ID   PHEP_ECOLI              Reviewed;         458 AA.
AC   P24207; P77090;
DT   01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-1992, sequence version 1.
DT   04-NOV-2026, entry version 180.
DE   RecName: Full=Phenylalanine-specific permease;
DE   AltName: Full=Phenylalanine:H(+) symporter PheP {ECO:0000305};
GN   Name=pheP {ECO:0000303|PubMed:1711024};
GN   OrderedLocusNames=b0576, JW0565;
OS   Escherichia coli (strain K12).
OC   Bacteria; Pseudomonadati; Pseudomonadota; Gammaproteobacteria;
OC   Enterobacterales; Enterobacteriaceae; Escherichia.
OX   NCBI_TaxID=83333;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND CATALYTIC ACTIVITY.
RC   STRAIN=K12;
RX   PubMed=1711024; DOI=10.1128/jb.173.12.3622-3629.1991;
RA   Pi J., Wookey P.J., Pittard A.J.;
RT   "Cloning and sequencing of the pheP gene, which encodes the phenylalanine-
RT   specific transport system of Escherichia coli.";
RL   J. Bacteriol. 173:3622-3629(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX   PubMed=8905232; DOI=10.1093/dnares/3.3.137;
RA   Oshima T., Aiba H., Baba T., Fujita K., Hayashi K., Honjo A., Ikemoto K.,
RA   Inada T., Itoh T., Kajihara M., Kanai K., Kashimoto K., Kimura S.,
RA   Kitagawa M., Makino K., Masuda S., Miki T., Mizobuchi K., Mori H.,
RA   Motomura K., Nakamura Y., Nashimoto H., Nishio Y., Saito N., Sampei G.,
RA   Seki Y., Tagami H., Takemoto K., Wada C., Yamamoto Y., Yano M.,
RA   Horiuchi T.;
RT   "A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to
RT   the 12.7-28.0 min region on the linkage map.";
RL   DNA Res. 3:137-155(1996).
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   FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ARG-26; PHE-87; PHE-90;
RP   TYR-92; TYR-94; TRP-95; PHE-98; PHE-101; TRP-105; TYR-107; TRP-108;
RP   PHE-111; GLU-118; LYS-168; GLU-226 AND ARG-252.
RX   PubMed=8226700; DOI=10.1128/jb.175.22.7500-7504.1993;
RA   Pi J., Wookey P.J., Pittard A.J.;
RT   "Site-directed mutagenesis reveals the importance of conserved charged
RT   residues for the transport activity of the PheP permease of Escherichia
RT   coli.";
RL   J. Bacteriol. 175:7500-7504(1993).
RN   [7]
RP   SUBCELLULAR LOCATION, AND TOPOLOGY.
RX   PubMed=8626334; DOI=10.1128/jb.178.9.2650-2655.1996;
RA   Pi J., Pittard A.J.;
RT   "Topology of the phenylalanine-specific permease of Escherichia coli.";
RL   J. Bacteriol. 178:2650-2655(1996).
RN   [8]
RP   FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF PRO-54; PRO-341 AND
RP   PRO-442.
RC   STRAIN=K12;
RX   PubMed=9791098; DOI=10.1128/jb.180.21.5515-5519.1998;
RA   Pi J., Dogovski C., Pittard A.J.;
RT   "Functional consequences of changing proline residues in the phenylalanine-
RT   specific permease of Escherichia coli.";
RL   J. Bacteriol. 180:5515-5519(1998).
RN   [9]
RP   FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF PHE-111.
RC   STRAIN=K12;
RX   PubMed=10735864; DOI=10.1128/jb.182.8.2207-2217.2000;
RA   Cosgriff A.J., Brasier G., Pi J., Dogovski C., Sarsero J.P., Pittard A.J.;
RT   "A study of AroP-PheP chimeric proteins and identification of a residue
RT   involved in tryptophan transport.";
RL   J. Bacteriol. 182:2207-2217(2000).
RN   [10]
RP   TOPOLOGY [LARGE SCALE ANALYSIS], AND SUBCELLULAR LOCATION.
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).
