Protein: Phosphatidylinositol-3-phosphatase (PI3P phosphatase) (EC 3.1.3.64) (Acid phosphatase SapM) (EC 3.1.3.2) (Secreted acid phosphatase) (O53361)
Organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Function: Virulence factor that plays an important role in blocking phagosome-lysosome fusion and thus participates in the intracellular survival of the pathogen. Acts as a phosphatase that dephosphorylates phosphatidylinositol 3-phosphate (PI3P), a membrane trafficking regulatory lipid essential for phagosomal acquisition of lysosomal constituents. Therefore, SapM eliminates PI3P from the phagosomal membrane by catalyzing its hydrolysis, and thus contributes to inhibition of phagosome maturation. Also interferes with autophagy: SapM blocks autophagosome-lysosome fusion in macrophages by binding to the small GTPase RAB7, which prevents RAB7 from being involved in this process and thus negatively regulates autophagy flux. In vitro, displays phosphatase activity with broad specificity; can dephosphorylate a variety of phosphoester substrates, with the highest activity against phosphoenolpyruvate, glycerophosphate, GTP, NADPH, phosphotyrosine and trehalose-6-phosphate. In contrast, the enzyme exhibits poor activity against glucose-6-phosphate, phosphothreonine, and a number of nucleotides (NADP, ATP, AMP, and GMP).
Subcellular location: Secreted {ECO:0000269|PubMed:11073936, ECO:0000269|PubMed:15753315}. Host cytoplasmic vesicle, host phagosome {ECO:0000305|PubMed:15753315}. Note=It remains to be determined how SapM, once secreted into the phagosomal lumen, gains access to PI3P within the cytofacial membrane leaflet. It is possible that SapM is exported to the cytosolic side, or alternatively there may be a mechanism for PI3P presentation to SapM remaining on the luminal side. {ECO:0000305|PubMed:15753315}.
Sequence: MLRGIQALSRPLTRVYRALAVIGVLAASLLASWVGAVPQVGLAASALPTFAHVVIVVEENRSQAAIIGNKSAPFINSLAANGAMMAQAFAETHPSEPNYLALFAGNTFGLTKNTCPVNGGALPNLGSELLSAGYTFMGFAEDLPAVGSTVCSAGKYARKHVPWVNFSNVPTTLSVPFSAFPKPQNYPGLPTVSFVIPNADNDMHDGSIAQGDAWLNRHLSAYANWAKTNNSLLVVTWDEDDGSSRNQIPTVFYGAHVRPGTYNETISHYNVLSTLEQIYGLPKTGYATNAPPITDIWGD
InterPro domains: - IPR017850: Alkaline-phosphatase-like, core domain superfamily (homologous_superfamily) [67-297]
- IPR007312: Phosphoesterase (family) [33-286]
Interaction partners: - Phospholipase C A
- Phospholipase C C
- Phospholipase C D
- Phospholipase C B
- Triple specificity protein phosphatase PtpB
- Low molecular weight protein-tyrosine phosphatase A
- Conserved protein
- Uracil phosphoribosyltransferase
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016787 (hydrolase activity), GO:0016788 (hydrolase activity, acting on ester bonds), GO:0016298 (lipase activity), GO:0042578 (phosphoric ester hydrolase activity), GO:0008081 (phosphoric diester hydrolase activity), GO:0004620 (phospholipase activity), GO:0004629 (phospholipase C activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0044237 (cellular metabolic process), GO:0071704 (organic substance metabolic process), GO:0009056 (catabolic process), GO:0044238 (primary metabolic process), GO:0044255 (cellular lipid metabolic process), GO:0006629 (lipid metabolic process), GO:1901575 (organic substance catabolic process), GO:1901135 (carbohydrate derivative metabolic process), GO:0044248 (cellular catabolic process), GO:1903509 (liposaccharide metabolic process), GO:0044242 (cellular lipid catabolic process), GO:1901136 (carbohydrate derivative catabolic process), GO:0016042 (lipid catabolic process), GO:0006643 (membrane lipid metabolic process), GO:0019377 (glycolipid catabolic process), GO:0006664 (glycolipid metabolic process), GO:0046466 (membrane lipid catabolic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0110165 (cellular anatomical entity), GO:0005576 (extracellular region)