Chimerin 1 (CHN1), also known as alpha-1-chimerin, n-chimerin, is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

which in humans is encoded by the ''CHN1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Chimerin Chimerin is a type of nerve tissue protein. Chimerins are a family of non-protein kinase C phorbol ester receptors. They were the first phorbol ester receptors to be discovered within this family. They are represented as a family of four closely ...

1 is a

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 ...

specific for

RAC RAC or Rac may refer to: Organizations * Radio Amateurs of Canada * RATCH-Australia Corporation, electricity generator * Refugee Action Collective (Victoria), Melbourne, Australia * Religious Action Center of Reform Judaism, US * Rent-A-Cent ...

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 p21Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) that is capable of inhibiting all cyclin/ CDK complexes, though is primarily associ ...

rac RAC or Rac may refer to: Organizations * Radio Amateurs of Canada * RATCH-Australia Corporation, electricity generator * Refugee Action Collective (Victoria), Melbourne, Australia * Religious Action Center of Reform Judaism, US * Rent-A-Cent ...

and a

phorbol Phorbol is a natural, plant-derived organic compound. It is a member of the tigliane family of terpene, diterpenes. Phorbol was first isolated in 1934 via the hydrolysis of croton oil, which is derived from the seeds of the purging croton, ''Crot ...

ester receptor. It plays an important role in ocular motor axon pathfinding.

Function

CHN1 is a three-domain

with the

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

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 bind to phosphorylated tyrosine residues on other proteins, ...

, the

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...

RhoGAP domain RhoGAP domain is an evolutionary conserved protein domain of GTPase activating proteins towards Rho/Rac/Cdc42-like small GTPases. Human proteins containing this domain ABR; ARHGAP1; ARHGAP10; ARHGAP11A; ARHGAP11B; ARHGAP12; ARHG ...

and the central

C1 domain C1 domain (also known as phorbol esters/diacylglycerol binding domain) binds an important secondary messenger diacylglycerol (DAG), as well as the analogous phorbol esters. Phorbol esters can directly stimulate protein kinase C, PKC. Phorbol es ...

similar to

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 ...

. When lipid

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. Diglycerides are n ...

(DAG) binds to the C1 domain, CHN1 is transferred to the plasma membrane and negatively regulates Rho-family small GTPases

RAC1 Ras-related C3 botulinum toxin substrate 1, is a protein that in humans is encoded by the ''RAC1'' gene. This gene can produce a variety of alternatively spliced versions of the Rac1 protein, which appear to carry out different functions. Func ...

and

CDC42 Cell division control protein 42 homolog (Cdc42 or CDC42) is a protein that in humans is encoded by the ''CDC42'' gene. Cdc42 is involved in regulation of the cell cycle. It was originally identified in ''S. cerevisiae'' (yeast) as a mediator of ...

, thus causing the morphological change of axons by pruning the ends of axon dendrites. Mutational analysis suggests that un-overlapping residues of the

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 ( DURS2).

References

External links

GeneReviews/NCBI/NIH/UW entry on Duane syndrome
* GTP-binding protein regulators Proteins {{gene-2-stub