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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

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

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

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 phorbal ester receptors to be discovered within this family. They are represented as a family of four closely b ...

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 protein G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that 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-Center, ...

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 associated ...

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-Center, ...

and a

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

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 ami ...

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 ...

, the

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal 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 the protein is ...

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; AR ...

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 este ...

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. DAGs can act as sur ...

(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

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