FADK_ECOLI
ID FADK_ECOLI Reviewed; 566 AA.
AC P38135; P76202; P76902; P76903;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 07-SEP-2016, sequence version 4.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Medium-chain fatty-acid--CoA ligase {ECO:0000305|PubMed:15213221, ECO:0000305|PubMed:19477415};
DE EC=6.2.1.- {ECO:0000269|PubMed:15213221, ECO:0000269|PubMed:19477415};
DE AltName: Full=Acyl-CoA synthetase {ECO:0000303|PubMed:15213221};
DE Short=ACS {ECO:0000303|PubMed:15213221};
DE AltName: Full=Fatty acyl-CoA synthetase FadK {ECO:0000305};
GN Name=fadK {ECO:0000303|PubMed:15213221}; Synonyms=ydiD;
GN OrderedLocusNames=b1701, JW5910;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC 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=9097039; DOI=10.1093/dnares/3.6.363;
RA Aiba H., Baba T., Fujita K., Hayashi K., Inada T., Isono K., Itoh T.,
RA Kasai H., Kashimoto K., Kimura S., Kitakawa M., Kitagawa M., Makino K.,
RA Miki T., Mizobuchi K., Mori H., Mori T., Motomura K., Nakade S.,
RA Nakamura Y., Nashimoto H., Nishio Y., Oshima T., Saito N., Sampei G.,
RA Seki Y., Sivasundaram S., Tagami H., Takeda J., Takemoto K., Takeuchi Y.,
RA Wada C., Yamamoto Y., Horiuchi T.;
RT "A 570-kb DNA sequence of the Escherichia coli K-12 genome corresponding to
RT the 28.0-40.1 min region on the linkage map.";
RL DNA Res. 3:363-377(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 374-566.
RC STRAIN=K12;
RA Holzschu D.L., McElver J.A., Liao C.C., Berry A.;
RT "The cloning and sequence of the E. coli pps gene.";
RL Submitted (JUN-1991) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP IDENTIFICATION.
RX PubMed=7984428; DOI=10.1093/nar/22.22.4756;
RA Borodovsky M., Rudd K.E., Koonin E.V.;
RT "Intrinsic and extrinsic approaches for detecting genes in a bacterial
RT genome.";
RL Nucleic Acids Res. 22:4756-4767(1994).
RN [6]
RP FUNCTION IN ANAEROBIC BETA-OXIDATION PATHWAY, INDUCTION, DISRUPTION
RP PHENOTYPE, AND PATHWAY.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=12535077; DOI=10.1046/j.1365-2958.2003.03341.x;
RA Campbell J.W., Morgan-Kiss R.M., Cronan J.E. Jr.;
RT "A new Escherichia coli metabolic competency: growth on fatty acids by a
RT novel anaerobic beta-oxidation pathway.";
RL Mol. Microbiol. 47:793-805(2003).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBSTRATE SPECIFICITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, INDUCTION, AND
RP IDENTIFICATION OF START CODON.
RC STRAIN=K12 / MC1061 / ATCC 53338 / DSM 7140;
RX PubMed=15213221; DOI=10.1074/jbc.m405233200;
RA Morgan-Kiss R.M., Cronan J.E.;
RT "The Escherichia coli fadK (ydiD) gene encodes an anerobically regulated
RT short chain acyl-CoA synthetase.";
RL J. Biol. Chem. 279:37324-37333(2004).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY.
RX PubMed=19477415; DOI=10.1016/j.chembiol.2009.03.012;
RA Leger M., Gavalda S., Guillet V., van der Rest B., Slama N., Montrozier H.,
RA Mourey L., Quemard A., Daffe M., Marrakchi H.;
RT "The dual function of the Mycobacterium tuberculosis FadD32 required for
RT mycolic acid biosynthesis.";
RL Chem. Biol. 16:510-519(2009).
CC -!- FUNCTION: Catalyzes the esterification, concomitant with transport, of
CC exogenous fatty acids into metabolically active CoA thioesters for
CC subsequent degradation or incorporation into phospholipids. Is
CC maximally active on C6:0, C8:0 and C12:0 fatty acids, while has a low
CC activity on C14-C18 chain length fatty acids (PubMed:15213221,
CC PubMed:19477415). Is involved in the anaerobic beta-oxidative
CC degradation of fatty acids, which allows anaerobic growth of E.coli on
CC fatty acids as a sole carbon and energy source in the presence of
CC nitrate or fumarate as a terminal electron acceptor (PubMed:12535077).
CC Can functionally replace FadD under anaerobic conditions
CC (PubMed:12535077). {ECO:0000269|PubMed:12535077,
CC ECO:0000269|PubMed:15213221, ECO:0000269|PubMed:19477415}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + CoA + hexanoate = AMP + diphosphate + hexanoyl-CoA;
CC Xref=Rhea:RHEA:43740, ChEBI:CHEBI:17120, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:62620,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:15213221};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + CoA + octanoate = AMP + diphosphate + octanoyl-CoA;
CC Xref=Rhea:RHEA:33631, ChEBI:CHEBI:25646, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57386,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:15213221,
CC ECO:0000269|PubMed:19477415};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + CoA + dodecanoate = AMP + diphosphate + dodecanoyl-CoA;
CC Xref=Rhea:RHEA:33623, ChEBI:CHEBI:18262, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57375,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:19477415};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15213221};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.7-8.2. {ECO:0000269|PubMed:15213221};
CC -!- PATHWAY: Lipid metabolism; fatty acid beta-oxidation.
