Solute carrier family 22 members 1, 2, and 3 (also called Organic cation transporters 1, 2, and 3) of the Major Facilitator Superfamily of transporters; This sufamily includes solute carrier family 22 member 1 (SLC22A1, also called organic cation transporter 1 or OCT1), SLC22A2 (or OCT2), SLC22A3 (or OCT3), and similar proteins. OCT1-3 have similar basic functional properties: they are able to translocate a variety of structurally different organic cations in both directions across the plasma membrane; to translocate organic cations independently from sodium, chloride or proton gradients; and to function as electrogenic uniporters for cations or as electroneutral cation exchangers. They show overlapping but distinct substrate and inhibitor specificities, and different tissue expression pattern. In humans, OCT1 is strongly expressed in the liver, OCT2 is highly expressed in the kidney where it is localized at the basolateral membrane of renal proximal tubules, and OCT3 is most strongly expressed in skeletal muscle. OCTs 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. The SLC22A1-3 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 530383981 120 RSAPLVPCRGGWRYAQAHSTIVSEFDLVCVNAWMLDLTQAILNLGFLTGAFTLGYAADRYGRIVIYLLSCLGVGVTGVVV 199
Cdd:cd17379    1 SMLPLSPCQDGWVYNTPRSSIVTEFNLVCEDAWKLDLFQSSLNLGFLIGSIVIGYLADRFGRKVCFLISILGNGVSGVLM 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383981 200 AFAPNFPVFVIFRFLQGVFGKGTWMTCYVIVTEIVGSKQRRIVGIVIQMFFTLGIIILPGIAYFIPNWQGIQLAITLPSF 279
Cdd:cd17379   81 AFSPNYPWFLIFRFLQGLFGKGGWMTGYVLVTEFVGSKYRRTVGIVYQMFFTLGLLILPGIAYFIPHWRWLQLAVTLPNF 160

                        170
                 ....*....|
gi 530383981 280 LFLLYYWVVP 289
Cdd:cd17379  161 LFLLYYWFIP 170

Major Facilitator Superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383981  159 AILNLGFLTGAFTLGYAADRYGRIVIYLLSCLGVGVTGVVVAFAPNFPVFVIFRFLQGVFGKGTWMTCYVIVTEIVGSKQ 238
Cdd:pfam07690  39 TLFSLGYALAQPLAGRLSDRFGRRRVLLIGLLLFALGLLLLLFASSLWLLLVLRVLQGLGAGALFPAALALIADWFPPEE 118

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 530383981  239 R-RIVGIViQMFFTLGIIILPGIAYFI---PNWQGIQLAITLPSFLFLLYYWVVPESPR 293
Cdd:pfam07690 119 RgRALGLV-SAGFGLGAALGPLLGGLLaslFGWRAAFLILAILSLLAAVLLLLPRPPPE 176

Solute carrier family 22 members 1, 2, and 3 (also called Organic cation transporters 1, 2, and 3) of the Major Facilitator Superfamily of transporters; This sufamily includes solute carrier family 22 member 1 (SLC22A1, also called organic cation transporter 1 or OCT1), SLC22A2 (or OCT2), SLC22A3 (or OCT3), and similar proteins. OCT1-3 have similar basic functional properties: they are able to translocate a variety of structurally different organic cations in both directions across the plasma membrane; to translocate organic cations independently from sodium, chloride or proton gradients; and to function as electrogenic uniporters for cations or as electroneutral cation exchangers. They show overlapping but distinct substrate and inhibitor specificities, and different tissue expression pattern. In humans, OCT1 is strongly expressed in the liver, OCT2 is highly expressed in the kidney where it is localized at the basolateral membrane of renal proximal tubules, and OCT3 is most strongly expressed in skeletal muscle. OCTs 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. The SLC22A1-3 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 530383981 120 RSAPLVPCRGGWRYAQAHSTIVSEFDLVCVNAWMLDLTQAILNLGFLTGAFTLGYAADRYGRIVIYLLSCLGVGVTGVVV 199
Cdd:cd17379    1 SMLPLSPCQDGWVYNTPRSSIVTEFNLVCEDAWKLDLFQSSLNLGFLIGSIVIGYLADRFGRKVCFLISILGNGVSGVLM 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383981 200 AFAPNFPVFVIFRFLQGVFGKGTWMTCYVIVTEIVGSKQRRIVGIVIQMFFTLGIIILPGIAYFIPNWQGIQLAITLPSF 279
Cdd:cd17379   81 AFSPNYPWFLIFRFLQGLFGKGGWMTGYVLVTEFVGSKYRRTVGIVYQMFFTLGLLILPGIAYFIPHWRWLQLAVTLPNF 160

