GTPase-activating protein for p21-rac. Insufficient expression of beta-2 chimaerin is expected to lead to higher Rac activity and could therefore play a role in the progression from low-grade to high-grade tumors.
Interacting selectively and non-covalently and simultaneously with one or more signal transduction molecules, usually acting as a scaffold to bring these molecules into close proximity either using their own SH2/SH3 domains (e.g. Grb2) or those of their target molecules (e.g. SAM68).
J. Biol. Chem. 269, 12888-12892 (1994)[PubMed:8175705]
beta-Chimaerin, a 30-kDa GTPase-activating protein (GAP) for the p21 Ras-related Rac, is expressed specifically in late stage spermatocytes (Leung, T., How, B.-E., Manser, E., and Lim, L. (1993) J. Biol. Chem. 268, 3813-3816). Using antibodies raised against beta-chimaerin, we detected a major 46-kDa RacGAP in the rat cerebellum. With beta-chimaerin cDNA as a probe and using polymerase chain reaction, cDNAs from both human and rat cerebellum were isolated. The human and rat cDNAs encoded sequences containing cysteine-rich and GAP domains identical to those of testis beta-chimaerin. The cDNAs also encoded an additional N-terminal SH2 (Src homology 2) domain, probably derived from the beta-chimaerin gene by alternate splicing. This SH2 domain of the predicted 54-kDa protein was strikingly similar to that of alpha 2-chimaerin, including replacement by glutamic acid of the invariant tryptophan present at the start of other SH2 domains. The SH2 domains of alpha- and beta-chimaerin thus represent a subset of SH2 domains. The cerebellar beta-chimaerin (beta 2-) is expressed mainly in granule cells and exhibits postnatal developmental increases. beta 2-Chimaerin was enriched in particulate/synaptosomal fractions. In the mouse weaver mutant lacking mature granule cells, there is a corresponding decrease in beta 2-chimaerin, which could well serve as a marker of granule cell differentiation.
Molecular processes resulting in the malignant transformation from low- to high-grade astrocytoma remain poorly understood. Using reverse transcriptase PCR, we identified a gene that is differentially expressed in normal brain and low-grade astrocytoma compared to glioblastoma tissues. This gene is identical to human beta 2-chimaerin, which encodes a 468-amino acid GTPase-activating protein for p21rac. The gene was localized to human chromosome 7p15.3 by fluorescence in situ hybridization mapping. Human beta 2-chimaerin is expressed in a variety of human tissues, with the highest expression level detected in human brain and pancreas. RNase protection assays indicated that the expression level of this gene is high in all the normal brain and low-grade astrocytoma samples tested compared to malignant gliomas. The down-regulation of beta 2-chimaerin expression in the high-grade gliomas suggests that decreased expression of this gene may be a feature of progression in the development of malignant glioma.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
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