ID   MNTP_ECOLI              Reviewed;         188 AA.
AC   P76264; O07974;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   27-SEP-2004, sequence version 2.
DT   02-SEP-2026, entry version 161.
DE   RecName: Full=Manganese exporter MntP {ECO:0000255|HAMAP-Rule:MF_01521, ECO:0000303|PubMed:29440394};
DE   AltName: Full=Manganese efflux protein MntP {ECO:0000303|PubMed:36190429};
GN   Name=mntP {ECO:0000255|HAMAP-Rule:MF_01521,
GN   ECO:0000303|PubMed:21908668}; Synonyms=yebN;
GN   OrderedLocusNames=b1821, JW5830;
OS   Escherichia coli (strain K12).
OC   Bacteria; Pseudomonadati; Pseudomonadota; Gammaproteobacteria;
OC   Enterobacterales; Enterobacteriaceae; Escherichia.
OX   NCBI_TaxID=83333;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX   PubMed=9097040; DOI=10.1093/dnares/3.6.379;
RA   Itoh T., Aiba H., Baba T., Fujita K., Hayashi K., Inada T., Isono K.,
RA   Kasai H., Kimura S., Kitakawa M., Kitagawa M., Makino K., Miki T.,
RA   Mizobuchi K., Mori H., Mori T., Motomura K., Nakade S., Nakamura Y.,
RA   Nashimoto H., Nishio Y., Oshima T., Saito N., Sampei G., Seki Y.,
RA   Sivasundaram S., Tagami H., Takeda J., Takemoto K., Wada C., Yamamoto Y.,
RA   Horiuchi T.;
RT   "A 460-kb DNA sequence of the Escherichia coli K-12 genome corresponding to
RT   the 40.1-50.0 min region on the linkage map.";
RL   DNA Res. 3:379-392(1996).
RN   [2]
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   [3]
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   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-53.
RX   PubMed=8107138; DOI=10.1006/jmbi.1994.1163;
RA   Stojiljkovic I., Baumler A.J., Hantke K.;
RT   "Fur regulon in Gram-negative bacteria. Identification and characterization
RT   of new iron-regulated Escherichia coli genes by a fur titration assay.";
RL   J. Mol. Biol. 236:531-545(1994).
RN   [5]
RP   SUBCELLULAR LOCATION, AND 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   [6]
RP   FUNCTION IN MANGANESE HOMEOSTASIS, INDUCTION, DISRUPTION PHENOTYPE, AND
RP   GENE NAME.
RX   PubMed=21908668; DOI=10.1128/jb.05872-11;
RA   Waters L.S., Sandoval M., Storz G.;
RT   "The Escherichia coli MntR miniregulon includes genes encoding a small
RT   protein and an efflux pump required for manganese homeostasis.";
RL   J. Bacteriol. 193:5887-5897(2011).
RN   [7]
RP   REGULATION OF EXPRESSION.
RC   STRAIN=K12 / MG1655 / ATCC 47076;
RX   PubMed=25794618; DOI=10.1016/j.molcel.2015.01.035;
RA   Dambach M., Sandoval M., Updegrove T.B., Anantharaman V., Aravind L.,
RA   Waters L.S., Storz G.;
RT   "The ubiquitous yybP-ykoY riboswitch is a manganese-responsive regulatory
RT   element.";
RL   Mol. Cell 57:1099-1109(2015).
RN   [8]
RP   FUNCTION, AND ACTIVITY REGULATION.
RC   STRAIN=K12 / MG1655 / ATCC 47076;
RX   PubMed=25774656; DOI=10.1371/journal.pgen.1004977;
RA   Martin J.E., Waters L.S., Storz G., Imlay J.A.;
RT   "The Escherichia coli small protein MntS and exporter MntP optimize the
RT   intracellular concentration of manganese.";
RL   PLoS Genet. 11:e1004977-e1004977(2015).
RN   [9]
RP   ERRATUM OF PUBMED:25774656.
RX   PubMed=26076491; DOI=10.1371/journal.pgen.1005322;
RG   PLOS Genetics Staff;
RL   PLoS Genet. 11:e1005322-e1005322(2015).
RN   [10]
RP   FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE,
RP   AND MUTAGENESIS OF ASP-16; HIS-29; GLU-35; GLU-47; HIS-70; ASP-118 AND
RP   GLU-167.
