LACY_ECOLI
ID LACY_ECOLI Reviewed; 417 AA.
AC P02920; Q2MC81;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Lactose permease {ECO:0000303|PubMed:6444453};
DE AltName: Full=Lactose-proton symport;
GN Name=lacY {ECO:0000303|PubMed:6444453}; OrderedLocusNames=b0343, JW0334;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6444453; DOI=10.1038/283541a0;
RA Buechel D.E., Gronenborn B., Mueller-Hill B.;
RT "Sequence of the lactose permease gene.";
RL Nature 283:541-545(1980).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RA Pastore J.C., Larigan J.D., Consler T.G., Kaback H.R.;
RL Submitted (SEP-1990) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RA Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M.,
RA Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D.,
RA Namath A., Oefner P., Roberts D., Schramm S., Davis R.W.;
RT "Sequence of minutes 4-25 of Escherichia coli.";
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [6]
RP TOPOLOGY.
RX PubMed=16453726;
RA von Heijne G.;
RT "The distribution of positively charged residues in bacterial inner
RT membrane proteins correlates with the trans-membrane topology.";
RL EMBO J. 5:3021-3027(1986).
RN [7]
RP SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=2164211; DOI=10.1073/pnas.87.13.4937;
RA Calamia J., Manoil C.;
RT "lac permease of Escherichia coli: topology and sequence elements promoting
RT membrane insertion.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:4937-4941(1990).
RN [8]
RP TOPOLOGY.
RX PubMed=7578103; DOI=10.1021/bi00045a036;
RA Ujwal M.L., Jung H., Bibi E., Manoil C., Altenbach C., Hubbell W.L.,
RA Kaback H.R.;
RT "Membrane topology of helices VII and XI in the lactose permease of
RT Escherichia coli studied by lacY-phoA fusion analysis and site-directed
RT spectroscopy.";
RL Biochemistry 34:14909-14917(1995).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF ASP-237 AND LYS-358.
RX PubMed=1848449; DOI=10.1016/0005-2736(91)90390-t;
RA King S.C., Hansen C.L., Wilson T.H.;
RT "The interaction between aspartic acid 237 and lysine 358 in the lactose
RT carrier of Escherichia coli.";
RL Biochim. Biophys. Acta 1062:177-186(1991).
RN [10]
RP MUTAGENESIS.
RX PubMed=1644770; DOI=10.1128/jb.174.16.5436-5441.1992;
RA Huang A.-M., Lee J.-I., King S.C., Wilson T.H.;
RT "Amino acid substitution in the lactose carrier protein with the use of
RT amber suppressors.";
RL J. Bacteriol. 174:5436-5441(1992).
RN [11]
RP REVIEW.
RX PubMed=2203471; DOI=10.1016/0005-2728(90)90239-z;
RA Kaback H.R.;
RT "The lac permease of Escherichia coli: a prototypic energy-transducing
RT membrane protein.";
RL Biochim. Biophys. Acta 1018:160-162(1990).
RN [12]
RP FORMYLATION AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=10485888; DOI=10.1073/pnas.96.19.10695;
RA Whitelegge J.P., le Coutre J., Lee J.C., Engel C.K., Prive G.G.,
RA Faull K.F., Kaback H.R.;
RT "Toward the bilayer proteome, electrospray ionization-mass spectrometry of
RT large, intact transmembrane proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:10695-10698(1999).
RN [13]
RP TOPOLOGY [LARGE SCALE ANALYSIS].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=15919996; DOI=10.1126/science.1109730;
RA Daley D.O., Rapp M., Granseth E., Melen K., Drew D., von Heijne G.;
RT "Global topology analysis of the Escherichia coli inner membrane
RT proteome.";
RL Science 308:1321-1323(2005).
RN [14]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF LEU-65; GLY-96;
RP ALA-122; VAL-264; ALA-279; CYS-355 AND VAL-367.