CC   -!- FUNCTION: Permease that is involved in the active transport across the
CC       cytoplasmic membrane of phenylalanine (PubMed:10735864, PubMed:1711024,
CC       PubMed:8226700, PubMed:9791098). Can also transport tyrosine, but not
CC       tryptophan (PubMed:10735864). {ECO:0000269|PubMed:10735864,
CC       ECO:0000269|PubMed:1711024, ECO:0000269|PubMed:8226700,
CC       ECO:0000269|PubMed:9791098}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-phenylalanine(in) + H(+)(in) = L-phenylalanine(out) +
CC         H(+)(out); Xref=Rhea:RHEA:28923, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:58095; Evidence={ECO:0000305|PubMed:10735864,
CC         ECO:0000305|PubMed:1711024, ECO:0000305|PubMed:8226700};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:28925;
CC         Evidence={ECO:0000305|PubMed:10735864, ECO:0000305|PubMed:1711024,
CC         ECO:0000305|PubMed:8226700};
CC   -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000269|PubMed:15919996,
CC       ECO:0000269|PubMed:8626334, ECO:0000269|PubMed:9791098}; Multi-pass
CC       membrane protein {ECO:0000269|PubMed:8626334}.
CC   -!- SIMILARITY: Belongs to the amino acid-polyamine-organocation (APC)
CC       superfamily. Amino acid transporter (AAT) (TC 2.A.3.1) family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB40774.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; M58000; AAA24334.1; -; Genomic_DNA.
DR   EMBL; U82598; AAB40774.1; ALT_INIT; Genomic_DNA.
DR   EMBL; U00096; AAC73677.1; -; Genomic_DNA.
DR   EMBL; AP009048; BAA35216.1; -; Genomic_DNA.
DR   PIR; A39431; A39431.
DR   RefSeq; NP_415108.1; NC_000913.3.
DR   RefSeq; WP_000786319.1; NZ_CP009789.1.
DR   SMR; P24207; -.
DR   BioGRID; 4259879; 7.
DR   DIP; DIP-10479N; -.
DR   IntAct; P24207; 2.
DR   STRING; 511145.b0576; -.
DR   TCDB; 2.A.3.1.1; the amino acid-polyamine-organocation (apc) family.
DR   PaxDb; 511145-b0576; -.
DR   EnsemblBacteria; AAC73677; AAC73677; b0576.
DR   GeneID; 945199; -.
DR   KEGG; ecj:JW0565; -.
DR   KEGG; eco:b0576; -.
DR   KEGG; ecoc:C3026_02860; -.
DR   PATRIC; fig|1411691.4.peg.1698; -.
DR   EchoBASE; EB0702; -.
DR   eggNOG; COG1113; Bacteria.
DR   HOGENOM; CLU_007946_9_3_6; -.
DR   InParanoid; P24207; -.
DR   OMA; AAKYQIW; -.
DR   OrthoDB; 5297508at2; -.
DR   PhylomeDB; P24207; -.
DR   BioCyc; EcoCyc:PHEP-MONOMER; -.
DR   BioCyc; MetaCyc:PHEP-MONOMER; -.
DR   PRO; PR:P24207; -.
DR   AbasyAtlas; P24207; -.
DR   FunFam; 1.20.1740.10:FF:000001; Amino acid permease; 1.
DR   Gene3D; 1.20.1740.10; Amino acid/polyamine transporter I; 1.
DR   InterPro; IPR004841; AA-permease/SLC12A_dom.
DR   InterPro; IPR004840; Amino_acid_permease_CS.
DR   PANTHER; PTHR43495; GABA PERMEASE; 1.
DR   PANTHER; PTHR43495:SF3; PHENYLALANINE-SPECIFIC PERMEASE; 1.
DR   Pfam; PF00324; AA_permease; 1.
DR   PIRSF; PIRSF006060; AA_transporter; 1.
DR   NCBIfam; NF007602; pheP; 1.
DR   PROSITE; PS00218; AMINO_ACID_PERMEASE_1; 1.
DR   GO; GO:0005886; C:plasma membrane; IDA:EcoCyc.
