LPXF_FRATN
ID LPXF_FRATN Reviewed; 222 AA.
AC A0Q4N6; Q1WDN3;
DT 29-APR-2015, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 70.
DE RecName: Full=Lipid A 4'-phosphatase {ECO:0000303|PubMed:16467300};
DE EC=3.1.-.- {ECO:0000305};
GN Name=lpxF {ECO:0000303|PubMed:16467300}; OrderedLocusNames=FTN_0295;
GN ORFNames=AW25_1746;
OS Francisella tularensis subsp. novicida (strain U112).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Thiotrichales;
OC Francisellaceae; Francisella.
OX NCBI_TaxID=401614;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBSTRATE SPECIFICITY,
RP SUBCELLULAR LOCATION, EXPRESSION IN E.COLI, AND ANTIBIOTIC RESISTANCE.
RC STRAIN=U112;
RX PubMed=16467300; DOI=10.1074/jbc.m600435200;
RA Wang X., McGrath S.C., Cotter R.J., Raetz C.R.;
RT "Expression cloning and periplasmic orientation of the Francisella novicida
RT lipid A 4'-phosphatase LpxF.";
RL J. Biol. Chem. 281:9321-9330(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=U112;
RX PubMed=17550600; DOI=10.1186/gb-2007-8-6-r102;
RA Rohmer L., Fong C., Abmayr S., Wasnick M., Larson Freeman T.J., Radey M.,
RA Guina T., Svensson K., Hayden H.S., Jacobs M., Gallagher L.A., Manoil C.,
RA Ernst R.K., Drees B., Buckley D., Haugen E., Bovee D., Zhou Y., Chang J.,
RA Levy R., Lim R., Gillett W., Guenthener D., Kang A., Shaffer S.A.,
RA Taylor G., Chen J., Gallis B., D'Argenio D.A., Forsman M., Olson M.V.,
RA Goodlett D.R., Kaul R., Miller S.I., Brittnacher M.J.;
RT "Comparison of Francisella tularensis genomes reveals evolutionary events
RT associated with the emergence of human pathogenic strains.";
RL Genome Biol. 8:R102.1-R102.16(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=U112;
RA Bishop-Lilly K.A., Broomall S.M., Chain P.S., Chertkov O., Coyne S.R.,
RA Daligault H.E., Davenport K.W., Erkkila T., Frey K.G., Gibbons H.S., Gu W.,
RA Jaissle J., Johnson S.L., Koroleva G.I., Ladner J.T., Lo C.-C.,
RA Minogue T.D., Munk C., Palacios G.F., Redden C.L., Rosenzweig C.N.,
RA Scholz M.B., Teshima H., Xu Y.;
RL Submitted (OCT-2014) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP LIPID A STRUCTURE.
RC STRAIN=U112;
RX PubMed=17263332; DOI=10.1021/ac061654e;
RA Schilling B., McLendon M.K., Phillips N.J., Apicella M.A., Gibson B.W.;
RT "Characterization of lipid A acylation patterns in Francisella tularensis,
RT Francisella novicida, and Francisella philomiragia using multiple-stage
RT mass spectrometry and matrix-assisted laser desorption/ionization on an
RT intermediate vacuum source linear ion trap.";
RL Anal. Chem. 79:1034-1042(2007).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, LIPID A STRUCTURE,
RP AND ANTIBIOTIC RESISTANCE.
RC STRAIN=U112;
RX PubMed=17360489; DOI=10.1073/pnas.0611606104;
RA Wang X., Ribeiro A.A., Guan Z., Abraham S.N., Raetz C.R.;
RT "Attenuated virulence of a Francisella mutant lacking the lipid A 4'-
RT phosphatase.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:4136-4141(2007).
CC -!- FUNCTION: Removes the 4'-phosphate moiety from lipid IV(A) (a
CC tetraacylated precursor of lipid A) and from pentaacylated lipid A, but
CC not from hexaacylated lipid A (as is found in E.coli). Does not
CC dephosphorylate phosphatidic acid, phosphatidylglycerophosphate, or the
CC 1-phosphate group of lipid A and lipid A precursors. Its expression in
CC E.coli confers resistance to the cationic antimicrobial peptide (CAMP)
CC polymyxin B (PubMed:16467300). Plays a critical role in the ability of
CC the bacteria to avoid the host's innate immune system, especially the
CC bactericidal action of CAMPs, although whether it is CAMP-sensitivity
CC or increased sensitivity to the immune system is not clear
CC (PubMed:17360489). {ECO:0000269|PubMed:16467300,
CC ECO:0000269|PubMed:17360489}.