RX PubMed=18177889; DOI=10.1016/j.jmb.2007.12.015;
RA Tavoulari S., Frillingos S.;
RT "Substrate selectivity of the melibiose permease (MelY) from Enterobacter
RT cloacae.";
RL J. Mol. Biol. 376:681-693(2008).
RN [15]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=22106930; DOI=10.1021/bi201592y;
RA Sugihara J., Smirnova I., Kasho V., Kaback H.R.;
RT "Sugar recognition by CscB and LacY.";
RL Biochemistry 50:11009-11014(2011).
RN [16] {ECO:0007744|PDB:1PV6, ECO:0007744|PDB:1PV7}
RP X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF MUTANT GLY-154.
RX PubMed=12893935; DOI=10.1126/science.1088196;
RA Abramson J., Smirnova I., Kasho V., Verner G., Kaback H.R., Iwata S.;
RT "Structure and mechanism of the lactose permease of Escherichia coli.";
RL Science 301:610-615(2003).
CC -!- FUNCTION: Responsible for transport of beta-galactosides into the cell,
CC with the concomitant import of a proton (symport system). Can transport
CC lactose, melibiose, lactulose or the analog methyl-1-thio-beta,D-
CC galactopyranoside (TMG), but not sucrose or fructose (PubMed:1848449,
CC PubMed:18177889, PubMed:22106930). The substrate specificity is
CC directed toward the galactopyranosyl moiety of the substrate
CC (PubMed:22106930). {ECO:0000269|PubMed:18177889,
CC ECO:0000269|PubMed:1848449, ECO:0000269|PubMed:22106930}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.62 mM for lactose {ECO:0000269|PubMed:18177889};
CC KM=0.24 mM for melibiose {ECO:0000269|PubMed:18177889};
CC KM=0.24 mM for lactulose {ECO:0000269|PubMed:22106930};
CC KM=0.54 mM for TMG {ECO:0000269|PubMed:18177889};
CC Vmax=191 nmol/min/mg enzyme with lactose as substrate
CC {ECO:0000269|PubMed:18177889};
CC Vmax=105 nmol/min/mg enzyme with melibiose as substrate
CC {ECO:0000269|PubMed:18177889};
CC Vmax=49 nmol/min/mg enzyme with lactulose as substrate
CC {ECO:0000269|PubMed:22106930};
CC Vmax=180 nmol/min/mg enzyme with TMG as substrate
CC {ECO:0000269|PubMed:18177889};
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000269|PubMed:2164211};
CC Multi-pass membrane protein {ECO:0000269|PubMed:2164211}.
CC -!- MASS SPECTROMETRY: Mass=47357; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:10485888};
CC -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC Oligosaccharide:H(+) symporter (OHS) (TC 2.A.1.5) family.
CC {ECO:0000305}.
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DR EMBL; J01636; AAA24054.1; -; Genomic_DNA.
DR EMBL; V00295; CAA23571.1; -; Genomic_DNA.
DR EMBL; X56095; CAA39575.1; -; Genomic_DNA.
DR EMBL; U73857; AAB18067.1; -; Genomic_DNA.
DR EMBL; U00096; AAC73446.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE76125.1; -; Genomic_DNA.
DR PIR; A03418; GREC.
DR RefSeq; NP_414877.1; NC_000913.3.
DR RefSeq; WP_000291549.1; NZ_SSZK01000061.1.
DR PDB; 1PV6; X-ray; 3.50 A; A/B=1-417.
DR PDB; 1PV7; X-ray; 3.60 A; A/B=1-417.
DR PDB; 2CFP; X-ray; 3.30 A; A=1-417.
DR PDB; 2CFQ; X-ray; 2.95 A; A=1-417.
DR PDB; 2V8N; X-ray; 3.60 A; A/B=1-417.
DR PDB; 2Y5Y; X-ray; 3.38 A; A/B=1-417.
DR PDB; 4ZYR; X-ray; 3.31 A; A/B=1-417.
