1. Abigail Mabe Cell Biology 11-02-03

3. * All are indicated as diapause-down regulated (all negative values)

4. Non-Diapause Genes

5. CG7012 : Nicastrin (nct) Nicastrin is one of the two major components of the gamma- secretase complex, the other being presenilin, which executes the breakdown of type I integral membrane proteins such as the amyloid precursor protein (APP) and Notch. Nicastrin is produces in fibroblasts and neurons as an endoglycosidase-H-sensitive glycosylated precursor protein (immature nicastrin) and is then changed by glycosylation in the Golgi apparatus and by sialylation in the trans-Golgi network (mature nicastrin)

6. Subcellular Location plasma membrane Classification Zn-dependent exopeptidase Structure There are 17 alleles that code for nct The nicastrin locus is composed of seven exons (3.4 kb) conserved signal peptide and a C-terminal transmembrane domain.

7. The nct gene product is required for Psn-mediated transmembrane cleavage Loss of nct activity blocks the build-up of Psn gene product associated with the apical plasma membrane, stops Psn-dependent cleavage of the transmembrane domain of N and stops N signal transduction Transmembrane cleavage of Notch is essential for signal transduction, and transmembrane cleavage of beta-APP creates harmful amyloid peptides connected with Alzheimer's disease

8. Developmental Biology The transmembrane glycoprotein Nicastrin was identified in a complex with the multipass membrane protein Presenilin. Drosophila nicastrin mutations have been isolated by systematic lethal mutagenesis screening. nicastrin mutants exhibit defective cell fate characterizations at all stages of development, similar to what has been observed in Notch and Presenilin mutants. Loss-of-function mutations have been isolated which affect the larval stage and are larval recessive lethal

9. Mapped Location of Nicastrin

10. Amino Acid Sequence MEMRLNAASIWLLILSYGATIAQGERTRDKMYEPIGGASCFRRLNGTHQTGCSSY SGSVGVLHLINVEADLEFLLSSPPSPPYAPMIPPHLFTRNNLMRLKEAGPKNISV LLINRTNQMKQFSHELNCPNQYSGLNSTSETCDASNPAKNWNPWGTGLLHE DFFPIYYIADLDQVTKLEKCFQDFNNHNYETHALRSLCAVEVKSFMSAAVNTEV CMRRTNFINNLGGSKYCDPLEGRNVYATLYPRKPAIENNLETVHTNEKFILVTC RLDTTTMFDGVGLGAMDSLMGFAVFTHVAYLLKQLLPPQSKDLHNVLFVTFNG ESYDYIGSQRFVYDMEKLQFPTESTGTPPIAFDNIDFMLDIGTLDDISNIKLHAL NGTTLAQQILERLNNYAKSPRYGFNLNIQSEMSAHLPPTSAQSFLRRDPNFNA LILNARPTNKYYHSIYDDADNVDFTYANTSKDFTQLTEVNDFKSLNPDSLQMK VRNVSSIVAMALYQTITGKEYTGTKVANPLMADEFLYCFLQSADCPLFKAASYP GSQLTNLPPMRYISVLGGSQESSGYTYRLLGYLLSQLQPDIHRDNCTDLPLHYF AGFNNIGECRLTTQNYSHALSPAFLIDGYDWSSGMYSTWTESTWSQFSARIFL RPSNVHQVTTLSVGIVVLIISFCLVYIISSRSEVLFEDLPASNAALFG

11. Sequence Comparison..\Clustal Alignment.doc