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 2217268935  71 AFGDWLLTANGSEIHKHVHFSSSFTSIASEWFLIANRSYKVSAASSFFFSGVFVGVISFGQLSDRFGRKKVYLTGFALDI 150
Cdd:cd17377     1 AFGEWLLTANDSEVHKHVHFSSSFTSIVSEWFLVGNAAYKVSLASSFFFAGVLIGVVSFGQLSDRFGRKPVYLTGLALDI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217268935 151 LFAIANGFSPSYEFFAVTRFLVGMMNGGMSLVAFVLLNECVGTAYWALAGSIGGLFFAVGIAQYALLGYFIRSWRTLAIL 230
Cdd:cd17377    81 LFAYFNALAPSYEFFAVSRFLVGVMNGGMSLVAFVLLNECVGKSYWALAGSLGGLFFAVGIAQYALLGYFIRSWRTLAVV 160

                         170
                  ....*....|....
gi 2217268935 231 VNLQGTVVFLLSLV 244
Cdd:cd17377   161 VNLQGTLVFLLSLF 174

Solute carrier family 22 member 15 of the Major Facilitator Superfamily of transporters; Solute carrier family 22 member 15 (SLC22A15) is also called fly-like putative transporter 1 (FLIPT1). It is expressed at the highest levels in the kidney and brain. It is a member of the SLC22 family of transporters, which includes organic cation transporters (OCTs), organic zwitterion/cation transporters (OCTNs), and organic anion transporters (OATs). SLC22 transporters interact with a variety of compounds that include drugs of abuse, environmental toxins, opioid analgesics, antidepressant and anxiolytic agents, and neurotransmitters and their metabolites. SLC22A15 belongs to the Major Facilitator Superfamily (MFS) of membrane transport proteins. MFS proteins 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 2217268935  71 AFGDWLLTANGSEIHKHVHFSSSFTSIASEWFLIANRSYKVSAASSFFFSGVFVGVISFGQLSDRFGRKKVYLTGFALDI 150
Cdd:cd17377     1 AFGEWLLTANDSEVHKHVHFSSSFTSIVSEWFLVGNAAYKVSLASSFFFAGVLIGVVSFGQLSDRFGRKPVYLTGLALDI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217268935 151 LFAIANGFSPSYEFFAVTRFLVGMMNGGMSLVAFVLLNECVGTAYWALAGSIGGLFFAVGIAQYALLGYFIRSWRTLAIL 230
Cdd:cd17377    81 LFAYFNALAPSYEFFAVSRFLVGVMNGGMSLVAFVLLNECVGKSYWALAGSLGGLFFAVGIAQYALLGYFIRSWRTLAVV 160

                         170
                  ....*....|....
gi 2217268935 231 VNLQGTVVFLLSLV 244
Cdd:cd17377   161 VNLQGTLVFLLSLF 174

Predicted arabinose efflux permease AraJ, MFS family [Carbohydrate transport and metabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217268935 111 VSAASSFFFSGVFVGVISFGQLSDRFGRKKVYLTGFALDILFAIANGFSPSYEFFAVTRFLVGMMNGGMSLVAFVLLNEC 190
Cdd:COG2814    47 AGLVVTAYLLGAALGAPLAGRLADRFGRRRVLLLGLLLFALGSLLCALAPSLWLLLAARFLQGLGAGALFPAALALIADL 126

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2217268935 191 VGTAYWALAGSIGGLFFAVGIAQYALLGYFI---RSWRTLAILVNLQGTVVFLLSL 243
Cdd:COG2814   127 VPPERRGRALGLLGAGLGLGPALGPLLGGLLadlFGWRWVFLVNAVLALLALLLLL 182

MdfA family multidrug efflux MFS transporter;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2217268935 112 SAASSFFFSGVFVGVIsFGQLSDRFGRKKVYLTGFALDILFAIANGFSPSYEFFAVTRFLVGM 174
Cdd:PRK15402   52 TSMTAYLAGGMFLQWL-LGPLSDRIGRRPVMLAGVAFFILTCLAILLAQSIEQFTLLRFLQGI 113

