Table 1.
LIR Motif in known LC3 Targets Compared to NCOA4 and Potential LIR Domains.
| Protein | Residue Location (Residue Number) |
Flanking Residues | Motif | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y-type | ||||||||||||||||
| FUND1 | 18–21 | S | D | D | D | S | Y-E-V-L | D | L | T | E | Y | Y | E | V | L |
| CRY1 | 273–276 | K | L | T | D | L | Y-K-K-V | K | K | N | S | S | Y | K | K | V |
| MAVS | 9–12 | A | E | D | K | T | Y-K-Y-I | C | R | N | F | S | Y | K | Y | I |
| MAPK15 | 340–343 | Y | R | S | R | V | Y-Q-M-I | L | E | C | G | G | Y | Q | M | I |
| NCOA4 | 71–74 | R | E | V | W | L | Y-E-Q-V | D | L | I | T | Q | Y | E | Q | V |
| NCOA4 | 428–431 | E | K | E | A | L | Y-K-W-L | L | K | K | E | G | Y | K | W | L |
| F-type | ||||||||||||||||
| ULK1 | 367–370 | C | D | T | D | D | F-V-M-V | P | A | Q | F | P | F | V | M | V |
| WDFY3 | 3346–3349 | D | E | K | D | G | F-I-F-V | N | Y | S | E | G | F | I | F | V |
| ATG2A | 1362–1365 | L | D | S | D | E | F-C-I-L | D | A | P | G | L | F | C | I | L |
| ATG13 | 444–447 | N | T | H | D | D | F-V-M-I | D | F | K | P | A | F | V | M | I |
| BECL1 | 97–100 | E | S | A | N | S | F-T-L-I | I | G | E | A | S | F | T | L | I |
| DISC1 | 210–213 | A | F | T | S | S | F-S-F-I | R | L | S | L | G | F | S | F | I |
| ATX3 | 74–77 | M | D | D | S | G | F-F-S-I | Q | V | I | S | N | F | F | S | I |
| NCOA4 | 99–102 | S | L | L | G | Q | F-N-C-L | T | H | Q | L | E | F | N | C | L |
| NCOA4 | 154–157 | Q | T | I | T | T | F-G-S-L | K | T | I | Q | I | F | G | S | L |
| NCOA4 | 328–331 | E | T | S | E | K | F-K-L-L | F | Q | S | Y | N | F | K | L | L |
| NCOA4 | 486–489 | R | I | A | D | S | F-Q-V-I | K | N | S | P | L | F | Q | V | I |
| W-type | ||||||||||||||||
| NEDD4 | 685–688 | E | S | S | E | N | W-E-I-I | R | E | D | E | A | W | E | I | I |
| p62 | 338–341 | G | G | D | D | D | W-T-H-L | S | S | K | E | V | W | T | H | L |
| Htt | 3035–3038 | S | M | V | R | D | W-V-M-L | S | L | S | N | F | W | V | M | L |
| Confirmed Motif | Positively Residues | Polar Residues | ||||||||||||||
| Speculated Motif | Negatively Charged | Non-Polar Residues | ||||||||||||||
Comparison of LC3-interacting proteins that utilize a classical LIR motif (green) with the ferritinophagy-specific adaptor protein NCOA4 (yellow). LIRs are grouped depending upon the first residue (Y, F, or W). The NCOA4 region 71–74 (YEQV) and 428–431 (YKWL) has high homology to the canonical LIR Y-type motifs of (Y/F/W)-x-x-(L/I/V), including the flanking acidic residue. Additionally, the residues 99–102 (FNCL), 154–157 (FGSL), 328–331 (FKLL), and 486–489 (FQVI) area also homologous to the canonical LIR F-type motif. C-terminal regions 99–102 and 154–157 do not contain flanking acidic residues but upon cross-referencing, it was observed that neither Beclin1 nor DISC1 contained flanking acidic resides. N-terminal regions 328–331 and 486–489 do contain a flanking residue. In all, there are six independent regions that conform to the LIR stipulations. Mutational experiments are required to determine the functionality of the potential motif sequences. Green = confirmed LIR motif sequences, yellow = possible NCOA4 LIR motif regions based upon established criterion, pink = negatively charged residues, orange = positively charged residues, cyan = polarized residues, blue = non-polar residues. NCOA4: nuclear coactivator 4. Y-type motif positive, FUND1: FUN14 domain-containing protein 1, CRY1: Cryptochrome-1, MAVS: Mitochondrial antiviral-signaling protein, MAPK15: Mitogen-activated protein kinase 15, ULK1: Unc-51 like autophagy activating kinase 1, WDFY3: WD Repeat And FYVE Domain Containing 3, ATG2A: Autophagy protein 2A, ATG13: Autophagy protein 13, BECL1: Beclin1, DISC1: Disrupted in schizophrenia 1, ATX3: Ataxin 3, NEDD4: E3-ubiquitin protein ligase neuronal precursor cell-expressed developmentally downregulated 4, p62: Sequestosome 1, Htt: Huntingtin.