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cd06174: MFS 
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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.
BioAssay Targets and Results
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CID: 15925918
AID: 216228
GI: 34924880
IC50: 5.5e-005µM
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In vitro binding affinity to vesamicol receptor using [3H]vesamicol.
Target Name: Vesicular acetylcholine transporter
Chemical Name: BENZOVESAMICOL
IC50: 5.5e-005µM
CID: 10019050
AID: 216228
GI: 34924880
IC50: 6.5e-006µM
more
In vitro binding affinity to vesamicol receptor using [3H]vesamicol.
Target Name: Vesicular acetylcholine transporter
Chemical Name: CHEMBL87381
IC50: 6.5e-006µM
CID: 10096519
AID: 216228
GI: 34924880
IC50: 5e-005µM
more
In vitro binding affinity to vesamicol receptor using [3H]vesamicol.
Target Name: Vesicular acetylcholine transporter
Chemical Name: CHEMBL86366
IC50: 5e-005µM
Statistics
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PSSM-Id: 119392
View PSSM: cd06174
Aligned: 440 rows
Threshold Bit Score: 39.2193
Threshold Setting Gi: 75419378
Created: 9-Jul-2008
Updated: 17-Jan-2013
Structure
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Program:
Drawing:
Aligned Rows:
Hierarchy
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putative
Conserved site includes 51 residues -Click on image for an interactive view with Cn3D
Feature 1:putative substrate translocation pore
Evidence:
  • Comment:based on the structure of Escherichia coli lactose permease.
  • Comment:substrates bind at the substrate translocation pore, which has access to both sides of the membrane in an alternating fashion through a conformational change of the MFS.
  • Comment:since MFS proteins facilitate the transport of many different substrates, the residues involved in substrate binding may not be strictly conserved among superfamily members.
  • Structure:1PV7_A; Escherichia coli Lactose Permease binds the substrate homolog TDG; defined at 5A contacts
    View structure with Cn3D

cd06174 is part of a hierarchy of related CD models.
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cd06174 is a member of the superfamily cl18950.
cd06174:MFS1PW4 A585209997918813677039137188162293984029415817593647496037582180880821253709973270821877148162249675426912815924915868198181035385690756117013281622369767402281761985745761488162113676363851746386291723769135171440334817542834959799780140479172367473129874626927118233746272363134049374676557752626297522024229428061484286888218476218766397973222974844451249805674957183187608848749594184760554074947906731995250726828298021172741548630821988077472828175097623751862198218028574733566821883908568756613467102715173013177174654864250741925009397388471448890011238981257475100715211230712388864374762099448890518220974074750790504011207475047419035221089282571662150498218133282185960747305875868446176591668632651704320517042346093708549755738789073884567387918313402363916012250093458668581174989811710698402949911647973093867477413250093672978412230093134629046397785171156112593511759465980253884029535134613720177811172361282237277747