HAMAP rule MF_01249
General rule information
[?]
| Accession | MF_01249 |
| Dates | 26-APR-2004 (Created)
1-JUN-2023 (Last updated, Version 28) |
| Name | HPr_kinase |
| Scope(s) |
Bacteria |
| Template(s) | O34483 (HPRK_BACSU); Q9RE09 (HPRK_LACCA); P75548 (HPRK_MYCPN); Q9S1H5 (HPRK_STAXY); Q9WXK7 (HPRK_STREI); Q9ZA98 (HPRK_STRSL); [ Recover all ] |
| Triggered by |
HAMAP; MF_01249 (Get profile general information and statistics) |
Propagated annotation
[?]
Identifier, protein and gene names
[?]
| Identifier | HPRK |
| Protein name | RecName: Full=HPr kinase/phosphorylase; Short=HPrK/P; EC=2.7.11.-; EC=2.7.4.-; AltName: Full=HPr(Ser) kinase/phosphorylase; |
| Gene name | Name=hprK; |
Comments
[?]
| case <OC:Bacillaceae> | |
| FUNCTION | Catalyzes the ATP- as well as the pyrophosphate-dependent phosphorylation of a specific serine residue in HPr, a phosphocarrier protein of the phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS). HprK/P also catalyzes the pyrophosphate-producing, inorganic phosphate-dependent dephosphorylation (phosphorolysis) of seryl-phosphorylated HPr (P-Ser-HPr). The two antagonistic activities of HprK/P are regulated by several intracellular metabolites, which change their concentration in response to the absence or presence of rapidly metabolisable carbon sources (glucose, fructose, etc.) in the growth medium. Also phosphorylates/dephosphorylates the HPr-like catabolite repression protein crh on a specific serine residue. Therefore, by controlling the phosphorylation state of HPr and crh, HPrK/P is a sensor enzyme that plays a major role in the regulation of carbon metabolism and sugar transport: it mediates carbon catabolite repression (CCR), and regulates PTS-catalyzed carbohydrate uptake and inducer exclusion. |
| end case | |
| case <OC:Bacillota> and not <OC:Bacillaceae> | |
| FUNCTION | Catalyzes the ATP- as well as the pyrophosphate-dependent phosphorylation of a specific serine residue in HPr, a phosphocarrier protein of the phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS). HprK/P also catalyzes the pyrophosphate-producing, inorganic phosphate-dependent dephosphorylation (phosphorolysis) of seryl-phosphorylated HPr (P-Ser-HPr). The two antagonistic activities of HprK/P are regulated by several intracellular metabolites, which change their concentration in response to the absence or presence of rapidly metabolisable carbon sources (glucose, fructose, etc.) in the growth medium. Therefore, by controlling the phosphorylation state of HPr, HPrK/P is a sensor enzyme that plays a major role in the regulation of carbon metabolism and sugar transport: it mediates carbon catabolite repression (CCR), and regulates PTS-catalyzed carbohydrate uptake and inducer exclusion. |
| end case | |
| case not <OC:Bacillota> | |
| FUNCTION | Catalyzes the ATP- as well as the pyrophosphate-dependent phosphorylation of a specific serine residue in HPr, a phosphocarrier protein of the phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS). HprK/P also catalyzes the pyrophosphate-producing, inorganic phosphate-dependent dephosphorylation (phosphorolysis) of seryl-phosphorylated HPr (P-Ser-HPr). |
| end case | |
| CATALYTIC ACTIVITY | Reaction=[HPr protein]-L-serine + ATP = [HPr protein]-O-phospho-L- serine + ADP + H(+); Xref=Rhea:RHEA:46600, Rhea:RHEA-COMP:11602, Rhea:RHEA-COMP:11603, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; |
| CATALYTIC ACTIVITY | Reaction=[HPr protein]-O-phospho-L-serine + H(+) + phosphate = [HPr protein]-L-serine + diphosphate; Xref=Rhea:RHEA:46604, Rhea:RHEA- COMP:11602, Rhea:RHEA-COMP:11603, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:33019, ChEBI:CHEBI:43474, ChEBI:CHEBI:83421; |
| COFACTOR | Name=Mg(2+); Xref=ChEBI:CHEBI:18420; |
| SUBUNIT | Homohexamer. |
| DOMAIN | The Walker A ATP-binding motif also binds Pi and PPi. |
| MISCELLANEOUS | Both phosphorylation and phosphorolysis are carried out by the same active site and suggest a common mechanism for both reactions. |
| SIMILARITY | Belongs to the HPrK/P family. |
Keywords
[?]
