SAPM_MYCTU
ID SAPM_MYCTU Reviewed; 299 AA.
AC O53361; F2GKY3; I6X6Y4; Q7D5Q7;
DT 15-FEB-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Phosphatidylinositol-3-phosphatase {ECO:0000303|PubMed:15753315};
DE Short=PI3P phosphatase {ECO:0000303|PubMed:15753315};
DE EC=3.1.3.64 {ECO:0000269|PubMed:15753315};
DE AltName: Full=Acid phosphatase SapM {ECO:0000303|PubMed:11073936};
DE EC=3.1.3.2 {ECO:0000269|PubMed:11073936};
DE AltName: Full=Secreted acid phosphatase {ECO:0000303|PubMed:11073936};
DE Flags: Precursor;
GN Name=sapM {ECO:0000303|PubMed:11073936};
GN OrderedLocusNames=Rv3310 {ECO:0000312|EMBL:CCP46129.1},
GN LH57_18080 {ECO:0000312|EMBL:AIR16102.1};
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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RA Hazbon M.H., Riojas M.A., Damon A.M., Alalade R.O., Cantwell B.J.,
RA Monaco A., King S., Sohrabi A.;
RT "Phylogenetic analysis of Mycobacterial species using whole genome
RT sequences.";
RL Submitted (SEP-2014) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PROTEIN SEQUENCE OF 44-55, IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY,
RP COFACTOR, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=11073936; DOI=10.1128/jb.182.23.6850-6853.2000;
RA Saleh M.T., Belisle J.T.;
RT "Secretion of an acid phosphatase (SapM) by Mycobacterium tuberculosis that
RT is similar to eukaryotic acid phosphatases.";
RL J. Bacteriol. 182:6850-6853(2000).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RC STRAIN=H37Rv;
RX PubMed=15753315; DOI=10.1073/pnas.0409716102;
RA Vergne I., Chua J., Lee H.H., Lucas M., Belisle J., Deretic V.;
RT "Mechanism of phagolysosome biogenesis block by viable Mycobacterium
RT tuberculosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:4033-4038(2005).
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).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=23923000; DOI=10.1371/journal.pone.0070514;
RA Puri R.V., Reddy P.V., Tyagi A.K.;
RT "Secreted acid phosphatase (SapM) of Mycobacterium tuberculosis is
RT indispensable for arresting phagosomal maturation and growth of the
RT pathogen in guinea pig tissues.";
RL PLoS ONE 8:E70514-E70514(2013).
RN [7]
RP FUNCTION, INTERACTION WITH RAB7, AND DOMAIN.
RX PubMed=25896765; DOI=10.1016/j.bbrc.2015.04.051;
RA Hu D., Wu J., Wang W., Mu M., Zhao R., Xu X., Chen Z., Xiao J., Hu F.,
RA Yang Y., Zhang R.;
RT "Autophagy regulation revealed by SapM-induced block of autophagosome-
RT lysosome fusion via binding RAB7.";
RL Biochem. Biophys. Res. Commun. 461:401-407(2015).
CC -!- FUNCTION: Virulence factor that plays an important role in blocking
CC phagosome-lysosome fusion and thus participates in the intracellular
CC survival of the pathogen (PubMed:15753315, PubMed:23923000). Acts as a
CC phosphatase that dephosphorylates phosphatidylinositol 3-phosphate
CC (PI3P), a membrane trafficking regulatory lipid essential for
CC phagosomal acquisition of lysosomal constituents (PubMed:15753315).
CC Therefore, SapM eliminates PI3P from the phagosomal membrane by
CC catalyzing its hydrolysis, and thus contributes to inhibition of
CC phagosome maturation (PubMed:15753315). Also interferes with autophagy:
CC SapM blocks autophagosome-lysosome fusion in macrophages by binding to
CC the small GTPase RAB7, which prevents RAB7 from being involved in this
CC process and thus negatively regulates autophagy flux (PubMed:25896765).
CC In vitro, displays phosphatase activity with broad specificity; can
CC dephosphorylate a variety of phosphoester substrates, with the highest
CC activity against phosphoenolpyruvate, glycerophosphate, GTP, NADPH,
CC phosphotyrosine and trehalose-6-phosphate (PubMed:11073936). In
CC contrast, the enzyme exhibits poor activity against glucose-6-
CC phosphate, phosphothreonine, and a number of nucleotides (NADP, ATP,
CC AMP, and GMP) (PubMed:11073936). {ECO:0000269|PubMed:11073936,
CC ECO:0000269|PubMed:15753315, ECO:0000269|PubMed:23923000,
CC ECO:0000269|PubMed:25896765}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a phosphate monoester + H2O = an alcohol + phosphate;
CC Xref=Rhea:RHEA:15017, ChEBI:CHEBI:15377, ChEBI:CHEBI:30879,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:67140; EC=3.1.3.2;
CC Evidence={ECO:0000269|PubMed:11073936};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-
CC phosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol) + phosphate; Xref=Rhea:RHEA:12316, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57880, ChEBI:CHEBI:58088; EC=3.1.3.64;
CC Evidence={ECO:0000269|PubMed:15753315};
CC -!- COFACTOR:
CC Name=a metal cation; Xref=ChEBI:CHEBI:25213;
CC Evidence={ECO:0000305|PubMed:11073936};
CC -!- ACTIVITY REGULATION: Phosphatase activity is inhibited in vitro by low
CC concentrations of several heavy metals (zinc chloride, sodium
CC molybdate, magnesium chloride, and copper sulfate) and moderately high
CC concentrations (>8 mM) of EDTA. {ECO:0000269|PubMed:11073936}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.43 mM for p-nitrophenyl phosphate {ECO:0000269|PubMed:11073936};
CC Vmax=2100000 nmol/h/mg enzyme with p-nitrophenyl phosphate as
CC substrate {ECO:0000269|PubMed:11073936};
CC pH dependence:
CC Optimum pH is 6.5-7.5. Significant phosphatase activity is observed
CC between pH 5.5 and 8.0. {ECO:0000269|PubMed:11073936};
CC -!- SUBUNIT: Monomer (PubMed:11073936). SapM interacts with host RAB7 via
CC its C-terminus (PubMed:25896765). {ECO:0000269|PubMed:11073936,
CC ECO:0000269|PubMed:25896765}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11073936,
CC ECO:0000269|PubMed:15753315}. Host cytoplasmic vesicle, host phagosome
CC {ECO:0000305|PubMed:15753315}. Note=It remains to be determined how
CC SapM, once secreted into the phagosomal lumen, gains access to PI3P
CC within the cytofacial membrane leaflet. It is possible that SapM is
CC exported to the cytosolic side, or alternatively there may be a
CC mechanism for PI3P presentation to SapM remaining on the luminal side.
