CULP1_MYCTU
ID CULP1_MYCTU Reviewed; 217 AA.
AC P9WP43; L0TB60; P63879; Q10837;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 39.
DE RecName: Full=Carboxylesterase Culp1 {ECO:0000305};
DE EC=3.1.1.- {ECO:0000269|PubMed:16716602, ECO:0000269|PubMed:19225166, ECO:0000269|PubMed:20103719, ECO:0000269|PubMed:23843969};
DE AltName: Full=CFP21 {ECO:0000303|PubMed:9673225};
DE AltName: Full=Cutinase-like protein 1 {ECO:0000303|PubMed:19225166};
DE Short=Culp1 {ECO:0000303|PubMed:19225166};
DE Flags: Precursor;
GN Name=cut7; OrderedLocusNames=Rv1984c; ORFNames=MTCY39.35;
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 PROTEIN SEQUENCE OF 33-47, FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=H37Rv;
RX PubMed=9673225; DOI=10.1128/iai.66.8.3492-3500.1998;
RA Weldingh K., Rosenkrands I., Jacobsen S., Rasmussen P.B., Elhay M.J.,
RA Andersen P.;
RT "Two-dimensional electrophoresis for analysis of Mycobacterium tuberculosis
RT culture filtrate and purification and characterization of six novel
RT proteins.";
RL Infect. Immun. 66:3492-3500(1998).
RN [3]
RP FUNCTION.
RX PubMed=10076913; DOI=10.1111/j.1574-695x.1999.tb01235.x;
RA Weldingh K., Andersen P.;
RT "Immunological evaluation of novel Mycobacterium tuberculosis culture
RT filtrate proteins.";
RL FEMS Immunol. Med. Microbiol. 23:159-164(1999).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=16716602; DOI=10.1016/j.pep.2006.03.010;
RA Grover A., Ahmed M.F., Verma I., Sharma P., Khuller G.K.;
RT "Expression and purification of the Mycobacterium tuberculosis complex-
RT restricted antigen CFP21 to study its immunoprophylactic potential in mouse
RT model.";
RL Protein Expr. Purif. 48:274-280(2006).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND SUBCELLULAR
RP LOCATION.
RC STRAIN=H37Rv;
RX PubMed=19225166; DOI=10.1096/fj.08-114421;
RA West N.P., Chow F.M., Randall E.J., Wu J., Chen J., Ribeiro J.M.,
RA Britton W.J.;
RT "Cutinase-like proteins of Mycobacterium tuberculosis: characterization of
RT their variable enzymatic functions and active site identification.";
RL FASEB J. 23:1694-1704(2009).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, MUTAGENESIS OF SER-118; ASP-180; ASP-181 AND HIS-193, AND
RP ACTIVE SITE.
RX PubMed=20103719; DOI=10.1096/fj.09-144766;
RA Schue M., Maurin D., Dhouib R., Bakala N'Goma J.C., Delorme V., Lambeau G.,
RA Carriere F., Canaan S.;
RT "Two cutinase-like proteins secreted by Mycobacterium tuberculosis show
RT very different lipolytic activities reflecting their physiological
RT function.";
RL FASEB J. 24:1893-1903(2010).
RN [7]
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 [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-54; 83-ASP--ARG-86 AND
RP 189-ASN--MET-191.
RX PubMed=23843969; DOI=10.1371/journal.pone.0066913;
RA Dedieu L., Serveau-Avesque C., Canaan S.;
RT "Identification of residues involved in substrate specificity and
RT cytotoxicity of two closely related cutinases from Mycobacterium
RT tuberculosis.";
RL PLoS ONE 8:e66913-e66913(2013).
RN [9]
RP IMMUNOGENICITY.
RX PubMed=29709002; DOI=10.1371/journal.pone.0196470;
RA Renier W., Bourdin A., Rubbo P.A., Peries M., Dedieu L., Bendriss S.,
RA Kremer L., Canaan S., Terru D., Godreuil S., Nagot N., Van de Perre P.,
RA Tuaillon E.;
RT "B cells response directed against Cut4 and CFP21 lipolytic enzymes in
RT active and latent tuberculosis infections.";
RL PLoS ONE 13:e0196470-e0196470(2018).
CC -!- FUNCTION: Shows esterase activity, with a preference for short- and
CC medium-chain fatty acids (PubMed:19225166, PubMed:20103719,
CC PubMed:16716602, PubMed:23843969). Has also weak lipase activity, but
CC does not exhibit cutinase activity (PubMed:19225166, PubMed:23843969).
CC Hydrolyzes various p-nitrophenol-linked aliphatic esters, including
CC pNP-butyrate (C4), pNP-valerate (C5), pNP-hexanoate (C6), pNP-octanoate
CC (C8) and pNP-decanoate (C10) (PubMed:19225166, PubMed:20103719,
CC PubMed:16716602). Can use pNP-laurate (C12) and pNP-myristate (C14),
CC with lower efficiency (PubMed:19225166). Can also hydrolyze
CC monocaprylin and triolein, with a slow turnover (PubMed:20103719).
