3O7P,1PW4,2Y5Y,4GBY,4GC0,4J05,4LEP,4M64,4OAA,4U4T,4ZOW,4ZP0,4ZW9,5A2N,5AYM,5EQG


Conserved Protein Domain Family
MFS

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cd06174: MFS 
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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.
Statistics
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PSSM-Id: 349949
View PSSM: cd06174
Aligned: 86 rows
Threshold Bit Score: 45.8806
Threshold Setting Gi: 835020571
Created: 9-Jul-2008
Updated: 11-Jul-2018
Structure
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Program:
Drawing:
Aligned Rows:
 
putative
Conserved site includes 35 residues -Click on image for an interactive view with Cn3D
Feature 1:putative chemical substrate binding pocket [chemical binding site]
Evidence:
  • Comment:based on the structures of MFS transporters with bound substrates, substrate analogs, and/or inhibitors
  • Comment:since MFS proteins facilitate the transport of many different substrates including ions, sugar phosphates, drugs, neurotransmitters, nucleosides, amino acids, and peptides, the residues involved in substrate binding may not be strictly conserved among superfamily members
  • Comment:the substrate binding site or translocation pore has access to both sides of the membrane in an alternating fashion through a conformational change of the MFS transporter
  • Structure:3O7P; Escherichia coli FucP binds B-nonylglucoside; contacts at 5A
    View structure with Cn3D
  • Structure:4OAA; Escherichia coli Lactose permease binds high-affinity lactose analog; contacts at 5A
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  • Structure:4ZP0; Escherichia coli MdfA binds deoxycholate; contacts at 5A
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  • Structure:4ZOW; Escherichia coli MdfA binds chloramphenicol; contacts at 5A
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  • Structure:4GBY; Escherichia coli Proton:xylose symporter XylE binds D-xylose; contacts at 5A
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  • Structure:4GC0; Escherichia coli Proton:xylose symporter XylE binds 6-bromo-6-deoxy-D-glucose; contacts at 5A
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  • Structure:4J05; Serendipita indica Phosphate transporter binds inorganic phosphate; contacts at 5A
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  • Structure:4LEP; Shewanella oneidensis proton dependent oligopeptide transporter in complex with the peptidomimetic alafosfalin; contacts at 5A
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  • Structure:2Y5Y; Escherichia coli LacY binds affinity inactivator; contacts at 5A
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  • Structure:4ZW9; Human Glut3 binds D-glucose; contacts at 5A
    View structure with Cn3D
  • Structure:5EQG; Human GLUT1 binds inhibitor; contacts at 5A
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1            ##  ##  #                                  #                             
3O7P_A     31 LCSLFFLWAVANNLNDILLPqfqqaf---tltnfqAGLIQSAFYFGYFIIPIPAGILMKkls-ykaGIITGLFLYALGAA 106 Escherichia coli K-12
4U4T_A     41 SVPCLLLAFCVWMLFSAVAVnlpkvgf--nfttdqLFMLTALPSVSGALLRVPYSFMVPifg-grrWTAFSTGILIIPCV 117 Escherichia coli s...
P25621     41 VCLQYWINYVDRVGFTNAYIsgmkedl--kmvgndLTVSNTVFMIGYIVGMVPNNLMLLcvp-priWLSFCTFAWGLLTL 117 baker's yeast
P77726     17 LGTVFSLRMLGMFMVLPVLTtygmalq--gasealIGIAIGIYGLTQAVFQIPFGLLSDrig-rkpLIVGGLAVFAAGSV 93  Escherichia coli K12
NP_215357  28 LLGGNLLVRSAGFGYPFLAYhvagrg----hgagaVGAVVAAYGLGWAVGQLLCGWLVDrvg-arvTLVSTMLVAAAVLV 102 Mycobacterium tube...
