Protein kinase C zeta type
Protein kinase C, zeta (PKC), also known as PRKCZ, is a protein that in humans is encoded by the PRKCZ gene.  The PRKCZ gene encodes at least two alternative transcripts, the full-length PKC and an N-terminal truncated form PKM. PKM is thought to be responsible for maintaining long-term memories in the brain. The importance of PKC in the creation and maintenance of long-term potentiation was first described by Todd Sacktor and his colleagues at the State University of New York at Brooklyn in 1993.

# Structure
PKC-zeta has an N-terminal regulatory domain, followed by a hinge region and a C-terminal catalytic domain. Second messengers stimulate PKCs by binding to the regulatory domain, translocating the enzyme from cytosol to membrane, and producing a conformational change that removes auto-inhibition of the PKC catalytic protein kinase activity. PKM-zeta, a brain-specific isoform of PKC-zeta generated from an alternative transcript, lacks the regulatory region of full-length PKC-zeta and is therefore constitutively active.
PKM is the independent catalytic domain of PKC and, lacking an autoinhibitory regulatory domain of the full-length PKC, is constitutively and persistently active, without the need of a second messenger. It was originally thought of as being a cleavage product of full-length PKC, an atypical isoform of protein kinase C (PKC). Like other PKC isoforms, PKC is a serine/threonine kinase that adds phosphate groups to target proteins. It is atypical in that unlike other PKC isoforms, PKC does not require calcium or diacylglycerol (DAG) to become active, but rather relies on a different second messenger, presumably generated through a phosphoinositide 3-kinase (PI3-kinase) pathway.  It is now known that PKM is not the result of cleavage of full-length PKC, but rather, in the mammalian brain, is translated from its own brain-specific mRNA, that is transcribed by an internal promoter within the PKC gene. The promoter for full-length PKC is largely inactive in the forebrain and so PKM is the dominant form of  in the forebrain and the only PKM that is translated from its own mRNA.

# Function

## PKC
Atypical PKC (aPKC) isoforms  play important roles in insulin-stimulated glucose transport. Human adipocytes contain PKC-zeta, rather than PKC-lambda/iota, as their major aPKC. Inhibition of the PKC enzyme inhibits insulin-stimulated glucose transport while activation of PKC increases glucose transport.

## PKM
PKM is thought to be responsible for maintaining the late phase of long-term potentiation (LTP). LTP is one of the major cellular mechanisms that are widely considered to underlie learning and memory. This theory arose from the observation that PKM perfused post synaptically into neurons causes synaptic potentiation, and selective inhibitors of PKM like zeta inhibitory peptide (ZIP), when bath applied one hour after tetanization, inhibit the late phase or maintenance of LTP. Thus PKM is both necessary and sufficient for maintaining LTP. Subsequent work showed that inhibiting PKM reversed LTP maintenance when applied up to 5 hours after LTP was induced in hippocampal slices, and after 22 hours in vivo. Inhibiting PKM in behaving animals erased spatial long-term memories in the hippocampus that were up to one month old, without affecting spatial short-term memories, and erased long-term memories for fear conditioning and inhibitory avoidance in the basolateral amygdala. When ZIP was injected into rats' sensorimotor cortices, it erased muscle memories for a task, even after several weeks of training. In the neocortex, thought to be the site of storage for most long-term memories, PKM inhibition erased associative memories for conditioned taste aversion in the insular cortex, up to 3 months after training. The protein also seems to be involved, through the nucleus accumbens, in the consolidation and reconsolidation of the memory related to drug addiction. PKM is thus the first molecule shown to be a component of the storage mechanism of long-term memory. Although results from PKC/PKM-null mice demonstrate LTP and memory appear largely the same as wild-type mice, the normal function of PKM in LTP and long-term memory storage was shown to be compensated by the other atypical PKC isoform, PKC/  in the knock-out.
Alteration in PKM may be involved in neurodegeneration Alzheimer's disease.

# Model organisms
Model organisms have been used in the study of PRKCZ function. A conditional knockout mouse line, called Prkcztm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program  a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on mutant mice and three significant abnormalities were observed. Homozygous mutant males had Bergmeister's papilla, while both sexes had atypical plasma chemistry and abnormal melanocyte morphology.

# Inhibitors
- 1,3,5-Trisubstituted Pyrazolines

# Interactions
PRKCZ has been shown to interact with:
- AKT3,
- C-Raf,
- C1QBP,
- CENTA1,
- FEZ1,
- FEZ2,
- MAP2K5,
- NFATC2,
- PARD6A,
- PARD6B,
- PAWR,
- PDPK1,
- RELA,
- Src,
- WWC1,
- YWHAB, and
- YWHAQ,
- YWHAZ.