Chimerin 1

Last updated
chimerin (chimaerin) 1
Chimerinjmol.png
Crystal structure of human chimerin 1 (CHN1) [1]
Identifiers
SymbolCHN1
Alt. symbolsCHN
NCBI gene 1123
HGNC 1943
OMIM 118423
RefSeq NM_001822
UniProt P15882
Other data
Locus Chr. 2 q31-q32.1
Search for
Structures Swiss-model
Domains InterPro

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]

Contents

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]

Related Research Articles

In cell signalling, Son of Sevenless (SOS) refers to a set of genes encoding guanine nucleotide exchange factors that act on the Ras subfamily of small GTPases.

<span class="mw-page-title-main">C1 domain</span>

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

<span class="mw-page-title-main">Guanine nucleotide exchange factor</span> Proteins which remove GDP from GTPases

Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). A variety of unrelated structural domains have been shown to exhibit guanine nucleotide exchange activity. Some GEFs can activate multiple GTPases while others are specific to a single GTPase.

The Rho family of GTPases is a family of small signaling G proteins, and is a subfamily of the Ras superfamily. The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found in all eukaryotic kingdoms, including yeasts and some plants. Three members of the family have been studied in detail: Cdc42, Rac1, and RhoA. All G proteins are "molecular switches", and Rho proteins play a role in organelle development, cytoskeletal dynamics, cell movement, and other common cellular functions.

<span class="mw-page-title-main">CDC42</span> Protein-coding gene in the species Homo sapiens

Cell division control protein 42 homolog 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 cell division, and is now known to influence a variety of signaling events and cellular processes in a variety of organisms from yeast to mammals.

<span class="mw-page-title-main">FGD1</span> Protein-coding gene in the species Homo sapiens

FYVE, RhoGEF and PH domain-containing protein 1 (FGD1) also known as faciogenital dysplasia 1 protein (FGDY), zinc finger FYVE domain-containing protein 3 (ZFYVE3), or Rho/Rac guanine nucleotide exchange factor FGD1 is a protein that in humans is encoded by the FGD1 gene that lies on the X chromosome. Orthologs of the FGD1 gene are found in dog, cow, mouse, rat, and zebrafish, and also budding yeast and C. elegans. It is a member of the FYVE, RhoGEF and PH domain containing family.

<span class="mw-page-title-main">RAC1</span> Protein-coding gene in the species Homo sapiens

Rac1, also known as Ras-related C3 botulinum toxin substrate 1, is a protein found in human cells. It 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.

<span class="mw-page-title-main">Transforming protein RhoA</span> Protein and coding gene in humans

Transforming protein RhoA, also known as Ras homolog family member A (RhoA), is a small GTPase protein in the Rho family of GTPases that in humans is encoded by the RHOA gene. While the effects of RhoA activity are not all well known, it is primarily associated with cytoskeleton regulation, mostly actin stress fibers formation and actomyosin contractility. It acts upon several effectors. Among them, ROCK1 and DIAPH1 are the best described. RhoA, and the other Rho GTPases, are part of a larger family of related proteins known as the Ras superfamily, a family of proteins involved in the regulation and timing of cell division. RhoA is one of the oldest Rho GTPases, with homologues present in the genomes since 1.5 billion years. As a consequence, RhoA is somehow involved in many cellular processes which emerged throughout evolution. RhoA specifically is regarded as a prominent regulatory factor in other functions such as the regulation of cytoskeletal dynamics, transcription, cell cycle progression and cell transformation.

<span class="mw-page-title-main">PRKCB1</span> Protein-coding gene in the species Homo sapiens

Protein kinase C beta type is an enzyme that in humans is encoded by the PRKCB gene.

<span class="mw-page-title-main">RACGAP1</span> Protein-coding gene in the species Homo sapiens

Rac GTPase-activating protein 1 is an enzyme that in humans is encoded by the RACGAP1 gene.

<span class="mw-page-title-main">LIMK1</span> Protein-coding gene in the species Homo sapiens

LIM domain kinase 1 is an enzyme that in humans is encoded by the LIMK1 gene.

<span class="mw-page-title-main">ARHGAP1</span> Protein-coding gene in humans

Rho GTPase-activating protein 1 is an enzyme that in humans is encoded by the ARHGAP1 gene.

<span class="mw-page-title-main">RAC2</span> Protein-coding gene in the species Homo sapiens

Rac2 is a small signaling G protein, and is a member of the Rac subfamily of the family Rho family of GTPases. It is encoded by the gene RAC2.

<span class="mw-page-title-main">ARHGEF7</span> Protein-coding gene in the species Homo sapiens

Rho guanine nucleotide exchange factor 7 is a protein that in humans is encoded by the ARHGEF7 gene.

<span class="mw-page-title-main">ARHGEF6</span> Protein-coding gene in the species Homo sapiens

Rho guanine nucleotide exchange factor 6 is a protein that, in humans, is encoded by the ARHGEF6 gene.

<span class="mw-page-title-main">Chimerin 2</span> Protein-coding gene in the species Homo sapiens

Chimerin 2 (beta-chimaerin) is a protein that in humans is encoded by the CHN2 gene.

<span class="mw-page-title-main">RASGRP2</span> Protein-coding gene in the species Homo sapiens

RAS guanyl-releasing protein 2 is a protein that in humans is encoded by the RASGRP2 gene.

Chimerin is a type of nerve tissue protein.

Unc-51-like kinase 2 also known as ULK2 is an enzyme which in humans is encoded by the ULK2 gene. The gene is located within the Smith–Magenis syndrome region on chromosome 17.

<span class="mw-page-title-main">ARHGAP31</span> Protein-coding gene in the species Homo sapiens

The Rho GTPase activating protein 31 is encoded in humans by the ARHGAP31 gene. It is a Cdc42/Rac1 GTPase regulator.

References

  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. S2CID   39605825.
  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. Bibcode:2006PNAS..103.1924B. 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. doi:10.1128/mcb.16.9.5069. 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. Bibcode:2008Sci...321..839M. doi:10.1126/science.1156121. PMC   2593867 . PMID   18653847.

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


This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.