626158223645551316137753312055444461708578321981211857310884028324215424582851499117940085117940084173666851217601217595863681504215651179401781185722937467659613464931731015249682674738207821863488219280146396053463970857454972312389882612401515881635585815562881171655134582375450214250699930251405868128155107617069167467362074630590586703549759173077374645014622694313432183622570874723222821927878218400174738645747232237557129311415284116621898362257068151334374549602745579921400432154216781345609754735528181342374549737732089815923978143977581776801817402828173593375426674418476249565574549728816223077546894081786306731351816225388159115981776797755283992GFP A816107784168096039011381493813331126337320945404232581635441201404505864691351702746272357462673874626725731655746763967463863431231841708281586312746390058181099474627205135546817868568162053117307418181227475426101817644382017820116620006020139967152032623754276268162370381759567732369754889352053230281621373586828250745081623108816220118162478375448655816212288162576139159908159586781620530754275938150332984027815816224712507449817936577309081272092665388154741860392976201417371172762815562665440457545127913634050814997822828202250116419862871746304357463900325091408549651135169012172795775426150815498747462724774630455170375781761826816387378162160775419378754214251148517463837751316579513164395131657073161628426885131649874938574748716108117064181170644747326362V8N A2CFQ A1PV7 A2319143025166816211207323368166927181764437745579988328776681590605613645839155167457033174551853745521714101842410886077674870233309231977455155273092481550827817913647496366574735668832883331587061337496412674730313821844671239119881670089948177806517310828162290025066708162619681592759745760837457592381762324816200358162195781623319816233443269988974576176134322788155584928516768185038581772184123148220817620147456331674552261817881771617843125597787081592814816377388176028275016840747489757462691734924885349248773492487346499841018444745492867289707452432175425935471173598178813981785407745711978163751381672474754643587542625224967468179373774575184816201571229908564842922614038881590405754496547457349311752168176264882186846158706134749627907502855167462027674620406746206667462083625112208179100511769908162513575467969736196297463041015203261612059388911328816211892820190720140512740440861366758155599061366747544962081531714767444376739891PW4 A585209997918813677039137188162293984029415817593647496037582180880821253709973270821877148162249675426912815924915868198181035385690756117013281622369767402281761985745761488162113676363851746386291723769135171440334817542834959799780140479172367473129874626927118233746272363134049374676557752626297522024229428061484286888218476218766397973222974844451249805674957183187608848749594184760554074947906731995250726828298021172741548630821988077472828175097623751862198218028574733566821883908568756613467102715173013177174654864250741925009397388471448890011238981257475100715211230712388864374762099448890518220974074750790504011207475047419035221089282571662150498218133282185960747305875868446176591668632651704320517042346093708549755738789073884567387918313