Solute carrier family 22 member 15 of the Major Facilitator Superfamily of transporters; Solute carrier family 22 member 15 (SLC22A15) is also called fly-like putative transporter 1 (FLIPT1). It is expressed at the highest levels in the kidney and brain. It is a member of the SLC22 family of transporters, which includes organic cation transporters (OCTs), organic zwitterion/cation transporters (OCTNs), and organic anion transporters (OATs). SLC22 transporters interact with a variety of compounds that include drugs of abuse, environmental toxins, opioid analgesics, antidepressant and anxiolytic agents, and neurotransmitters and their metabolites. SLC22A15 belongs to the Major Facilitator Superfamily (MFS) of membrane transport proteins. MFS proteins 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 2217268935  71 AFGDWLLTANGSEIHKHVHFSSSFTSIASEWFLIANRSYKVSAASSFFFSGVFVGVISFGQLSDRFGRKKVYLTGFALDI 150
Cdd:cd17377     1 AFGEWLLTANDSEVHKHVHFSSSFTSIVSEWFLVGNAAYKVSLASSFFFAGVLIGVVSFGQLSDRFGRKPVYLTGLALDI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217268935 151 LFAIANGFSPSYEFFAVTRFLVGMMNGGMSLVAFVLLNECVGTAYWALAGSIGGLFFAVGIAQYALLGYFIRSWRTLAIL 230
Cdd:cd17377    81 LFAYFNALAPSYEFFAVSRFLVGVMNGGMSLVAFVLLNECVGKSYWALAGSLGGLFFAVGIAQYALLGYFIRSWRTLAVV 160

                         170
                  ....*....|....
gi 2217268935 231 VNLQGTVVFLLSLV 244
Cdd:cd17377   161 VNLQGTLVFLLSLF 174

cation transport protein; [Transport and binding proteins, Cations and iron carrying compounds]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217268935  94 FTSIASEWFLIANRSYKVSAASSFFFSGVFVGVISFGQLSDRFGRKKVYLTGFALDILFAIANGFSPSYEFFAVTRFLVG 173
Cdd:TIGR00898 112 SSTIVTEWDLVCEDAWKVDLTQSCFFVGVLLGSFVFGYLSDRFGRKKVLLLSTLVTAVSGVLTAFSPNYTVFLVFRLLVG 191

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2217268935 174 MMNGGMSLVAFVLLNECVGTAYWALAGSIGGLFFAVGIAQYALLGYFIRSWRTLAILVNLQGTVVFLLSLV 244
Cdd:TIGR00898 192 MGIGGIWVQAVVLNTEFLPKKQRAIVGTLIQVFFSLGLVLLPLVAYFIPDWRWLQLAVSLPTFLFFLLSWF 262

Solute carrier family 22 members 4 and 5 (also called Organic cation/carnitine transporters 1 and 2) of the Major Facilitator Superfamily of transporters; This subfamily is composed of solute carrier family 22 members 4 (SLC22A4) and 5 (SLC22A5), and similar proteins. SLC22A4 is also called ergothioneine transporter (ETT) or organic cation/carnitine transporter 1 (OCTN1). It is a sodium-ion dependent, low affinity carnitine transporter, and a highly specific transporter for the uptake of ergothioneine (ET), a thiolated derivative of histidine with antioxidant properties. ET is a natural compound produced only by certain fungi and bacteria and must be absorbed from the diet by humans and other vetebrates. SLC22A5, also called organic cation/carnitine transporter 2 (OCTN2), is a sodium-ion dependent, high affinity carnitine transporter involved in the active cellular uptake of carnitine. SLC22A4/5 belongs to the Solute carrier 22 (SLC22) family of organic cation/anion/zwitterion transporters of the Major Facilitator Superfamily (MFS) of membrane transport proteins. MFS proteins 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 2217268935  95 TSIASEWFLIANRSYKVSAASSFFFSGVFVGVISFGQLSDRFGRKKVYLTGFALDILFAIANGFSPSYEFFAVTRFLVGM 174
Cdd:cd17376    21 STIVTEWNLVCEDDWKVPLTTSLFFVGVLLGSFISGQLSDRFGRKKVLFATMAVQTGFSFLQIFSPSWEMFTVLFVIVGM 100

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2217268935 175 MNGGMSLVAFVLLNECVGTAYWALAGSIGG-LFFAVGIAQYALLGYFIRSWRTLAILVNLQGTVVFLL 241
Cdd:cd17376   101 GQISNYVVAFVLGTEILGKSVRILFSTLGVcIFYAIGYMLLPLFAYFIRDWRMLLLALTLPGVLCVPL 168