DR PDB; 5GXB; X-ray; 3.30 A; A=1-417.
DR PDB; 6C9W; X-ray; 3.00 A; A=1-417.
DR PDB; 6VBG; X-ray; 2.80 A; A/B=1-417.
DR PDBsum; 1PV6; -.
DR PDBsum; 1PV7; -.
DR PDBsum; 2CFP; -.
DR PDBsum; 2CFQ; -.
DR PDBsum; 2V8N; -.
DR PDBsum; 2Y5Y; -.
DR PDBsum; 4ZYR; -.
DR PDBsum; 5GXB; -.
DR PDBsum; 6C9W; -.
DR PDBsum; 6VBG; -.
DR AlphaFoldDB; P02920; -.
DR PCDDB; P02920; -.
DR SMR; P02920; -.
DR BioGRID; 4263185; 8.
DR DIP; DIP-10080N; -.
DR IntAct; P02920; 1.
DR STRING; 511145.b0343; -.
DR DrugBank; DB04396; Thiodigalactoside.
DR TCDB; 2.A.1.5.1; the major facilitator superfamily (mfs).
DR PaxDb; P02920; -.
DR PRIDE; P02920; -.
DR ABCD; P02920; 2 sequenced antibodies.
DR EnsemblBacteria; AAC73446; AAC73446; b0343.
DR EnsemblBacteria; BAE76125; BAE76125; BAE76125.
DR GeneID; 66671353; -.
DR GeneID; 949083; -.
DR KEGG; ecj:JW0334; -.
DR KEGG; eco:b0343; -.
DR PATRIC; fig|1411691.4.peg.1934; -.
DR EchoBASE; EB0521; -.
DR eggNOG; COG2223; Bacteria.
DR HOGENOM; CLU_055585_0_0_6; -.
DR InParanoid; P02920; -.
DR OMA; KNFWIFG; -.
DR PhylomeDB; P02920; -.
DR BioCyc; EcoCyc:LACY-MON; -.
DR BioCyc; MetaCyc:LACY-MON; -.
DR BRENDA; 2.7.1.207; 2026.
DR EvolutionaryTrace; P02920; -.
DR PRO; PR:P02920; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IDA:EcoliWiki.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:EcoCyc.
DR GO; GO:0016020; C:membrane; IDA:EcoliWiki.
DR GO; GO:0005886; C:plasma membrane; IDA:EcoCyc.
DR GO; GO:0005351; F:carbohydrate:proton symporter activity; IDA:EcoliWiki.
DR GO; GO:0030395; F:lactose binding; IDA:EcoliWiki.
DR GO; GO:0015528; F:lactose:proton symporter activity; IDA:EcoCyc.
DR GO; GO:0008643; P:carbohydrate transport; IMP:CACAO.
DR GO; GO:0015767; P:lactose transport; IDA:EcoCyc.
DR GO; GO:0071702; P:organic substance transport; IBA:GO_Central.
DR Gene3D; 1.20.1250.20; -; 2.
DR InterPro; IPR000576; LacY/RafB_perm_fam.
DR InterPro; IPR018457; LacY/RafB_perm_fam_CS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR036259; MFS_trans_sf.
DR Pfam; PF01306; LacY_symp; 1.
DR PRINTS; PR00174; LACYSMPORT.
DR SUPFAM; SSF103473; SSF103473; 1.
DR TIGRFAMs; TIGR00882; 2A0105; 1.
DR PROSITE; PS00896; LACY_1; 1.
DR PROSITE; PS00897; LACY_2; 1.
