PHLA_MYCTU
ID PHLA_MYCTU Reviewed; 520 AA.
AC P9WIB5; L0T9D3; O08223; Q04001; Q50560; Q50771; Q50772; Q53408;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 45.
DE RecName: Full=Phospholipase C A {ECO:0000305};
DE Short=PLC-A {ECO:0000303|PubMed:20736081};
DE EC=3.1.4.3 {ECO:0000269|PubMed:20736081, ECO:0000269|PubMed:8757862};
DE AltName: Full=MTP40 antigen;
DE AltName: Full=Mycobacterial phospholipase C A {ECO:0000303|PubMed:8757862};
DE Flags: Precursor;
GN Name=plcA {ECO:0000303|PubMed:12100560};
GN Synonyms=mpcA {ECO:0000303|PubMed:8757862},
GN mtp40 {ECO:0000303|PubMed:1909999}; OrderedLocusNames=Rv2351c;
GN ORFNames=MTCY98.20c;
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 [GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=7591062; DOI=10.1128/iai.63.11.4301-4306.1995;
RA Leao S.C., Rocha C.L., Murillo L.A., Parra C.A., Patarroyo M.E.;
RT "A species-specific nucleotide sequence of Mycobacterium tuberculosis
RT encodes a protein that exhibits hemolytic activity when expressed in
RT Escherichia coli.";
RL Infect. Immun. 63:4301-4306(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP SUBCELLULAR LOCATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=8757862; DOI=10.1128/iai.64.8.3259-3266.1996;
RA Johansen K.A., Gill R.E., Vasil M.L.;
RT "Biochemical and molecular analysis of phospholipase C and phospholipase D
RT activity in mycobacteria.";
RL Infect. Immun. 64:3259-3266(1996).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 323-520.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=1909999; DOI=10.1128/iai.59.10.3411-3417.1991;
RA Parra C.A., Londono L.P., del Portillo P., Patarroyo M.E.;
RT "Isolation, characterization, and molecular cloning of a specific
RT Mycobacterium tuberculosis antigen gene: identification of a species-
RT specific sequence.";
RL Infect. Immun. 59:3411-3417(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 355-496.
RX PubMed=8298518;
RA Leao S.C.;
RT "Tuberculosis: new strategies for the development of diagnostic tests and
RT vaccines.";
RL Braz. J. Med. Biol. Res. 26:827-833(1993).
RN [6]
RP POLYMORPHISM.
RX PubMed=9114405; DOI=10.1128/jcm.35.5.1190-1195.1997;
RA Vera-Cabrera L., Howard S.T., Laszlo A., Johnson W.M.;
RT "Analysis of genetic polymorphism in the phospholipase region of
RT Mycobacterium tuberculosis.";
RL J. Clin. Microbiol. 35:1190-1195(1997).
RN [7]
RP SUBCELLULAR LOCATION, AND EXPRESSION.
RC STRAIN=H37Rv;
RX PubMed=11050656; DOI=10.1590/s0100-879x2000001100003;
RA Matsui T., Carneiro C.R., Leao S.C.;
RT "Evidence for the expression of native Mycobacterium tuberculosis
RT phospholipase C: recognition by immune sera and detection of promoter
RT activity.";
RL Braz. J. Med. Biol. Res. 33:1275-1282(2000).
RN [8]
RP INDUCTION.
RC STRAIN=H37Rv;
RX PubMed=12100560; DOI=10.1046/j.1365-2958.2002.03009.x;
RA Raynaud C., Guilhot C., Rauzier J., Bordat Y., Pelicic V., Manganelli R.,
RA Smith I., Gicquel B., Jackson M.;
RT "Phospholipases C are involved in the virulence of Mycobacterium
RT tuberculosis.";
RL Mol. Microbiol. 45:203-217(2002).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBCELLULAR LOCATION.
