HAMAP

Accession	MF_01249
Dates	26-APR-2004 (Created) 22-OCT-2010 (Last updated, Version 19)

Data class

Protein

Predictors

HAMAP; MF_01249; [distribution of match scores in UniProtKB];[seed alignment for MF_01249]

Names

HPr_kinase

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

hprK

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 (By similarity).

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 (By similarity).

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) (By similarity).

CATALYTIC ACTIVITY: ATP + HPr = ADP + P-Ser-HPr.

CATALYTIC ACTIVITY: P-Ser-HPr + phosphate = HPr + diphosphate.

COFACTOR: Magnesium (By similarity).

SUBUNIT: Homohexamer (By similarity).

DOMAIN: The Walker A ATP-binding motif also binds Pi and PPi (By similarity).

MISCELLANEOUS: Both phosphorylation and phosphorolysis are carried out by the same active site and suggest a common mechanism for both reactions (By similarity).

SIMILARITY: Belongs to the HPrK/P family.

Pfam	PF07475; Hpr_kinase_C; 1; PF02603; Hpr_kinase_N; 1;
TIGRFAMs	TIGR00679; hpr-ser; 1;

Multifunctional enzyme, Transferase, Kinase, Serine/threonine-protein kinase.

Carbohydrate metabolism.

ATP-binding, Nucleotide-binding, Magnesium, Metal-binding.

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.

From: HPRK_LACCA (Q9RE09)
Key		From		To		Description		Condition		FTGroup
NP_BIND		155		162		ATP (By similarity)		G-x-[SA]-G-x-G-K-S
ACT_SITE		140		140		By similarity		H
ACT_SITE		161		161		By similarity		K
ACT_SITE		179		179		Proton acceptor; for phosphorylation activity. Proton donor; for dephosphorylation activity (By similarity)		D
ACT_SITE		245		245		By similarity		R
METAL		162		162		Magnesium (Potential)		S
METAL		204		204		Magnesium (Potential)		E
REGION		203		212		Important for the catalytic mechanism of both phosphorylation and dephosphorylation (By similarity)
REGION		266		271		Important for the catalytic mechanism of dephosphorylation (By similarity)

Size range:	301-342 amino acids
Related UniRules:	None
Template:	O34483 (HPRK_BACSU); Q9RE09 (HPRK_LACCA); P75548 (HPRK_MYCPN); Q9S1H5 (HPRK_STAXY); Q9WXK7 (HPRK_STREI); Q9ZA98 (HPRK_STRSL): [Recover all]
Scope:	Bacteria
Fusion:	Nter: None; Cter: None
Duplicate:	in OCEIH
Plasmid encoded:	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.