CAR_MYCTU
ID CAR_MYCTU Reviewed; 1168 AA.
AC Q50631; F2GGJ8; I6YDT5;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Carboxylic acid reductase {ECO:0000250|UniProtKB:B2HN69, ECO:0000255|HAMAP-Rule:MF_02247};
DE Short=CAR {ECO:0000250|UniProtKB:B2HN69, ECO:0000255|HAMAP-Rule:MF_02247};
DE EC=1.2.1.- {ECO:0000250|UniProtKB:B2HN69, ECO:0000255|HAMAP-Rule:MF_02247};
DE AltName: Full=ATP/NADPH-dependent carboxylic acid reductase {ECO:0000250|UniProtKB:B2HN69, ECO:0000255|HAMAP-Rule:MF_02247};
DE AltName: Full=FAAL9 {ECO:0000303|PubMed:19182784};
DE AltName: Full=Medium/long-chain-fatty-acid--AMP ligase FadD9 {ECO:0000305};
DE EC=6.2.1.- {ECO:0000269|PubMed:19182784};
GN Name=car {ECO:0000255|HAMAP-Rule:MF_02247};
GN Synonyms=fadD9 {ECO:0000312|EMBL:CCP45386.1};
GN OrderedLocusNames=Rv2590 {ECO:0000312|EMBL:CCP45386.1};
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=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 [3]
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 ATP- and NADPH-dependent reduction of
CC carboxylic acids to the corresponding aldehydes (By similarity). In
CC vitro, also catalyzes the activation of medium/long-chain fatty acids
CC as acyl-adenylates (acyl-AMP) (PubMed:19182784).
CC {ECO:0000250|UniProtKB:B2HN69, ECO:0000269|PubMed:19182784}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a carboxylate + ATP + H(+) + NADPH = AMP + an aldehyde +
CC diphosphate + NADP(+); Xref=Rhea:RHEA:50916, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17478, ChEBI:CHEBI:29067, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000250|UniProtKB:B2HN69,
CC ECO:0000255|HAMAP-Rule:MF_02247};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a medium chain fatty acid + ATP + H(+) = a medium-chain fatty
CC acyl-AMP + diphosphate; Xref=Rhea:RHEA:56920, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:59558,
CC ChEBI:CHEBI:141140; Evidence={ECO:0000269|PubMed:19182784};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:56921;
CC Evidence={ECO:0000269|PubMed:19182784};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a long-chain fatty acid + ATP + H(+) = a long-chain fatty
CC acyl-AMP + diphosphate; Xref=Rhea:RHEA:52336, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57560,
CC ChEBI:CHEBI:136562; Evidence={ECO:0000269|PubMed:19182784};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52337;
CC Evidence={ECO:0000269|PubMed:19182784};
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 -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000250|UniProtKB:B2HN69,
CC ECO:0000255|HAMAP-Rule:MF_02247};
CC Note=Binds 1 phosphopantetheine covalently.
CC {ECO:0000250|UniProtKB:B2HN69, ECO:0000255|HAMAP-Rule:MF_02247};
CC -!- DOMAIN: The N-terminal domain likely catalyzes substrate activation by
CC formation of an initial acyl-AMP intermediate, the central region
CC contains the phosphopantetheine attachment site, and the C-terminal
CC domain catalyzes the reduction by NADPH of the intermediate thioester
CC formed from the attack of the phosphopantetheine thiol at the carbonyl
CC carbon of acyl-AMP. {ECO:0000250|UniProtKB:Q6RKB1, ECO:0000255|HAMAP-
CC Rule:MF_02247}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC Carboxylic acid reductase subfamily. {ECO:0000255|HAMAP-Rule:MF_02247,
CC ECO:0000305}.
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DR EMBL; AL123456; CCP45386.1; -; Genomic_DNA.
DR RefSeq; NP_217106.1; NC_000962.3.
DR RefSeq; WP_003413409.1; NZ_NVQJ01000023.1.
DR AlphaFoldDB; Q50631; -.
DR SMR; Q50631; -.
DR STRING; 83332.Rv2590; -.
DR SwissLipids; SLP:000000983; -.
DR PaxDb; Q50631; -.
DR PRIDE; Q50631; -.
DR DNASU; 888574; -.
DR GeneID; 888574; -.
