Biology:Chimerin 1
| chimerin (chimaerin) 1 | |
|---|---|
 Crystal structure of human chimerin 1 (CHN1)[1] | |
| Identifiers | |
| Symbol | CHN1 |
| Alt. symbols | CHN |
| NCBI gene | 1123 |
| HGNC | 1943 |
| OMIM | 118423 |
| RefSeq | NM_001822 |
| UniProt | P15882 |
| Other data | |
| Locus | Chr. 2 q31-q32.1 |
Chimerin 1 (CHN1), also known as alpha-1-chimerin, n-chimerin, is a protein which in humans is encoded by the CHN1 gene.[2][3]
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.
Function
CHN1 is a three-domain protein 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.[4][5]
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.[6]
Clinical significance
Heterozygous missense mutations in this gene cause Duane's retraction syndrome 2 (DURS2).[7]
References
- ↑ "RCSB Protein Data Bank - Structure Summary for 3CXL - Crystal structure of human chimerin 1 (CHN1)". http://www.rcsb.org/pdb/explore/explore.do?structureId=3CXL.
- ↑ "Novel human brain cDNA encoding a 34,000 Mr protein n-chimaerin, related to both the regulatory domain of protein kinase C and BCR, the product of the breakpoint cluster region gene". J. Mol. Biol. 211 (1): 11–6. January 1990. doi:10.1016/0022-2836(90)90006-8. PMID 2299665.
- ↑ "Alpha-chimaerin exists in a functional complex with the Cdk5 kinase in brain". FEBS Lett. 561 (1–3): 177–80. March 2004. doi:10.1016/S0014-5793(04)00174-7. PMID 15013773.
- ↑ "The diacylglycerol-binding protein α1-chimaerin regulates dendritic morphology". Proc. Natl. Acad. Sci. U.S.A. 103 (6): 1924–9. February 2006. doi:10.1073/pnas.0510655103. PMID 16446429. Bibcode: 2006PNAS..103.1924B.
- ↑ "The GTPase-activating protein n-chimaerin cooperates with Rac1 and Cdc42Hs to induce the formation of lamellipodia and filopodia". Mol. Cell. Biol. 16 (9): 5069–80. September 1996. doi:10.1128/mcb.16.9.5069. PMID 8756665.
- ↑ Kazanietz MG (December 2005). "Targeting protein kinase C and "non-kinase" phorbol ester receptors: emerging concepts and therapeutic implications". Biochim. Biophys. Acta 1754 (1–2): 296–304. doi:10.1016/j.bbapap.2005.07.034. PMID 16202672.
- ↑ "Human CHN1 mutations hyperactivate α2-chimaerin and cause Duane's retraction syndrome". Science 321 (5890): 839–43. August 2008. doi:10.1126/science.1156121. PMID 18653847. Bibcode: 2008Sci...321..839M.
External links
- GeneReviews/NCBI/NIH/UW entry on Duane syndrome
- Chimerin+1 at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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