MCR1_ECOLX
ID MCR1_ECOLX Reviewed; 541 AA.
AC A0A0R6L508;
DT 16-MAR-2016, integrated into UniProtKB/Swiss-Prot.
DT 17-FEB-2016, sequence version 1.
DT 03-AUG-2022, entry version 44.
DE RecName: Full=Probable phosphatidylethanolamine transferase Mcr-1;
DE EC=2.7.-.-;
DE AltName: Full=Polymyxin resistance protein MCR-1 {ECO:0000303|PubMed:26603172};
GN Name=mcr1; Synonyms=mcr-1 {ECO:0000303|PubMed:26603172};
GN ORFNames=APZ14_31440;
OS Escherichia coli.
OG Plasmid pHNSHP45.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=562;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND ANTIBIOTIC RESISTANCE.
RC STRAIN=SHP45;
RX PubMed=26603172; DOI=10.1016/s1473-3099(15)00424-7;
RA Liu Y.Y., Wang Y., Walsh T.R., Yi L.X., Zhang R., Spencer J., Doi Y.,
RA Tian G., Dong B., Huang X., Yu L.F., Gu D., Ren H., Chen X., Lv L., He D.,
RA Zhou H., Liang Z., Liu J.H., Shen J.;
RT "Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in
RT animals and human beings in China: a microbiological and molecular
RT biological study.";
RL Lancet Infect. Dis. 16:161-168(2016).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=22593;
RA Valat C., Goldstone R.J., Hirchaud E., Haenni M., Smith D.G., Madec J.-Y.;
RT "Shiga toxin-producing Escherichia coli (STEC) encoding extended-Spectrum
RT beta-lactamases (ESBLs) recovered from diarrheic cattle.";
RL Submitted (OCT-2015) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Probably catalyzes the addition of a phosphoethanolamine
CC moiety to lipid A. Phosphoethanolamine modification of lipid A gives
CC polymyxin resistance (PubMed:26603172). {ECO:0000269|PubMed:26603172}.
CC -!- FUNCTION: Confers resistance to polymyxin-type antibiotics; expression
CC of the Mcr-1 protein in E.coli increases colistin and polymyxin B
CC minimal inhibitory concentration (MIC) from 0.5 mg/ml to 2.0 mg/ml. The
CC pHNSHP45 plasmid can transfer efficiently (0.1 to 0.001) to other
CC E.coli strains by conjugation and increases polymxin MIC by 8- to 16-
CC fold; it may not require selective pressure to be maintained in the
CC cell. When transformed into K.pneumoniae or P.aeruginosa it also
CC increases polymxin MIC 8- to 16-fold. In a murine (BALB/c mice) thigh
CC infection study using an mcr1-encoding plasmid isolated from a human
CC patient, the plasmid confers in vivo protection against colistin
CC (PubMed:26603172). {ECO:0000269|PubMed:26603172}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane
CC {ECO:0000250|UniProtKB:P30845}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- MISCELLANEOUS: This is the first (as of November 2015) reported
CC plasmid-mediated resistance to polymyxin antibiotics; although it does
CC not confer a high MIC it protects against colistin treatment in an
CC infection model. Colistin is one of the last-resort antibiotics
CC available for multidrug-resistant Gram-negative bacteria such as
CC K.pneumoniae, P.aeruginosa and Acinetobacter. First identified from a
CC pig farm in Shanghai, China in July 2013, retrospective screening
CC detects the gene in (slowly) increasing proportions between 2011 and
CC 2015 from pigs and chickens, and also in hospitalized patients in
CC China. Colistin is very widely used in veterinary agriculture
CC (PubMed:26603172). {ECO:0000269|PubMed:26603172}.
CC -!- SIMILARITY: Belongs to the phosphoethanolamine transferase family.
CC {ECO:0000305}.
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DR EMBL; KP347127; AKF16168.1; -; Genomic_DNA.
DR EMBL; LMBK01000308; KST31405.1; -; Genomic_DNA.