DR PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell inner membrane; Cell membrane; Formylation; Membrane;
KW Reference proteome; Sugar transport; Symport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..417
FT /note="Lactose permease"
FT /id="PRO_0000196184"
FT TOPO_DOM 1..7
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:2164211"
FT TRANSMEM 8..34
FT /note="Helical; Name=1"
FT TOPO_DOM 35..41
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:2164211"
FT TRANSMEM 42..70
FT /note="Helical; Name=2"
FT TOPO_DOM 71..74
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:2164211"
FT TRANSMEM 75..100
FT /note="Helical; Name=3"
FT TOPO_DOM 101..104
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:2164211"
FT TRANSMEM 105..129
FT /note="Helical; Name=4"
FT TOPO_DOM 130..140
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:2164211"
FT TRANSMEM 141..163
FT /note="Helical; Name=5"
FT TOPO_DOM 164..166
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:2164211"
FT TRANSMEM 167..186
FT /note="Helical; Name=6"
FT TOPO_DOM 187..220
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:2164211"
FT TRANSMEM 221..249
FT /note="Helical; Name=7"
FT TOPO_DOM 250..253
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:2164211"
FT TRANSMEM 254..278
FT /note="Helical; Name=8"
FT TOPO_DOM 279..288
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:2164211"
FT TRANSMEM 289..308
FT /note="Helical; Name=9"
FT TOPO_DOM 309..311
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:2164211"
FT TRANSMEM 312..334
FT /note="Helical; Name=10"
FT TOPO_DOM 335..346
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:2164211"
FT TRANSMEM 347..374
FT /note="Helical; Name=11"
FT TOPO_DOM 375..377
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:2164211"
FT TRANSMEM 378..398
FT /note="Helical; Name=12"
FT TOPO_DOM 399..417
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:15919996,
FT ECO:0000269|PubMed:2164211"
FT SITE 126
FT /note="Substrate binding"
FT /evidence="ECO:0000305|PubMed:12893935"
FT SITE 144
FT /note="Substrate binding"
FT /evidence="ECO:0000305|PubMed:12893935"
FT SITE 269
FT /note="Substrate binding and proton translocation"
FT /evidence="ECO:0000305|PubMed:12893935"
FT SITE 302
FT /note="Proton translocation"
FT /evidence="ECO:0000305|PubMed:12893935"
FT SITE 322
FT /note="Proton translocation"
FT /evidence="ECO:0000305|PubMed:12893935"
FT SITE 325
FT /note="Proton translocation"
FT /evidence="ECO:0000305|PubMed:12893935"
FT MOD_RES 1
FT /note="N-formylmethionine; partial"
FT /evidence="ECO:0000269|PubMed:10485888"
FT MUTAGEN 65
FT /note="L->V: No change in transport activity."
FT /evidence="ECO:0000269|PubMed:18177889"
FT MUTAGEN 96
FT /note="G->A: No change in transport activity."
FT /evidence="ECO:0000269|PubMed:18177889"
FT MUTAGEN 122
FT /note="A->S: No change in transport activity."
FT /evidence="ECO:0000269|PubMed:18177889"
FT MUTAGEN 237
FT /note="D->N,G: Loss of activity."
FT /evidence="ECO:0000269|PubMed:1848449"
FT MUTAGEN 264
FT /note="V->A: No change in transport activity."
FT /evidence="ECO:0000269|PubMed:18177889"
FT MUTAGEN 279
FT /note="A->S: No change in transport activity."
FT /evidence="ECO:0000269|PubMed:18177889"
FT MUTAGEN 355
FT /note="C->Q: No change in transport activity."
FT /evidence="ECO:0000269|PubMed:18177889"
FT MUTAGEN 358
FT /note="K->T: Loss of activity."
FT /evidence="ECO:0000269|PubMed:1848449"
FT MUTAGEN 367
FT /note="V->A: Increases transport of melibiose and impairs
FT transport of TMG."
