Abigail Mabe

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Bioinformatics

• Abigail Mabe
• Cell Biology
• 11-02-03

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(No Transcript)
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All are indicated as diapause-down regulated
(all negative values)
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Non-Diapause Genes
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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)
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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.
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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
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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
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Mapped Location of Nicastrin
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• Amino Acid Sequence
• MEMRLNAASIWLLILSYGATIAQGERTRDKMYEPIGGASCFRRLNGTHQT
  GCSSYSGSVGVLHLINVEADLEFLLSSPPSPPYAPMIPPHLFTRNNLMRL
  KEAGPKNISVLLINRTNQMKQFSHELNCPNQYSGLNSTSETCDASNPAKN
  WNPWGTGLLHEDFFPIYYIADLDQVTKLEKCFQDFNNHNYETHALRSLCA
  VEVKSFMSAAVNTEVCMRRTNFINNLGGSKYCDPLEGRNVYATLYPRKPA
  IENNLETVHTNEKFILVTCRLDTTTMFDGVGLGAMDSLMGFAVFTHVAYL
  LKQLLPPQSKDLHNVLFVTFNGESYDYIGSQRFVYDMEKLQFPTESTGTP
  PIAFDNIDFMLDIGTLDDISNIKLHALNGTTLAQQILERLNNYAKSPRYG
  FNLNIQSEMSAHLPPTSAQSFLRRDPNFNALILNARPTNKYYHSIYDDAD
  NVDFTYANTSKDFTQLTEVNDFKSLNPDSLQMKVRNVSSIVAMALYQTIT
  GKEYTGTKVANPLMADEFLYCFLQSADCPLFKAASYPGSQLTNLPPMRYI
  SVLGGSQESSGYTYRLLGYLLSQLQPDIHRDNCTDLPLHYFAGFNNIGEC
  RLTTQNYSHALSPAFLIDGYDWSSGMYSTWTESTWSQFSARIFLRPSNVH
  QVTTLSVGIVVLIISFCLVYIISSRSEVLFEDLPASNAALFG

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Sequence Comparison ..\Clustal Alignment.doc