Plant organic cation/carnitine transporters of the Major Facilitator Superfamily of transporters; Plant organic cation/carnitine transporters (OCTs) are sequence-similar to their animal counterparts, which are broad-specificity transporters that play a critical role in the excretion and distribution of endogeneous organic cations and for the uptake, elimination and distribution of cationic drugs, toxins, and environmental waste products. Little is know about plant OCTs. In Arabidopsis, there are six genes belonging to this family that show distinct, organ-specific expression pattern of the individual genes. AtOCT1 has been found to affect root development and carnitine-related responses in Arabidopsis. AtOCT4, 5 and 6 are up-regulated during drought stress, AtOCT3 and 5 during cold stress and AtOCT5 and 6 during salt stress treatments. Plant OCTs belongs to the Solute carrier 22 (SLC22) family of organic cation/anion/zwitterion transporters of the Major Facilitator Superfamily (MFS) of membrane transport proteins. MFS proteins 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 2217268935  96 SIASEWFLIANRSYKVSAASSFFFSGVFVGVISFGQLSD-RFGRKKVYLTGFALDILFAIANGFSPSYEFFAVTRFLVGM 174
Cdd:cd17378    20 SIVSEWGLICAGSFLVGLPQSSFFVGCLIGSGVLGHLADsSLGRKNLLFLSCLLMALSGIATAFSPNYWVYAFLRFLTGF 99

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2217268935 175 MNGGMSLVAFVLLNECVGTAYWALAGSIGGLFFAVGIAQYALLGYFI-RSWRTL 227
Cdd:cd17378   100 GRSGIGTCALVLATEPVGPKWRGQVGMSTFFFFVLGFMSLPGIAYLNgSSWRVL 153

Solute carrier family 22 member 6 (also called Organic anion transporter 1) and similar transporters of the Major Facilitator Superfamily; This subfamily includes solute carrier family 22 member 6 (SLC22A6, also called organic anion transporter 1 or OAT1 or para-aminohippurate (PAH) transporter), SLC22A8 (or OAT3), and SLC22A20 (or OAT6). OAT1 and OAT3 are involved in the renal elimination of endogenous and exogenous organic anions (OAs). They function as OA exchangers, coupling the uptake of OAs against an electrochemical gradient with the efflux of intracellular dicarboxylates. SLC22A20 is an OA transporter that mediates the uptake of estrone sulfate. The OAT1-like subfamily belongs to the Solute carrier 22 (SLC22) family of organic cation/anion/zwitterion transporters of the Major Facilitator Superfamily (MFS) of membrane transport proteins. MFS proteins 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 2217268935  92 SSFTS-IASEWFLIANRSYKVSAASSFFFSGVFVGVISFGQLSDRFGRKKVYLTGFALDILFAIANGFSPSYEFFAVTRF 170
Cdd:cd17446    15 SEFPStIITEWDLVCNHRALRQLAQSIYMAGVLVGAIVFGGLSDRFGRRPLLIWSYLQMAVSGTCAAFSPSFPIYCVFRF 94

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217268935 171 LVGMMNGGMSLVAFVLLNECVGTAYWALAGSIGGLFFAVGIAQYALLGYFIRSWRTLAILVNLQGTVVFLLS 242
Cdd:cd17446    95 LTGMALSGIVLNSVSLNVEWMPTRVRAVVGTLLGYCYTLGQLILAGVAYAIRDWRWLQLAVSLPFFIFFLYS 166

Solute carrier family 22, member 31 of the Major Facilitator Superfamily; Solute carrier family 22, member 31 (SLC22A31) is an uncharacterized member of the SLC22 family of transporters, which includes organic cation transporters (OCTs), organic zwitterion/cation transporters (OCTNs), and organic anion transporters (OATs). SLC22 transporters interact with a variety of compounds that include drugs of abuse, environmental toxins, opioid analgesics, antidepressant and anxiolytic agents, and neurotransmitters and their metabolites. SLC22A31 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 2217268935  95 TSIASEWFLIANRSYKVSAASSFFFSGVFVGVISFGQLSDRFGRKKVYLTGFALDILFAIANGFSPSYEFFAVTRFLVGM 174
Cdd:cd17443    22 SNLVTEWNLVCDDGWKVPLEKISYLLGWLLGYIILGAGCDRLGRRAAFVLSLVLATLLGVSVALSASPPTFLVLRLLQGG 101

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2217268935 175 MNGGMSLVAFVLLNECVGTAYWALAGSIGGLFFAVGIAQYALLGYFIRSWRTLAILVNL 233
Cdd:cd17443   102 TLAGVFLSLYIARLELCDPSHRLMVSMGAGFFSVAGELLLPGLAVLCRDWRVLQGVGTL 160

