Chimerin is a type of nerve tissue protein. Chimerins are a family of non-

protein kinase C In cell biology, Protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and t ...

phorbol ester Phorbol esters are a class of chemical compounds found in a variety of plants, particularly in the families Euphorbiaceae and Thymelaeaceae. Chemically, they are ester derivatives of the tetracyclic diterpenoid phorbol. Biological activity Prot ...

receptors. They were the first phorbal ester receptors to be discovered within this family. They are represented as a family of four closely bound GAPs1 (

GTPase-activating protein GTPase-activating proteins or GTPase-accelerating proteins (GAPs) are a family of regulatory proteins whose members can bind to activated G proteins and stimulate their GTPase activity, with the result of terminating the signaling event. GAPs are a ...

s). These small GTPases were once characterized as high affinity intracellular receptors for the second messenger

diacylglycerol A diglyceride, or diacylglycerol (DAG), is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages. Two possible forms exist, 1,2-diacylglycerols and 1,3-diacylglycerols. DAGs can act as sur ...

(DAG) and the phorbol ester tumor promoters. The name stems from their resemblance to the "chimera."

Types

Types include: * Chimerin 1 *

Chimerin 2 Chimerin 2 (beta-chimaerin) is a protein that in humans is encoded by the ''CHN2'' gene. This gene is a member of the chimerin family and encodes a protein with a phorbol-ester/diacylglycerol-type zinc finger, a Rho-GAP domain and an SH2 domain. ...

There are four known

isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...

of the chimerin protein. These include α1, α2, β1, and β2. α1-Chimerin was the first protein to be isolated from the brain. The other domains were discovered through

alternative splicing Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be ...

. The α and β isoforms are almost identical, the key difference stems from the

SH2 domain The SH2 (Src Homology 2) domain is a structurally conserved protein domain contained within the Src oncoprotein and in many other intracellular signal-transducing proteins. SH2 domains allow proteins containing those domains to dock to phosphory ...

at the N-terminal.

α1

α1-Chimerin is a GTPase-activating protein in the brain that effects the ras related p21rac. α1-Chimerin is also able to regulate dendritic spinal density by binding to NMDA receptors at the NR2A subunit. Over expression of this protein in hippocampus tissue can inhibit the formation of new spines and remove existing spines. Mutations found in α-chi-merin lead to the Duane retraction syndrome 2. Beta-chimerin (Rho GTPase-activating protein 3, 468aa) is mainly found in the brain and pancreas and the expression is in the form of reduced malignant gliomas. Changes in cytoskeletal organization are due to the action on Rac.

α2

α2-Chimerin acts in a similar manner to α1-chimerin, but is primarily found in the brain and testes. It is also an SH2 containing GTPase activating protein and bears many similarities in function. It Is derived from alternative splicing of the α-chimera gene. α2-Chimerin was shown to be involved and important in cognitive development. The expression of α2-chimerin is present in development so α2-chimerin is essential for cognitive function as it directly leads to functioning cognitive ability in adulthood. α2-Chimerin also plays a role in the ocular motor system. Mutations in α2-chimerin can cause disorders such as Duane Retraction Syndrome as it changes the signals on how the eye moves.

β2

β2-Chimerin has been shown to play a role in breast cancer. In breast cancer cells the amount of β2-chimerin messengers are extremely low. When introduced to the cancerous cells β2-chimerin then causes the G1 cell cycle to stop and therefore it stops the cells from multiplying. β2-Chimerin can be linked to a fusion gene that is associated with a key insulin receptor that causes people to have decreased levels of insulin.

References

{{Nerve tissue protein Protein families