                        170
                 ....*....|
gi 530383981 280 LFLLYYWVVP 289
Cdd:cd17379  161 LFLLYYWFIP 170

Organic anion transporters of the Major Facilitator Superfamily of transporters; Organic anion transporters (OATs) generally display broad substrate specificity and they facilitate the exchange of extracellular with intracellular organic anions (OAs). Several OATs have been characterized including OAT1-10 and urate anion exchanger 1 (URAT1, also called SLC22A12). Many OATs occur in renal proximal tubules, the site of active drug secretion. OATs mediate the absorption, distribution, and excretion of a diverse array of environmental toxins, and clinically important drugs, including anti-HIV therapeutics, anti-tumor drugs, antibiotics, anti-hypertensives, and anti-inflammatories, and therefore is critical for the survival of the mammalian species. OAT falls into the SLC22 (solute carrier 22) family of 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 530383981 126 PCRGGWRYAQAH--STIVSEFDLVCVNAWMLDLTQAILNLGFLTGAFTLGYAADRYGRIVIYLLSCLGVGVTGVVVAFAP 203
Cdd:cd17374    7 PCVDGWVYDRSKftSTIVTEWDLVCESQSLKSVAQSIFMAGLLVGALIFGHLSDRFGRKFILLLSLLQLAIFGTCAAFAP 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383981 204 NFPVFVIFRFLQGVFGKGTWMTCYVIVTEIVGSKQRRIVGIVIQMFFTLGIIILPGIAYFIPNWQGIQLAITLPSFLFLL 283
Cdd:cd17374   87 TFPVYCVLRFLAGFAVSGISINTLILGTEWTTPRHRALAITLTSCFFSIGQMLLAGLAYAIRDWRLLQLVVSVPFFLFFL 166

                 ....*.
gi 530383981 284 YYWVVP 289
Cdd:cd17374  167 YSWWLP 172

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 530383981 126 PCRGGWRYAQA--HSTIVSEFDLVCVNAWMLDLTQAILNLGFLTGAFTLGYAADRYGRIVIYLLSCLGVGVTGVVVAFAP 203
Cdd:cd17376    7 PCLDGWEYSQDvyLSTIVTEWNLVCEDDWKVPLTTSLFFVGVLLGSFISGQLSDRFGRKKVLFATMAVQTGFSFLQIFSP 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383981 204 NFPVFVIFRFLQGVFGKGTWMTCYVIVTEIVGSKQRRIVGIV-IQMFFTLGIIILPGIAYFIPNWQGIQLAITLPSFLFL 282
Cdd:cd17376   87 SWEMFTVLFVIVGMGQISNYVVAFVLGTEILGKSVRILFSTLgVCIFYAIGYMLLPLFAYFIRDWRMLLLALTLPGVLCV 166

                 ....*..
gi 530383981 283 LYYWVVP 289
Cdd:cd17376  167 PLWWFIP 173

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 530383981 128 RGGWRYAQ-AHSTIVSEFDLVCVNAWMLDLTQAILNLGFLTGAFTLGYAAD-RYGRIVIYLLSCLGVGVTGVVVAFAPNF 205
Cdd:cd17378    8 RSSWEWDGgSKVSIVSEWGLICAGSFLVGLPQSSFFVGCLIGSGVLGHLADsSLGRKNLLFLSCLLMALSGIATAFSPNY 87

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 530383981 206 PVFVIFRFLQGVFGKGTWMTCYVIVTEIVGSKQRRIVGIVIQMFFTLGIIILPGIAYFIPN-WQGIQLAITLPSFLFLL 283
Cdd:cd17378   88 WVYAFLRFLTGFGRSGIGTCALVLATEPVGPKWRGQVGMSTFFFFVLGFMSLPGIAYLNGSsWRVLYFWTSIPALIYCI 166

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 530383981 140 IVSEFDLVCVNAWMLDLTQAILNLGFLTGAFTLGYAADRYGRIVIYLLSCLGVGVTGVVVAFAPNFPVFVIFRFLQGVFG 219
Cdd:cd17373   13 AVSKWDLVCDNGWKVHLEQFSLLLGLIFGYLILGCIADRFGRRPVLLFSLILILIFGLTVALAVSVTMFSTLRFLEGFCL 92

