Chimaerin Alfa 2

Chimaerins are members of a Rho GTPase-activating proteins (GAPs) that comprises of beta1, alfa1 and alfa 2-chimaerins and the alternatively spliced variants from the beta and alfa-chimaerin genes.  These proteins bind to diacylglycerol and phorbol esters like protein kinaseC.  They all have a common single C1 domain which is capable of binding phorbol esters and other DAG-mimetics with low nonomolar affinity in the presence of acidic phospholipids.  There are two types of chimaerins, alfa2 and beta2 Chimaerins both exhibit an N-terminal SH2 binding domain that interacts with phosphotyrosine containing proteins.  The C-terminal chimaerin GTPase activating proteins (GAP)domain is structurally homologus to other Rho and GAP domains such as those found in p190RhoGAP, p50RhoGAP and BCR (1).  It is shown that β2-chimaerin accelerates GTP hydrolysis from the small G-protein Rac1, leading to the conversion to the inactive GDP-bound form of Rac (2).   Rac1 plays a fundamental role in the control of actin cytoskeleton reorganization, migration, adhesion, transcription, and cell cycle progression (3).  An N-terminal SH2 domain in both alfa and beta chimaerins interacts with phosphotyrosine containing proteins while a C-terminalGAP doamain is structurally homologuas to other RhoGAP domains such as those found in other GAP proteins.  The beta 2 chimaerins have been shown to accelerate GTP hydrolysis from the small G-protein Rac1 and converts it to inactive GDP  bound form.  Since Rac1 plays an important role in actin cytoskeletal reorganization, adhesion, migration, transcription and cell cycle progression and chimaerins regulate the activity of Rac1, it is conceivable that chimaerins could play an equally important negatively regulated role in concert with Rac1 responses (4).

Chimaerin beta 2 is a 468 amino acid protein (MW 50kDa) protein and chimaerin alfa is a 433 amino acid (45kDa) in size.  Chimaerins are expressed in majority of cells and are important regulators of divergence in diacylglycerol (DAG) signaling downstream of tyrosine kinase receptor via a protein kinase C independent mechanisms (1). Beta 2-Chimaerins also undergo phosphorylation to regulate their activity.  Alfa-chimaerins are alternatively spliced to give two variants (alfa1 and alfa 2-chiamerins), the alfa-1 is a GTPase activating protein for Ras related p21rac while alfa 2-chimaerin exhibted Rac-GAP activity which is stimulated by phosophotidyl serine.  Discrete expression of alfa 1-chimaerin and alfa 2-chimerins are seen in brain, alfa 1-chimaerin is expressed in Purkinje cell while both alfa 1 and alfa 2 are expressed in neurons of the cerebral cortex, hippocampus, and thalamus.  The alfa 2 variant is expressed only in testis, in early pachytene spermatocytes (4).

The chimaerin beta 2-selective antibody was generated against synthetic peptide corresponsing to (163-178) from the human beta chimaerin isoform 2 sequence.  This epitope is unique to chimaerin beta 2 only and antibodies to this peptide does not cross react to chimaerin alfa1 or alfa 2 isoforms.  The affinity purified antibodies isolated on immobilized antigen based affinity chromatography are stabilized, these antibdoies strongly label a beta 2 chimaerin at 48-50kDa range in western blot positive control samples for chimaerin beta (PC-CHIM2).  FabGennix Inc. will also conjugate antibodies with fluorescent probes upon request at extra charge.  FabGennix, Inc., provides Western blot positive controls for beta 2-chimaerin in ready-to-use buffer for easy identification of target protein.  Limited quantities of antigenic blocking peptide is also available.  Please enquire for their availability before ordering.

For research use only, not for diagnostic or therapeutic use.