CC -!- PATHWAY: Bacterial outer membrane biogenesis; LPS lipid A biosynthesis.
CC {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000305|PubMed:16467300,
CC ECO:0000305|PubMed:17360489}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Activity depends on msbA function when expressed in
CC E.coli, strongly suggesting this protein acts in the periplasm (MsbA
CC flips the lipopolysaccharide precursor across the cell inner membrane).
CC {ECO:0000269|PubMed:16467300}.
CC -!- DISRUPTION PHENOTYPE: Lipid A retains the 4'-phosphate group (giving
CC bi-phosphorylated lipid A) and a 3'-hydroxyacyl chain not usually seen
CC in wild-type cells. Cells grow more slowly in liquid culture and are
CC more sensitive to the CAMP polymyxin B. Bacteria are avirulent upon
CC infection of C57BL/6 mice, the natural host of this bacterium; they do
CC not colonize mouse spleen. Upon mouse intraperitoneal injection induces
CC pro-inflammatory cytokine IL-6 and monocyte chemoattractant protein 1
CC and keratinocyte-derived chemokine, two potent chemoattractants;
CC bacterial viability decreases about 100-fold.
CC {ECO:0000269|PubMed:17360489}.
CC -!- MISCELLANEOUS: In Francisella lipid A is mono-phosphorylated at
CC position 1- and tetraacylated, it lacks the 4'-phosphate residue found
CC in E.coli (PubMed:17263332, PubMed:17360489). More than 90% of lipid A
CC is in a free form that lacks core oligosaccharide and O-antigen
CC (PubMed:17360489). {ECO:0000269|PubMed:17263332,
CC ECO:0000269|PubMed:17360489}.
CC -!- SIMILARITY: Belongs to the lipid A LpxF 4'-phosphatase family.
CC {ECO:0000305}.
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DR EMBL; DQ364143; ABC96319.1; -; Genomic_DNA.
DR EMBL; CP000439; ABK89201.1; -; Genomic_DNA.
DR EMBL; CP009633; AJI61280.1; -; Genomic_DNA.
DR RefSeq; WP_003032934.1; NZ_CP009633.1.
DR AlphaFoldDB; A0Q4N6; -.
DR EnsemblBacteria; ABK89201; ABK89201; FTN_0295.
DR GeneID; 60805821; -.
DR KEGG; ftn:FTN_0295; -.
DR KEGG; ftx:AW25_1746; -.
DR HOGENOM; CLU_070327_1_1_6; -.
DR OMA; CSFFSGE; -.
DR OrthoDB; 1928533at2; -.
DR BioCyc; FTUL401614:G1G75-306-MON; -.
DR UniPathway; UPA00973; -.
DR Proteomes; UP000000762; Chromosome.
DR Proteomes; UP000031872; Chromosome.
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:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0009245; P:lipid A biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0009103; P:lipopolysaccharide biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR InterPro; IPR036938; P_Acid_Pase_2/haloperoxi_sf.
DR InterPro; IPR000326; P_Acid_Pase_2/haloperoxidase.
DR Pfam; PF01569; PAP2; 1.
DR SUPFAM; SSF48317; SSF48317; 1.
PE 3: Inferred from homology;
KW Antibiotic resistance; Cell inner membrane; Cell membrane; Hydrolase;
KW Lipid A biosynthesis; Lipid biosynthesis; Lipid metabolism;
KW Lipopolysaccharide biosynthesis; Membrane; Transmembrane;
KW Transmembrane helix; Virulence.
FT CHAIN 1..222
FT /note="Lipid A 4'-phosphatase"
FT /id="PRO_0000432495"
FT TOPO_DOM 1..3
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 4..24
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 25..58
FT /note="Periplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 59..79
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 80..87
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 88..108
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 109..144
FT /note="Periplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 145..165
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 166..169
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 170..190
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 191..193
FT /note="Periplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 194..214
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 215..222
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
SQ SEQUENCE 222 AA; 25552 MW; 15B8850E5BD330E3 CRC64;
MARFHIILGL VVCFFAWIFF LIFPNLDIQF AGHFYNSSAH QFIGGYDGFL GFLHWFARFF
PIFFSIIVIL FLLGSLFIDK FKIKYRKAIF FIAVCLWIGP GLVVNYVFKD HWGRPRPVMV
EQFNGDKIFQ PPFVISSQCD KNCSFVCGDA SMGFWLFAFM PLLATRKKKL VAFIAAVVAG
GGLGLMRMSQ GGHFFSDVVF CGIFVYISTW VVYALMYRKK EY