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530383981 220 KGTWMTCYVIVTEIVGSKQRRIVGIVIQMFFTLGIIILPGIAYFIPNWQGIQLAITLPSFLFLLYYWVVPES 291
Cdd:cd17373   93 AGIILTLYLLRLELCDPGKRLMITMVASLVAVAGQFLMPGLAALCRDWRVLQALIICPFLLMLLYWSIFPKN 164

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 530383981 127 CRGGWRYAQA---HSTIVSEFDLVCVNAWMLDLTQAILNLGFLTGAFTLGYAADRYGRIVIYLLSCLGVGVTGVVVAFAP 203
Cdd:cd17445    8 CDAGWNYTGLpglTNNIVTEWDLVCSRYWLVPLEQVCFILGFASGYLCLGYTADRLGRRRTLLLSLTLAVPFGVLVAVAA 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383981 204 NFPVFVIFRFLQGVFGKGTWMTCYVIVTEIVGSKQRRIVGIVIQMFFTLGIIILPGIAYFIPNWQGIQLAITLPSFLFLL 283
Cdd:cd17445   88 SPSLFMAMRFLLGAALAGVYLTLYLTRLELCDPPQRLLVAMAGGLTMVGGHFLLLGLALGCGSWRVLQGTITAPLSLFLC 167

                 ...
gi 530383981 284 YYW 286
Cdd:cd17445  168 YGC 170

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 530383981 133 YAQAHSTIVSEFDLVCVNAWMLDLTQAILNLGFLTGAFTLGYAADRYGRIVIYLLSCLGVGVTGVVVAFAPNFPVFVIFR 212
Cdd:cd17377   20 FSSSFTSIVSEWFLVGNAAYKVSLASSFFFAGVLIGVVSFGQLSDRFGRKPVYLTGLALDILFAYFNALAPSYEFFAVSR 99

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530383981 213 FLQGVFGKGTWMTCYVIVTEIVGSKQRRIVGIVIQMFFTLGIIILPGIAYFIPNWQGIQLAITLPSFLFLLYYWVVP 289
Cdd:cd17377  100 FLVGVMNGGMSLVAFVLLNECVGKSYWALAGSLGGLFFAVGIAQYALLGYFIRSWRTLAVVVNLQGTLVFLLSLFIP 176

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383981 138 STIVSEFDlvcVNAWMLDLTQAILNLGFLTGAFTLGYAADRYGRIVIYLLSCLGVGVTGVVVAFAPNFPVFVIFRFLQGV 217
Cdd:COG2814   34 PLIAADLG---ASPAQAGLVVTAYLLGAALGAPLAGRLADRFGRRRVLLLGLLLFALGSLLCALAPSLWLLLAARFLQGL 110

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383981 218 FGKGTWMTCYVIVTEIVGSKQRRIVGIVIQMFFTLGIIILPGIAYFIPN---WQGIQLAITLPSFLFLLY-YWVVPESPR 293
Cdd:COG2814  111 GAGALFPAALALIADLVPPERRGRALGLLGAGLGLGPALGPLLGGLLADlfgWRWVFLVNAVLALLALLLlLRLLPESRP 190

                        170
                 ....*....|....*..
gi 530383981 294 WLITRKKGDKALQILRR 310
Cdd:COG2814  191 AARARLRGSLRELLRRP 207

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 530383981 133 YAQAHSTIVSEFDLVcVNAWMLDLTQAILNLGFLTGAFTLGYAADRYGRIVIYLLSCLGVGVTGVVVAFAPNFPVFVIFR 212
Cdd:cd17316   18 IGFVAPVLAAEFSLG-LSLLQTGLLFAAGFLGRPIGALLFGYLGDRIGRKKALILTLLLFGLATLLIGLLPTPILLLVLR 96

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 530383981 213 FLQGVFGKGTWMTCYVIVTEIVGSKQRRIVGIVIQMFFTLGIIILPGIAYFI 264
Cdd:cd17316   97 FLQGIGIGGEYPGASTYVAEFAPSKRRGFALGLLQSGWALGALLAALVASLL 148

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383981  133 YAQAHSTIVSEFDLVCVNAWMLdLTQAILnlGFLTGAFTLGYAADRYGRIVIYLLSCLGVGVTGVVVAFAPNFPVFVIFR 212
Cdd:TIGR00895  36 MGFAAPAISAEWGLDPVQLGFL-FSAGLI--GMAFGALFFGPLADRIGRRRVLLWSILLFSVFTLLCALATNVTQLLILR 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383981  213 FLQGVFGKGTWMTCYVIVTEIVGSKQRRIVGIVIQMFFTLGIIILPGIAYF-IPN--WQGI-QLAITLPSFLFLLYYWVV 288
Cdd:TIGR00895 113 FLAGLGLGGLMPNLNALVSEYAPKRFRGTAVGLMFCGYPIGAAVGGFLAGWlIPVfgWRSLfYVGGIAPLLLLLLLMRFL 192

