phoR1

UniProt ID: A0A0H2MMT2
Organism: Variovorax paradoxus
Review Status: COMPLETE
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Gene Description

Phosphate regulon sensor histidine kinase PhoR1 (VPARA_10420, A0A0H2MMT2; EC 2.7.13.3) in Variovorax paradoxus strain TBEA6 is a 464-amino-acid inner-membrane bifunctional sensor kinase and phospho-PhoB1 phosphatase (InterPro IPR014310, NCBIfam TIGR02966, PANTHER PTHR45453:SF1) encoded on genomic contig JZWI01000005 (EMBL KLN58030.1) immediately adjacent to its cognate response regulator phoB1 (VPARA_10430) at the 5' boundary of the phoR1-phoB1-phoU-pstB-pstA-pstC-pstS-ppx cluster (VPARA_10420-VPARA_10490). PhoR1 comprises an N-terminal membrane-anchoring region (Pfam PF11808, InterPro IPR021766, transmembrane helix at residues 29-45), a cytoplasmic Per-ARNT-Sim (PAS) sensory domain (Pfam PF00989, CDD cd00130, InterPro IPR000014), and a C-terminal histidine kinase dimerization/phosphoacceptor (HisKA, Pfam PF00512, CDD cd00082) and catalytic ATP-binding (HATPase_c, Pfam PF02518; PROSITE PS50109, residues 216-436) module housing the autocatalytic phosphohistidine acceptor His219 (within 216-NVSHEIRTPL-225). When extracellular inorganic phosphate is limiting, PhoR1 autophosphorylates at His219 and transfers the phosphoryl group to Asp54 of PhoB1 to activate the Pho starvation regulon; when phosphate is abundant, interaction of its PAS domain with the PstSCAB-PhoU signaling complex switches PhoR1 into a phospho-PhoB1 phosphatase.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000155 phosphorelay sensor kinase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: Core molecular function; under phosphate limitation, PhoR1 undergoes ATP-dependent autophosphorylation at His219 and transfers the phosphoryl group to its cognate response regulator PhoB1.
Reason: PhoR1 contains the complete proteobacterial PhoR sensor histidine kinase architecture (NCBIfam TIGR02966, InterPro IPR014310, PANTHER PTHR45453:SF1, PROSITE PS50109 residues 216-436) including the conserved autocatalytic phosphohistidine residue His219 (MOD_RES 219; PMID:24563032).
Supporting Evidence:
file:VARPD/phoR1/phoR1-uniprot.txt
FT DOMAIN 216..436 FT /note="Histidine kinase" FT /evidence="ECO:0000259|PROSITE:PS50109"
file:VARPD/phoR1/phoR1-uniprot.txt
FT MOD_RES 219 FT /note="Phosphohistidine; by autocatalysis" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00107"
PMID:24563032
PhoR is the bifunctional histidine autokinase/phospho-PhoB phosphatase that donates a phosphoryl group to PhoB when environmental P i is limiting and removes the phosphoryl group from phosphorylated PhoB (PhoB∼P) when environmental P i is abundant ( 11 , 12 ).
GO:0000160 phosphorelay signal transduction system
IEA
GO_REF:0000002 		ACCEPT
Summary: Core biological process of the PhoR1-PhoB1 two-component phosphorelay system.
Reason: PhoR1 and PhoB1 (VPARA_10420-VPARA_10430) form the canonical two-component phosphorelay system that senses phosphate availability via PstSCAB-PhoU and regulates the Pho regulon (PMID:24563032).
Supporting Evidence:
file:VARPD/phoR1/phoR1-uniprot.txt
DR InterPro; IPR014310; Sig_transdc_His_kinase_PhoR. DR NCBIfam; TIGR02966; phoR_proteo; 1. DR PANTHER; PTHR45453; PHOSPHATE REGULON SENSOR PROTEIN PHOR; 1. DR PANTHER; PTHR45453:SF1; PHOSPHATE REGULON SENSOR PROTEIN PHOR; 1.
PMID:24563032
The hub of the signaling pathway consists of the two-component signaling proteins PhoB and PhoR ( 6 ).
GO:0004673 protein histidine kinase activity
IEA
GO_REF:0000120 		TOO GENERAL
Summary: True but uninformative parent molecular function already entailed by the accepted specific child term GO:0000155 (phosphorelay sensor kinase activity).
Reason: GO:0004673 (protein histidine kinase activity) is the direct parent of GO:0000155 (phosphorelay sensor kinase activity) already accepted in this review.
Supporting Evidence:
file:VARPD/phoR1/phoR1-uniprot.txt
FT DOMAIN 216..436 FT /note="Histidine kinase" FT /evidence="ECO:0000259|PROSITE:PS50109"
GO:0004721 phosphoprotein phosphatase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: Core second catalytic activity of bifunctional PhoR1, which dephosphorylates phospho-PhoB1 under phosphate-replete conditions when stimulated by PstSCAB-PhoU.
Reason: PhoR is a bifunctional histidine autokinase / phospho-PhoB phosphatase that dephosphorylates PhoB~P when external Pi is abundant and PstSCAB-PhoU interacts with the PhoR PAS domain (PMID:24563032).
Supporting Evidence:
PMID:24563032
PhoR is the bifunctional histidine autokinase/phospho-PhoB phosphatase that donates a phosphoryl group to PhoB when environmental P i is limiting and removes the phosphoryl group from phosphorylated PhoB (PhoB∼P) when environmental P i is abundant ( 11 , 12 ).
