Chimerin 1

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chimerin (chimaerin) 1
Chimerinjmol.png
Crystal structure of human chimerin 1 (CHN1)[1]
Identifiers
Symbol CHN1
Alt. symbols CHN
Entrez 1123
HUGO 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[edit]

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[edit]

Heterozygous missense mutations in this gene cause Duane's retraction syndrome 2 (DURS2).[7]

References[edit]

  1. ^ "RCSB Protein Data Bank - Structure Summary for 3CXL - Crystal structure of human chimerin 1 (CHN1)". 
  2. ^ Hall C, Monfries C, Smith P, Lim HH, Kozma R, Ahmed S, Vanniasingham V, Leung T, Lim L (January 1990). "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. doi:10.1016/0022-2836(90)90006-8. PMID 2299665. 
  3. ^ Qi RZ, Ching YP, Kung HF, Wang JH (March 2004). "Alpha-chimaerin exists in a functional complex with the Cdk5 kinase in brain". FEBS Lett. 561 (1–3): 177–80. doi:10.1016/S0014-5793(04)00174-7. PMID 15013773. 
  4. ^ Buttery P, Beg AA, Chih B, Broder A, Mason CA, Scheiffele P (February 2006). "The diacylglycerol-binding protein α1-chimaerin regulates dendritic morphology". Proc. Natl. Acad. Sci. U.S.A. 103 (6): 1924–9. doi:10.1073/pnas.0510655103. PMC 1413663. PMID 16446429. 
  5. ^ Kozma R, Ahmed S, Best A, Lim L (September 1996). "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. PMC 231508. PMID 8756665. 
  6. ^ 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. 
  7. ^ 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 (August 2008). "Human CHN1 mutations hyperactivate α2-chimaerin and cause Duane's retraction syndrome". Science 321 (5890): 839–43. doi:10.1126/science.1156121. PMC 2593867. PMID 18653847. 

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.