Q86WB7     11 VSFGFLLLFTAYGGLQSLQSslys-------eeglGVTALSTLYGGMLLSSMFLPPLLIerlgckgTIILSMCGYVAFSV 83  human
Q7RTY1     16 VFVSFLTQFLCYGSPLAVGVlyiewldafgegkgkTAWVGSLASGVGLLASPVCSLCVSsfg-arpVTIFSGFMVAGGLM 94  human
P95827     14 IWAGQAVSLITSAILQMAIIfyltek---tgsamvLSMASLLGFLPYAVFGPAIGVLVDrhd-rkkIMIGADLIIAAAGS 89  Streptococcus
Q9L8Q4     21 AMGMPMMIFYAIGILGPHLVadlgi------srqqLGWLTASTFGLAALLSPWAGALVQrmg-traGLICMFLLVGLSFS 93  Pseudomonas stutzeri
A7ZZ23     15 LLIDNMLVVLGFFVVFPLISirfvdqm--gwaavmVGIALGLRQFIQQGLGIFGGAIADrfg-akpMIVTGMLMRAAGFA 91  Escherichia coli HS
Feature 1                               ## ###  #                                 #  ##  #    
3O7P_A    107 Lfwpaaei--mnytlfLVGLFIIAAGLGCLETAANPFvtvlgpess--------------ghfrlnlaQTFASFGAIIAV 170 Escherichia coli K-12
4U4T_A    118 WlgfavqdtstpysvfIIISLLCGFAGANFASSMANIsfffpkqk---------------qggalglnGGLGNMGVSVMQ 182 Escherichia coli s...
P25621    118 Gmykvt-----sfkhiCAIRFFQALFESCTFSGTHFVlgswykede--------------lpirsaifTGSGLVGSMFSG 178 baker's yeast
P77726     94 Iaalsd-----siwgiILGRALQGSGAIAAAVMALLSdltreqnrtk------------amafigvsfGITFAIAMVLGP 156 Escherichia coli K12
NP_215357 103 Lmaglh-----tvpglLVGAMIAGLVCDAPRPVLGAViaelvadpqrra--------qldgwrygwvlNIGAAITGGVGG 169 Mycobacterium tube...
Q86WB7     84 Gnffas------wytlIPTSILLGLGAAPLWSAQCTYltitgnthaekagkrgkdmvnqyfgifflifQSSGVWGNLISS 157 human
Q7RTY1     95 Lssfapn----iyflfFSYGIVVGLGCGLLYTATVTItcqyfddr---------------rglalgliSTGSSVGLFIYA 155 human
P95827     90 VltivafymelpvwmvMIVLFIRSIGTAFHTPALNAVtpllvpeeq--------------ltkcagysQSLQSISYIVSP 155 Streptococcus
Q9L8Q4     94 Lmavlp-----gfgglVTALLLCGTAQSLANPATNQAiahsvpvar--------------kagvvglkQSGVQASALLAG 154 Pseudomonas stutzeri
A7ZZ23     92 Tmgiah-----epwllWFSCLLSGLGGTLFDPPRSALvvklirpqq--------------rgrffsllMMQDSAGAVIGA 152 Escherichia coli HS
Feature 1                                                                                     
3O7P_A    171 VFGQSLilsnvphqsqdvldkm--------speqlsaykhslvlsvQTPYMIIVAIVLLVALLImltkfpalqsdnhsda 242 Escherichia coli K-12
4U4T_A    183 LVAPLVvslsifavfgsq----------------gvkqpdgtelylANASWIWVPFLAIFTIAAwfgmndlatska---- 242 Escherichia coli s...
P25621    179 FMQTSIfthlngr---------------------------nglagwRWLFIIDFCITLPIAIYGfiffpglpdqtsavsk 231 baker's yeast
P77726    157 IITHKLg--------------------------------------lHALFWMIAILATTGIALTiwvvpnssthvlnre- 197 Escherichia coli K12
NP_215357 170 VVAGWLd--------------------------------------tPVLYWINGIGCAIFAGLAgrcipadvcrrtesgl 211 Mycobacterium tube...