CC {ECO:0000269|PubMed:16716602, ECO:0000269|PubMed:19225166,
CC ECO:0000269|PubMed:20103719, ECO:0000269|PubMed:23843969}.
CC -!- FUNCTION: Induces a strong delayed-type hypersensitivity (DTH) response
CC in animal model of tuberculosis, cellular and humoral immune responses
CC (PubMed:9673225, PubMed:10076913, PubMed:16716602). Induces interferon-
CC gamma (IFN-gamma) release in animal models and in human TB patients
CC (PubMed:9673225, PubMed:10076913, PubMed:16716602). Also induces IL-12
CC responses in mouse model (PubMed:16716602).
CC {ECO:0000269|PubMed:10076913, ECO:0000269|PubMed:16716602,
CC ECO:0000269|PubMed:9673225}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a fatty acid ester + H2O = a fatty acid + an aliphatic alcohol
CC + H(+); Xref=Rhea:RHEA:59388, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28868, ChEBI:CHEBI:35748;
CC Evidence={ECO:0000269|PubMed:16716602, ECO:0000269|PubMed:19225166,
CC ECO:0000269|PubMed:20103719, ECO:0000269|PubMed:23843969};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59389;
CC Evidence={ECO:0000269|PubMed:16716602, ECO:0000269|PubMed:19225166,
CC ECO:0000269|PubMed:20103719, ECO:0000269|PubMed:23843969};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a butanoate ester + H2O = an aliphatic alcohol + butanoate +
CC H(+); Xref=Rhea:RHEA:47348, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17968, ChEBI:CHEBI:50477;
CC Evidence={ECO:0000269|PubMed:16716602, ECO:0000269|PubMed:19225166,
CC ECO:0000269|PubMed:20103719};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47349;
CC Evidence={ECO:0000269|PubMed:16716602, ECO:0000269|PubMed:19225166,
CC ECO:0000269|PubMed:20103719};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + pentanoate ester = an aliphatic alcohol + H(+) +
CC pentanoate; Xref=Rhea:RHEA:48436, ChEBI:CHEBI:2571,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:31011,
CC ChEBI:CHEBI:50871; Evidence={ECO:0000269|PubMed:20103719};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48437;
CC Evidence={ECO:0000269|PubMed:20103719};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a hexanoate ester + H2O = an aliphatic alcohol + H(+) +
CC hexanoate; Xref=Rhea:RHEA:47352, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17120, ChEBI:CHEBI:87656;
CC Evidence={ECO:0000269|PubMed:20103719, ECO:0000269|PubMed:23843969};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47353;
CC Evidence={ECO:0000269|PubMed:20103719, ECO:0000269|PubMed:23843969};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an octanoate ester + H2O = an aliphatic alcohol + H(+) +
CC octanoate; Xref=Rhea:RHEA:47356, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:25646, ChEBI:CHEBI:87657;
CC Evidence={ECO:0000269|PubMed:20103719, ECO:0000269|PubMed:23843969};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47357;
CC Evidence={ECO:0000269|PubMed:20103719, ECO:0000269|PubMed:23843969};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=decanoate ester + H2O = an aliphatic alcohol + decanoate +
CC H(+); Xref=Rhea:RHEA:47360, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:27689, ChEBI:CHEBI:87658;
CC Evidence={ECO:0000269|PubMed:20103719};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47361;
CC Evidence={ECO:0000269|PubMed:20103719};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a dodecanoate ester + H2O = an aliphatic alcohol + dodecanoate
CC + H(+); Xref=Rhea:RHEA:47364, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:18262, ChEBI:CHEBI:87659;
CC Evidence={ECO:0000269|PubMed:19225166};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47365;
CC Evidence={ECO:0000269|PubMed:19225166};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a tetradecanoate ester + H2O = an aliphatic alcohol + H(+) +
CC tetradecanoate; Xref=Rhea:RHEA:47388, ChEBI:CHEBI:2571,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30807,
CC ChEBI:CHEBI:87691; Evidence={ECO:0000269|PubMed:19225166};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47389;
CC Evidence={ECO:0000269|PubMed:19225166};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + octanoylglycerol = glycerol + H(+) + octanoate;
CC Xref=Rhea:RHEA:48500, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17754, ChEBI:CHEBI:25646, ChEBI:CHEBI:88070;
CC Evidence={ECO:0000269|PubMed:20103719};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48501;
CC Evidence={ECO:0000269|PubMed:20103719};
CC -!- ACTIVITY REGULATION: Almost completely inhibited by paraoxon
CC (PubMed:19225166). Inhibited by tetrahydrolipstatin (THL), a specific
CC lipase inhibitor (PubMed:20103719). {ECO:0000269|PubMed:19225166,
CC ECO:0000269|PubMed:20103719}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.5. {ECO:0000269|PubMed:20103719};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius.
CC {ECO:0000269|PubMed:20103719};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:19225166,
CC ECO:0000269|PubMed:9673225}.
CC -!- MISCELLANEOUS: Circulating B cells able to spontaneously generate
CC specific antibodies directed against Culp1 are detected during active
CC tuberculosis and in some latent-tuberculosis cases.
