FAC6_MYCTU
ID FAC6_MYCTU Reviewed; 597 AA.
AC O05307; F2GFY2; I6Y9X8; Q7D8M1;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Medium/long-chain-fatty-acid--CoA ligase FadD6 {ECO:0000305};
DE EC=6.2.1.2 {ECO:0000269|PubMed:15984864, ECO:0000269|PubMed:19182784};
DE EC=6.2.1.3 {ECO:0000269|PubMed:15984864, ECO:0000269|PubMed:19182784, ECO:0000269|PubMed:25490545};
DE AltName: Full=FACL6 {ECO:0000303|PubMed:19182784};
GN Name=fadD6 {ECO:0000312|EMBL:CCP43962.1};
GN OrderedLocusNames=Rv1206 {ECO:0000312|EMBL:CCP43962.1};
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15984864; DOI=10.1021/ja052991s;
RA Arora P., Vats A., Saxena P., Mohanty D., Gokhale R.S.;
RT "Promiscuous fatty acyl CoA ligases produce acyl-CoA and acyl-SNAC
RT precursors for polyketide biosynthesis.";
RL J. Am. Chem. Soc. 127:9388-9389(2005).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=19182784; DOI=10.1038/nchembio.143;
RA Arora P., Goyal A., Natarajan V.T., Rajakumara E., Verma P., Gupta R.,
RA Yousuf M., Trivedi O.A., Mohanty D., Tyagi A., Sankaranarayanan R.,
RA Gokhale R.S.;
RT "Mechanistic and functional insights into fatty acid activation in
RT Mycobacterium tuberculosis.";
RL Nat. Chem. Biol. 5:166-173(2009).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=25490545; DOI=10.1371/journal.pone.0114877;
RA Daniel J., Sirakova T., Kolattukudy P.;
RT "An acyl-CoA synthetase in Mycobacterium tuberculosis involved in
RT triacylglycerol accumulation during dormancy.";
RL PLoS ONE 9:e114877-e114877(2014).
CC -!- FUNCTION: Catalyzes the activation of medium/long-chain fatty acids as
CC acyl-coenzyme A (acyl-CoA) (PubMed:15984864, PubMed:19182784,
CC PubMed:25490545). May play a role in the uptake of fatty acids by
CC trapping them metabolically as CoA esters (PubMed:25490545). May also
CC play an important role in the channeling of fatty acids into
CC triacylglycerol (TAG) for use by Mycobacterium during its dormancy
CC (PubMed:25490545). {ECO:0000269|PubMed:15984864,
CC ECO:0000269|PubMed:19182784, ECO:0000269|PubMed:25490545}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a medium chain fatty acid + ATP + CoA = a medium-chain fatty
CC acyl-CoA + AMP + diphosphate; Xref=Rhea:RHEA:48340,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:59558, ChEBI:CHEBI:90546, ChEBI:CHEBI:456215; EC=6.2.1.2;
CC Evidence={ECO:0000269|PubMed:15984864, ECO:0000269|PubMed:19182784};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48341;
CC Evidence={ECO:0000269|PubMed:15984864, ECO:0000269|PubMed:19182784};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a long-chain fatty acid + ATP + CoA = a long-chain fatty acyl-
CC CoA + AMP + diphosphate; Xref=Rhea:RHEA:15421, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57560,
CC ChEBI:CHEBI:83139, ChEBI:CHEBI:456215; EC=6.2.1.3;
CC Evidence={ECO:0000269|PubMed:15984864, ECO:0000269|PubMed:19182784,
CC ECO:0000269|PubMed:25490545};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15422;
CC Evidence={ECO:0000269|PubMed:15984864, ECO:0000269|PubMed:19182784,
CC ECO:0000269|PubMed:25490545};
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:15984864,
CC ECO:0000269|PubMed:19182784};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43741;
CC Evidence={ECO:0000269|PubMed:15984864, ECO:0000269|PubMed:19182784};
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:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33632;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + CoA + decanoate = AMP + decanoyl-CoA + diphosphate;
CC Xref=Rhea:RHEA:33627, ChEBI:CHEBI:27689, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:61430,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33628;
CC Evidence={ECO:0000269|PubMed:15984864};
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:15984864,
CC ECO:0000269|PubMed:19182784};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33624;
CC Evidence={ECO:0000269|PubMed:15984864, ECO:0000269|PubMed:19182784};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + CoA + tetradecanoate = AMP + diphosphate +
CC tetradecanoyl-CoA; Xref=Rhea:RHEA:33619, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:30807, ChEBI:CHEBI:33019, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57385, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33620;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + CoA + hexadecanoate = AMP + diphosphate + hexadecanoyl-