DR   GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR   GO; GO:0006865; P:amino acid transport; IEA:InterPro.
DR   GO; GO:0015823; P:phenylalanine transport; EXP:EcoCyc.
DR   Proteomes; UP000000625; Chromosome.
DR   AlphaFoldDB; P24207; -.
DR   FunCoup; P24207; 44.
PE   1: Evidence at protein level;
KW   Amino-acid transport; Cell inner membrane; Cell membrane; Membrane;
KW   Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..458
FT                   /note="Phenylalanine-specific permease"
FT                   /id="PRO_0000054206"
FT   TOPO_DOM        1..27
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:8626334"
FT   TRANSMEM        28..48
FT                   /note="Helical; Name=I"
FT                   /evidence="ECO:0000305|PubMed:8626334"
FT   TOPO_DOM        49..50
FT                   /note="Periplasmic"
FT                   /evidence="ECO:0000269|PubMed:8626334"
FT   TRANSMEM        51..71
FT                   /note="Helical; Name=II"
FT                   /evidence="ECO:0000305|PubMed:8626334"
FT   TOPO_DOM        72..105
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:8626334"
FT   TRANSMEM        106..126
FT                   /note="Helical; Name=III"
FT                   /evidence="ECO:0000305|PubMed:8626334"
FT   TOPO_DOM        127..132
FT                   /note="Periplasmic"
FT                   /evidence="ECO:0000269|PubMed:8626334"
FT   TRANSMEM        133..153
FT                   /note="Helical; Name=IV"
FT                   /evidence="ECO:0000305|PubMed:8626334"
FT   TOPO_DOM        154..160
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:8626334"
FT   TRANSMEM        161..181
FT                   /note="Helical; Name=V"
FT                   /evidence="ECO:0000305|PubMed:8626334"
FT   TOPO_DOM        182..196
FT                   /note="Periplasmic"
FT                   /evidence="ECO:0000269|PubMed:8626334"
FT   TRANSMEM        197..217
FT                   /note="Helical; Name=VI"
FT                   /evidence="ECO:0000305|PubMed:8626334"
FT   TOPO_DOM        218..250
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:8626334"
FT   TRANSMEM        251..271
FT                   /note="Helical; Name=VII"
FT                   /evidence="ECO:0000305|PubMed:8626334"
FT   TOPO_DOM        272..288
FT                   /note="Periplasmic"
FT                   /evidence="ECO:0000269|PubMed:8626334"
FT   TRANSMEM        289..309
FT                   /note="Helical; Name=VIII"
FT                   /evidence="ECO:0000305|PubMed:8626334"
FT   TOPO_DOM        310..341
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:8626334"
FT   TRANSMEM        342..362
FT                   /note="Helical; Name=IX"
FT                   /evidence="ECO:0000305|PubMed:8626334"
FT   TOPO_DOM        363..367
FT                   /note="Periplasmic"
FT                   /evidence="ECO:0000269|PubMed:8626334"
FT   TRANSMEM        368..388
FT                   /note="Helical; Name=X"
FT                   /evidence="ECO:0000305|PubMed:8626334"
FT   TOPO_DOM        389..411
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:8626334"
FT   TRANSMEM        412..432
FT                   /note="Helical; Name=XI"
FT                   /evidence="ECO:0000305|PubMed:8626334"
FT   TOPO_DOM        433..434
FT                   /note="Periplasmic"
FT                   /evidence="ECO:0000269|PubMed:8626334"
FT   TRANSMEM        435..455
FT                   /note="Helical; Name=XII"
FT                   /evidence="ECO:0000305|PubMed:8626334"
FT   TOPO_DOM        456..458
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:15919996,
FT                   ECO:0000269|PubMed:8626334"
FT   MUTAGEN         26
FT                   /note="R->G,S,Q: Strong decrease in phenylalanine transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:8226700"
FT   MUTAGEN         54
FT                   /note="P->A: 50% of wild-type phenylalanine transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:9791098"
FT   MUTAGEN         54
FT                   /note="P->G: No change in phenylalanine transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:9791098"
FT   MUTAGEN         54
FT                   /note="P->L: 26% of wild-type phenylalanine transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:9791098"