402363916012250093458668581174989811710698402949911647973093867477413250093672978412230093134629046397785171156112593511759465980253884029535134613720177811172361282237277747626158223645551316137753312055444461708578321981211857310884028324215424582851499117940085117940084173666851217601217595863681504215651179401781185722937467659613464931731015249682674738207821863488219280146396053463970857454972312389882612401515881635585815562881171655134582375450214250699930251405868128155107617069167467362074630590586703549759173077374645014622694313432183622570874723222821927878218400174738645747232237557129311415284116621898362257068151334374549602745579921400432154216781345609754735528181342374549737732089815923978143977581776801817402828173593375426674418476249565574549728816223077546894081786306731351816225388159115981776797755283992GFP A816107784168096039011381493813331126337320945404232581635441201404505864691351702746272357462673874626725731655746763967463863431231841708281586312746390058181099474627205135546817868568162053117307418181227475426101817644382017820116620006020139967152032623754276268162370381759567732369754889352053230281621373586828250745081623108816220118162478375448655816212288162576139159908159586781620530754275938150332984027815816224712507449817936577309081272092665388154741860392976201417371172762815562665440457545127913634050814997822828202250116419862871746304357463900325091408549651135169012172795775426150815498747462724774630455170375781761826816387378162160775419378754214251148517463837751316579513164395131657073161628426885131649874938574748716108117064181170644747326362V8N A2CFQ A1PV7 A231914302516681621120732336816692718176443774557998832877668159060561364583915516745703317455185374552171410184241088607767487023330923197745515527309248155082781791364749636657473566883288333158706133749641267473031382184467123911988167008994817780651731082816229002506670816261968159275974576083745759238176232481620035816219578162331981623344326998897457617613432278815558492851676818503858177218412314822081762014745633167455226181788177161784312559778708159281481637738817602827501684074748975746269173492488534924877349248734649984101844474549286728970745243217542593547117359817881398178540774571197816375138167247475464358754262522496746817937377457518481620157122990856484292261403888159040575449654745734931175216817626488218684615870613474962790750285516746202767462040674620666746208362511220817910051176990816251357546796973619629746304101520326161205938891132881621189282019072014051274044086136675815559906136674754496208153171476744437673989
cd06174 Sequence Cluster
cd06174 Sequence Cluster
Sub-family Hierarchy
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CD Hierarchy
Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                     #  ### ##                       #  ##  #   ## ##                  
1PW4_A       30 FLGIFFGYAAYYLVRKNFALAMPYLVeqg--------fsRGDLGFALSGISIAYGFSKFIMGsvSDRSNPRv---FLPAG 98
1PV7_A        9 FWMFGLFFFFYFFIMGAYFPFFPIWLhdin------hisKSDTGIIFAAISLFSLLFQPLFGllSDKLGLRkyllWIITG 82
gi 2500934   24 ALGSFAGAVVDWYDFLLYGITAALVFnreffpqvspamgTLAAFATFGVGFLFRPLGGVIFGhfGDRLGRKr---MLMLT 100
