TABLE I.
Potential MUC1 γ-Secretase Cleavage Sites
| γ-secretase cleavage sitea |
||
|---|---|---|
| Substrate | P10-P1 | P1′-PX′b |
| SDC3 | VVGALFAAFL | VTLLIYRMKKK |
| NGFR | VYCSILAAVV | VGLVAYIAFKR |
| CD44 | ALALILAVCI | AVNSRRR |
| CDH1 | ILILLLLLFL | RRR |
| APP | VIATVIVITL | VMLKKK |
| APLP2 | AIATVIVISL | VMLRKR |
| APLP1 | GGGSLIVLSL | LLLRKKK |
| NOTCH1 | FVLLFFVGCG | VLLSRKRRR |
| MUC1c | ||
| I | IALLVLVCVL | VALAIVYLIA |
| II | LVCVLVALAI | VYLIALAVCQ |
| III | LAIVYLIALA | VCQCRRKNYG |
Sequences of substrates other than MUC1 are from references [Gu et al., 2001; Kopan and Ilagan, 2004]. Cleavage sites between P1 and P1′ are MEROPS style [Rawlings et al., 2008].
P1′–PX′ indicates cleavage site with C-terminal sequence arbitrarily included up to the nearest cluster of positively charged amino acids. In the case of the MUC1 sequences (I–III) 10 amino acids have been included.
These products are expected based on the preference for γ-secretase cleavage (39,52) and would generate CTD fragments (top to bottom) of 85 amino acids (9,222 MW), 80 amino acids (8,755 MW), and 73 amino acids(8,010 MW). The MW represent unmodified, average mass calculated in ExPASY program based on the 72 amino acid MUC1 cytoplasmic tail plus the portion of the sequence up to the predicted cleavage site.