Q86WB7    158 LVFGQTpsqetlpeeqltscgasdclmattttnstqrpsqqlvytlLGIYTGSGVLAVLMIAAFlqpirdvqresegekk 237 human
Q7RTY1    156 ALQRMLvef----------------------------------yglDGCLLIVGALALNILACGslmrplqssdcplpkk 201 human
P95827    156 AVAALLysv----------------------------------welNAIIAIDVLGAVIASITVaivripklgdrvqsld 201 Streptococcus
Q9L8Q4    155 VALPPLvlm----------------------------------wgwRGALAAWVPVALVMAALVtywvpaksvsa----- 195 Pseudomonas stutzeri
A7ZZ23    153 LLGSWLlqy-----------------------------------dfRLVCATGAVLFVLCAAFNawllpawklstvr--- 194 Escherichia coli HS
Feature 1                                                                                     
3O7P_A        --------------------------------------------------------------------------------     Escherichia coli K-12
4U4T_A        --------------------------------------------------------------------------------     Escherichia coli s...
P25621    232 fsmtryifneqe--------------------------------------------------------------lhyarr 249 baker's yeast
P77726        --------------------------------------------------------------------------------     Escherichia coli K12
NP_215357 212 r------------------------------------------------------------------------------- 212 Mycobacterium tube...
Q86WB7    238 s------------------------------------------------------------------------------- 238 human
Q7RTY1    202 iapedlpdkysiynekgknleeninildksysseekcritlangdwkqdsllhknptvthtkepetykkkvaeqtyfckq 281 human
P95827    202 p------------------------------------------------------------------------------- 202 Streptococcus
Q9L8Q4        --------------------------------------------------------------------------------     Pseudomonas stutzeri
A7ZZ23        --------------------------------------------------------------------------------     Escherichia coli HS
Feature 1                                    #  ##  ###  #                            #   #   
3O7P_A    243 -------kqgsfsaslsrlariRHWRWAVLAQFCYVGAQTACWSYLiryaveeipgmtagfaanYLTGTMVCFFIGRFTG 315 Escherichia coli K-12
4U4T_A    243 -----------sikeqlpvlkrGHLWIMSLLYLATFGSFIGFSAGFamlsktqf---pdvqilqYAFFGPFIGALARSAG 308 Escherichia coli s...
P25621    250 rlpardestrldwstiprvlkrWHWWMFSLVWVLGGENLGFASNSTfalwlqnqk-ytlaqrnnYPSGIFAVGIVSTLCS 328 baker's yeast
P77726    198 --------sgmvkgsfskvlaePRLLKLNFGIMCLHILLMSTFVALpgqladag--fpaaehwkVYLATMLIAFGSVVPF 267 Escherichia coli K12
NP_215357 213 ------actamskvgyrqalsdKRLVLLAVSGLATLTTLMGFFAAVpmlmsasg--lgvgaygwVQLINALAVVAVTPLL 284 Mycobacterium tube...
Q86WB7    239 ------vpfwstllstfklyrdKRLCLLILLPLYSGLQQGFLSSEYtrsyvtct--lgiqfvgyVMICFSATDALCSVLY 310 human
Q7RTY1    282 lakrkwqlyknycgetvalfknKVFSALFIAILLFDIGGFPPSLLMedvarssnv-keeefimpLISIIGIMTAVGKLLL 360 human
P95827    203 ------nfiremqegmavlrqnKGLFALLLVGTLYMFVYMPINALFplismdy-----fngtpvHISITEISFASGMLIG 271 Streptococcus
Q9L8Q4    196 -----------pslplrvrgpnVWLSILMAIQLCAGLALSSFMTFLgvyaaqig--vsvstigaMVSCFGAMGILSRVLL 262 Pseudomonas stutzeri
A7ZZ23    195 ---------tpvregmtrvmrdKRFVTYVLTLAGYYMLAVQVMLMLpimvndva--gapsavkwMYAIEACLSLTLLYPI 263 Escherichia coli HS
Feature 1                                                             ##   #   #              
3O7P_A    316 TWLisr---fapHKVLAAYALIAMALCLIsafagghv---------glialtlCSAFMSIQYPTIFSLgiknl------- 376 Escherichia coli K-12
4U4T_A    309 GALsdr----lgGTRVTLVNFILMAIFSGllfltlptdgqggsfmaffavflaLFLTAGLGSGSTFQMisvifrkltmdr 384 Escherichia coli s...
