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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002232757  30 WRACPYILANECCERLAYYGMSTNLVNYMKTRLGQESAIAANNVTNWSGTCYITPLLGAFLADAYMGRFWTIASFMIIYI 109
Cdd:cd17418     1 WKACPFILGNECCERLAYYGIATNLITYLTKELHQGNVSAANNVTNWSGTCYITPLIGAFIADAYWGRYWTIASFSAIYF 80

                  .
gi 1002232757 110 L 110
Cdd:cd17418    81 I 81

NRT1/PTR family (NPF), subfamily 8 of the Major Facilitator Superfamily of transporters; The plant Nitrate transporter/Peptide transporter (NRT1/PTR) family (NPF) is related to the POT (proton-coupled oligopeptide transporter), Peptide transporter (PepT/PTR), or Solute Carrier 15 (SLC15) family in animals. In contrast to related animal and bacterial counterparts, the plant proteins transport a wide variety of substrates including nitrate, peptides, amino acids, dicarboxylates, glucosinolates, as well as the plant hormones indole-3-acetic acid (IAA) and abscisic acid (ABA). A recent study identified eight subfamilies within this family, named NPF1-NPF8. NPF8 contains the Arabidopsis dipeptide transporters AtNPF8.1 (PTR1), AtNPF8.2 (PTR5), and AtNPF8.3 (PTR2), as well as tonoplast-localized transporters AtNPF8.4 (PTR4) and AtNPF8.5 (PTR6). Oryza sativa NRT1 (now called OsNPF8.9) is a low-affinity nitrate transporter. NPF8 belongs 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002232757  30 WRACPYILANECCERLAYYGMSTNLVNYMKTRLGQESAIAANNVTNWSGTCYITPLLGAFLADAYMGRFWTIASFMIIYI 109
Cdd:cd17418     1 WKACPFILGNECCERLAYYGIATNLITYLTKELHQGNVSAANNVTNWSGTCYITPLIGAFIADAYWGRYWTIASFSAIYF 80

                  .
gi 1002232757 110 L 110
Cdd:cd17418    81 I 81

Dipeptide/tripeptide permease [Amino acid transport and metabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002232757  34 PYILANECCERLAYYGMSTNLVNYM-----KTRLGQESAIAANNVTNWSGTCYITPLLGAFLADAYMGRFWTIASFMIIY 108
Cdd:COG3104    17 YTLFFTEMWERFSFYGMRAILVLYLtaslaDGGLGLSEADAAAIYGAYTALVYLTPLLGGWLADRLLGQRRAILLGGILM 96

                          90
                  ....*....|....*....
gi 1002232757 109 IlvtnrLGfQFLIAMIDGV 127
Cdd:COG3104    97 A-----LG-HFLLALPGGV 109

NRT1/PTR family (NPF), subfamily 8 of the Major Facilitator Superfamily of transporters; The plant Nitrate transporter/Peptide transporter (NRT1/PTR) family (NPF) is related to the POT (proton-coupled oligopeptide transporter), Peptide transporter (PepT/PTR), or Solute Carrier 15 (SLC15) family in animals. In contrast to related animal and bacterial counterparts, the plant proteins transport a wide variety of substrates including nitrate, peptides, amino acids, dicarboxylates, glucosinolates, as well as the plant hormones indole-3-acetic acid (IAA) and abscisic acid (ABA). A recent study identified eight subfamilies within this family, named NPF1-NPF8. NPF8 contains the Arabidopsis dipeptide transporters AtNPF8.1 (PTR1), AtNPF8.2 (PTR5), and AtNPF8.3 (PTR2), as well as tonoplast-localized transporters AtNPF8.4 (PTR4) and AtNPF8.5 (PTR6). Oryza sativa NRT1 (now called OsNPF8.9) is a low-affinity nitrate transporter. NPF8 belongs 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002232757  30 WRACPYILANECCERLAYYGMSTNLVNYMKTRLGQESAIAANNVTNWSGTCYITPLLGAFLADAYMGRFWTIASFMIIYI 109
Cdd:cd17418     1 WKACPFILGNECCERLAYYGIATNLITYLTKELHQGNVSAANNVTNWSGTCYITPLIGAFIADAYWGRYWTIASFSAIYF 80