RC STRAIN=H37Rv;
RX PubMed=20736081; DOI=10.1016/j.bbalip.2010.08.007;
RA Bakala N'goma J.C., Schue M., Carriere F., Geerlof A., Canaan S.;
RT "Evidence for the cytotoxic effects of Mycobacterium tuberculosis
RT phospholipase C towards macrophages.";
RL Biochim. Biophys. Acta 1801:1305-1313(2010).
RN [10]
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: Involved in virulence (PubMed:20736081). Induces cytotoxic
CC effects on mouse macrophage cell lines, via direct or indirect
CC enzymatic hydrolysis of cell membrane phospholipids (PubMed:20736081).
CC Hydrolyzes phosphatidylcholine and sphingomyelin (PubMed:8757862,
CC PubMed:20736081). Does not have hemolytic activity (PubMed:20736081).
CC {ECO:0000269|PubMed:20736081, ECO:0000269|PubMed:8757862}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1,2-diacyl-
CC sn-glycerol + H(+) + phosphocholine; Xref=Rhea:RHEA:10604,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17815,
CC ChEBI:CHEBI:57643, ChEBI:CHEBI:295975; EC=3.1.4.3;
CC Evidence={ECO:0000269|PubMed:20736081, ECO:0000269|PubMed:8757862};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10605;
CC Evidence={ECO:0000269|PubMed:20736081, ECO:0000269|PubMed:8757862};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a sphingomyelin + H2O = an N-acylsphing-4-enine + H(+) +
CC phosphocholine; Xref=Rhea:RHEA:19253, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17636, ChEBI:CHEBI:52639,
CC ChEBI:CHEBI:295975; Evidence={ECO:0000269|PubMed:8757862};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19254;
CC Evidence={ECO:0000269|PubMed:8757862};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1,2-
CC dihexadecanoyl-sn-glycerol + H(+) + phosphocholine;
CC Xref=Rhea:RHEA:45304, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:72999, ChEBI:CHEBI:82929, ChEBI:CHEBI:295975;
CC Evidence={ECO:0000269|PubMed:20736081};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45305;
CC Evidence={ECO:0000269|PubMed:20736081};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.5. {ECO:0000269|PubMed:20736081};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius.
CC {ECO:0000269|PubMed:20736081};
CC -!- SUBCELLULAR LOCATION: Secreted, cell wall
CC {ECO:0000269|PubMed:20736081}. Note=Remains associated with the cell.
CC {ECO:0000269|PubMed:11050656, ECO:0000269|PubMed:20736081,
CC ECO:0000269|PubMed:8757862}.
CC -!- INDUCTION: Constitutively expressed (PubMed:11050656). Expression is
CC induced in vitro in the presence of phosphatidylcholine. Also induced
CC upon infection of THP-1 macrophages (PubMed:12100560).
CC {ECO:0000269|PubMed:11050656, ECO:0000269|PubMed:12100560}.
CC -!- PTM: Predicted to be exported by the Tat system. The position of the
CC signal peptide cleavage has not been experimentally proven.
CC {ECO:0000255|PROSITE-ProRule:PRU00648}.
CC -!- MISCELLANEOUS: Polymorphism was discovered in the phospholipase
CC plcA/B/C region. Some strains seem to lack both plcA and plcB genes,
CC while others lack only plcB. {ECO:0000305|PubMed:9114405}.
CC -!- MISCELLANEOUS: An IS6110 insertion element has been found in strain
CC LCDC-194, interrupting the plcA gene. {ECO:0000305|PubMed:9114405}.
CC -!- SIMILARITY: Belongs to the bacterial phospholipase C family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA63288.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAB59164.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAC60465.2; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CCP45139.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; L11868; AAB59164.1; ALT_INIT; Genomic_DNA.
DR EMBL; L11868; AAB59165.1; ALT_SEQ; Genomic_DNA.
DR EMBL; U49511; AAC18943.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP45139.1; ALT_INIT; Genomic_DNA.
