N-chimerin encodes a 34,000 M(r) protein. Its N-terminal half shared almost 50% identity with sequences in the regulatory domain of protein kinase C (OMIM 176960); the C-terminal half had 42% identity with the C-terminal region of BCR, the product of the breakpoint cluster region gene involved in the Philadelphia chromosome translocation (151410).
Also known as alpha-1-chimerin, n-chimerin is a brain GTPase-activating protein (GAP) for the RAS-related p21 (RAC).
Chimaerin is a phorbol ester receptor with racGAP activity .
NCBI Summary:
This gene encodes GTPase-activating protein for ras-related p21-rac and a phorbol ester receptor. It is predominantly expressed in neurons, and plays an important role in neuronal signal-transduction mechanisms. Mutations in this gene are associated with Duane's retraction syndrome 2 (DURS2). Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2011]
General function
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Cellular localization
Plasma membrane
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Ovarian function
Oogenesis
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Involvement of obesity-associated upregulation of chemerin/chemokine-like receptor 1 in oxidative stress and apoptosis in ovaries and granulosa cells. Yao J et al. (2019) In this study, we evaluated the expression and function of chemerin and CMKLR1 in the ovaries and granulosa cells of high-fat diet-induced obese (OB) mice. In vivo, chemerin/CMKLR1 system was upregulated in the serum, ovaries, and granulosa cells of OB mice compared with those in control mice. Apoptotic ovarian follicles, oxidative stress, and apoptosis biomarkers were also increased in the ovaries of OB mice. In vitro, mouse granulosa cells (mGCs) were cultured and treated with different concentrations of chemerin to investigate the effects of chemerin on viability, reactive oxygen species (ROS), and apoptosis and on the phosphorylation of AKT, AMP-activated protein kinase α (AMPKα), and nuclear factor-κB p65. Chemerin suppressed mGC viability with or without gonadotrophin and induced ROS accumulation and apoptosis in mGCs. Moreover, AMPKα and p65 were activated by chemerin, whereas AKT was suppressed. These changes in phosphorylation were blocked with CMKLR1 knockdown. Our findings showed that chemerin contributed to ROS accumulation and apoptotic cell death through three signaling pathways, suggesting that upregulation of chemerin and CMKLR1 may explain the imbalance of oxidative stress and apoptosis in the ovaries of OB mice.//////////////////
Expression regulated by
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Ovarian localization
Oocyte
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Robert A. Taft et al 2002 reported the identification of Genes Encoding Mouse Oocyte Secretory and Transmembrane Proteins by a Signal Sequence Trap.
. At all stages of follicular development, oocytes interact with surrounding granulosa cells and promote their differentiation into the types of cells that support further oocyte growth and developmental competence. These interactions suggest the existence of an oocyte-granulosa cell regulatory loop that includes both secreted proteins and cell surface receptors on both cell types. Factors involved in the regulatory loop will therefore contain a signal sequence, which can be used to identify them through a signal sequence trap (SST). A screen of an oocyte SST library identified three classes of oocyte-expressed sequences: known mouse genes, sequences homologous to known mammalian genes, and novel sequences of unknown function. Many of the recovered genes may have roles in the oocyte-granulosa cell regulatory loop. For several of the known mouse genes, new roles in follicular development are implied by identification of their expression, for the first time, in the oocyte. The future characterization of novel sequences may lead to the identification of novel proteins participating in the regulatory loop.
Chimerin is one of the oocyte genes identified by the SST approach. It is expressed by oocytes of preantral and antral follicles and by their companion granulosa cells.