Sugar phosphate permease [Carbohydrate transport and metabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217268935 112 SAASSFFFSGVFVGVISFGQLSDRFGRKKVYLTGFALDILFAIANGFSPSYEFFAVTRFLVGMMNGGMSLVAFVLLNECV 191
Cdd:COG2271    48 GLLASAFFLGYALGQIPAGLLADRFGRRRVLAIGLLLWGLATLLFGFATSFWQLLLLRFLLGLGEAGFFPAALKLIAEWF 127

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2217268935 192 GTAYWALAGSIGGLFFAVGIAQYALLGYFI---RSWRTLAILVNLQGTVVFLLSL 243
Cdd:COG2271   128 PPKERGRALGIFNAGGPLGGALAPPLLGWLlaaFGWRAAFLILGLPGLLLALLRF 182

Metazoan Synaptic vesicle glycoprotein 2 (SV2) and related small molecule transporters of the Major Facilitator Superfamily; This family is composed of metazoan synaptic vesicle glycoprotein 2 (SV2) and related small molecule transporters including those that transport inorganic phosphate (Pht), aromatic compounds (PcaK and related proteins), proline/betaine (ProP), alpha-ketoglutarate (KgtP), citrate (CitA), shikimate (ShiA), and cis,cis-muconate (MucK), among others. SV2 is a transporter-like protein that serves as the receptor for botulinum neurotoxin A (BoNT/A), one of seven neurotoxins produced by the bacterium Clostridium botulinum. BoNT/A blocks neurotransmitter release by cleaving synaptosome-associated protein of 25 kD (SNAP-25) within presynaptic nerve terminals. Also included in this family is synaptic vesicle 2 (SV2)-related protein (SVOP) and similar proteins. SVOP is a transporter-like nucleotide binding protein that localizes to neurotransmitter-containing vesicles. The SV2-like family 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 2217268935 111 VSAASSFFFSGVFVGVISFGQLSDRFGRKKVYLTGFALDILFAIANGFSPSYEFFAVTRFLVGMMNGGMSLVAFVLLNEC 190
Cdd:cd17316    38 TGLLFAAGFLGRPIGALLFGYLGDRIGRKKALILTLLLFGLATLLIGLLPTPILLLVLRFLQGIGIGGEYPGASTYVAEF 117

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2217268935 191 VGTAYWALAGSIGGLFFAVGIAQYALLGYFI 221
Cdd:cd17316   118 APSKRRGFALGLLQSGWALGALLAALVASLL 148

Solute carrier family 22, member 17 of the Major Facilitator Superfamily; Solute carrier family 22, member 17 (SLC22A17) is also called 24p3 receptor (24p3R), lipocalin-2 receptor, or neutrophil gelatinase-associated lipocalin (NGAL) receptor (NGALR). It functions as a cell surface receptor for lipocalin-2 (LCN2), also called NGAL or 24p3, which plays a key role in iron homeostasis and transport. LCN2 is a secreted protein of the lipocalin family that induces apoptosis in some types of cells and inhibits bacterial growth by sequestration of the iron-laden bacterial siderophore. Over-expressions of NGAL and NGALR have been found to be correlated with unfavorable clinicopathologic features and poor prognosis of patients with hepatocellular carcinoma. SLC22A17 is a member of the SLC22 family of organic cation/anion/zwitterion transporters, which includes organic cation transporters (OCTs/OCTNs) and organic anion transporters (OATs). It 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 2217268935  95 TSIASEWFLIANRSYKVSAASSFFFSGVFVGVISFGQLSDRFGRKKVYLTGFALDILFAIANGFSPSYEFFAVTRFLVGM 174
Cdd:cd17445    22 NNIVTEWDLVCSRYWLVPLEQVCFILGFASGYLCLGYTADRLGRRRTLLLSLTLAVPFGVLVAVAASPSLFMAMRFLLGA 101

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2217268935 175 MNGGMSLVAFVLLNECVGTAYWALAGSIGGLFFAVGiaQYALLGYFI--RSWRTlailvnLQGTVVFLLSL 243
Cdd:cd17445   102 ALAGVYLTLYLTRLELCDPPQRLLVAMAGGLTMVGG--HFLLLGLALgcGSWRV------LQGTITAPLSL 164

benzoate transport; [Transport and binding proteins, Carbohydrates, organic alcohols, and acids]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217268935 121 GVFVGVISFGQLSDRFGRKKVYLTGFALDILFAIANGFSPSYEFFAVTRFLVGMMNGGMSLVAFVLLNECVGTAYWALAG 200
Cdd:TIGR00895  64 GMAFGALFFGPLADRIGRRRVLLWSILLFSVFTLLCALATNVTQLLILRFLAGLGLGGLMPNLNALVSEYAPKRFRGTAV 143