gi 84029499  24 IVGASSGNLVEWFDFYVYSFCSLYFAhiffps-gntttqLLQTAGVFAAGFLMRPIGGWLFGriADKHGRKk---SMLLS 99
gi 81174989  11 VIATGIGNAMEWFDFGLYSYLAVIISknffsqvdndqlkLVFTFATFAIAFLLRPIGGIVFGiiGDKYGRKi---VLTTT 87
gi 7387890   16 FWACYSGWALDSFDMQMFSFLLPALTltw-------gltKAEVGVLGTVALVVTAIGGWGAGilSDRYGRAr---ILVLA 85
gi 81171069  27 ITAASLGNAMEWFDFGVYGFVAYALGkvffpg-adpsvqMVAALATFSVPFLIRPLGGLFFGmlGDKYGRQk---ILAIT 102
gi 586685    24 LVASLIGTAIEFFDFYIYATAAVIVFphiffpqgdptaaTLQSLATFAIAFVARPIGSAVFGhfGDRVGRKa---TLVAS 100
gi 7388456   13 LIGSAVGYGMDGFDLLILGFMLSAISadl-------nltPAQGGSLVTWTLIGAVFGGILFGalSDKYGRVr---VLTWT 82
gi 7387918   19 FLFAFLALLVDGADLMLLSYSLNSIKaef-------nlsTVEAGMLGSFTLAGMAIGGIFGGwaCDRFGRVr---IVVIS 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                             ##  ##  ##  #           ##  ##     #      
1PW4_A       99 LILAAAVMLfmgfvpw----atssiavMFVLLFLCGWFQGMGWPPCGRTMVhwwsqkerggIVSVWNCAHNVGGGIPPLL 174
1PV7_A       83 MLVMFAPFFififgpll---qynilvgSIVGGIYLGFCFNAGAPAVEAFIEkvsr--rsnfEFGRARMFGCVGWALGASI 157
gi 2500934  101 VWMMGIATAligilpsfstigwwapilLVTLRAIQGFAVGGEWGGAALLSVesapknkkafYSSGVQVGYGVGLLLSTGL 180
gi 84029499 100 VCMMCFGSLviaclpgyetigtwapalLLLARLFQGLSVGGEYGTSATYMSevavegrkgfYASFQYVTLIGGQLLALLV 179
gi 81174989  88 IILMAFSTLligvlptyneigvwapilLLLARVLQGFSTGGEYAGAMVYVAesspdrkrnsLGCGLEIGTLSGYIAASIL 167
gi 7387890   86 IIWFTLFGVlagfa--------qsyqqLLIARTLQGLGFGGEWAVGAALMAevidsrhrgkAIGFVQSGFALGWALAVVV 157
gi 81171069 103 IVIMSISTFciglipsydtigiwapilLLICKMAQGFSVGGEYTGASIFVAeyspdrkrgfMGSWLDFGSIAGFVLGAGV 182
gi 586685   101 LLTMGISTVvigllpgyatigifapllLALARFGQGLGLGGEWGGAALLATenapprkralYGSFPQLGAPIGFFFANGT 180
gi 7388456   83 ILLFAVFTGlcaia--------qgywdLLIYRTIAGIGLGGEFGIGMALAAeawparhrakAASYVALGWQVGVLGAALL 154
gi 7387918   89 ILTFSILTCglglt--------qsfiqFGVLRFFASLGLGSLYIACNTLMAeyvptkyrttVLGTLQAGWTVGYIVATLL 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                       
1PW4_A      175 FLLGmawfndw----haalymPAFCAILVALFAFAMMRDTpqscglppieeykndypddynekaeqeltakqifmqyvlp 250
1PV7_A      158 VGIMftin---------nqfvFWLGSGCALILAVLLFFAKtdapssatvanavgan----------hsafslklalelfr 218
gi 2500934  181 VSLIsmmttdeqflswgwripFLFSIVLVLGALWVRNGMEesaefeqqqhyqaaa------------kkripvieallrh 248
gi 84029499 180 VVVLqhtmeda----alrewgWRIPFALGAVLAVVALWLRrqldetsqqetral--------------keagslkglwrn 241
gi 81174989 168 VFALnisltetqlnswgwripFLLGMFLGLFGLYLRRKLEespiyeneqrelqkhp----------trepigvftlirfy 237
gi 7387890  158 ATLLlawlpke----mawrvaFWSGIIPALIVLFIRRHVKdssmferarqsrap--------------raslssvfnrky 219
gi 81171069 183 VVLIstivgeanfldwgwripFFIALPLGIIGLYLRHALEetpafqqhvdkleqgdre-----glqdgpkvsfkeiatky 257
gi 586685   181 FLLLswlltdeqfmswgwrvpFIFSAVLVIIGLYVRVSLHespvfekvakakkq--------------vkiplgtlltkh 246
gi 7388456  155 TPLLlphig--------wrgmFLVGIFPAFVAWFLRSHLHepeiftqkqtalstqssf------tdklrsfqllikdkat 220
gi 7387918  161 AGWLipdhg--------wrvlFYVAIIPVLMAVLMHFFVPepaawqqsrlapskqte-------tvktsafklifqdkrn 225
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                     #  ##  ##  #                 #   #   #  #   #                     
1PW4_A      251 nKLLWYIAIANVFVYLLRYGILDWSPtylkevk----hfaldkSSWAYFLYEYAGIPGTLLCgw----msDKVFRGnrg- 321
