TABLE 2.
List of recurrent pathogenic nonsense mutation and their degrons in comparison to the wild-type profilaggrin.
| E3 ligase-binding motifs | Mutation | ||
|---|---|---|---|
| N-terminus | Internal | C-terminus | |
| Ac/N degron; motif recognized by Teb4 and Not4 E3 ligases | SPOP, APC/C (ABBA, KEN, DBOX), SCF-TRCP1 recognition motifs | — | Full-length WT |
| Motif -G end, likely CRL substrate | p.Lys4022Ter | ||
| — | p.Arg3879Ter | ||
| Motif -R end, likely CRL substrate | p.Gln3859Ter | ||
| Motif -EE end, likely CRL substrate | p.Gln3818Ter | ||
| — | p.Ser3749Ter | ||
| Motif -A end, likely CRL substrate | p.Arg3743Ter | ||
| Motif -G end, likely CRL substrate | p.Gln3684Ter | ||
| — | p.Arg3657Ter | ||
| Motif R at -3, likely CRL substrate | p.Gln3520Ter | ||
| — | p.Arg3442Ter | ||
| Motif -A end, likely CRL substrate | p.Arg3419Ter | ||
| Motif -G end, likely CRL substrate | p.Arg3409Ter | ||
| p.Ser3316Ter | |||
| Motif A at -2, likely CRL substrate | p.Ser3296Ter | ||
| — | p.Ser3247Ter | ||
| — | p.Gln3029Ter | ||
| — | p.Arg3009Ter | ||
| Motif -A end, likely CRL substrate | p.Arg2971Ter | ||
| — | p.Trp2907Ter | ||
| — | p.Ser2706Ter | ||
| — | p.Arg2685Ter | ||
| — | p.Arg2613Ter | ||
| — | p.Ser2554Ter | ||
| — | p.Ser2544Ter | ||
| — | p.Ser2453Ter | ||
| Motif -A end, likely CRL substrate | p.Arg2447Ter | ||
| — | p.Glu2422Ter | ||
| — | p.Gln2417Ter | ||
| — | p.Gln2397Ter | ||
| — | p.Arg2361Ter | ||
| — | p.Ser2344Ter | ||
| Motif -A end, likely CRL substrate | p.Ser2317Ter | ||
| — | p.Gly2228Ter | ||
| — | p.Tyr2092Ter | ||
| Motif R at -3, likely CRL substrate | p.Ser2080Ter | ||
| — | p.Gln2070Ter | ||
| — | p.Arg2037Ter | ||
| — | p.Ser1977Ter | ||
| — | p.Trp1947Ter | ||
| — | p.Ser1906Ter | ||
| — | p.Gly1826Ter | ||
| — | p.Arg1798Ter | ||
| — | p.Glu1795Ter | ||
| — | p.Gln1790Ter | ||
| — | p.Ser1733Ter | ||
| Motif -EE end, likely CRL substrate | p.Ser1729Ter | ||
| — | p.Gly1724Ter | ||
| — | p.Arg1712Ter | ||
| — | p.Gln1701Ter | ||
| — | p.Ser1695Ter | ||
| — | p.Ser1515Ter | ||
| Motif -A end, likely CRL substrate | p.Arg1474Ter | ||
| SPOP, APC/C (ABBA, KEN), SCF-TRCP1 recognition motifs | Motif R at -3, likely CRL substrate | p.Ser1302Ter | |
| — | p.Gln1256Ter | ||
| — | p.Gly1253Ter | ||
| Motif -G end, likely CRL substrate | p.Arg1140Ter | ||
| — | p.Gly1139Ter | ||
| — | p.Ser1040Ter | ||
| Motif -A end, likely CRL substrate | p.Ser1020Ter | ||
| — | p.Gln977Ter | ||
| Motif -A end, likely CRL substrate | p.Arg826Ter | ||
| — | p.Arg788Ter | ||
| SPOP, APC/C (ABBA, KEN) recognition motifs | — | p.Arg740Ter | |
| — | p.Ser609Ter | ||
| Motif -A end, likely CRL substrate | p.Arg501Ter | ||
| APC/C (ABBA, KEN) recognition motifs | — | p.Gln355Ter | |
| — | p.Trp326Ter | ||
| — | p.Ser260Ter | ||
| — | p.Lys182Ter | ||
| Sequence too short for analysis | p.Glu32Ter | ||