RX   PubMed=29440394; DOI=10.1074/jbc.m117.790717;
RA   Zeinert R., Martinez E., Schmitz J., Senn K., Usman B., Anantharaman V.,
RA   Aravind L., Waters L.S.;
RT   "Structure-function analysis of manganese exporter proteins across
RT   bacteria.";
RL   J. Biol. Chem. 293:5715-5730(2018).
RN   [11]
RP   REGULATION OF EXPRESSION.
RC   STRAIN=K12 / BW25113;
RX   PubMed=36190429; DOI=10.1128/spectrum.03368-22;
RA   Kalita A., Mishra R.K., Kumar V., Arora A., Dutta D.;
RT   "An Intrinsic Alkalization Circuit Turns on mntP Riboswitch under Manganese
RT   Stress in Escherichia coli.";
RL   Microbiol. Spectr. 10:e0336822-e0336822(2022).
RN   [12]
RP   FUNCTION, AND REGULATION OF EXPRESSION.
RC   STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX   PubMed=38869303; DOI=10.1128/jb.00168-24;
RA   Sharma R., Mishanina T.V.;
RT   "A riboswitch-controlled TerC family transporter Alx tunes intracellular
RT   manganese concentration in Escherichia coli at alkaline pH.";
RL   J. Bacteriol. 206:e0016824-e0016824(2024).
RN   [13]
RP   REGULATION OF EXPRESSION.
RC   STRAIN=K12 / BW25113;
RX   PubMed=39510182; DOI=10.1016/j.jbc.2024.107967;
RA   Prakash A., Kalita A., Bhardwaj K., Mishra R.K., Ghose D., Kaur G.,
RA   Verma N., Pani B., Nudler E., Dutta D.;
RT   "Rho and riboswitch-dependent regulations of mntP gene expression evade
RT   manganese and membrane toxicities.";
RL   J. Biol. Chem. 300:107967-107967(2024).
RN   [14]
RP   ACTIVITY REGULATION, AND INTERACTION WITH MNTS.
RC   STRAIN=K12 / MG1655 / ATCC 47076;
RX   PubMed=38104967; DOI=10.1111/mmi.15206;
RA   Wright Z., Seymour M., Paszczak K., Truttmann T., Senn K., Stilp S.,
RA   Jansen N., Gosz M., Goeden L., Anantharaman V., Aravind L., Waters L.S.;
RT   "The small protein MntS evolved from a signal peptide and acquired a novel
RT   function regulating manganese homeostasis in Escherichia coli.";
RL   Mol. Microbiol. 121:152-166(2024).
CC   -!- FUNCTION: Functions as a manganese exporter (PubMed:29440394,
CC       PubMed:38869303). Involved in manganese homeostasis (PubMed:21908668,
CC       PubMed:25774656, PubMed:29440394). Important for reducing the
CC       concentration of manganese in the cell when manganese levels are high,
CC       thus reducing its toxicity (PubMed:25774656). Transport of Mn(2+) by
CC       MntP is unlikely to be accompanied by an H(+) antiport
CC       (PubMed:38869303). Alters cellular resistance to reactive oxygen
CC       species (ROS) (PubMed:29440394). {ECO:0000269|PubMed:21908668,
CC       ECO:0000269|PubMed:25774656, ECO:0000269|PubMed:29440394,
CC       ECO:0000269|PubMed:38869303}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Mn(2+)(in) = Mn(2+)(out); Xref=Rhea:RHEA:28699,
CC         ChEBI:CHEBI:29035; Evidence={ECO:0000255|HAMAP-Rule:MF_01521,
CC         ECO:0000269|PubMed:29440394, ECO:0000305|PubMed:21908668};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28700;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_01521,
CC         ECO:0000269|PubMed:29440394, ECO:0000305|PubMed:21908668};
CC   -!- ACTIVITY REGULATION: When manganese levels drop, MntP export activity
CC       is inhibited by MntS (PubMed:25774656, PubMed:38104967). MntS acts by
CC       binding directly to MntP (PubMed:38104967). Inhibition of MntP by MntS
CC       could modestly increase the intracellular manganese pool and thereby
CC       enhance manganese entry into proteins (PubMed:25774656).