CC {ECO:0000269|PubMed:29709002}.
CC -!- SIMILARITY: Belongs to the cutinase family. {ECO:0000305}.
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DR EMBL; AL123456; CCP44754.1; -; Genomic_DNA.
DR PIR; F70756; F70756.
DR RefSeq; NP_216500.1; NC_000962.3.
DR RefSeq; WP_003409976.1; NZ_NVQJ01000043.1.
DR AlphaFoldDB; P9WP43; -.
DR SMR; P9WP43; -.
DR STRING; 83332.Rv1984c; -.
DR SwissLipids; SLP:000001377; -.
DR ESTHER; myctu-cutas1; Cutinase.
DR PaxDb; P9WP43; -.
DR DNASU; 885813; -.
DR GeneID; 45425962; -.
DR GeneID; 885813; -.
DR KEGG; mtu:Rv1984c; -.
DR TubercuList; Rv1984c; -.
DR eggNOG; ENOG5030PZC; Bacteria.
DR OMA; TYPMDGS; -.
DR PhylomeDB; P9WP43; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0047372; F:acylglycerol lipase activity; IDA:MTBBASE.
DR GO; GO:0052689; F:carboxylic ester hydrolase activity; IDA:MTBBASE.
DR GO; GO:0034338; F:short-chain carboxylesterase activity; IDA:MTBBASE.
DR GO; GO:0051793; P:medium-chain fatty acid catabolic process; IDA:MTBBASE.
DR GO; GO:0052651; P:monoacylglycerol catabolic process; IDA:MTBBASE.
DR GO; GO:0019626; P:short-chain fatty acid catabolic process; IDA:MTBBASE.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR000675; Cutinase/axe.
DR InterPro; IPR043580; CUTINASE_1.
DR InterPro; IPR043579; CUTINASE_2.
DR PANTHER; PTHR33630; PTHR33630; 1.
DR Pfam; PF01083; Cutinase; 1.
DR SMART; SM01110; Cutinase; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS00155; CUTINASE_1; 1.
DR PROSITE; PS00931; CUTINASE_2; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Hydrolase; Reference proteome;
KW Secreted; Serine esterase; Signal; Virulence.
FT SIGNAL 1..32
FT /evidence="ECO:0000269|PubMed:9673225"
FT CHAIN 33..217
FT /note="Carboxylesterase Culp1"
FT /id="PRO_0000006447"
FT ACT_SITE 118
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:20103719"
FT ACT_SITE 181
FT /evidence="ECO:0000305|PubMed:20103719"
FT ACT_SITE 193
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000305|PubMed:20103719"
FT SITE 119
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:P00590"
FT DISULFID 35..107
FT /evidence="ECO:0000250|UniProtKB:O53581"
FT DISULFID 177..184
FT /evidence="ECO:0000250|UniProtKB:O53581"
FT MUTAGEN 54
FT /note="D->R: Shows a strong preference for substrates with
FT a medium chain length ranging between 6 and 8 carbon atoms.
FT 31% and 25% decrease in activity with 6 carbon atoms vinyl
FT esters (VC6) or 8 carbon atoms vinyl esters (VC8) as
FT substrates. Enhances lipase activity on triglycerides.
FT Aquires phospholipase A activity and shows cytotoxic
FT effects on macrophages."
FT /evidence="ECO:0000269|PubMed:23843969"
FT MUTAGEN 83..86
FT /note="DDYR->GDFL: Shows a strong preference for substrates
FT with a medium chain length ranging between 6 and 8 carbon
FT atoms. 17-18% increase in activity with VC6 or VC8 as
FT substrates. Aquires phospholipase A activity and shows
FT cytotoxic effects on macrophages."
FT /evidence="ECO:0000269|PubMed:23843969"
FT MUTAGEN 118
FT /note="S->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:20103719"
FT MUTAGEN 180
FT /note="D->A: 30% decrease in activity with pNP-octanoate
FT and vinyl-caprylate as substrates."
FT /evidence="ECO:0000269|PubMed:20103719"
FT MUTAGEN 181
FT /note="D->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:20103719"
FT MUTAGEN 189..191
FT /note="NIM->RWR: Shows a strong preference for substrates
FT with a medium chain length ranging between 6 and 8 carbon
FT atoms. Loses 99% and 80% of activity with VC6 or VC8 as
FT substrates. Loss of lipase activity."
FT /evidence="ECO:0000269|PubMed:23843969"
FT MUTAGEN 193
FT /note="H->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:20103719"
SQ SEQUENCE 217 AA; 21782 MW; 500589547B9A87B0 CRC64;
MTPRSLVRIV GVVVATTLAL VSAPAGGRAA HADPCSDIAV VFARGTHQAS GLGDVGEAFV
DSLTSQVGGR SIGVYAVNYP ASDDYRASAS NGSDDASAHI QRTVASCPNT RIVLGGYSQG
ATVIDLSTSA MPPAVADHVA AVALFGEPSS GFSSMLWGGG SLPTIGPLYS SKTINLCAPD
DPICTGGGNI MAHVSYVQSG MTSQAATFAA NRLDHAG