                          90       100       110
                  ....*....|....*....|....*....|
gi 2217268935 201 SIGGLFFAVGIAQYALLGYFIRS---WRTL 227
Cdd:TIGR00895 144 GLMFCGYPIGAAVGGFLAGWLIPvfgWRSL 173

4-hydroxybenzoate transporter PcaK and similar transporters of the Major Facilitator Superfamily; This aromatic acid:H(+) symporter subfamily includes Acinetobacter sp. 4-hydroxybenzoate transporter PcaK, Pseudomonas putida gallate transporter (GalT), Corynebacterium glutamicum gentisate transporter (GenK), Nocardioides sp. 1-hydroxy-2-naphthoate transporter (PhdT), Escherichia coli 3-(3-hydroxy-phenyl)propionate (3HPP) transporter (MhpT), and similar proteins. These transporters are involved in the uptake across the cytoplasmic membrane of specific aromatic compounds such as 4-hydroxybenzoate, gallate, gentisate (2,5-dihydroxybenzoate), 1-hydroxy-2-naphthoate, and 3HPP, respectively. The PcaK-like aromatic acid:H(+) symporter subfamily belongs to the Metazoan Synaptic Vesicle Glycoprotein 2 (SV2) and related small molecule transporter family (SV2-like) of the Major Facilitator Superfamily (MFS) of membrane transport proteins. MFS proteins 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 2217268935 121 GVFVGVISFGQLSDRFGRKKVYLTGFALDILFAIANGFSPSYEFFAVTRFLVGMMNGGMSLVAFVLLNECVGTAYWALAG 200
Cdd:cd17365    46 GMAIGALLAGPLADRFGRKRVLLVSVALFGLFTLLTAFAQSVLQLALLRFLTGLGLGAAMPNAITLVSEYAPARRRSLAV 125

                          90       100
                  ....*....|....*....|.
gi 2217268935 201 SIGGLFFAVGIAQYALLGYFI 221
Cdd:cd17365   126 TLMFCGYPLGAALGGFLAAAL 146

Sugar (and other) transporter;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217268935 116 SFFFSGVFVGVISFGQLSDRFGRKKVYLTGFALDILFAIANGFSP---SYEFFAVTRFLVGMMNGGMSLVAFVLLNEcvg 192
Cdd:pfam00083  53 SIFSVGCFIGSLFAGKLGDRFGRKKSLLIANVLFVIGAVLQGAAKgkwSVYQLIVGRVLVGIGVGGASVLAPMYISE--- 129

                          90       100
                  ....*....|....*....|....*....
gi 2217268935 193 TAYWALAGSIGGLFFaVGIAQYALLGYFI 221
Cdd:pfam00083 130 IAPKKLRGALGSLYQ-LAITFGILLAYIF 157

Synaptic vesicle 2-related protein (SVOP) of the Major Facilitator Superfamily; Synaptic vesicle 2 (SV2)-related protein (SVOP) is a transporter-like nucleotide binding protein that localizes to neurotransmitter-containing vesicles. Like SV2, SVOP is expressed in all brain regions, with highest levels in cerebellum, hindbrain and pineal gland. Studies with knockout mice suggets that SVOP may perform a subtle function that is not necessary for survival under normal conditions, since mice lacking SVOP are viable, fertile, and phenotypically normal. SVOP shares structural similarity to the solute carrier family 22 (SLC22), a large family of organic cation and anion transporters. This SVOP subfamily belongs to the Metazoan Synaptic Vesicle Glycoprotein 2 (SV2) and related small molecule transporter family (SV2-like) of the Major Facilitator Superfamily (MFS) of membrane transport proteins. MFS proteins 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 2217268935  96 SIASEWFLianRSYKVSAASSFFFSGVFVGVISFGQLSDRFGRKKVYLTGFALDILFAIANGFSPSYEFFAVTRFLVGMM 175
Cdd:cd17441    24 QLHCEWRL---PSWQVALLTSVVFIGMMLSSSLWGNISDQYGRKTGLKISVLWTLYYGILSAFAPIYSWILVLRGLVGFG 100

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2217268935 176 NGGMSLvAFVLLNECVGTAYWALAGSIGGLFFAVGIAQYALLGYFIR---SWRTLAIL 230
Cdd:cd17441   101 IGGVPQ-SVTLYAEFLPMKSRAKCILLIEVFWALGTVFEVLLAVFVMptlGWRWLLIL 157