                  .
gi 1002232757 110 L 110
Cdd:cd17418    81 I 81

NRT1/PTR family (NPF), subfamily 5 of the Major Facilitator Superfamily of transporters; The plant Nitrate transporter/Peptide transporter (NRT1/PTR) family (NPF) is related to the POT (proton-coupled oligopeptide transporter), Peptide transporter (PepT/PTR), or Solute Carrier 15 (SLC15) family in animals. In contrast to related animal and bacterial counterparts, the plant proteins transport a wide variety of substrates including nitrate, peptides, amino acids, dicarboxylates, glucosinolates, as well as the plant hormones indole-3-acetic acid (IAA) and abscisic acid (ABA). A recent study identified eight subfamilies within this family, named NPF1-NPF8. NPF5 includes Arabidopsis thaliana PTR3 (AtPTR3, now named AtNPF5.2), which is a wound-induced peptide transporter that is necessary for defense against virulent bacterial pathogens. NPF5 belongs 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002232757  30 WRACPYILANECCERLAYYGMSTNLVNYMKTRLGQESAIAANNVTNWSGTCYITPLLGAFLADAYMGRFWTIASFMIIYI 109
Cdd:cd17417     1 WKACSFIIGIEVAERFAYYGIASNLVTYLTTPLHQSTARAAKNVNNWSGTATLLPLLGAFVADAYLGRYRTILISSLIYL 80

                  .
gi 1002232757 110 L 110
Cdd:cd17417    81 L 81

NRT1/PTR family (NPF), subfamily 3 of the Major Facilitator Superfamily of transporters; The plant Nitrate transporter/Peptide transporter (NRT1/PTR) family (NPF) is related to the POT (proton-coupled oligopeptide transporter), Peptide transporter (PepT/PTR), or Solute Carrier 15 (SLC15) family in animals. In contrast to related animal and bacterial counterparts, the plant proteins transport a wide variety of substrates including nitrate, peptides, amino acids, dicarboxylates, glucosinolates, as well as the plant hormones indole-3-acetic acid (IAA) and abscisic acid (ABA). A recent study identified eight subfamilies within this family, named NPF1-NPF8. NPF3 is the smallest NPF subfamily and it includes Cucumis sativus nitrite transporter (CsNitr1), now named CsNPF3.2. It functions as a chloroplast nitrite uptake transporter to remove toxic nitrite from the cytosol. NPF3 belongs 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002232757  30 WRACPYILANECCERLAYYGMSTNLVNYMKTRLGQESAIAANNVTNWSGTCYITPLLGAFLADAYMGRFWTIASFMIIYI 109
Cdd:cd17415     1 WKTMPFIFGNEICERLASVGFHTNLITYLTLQLHMPLVKAANILTNFNGTASLTPLLGAFIADSFAGRFWTITIGSIIYQ 80