FT /evidence="ECO:0000269|PubMed:18177889"
FT TURN 2..4
FT /evidence="ECO:0007829|PDB:2CFQ"
FT HELIX 7..26
FT /evidence="ECO:0007829|PDB:6VBG"
FT TURN 27..29
FT /evidence="ECO:0007829|PDB:2CFQ"
FT HELIX 30..37
FT /evidence="ECO:0007829|PDB:6VBG"
FT TURN 42..44
FT /evidence="ECO:0007829|PDB:2CFQ"
FT HELIX 45..70
FT /evidence="ECO:0007829|PDB:6VBG"
FT HELIX 71..73
FT /evidence="ECO:0007829|PDB:2Y5Y"
FT HELIX 75..84
FT /evidence="ECO:0007829|PDB:6VBG"
FT HELIX 87..93
FT /evidence="ECO:0007829|PDB:6VBG"
FT HELIX 95..101
FT /evidence="ECO:0007829|PDB:6VBG"
FT HELIX 103..117
FT /evidence="ECO:0007829|PDB:6VBG"
FT TURN 118..120
FT /evidence="ECO:0007829|PDB:6VBG"
FT HELIX 121..135
FT /evidence="ECO:0007829|PDB:6VBG"
FT STRAND 136..138
FT /evidence="ECO:0007829|PDB:2Y5Y"
FT HELIX 140..161
FT /evidence="ECO:0007829|PDB:6VBG"
FT TURN 162..164
FT /evidence="ECO:0007829|PDB:6VBG"
FT HELIX 168..186
FT /evidence="ECO:0007829|PDB:6VBG"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:1PV6"
FT STRAND 197..203
FT /evidence="ECO:0007829|PDB:2CFQ"
FT HELIX 210..214
FT /evidence="ECO:0007829|PDB:6VBG"
FT HELIX 215..218
FT /evidence="ECO:0007829|PDB:6VBG"
FT HELIX 220..231
FT /evidence="ECO:0007829|PDB:6VBG"
FT HELIX 233..239
FT /evidence="ECO:0007829|PDB:6VBG"
FT HELIX 243..248
FT /evidence="ECO:0007829|PDB:6VBG"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:6VBG"
FT HELIX 255..285
FT /evidence="ECO:0007829|PDB:6VBG"
FT HELIX 288..308
FT /evidence="ECO:0007829|PDB:6VBG"
FT HELIX 312..320
FT /evidence="ECO:0007829|PDB:6VBG"
FT HELIX 322..340
FT /evidence="ECO:0007829|PDB:6VBG"
FT HELIX 343..345
FT /evidence="ECO:0007829|PDB:6VBG"
FT HELIX 346..353
FT /evidence="ECO:0007829|PDB:6VBG"
FT HELIX 356..375
FT /evidence="ECO:0007829|PDB:6VBG"
FT HELIX 378..399
FT /evidence="ECO:0007829|PDB:6VBG"
FT STRAND 400..402
FT /evidence="ECO:0007829|PDB:6VBG"
FT HELIX 406..408
FT /evidence="ECO:0007829|PDB:6VBG"
FT TURN 414..416
FT /evidence="ECO:0007829|PDB:2CFQ"
SQ SEQUENCE 417 AA; 46503 MW; 24A8062F628CDA32 CRC64;
MYYLKNTNFW MFGLFFFFYF FIMGAYFPFF PIWLHDINHI SKSDTGIIFA AISLFSLLFQ
PLFGLLSDKL GLRKYLLWII TGMLVMFAPF FIFIFGPLLQ YNILVGSIVG GIYLGFCFNA
GAPAVEAFIE KVSRRSNFEF GRARMFGCVG WALCASIVGI MFTINNQFVF WLGSGCALIL
AVLLFFAKTD APSSATVANA VGANHSAFSL KLALELFRQP KLWFLSLYVI GVSCTYDVFD
QQFANFFTSF FATGEQGTRV FGYVTTMGEL LNASIMFFAP LIINRIGGKN ALLLAGTIMS
VRIIGSSFAT SALEVVILKT LHMFEVPFLL VGCFKYITSQ FEVRFSATIY LVCFCFFKQL
AMIFMSVLAG NMYESIGFQG AYLVLGLVAL GFTLISVFTL SGPGPLSLLR RQVNEVA