Major Facilitator Superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217268935 111 VSAASSFFFSGVFVGVISFGQLSDRFGRKKVYLTGFALDILFAIANGFSPSYEFFAVTRFLVGMMNGGMSLVAFVLLNEC 190
Cdd:pfam07690  34 IGLLLTLFSLGYALAQPLAGRLSDRFGRRRVLLIGLLLFALGLLLLLFASSLWLLLVLRVLQGLGAGALFPAALALIADW 113

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2217268935 191 VGTAYWALAGSIGGLFFAVGIAQYALLGYFI 221
Cdd:pfam07690 114 FPPEERGRALGLVSAGFGLGAALGPLLGGLL 144

Class 1 and Class 2 Glucose transporters (GLUTs) of the Major Facilitator Superfamily; This subfamily includes Class 1 and Class 2 glucose transporters (GLUTs) including Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1, also called glucose transporter type 1 or GLUT1), SLC2A2-5 (GLUT2-5), SLC2A7 (GLUT7), SLC2A9 (GLUT9), SLC2A11 (GLUT11), SLC2A14 (GLUT14), and similar proteins. GLUTs are a family of proteins that facilitate the transport of hexoses such as glucose and fructose. There are fourteen GLUTs found in humans; they display different substrate specificities and tissue expression. They have been categorized into three classes based on sequence similarity: Class 1 (GLUTs 1-4, 14); Class 2 (GLUTs 5, 7, 9, and 11); and Class 3 (GLUTs 6, 8, 10, 12, and HMIT). GLUTs 1-5 are the most thoroughly studied and are well-established as glucose and/or fructose transporters in various tissues and cell types. GLUT proteins are comprised of about 500 amino acid residues, possess a single N-linked oligosaccharide, and have 12 transmembrane segments. They belong to the Glucose transporter -like (GLUT-like) family of the Major Facilitator Superfamily (MFS) of membrane transport proteins. MFS proteins 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 2217268935 112 SAASSFFFSGVFVGVISFGQLSDRFGRKKVYLTGFALDILFAIANGFS---PSYEFFAVTRFLVGMMNGGMSLVAFVLLN 188
Cdd:cd17357    52 SLIVSIFFIGGAIGSFISAFLANRFGRKNGLLISNALLVVSSLLMFLSksaKSPELLIFGRFLVGIACGLSTGFVPMYLQ 131

                          90       100       110
                  ....*....|....*....|....*....|
gi 2217268935 189 ECVGTAYWALAGSIGGLFFAVGIAQYALLG 218
Cdd:cd17357   132 EISPSELRGALGSLTQIGVTLGILLGQVFG 161

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 2217268935 111 VSAASSFFFSGVFVGVISFGQLSDRFGRKKVYLTGFALDILFAIANGFSPSYEFFAVTRFLVGMMNGGMSLVAFVLLNEC 190
Cdd:cd06174    33 LGLLFALFSLGYALLQPLAGLLADRFGRRPVLLLGLLLFALGALLFAFAPSFWLLLLGRFLLGLGSGLIDPAVLALIADL 112

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2217268935 191 VGTAYWALAGSIGGLFFAVGIAQYALLGYFI 221
Cdd:cd06174   113 FPERERGRALGLLQAFGSVGGILGPLLGGIL 143

Methylenomycin A resistance protein (also called MMR peptide) and similar multidrug resistance (MDR) transporters of the Major Facilitator Superfamily; This family is composed of bacterial, fungal, and archaeal multidrug resistance (MDR) transporters including several proteins from Bacilli such as methylenomycin A resistance protein (also called MMR peptide), tetracycline resistance protein (TetB), and lincomycin resistance protein LmrB, as well as fungal proteins such as vacuolar basic amino acid transporters, which are involved in the transport into vacuoles of the basic amino acids histidine, lysine, and arginine in Saccharomyces cerevisiae, and aminotriazole/azole resistance proteins. MDR transporters are drug/H+ antiporters (DHA) that mediate the efflux of a variety of drugs and toxic compounds, and confer resistance to these compounds. For example, MMR confers resistance to the epoxide antibiotic methylenomycin while TetB resistance to tetracycline by an active tetracycline efflux. MMR-like MDR transporters 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217268935 124 VGVISFGQLSDRFGRKKVYLTGFALDILFAIANGFSPSYEFFAVTRFLVG-----MMNGGMSLVAFVLLNECVGTAyWAL 198
Cdd:cd17321    46 ALLLLAGRLGDRFGRKRVFLIGLALFGLASLLCALAPSLAFLIAARALQGigaaaIMPASLALIAATFPGERRGRA-LGL 124