                  .
gi 1002232757 110 L 110
Cdd:cd17415    81 L 81

NRT1/PTR family (NPF), subfamily 6 of the Major Facilitator Superfamily of transporters; The plant Nitrate transporter 1/Peptide transporter (NRT1/PTR) family (NPF) is related to the POT (proton-coupled oligopeptide transporter), Peptide transporter (PepT/PTR), or Solute Carrier 15 (SLC15) family in animals. In contrast to related animal and bacterial counterparts, the plant proteins transport a wide variety of substrates including nitrate, peptides, amino acids, dicarboxylates, glucosinolates, as well as the plant hormones indole-3-acetic acid (IAA) and abscisic acid (ABA). A recent study identified eight subfamilies within this family, named NPF1-NPF8. NPF6 includes the first identified member of the NRT1/PTR family: Arabidopsis thaliana NRT1.1, now called AtNPF6.3. It is a dual affinity nitrate influx transporter and a nitrate sensor. It also transports auxin and has nitrate efflux activity. NPF6 belongs 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002232757  30 WRACPYILANECCERLAYYGMSTNLVNYMKTRLGQESAIAANNVTNWSGTCYITPLLGAFLADAYMGRFWTIASFMIIYI 109
Cdd:cd17413     1 WKSAALILGIEMCERLTTLGIGVNLVTYLTGTMHLPSATSANIVTNFLGTSFLLCLLGGFIADTFLGRYLTIAIFASIQA 80

                  .
gi 1002232757 110 L 110
Cdd:cd17413    81 L 81

NRT1/PTR family (NPF), subfamily 1 and 2 of the Major Facilitator Superfamily of transporters; The plant Nitrate transporter/Peptide transporter (NRT1/PTR) family (NPF) is related to the POT (proton-coupled oligopeptide transporter), Peptide transporter (PepT/PTR), or Solute Carrier 15 (SLC15) family in animals. In contrast to related animal and bacterial counterparts, the plant proteins transport a wide variety of substrates including nitrate, peptides, amino acids, dicarboxylates, glucosinolates, as well as the plant hormones indole-3-acetic acid (IAA) and abscisic acid (ABA). A recent study identified eight subfamilies within this family, named NPF1-NPF8. NPF1 includes Medicago truncatula LATD/NIP, now named MtNPF1.7, which is a high-affinity nitrate transporter and is involved in nodulation and root architecture. NPF2 members are well-established nitrate and glucosinolate transporters, including Arabidopsis nitrate influx and efflux transporters with varied tissue and developmental specificity. Examples are AtNPF2.7, which is expressed in the cortex of mature roots, and AtNPF2.9, which is expressed in root companion cells where it is involved in phloem loading. NPF1/2 belongs 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002232757  34 PYILANECCERLAYYGMSTNLVNYMKTRLGQESAIAANNVTNWSGTCYITPLLGAFLADAYMGRFWTI-----ASFMIIY 108
Cdd:cd17416     2 PFIIGNETGEKLASYGLLANLIVYLIEEYNMKSIAAANIINIWSGTTNFLPVVGAFLSDSYFGRFPTIsvgsfASLLGMV 81

                          90
                  ....*....|....*..
gi 1002232757 109 ILvtnrlgfqFLIAMID 125
Cdd:cd17416    82 LL--------TLTAAIP 90

Solute Carrier family 15 member 1 of the Major Facilitator Superfamily of transporters; Solute carrier family 15 member 1 (SLC15A1), also called peptide transporter 1 (PepT1), is a member of the proton-coupled oligopeptide transporter (POT) family of integral membrane proteins that mediate the cellular uptake of di/tripeptides and peptide-like drugs. SLC15A1, as well as SLC15A2, mediate the proton-coupled active transport of a broad range of dipeptides and tripeptides, including zwitterionic, anionic and cationic peptides, as well as a variety of peptide-like drugs such as cefadroxil, enalapril, and valacyclovir. SLC15A1 is primarily expressed in the brush border membranes of enterocytes of the small intestine and is also known as the intestinal isoform. It is a high-capacity/low-affinity transporter that drives the transport of di-and tripeptides for metabolic purposes. It's expression is upregulated in the colon during chronic inflammation associated with inflammatory bowel disease. SLC15A1/PepT1 belongs 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 1002232757  35 YILANECCERLAYYGMSTNLVNYMKTRLGQESAIAANNVTNWSGTCYITPLLGAFLADAYMGRFWTIASFMIIY 108
Cdd:cd17412     6 FIVVNEFCERFSYYGMRAVLVLYFKYFLRWDDDLSTAIYHTFVALCYLTPILGAIIADSWLGKFKTIVYLSIVY 79