CC CoA; Xref=Rhea:RHEA:30751, ChEBI:CHEBI:7896, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:15984864,
CC ECO:0000269|PubMed:19182784, ECO:0000269|PubMed:25490545};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30752;
CC Evidence={ECO:0000269|PubMed:15984864, ECO:0000269|PubMed:19182784,
CC ECO:0000269|PubMed:25490545};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + CoA + octadecanoate = AMP + diphosphate + octadecanoyl-
CC CoA; Xref=Rhea:RHEA:33615, ChEBI:CHEBI:25629, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57394,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:15984864,
CC ECO:0000269|PubMed:25490545};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33616;
CC Evidence={ECO:0000269|PubMed:15984864, ECO:0000269|PubMed:25490545};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=9-decenoate + ATP + CoA = 9-decenoyl-CoA + AMP + diphosphate;
CC Xref=Rhea:RHEA:44228, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:33163, ChEBI:CHEBI:57287, ChEBI:CHEBI:84214,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44229;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoate + ATP + CoA = (9Z)-octadecenoyl-CoA + AMP +
CC diphosphate; Xref=Rhea:RHEA:33607, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:33019, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57387, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:15984864, ECO:0000269|PubMed:25490545};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33608;
CC Evidence={ECO:0000269|PubMed:15984864, ECO:0000269|PubMed:25490545};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxyhexadecanoate + ATP + CoA = 2-hydroxyhexadecanoyl-CoA
CC + AMP + diphosphate; Xref=Rhea:RHEA:44204, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:65097,
CC ChEBI:CHEBI:74115, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44205;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-hydroxytetradecanoate + ATP + CoA = 3-hydroxytetradecanoyl-
CC CoA + AMP + diphosphate; Xref=Rhea:RHEA:44212, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:84197,
CC ChEBI:CHEBI:84198, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44213;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=12-hydroxyoctadecanoate + ATP + CoA = 12-hydroxyoctadecanoyl-
CC CoA + AMP + diphosphate; Xref=Rhea:RHEA:44216, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:84201,
CC ChEBI:CHEBI:84202, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44217;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=15-hydroxypentadecanoate + ATP + CoA = 15-
CC hydroxypentadecanoyl-CoA + AMP + diphosphate; Xref=Rhea:RHEA:44220,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:84203, ChEBI:CHEBI:84205, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44221;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=16-hydroxyhexadecanoate + ATP + CoA = 16-hydroxyhexadecanoyl-
CC CoA + AMP + diphosphate; Xref=Rhea:RHEA:44224, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:55329, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:84207, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44225;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-methylhexadecanoate + ATP + CoA = 2-methylhexadecanoyl-CoA +
CC AMP + diphosphate; Xref=Rhea:RHEA:44192, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:84175,
CC ChEBI:CHEBI:84182, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44193;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-methylundecanoate + ATP + CoA = 3-methylundecanoyl-CoA + AMP
CC + diphosphate; Xref=Rhea:RHEA:44196, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:84183,
CC ChEBI:CHEBI:84184, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44197;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=12-methyltridecanoate + ATP + CoA = 12-methyltridecanoyl-CoA +
CC AMP + diphosphate; Xref=Rhea:RHEA:44208, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:84193,
CC ChEBI:CHEBI:84195, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44209;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=12-methyloctadecanoate + ATP + CoA = 12-methyloctadecanoyl-CoA
CC + AMP + diphosphate; Xref=Rhea:RHEA:44200, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:84176,
CC ChEBI:CHEBI:84181, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44201;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- INDUCTION: Expression is significantly increased during in vitro
CC dormancy (at protein level). {ECO:0000269|PubMed:25490545}.
