Tchem PRKCZ Protein kinase C zeta type

Protein Summary

Description

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'. In vein endothelial cells treated with the oxidant peroxynitrite, phosphorylates STK11 leading to nuclear export of STK11, subsequent inhibition of PI3K/Akt signaling, and increased apoptosis. 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. 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]

Uniprot Accession IDs

• Q05513
• A8K4N0
• A8MU64
• B7Z2J7
• E9PCW2
• Q15207
• Q5SYT5
• Q969S4

Gene Name

• PRKCZ

Ensembl ID

• ENST00000378567
• ENSP00000367830
• ENSG00000067606
• ENST00000400921
• ENSP00000383712
• ENST00000461106
• ENSP00000426412

Symbol

• PKC2
• PKC2
• PKC-ZETA

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
hub protein	1
protein domain	1
molecular function	0.99
biological term	0.98

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Protein Kinase C Zeta Type

Protein / Transfer/carrier Protein / Protein Kinase C Zeta Type

Protein / Calcium-binding Protein / Intracellular Calcium-sensing Protein / Calmodulin / Protein Kinase C Zeta Type

Protein / Calcium-binding Protein / Annexin / Protein Kinase C Zeta Type

DTO Classes

Protein / Kinase / Protein Kinase / Agc Group / Pkc Family / Pkc Iota Subfamily / Protein Kinase C Zeta Type

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 526.42   (req: < 5)

Gene RIFs: 179   (req: <= 3)

Antibodies: 774   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 526.42   (req: >= 5)

Gene RIFs: 179   (req: > 3)

Antibodies: 774   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 50

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 36

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0