FAA23_MYCTU
ID FAA23_MYCTU Reviewed; 584 AA.
AC P9WQ47; L0TGV3; O07797; Q7D4S9;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 46.
DE RecName: Full=Long-chain-fatty-acid--AMP ligase FadD23 {ECO:0000305};
DE EC=6.2.1.57 {ECO:0000305|PubMed:17768256};
DE AltName: Full=FAAL23 {ECO:0000303|PubMed:19182784};
DE AltName: Full=Long-chain fatty acid adenylyltransferase FadD23 {ECO:0000305};
DE AltName: Full=Long-chain-fatty-acid adenylase/transferase FadD23 {ECO:0000305};
GN Name=fadD23; OrderedLocusNames=Rv3826;
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 PATHWAY.
RX PubMed=17389997; DOI=10.1039/b616817p;
RA Gokhale R.S., Saxena P., Chopra T., Mohanty D.;
RT "Versatile polyketide enzymatic machinery for the biosynthesis of complex
RT mycobacterial lipids.";
RL Nat. Prod. Rep. 24:267-277(2007).
RN [3]
RP FUNCTION IN SULFOLIPID BIOSYNTHESIS, PATHWAY, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=17768256; DOI=10.1099/mic.0.2007/007864-0;
RA Lynett J., Stokes R.W.;
RT "Selection of transposon mutants of Mycobacterium tuberculosis with
RT increased macrophage infectivity identifies fadD23 to be involved in
RT sulfolipid production and association with macrophages.";
RL Microbiology 153:3133-3140(2007).
RN [4]
RP 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 [5]
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).
CC -!- FUNCTION: Catalyzes the activation of long-chain fatty acids as acyl-
CC adenylates (acyl-AMP), which are then transferred to the
CC multifunctional polyketide synthase (PKS) type III for further chain
CC extension (Probable). Involved in the biosynthesis of sulfolipid 1 (SL-
CC 1) (PubMed:17389997, PubMed:17768256). {ECO:0000269|PubMed:17389997,
CC ECO:0000269|PubMed:17768256, ECO:0000305|PubMed:17768256}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + hexadecanoate + holo-[(hydroxy)phthioceranic acid
CC synthase] = AMP + diphosphate + hexadecanoyl-[(hydroxy)phthioceranic
CC acid synthase]; Xref=Rhea:RHEA:59164, Rhea:RHEA-COMP:15244,
CC Rhea:RHEA-COMP:15305, ChEBI:CHEBI:7896, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:64479, ChEBI:CHEBI:78483,
CC ChEBI:CHEBI:456215; EC=6.2.1.57;
CC Evidence={ECO:0000305|PubMed:17768256};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + holo-[(hydroxy)phthioceranic acid synthase] +
CC octadecanoate = AMP + diphosphate + octadecanoyl-
CC [(hydroxy)phthioceranic acid synthase]; Xref=Rhea:RHEA:59168,
CC Rhea:RHEA-COMP:15305, Rhea:RHEA-COMP:15306, ChEBI:CHEBI:25629,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:78495, ChEBI:CHEBI:456215; EC=6.2.1.57;
CC Evidence={ECO:0000305|PubMed:17768256};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + dodecanoate + H(+) = diphosphate + dodecanoyl-AMP;
CC Xref=Rhea:RHEA:43712, ChEBI:CHEBI:15378, ChEBI:CHEBI:18262,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:83623;
CC Evidence={ECO:0000269|PubMed:19182784};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43713;
CC Evidence={ECO:0000269|PubMed:19182784};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H(+) + hexadecanoate = diphosphate + hexadecanoyl-AMP;
CC Xref=Rhea:RHEA:43708, ChEBI:CHEBI:7896, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:83627;
CC Evidence={ECO:0000269|PubMed:19182784};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43709;
CC Evidence={ECO:0000269|PubMed:19182784};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000305|PubMed:17389997, ECO:0000305|PubMed:17768256}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Disruption of fadD23 increases binding affinity
CC to human macrophage-like cell THP-1 and shows a lack of sulfolipid 1
CC production as compared to wild-type. {ECO:0000269|PubMed:17768256}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP46655.1; -; Genomic_DNA.
DR PIR; F70522; F70522.
DR RefSeq; NP_218343.1; NC_000962.3.
DR RefSeq; WP_003899713.1; NZ_NVQJ01000022.1.
DR AlphaFoldDB; P9WQ47; -.
DR SMR; P9WQ47; -.
DR STRING; 83332.Rv3826; -.
DR SwissLipids; SLP:000000984; -.
DR PaxDb; P9WQ47; -.
DR DNASU; 886154; -.
DR GeneID; 886154; -.
DR KEGG; mtu:Rv3826; -.
DR TubercuList; Rv3826; -.
DR eggNOG; COG0318; Bacteria.
DR OMA; FRPEAMC; -.
DR PhylomeDB; P9WQ47; -.
DR BioCyc; MetaCyc:G185E-8122-MON; -.
DR UniPathway; UPA00094; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0070566; F:adenylyltransferase activity; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0071766; P:Actinobacterium-type cell wall biogenesis; IMP:UniProtKB.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:0046506; P:sulfolipid biosynthetic process; IMP:MTBBASE.
DR CDD; cd05931; FAAL; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR040097; FAAL/FAAC.
DR Pfam; PF00501; AMP-binding; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Fatty acid metabolism; Ligase; Lipid metabolism; Membrane;
KW Nucleotide-binding; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..584
FT /note="Long-chain-fatty-acid--AMP ligase FadD23"
FT /id="PRO_0000406793"
FT TRANSMEM 199..219
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 225..245
FT /note="Helical"
FT /evidence="ECO:0000255"
SQ SEQUENCE 584 AA; 62841 MW; 99639AB9BEEA39EF CRC64;
MVSLSIPSML RQCVNLHPDG TAFTYIDYER DSEGISESLT WSQVYRRTLN VAAEVRRHAA
IGDRAVILAP QGLDYIVAFL GALQAGLIAV PLSAPLGGAS DERVDAVVRD AKPNVVLTTS
AIMGDVVPRV TPPPGIASPP TVAVDQLDLD SPIRSNIVDD SLQTTAYLQY TSGSTRTPAG
VMITYKNILA NFQQMISAYF ADTGAVPPLD LFIMSWLPFY HDMGLVLGVC APIIVGCGAV
LTSPVAFLQR PARWLQLMAR EGQAFSAAPN FAFELTAAKA IDDDLAGLDL GRIKTILCGS
ERVHPATLKR FVDRFSRFNL REFAIRPAYG LAEATVYVAT SQAGQPPEIR YFEPHELSAG
QAKPCATGAG TALVSYPLPQ SPIVRIVDPN TNTECPPGTI GEIWVHGDNV AGGYWEKPDE
TERTFGGALV APSAGTPVGP WLRTGDSGFV SEDKFFIIGR IKDLLIVYGR NHSPDDIEAT
IQEITRGRCA AIAVPSNGVE KLVAIVELNN RGNLDTERLS FVTREVTSAI STSHGLSVSD
LVLVAPGSIP ITTSGKVRRA ECVKLYRHNE FTRLDAKPLQ ASDL