Peptide:H+ symporter (also transports b-lactam antibiotics, the antitumor agent, bestatin, and various protease inhibitors); [Transport and binding proteins, Amino acids, peptides and amines]

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1002232757  47 YYGMSTNLVNYMKTRLGQESAIAANNVTNWSGTCYITPLLGAFLADAYMGRFWTIASFMIIYILV 111
Cdd:TIGR00926   3 YYGMRTILVLYFLNFLGFSESTSTVLFHTFTYLCYLTPLIGAIIADGWLGKFKTILYLSIVYVVG 67

Solute Carrier family 15 members 3 and 4 of the Major Facilitator Superfamily of transporters; Solute carrier family 15 members 3 (SLC15A3) and 4 (SLC15A4) are members of the proton-coupled oligopeptide transporter (POT) family of integral membrane proteins that mediate the cellular uptake of di/tripeptides and peptide-like drugs. They are peptide/histidine transporters (PHTs) that transport free histidine in addition to di/tripeptides. SLC15A4, also called peptide transporter 4 or peptide/histidine transporter 1 (PHT1), is expressed in the human brain, retina, placenta, and immune cells. It is required for Toll-like receptor 7 (TLR7)- and TLR9-mediated type I interferon production in plasmacytoid dendritic cells (pDCs) and is involved in the pathogenesis of lupus-like autoimmunity. SLC15A3, also called osteoclast transporter, peptide transporter 3, or peptide/histidine transporter 2 (PHT2), is expressed in immune tissues including the spleen and thymus. The SLC15A3/SLC15A4 group belongs 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002232757  32 ACPYILANECCERLAYYGMSTNLVNYMK-TRLGQESAIAANNVTNWSGTCYITPLLGAFLADAYMGRFWTIASFMIIYIL 110
Cdd:cd17348     3 ACAAVLLVELLERAAFYGITSNLVLFLNgSPFNWEGTQASQALLLFMGATYLLSPFGGWLADAYLGRFWTILLSLLLYLL 82

Dipeptide and tripeptide permease A (DtpA)-like subfamily of the Major Facilitator Superfamily of transporters; The DtpA-like subfamily includes four Escherichia coli proteins: dipeptide and tripeptide permeases A (DtpA, TppB or YdgR), B (DtpB or YhiP), C (DtpC or YjdL), and D (DtpD or YbgH). They are proton-dependent permeases that transport di- and tripeptides. DtpA and DtpB display a preference for di- and tripeptides composed of L-amino acids. DtpC shows higher specificity for dipeptides compared to tripeptides, and prefers dipeptides containing a C-terminal lysine residue. The DtpA-like subfamily belongs 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002232757  43 ERLAYYGMSTNLVNYMKTRLGQE--SAIAANNVTNWSGTCYITPLLGAFLADAYMGRFWTI---ASFMII-YILV----T 112
Cdd:cd17346    14 ERFSYYGMRAILILYLTAQLGDGfsEADAASIYGAYTALVYLTPIIGGWLADKVLGARRTVfigGILMALgYLLLalspF 93

                          90
                  ....*....|..
gi 1002232757 113 NRLGFQFLIAMI 124
Cdd:cd17346    94 SVSMLYLGLALI 105

Solute Carrier family 15 member 5 of the Major Facilitator Superfamily of transporters; Solute carrier family 15 member 5 (SLC15A5) is a member of the proton-coupled oligopeptide transporter (POT) family of integral membrane proteins that mediate the cellular uptake of di/tripeptides and peptide-like drugs. The specific function of SLC15A5 is unknown. SLC15A5 belongs 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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1002232757  40 ECCERLAYYGMSTNLVNYMKTRLGQESAIAANNVTNWSGTCYITPLLGAFLADAYMGR 97
Cdd:cd17349    11 ELCERFTFFGIVCNMILFCTIKLGYRNHQAAIVNLCFVGTSTLTPVFVGWLAEECMGR 68