                          90
                  ....*....|..
gi 2217268935 199 AGSIGGLFFAVG 210
Cdd:cd17321   125 WGAVVGIGAALG 136

Solute carrier family 22, member 17 and similar proteins of the Major Facilitator Superfamily; This group is composed of Solute carrier family 22, members 17, 23, and 31. They are members of the SLC22 family of organic cation/anion/zwitterion transporters, which includes organic cation transporters (OCTs/OCTNs) and organic anion transporters (OATs). SLC22A17 functions as a cell surface receptor for lipocalin-2 (LCN2), also called NGAL or 24p3, which plays a key role in iron homeostasis and transport. SLC22A23 and SLC22A31 are orphan members of the SLC22 family. SLC22 transporters interact with a variety of compounds that include drugs of abuse, environmental toxins, opioid analgesics, antidepressant and anxiolytic agents, and neurotransmitters and their metabolites. The SLC22A17-like 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 2217268935  91 SSSFTSIASEWFLIANRSYKVSAASSFFFSGVFVGVISFGQLSDRFGRKKVYLTGFALDILFAIANGFSPSYEFFAVTRF 170
Cdd:cd17373     7 AGLVQNAVSKWDLVCDNGWKVHLEQFSLLLGLIFGYLILGCIADRFGRRPVLLFSLILILIFGLTVALAVSVTMFSTLRF 86

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2217268935 171 LVGMMNGGMSLVAFVLLNECVGTAYWALAGSIGGLFFAVGIAQYALLGYFIRSWRTLAILVNL 233
Cdd:cd17373    87 LEGFCLAGIILTLYLLRLELCDPGKRLMITMVASLVAVAGQFLMPGLAALCRDWRVLQALIIC 149

Yeast Polyamine transporter 1 (Tpo1) and similar multidrug resistance (MDR) transporters of the Major Facilitator Superfamily; This family is composed of fungal multidrug resistance (MDR) transporters including several proteins from Saccharomyces cerevisiae such as polyamine transporters 1-4 (Tpo1-4), quinidine resistance proteins 1-3 (Qdr1-3), dityrosine transporter 1 (Dtr1), fluconazole resistance protein 1 (Flr1), and protein HOL1. MDR transporters are drug/H+ antiporters (DHA) that mediate the efflux of a variety of drugs and toxic compounds, and confer resistance to these compounds. For example, Flr1 confers resistance to the azole derivative fluconazole while Tpo1 confers resistance and adaptation to quinidine and ketoconazole. The polyamine transporters are involved in the detoxification of excess polyamines in the cytoplasm. Tpo1-like MDR transporters 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217268935  90 FSSSFTSIASEWfliaNRSYKVSAAS-SFFFSGVFVGVISFGQLSDRFGRKKVYLTGFALDILFAIANGFSPSYEFFAVT 168
Cdd:cd17323    18 YSPALPQIAEDF----HVSEEVANLGvSLFVLGFGLGPLIWAPLSELYGRRPVYLVSLFIFVIFQIGCALAPNIAMLIIL 93

                  ....*
gi 2217268935 169 RFLVG 173
Cdd:cd17323    94 RFLQG 98

bacterial MdtG-like and eukaryotic solute carrier 18 (SLC18) family of the Major Facilitator Superfamily of transporters; This family is composed of eukaryotic solute carrier 18 (SLC18) family transporters and related bacterial multidrug resistance (MDR) transporters including several proteins from Escherichia coli such as multidrug resistance protein MdtG, from Bacillus subtilis such as multidrug resistance proteins 1 (Bmr1) and 2 (Bmr2), and from Staphylococcus aureus such as quinolone resistance protein NorA. The family also includes Escherichia coli arabinose efflux transporters YfcJ and YhhS. MDR transporters are drug/H+ antiporters (DHA) that mediate the efflux of a variety of drugs and toxic compounds, and confer resistance to these compounds. The SLC18 transporter family includes vesicular monoamine transporters (VAT1 and VAT2), vesicular acetylcholine transporter (VAChT), and SLC18B1, which is proposed to be a vesicular polyamine transporter (VPAT). The MdtG/SLC18 family 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 2217268935 113 AASSFFFSGVFVGVIsFGQLSDRFGRKKVYLTGFALDILFAIANGFSPSYEFFAVTRFLVGM-----MNGGMSLVAFVLL 187
Cdd:cd17325    36 IVAAYALAQLLFSPP-AGRLSDRFGRKRLLLLGLLLLAVSTLLFAFATSYWQLLLARFLQGLasaavWPAAMALIADIAP 114