                         170       180
                  ....*....|....*....|....
gi 530383981  289 PESPRWLItRKKGDKALQILRRIA 312
Cdd:TIGR00895 193 PESIDFLV-SKRPETVRRIVNAIA 215

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 530383981 159 AILNLGFLTGAFTLGYAADRYGRIVIYLLSCLGVGVTGVVVAFA---PNFPVFVIFRFLQGVFGKGTWMTCYVIVTEIVG 235
Cdd:cd17357   56 SIFFIGGAIGSFISAFLANRFGRKNGLLISNALLVVSSLLMFLSksaKSPELLIFGRFLVGIACGLSTGFVPMYLQEISP 135

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383981 236 SKQRRIVGIVIQMFFTLGIII-----LPGIAYFIPNWQGIQLAITLPSFLFLLYYWVVPESPRWL-ITRKKGDKALQILR 309
Cdd:cd17357  136 SELRGALGSLTQIGVTLGILLgqvfgLPSVLGTETLWPYLLFFPGIPALLQLAALPFFPESPKFLlISKGDEEEAEKSLK 215

                 .
gi 530383981 310 R 310
Cdd:cd17357  216 F 216

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 530383981 149 VNAWMLDLTQAILNLGFLTGAFTLGYAADRYGRIVIYLLSCLGVGVTGVVVAFAPNFPVFVIFRFLQGVFGKGTWMTCYV 228
Cdd:cd06174   28 LSASQLGLLFALFSLGYALLQPLAGLLADRFGRRPVLLLGLLLFALGALLFAFAPSFWLLLLGRFLLGLGSGLIDPAVLA 107

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383981 229 IVTEIVGSKQRRIVGIVIQMFFTLGIIILPGIAYFIP-----NWQGIQLAITLPSFLFLLYYWVVPESPRWLITRKKGDK 303
Cdd:cd06174  108 LIADLFPERERGRALGLLQAFGSVGGILGPLLGGILAsslgfGWRAVFLIAAALALLAAILLLLVVPDPPESARAKNEEA 187

                        170
                 ....*....|....*
gi 530383981 304 ALQILRRIAKCNGKY 318
Cdd:cd06174  188 SSKSVLKLLKRVLKN 202

Cis,cis-muconate transport protein and similar proteins of the Major Facilitator Superfamily; This subfamily is composed of Acinetobacter sp. Cis,cis-muconate transport protein (MucK), Escherichia coli putative sialic acid transporter 1, and similar proteins. MucK functions in the uptake of muconate and allows Acinetobacter calcoaceticus ADP1 (BD413) to grow on exogenous cis,cis-muconate as the sole carbon source. The MucK 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 530383981 163 LGFLTGAFTLGYAADRYGRIVIYLLSCLGVGVTGVVVAFAPNFPVFVIFRFLQGVFGKGTWMTCYVIVTEIVGSKQRRIV 242
Cdd:cd17371   45 AGGAIGGILGGILADRFGRVRVLVITILLFAVFTLLCGFAQNYWQLLILRALAGLGFGGEWAAGAALMAEYVPARHRGKA 124

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 530383981 243 GIVIQMFFTLGIIILPGIAYFI-------PNWQGIQLAITLPSFLFLLYYWVVPESPRWLITRKKG 301
Cdd:cd17371  125 LGYVQSGWAVGWLLATLLAALLfpllppeIAWRVLFLLGALPALLVLFIRRFVKEPPQWQAARAAR 190

MFS transporter, sugar porter (SP) family; This model represent the sugar porter subfamily of the major facilitator superfamily (pfam00083) [Transport and binding proteins, Carbohydrates, organic alcohols, and acids]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383981  156 LTQAILNLGFLTGAFTLGYAADRYGRIVIYLLSCLGV---GVTGVVVAFAPNFPVFVIFRFLQGVFGKGTWMTCYVIVTE 232
Cdd:TIGR00879  75 LVVSIFLVGGFIGALFAGWLSDRFGRKKSLLIIALLFvigAILMGLAAFALSVEMLIVGRVLLGIGVGIASALVPMYLSE 154

