Chimerin 1
Encyclopedia
Chimerin 1, also known as alpha-1-chimerin, n-chimerin is a protein
which in humans is encoded by the CHN1 gene
.
Chimerin 1 is a GTPase activating protein
specific for RAC GTP-binding proteins. It is expressed primarily in the brain and may be involved in signal transduction.
This gene encodes GTPase-activating protein for p21
-rac
and a phorbol
ester receptor. It plays an important role in ocular motor axon pathfinding.
with the N-terminal SH2 domain
, the C-terminal RhoGAP domain
and the central C1 domain
similar to protein kinase C
. When lipid diacylglycerol (DAG) binds to the C1 domain, CHN1 is transferred to the plasma membrane and negatively regulates Rho-family small GTPases RAC1
and CDC42
, thus causing the morphological change of axons by pruning the ends of axon dendrites.
Mutational analysis suggests that un-overlapping residues of the RhoGAP domain
are involved in RAC1-binding and the RAC1-GAP activity. Regulation of the RhoGAP activity of CHN1 by phorbol esters, natural compounds mimic of the lipid second messenger DAG, presents a possible way of designing agents for therapeutics.
).
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
which in humans is encoded by the CHN1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Chimerin 1 is a GTPase activating protein
GTPase activating protein
GTPase-Activating Proteins, or GAPs, or GTPase-Accelerating Proteins 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...
specific for RAC GTP-binding proteins. It is expressed primarily in the brain and may be involved in signal transduction.
This gene encodes GTPase-activating protein for p21
P21
p21 / WAF1 also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1 is a protein that in humans is encoded by the CDKN1A gene located on chromosome 6 .- Function :...
-rac
Rac (GTPase)
Rac is a subfamily of the Rho family of GTPases, small signaling G proteins .The subgroup include:*Rac1*Rac2*Rac3*RhoG...
and a phorbol
Phorbol
Phorbol is a natural, plant-derived organic compound. It is a member of the tigliane family of diterpenes. It was first isolated in 1934 as the hydrolysis product of croton oil, which is derived from the seeds of Croton tiglium. Phorbol's structure was determined in 1967...
ester receptor. It plays an important role in ocular motor axon pathfinding.
Function
CHN1 is a three-domain proteinProtein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
with the N-terminal SH2 domain
SH2 domain
The SH2 domain is a structurally conserved protein domain contained within the Src oncoprotein and in many other intracellular signal-transducing proteins...
, the C-terminal RhoGAP domain
RhoGAP domain
RhoGAP domain is an evolutionary conserved protein domain ofGTPase activating proteins towards Rho/Rac/Cdc42-like small GTPases.-Human proteins containing this domain :ABR; ARHGAP1; ARHGAP10; ARHGAP11A; ARHGAP11B; ARHGAP12; ARHGAP15; ARHGAP17;...
and the central C1 domain
C1 domain
C1 domain binds an important secondary messenger diacylglycerol , as well as the analogous phorbol esters. Phorbol esters can directly stimulate protein kinase C, PKC...
similar to protein kinase C
Protein kinase C
Protein kinase C also known as PKC is a family of enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins. PKC enzymes in turn are activated by signals such as increases in...
. When lipid diacylglycerol (DAG) binds to the C1 domain, CHN1 is transferred to the plasma membrane and negatively regulates Rho-family small GTPases RAC1
RAC1
Ras-related C3 botulinum toxin substrate 1 also known as Rac1 is a protein that in humans is encoded by the RAC1 gene. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.- Function :Rac1 is...
and CDC42
CDC42
Cell division control protein 42 homolog also known as CDC42 is a protein involved in regulation of the cell cycle. In humans, CDC42 is encoded by the CDC42 gene.- Function :...
, thus causing the morphological change of axons by pruning the ends of axon dendrites.
Mutational analysis suggests that un-overlapping residues of the RhoGAP domain
RhoGAP domain
RhoGAP domain is an evolutionary conserved protein domain ofGTPase activating proteins towards Rho/Rac/Cdc42-like small GTPases.-Human proteins containing this domain :ABR; ARHGAP1; ARHGAP10; ARHGAP11A; ARHGAP11B; ARHGAP12; ARHGAP15; ARHGAP17;...
are involved in RAC1-binding and the RAC1-GAP activity. Regulation of the RhoGAP activity of CHN1 by phorbol esters, natural compounds mimic of the lipid second messenger DAG, presents a possible way of designing agents for therapeutics.
Clinical significance
Heterozygous missense mutations in this gene cause Duane's retraction syndrome 2 (DURS2Duane syndrome
Duane syndrome is a rare, congenital eye movement disorder most commonly characterized by the inability of the eye to abduct or move outwards...
).