                          90       100
                  ....*....|....*....|...
gi 2217268935 188 NECVGTAYwALAGSIGGLFFAVG 210
Cdd:cd17325   115 PEERGRAM-GIFSSAIGLGFLIG 136

synaptic vesicle protein SV2; This model describes a tightly conserved subfamily of the larger family of sugar (and other) transporters described by pfam00083. Members of this subfamily include closely related forms SV2A and SV2B of synaptic vesicle protein from vertebrates and a more distantly related homolog (below trusted cutoff) from Drosophila melanogaster. Members are predicted to have two sets of six transmembrane helices.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2217268935 116 SFFFSGVFVGVISFGQLSDRFGRKKVYLTGFALDILFAIANGFSPSYEFFAVTRFLVGMMNGGMSLVAFVLLNE 189
Cdd:TIGR01299 209 LIVYLGMMVGAFFWGGLADKLGRKQCLLICLSVNGFFAFFSSFVQGYGFFLFCRLLSGFGIGGAIPIVFSYFAE 282

Inorganic Phosphate Transporter of the Major Facilitator Superfamily of transporters; This subfamily is composed of predominantly fungal and plant high-affinity inorganic phosphate transporters (PhT or PiPT), which are involved in the uptake, translocation, and internal transport of inorganic phosphate. They also function in sensing external phosphate levels as transceptors. Phosphate is crucial for structural and metabolic needs, including nucleotide and lipid synthesis, signalling and chemical energy storage. The Pht subfamily belongs to the Metazoan Synaptic Vesicle Glycoprotein 2 (SV2) and related small molecule transporter family (SV2-like) of the Major Facilitator Superfamily (MFS) of membrane transport proteins. MFS proteins 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 2217268935 111 VSAASSFffsGVFVGVISFGQLSDRFGRKKVYLTGFALDILFAIANGFSPSYEFFAVT------RFLVGMMNGG 178
Cdd:cd17364    44 VNAAALV---GTIIGQLFFGFLGDRFGRKRVYGVELIIMIIGTILSALSPGSTPLGVMgwliffRFLLGIGIGG 114

Sugar phosphate permease [Carbohydrate transport and metabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217268935 110 KVSAASSFFFSGVFVGVISFGQLSDRFGR--KKVYLTGFALDILFAIANGFSPSYEFFAVTRFLVGMMNGGMSLVAFVLL 187
Cdd:COG2271   217 QAGLLLSLPFLAGIVGSLLGGWLSDRLGRrrKLVLAIGLLLAALALLLLALLPSPALAIALLFLAGFGLGGAFGLLWALA 296

                          90       100
                  ....*....|....*....|....*
gi 2217268935 188 NECVGTAYWALAGSIGGLFFAVGIA 212
Cdd:COG2271   297 AELFPKKARGTASGLVNTFGFLGGA 321

H(+)-myo-inositol cotransporter and similar transporters of the Major Facilitator Superfamily; This subfamily is composed of myo-inositol/inositol transporters and similar transporters from vertebrates, plant, and fungi. The human protein is called H(+)-myo-inositol cotransporter/Proton myo-inositol cotransporter (HMIT), or H(+)-myo-inositol symporter, or Solute carrier family 2 member 13 (SLC2A13). HMIT is classified as a Class 3 GLUT (glucose transporter) based on sequence similarity with GLUTs, but it does not transport glucose. It specifically transports myo-inositol and is expressed predominantly in the brain, with high expression in the hippocampus, hypothalamus, cerebellum and brainstem. HMIT may be involved in regulating processes that require high levels of myo-inositol or its phosphorylated derivatives, such as membrane recycling, growth cone dynamics, and synaptic vesicle exocytosis. Arabidopsis Inositol transporter 4 (AtINT4) mediates high-affinity H+ symport of myo-inositol across the plasma membrane. The HMIT-like subfamily belongs to the Glucose transporter -like (GLUT-like) family of the Major Facilitator Superfamily (MFS) of membrane transport proteins. MFS proteins 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 2217268935 111 VSAASSfffsGVFVGVISFGQLSDRFGRKKVYLTGFALDILFAIANGFSPSYEFFAVTRFLVGMMNGGMSLVAFVLLNE 189
Cdd:cd17360    41 VSSTVA----GAAVGAAIGGWLNDRFGRRPCILLADALFTIGAIVMAAAPNKEVLIVGRVLVGLGVGIASMTVPLYIAE 115