B.104.6.1 Q1D006 242 7 Rhomboid Family Proteins were retrieved with GBLAST e-values between 0.1 and 0.001, individually verified and assigned TC numbers as indicated. A single protein (Q1D5P4; 432 aas; 14 TMSs) proved to be a member of the Monovalent Cation:Proton Antiporter-2 (CPA2) Family, and it was assigned TC# 2.A.37.6.1 in a novel subfamily. It could be a K+:H+ or Na+:H+ antiporter. A second protein (Q1DCP3;

290 aas; 10 TMSs) was shown to be a member of the Drug/Metabolite Transporter (DMT) Superfamily, distantly related to members of the Drug Metabolite Exporter (DME) Family. It was assigned TC # 2.A.7.31.1, also in a novel subfamily. A third protein (Q1D7B4; 506 aas; 14 TMSs) was assigned TC# 2.A.66.12.1 as a member of the Multidrug/Oligosaccharidyl-lipid/Polysaccharide (MOP) Flippase Superfamily. It belongs to a family within this superfamily for which Entinostat in vitro no functional data are available. A fourth protein (Q1DA07; 731 aas; 13 TMSs) belongs to the Major Facilitator Superfamily (MFS) and was assigned TC# 2.A.1.15.16. The gene of this protein is adjacent to a putative S-adenosyl methionine (SAM)-dependent methyltransferase

whose homologues include puromycin methyltransferases. The substrate of this protein is potentially a drug that undergoes modification by methylation for detoxification purposes. Two proteins proved to be else members of the ABC-2 Superfamily within the ATP-binding Cassette (ABC) Functional Superfamily [28]. One protein (Q1D520; 1200 P-gp inhibitor aas; 13 TMSs) was assigned to a new ABC family with TC# 3.A.1.145.1. Notably, this exporter proved to be a fusion between an N-terminal ABC-2 domain with 13 putative TMSs and a hydrophilic C-terminal zinc dependent amino peptidase domain (Peptidase M1 Family), suggesting that the transporter domain

could be involved in the export of an amino acid, amino acid derivative, or product of amino acid metabolism. In addition, Q1D520 resembles (35.4% identity and 54.6% similarity with 4 gaps) 3.A.1.145.3, another ABC-2 export permease fusion protein annotated as being involved in multi-copper enzyme maturation. The other ABC protein (Q1D0V1; 266 aas; 6 TMSs) was assigned TC# 3.A.1.144.3 and is functionally uncharacterized. Two proteins were shown to be homologous to proteins in TC Category 9. The first protein (Q1CXZ2; 211 aas; 3 TMSs) was found to be a member of the Protein Tyrosine Kinase inhibitor Cannabalism Toxin SdpC (SdpC) Family and was assigned TC# 9.B.139.2.1. The second protein (Q1D006; 242 aas; 7 TMSs) was assigned TC# 9.B.104.6.1. It belongs to the Rhomboid Protease Family and shows sequence similarity to members of the MFS; this result provides preliminary evidence that the MFS and Rhomboid Protease Family may in fact be homologous and warrants future investigation.