P25621    329 AVYmski--praRHWHVSVFISLVMVIVAvliradpln------pkvvfsaqyLGGVAYAGQAVFFSWaniicha----- 395 baker's yeast
P77726    268 IIYaev---krkMKQVFVFCVGLIVVAEIvlwnaq-------------tqfwqLVVGVQLFFVAFNLMeallpslis--- 328 Escherichia coli K12
NP_215357 285 TPWlskqlalgpRPDILAGAGVWVTLCMAaaglartt--------vgfsvaaaACSPGEIAWFVVAAGivhria------ 350 Mycobacterium tube...
Q86WB7    311 GKVsqy----tgRAVLYVLGAVTHVSCMIalllwrp-----------radhlaVFFVFSGLWGVADAVwqtqnnaly--- 372 human
Q7RTY1    361 GILadfk--winTLYLYVATLIIMGLALCaipfaksyv-------tlallsgiLGFLTGNWSIFPYVTtktvg------- 424 human
P95827    272 GLLlglfgnyqkRILLITASIFMMGISLTisgllpqsgf-----fifvvccaiMGLSVPFYSGVQTALfqekik------ 340 Streptococcus
Q9L8Q4    263 TPIadk---lkdETILLGVLFILAGLALAvmreantqqh-----wplwlgvtgMGLTVAASNAIAMSMllrdgr------ 328 Pseudomonas stutzeri
A7ZZ23    264 ARWsek---hfrLEHRLMAGLLIMSLSMMpvgmvsglq-------qlfnliclFYIGSIIAEPARETLsaslad------ 327 Escherichia coli HS
Feature 1                           #  ##  ##  #                                           
3O7P_A    377 ---------------gqdtkYGSSFIVMTIIGGGIVTPVmgfvs--------daagnIPTAELIPALCFAVIFIFAR 430 Escherichia coli K-12
4U4T_A    385 vkaeggsderamreaatdtaAALGFISAIGAIGGFFIPKafgssl-------altgsPVGAMKVFLIFYIACVVITW 454 Escherichia coli str....
P25621    396 --------------dlqeraIVLASMNMFSGAVNAWWSIlffas--------dmvpkFERGCYALLATAISSGIVSV 450 baker's yeast
P77726    329 -----------kespagykgTAMGVYSTSQFLGVAIGGSlggwi--------ngmfdGQGVFLAGAMLAAVWLTVAS 386 Escherichia coli K12
NP_215357 351 --------------ppahggRYHGIWSMAVAASSVAAPIlaafnlanggrlvlaattVTVGFFGAALCLPLARVLAA 413 Mycobacterium tubercu...
Q86WB7    373 -----------gvlfekskeAAFANYRLWEALGFVIAFGysm------------flcVHVKLYILLGVLSLTMVAYG 426 human
Q7RTY1    425 ---------------ieklaHAYGILMFFAGLGNSLGPPivgwfy-------dwtqtYDIAFYFSGFCVLLGGFILL 479 human
P95827    341 ---------------peylgRVFSLTGSIMSLAMPIGLIlsalf--------adrigVNHWFLLSGTLIICIAIVCP 394 Streptococcus
Q9L8Q4    329 ---------------fggaaTSAGMLSVGFFGGFAVGPPafgwfl-------ahsegFAAAWLSLIGILVAGGLLCL 383 Pseudomonas stutzeri
A7ZZ23    328 ---------------arargSYMGFSRLGLAIGGAIGYIgggwlfd----lgksahqPELPWMMLGIIGIFTFLALG 385 Escherichia coli HS

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