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383981  233 IVGSKQRRIVGIVIQMFFTLGIIILPGIAY--FIPN----WQGIQLAITLPSFLFLLYYWVVPESPRWLITRKKGDKALQ 306
Cdd:TIGR00879 155 IAPKALRGALTSLYQLAITFGILVAYGFGSgkVSLNntlgWRIPLGLQLIPAGLLFLGLFFLPESPRWLVGKGRVEEARK 234

                  ....*
gi 530383981  307 ILRRI 311
Cdd:TIGR00879 235 SLARL 239

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 530383981 163 LGFLTGAFTL---------GYAADRYGRIVIYLLSCLGVGVTGVVVAFAPNFPVFVIFRFLQGVFGKGTWMTCYVIVTEI 233
Cdd:cd17325   33 IGLIVAAYALaqllfsppaGRLSDRFGRKRLLLLGLLLLAVSTLLFAFATSYWQLLLARFLQGLASAAVWPAAMALIADI 112

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530383981 234 VGSKQRRIVGIVIQMFFTLGIIILPGIAYFIPNWQGIQ----LAITLPSFLFLLYYWVVPESPR 293
Cdd:cd17325  113 APPEERGRAMGIFSSAIGLGFLIGPLLGGLLADALGYRapflVCAALALLALVLALLLLPEPRP 176

Synaptic vesicle glycoprotein 2 of the Major Facilitator Superfamily of transporters; Synaptic vesicle glycoprotein 2 (SV2) is a transporter-like integral membrane glycoprotein, with 12 transmembrane regions, expressed in vertebrates and is localized to synaptic and endocrine secretory vesicles. Three isoforms have been identified, SV2A, SV2B, and SV2C. SV2A and SV2B are widely expressed in the brain, while SV2C is more restricted to evolutionarily older brain. SV2 isoforms have been shown to be critical for the proper function of the central nervous system. SV2 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. The SV2 family 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 530383981 160 ILNLGFLTGAFTLGYAADRYGRIVIYLLSCLGVGVTGVVVAFAPNFPVFVIFRFLQGVFGKGTWMTCYVIVTEIVGSKQR 239
Cdd:cd17363   42 IVYLGMMVGAFVWGGLADKLGRKQCLLIALSVNGVFAFLSSFVQGYGFFLFCRLLSGIGIGGSIPIVFSYFAEFLAREKR 121

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383981 240 RIVGIVIQMFFTLGII--------ILP--------GIAYFIPNWQGIQLAITLPSFLFLLYYWVVPESPRWLITRKKGDK 303
Cdd:cd17363  122 GEHLSWLCMFWMIGGLyasamawaIIPhygwgfsmGTAYQFHSWRVFVIVCALPSVASVVALTFMPESPRFLLEVGKHDE 201

                        170
                 ....*....|..
gi 530383981 304 ALQILRRIAKCN 315
Cdd:cd17363  202 AWMILKQVHDTN 213

Multidrug transporter MdfA and similar multidrug resistance (MDR) transporters of the Major Facilitator Superfamily; This family is composed of bacterial multidrug resistance (MDR) transporters including several proteins from Escherichia coli such as MdfA (also called chloramphenicol resistance pump Cmr), EmrD, MdtM, MdtL, bicyclomycin resistance protein (also called sulfonamide resistance protein), and the uncharacterized inner membrane transport protein YdhC. EmrD is a proton-dependent secondary transporter, first identified as an efflux pump for uncouplers of oxidative phosphorylation. It expels a range of drug molecules and amphipathic compounds across the inner membrane of E. coli. Similarly, MdfA is a secondary multidrug transporter that exports a broad spectrum of structurally and electrically dissimilar toxic compounds. These MDR transporters are drug/H+ antiporters (DHA) belonging 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 530383981 163 LGFLTGAFTLGYAADRYGR-------IVIYLLSCLGVgvtgvvvAFAPNFPVFVIFRFLQGVFGKGTWMTCYVIVTEIVG 235
Cdd:cd17320   45 LGFALGQLLYGPLSDRFGRrpvllagLLLFILASLLC-------ALASSIEQLLIARFLQGLGAAAGSVVARAIVRDLYS 117

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530383981 236 SKQRRIVGIVIQMFFTLGIIILPGI-----AYFipNWQGIQLAITLPSF-LFLLYYWVVPESP 292
Cdd:cd17320  118 GAELAKIFSLLMMILAIAPALAPLLgglllLFF--GWRAIFVFLALLGLlLLLLVLLFLPETL 178