CC {ECO:0000269|PubMed:12535077, ECO:0000305|PubMed:15213221}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P9WQ37}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein.
CC Note=Partially membrane-associated. {ECO:0000305|PubMed:15213221}.
CC -!- INDUCTION: Expression independent of FadR (PubMed:12535077). FadK is
CC not expressed under aerobic growth conditions, the levels of anaerobic
CC expression vary with the terminal electron acceptor, with more
CC expression during growth on fumarate than on nitrate (at protein level)
CC (PubMed:15213221). {ECO:0000269|PubMed:12535077,
CC ECO:0000269|PubMed:15213221}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene grow normally on aerobic
CC oleate plates, but grow relatively poorly on oleate plus nitrate plates
CC under anaerobic conditions. The double fadD fadK deletion mutant fails
CC to grow on fatty acids under either aerobic or anaerobic conditions,
CC although fadD mutants grow on fatty acids under anaerobic conditions.
CC {ECO:0000269|PubMed:12535077}.
CC -!- MISCELLANEOUS: Probably starts on Met-1; overexpressed protein starting
CC at Met-19 has lower activity, forms aggregates during reaction and is
CC unstable in storage at -80 degrees Celsius (PubMed:15213221).
CC {ECO:0000269|PubMed:15213221}.
CC -!- MISCELLANEOUS: The enzymatic mechanism is a two-step reaction that
CC proceeds via the intermediate formation of an acyl-adenylate (acyl-AMP)
CC intermediate. {ECO:0000269|PubMed:15213221}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC74771.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=M69116; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U00096; AAC74771.2; ALT_INIT; Genomic_DNA.
DR EMBL; AP009048; BAA15470.2; -; Genomic_DNA.
DR EMBL; M69116; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; E64928; E64928.
DR RefSeq; NP_416216.4; NC_000913.3.
DR AlphaFoldDB; P38135; -.
DR SMR; P38135; -.
DR BioGRID; 4260285; 308.
DR STRING; 511145.b1701; -.
DR SwissLipids; SLP:000000973; -.
DR PaxDb; P38135; -.
DR PRIDE; P38135; -.
DR EnsemblBacteria; AAC74771; AAC74771; b1701.
DR EnsemblBacteria; BAA15470; BAA15470; BAA15470.
DR GeneID; 946213; -.
DR KEGG; ecj:JW5910; -.
DR KEGG; eco:b1701; -.
DR PATRIC; fig|511145.12.peg.1772; -.
DR EchoBASE; EB2260; -.
DR eggNOG; COG0318; Bacteria.
DR HOGENOM; CLU_000022_59_7_6; -.
DR InParanoid; P38135; -.
DR BioCyc; EcoCyc:EG12357-MON; -.
DR BioCyc; MetaCyc:EG12357-MON; -.
DR UniPathway; UPA00659; -.
DR PRO; PR:P38135; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0031956; F:medium-chain fatty acid-CoA ligase activity; IDA:EcoCyc.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR025110; AMP-bd_C.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Fatty acid metabolism; Ligase;
KW Lipid metabolism; Magnesium; Membrane; Nucleotide-binding;
KW Reference proteome.
FT CHAIN 1..566
FT /note="Medium-chain fatty-acid--CoA ligase"
FT /id="PRO_0000193132"
FT BINDING 231..242
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
SQ SEQUENCE 566 AA; 62759 MW; 057236D5F7F2FCE7 CRC64;
MHPTGPHLGP DVLFRESNMK VTLTFNEQRR AAYRQQGLWG DASLADYWQQ TARAMPDKIA
VVDNHGASYT YSALDHAASC LANWMLAKGI ESGDRIAFQL PGWCEFTVIY LACLKIGAVS
VPLLPSWREA ELVWVLNKCQ AKMFFAPTLF KQTRPVDLIL PLQNQLPQLQ QIVGVDKLAP
ATSSLSLSQI IADNTSLTTA ITTHGDELAA VLFTSGTEGL PKGVMLTHNN ILASERAYCA
RLNLTWQDVF MMPAPLGHAT GFLHGVTAPF LIGARSVLLD IFTPDACLAL LEQQRCTCML
GATPFVYDLL NVLEKQPADL SALRFFLCGG TTIPKKVARE CQQRGIKLLS VYGSTESSPH
AVVNLDDPLS RFMHTDGYAA AGVEIKVVDD ARKTLPPGCE GEEASRGPNV FMGYFDEPEL
TARALDEEGW YYSGDLCRMD EAGYIKITGR KKDIIVRGGE NISSREVEDI LLQHPKIHDA
CVVAMSDERL GERSCAYVVL KAPHHSLSLE EVVAFFSRKR VAKYKYPEHI VVIEKLPRTT
SGKIQKFLLR KDIMRRLTQD VCEEIE