CC {ECO:0000305|PubMed:15753315}.
CC -!- DOMAIN: The C-terminus of SapM is required for interaction with RAB7
CC and SapM-mediated autophagy block. {ECO:0000269|PubMed:25896765}.
CC -!- DISRUPTION PHENOTYPE: Strain lacking this gene is defective in the
CC arrest of phagosomal maturation as well as for growth in human THP-1
CC macrophages. The mutant strain is severely attenuated for growth in the
CC lungs and spleen of guinea pigs and has a significantly reduced ability
CC to cause pathological damage in the host when compared with the
CC parental strain. Also, the guinea pigs infected with the mutant strain
CC exhibit a significantly enhanced survival when compared with
CC M.tuberculosis infected animals. {ECO:0000269|PubMed:23923000}.
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DR EMBL; AL123456; CCP46129.1; -; Genomic_DNA.
DR EMBL; CP009480; AIR16102.1; -; Genomic_DNA.
DR RefSeq; NP_217827.1; NC_000962.3.
DR RefSeq; WP_003900013.1; NZ_NVQJ01000003.1.
DR AlphaFoldDB; O53361; -.
DR SMR; O53361; -.
DR STRING; 83332.Rv3310; -.
DR PaxDb; O53361; -.
DR PRIDE; O53361; -.
DR DNASU; 887988; -.
DR GeneID; 887988; -.
DR KEGG; mtu:Rv3310; -.
DR PATRIC; fig|83332.111.peg.3693; -.
DR TubercuList; Rv3310; -.
DR eggNOG; COG3511; Bacteria.
DR HOGENOM; CLU_027977_3_0_11; -.
DR OMA; GYVNWEV; -.
DR Reactome; R-HSA-9636383; Prevention of phagosomal-lysosomal fusion.
DR Reactome; R-HSA-9636569; Suppression of autophagy.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; TAS:Reactome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; IDA:MTBBASE.
DR GO; GO:0044161; C:host cell cytoplasmic vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; IDA:MTBBASE.
DR GO; GO:0003993; F:acid phosphatase activity; IDA:MTBBASE.
DR GO; GO:0016791; F:phosphatase activity; TAS:Reactome.
DR GO; GO:0004438; F:phosphatidylinositol-3-phosphatase activity; IDA:MTBBASE.
DR GO; GO:0050189; F:phosphoenolpyruvate phosphatase activity; IDA:MTBBASE.
DR GO; GO:0050192; F:phosphoglycerate phosphatase activity; IDA:MTBBASE.
DR GO; GO:0004805; F:trehalose-phosphatase activity; IDA:MTBBASE.
DR GO; GO:0006742; P:NADP catabolic process; IDA:MTBBASE.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IDA:MTBBASE.
DR GO; GO:0052170; P:suppression by symbiont of host innate immune response; TAS:Reactome.
DR Gene3D; 3.40.720.10; -; 1.
DR InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR InterPro; IPR007312; Phosphoesterase.
DR PANTHER; PTHR31956; PTHR31956; 1.
DR Pfam; PF04185; Phosphoesterase; 1.
DR SUPFAM; SSF53649; SSF53649; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Host cytoplasmic vesicle; Hydrolase;
KW Reference proteome; Secreted; Signal; Virulence.
FT SIGNAL 1..43
FT /evidence="ECO:0000269|PubMed:11073936"
FT CHAIN 44..299
FT /note="Phosphatidylinositol-3-phosphatase"
FT /id="PRO_5008778597"
SQ SEQUENCE 299 AA; 31807 MW; C5E8C49CF62C8BF8 CRC64;
MLRGIQALSR PLTRVYRALA VIGVLAASLL ASWVGAVPQV GLAASALPTF AHVVIVVEEN
RSQAAIIGNK SAPFINSLAA NGAMMAQAFA ETHPSEPNYL ALFAGNTFGL TKNTCPVNGG
ALPNLGSELL SAGYTFMGFA EDLPAVGSTV CSAGKYARKH VPWVNFSNVP TTLSVPFSAF
PKPQNYPGLP TVSFVIPNAD NDMHDGSIAQ GDAWLNRHLS AYANWAKTNN SLLVVTWDED
DGSSRNQIPT VFYGAHVRPG TYNETISHYN VLSTLEQIYG LPKTGYATNA PPITDIWGD
