Chimerin 1 Explained
| chimerin (chimaerin) 1 |
| Caption: | Crystal structure of human chimerin 1 (CHN1)[1] |
| Hgncid: | 1943 |
| Symbol: | CHN1 |
| Altsymbols: | CHN |
| Entrezgene: | 1123 |
| Omim: | 118423 |
| Refseq: | NM_001822 |
| Uniprot: | P15882 |
| Chromosome: | 2 |
| Arm: | q |
| Band: | 31 |
| Locussupplementarydata: | -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]
External links
Notes and References
- Web site: RCSB Protein Data Bank - Structure Summary for 3CXL - Crystal structure of human chimerin 1 (CHN1) .
- Hall C, Monfries C, Smith P, Lim HH, Kozma R, Ahmed S, Vanniasingham V, Leung T, Lim L . 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 . 2299665 . 10.1016/0022-2836(90)90006-8.
- Qi RZ, Ching YP, Kung HF, Wang JH . Alpha-chimaerin exists in a functional complex with the Cdk5 kinase in brain . FEBS Lett. . 561 . 1–3 . 177–80 . March 2004 . 15013773 . 10.1016/S0014-5793(04)00174-7 . 39605825 . free .
- Buttery P, Beg AA, Chih B, Broder A, Mason CA, Scheiffele P . The diacylglycerol-binding protein α1-chimaerin regulates dendritic morphology . Proc. Natl. Acad. Sci. U.S.A. . 103 . 6 . 1924–9 . February 2006 . 16446429 . 1413663 . 10.1073/pnas.0510655103 . 2006PNAS..103.1924B . free .
- Kozma R, Ahmed S, Best A, Lim L . 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 . 8756665 . 231508 . 10.1128/mcb.16.9.5069.
- Kazanietz MG . Targeting protein kinase C and "non-kinase" phorbol ester receptors: emerging concepts and therapeutic implications . Biochim. Biophys. Acta . 1754 . 1–2 . 296–304 . December 2005 . 16202672 . 10.1016/j.bbapap.2005.07.034 .
- Miyake N, Chilton J, Psatha M, Cheng L, Andrews C, Chan WM, Law K, Crosier M, Lindsay S, Cheung M, Allen J, Gutowski NJ, Ellard S, Young E, Iannaccone A, Appukuttan B, Stout JT, Christiansen S, Ciccarelli ML, Baldi A, Campioni M, Zenteno JC, Davenport D, Mariani LE, Sahin M, Guthrie S, Engle EC . Human CHN1 mutations hyperactivate α2-chimaerin and cause Duane's retraction syndrome . Science . 321 . 5890 . 839–43 . August 2008 . 18653847 . 2593867 . 10.1126/science.1156121 . 2008Sci...321..839M .