FT   MUTAGEN         87
FT                   /note="F->L: No effect on phenylalanine transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:8226700"
FT   MUTAGEN         90
FT                   /note="F->L: 65% of wild-type phenylalanine transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:8226700"
FT   MUTAGEN         92
FT                   /note="Y->L: 41% of wild-type phenylalanine transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:8226700"
FT   MUTAGEN         94
FT                   /note="Y->L: 69% of wild-type phenylalanine transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:8226700"
FT   MUTAGEN         95
FT                   /note="W->L: 10% of wild-type phenylalanine transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:8226700"
FT   MUTAGEN         98
FT                   /note="F->L: No effect on phenylalanine transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:8226700"
FT   MUTAGEN         101
FT                   /note="F->L: 38% of wild-type phenylalanine transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:8226700"
FT   MUTAGEN         105
FT                   /note="W->L: 39% of wild-type phenylalanine transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:8226700"
FT   MUTAGEN         107
FT                   /note="Y->L: No effect on phenylalanine transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:8226700"
FT   MUTAGEN         108
FT                   /note="W->L: 71% of wild-type phenylalanine transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:8226700"
FT   MUTAGEN         111
FT                   /note="F->L: 60% of wild-type phenylalanine transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:8226700"
FT   MUTAGEN         111
FT                   /note="F->Y: Enables the transport of tryptophan to almost
FT                   the same steady-state level as that of phenylalanine."
FT                   /evidence="ECO:0000269|PubMed:10735864"
FT   MUTAGEN         118
FT                   /note="E->G,L,V,N: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:8226700"
FT   MUTAGEN         168
FT                   /note="K->L,R: Strong decrease in phenylalanine transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:8226700"
FT   MUTAGEN         168
FT                   /note="K->N: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:8226700"
FT   MUTAGEN         226
FT                   /note="E->A,Q,K,R,W: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:8226700"
FT   MUTAGEN         252
FT                   /note="R->D,E,F,W,P: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:8226700"
FT   MUTAGEN         341
FT                   /note="P->A: 5% of wild-type phenylalanine transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:9791098"
FT   MUTAGEN         341
FT                   /note="P->G,Q,K,R: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:9791098"
FT   MUTAGEN         341
FT                   /note="P->S: 3% of wild-type phenylalanine transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:9791098"
FT   MUTAGEN         341
FT                   /note="P->T: 17% of wild-type phenylalanine transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:9791098"
FT   MUTAGEN         442
FT                   /note="P->A: 46% of wild-type phenylalanine transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:9791098"
FT   MUTAGEN         442
FT                   /note="P->G: 52% of wild-type phenylalanine transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:9791098"
FT   MUTAGEN         442
FT                   /note="P->L: 43% of wild-type phenylalanine transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:9791098"
SQ   SEQUENCE   458 AA;  50677 MW;  69D865369249A1A8 CRC64;
     MKNASTVSED TASNQEPTLH RGLHNRHIQL IALGGAIGTG LFLGIGPAIQ MAGPAVLLGY
     GVAGIIAFLI MRQLGEMVVE EPVSGSFAHF AYKYWGPFAG FLSGWNYWVM FVLVGMAELT
     AAGIYMQYWF PDVPTWIWAA AFFIIINAVN LVNVRLYGET EFWFALIKVL AIIGMIGFGL
     WLLFSGHGGE KASIDNLWRY GGFFATGWNG LILSLAVIMF SFGGLELIGI TAAEARDPEK
     SIPKAVNQVV YRILLFYIGS LVVLLALYPW VEVKSNSSPF VMIFHNLDSN VVASALNFVI
     LVASLSVYNS GVYSNSRMLF GLSVQGNAPK FLTRVSRRGV PINSLMLSGA ITSLVVLINY
     LLPQKAFGLL MALVVATLLL NWIMICLAHL RFRAAMRRQG RETQFKALLY PFGNYLCIAF
     LGMILLLMCT MDDMRLSAIL LPVWIVFLFM AFKTLRRK
//