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Protein

HPr kinase/phosphorylase

Gene

hprK

Organism
Lactobacillus casei
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the ATP- as well as the pyrophosphate-dependent phosphorylation of 'Ser-46' 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.

Catalytic activityi

ATP + HPr = ADP + P-Ser-HPr.
P-Ser-HPr + phosphate = HPr + diphosphate.

Cofactori

Enzyme regulationi

Kinase activity is slightly activated by fructose 1,6-bisphosphate (FBP), and inhibited by inorganic phosphate (Pi), but FBP prevents kinase inhibition by Pi. Dephosphorylation of P-Ser-HPr is slightly inhibited by FBP.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei140 – 1401
Active sitei161 – 1611
Metal bindingi162 – 1621MagnesiumCurated
Active sitei179 – 1791Proton acceptor; for phosphorylation activity. Proton donor; for dephosphorylation activity
Metal bindingi204 – 2041MagnesiumCurated
Active sitei245 – 2451

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi155 – 1628ATPCurated

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Carbohydrate metabolism

Keywords - Ligandi

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

Names & Taxonomyi

Protein namesi
Recommended name:
HPr kinase/phosphorylase (EC:2.7.11.-, EC:2.7.4.-)
Short name:
HPrK/P
Alternative name(s):
HPr kinase/phosphatase
HPr(Ser) kinase/phosphorylase
Gene namesi
Name:hprK
OrganismiLactobacillus casei
Taxonomic identifieri1582 [NCBI]
Taxonomic lineageiBacteriaFirmicutesBacilliLactobacillalesLactobacillaceaeLactobacillus

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 319319HPr kinase/phosphorylasePRO_0000058959Add
BLAST

Interactioni

Subunit structurei

Homohexamer, arranged as bilayered trimers. Six HPr molecules bind to the hexamer at sites that overlap two of its subunits.1 Publication

Protein-protein interaction databases

IntActiQ9RE09. 1 interaction.
STRINGi543734.LCABL_10590.

Structurei

Secondary structure

1
319
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi139 – 1468Combined sources
Beta strandi149 – 1546Combined sources
Turni158 – 1614Combined sources
Helixi162 – 1698Combined sources
Turni170 – 1723Combined sources
Beta strandi174 – 18512Combined sources
Beta strandi187 – 1893Combined sources
Beta strandi191 – 1944Combined sources
Beta strandi197 – 1993Combined sources
Beta strandi202 – 2054Combined sources
Turni206 – 2083Combined sources
Beta strandi209 – 2124Combined sources
Helixi213 – 2175Combined sources
Helixi219 – 2213Combined sources
Beta strandi224 – 2274Combined sources
Beta strandi230 – 2345Combined sources
Beta strandi245 – 2473Combined sources
Beta strandi250 – 2578Combined sources
Beta strandi259 – 2657Combined sources
Helixi273 – 28715Combined sources
Turni288 – 2903Combined sources
Helixi293 – 30614Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1JB1X-ray2.80A128-319[»]
1KKLX-ray2.80A/B/C128-319[»]
1KKMX-ray2.80A/B/C128-319[»]
2QMHX-ray2.60A/B/C/D/E/F/G/H/I/J/K/L128-319[»]
ProteinModelPortaliQ9RE09.
SMRiQ9RE09. Positions 135-311.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9RE09.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni203 – 21210Important for the catalytic mechanism of both phosphorylation and dephosphorylation
Regioni266 – 2716Important for the catalytic mechanism of dephosphorylation

Domaini

The Walker A ATP-binding motif also binds Pi and PPi.Curated

Sequence similaritiesi

Belongs to the HPrK/P family.Curated

Phylogenomic databases

eggNOGiENOG4105D1C. Bacteria.
COG1493. LUCA.

Family and domain databases

Gene3Di3.40.1390.20. 1 hit.
3.40.50.300. 1 hit.
HAMAPiMF_01249. HPr_kinase.
InterProiIPR003755. HPr(Ser)_kin/Pase.
IPR011104. Hpr_kin/Pase_C.
IPR011126. Hpr_kin/Pase_Hpr_N.
IPR027417. P-loop_NTPase.
IPR028979. Ser_kin/Pase_Hpr_N-like.
[Graphical view]
PfamiPF07475. Hpr_kinase_C. 1 hit.
PF02603. Hpr_kinase_N. 1 hit.
[Graphical view]
SUPFAMiSSF75138. SSF75138. 1 hit.
TIGRFAMsiTIGR00679. hpr-ser. 1 hit.

Sequencei

Sequence statusi: Complete.

