UniProt functional annotation for P9WI81



	UniProt functional annotation for P9WI81

UniProt code: P9WI81.

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

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

Function: Protein kinase that regulates many aspects of mycobacterial physiology, and is critical for growth in vitro and survival of the pathogen in the host (PubMed:24706757). Is a key component of a signal transduction pathway that regulates cell growth, cell shape and cell division via phosphorylation of target proteins such as GarA, GlmU, PapA5, FhaB (Rv0019c), FhaA (Rv0020c), MviN, PstP, EmbR, Rv1422, Rv1747 and RseA (PubMed:15978616, PubMed:15985609, PubMed:15987910, PubMed:16817899, PubMed:16980473, PubMed:19121323, PubMed:19826007, PubMed:20025669, PubMed:21423706, PubMed:22275220). Also catalyzes the phosphorylation of the core proteasome alpha-subunit (PrcA), and thereby regulates the proteolytic activity of the proteasome (PubMed:25224505). Is a major regulator of the oxygen-dependent replication switch since PknB activity is necessary for reactivation of cells from the hypoxic state (PubMed:24409094). Shows a strong preference for Thr versus Ser as the phosphoacceptor. Overexpression of PknB alters cell morphology and leads to cell death (PubMed:24706757) (PubMed:24409094). {ECO:0000269|PubMed:15978616, ECO:0000269|PubMed:15985609, ECO:0000269|PubMed:15987910, ECO:0000269|PubMed:16817899, ECO:0000269|PubMed:16980473, ECO:0000269|PubMed:19121323, ECO:0000269|PubMed:19826007, ECO:0000269|PubMed:20025669, ECO:0000269|PubMed:21423706, ECO:0000269|PubMed:22275220, ECO:0000269|PubMed:24409094, ECO:0000269|PubMed:24706757, ECO:0000269|PubMed:25224505}.

Catalytic activity: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269|PubMed:10531215, ECO:0000269|PubMed:12548283, ECO:0000269|PubMed:12950916, ECO:0000269|PubMed:15978616, ECO:0000269|PubMed:15985609, ECO:0000269|PubMed:15987910, ECO:0000269|PubMed:19826007};

Catalytic activity: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269|PubMed:10531215, ECO:0000269|PubMed:12548283, ECO:0000269|PubMed:12950916, ECO:0000269|PubMed:15978616, ECO:0000269|PubMed:15985609, ECO:0000269|PubMed:15987910, ECO:0000269|PubMed:19826007};

Activity regulation: Interaction of the PASTA domains with peptidoglycan leads to septal and polar localization of PknB, and dimerization of the intracellular kinase domain. Dimerization activates the kinase domain via an allosteric mechanism, triggering autophosphorylation and phosphorylation of target proteins. Inhibited by mitoxantrone. Inhibition prevents mycobacterial growth. {ECO:0000269|PubMed:16674948, ECO:0000269|PubMed:20462494, ECO:0000269|PubMed:21134645, ECO:0000269|PubMed:21829358}.

Subunit: Homodimer. Interacts with the FHA domain of GarA, FhaB and FhaA. {ECO:0000269|PubMed:12548283, ECO:0000269|PubMed:12551895, ECO:0000269|PubMed:15978616, ECO:0000269|PubMed:16674948, ECO:0000269|PubMed:19008858, ECO:0000269|PubMed:19826007, ECO:0000269|PubMed:21134645, ECO:0000269|PubMed:22000520}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:21829358}; Single-pass membrane protein {ECO:0000269|PubMed:21829358}. Note=Localizes to septum and cell poles (PubMed:21829358). The localization of PknB to the cell membrane is essential for cell survival (PubMed:24706757). {ECO:0000269|PubMed:21829358, ECO:0000269|PubMed:24706757}.

Induction: Expressed predominantly in exponential phase (PubMed:15985609). PknB levels are regulated in response to hypoxia; its expression is down-regulated during hypoxia and recovers to aerated levels upon reaeration (at mRNA and protein level) (PubMed:24409094). {ECO:0000269|PubMed:15985609, ECO:0000269|PubMed:24409094}.

Domain: The intracellular kinase domain and all four extracytoplasmic PASTA domains are essential for PknB function and cell survival (PubMed:24706757). The PASTA domains interact with peptidoglycans and are required for PknB localization (PubMed:21829358). {ECO:0000269|PubMed:21829358, ECO:0000269|PubMed:24706757}.

Ptm: Autophosphorylated. Dephosphorylated by PstP. {ECO:0000269|PubMed:12548283, ECO:0000269|PubMed:12950916, ECO:0000269|PubMed:15967413, ECO:0000269|PubMed:15985609, ECO:0000269|PubMed:19008858}.

Disruption phenotype: Essential for growth, it cannot be disrupted (PubMed:16980473). PknB depletion in M.tuberculosis results in cell death and aberrant cell morphology, and leads to complete clearance of the pathogen from the host tissues using the murine infection model (PubMed:24706757). {ECO:0000269|PubMed:16980473, ECO:0000269|PubMed:24706757}.

Miscellaneous: Overexpression causes major growth and morphological changes that indicate defects in cell wall synthesis and possibly in cell division. {ECO:0000305|PubMed:15985609}.

Similarity: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.

Annotations taken from UniProtKB at the EBI.