| Multifunctional enzyme | |
| Transferase | |
| Kinase | |
| Serine/threonine-protein kinase | |
| case <OC:Bacillota> | |
| Carbohydrate metabolism | |
| end case | |
| ATP-binding | |
| Nucleotide-binding | |
| Magnesium | |
| Metal-binding | |
Gene Ontology
[?]
| GO:0000287; Molecular function:magnesium ion binding |
| GO:0004712; Molecular function:protein serine/threonine/tyrosine kinase activity |
| GO:0005524; Molecular function:ATP binding |
| GO:0006109; Biological process:regulation of carbohydrate metabolic process |
Cross-references
[?]
Features
[?]
| From: HPRK_LACCA (Q9RE09) | ||||||||||||
| Key | From | To | Description | Tag | Condition | FTGroup | ||||||
| BINDING | 155 | 162 | /ligand="ATP" /ligand_id="ChEBI:CHEBI:30616" |
G-x-[SA]-G-x-G-K-S | ||||||||
| ACT_SITE | 140 | 140 | H | |||||||||
| ACT_SITE | 161 | 161 | K | |||||||||
| ACT_SITE | 179 | 179 | /note="Proton acceptor; for phosphorylation activity. Proton donor; for dephosphorylation activity" | D | ||||||||
| ACT_SITE | 245 | 245 | R | |||||||||
| BINDING | 162 | 162 | /ligand="Mg(2+)" /ligand_id="ChEBI:CHEBI:18420" |
S | ||||||||
| BINDING | 204 | 204 | /ligand="Mg(2+)" /ligand_id="ChEBI:CHEBI:18420" |
E | ||||||||
| REGION | 203 | 212 | /note="Important for the catalytic mechanism of both phosphorylation and dephosphorylation" | |||||||||
| REGION | 266 | 271 | /note="Important for the catalytic mechanism of dephosphorylation" | |||||||||
Additional information
[?]
| Size range | 301-342 amino acids |
| Related rules |
None |
| Fusion | Nter: None Cter: None |
| Comments | This enzyme was originally called HPr kinase/phosphatase, but P-Ser-HPr dephosphorylation was recently found to follow a quite unique mechanism, in which Pi instead of H(2)O is used for the nucleophilic attack on the phosphoryl group. P-Ser-HPr dephosphorylation is therefore not a phosphohydrolysis but a phosphophosphorolysis reaction, and the bifunctional enzyme was dubbed HPr kinase/phosphorylase. The regulatory role(s) of HPrK/P in bacterial physiology may be quite diverse. In low GC Gram-positive bacteria, HPr kinase/phosphorylase plays a major role in the regulation of carbon metabolism as it is a bifunctional sensor enzyme for CCR, PTS-catalyzed sugar transport and inducer exclusion. But HPRK/P must carry out different regulatory functions in Gram-negative bacteria, as these bacteria are devoid of ccpA protein, and a functional PTS also seems to be absent. The gene organization in many hprK-containing Gram-negative bacteria strongly suggest that HPrK/P regulates either a two-component sensory system implicated in cell adhesion/virology or rpoN-like sigma-factors. In Fusobacterium nucleatum, this protein is composed of two complete HPrK/P domains fused in tandem. |