UniProt functional annotation for P9WI55



	UniProt functional annotation for P9WI55

UniProt code: P9WI55.

Organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).

Taxonomy: Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae; Mycobacterium; Mycobacterium tuberculosis complex.

Function: Catalyzes the hydrolysis of inorganic pyrophosphate (PPi) forming two phosphate ions. {ECO:0000269|PubMed:16239227, ECO:0000269|PubMed:26296329}.

Function: Antigen that activates dendritic cells (DCs), increasing their expression of cell surface molecules and augmenting their production of TNF-alpha, IL-1beta, IL-6, IL-23 and IL-12p70. Rv3628 mediates these effects by binding to TLR2 and activating downstream MyD88-, MAPK- and NF-kappaB-dependent signaling pathways. Rv3628- stimulated DCs induce the expansion of OVA-specific CD4+ and CD8+ T cells which secrete IFN-gamma and IL-2, and the generation of effector/memory T cells. Thus, Rv3628 polarizes DCs toward a Th1 immune response and promotes protective immunity against M.tuberculosis infection. Is not able to bind to TLR4 molecules on the cell surface. {ECO:0000269|PubMed:27097115}.

Catalytic activity: Reaction=diphosphate + H2O = H(+) + 2 phosphate; Xref=Rhea:RHEA:24576, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:43474; EC=3.6.1.1; Evidence={ECO:0000269|PubMed:16239227, ECO:0000269|PubMed:26296329};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:16239227}; Note=Other metal ions such as Mn(2+) and Zn(2+) can support activity, but at a much lower rate (PubMed:16239227). Three metal ions appear to be required for the activation of the enzyme and the substrate during the catalytic cycle (PubMed:26296329). {ECO:0000269|PubMed:16239227, ECO:0000305|PubMed:26296329};

Biophysicochemical properties: Kinetic parameters: KM=8.3 uM for diphosphate (at pH 7.2) {ECO:0000269|PubMed:16239227}; KM=64 uM for diphosphate (at pH 7.5) {ECO:0000269|PubMed:26296329}; Note=kcat is 240 sec(-1) at pH 7.2 (PubMed:16239227). kcat is 48 sec(-1) at pH 7.5 (PubMed:26296329). {ECO:0000269|PubMed:16239227, ECO:0000269|PubMed:26296329}; pH dependence: Optimum pH is around 7.5. {ECO:0000269|PubMed:16239227};

Subunit: Homohexamer. {ECO:0000269|PubMed:16239227, ECO:0000269|PubMed:26296329}.

Subcellular location: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00209}. Secreted {ECO:0000305|PubMed:27097115}. Host cell surface {ECO:0000269|PubMed:27097115}.

Induction: Is constitutively expressed and is not up-regulated upon macrophage infection or by exposure to environmental stress when grown in vitro. {ECO:0000269|PubMed:11339880}.

Biotechnology: Displays vaccine potential against the hyper-virulent M.tuberculosis Beijing K strain. Protective efficacy is correlated with the generation of Rv3628-specific CD4+ T cells co-producing IFN-gamma, TNF-alpha and IL-2 and exhibiting an elevated IFN-gamma recall response. {ECO:0000269|PubMed:27097115}.

Similarity: Belongs to the PPase family. {ECO:0000255|HAMAP- Rule:MF_00209}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
Taxonomy:		Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae; Mycobacterium; Mycobacterium tuberculosis complex.



Function:		Catalyzes the hydrolysis of inorganic pyrophosphate (PPi) forming two phosphate ions. {ECO:0000269\|PubMed:16239227, ECO:0000269\|PubMed:26296329}.



Function:		Antigen that activates dendritic cells (DCs), increasing their expression of cell surface molecules and augmenting their production of TNF-alpha, IL-1beta, IL-6, IL-23 and IL-12p70. Rv3628 mediates these effects by binding to TLR2 and activating downstream MyD88-, MAPK- and NF-kappaB-dependent signaling pathways. Rv3628- stimulated DCs induce the expansion of OVA-specific CD4+ and CD8+ T cells which secrete IFN-gamma and IL-2, and the generation of effector/memory T cells. Thus, Rv3628 polarizes DCs toward a Th1 immune response and promotes protective immunity against M.tuberculosis infection. Is not able to bind to TLR4 molecules on the cell surface. {ECO:0000269\|PubMed:27097115}.


Catalytic activity:		Reaction=diphosphate + H2O = H(+) + 2 phosphate; Xref=Rhea:RHEA:24576, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:43474; EC=3.6.1.1; Evidence={ECO:0000269\|PubMed:16239227, ECO:0000269\|PubMed:26296329};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:16239227}; Note=Other metal ions such as Mn(2+) and Zn(2+) can support activity, but at a much lower rate (PubMed:16239227). Three metal ions appear to be required for the activation of the enzyme and the substrate during the catalytic cycle (PubMed:26296329). {ECO:0000269\|PubMed:16239227, ECO:0000305\|PubMed:26296329};
Biophysicochemical properties:		Kinetic parameters: KM=8.3 uM for diphosphate (at pH 7.2) {ECO:0000269\|PubMed:16239227}; KM=64 uM for diphosphate (at pH 7.5) {ECO:0000269\|PubMed:26296329}; Note=kcat is 240 sec(-1) at pH 7.2 (PubMed:16239227). kcat is 48 sec(-1) at pH 7.5 (PubMed:26296329). {ECO:0000269\|PubMed:16239227, ECO:0000269\|PubMed:26296329}; pH dependence: Optimum pH is around 7.5. {ECO:0000269\|PubMed:16239227};
Subunit:		Homohexamer. {ECO:0000269\|PubMed:16239227, ECO:0000269\|PubMed:26296329}.
Subcellular location:		Cytoplasm {ECO:0000255\|HAMAP-Rule:MF_00209}. Secreted {ECO:0000305\|PubMed:27097115}. Host cell surface {ECO:0000269\|PubMed:27097115}.
Induction:		Is constitutively expressed and is not up-regulated upon macrophage infection or by exposure to environmental stress when grown in vitro. {ECO:0000269\|PubMed:11339880}.
Biotechnology:		Displays vaccine potential against the hyper-virulent M.tuberculosis Beijing K strain. Protective efficacy is correlated with the generation of Rv3628-specific CD4+ T cells co-producing IFN-gamma, TNF-alpha and IL-2 and exhibiting an elevated IFN-gamma recall response. {ECO:0000269\|PubMed:27097115}.
Similarity:		Belongs to the PPase family. {ECO:0000255\|HAMAP- Rule:MF_00209}.