DR RefSeq; WP_049589868.1; NZ_WVWF01000026.1.
DR PDB; 5GOV; X-ray; 2.33 A; A/B=200-541.
DR PDB; 5GRR; X-ray; 1.45 A; A=219-541.
DR PDB; 5K4P; X-ray; 1.32 A; A=214-541.
DR PDB; 5LRM; X-ray; 1.75 A; A=219-541.
DR PDB; 5LRN; X-ray; 1.55 A; A/B=219-541.
DR PDB; 5YLC; X-ray; 1.50 A; A=216-541.
DR PDB; 5YLE; X-ray; 1.85 A; A=216-541.
DR PDB; 5YLF; X-ray; 1.50 A; A=216-541.
DR PDB; 5ZJV; X-ray; 1.82 A; A=216-541.
DR PDB; 6LI4; X-ray; 1.78 A; A/B=219-541.
DR PDB; 6LI5; X-ray; 1.82 A; A/B=219-541.
DR PDB; 6LI6; X-ray; 1.68 A; A/B=219-541.
DR PDB; 7WAA; X-ray; 1.58 A; A/B=219-541.
DR PDBsum; 5GOV; -.
DR PDBsum; 5GRR; -.
DR PDBsum; 5K4P; -.
DR PDBsum; 5LRM; -.
DR PDBsum; 5LRN; -.
DR PDBsum; 5YLC; -.
DR PDBsum; 5YLE; -.
DR PDBsum; 5YLF; -.
DR PDBsum; 5ZJV; -.
DR PDBsum; 6LI4; -.
DR PDBsum; 6LI5; -.
DR PDBsum; 6LI6; -.
DR PDBsum; 7WAA; -.
DR AlphaFoldDB; A0A0R6L508; -.
DR SMR; A0A0R6L508; -.
DR EnsemblBacteria; KST31405; KST31405; APZ14_31440.
DR GeneID; 66606343; -.
DR BRENDA; 2.7.8.43; 2026.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008484; F:sulfuric ester hydrolase activity; IEA:InterPro.
DR GO; GO:0016772; F:transferase activity, transferring phosphorus-containing groups; IEA:InterPro.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR Gene3D; 3.40.720.10; -; 1.
DR InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR InterPro; IPR012549; EptA-like_N.
DR InterPro; IPR040423; PEA_transferase.
DR InterPro; IPR000917; Sulfatase_N.
DR PANTHER; PTHR30443; PTHR30443; 1.
DR Pfam; PF08019; EptA_B_N; 1.
DR Pfam; PF00884; Sulfatase; 1.
DR SUPFAM; SSF53649; SSF53649; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic resistance; Cell inner membrane; Cell membrane;
KW Membrane; Plasmid; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..541
FT /note="Probable phosphatidylethanolamine transferase Mcr-1"
FT /id="PRO_0000435624"
FT TOPO_DOM 1..14
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 15..35
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 36..47
FT /note="Periplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 48..68
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 69..73
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 74..94
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 95..122
FT /note="Periplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 123..143
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 144..157
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 158..178
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 179..541
FT /note="Periplasmic"
FT /evidence="ECO:0000305"
FT STRAND 227..230