CC       {ECO:0000269|PubMed:25774656, ECO:0000269|PubMed:38104967}.
CC   -!- SUBUNIT: Interacts with the small protein MntS.
CC       {ECO:0000269|PubMed:38104967}.
CC   -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000269|PubMed:15919996,
CC       ECO:0000269|PubMed:29440394}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- INDUCTION: Expression is regulated by manganese at both the
CC       transcriptional and post-transcriptional levels (PubMed:25794618).
CC       Transcription is up-regulated by Fur and MntR in response to Mn(2+)
CC       (PubMed:21908668, PubMed:25794618). The Fur and MntR repressors
CC       activate mntP transcription by counteracting the repressive effects of
CC       the histone-like H-NS protein (PubMed:25794618). Translation is then
CC       regulated by the Mn(2+)-responsive mntP riboswitch, a member of the
CC       yybP-ykoY riboswitch family, which is located in the 5' untranslated
CC       region (5'-UTR) of mntP (PubMed:25794618). When intracellular manganese
CC       levels are high, the riboswitch directly binds Mn(2+), resulting in a
CC       conformation that liberates the ribosome-binding site, leading to
CC       increased mntP translation and increased Mn(2+) export
CC       (PubMed:25794618). The riboswitch is also responsive to alkaline pH,
CC       which favors the interaction between manganese and the riboswitch,
CC       resulting in increased mntP translation (PubMed:36190429). Manganese
CC       and alkaline pH are both necessary for maximal mntP riboswitch
CC       activation to mitigate the manganese toxicity (PubMed:36190429).
CC       Alkaline pH alone has no impact on mntP expression (PubMed:38869303).
CC       The mntP riboswitch also serves as a platform for the Rho-dependent
CC       transcription termination to down-regulate mntP expression
CC       (PubMed:39510182). Rho-dependent termination acts to moderate MntP
CC       levels and protects the cell from excessive MntP expression, which
CC       causes membrane protein toxicity (PubMed:39510182).
CC       {ECO:0000269|PubMed:21908668, ECO:0000269|PubMed:25794618,
CC       ECO:0000269|PubMed:36190429, ECO:0000269|PubMed:38869303,
CC       ECO:0000269|PubMed:39510182}.
CC   -!- DISRUPTION PHENOTYPE: Deletion causes manganese sensitivity and leads
CC       to increased intracellular manganese levels (PubMed:21908668,
CC       PubMed:29440394). The deletion mutant can only tolerate up to 0.1 mM
CC       supplemental MnCl(2), whereas the wild-type strain can grow in the
CC       presence of up to 5 mM MnCl(2) (PubMed:29440394).
CC       {ECO:0000269|PubMed:21908668, ECO:0000269|PubMed:29440394}.
CC   -!- MISCELLANEOUS: E.coli may control manganese levels by balancing the
CC       actions of MntH, MntP and MntS against one another.
CC       {ECO:0000269|PubMed:25774656}.
CC   -!- SIMILARITY: Belongs to the MntP (TC 9.B.29) family. {ECO:0000255|HAMAP-
CC       Rule:MF_01521, ECO:0000305}.
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DR   EMBL; U00096; AAC74891.2; -; Genomic_DNA.
DR   EMBL; AP009048; BAA15632.2; -; Genomic_DNA.
DR   EMBL; X75948; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   PIR; E64943; E64943.
DR   RefSeq; NP_416335.4; NC_000913.3.
DR   RefSeq; WP_001296134.1; NZ_CP009789.1.
DR   AlphaFoldDB; P76264; -.
DR   BioGRID; 4263026; 7.
DR   FunCoup; P76264; 145.
DR   STRING; 511145.b1821; -.
DR   TCDB; 2.A.107.1.1; the mntp mn(2+) exporter (mntp) family.
DR   jPOST; P76264; -.
DR   PaxDb; 511145-b1821; -.
DR   EnsemblBacteria; AAC74891; AAC74891; b1821.
DR   GeneID; 93776070; -.
DR   GeneID; 946341; -.
DR   KEGG; ecj:JW5830; -.
DR   KEGG; eco:b1821; -.
DR   KEGG; ecoc:C3026_10375; -.