DR KEGG; mtu:Rv2590; -.
DR PATRIC; fig|83332.111.peg.2893; -.
DR TubercuList; Rv2590; -.
DR eggNOG; COG1022; Bacteria.
DR eggNOG; COG3320; Bacteria.
DR InParanoid; Q50631; -.
DR OMA; WRDSIME; -.
DR PhylomeDB; Q50631; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0000036; F:acyl carrier 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:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IBA:GO_Central.
DR CDD; cd05235; SDR_e1; 1.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR HAMAP; MF_02247; Carbox_acid_reduct; 1.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR046407; CAR.
DR InterPro; IPR013120; Far_NAD-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR010080; Thioester_reductase-like_dom.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF07993; NAD_binding_4; 1.
DR Pfam; PF00550; PP-binding; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR01746; Thioester-redct; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Fatty acid metabolism; Ligase; Lipid metabolism; NADP;
KW Nucleotide-binding; Oxidoreductase; Phosphopantetheine; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..1168
FT /note="Carboxylic acid reductase"
FT /id="PRO_0000451306"
FT DOMAIN 645..720
FT /note="Carrier"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 290
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 385
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 407..408
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 412
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 485
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 497..500
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 506
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 606
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 777..780
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 804
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 814
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 844..845
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 870..872
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 910
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 946
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 950
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT MOD_RES 679
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
SQ SEQUENCE 1168 AA; 127328 MW; 0DF885308289BD0A CRC64;
MSINDQRLTR RVEDLYASDA QFAAASPNEA ITQAIDQPGV ALPQLIRMVM EGYADRPALG
QRALRFVTDP DSGRTMVELL PRFETITYRE LWARAGTLAT ALSAEPAIRP GDRVCVLGFN
SVDYTTIDIA LIRLGAVSVP LQTSAPVTGL RPIVTETEPT MIATSIDNLG DAVEVLAGHA
PARLVVFDYH GKVDTHREAV EAARARLAGS VTIDTLAELI ERGRALPATP IADSADDALA
LLIYTSGSTG APKGAMYRES QVMSFWRKSS GWFEPSGYPS ITLNFMPMSH VGGRQVLYGT
LSNGGTAYFV AKSDLSTLFE DLALVRPTEL CFVPRIWDMV FAEFHSEVDR RLVDGADRAA
LEAQVKAELR ENVLGGRFVM ALTGSAPISA EMTAWVESLL ADVHLVEGYG STEAGMVLND
GMVRRPAVID YKLVDVPELG YFGTDQPYPR GELLVKTQTM FPGYYQRPDV TAEVFDPDGF
YRTGDIMAKV GPDQFVYLDR RNNVLKLSQG EFIAVSKLEA VFGDSPLVRQ IFIYGNSARA
YPLAVVVPSG DALSRHGIEN LKPVISESLQ EVARAAGLQS YEIPRDFIIE TTPFTLENGL
LTGIRKLARP QLKKFYGERL ERLYTELADS QSNELRELRQ SGPDAPVLPT LCRAAAALLG
STAADVRPDA HFADLGGDSL SALSLANLLH EIFGVDVPVG VIVSPASDLR ALADHIEAAR
TGVRRPSFAS IHGRSATEVH ASDLTLDKFI DAATLAAAPN LPAPSAQVRT VLLTGATGFL
GRYLALEWLD RMDLVNGKLI CLVRARSDEE AQARLDATFD SGDPYLVRHY RELGAGRLEV
LAGDKGEADL GLDRVTWQRL ADTVDLIVDP AALVNHVLPY SQLFGPNAAG TAELLRLALT
GKRKPYIYTS TIAVGEQIPP EAFTEDADIR AISPTRRIDD SYANGYANSK WAGEVLLREA
HEQCGLPVTV FRCDMILADT SYTGQLNLPD MFTRLMLSLA ATGIAPGSFY ELDAHGNRQR
AHYDGLPVEF VAEAICTLGT HSPDRFVTYH VMNPYDDGIG LDEFVDWLNS PTSGSGCTIQ
RIADYGEWLQ RFETSLRALP DRQRHASLLP LLHNYREPAK PICGSIAPTD QFRAAVQEAK
IGPDKDIPHL TAAIIAKYIS NLRLLGLL
