TABLE 2.

Mapping of the residues involved in LA binding of different eukaryotic Nav subtypes (isoforms 1) discussed in Section 5 to the human Nav1.7 (isoform 3). Multiple sequence alignment was performed using the T-Coffee package provided by JABAWS (Troshin et al., 2011). A red color is used to highlight the residues mentioned in Section 5. r represents rats and h humans. The mapping of the residues to the respective regions in the protein are based on the topology of hNav1.7 given in Uniprot (Uniprot ID: Q15858). DI-DIV represent the four domains, S1—S6 represent the six transmembrane segments for each domain, and PM represents the pore module that forms the SF.

Region	hNav1.7	rNav1.2	rNav1.3	rNav1.4	rNav1.5	hNav1.4	hNav1.5
DI-PM	T359	T382	T381	T398	T371	T404	T370
DI-PM	Q360	Q383	Q382	Q399	Q372	Q405	Q371
DI-S6	I386	I409	I408	I425	I398	I431	I397
DII-PM	C914	C940	C892	C753	C899	C759	C896
DII-PM	G915	G941	G893	G754	G900	G760	G897
DIII-S5	L1314	L1341	L1290	L1157	L1340	L1164	L1338
DIII-S5	L1318	L1345	L1294	L1161	L1344	L1168	L1342
DIII-S5	W1321	W1348	W1297	W1164	W1347	W1171	W1345
DIII-PM	L1386	L1413	L1359	L1228	L1412	L1235	L1410
DIII-PM	L1389	L1416	L1362	L1231	L1415	L1238	L1413
DIII-PM	Q1390	Q1417	Q1363	Q1232	Q1416	Q1239	Q1414
DIII-S6	L1438	L1465	L1411	L1280	L1464	L1287	L1462
DIII-S6	F1441	F1468	F1414	F1283	F1467	F1290	F1465
DIII-S6	I1442	I1469	I1415	I1284	I1468	I1291	I1466
DIV-PM	W1689	W1716	W1662	W1531	W1715	W1538	W1713
DIV-PM	L1693	L1720	L1666	L1535	L1719	L1542	L1717
DIV-PM	L1697	L1724	L1670	L1539	L1723	L1546	L1721
DIV-S6	I1726	I1753	I1699	I1568	I1751	I1575	I1749
DIV-S6	V1730	V1757	V1703	C1572	T1755	C1579	T1753
DIV-S6	Y1732	Y1759	Y1705	Y1574	Y1757	Y1581	Y1755
DIV-S6	I1733	I1760	I1706	I1575	I1758	I1582	I1756
DIV-S6	I1734	I1761	I1707	I1576	I1759	I1583	I1757
DIV-S6	F1737	F1764	F1710	F1579	F1762	F1586	F1760
DIV-S6	V1739	V1766	V1712	I1581	I1764	I1588	I1762
DIV-S6	V1740	V1767	V1768	V1582	V1765	V1589	V1763
DIV-S6	N1742	N1769	N1770	N1584	N1767	N1591	N1765
DIV-S6	Y1744	Y1771	Y1772	Y1586	Y1769	Y1593	Y1767