Major Facilitator Superfamily; The Major Facilitator Superfamily (MFS) is a large and diverse group of secondary transporters that includes uniporters, symporters, and antiporters. MFS proteins facilitate the transport across cytoplasmic or internal membranes of a variety of substrates including ions, sugar phosphates, drugs, neurotransmitters, nucleosides, amino acids, and peptides. They do so using the electrochemical potential of the transported substrates. Uniporters transport a single substrate, while symporters and antiporters transport two substrates in the same or in opposite directions, respectively, across membranes. MFS proteins are typically 400 to 600 amino acids in length, and the majority contain 12 transmembrane alpha helices (TMs) connected by hydrophilic loops. The N- and C-terminal halves of these proteins display weak similarity and may be the result of a gene duplication/fusion event. Based on kinetic studies and the structures of a few bacterial superfamily members, GlpT (glycerol-3-phosphate transporter), LacY (lactose permease), and EmrD (multidrug transporter), MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement. Bacterial members function primarily for nutrient uptake, and as drug-efflux pumps to confer antibiotic resistance. Some MFS proteins have medical significance in humans such as the glucose transporter Glut4, which is impaired in type II diabetes, and glucose-6-phosphate transporter (G6PT), which causes glycogen storage disease when mutated.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 11863156 633 CNCAD-QFVPVCGQNGRTYPSACIARC--VGLQDHQFEFG--SCMSKDPCNPNPCQKNQRCIPKPQVCLTTF 699
Cdd:cd17336 316 CNCSDsSFSPVCGSDGITYFSPCHAGCtsSDAGNGTKTYSncSCINSGTATSSGCPPDCSVAPNCCSKLIPF 387

Solute carrier organic anion transporters of the Major Facilitator Superfamily of transporters; Solute carrier organic anion transporters (SLCOs) are also called organic anion transporting polypeptides (OATPs) or SLC21 (Solute carrier family 21) proteins. They are sodium-independent transporters that mediate the transport of a broad range of endo- as well as xenobiotics. Their substrates are mainly amphipathic organic anions with a molecular weight of more than 300Da, although there are a few known neutral or positively charged substrates. These include drugs including statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, antibiotics, antihistaminics, antihypertensives, and anticancer drugs. SLCOs/OATPs can be classified into 6 families (SLCO1-6 or OATP1-6) and each family may have subfamilies (e.g. OATP1A, OATP1B, OATP1C). Within the subfamilies, individual members are numbered according to the chronology of their identification and if there is already an ortholog known, they are given the same number. For example, the first SLCO identified, is rat OATP1A1 (encoded by the Slco1a1 gene). The second SLCO identified is the first human SLCO from the same subfamily and is called OATP1A2 (encoded by the SLCO1A2 gene). There are 11 human SLCOs/OATPs. SLCOs belong to the Major Facilitator Superfamily (MFS) of membrane transport proteins, which are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 11863156 633 CNCAD-QFVPVCGQNGRTYPSACIARC--VGLQDHQFEFG--SCMSKDPCNPNPCQKNQRCIPKPQVCLTTF 699
Cdd:cd17336 316 CNCSDsSFSPVCGSDGITYFSPCHAGCtsSDAGNGTKTYSncSCINSGTATSSGCPPDCSVAPNCCSKLIPF 387

Solute carrier organic anion transporters of the Major Facilitator Superfamily of transporters; Solute carrier organic anion transporters (SLCOs) are also called organic anion transporting polypeptides (OATPs) or SLC21 (Solute carrier family 21) proteins. They are sodium-independent transporters that mediate the transport of a broad range of endo- as well as xenobiotics. Their substrates are mainly amphipathic organic anions with a molecular weight of more than 300Da, although there are a few known neutral or positively charged substrates. These include drugs including statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, antibiotics, antihistaminics, antihypertensives, and anticancer drugs. SLCOs/OATPs can be classified into 6 families (SLCO1-6 or OATP1-6) and each family may have subfamilies (e.g. OATP1A, OATP1B, OATP1C). Within the subfamilies, individual members are numbered according to the chronology of their identification and if there is already an ortholog known, they are given the same number. For example, the first SLCO identified, is rat OATP1A1 (encoded by the Slco1a1 gene). The second SLCO identified is the first human SLCO from the same subfamily and is called OATP1A2 (encoded by the SLCO1A2 gene). There are 11 human SLCOs/OATPs. SLCOs belong to the Major Facilitator Superfamily (MFS) of membrane transport proteins, which are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 11863156 633 CNCAD-QFVPVCGQNGRTYPSACIARC--VGLQDHQFEFG--SCMSKDPCNPNPCQKNQRCIPKPQVCLTTF 699
Cdd:cd17336 316 CNCSDsSFSPVCGSDGITYFSPCHAGCtsSDAGNGTKTYSncSCINSGTATSSGCPPDCSVAPNCCSKLIPF 387

Solute carrier organic anion transporter 1B subfamily of the Major Facilitator Superfamily of transporters; The Solute carrier organic anion transporter 1B (SLCO1B), also called organic anion-transporting polypeptide 1B (OATP1B), subfamily is composed of two human proteins, OATP1B1 (encoded by SLCO1B1) and OATP1B3 (encoded by SLCO1B3), and one rodent member, OATP1B2 (encoded by Slco1b2). OATP1B1 and OATP1B3 are almost exclusively expressed on the basal side of hepatocytes in normal human organs. They both can accept a wide variety of structurally-unrelated compounds as substrates including clinically-important drugs such as hydroxymethylglutaryl (HMG)-CoA reductase inhibitors (statins), angiotensin II receptor blockers (sartans), angiotensin converting enzyme (ACE) inhibitors, and anti-diabetes drugs (glinides). Loss-of-function mutations in both SLCO1B1 and SLCO1B3 genes result in the Rotor syndrome, a hereditary hyperbilirubinemia. The SLCO1B/OATP1B subfamily belongs to the Solute carrier organic anion transporter [SLCO, also called organic anion transporting polypeptides (OATPs) or Solute carrier family 21] family of the Major Facilitator Superfamily (MFS) of transporters. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.

                        10        20
                ....*....|....*....|....*..
gi 11863156 633 CNCAD-QFVPVCGQNGRTYPSACIARC 658
Cdd:cd17457 357 CNCDEsQWDPVCGNNGITYISACLAGC 383