UniProt functional annotation for P9WI83



	UniProt functional annotation for P9WI83

UniProt code: P9WI83.

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:25713147). 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 FtsZ, Wag31, GlmU, FhaB, PstP, EmbR and Rv1422 (PubMed:15985609, PubMed:16817899, PubMed:19121323, PubMed:20066037, PubMed:21190553, PubMed:21423706). Also catalyzes the phosphorylation of the proteasome alpha-subunit (PrcA) and unprocessed proteasome beta-subunit (pre-PrcB), which results in the inhibition of processing of pre-PrcB and assembly of the proteasome complex, and thereby enhances the mycobacterial resistance to H(2)O(2); PknA thus plays an important role in the oxidative stress response by impeding the formation of holo-proteasome in M.tuberculosis under H(2)O(2) stress (PubMed:25224505). Shows a strong preference for Thr versus Ser as the phosphoacceptor. {ECO:0000269|PubMed:15985609, ECO:0000269|PubMed:16817899, ECO:0000269|PubMed:19121323, ECO:0000269|PubMed:20066037, ECO:0000269|PubMed:21190553, ECO:0000269|PubMed:21423706, ECO:0000269|PubMed:25224505, ECO:0000269|PubMed:25713147}.

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:15985609};

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:15985609};

Activity regulation: Is activated by autophosphorylation of activation loop threonine residues, which results in conformational change and allows substrate binding. It seems that following ATP binding, phosphate is first transferred to Thr-180 via a cis mechanism to activate the kinase activity; phosphorylation of Thr-180 triggers PknA to phosphorylate Thr-172/Thr-174 via a trans mechanism. Phosphorylation of all of the activation loop threonines is necessary for efficient catalytic activity. {ECO:0000269|PubMed:25665034}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:21829358}; Single-pass membrane protein {ECO:0000269|PubMed:21829358}. Note=The majority of the cells displays PknA expression at the membrane perimeter along the length of the cell, whereas a minor population shows PknA to localize at either or both poles (uni- and bipolar; 16 and 14%, respectively) and occasionally to both the poles and the midcell (12%). {ECO:0000269|PubMed:25713147}.

Induction: Expressed predominantly in exponential phase. {ECO:0000269|PubMed:15985609}.

Domain: The extracellular domain is dispensable for cell growth and survival in vitro (PubMed:25713147). The catalytic activity of PknA is confined within the N-terminal 283 amino acids (PubMed:25665034). {ECO:0000269|PubMed:25665034, ECO:0000269|PubMed:25713147}.

Ptm: Autophosphorylated (PubMed:16739134) (PubMed:25665034) (PubMed:25586004). Phosphorylation of Thr-180 in the activation loop is critical for the functionality of PknA (PubMed:25665034). Autophosphorylation level increases in the presence of H(2)O(2) suggesting that PknA is activated by H(2)O(2) (PubMed:25224505). Phosphorylation of the activation loop at Thr-172 of PknA is critical for bacterial growth; PknA autophosphorylates its activation loop independent of PknB (PubMed:25713147). Dephosphorylated by PstP (PubMed:16817899). {ECO:0000269|PubMed:16739134, ECO:0000269|PubMed:16817899, ECO:0000269|PubMed:25224505, ECO:0000269|PubMed:25586004, ECO:0000269|PubMed:25665034, ECO:0000269|PubMed:25713147}.

Disruption phenotype: PknA 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. {ECO:0000269|PubMed:25713147}.

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:25713147). 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 FtsZ, Wag31, GlmU, FhaB, PstP, EmbR and Rv1422 (PubMed:15985609, PubMed:16817899, PubMed:19121323, PubMed:20066037, PubMed:21190553, PubMed:21423706). Also catalyzes the phosphorylation of the proteasome alpha-subunit (PrcA) and unprocessed proteasome beta-subunit (pre-PrcB), which results in the inhibition of processing of pre-PrcB and assembly of the proteasome complex, and thereby enhances the mycobacterial resistance to H(2)O(2); PknA thus plays an important role in the oxidative stress response by impeding the formation of holo-proteasome in M.tuberculosis under H(2)O(2) stress (PubMed:25224505). Shows a strong preference for Thr versus Ser as the phosphoacceptor. {ECO:0000269\|PubMed:15985609, ECO:0000269\|PubMed:16817899, ECO:0000269\|PubMed:19121323, ECO:0000269\|PubMed:20066037, ECO:0000269\|PubMed:21190553, ECO:0000269\|PubMed:21423706, ECO:0000269\|PubMed:25224505, ECO:0000269\|PubMed:25713147}.


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:15985609};
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:15985609};
Activity regulation:		Is activated by autophosphorylation of activation loop threonine residues, which results in conformational change and allows substrate binding. It seems that following ATP binding, phosphate is first transferred to Thr-180 via a cis mechanism to activate the kinase activity; phosphorylation of Thr-180 triggers PknA to phosphorylate Thr-172/Thr-174 via a trans mechanism. Phosphorylation of all of the activation loop threonines is necessary for efficient catalytic activity. {ECO:0000269\|PubMed:25665034}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:21829358}; Single-pass membrane protein {ECO:0000269\|PubMed:21829358}. Note=The majority of the cells displays PknA expression at the membrane perimeter along the length of the cell, whereas a minor population shows PknA to localize at either or both poles (uni- and bipolar; 16 and 14%, respectively) and occasionally to both the poles and the midcell (12%). {ECO:0000269\|PubMed:25713147}.
Induction:		Expressed predominantly in exponential phase. {ECO:0000269\|PubMed:15985609}.
Domain:		The extracellular domain is dispensable for cell growth and survival in vitro (PubMed:25713147). The catalytic activity of PknA is confined within the N-terminal 283 amino acids (PubMed:25665034). {ECO:0000269\|PubMed:25665034, ECO:0000269\|PubMed:25713147}.
Ptm:		Autophosphorylated (PubMed:16739134) (PubMed:25665034) (PubMed:25586004). Phosphorylation of Thr-180 in the activation loop is critical for the functionality of PknA (PubMed:25665034). Autophosphorylation level increases in the presence of H(2)O(2) suggesting that PknA is activated by H(2)O(2) (PubMed:25224505). Phosphorylation of the activation loop at Thr-172 of PknA is critical for bacterial growth; PknA autophosphorylates its activation loop independent of PknB (PubMed:25713147). Dephosphorylated by PstP (PubMed:16817899). {ECO:0000269\|PubMed:16739134, ECO:0000269\|PubMed:16817899, ECO:0000269\|PubMed:25224505, ECO:0000269\|PubMed:25586004, ECO:0000269\|PubMed:25665034, ECO:0000269\|PubMed:25713147}.
Disruption phenotype:		PknA 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. {ECO:0000269\|PubMed:25713147}.
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}.