DR   PATRIC; fig|511145.12.peg.1898; -.
DR   EchoBASE; EB3768; -.
DR   eggNOG; COG1971; Bacteria.
DR   HOGENOM; CLU_096410_0_0_6; -.
DR   InParanoid; P76264; -.
DR   OMA; WHFGLFQ; -.
DR   OrthoDB; 9811590at2; -.
DR   PhylomeDB; P76264; -.
DR   BioCyc; EcoCyc:G6999-MONOMER; -.
DR   BioCyc; MetaCyc:G6999-MONOMER; -.
DR   PRO; PR:P76264; -.
DR   Proteomes; UP000000625; Chromosome.
DR   AbasyAtlas; P76264; -.
DR   GO; GO:0005886; C:plasma membrane; IDA:EcoCyc.
DR   GO; GO:0005384; F:manganese ion transmembrane transporter activity; IMP:EcoCyc.
DR   GO; GO:0030026; P:intracellular manganese ion homeostasis; IDA:EcoCyc.
DR   GO; GO:0140048; P:manganese ion export across plasma membrane; IMP:EcoCyc.
DR   HAMAP; MF_01521; MntP_exporter; 1.
DR   InterPro; IPR022929; MntP.
DR   InterPro; IPR003810; Mntp/YtaF.
DR   NCBIfam; NF008546; PRK11469.1; 1.
DR   PANTHER; PTHR35529; MANGANESE EFFLUX PUMP MNTP-RELATED; 1.
DR   PANTHER; PTHR35529:SF1; MANGANESE EFFLUX PUMP MNTP-RELATED; 1.
DR   Pfam; PF02659; Mntp; 1.
PE   1: Evidence at protein level;
KW   Cell inner membrane; Cell membrane; Ion transport; Manganese; Membrane;
KW   Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..188
FT                   /note="Manganese exporter MntP"
FT                   /id="PRO_0000155649"
FT   TOPO_DOM        1..6
FT                   /note="Periplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        7..29
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        30..40
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        41..61
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        62..63
FT                   /note="Periplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        64..86
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        87..105
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        106..128
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        129..132
FT                   /note="Periplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        133..155
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        156..167
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        168..187
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        188
FT                   /note="Periplasmic"
FT                   /evidence="ECO:0000269|PubMed:15919996"
FT   MUTAGEN         16
FT                   /note="D->A: Loss of activity, cannot complement a deletion
FT                   mutant."
FT                   /evidence="ECO:0000269|PubMed:29440394"
FT   MUTAGEN         29
FT                   /note="H->A: Does not affect manganese export."
FT                   /evidence="ECO:0000269|PubMed:29440394"
FT   MUTAGEN         35
FT                   /note="E->A: Decrease in activity. Only partially restores
FT                   growth on plates with 5 mMMnCl(2)."
FT                   /evidence="ECO:0000269|PubMed:29440394"
FT   MUTAGEN         47
FT                   /note="E->A: Decrease in activity. Displays a significant
FT                   growth defect on plates with 1 mMMnCl(2)."
FT                   /evidence="ECO:0000269|PubMed:29440394"
FT   MUTAGEN         70
FT                   /note="H->A: Does not affect manganese export."
FT                   /evidence="ECO:0000269|PubMed:29440394"
FT   MUTAGEN         118
FT                   /note="D->A: Loss of activity, cannot complement a deletion
FT                   mutant."
FT                   /evidence="ECO:0000269|PubMed:29440394"
FT   MUTAGEN         167
FT                   /note="E->A: Decrease in activity. Only partially restores
FT                   growth on plates with 5 mMMnCl(2)."
FT                   /evidence="ECO:0000269|PubMed:29440394"
SQ   SEQUENCE   188 AA;  20117 MW;  09BBB5C3D6185A9B CRC64;
     MNITATVLLA FGMSMDAFAA SIGKGATLHK PKFSEALRTG LIFGAVETLT PLIGWGMGML
     ASRFVLEWNH WIAFVLLIFL GGRMIIEGFR GADDEDEEPR RRHGFWLLVT TAIATSLDAM
     AVGVGLAFLQ VNIIATALAI GCATLIMSTL GMMVGRFIGS IIGKKAEILG GLVLIGIGVQ
     ILWTHFHG
//