADLPSEETDGIAYISSSRKHDSIKDDSEDLKPVIDGMDG
  IKISQGLGLQDFDLIRVIGRGSYAKVLLVRLKKNDQIYAMKVVKKELVHDDEDIDWVQTE
  KHVFEQASSNPFLVGLHSCFQTTSRLFLVIEYVNGGDLMFHMQRQRKLPEEHARFYAAEI
  CIALNFLHERGIIYRDLKLDNVLLDADGHIKLTDYGMCKEGLGPGDTTSTFCGTPNYIAP
  EILRGEEYGFSVDWWALGVLMFEMMAGRSPFDIITDNPDMNTEDYLFQVILEKPIRIPRF
  LSVKASHVLKGFLNKDPKERLGCRPQTGFSDIKSHAFFRSIDWDLLEKKQALPPFQPQIT
  DDYGLDNFDTQFTSEPVQLTPDDEDAIKRIDQSEFEGFEYINPLLLSTEESV

• Sequence length: 592