DR EMBL; M57952; AAA63288.1; ALT_FRAME; Genomic_DNA.
DR EMBL; S69737; AAC60465.2; ALT_FRAME; Genomic_DNA.
DR PIR; H70662; H70662.
DR RefSeq; NP_216867.1; NC_000962.3.
DR RefSeq; WP_003904825.1; NC_000962.3.
DR AlphaFoldDB; P9WIB5; -.
DR SMR; P9WIB5; -.
DR STRING; 83332.Rv2351c; -.
DR SwissLipids; SLP:000001395; -.
DR PaxDb; P9WIB5; -.
DR DNASU; 885995; -.
DR GeneID; 885995; -.
DR KEGG; mtu:Rv2351c; -.
DR TubercuList; Rv2351c; -.
DR eggNOG; COG3511; Bacteria.
DR OMA; ECCSYMS; -.
DR BRENDA; 3.1.4.3; 3445.
DR PHI-base; PHI:5288; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0034480; F:phosphatidylcholine phospholipase C activity; IMP:MTBBASE.
DR GO; GO:0004629; F:phospholipase C activity; IDA:MTBBASE.
DR GO; GO:0004767; F:sphingomyelin phosphodiesterase activity; IEA:RHEA.
DR GO; GO:0052008; P:disruption by symbiont of host cellular component; IDA:MTBBASE.
DR Gene3D; 3.40.720.10; -; 2.
DR InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR InterPro; IPR007312; Phosphoesterase.
DR InterPro; IPR006311; TAT_signal.
DR PANTHER; PTHR31956; PTHR31956; 1.
DR Pfam; PF04185; Phosphoesterase; 1.
DR PROSITE; PS51318; TAT; 1.
PE 1: Evidence at protein level;
KW Cell wall; Hydrolase; Reference proteome; Secreted; Signal; Virulence.
FT SIGNAL 1..38
FT /note="Tat-type signal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00648"
FT CHAIN 39..520
FT /note="Phospholipase C A"
FT /id="PRO_0000023942"
FT CONFLICT 327
FT /note="T -> N (in Ref. 4)"
FT /evidence="ECO:0000305"
FT CONFLICT 369..370
FT /note="GE -> AQ (in Ref. 4)"
FT /evidence="ECO:0000305"
FT CONFLICT 406..407
FT /note="RG -> PR (in Ref. 4)"
FT /evidence="ECO:0000305"
FT CONFLICT 516..520
FT /note="SGLCS -> AGCAAEISR (in Ref. 4)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 520 AA; 56138 MW; 5844EF0C064288A7 CRC64;
MSASPLLGMS RREFLTKLTG AGAAAFLMDW AAPVIEKAYG AGPCPGHLTD IEHIVLLMQE
NRSFDHYFGT LSSTNGFNAA SPAFQQMGWN PMTQALDPAG VTIPFRLDTT RGPFLDGECV
NDPEHQWVGM HLAWNGGAND NWLPAQATTR AGPYVPLTMG YYTRQDIPIH YLLADTFTIC
DGYHCSLLTG TLPNRLYWLS ANIDPAGTDG GPQLVEPGFL PLQQFSWRIM PENLEDAGVS
WKVYQNKGLG RFINTPISNN GLVQAFRQAA DPRSNLARYG IAPTYPGDFA ADVRANRLPK
VSWLVPNILQ SEHPALPVAL GAVSMVTALR ILLSNPAVWE KTALIVSYDE NGGFFDHVTP
PTAPPGTPGE FVTVPNIDAV PGSGGIRGPL GLGFRVPCIV ISPYSRGPLM VSDTFDHTSQ
LKLIRARFGV PVPNMTAWRD GVVGDMTSAF NFATPPNSTR PNLSHPLLGA LPKLPQCIPN
VVLGTTDGAL PSIPYRVPYP QVMPTQETTP VRGTPSGLCS
