Table 6. Physical Significance of Lysine (K) Residue in PARP1 Acetylation, Ubiquitination, and SUMOylation through an Online Analysis Tool Known as MutPred2 (http://mutpred.mutdb.org/)a.
| lysine residue | mutation | affected molecular mechanism (p ≤ 0.05) | affected motifs | pathogenic score |
|---|---|---|---|---|
| K7 | Lys(K)-Gln(Q) | 0.273 | ||
| Lys(K)-Leu(L) | loss of intrinsic disorder, loss of acetylation at K7, loss of phosphorylation at Y9, loss of methylation at K7, loss of ubiquitination at K7 | ELME000149, PS00005 | 0.517 | |
| K97 | Lys(K)-Gln(Q) | 0.196 | ||
| Lys(K)-Leu(L) | 0.383 | |||
| K148 | Lys(K)-Gln(Q) | ELME000155, PS00347 | 0.545 | |
| Lys(K)-Leu(L) | gain of loop, altered transmembrane protein | 0.742 | ||
| K249 | Lys(K)-Gln(Q) | 0.479 | ||
| Lys(K)-Leu(L) | altered coiled, loss of intrinsic disorder, gain of loop, loss of helix, altered disordered interface, loss of acetylation at K249 | ELME000002 | 0.737 | |
| K262 | Lys(K)-Gln(Q) | 0.453 | ||
| Lys(K)-Leu(L) | altered coiled | 0.771 | ||
| K331 | Lys(K)-Gln(Q) | 0.272 | ||
| Lys(K)-Leu(L) | altered transmembrane protein | 0.575 | ||
| K337 | Lys(K)-Gln(Q) | loss of acetylation at K337 | ELME000064, ELME000117, ELME000133, ELME000136, ELME000159 | 0.694 |
| Lys(K)-Leu(L) | loss of ascetylation at K337 | 0.825 | ||
| K433 | Lys(K)-Gln(Q) | 0.113 | ||
| Lys(K)-Leu(L) | 0.385 | |||
| K528 | Lys(K)-Gln(Q) | 0.370 | ||
| Lys(K)-Leu(L) | loss of intrinsic disorder, loss of acetylation at K528, loss of strand, loss of helix, loss of SUMOylation at K524, loss of ubiquitination at K528, loss of methylation at K528 | ELME000051, ELME000231, ELME000336, PS00005 | 0.687 | |
| K600 | Lys(K)-Gln(Q) | loss of SUMOylation at K600, gain of GPI-anchor amidation at N599 | PS00005 | 0.718 |
| Lys(K)-Leu(L) | loss of SUMOylation at K600 | 0.862 | ||
| K637 | Lys(K)-Gln(Q) | gain of strand, loss of acetylation at K633, altered transmembrane protein | ELME000163, ELME000233 | 0.713 |
| Lys(K)-Leu(L) | loss of acetylation at K633, altered transmembrane protein | ELME000120, ELME000233 | 0.886 | |
| K653 | Lys(K)-Gln(Q) | 0.273 | ||
| Lys(K)-Leu(L) | 0.489 | |||
| K700 | Lys(K)-Gln(Q) | 0.499 | ||
| Lys(K)-Leu(L) | altered coiled | ELME000333 | 0.768 | |
| K748 | Lys(K)-Gln(Q) | 0.562 | ||
| Lys(K)-Leu(L) | altered coiled | 0.775 | ||
| K796 | Lys(K)-Gln(Q) | loss of acetylation at K796, altered transmembrane protein, altered coiled, gain of proteolytic cleavage at D791 | ELME000020, ELME000120, ELME000173, ELME000233 | 0.546 |
| Lys(K)-Leu(L) | altered ordered interface, loss of acetylation at K796, altered transmembrane protein, altered coiled, gain of proteolytic cleavage at D791 | 0.776 |
a
In the given table, the pathogenic score represents the probability that the amino acid substitution is pathogenic. A score threshold of 0.50 would suggest pathogenic for a particular substitution. However, a threshold of 0.68 yields a false positive rate of 10%, whereas a threshold of 0.80 yields a false positive rate of 5%.