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



Function:		Protein kinase that regulates many aspects of mycobacterial physiology, and is critical for growth in vitro and survival of the pathogen in the host (PubMed:24706757). Is a key component of a signal transduction pathway that regulates cell growth, cell shape and cell division via phosphorylation of target proteins such as GarA, GlmU, PapA5, FhaB (Rv0019c), FhaA (Rv0020c), MviN, PstP, EmbR, Rv1422, Rv1747 and RseA (PubMed:15978616, PubMed:15985609, PubMed:15987910, PubMed:16817899, PubMed:16980473, PubMed:19121323, PubMed:19826007, PubMed:20025669, PubMed:21423706, PubMed:22275220). Also catalyzes the phosphorylation of the core proteasome alpha-subunit (PrcA), and thereby regulates the proteolytic activity of the proteasome (PubMed:25224505). Is a major regulator of the oxygen-dependent replication switch since PknB activity is necessary for reactivation of cells from the hypoxic state (PubMed:24409094). Shows a strong preference for Thr versus Ser as the phosphoacceptor. Overexpression of PknB alters cell morphology and leads to cell death (PubMed:24706757) (PubMed:24409094). {ECO:0000269\|PubMed:15978616, ECO:0000269\|PubMed:15985609, ECO:0000269\|PubMed:15987910, ECO:0000269\|PubMed:16817899, ECO:0000269\|PubMed:16980473, ECO:0000269\|PubMed:19121323, ECO:0000269\|PubMed:19826007, ECO:0000269\|PubMed:20025669, ECO:0000269\|PubMed:21423706, ECO:0000269\|PubMed:22275220, ECO:0000269\|PubMed:24409094, ECO:0000269\|PubMed:24706757, ECO:0000269\|PubMed:25224505}.


Catalytic activity:		Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269\|PubMed:10531215, ECO:0000269\|PubMed:12548283, ECO:0000269\|PubMed:12950916, ECO:0000269\|PubMed:15978616, ECO:0000269\|PubMed:15985609, ECO:0000269\|PubMed:15987910, ECO:0000269\|PubMed:19826007};
Catalytic activity:		Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269\|PubMed:10531215, ECO:0000269\|PubMed:12548283, ECO:0000269\|PubMed:12950916, ECO:0000269\|PubMed:15978616, ECO:0000269\|PubMed:15985609, ECO:0000269\|PubMed:15987910, ECO:0000269\|PubMed:19826007};
Activity regulation:		Interaction of the PASTA domains with peptidoglycan leads to septal and polar localization of PknB, and dimerization of the intracellular kinase domain. Dimerization activates the kinase domain via an allosteric mechanism, triggering autophosphorylation and phosphorylation of target proteins. Inhibited by mitoxantrone. Inhibition prevents mycobacterial growth. {ECO:0000269\|PubMed:16674948, ECO:0000269\|PubMed:20462494, ECO:0000269\|PubMed:21134645, ECO:0000269\|PubMed:21829358}.
Subunit:		Homodimer. Interacts with the FHA domain of GarA, FhaB and FhaA. {ECO:0000269\|PubMed:12548283, ECO:0000269\|PubMed:12551895, ECO:0000269\|PubMed:15978616, ECO:0000269\|PubMed:16674948, ECO:0000269\|PubMed:19008858, ECO:0000269\|PubMed:19826007, ECO:0000269\|PubMed:21134645, ECO:0000269\|PubMed:22000520}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:21829358}; Single-pass membrane protein {ECO:0000269\|PubMed:21829358}. Note=Localizes to septum and cell poles (PubMed:21829358). The localization of PknB to the cell membrane is essential for cell survival (PubMed:24706757). {ECO:0000269\|PubMed:21829358, ECO:0000269\|PubMed:24706757}.
Induction:		Expressed predominantly in exponential phase (PubMed:15985609). PknB levels are regulated in response to hypoxia; its expression is down-regulated during hypoxia and recovers to aerated levels upon reaeration (at mRNA and protein level) (PubMed:24409094). {ECO:0000269\|PubMed:15985609, ECO:0000269\|PubMed:24409094}.
Domain:		The intracellular kinase domain and all four extracytoplasmic PASTA domains are essential for PknB function and cell survival (PubMed:24706757). The PASTA domains interact with peptidoglycans and are required for PknB localization (PubMed:21829358). {ECO:0000269\|PubMed:21829358, ECO:0000269\|PubMed:24706757}.
Ptm:		Autophosphorylated. Dephosphorylated by PstP. {ECO:0000269\|PubMed:12548283, ECO:0000269\|PubMed:12950916, ECO:0000269\|PubMed:15967413, ECO:0000269\|PubMed:15985609, ECO:0000269\|PubMed:19008858}.
Disruption phenotype:		Essential for growth, it cannot be disrupted (PubMed:16980473). PknB depletion in M.tuberculosis results in cell death and aberrant cell morphology, and leads to complete clearance of the pathogen from the host tissues using the murine infection model (PubMed:24706757). {ECO:0000269\|PubMed:16980473, ECO:0000269\|PubMed:24706757}.
Miscellaneous:		Overexpression causes major growth and morphological changes that indicate defects in cell wall synthesis and possibly in cell division. {ECO:0000305\|PubMed:15985609}.
Similarity:		Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. {ECO:0000255\|PROSITE-ProRule:PRU00159}.