A.3). However, in 2.A.3, all recognized members of this AC220 family were initially included under 2.A.3. This is a historical fact that cannot be readily corrected because the IUBMB and UniProt require a stable system of classification. Subsequently, we could show that other families previously existing in TCDB were members

of this superfamily. The same was true for the MFS. Thus, we call what would normally be called “subfamilies” the families for both the MFS (2.A.1) and the APC (2.A.3). The same is true for the ABC functional superfamily, except that the membrane proteins actually comprise three superfamilies, ABC1, ABC2 and ABC3 as discussed above [16]. 3 The numbers in bold indicate comparison scores expressed Nirogacestat solubility dmso in S.D [16]. Non-bolded numbers are the exponential numbers (e-values) obtained with TC-BLAST. For instance,

the number “12” in the first row of column 12 indicates that the comparison score between 1.6 CymF and 20.1 BitE was e-12. The TC# provided is the family/protein number (e.g. 1.1 for MalF and MalG, the two membrane constituents of the E. coli maltose transporter). The first three digits in the TC# (3.A.1.) refer to the ABC functional superfamily and are not shown. They are the same for all entries. The protein TC# is followed by the protein abbreviation. All members of a single family are demonstrably homologous, giving high comparison scores (greater than 15 S.D.). Any two families for which a number is provided in the table below this website are demonstrably homologous based on the criteria stated in the Methods Plasmin section. All proteins are within the ABC superfamily (3.A.1), but only the family and protein TC#s are provided below, e.g. 1.6 means 3.A.1.1.6, i.e., ABC family 1, member 6. Topological analyses of ABC uptake system ABC uptake systems, found only in prokaryotes and chloroplasts, contain porters of diverse topological types, and in this section we attempt to predict these topologies. Our studies, reported below, allow us to propose that the primordial transporter contained three TMSs, which duplicated internally to give six TMS homologues [1]. As demonstrated

here, membrane constituents of ABC uptake systems except those of family 21 are of the ABC2 type. However, the actual transporters appearing on the TCDB website contain various numbers of TMSs that range from four or five to twenty. For some families of uptake systems such as families 1, 3 and 14, the porters are more topologically diverse than those from other families such as 8, 11 and 17. Table 2 presents these families and summarizes the topological types predicted for members of uptake porter families. Table 2 Predicted topologies for members of the 34 families of uptake porters in the ABC superfamily (TC# 3.A.1) 1   Family name No. of membrane proteins in TCDB No. of membrane proteins/system Average predicted #TMSs No. of predicted TMSs for family members.