CC -!- DISRUPTION PHENOTYPE: Deletion mutant displays a diminished ability to
CC synthesize acyl-coenzyme A in cell-free extracts. Deletion of the gene
CC results in a significant decrease in the accumulation of intracellular
CC triacylglycerol (TAG) in Mycobacterium under dormancy-inducing
CC conditions in vitro. {ECO:0000269|PubMed:25490545}.
CC -!- MISCELLANEOUS: Stimulates fatty acid uptake in E.coli cells.
CC {ECO:0000269|PubMed:25490545}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP43962.1; -; Genomic_DNA.
DR RefSeq; NP_215722.1; NC_000962.3.
DR RefSeq; WP_003406240.1; NZ_NVQJ01000039.1.
DR AlphaFoldDB; O05307; -.
DR SMR; O05307; -.
DR STRING; 83332.Rv1206; -.
DR SwissLipids; SLP:000000977; -.
DR TCDB; 4.C.1.1.3; the fatty acid group translocation (fat) family.
DR PaxDb; O05307; -.
DR PRIDE; O05307; -.
DR DNASU; 887549; -.
DR GeneID; 45425176; -.
DR GeneID; 887549; -.
DR KEGG; mtu:Rv1206; -.
DR PATRIC; fig|83332.111.peg.1348; -.
DR TubercuList; Rv1206; -.
DR eggNOG; COG0318; Bacteria.
DR OMA; IVGMGQC; -.
DR PhylomeDB; O05307; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0047760; F:butyrate-CoA ligase activity; IEA:UniProtKB-EC.
DR GO; GO:0005324; F:long-chain fatty acid transporter activity; IBA:GO_Central.
DR GO; GO:0004467; F:long-chain fatty acid-CoA ligase activity; IBA:GO_Central.
DR GO; GO:0031956; F:medium-chain fatty acid-CoA ligase activity; IEA:UniProtKB-EC.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
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 InterPro; IPR030310; FadD17/FadD6-like.
DR PANTHER; PTHR43107:SF15; PTHR43107:SF15; 1.
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; Fatty acid metabolism; Ligase; Lipid metabolism;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..597
FT /note="Medium/long-chain-fatty-acid--CoA ligase FadD6"
FT /id="PRO_0000451298"
SQ SEQUENCE 597 AA; 64337 MW; A0BEB5EB19A05CB7 CRC64;
MSDYYGGAHT TVRLIDLATR MPRVLADTPV IVRGAMTGLL ARPNSKASIG TVFQDRAARY
GDRVFLKFGD QQLTYRDANA TANRYAAVLA ARGVGPGDVV GIMLRNSPST VLAMLATVKC
GAIAGMLNYH QRGEVLAHSL GLLDAKVLIA ESDLVSAVAE CGASRGRVAG DVLTVEDVER
FATTAPATNP ASASAVQAKD TAFYIFTSGT TGFPKASVMT HHRWLRALAV FGGMGLRLKG
SDTLYSCLPL YHNNALTVAV SSVINSGATL ALGKSFSASR FWDEVIANRA TAFVYIGEIC
RYLLNQPAKP TDRAHQVRVI CGNGLRPEIW DEFTTRFGVA RVCEFYAASE GNSAFINIFN
VPRTAGVSPM PLAFVEYDLD TGDPLRDASG RVRRVPDGEP GLLLSRVNRL QPFDGYTDPV
ASEKKLVRNA FRDGDCWFNT GDVMSPQGMG HAAFVDRLGD TFRWKGENVA TTQVEAALAS
DQTVEECTVY GVQIPRTGGR AGMAAITLRA GAEFDGQALA RTVYGHLPGY ALPLFVRVVG
SLAHTTTFKS RKVELRNQAY GADIEDPLYV LAGPDEGYVP YYAEYPEEVS LGRRPQG