1PV7_A      219 qPKLWFLSLYVIGVSCTYDVFDQQFAnfftsffa-tgeqgtrvFGYVTTMGELLNASIMFFApl----iiNRIGGKn--- 290
gi 2500934  249 pGAFLKIIALRLCELLTMYIVTAFALnystqnmg-lprelflnIGLLVGGLSCLTIPCFAWLa-------DRFGRRr--- 317
gi 84029499 242 rRAFIMVLGFTAAGSLCFYTFTTYMQkylvnta----gmhanvASGIMTAALFVFMLIQPLIga----lsDKIGRRt--- 310
gi 81174989 238 yKDIIVCFVAVAFFNVTNYMVTAYLPsylegvi----klngttTSIMITCIMVIMIPLALMFgr----iaDRIGEKk--- 306
gi 7387890  220 aRTLALSSVLVIGLQAGCYAILVWLPslln---------qrqvAAGSMIVTVFIMAFGSFCGfavtadlsDRIGRRptl- 289
gi 81171069 258 wRSLLTCIGLVIATNVTYYMLLTYMPsylshnl----hysedhGVLIIIAIMIGMLFVQPVMgl----lsDRFGRRpfvl 329
gi 586685   247 vRVTVLGTFIMLATYTLFYIMTVYSMtfstaaapvglglprneVLWMLMMAVIGFGVMVPVAgl----laDAFGRRks-- 320
gi 7388456  221 sKISLGIVVLTSVQNFGYYGIMIWLPnflskql----gfsltkSGLWTAVTVCGMMAGIWIFgq----laDRIGRKp--- 289
gi 7387918  226 rNMFILWALTAGFLQFGYYGVNNWMPsylesel----gmkfkeMTAYMVGTYTAMILGKILAgf----maDKLGRRf--- 294
                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                            #  ##  #   ##  #                  ##  ##  #
1PW4_A      322 atGVFFMTLVTIATIVywmnp-----agnptVDMICMIVIGFLIYGPVMLIGLHalela-----pkkaaGTAAGFTGLFG 391
1PV7_A      291 -aLLLAGTIMSVRIIGssfa--------tsaLEVVILKTLHMFEVPFLLVGCFKyitsqf---evrfsaTIYLVCFCFFK 358
gi 2500934  318 -vYITGTLIGTLSAFPffma-------leaqSIFWIVFFSIMLANIAHDMVVCVqqpmftemfgasyrySGAGVGYQVAS 389
gi 84029499 311 -sMLCFGSLAAIFTVPilsalqnvsspyaafGLVMCALLIVSFYTSISGILKAEmfpa--------qvrALGVGLSYAVA 381
gi 81174989 307 -vFLIGLGGLILLSVVafslmql-qslffvsIGVLILGFFLSTYEATMPGSLPTmfyt-------hvryRALAITFNVSV 377
gi 7387890  290 ilLSVCAWIVTVSYMLlplnt------tltaILGFLVGFSAIGMFAALGPFLSElfpt--------nvrTTCMGFAYNVG 355
gi 81171069 330 lgSVALFVLAIPAFILins----------nvIGLIFAGLLMLAVILNCFTGVMAstlpam---fpthirYSALAAAFNIS 396
gi 586685   321 -mVIITTLIILFALFAfnpllgs-gnpilvfAFLLLGLSLMGLTFGPMGALLPElfpt-------evryTGASFSYNVAS 391
gi 7388456  290 -sFLLFQLGAVISIVVysqltd----pdimlLAGAFLGMFVNGMLGGYGALMAEaypt--------earATAQNVLFNIG 356
gi 7387918  295 -tYAFGAIGTAIFLPLivfyns----pdnilYLLVIFGFLYGIPYGVNATYMTEsfpt--------airGTAIGGAYNVG 361
                       410       420       430       440
                ....*....|....*....|....*....|....*....|....*
Feature 1       #  #                                         
1PW4_A      392 YLGGSVAASAIVgytv--dffgWDGGFMVMIGGSILAVILLIVVM 434
1PV7_A      359 QLAMIFMSVLAGnmye---sigFQGAYLVLGLVALGFTLISVFTL 400
gi 2500934  390 VVGGGFTPFIAAalityfagnwHSVAIYLLAGCLISAMTALLMKD 434
gi 84029499 382 NAIFGGSAEYVAlslk--sigmETAFFWYVTLMAVVAFLVSLMLH 424
gi 81174989 378 SLLGGTTPLIASylvs--ttnnPLTPAYYLTVISIIGFIVIALLH 420
gi 7387890  356 KSIGAGSVVGVGvlst--higlANAMGTFCLVAYAFAVFGIMLLP 398
gi 81171069 397 VLVAGLTPTLAAwlve--ssqnLMMPAYYLMVVAVVGLITGVTMK 439
gi 586685   392 ILGASVAPYIAAwlqt---nygLGAVGLYLAAMAGLTLIALLLTH 433
gi 7388456  357 RAVGGFGPVVVGsvvl---aysFQTAIALLAIIYVIDMLATIFLI 398
gi 7387918  362 RLGAAIAPATIGflas---ggsIGLGFVVMGAAYFICGVIPALFI 403

Citing CDD
Marchler-Bauer A et al. (2013), "CDD: conserved domains and protein three-dimensional structure.", Nucleic Acids Res. 41(D1):D384-52.
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Click on image for an interactive view with Cn3D
Conserved site includes 51 residues -Click on image for an interactive view with Cn3D