Q9RE09-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MADSVTVRQL VKATKLEVYS GEEYLDQRQV VLSDISRPGL ELTGYFNYYP
60 70 80 90 100
HERIQLFGRT EISFARNMSS EERLLILKRM ATEDTPAFLV SRGLEAPAEM
110 120 130 140 150
ITAATAAHIP VLGSRLPTTR LSSLITEYLD SQLAERRSMH GVLVDIYGLG
160 170 180 190 200
VLITGDSGVG KSETALELVQ RGHRLIADDR VDVYQQDEQT IVGAAPPILS
210 220 230 240 250
HLLEIRGLGI IDVMNLFGAG AVREDTTISL IVHLENWTPD KTFDRLGSGE
260 270 280 290 300
QTQLIFDVPV PKITVPVKVG RNLAIIIEVA AMNFRAKSMG YDATKTFEKN
310
LNHLIEHNEE TDQNSSGDK
Length:319
Mass (Da):35,348
Last modified:May 1, 2000 - v1
Checksum:i96D27AE3D31132E8
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y18948 Genomic DNA. Translation: CAB65151.1.
RefSeqiWP_003564222.1. NZ_LTDP01000112.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y18948 Genomic DNA. Translation: CAB65151.1.
RefSeqiWP_003564222.1. NZ_LTDP01000112.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1JB1X-ray2.80A128-319[»]
1KKLX-ray2.80A/B/C128-319[»]
1KKMX-ray2.80A/B/C128-319[»]
2QMHX-ray2.60A/B/C/D/E/F/G/H/I/J/K/L128-319[»]
ProteinModelPortaliQ9RE09.
SMRiQ9RE09. Positions 135-311.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9RE09. 1 interaction.
STRINGi543734.LCABL_10590.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

eggNOGiENOG4105D1C. Bacteria.
COG1493. LUCA.

Miscellaneous databases

EvolutionaryTraceiQ9RE09.

Family and domain databases

Gene3Di3.40.1390.20. 1 hit.
3.40.50.300. 1 hit.
HAMAPiMF_01249. HPr_kinase.
InterProiIPR003755. HPr(Ser)_kin/Pase.
IPR011104. Hpr_kin/Pase_C.
IPR011126. Hpr_kin/Pase_Hpr_N.
IPR027417. P-loop_NTPase.
IPR028979. Ser_kin/Pase_Hpr_N-like.
[Graphical view]
PfamiPF07475. Hpr_kinase_C. 1 hit.
PF02603. Hpr_kinase_N. 1 hit.
[Graphical view]
SUPFAMiSSF75138. SSF75138. 1 hit.
TIGRFAMsiTIGR00679. hpr-ser. 1 hit.
ProtoNetiSearch...

Publicationsi

  1. "Phosphorylation of HPr by the bifunctional HPr kinase/P-Ser-HPr phosphatase from Lactobacillus casei controls catabolite repression and inducer exclusion but not inducer expulsion."
    Dossonnet V., Monedero V., Zagorec M., Galinier A., Perez-Martinez G., Deutscher J.
    J. Bacteriol. 182:2582-2590(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], CHARACTERIZATION.
    Strain: ATCC 393 / DSM 20011 / JCM 1134 / NBRC 15883 / NCIMB 11970 / NCDO 161.
  2. Cited for: DEPHOSPHORYLATION REACTION MECHANISM.
  3. "X-ray structure of HPr kinase: a bacterial protein kinase with a P-loop nucleotide-binding domain."
    Fieulaine S., Morera S., Poncet S., Monedero V., Gueguen-Chaignon V., Galinier A., Janin J., Deutscher J., Nessler S.
    EMBO J. 20:3917-3927(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT, X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 135-307 IN COMPLEX WITH PHOSPHATE.
  4. "X-ray structure of a bifunctional protein kinase in complex with its protein substrate HPr."
    Fieulaine S., Morera S., Poncet S., Mijakovic I., Galinier A., Janin J., Deutscher J., Nessler S.
    Proc. Natl. Acad. Sci. U.S.A. 99:13437-13441(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 128-319 IN COMPLEXES WITH B.SUBTILIS HPR AND B.SUBTILIS P-SER-HPR.

Entry informationi

Entry nameiHPRK_LACCA
AccessioniPrimary (citable) accession number: Q9RE09
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: May 1, 2000
Last modified: July 6, 2016
This is version 84 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

The truncated form that consists of amino acids 128-319 exhibits in vitro enzymatic activities identical to those of the full-length protein, and also forms a hexamer.
Both phosphorylation and phosphorolysis are carried out by the same active site and suggest a common mechanism for both reactions.

Caution

Was originally (PubMed:10762262) called HPr kinase/phosphatase, but P-Ser-HPr dephosphorylation was shown (PubMed:12359880) to follow a quite unique mechanism, in which Pi instead of H2O 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.2 Publications

Keywords - Technical termi

3D-structure, Multifunctional enzyme

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.