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endosulfine alpha OKDB#: 3834
 Symbols: ENSA Species: human
 Synonyms: ARPP-19e  Locus: 1q21.3 in Homo sapiens


For retrieval of Nucleotide and Amino Acid sequences please go to: OMIM Entrez Gene
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General Comment OMIM: Initiation and maintenance of mitosis require the inhibition of PP2A, which dephosphorylates mitotic substrates. The protein kinase Greatwall is required to maintain mitosis through PP2A inhibition. Gharbi-Ayachi et al. (2010) described how Gwl activation results in PP2A inhibition. They identified Arpp19 and Ensa as 2 substrates of Gwl that, when phosphorylated by this kinase, associate with and inhibit PP2A, thus promoting mitotic entry. Conversely, in the absence of Gwl activity, Arpp19 and Ensa are dephosphorylated and lose their capacity to bind and inhibit PP2A. Gharbi-Ayachi et al. (2010) stated that although both proteins can inhibit PP2A, endogenous Arpp19, but not Ensa, is responsible for PP2A inhibition and mitotic entry in Xenopus egg extracts.

NCBI Summary: The protein encoded by this gene belongs to a highly conserved cAMP-regulated phosphoprotein (ARPP) family. This protein was identified as an endogenous ligand for the sulfonylurea receptor, ABCC8/SUR1. ABCC8 is the regulatory subunit of the ATP-sensitive potassium (KATP) channel, which is located on the plasma membrane of pancreatic beta cells and plays a key role in the control of insulin release from pancreatic beta cells. This protein is thought to be an endogenous regulator of KATP channels. In vitro studies have demonstrated that this protein modulates insulin secretion through the interaction with KATP channel, and this gene has been proposed as a candidate gene for type 2 diabetes. At least eight alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]
General function Ligand
Comment
Cellular localization
Comment
Ovarian function Oocyte maturation
Comment
Expression regulated by
Comment
Ovarian localization Oocyte
Comment
Follicle stages
Comment
Phenotypes
Mutations 1 mutations

Species: D. melanogaster
Mutation name: None
type: null mutation
fertility: infertile - ovarian defect
Comment: {alpha}-Endosulfine is a conserved protein required for oocyte meiotic maturation in Drosophila. Von Stetina JR et al. Meiosis is coupled to gamete development and must be well regulated to prevent aneuploidy. During meiotic maturation, Drosophila oocytes progress from prophase I to metaphase I. The molecular factors controlling meiotic maturation timing, however, are poorly understood. We show that Drosophila alpha-endosulfine (endos) plays a key role in this process. endos mutant oocytes have a prolonged prophase I and fail to progress to metaphase I. This phenotype is similar to that of mutants of cdc2 (synonymous with cdk1) and of twine, the meiotic homolog of cdc25, which is required for Cdk1 activation. We found that Twine and Polo kinase levels are reduced in endos mutants, and identified Early girl (Elgi), a predicted E3 ubiquitin ligase, as a strong Endos-binding protein. In elgi mutant oocytes, the transition into metaphase I occurs prematurely, but Polo and Twine levels are unaffected. These results suggest that Endos controls meiotic maturation by regulating Twine and Polo levels, and, independently, by antagonizing Elgi. Finally, germline-specific expression of the human alpha-endosulfine ENSA rescues the endos mutant meiotic defects and infertility, and alpha-endosulfine is expressed in mouse oocytes, suggesting potential conservation of its meiotic function.

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Phenotypes and GWAS show phenotypes and GWAS
Links
OMIM (Online Mendelian Inheritance in Man: an excellent source of general gene description and genetic information.)
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created: Oct. 22, 2008, 2:59 p.m. by: hsueh   email:
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last update: May 3, 2016, 2:12 p.m. by: hsueh    email:



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