FT /evidence="ECO:0007829|PDB:5K4P"
FT TURN 232..234
FT /evidence="ECO:0007829|PDB:5K4P"
FT STRAND 238..245
FT /evidence="ECO:0007829|PDB:5K4P"
FT HELIX 250..252
FT /evidence="ECO:0007829|PDB:5K4P"
FT HELIX 254..256
FT /evidence="ECO:0007829|PDB:5K4P"
FT HELIX 264..267
FT /evidence="ECO:0007829|PDB:5K4P"
FT STRAND 272..276
FT /evidence="ECO:0007829|PDB:5K4P"
FT HELIX 285..292
FT /evidence="ECO:0007829|PDB:5K4P"
FT HELIX 297..300
FT /evidence="ECO:0007829|PDB:5K4P"
FT HELIX 303..308
FT /evidence="ECO:0007829|PDB:5K4P"
FT HELIX 312..318
FT /evidence="ECO:0007829|PDB:5K4P"
FT STRAND 322..330
FT /evidence="ECO:0007829|PDB:5K4P"
FT TURN 333..338
FT /evidence="ECO:0007829|PDB:5K4P"
FT HELIX 341..343
FT /evidence="ECO:0007829|PDB:5K4P"
FT STRAND 344..346
FT /evidence="ECO:0007829|PDB:5K4P"
FT TURN 350..352
FT /evidence="ECO:0007829|PDB:5K4P"
FT STRAND 357..359
FT /evidence="ECO:0007829|PDB:5K4P"
FT HELIX 366..370
FT /evidence="ECO:0007829|PDB:5K4P"
FT HELIX 373..379
FT /evidence="ECO:0007829|PDB:5K4P"
FT TURN 380..382
FT /evidence="ECO:0007829|PDB:5K4P"
FT STRAND 385..390
FT /evidence="ECO:0007829|PDB:5K4P"
FT HELIX 399..402
FT /evidence="ECO:0007829|PDB:5K4P"
FT HELIX 405..407
FT /evidence="ECO:0007829|PDB:5K4P"
FT HELIX 419..421
FT /evidence="ECO:0007829|PDB:5K4P"
FT HELIX 424..450
FT /evidence="ECO:0007829|PDB:5K4P"
FT TURN 451..455
FT /evidence="ECO:0007829|PDB:5K4P"
FT STRAND 456..465
FT /evidence="ECO:0007829|PDB:5K4P"
FT STRAND 469..471
FT /evidence="ECO:0007829|PDB:5K4P"
FT HELIX 472..474
FT /evidence="ECO:0007829|PDB:5K4P"
FT STRAND 476..478
FT /evidence="ECO:0007829|PDB:5K4P"
FT TURN 482..484
FT /evidence="ECO:0007829|PDB:5K4P"
FT HELIX 487..489
FT /evidence="ECO:0007829|PDB:5K4P"
FT STRAND 494..498
FT /evidence="ECO:0007829|PDB:5K4P"
FT HELIX 500..502
FT /evidence="ECO:0007829|PDB:5K4P"
FT HELIX 515..517
FT /evidence="ECO:0007829|PDB:5K4P"
FT HELIX 518..525
FT /evidence="ECO:0007829|PDB:5K4P"
FT HELIX 531..533
FT /evidence="ECO:0007829|PDB:5K4P"
SQ SEQUENCE 541 AA; 60124 MW; 2418130C94864FBE CRC64;
MMQHTSVWYR RSVSPFVLVA SVAVFLTATA NLTFFDKISQ TYPIADNLGF VLTIAVVLFG
AMLLITTLLS SYRYVLKPVL ILLLIMGAVT SYFTDTYGTV YDTTMLQNAL QTDQAETKDL
LNAAFIMRII GLGVLPSLLV AFVKVDYPTW GKGLMRRLGL IVASLALILL PVVAFSSHYA
SFFRVHKPLR SYVNPIMPIY SVGKLASIEY KKASAPKDTI YHAKDAVQAT KPDMRKPRLV
VFVVGETARA DHVSFNGYER DTFPQLAKID GVTNFSNVTS CGTSTAYSVP CMFSYLGADE
YDVDTAKYQE NVLDTLDRLG VSILWRDNNS DSKGVMDKLP KAQFADYKSA TNNAICNTNP
YNECRDVGML VGLDDFVAAN NGKDMLIMLH QMGNHGPAYF KRYDEKFAKF TPVCEGNELA
KCEHQSLINA YDNALLATDD FIAQSIQWLQ THSNAYDVSM LYVSDHGESL GENGVYLHGM
PNAFAPKEQR SVPAFFWTDK QTGITPMATD TVLTHDAITP TLLKLFDVTA DKVKDRTAFI
R