GO:0005886 plasma membrane
IEA
GO_REF:0000120 		ACCEPT
Summary: Core subcellular localization of the inner-membrane-anchored PhoR1 sensor histidine kinase.
Reason: PhoR1 is anchored in the bacterial inner (plasma) membrane via its N-terminal transmembrane region (Pfam PF11808, InterPro IPR021766, transmembrane helix at residues 29-45; PMID:24563032).
Supporting Evidence:
file:VARPD/phoR1/phoR1-uniprot.txt
FT TRANSMEM 29..45 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius"
GO:0006355 regulation of DNA-templated transcription
IEA
GO_REF:0000002 		KEEP AS NON CORE
Summary: Indirect upstream role; PhoR1 regulates transcription of the Pho regulon by phosphorylating or dephosphorylating the DNA-binding response regulator PhoB1.
Reason: PhoR1 does not bind DNA itself, but acts immediately upstream of PhoB1 (VPARA_10430) to control transcription of the Pho regulon in response to phosphate availability (PMID:24563032); retained as KEEP_AS_NON_CORE.
Supporting Evidence:
file:VARPD/phoR1/phoR1-uniprot.txt
DR InterPro; IPR014310; Sig_transdc_His_kinase_PhoR. DR NCBIfam; TIGR02966; phoR_proteo; 1. DR PANTHER; PTHR45453; PHOSPHATE REGULON SENSOR PROTEIN PHOR; 1. DR PANTHER; PTHR45453:SF1; PHOSPHATE REGULON SENSOR PROTEIN PHOR; 1.
GO:0007165 signal transduction
IEA
GO_REF:0000120 		TOO GENERAL
Summary: True but uninformative parent biological process already entailed by the accepted specific child term GO:0000160 (phosphorelay signal transduction system).
Reason: GO:0007165 (signal transduction) is a broad ancestor term already entailed by GO:0000160 (phosphorelay signal transduction system) accepted in this review.
Supporting Evidence:
file:VARPD/phoR1/phoR1-uniprot.txt
DR InterPro; IPR014310; Sig_transdc_His_kinase_PhoR. DR NCBIfam; TIGR02966; phoR_proteo; 1. DR PANTHER; PTHR45453; PHOSPHATE REGULON SENSOR PROTEIN PHOR; 1. DR PANTHER; PTHR45453:SF1; PHOSPHATE REGULON SENSOR PROTEIN PHOR; 1.
GO:0016020 membrane
IEA
GO_REF:0000002 		TOO GENERAL
Summary: True but uninformative parent cellular component already entailed by the accepted specific child term GO:0005886 (plasma membrane).
Reason: GO:0016020 (membrane) adds no specificity beyond GO:0005886 (plasma membrane) already accepted in this review.
Supporting Evidence:
file:VARPD/phoR1/phoR1-uniprot.txt
FT TRANSMEM 29..45 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius"
GO:0016036 cellular response to phosphate starvation
IEA
GO_REF:0000118 		ACCEPT
Summary: Core biological process; PhoR1 is the primary sensor kinase that initiates the cellular response to inorganic phosphate starvation.
Reason: When extracellular Pi drops below ~4 uM, the low-activity state of PstSCAB-PhoU relieves inhibition of PhoR1 autokinase activity, triggering phosphorylation of PhoB1 and induction of the phosphate starvation regulon (PMID:24563032).
Supporting Evidence:
file:VARPD/phoR1/phoR1-uniprot.txt
DR InterPro; IPR014310; Sig_transdc_His_kinase_PhoR. DR NCBIfam; TIGR02966; phoR_proteo; 1. DR PANTHER; PTHR45453; PHOSPHATE REGULON SENSOR PROTEIN PHOR; 1. DR PANTHER; PTHR45453:SF1; PHOSPHATE REGULON SENSOR PROTEIN PHOR; 1.
PMID:24563032
The low-activity-state transporter signals for the high autokinase activity of PhoR, which leads to elevated levels of phospho-PhoB.
GO:0016301 kinase activity
IEA
GO_REF:0000104 		TOO GENERAL
Summary: True but uninformative parent molecular function already entailed by the accepted specific child term GO:0000155 (phosphorelay sensor kinase activity).
Reason: GO:0016301 (kinase activity) is an ancestor of GO:0000155 (phosphorelay sensor kinase activity) already accepted in this review.
Supporting Evidence:
file:VARPD/phoR1/phoR1-uniprot.txt
FT DOMAIN 216..436 FT /note="Histidine kinase" FT /evidence="ECO:0000259|PROSITE:PS50109"
GO:0016740 transferase activity
IEA
GO_REF:0000104 		TOO GENERAL
Summary: True but uninformative high-level parent molecular function already entailed by GO:0000155 (phosphorelay sensor kinase activity).
Reason: GO:0016740 (transferase activity) is a root-adjacent ancestor of GO:0000155 already accepted in this review.
Supporting Evidence:
file:VARPD/phoR1/phoR1-uniprot.txt
FT DOMAIN 216..436 FT /note="Histidine kinase" FT /evidence="ECO:0000259|PROSITE:PS50109"
GO:0016772 transferase activity, transferring phosphorus-containing groups
IEA
GO_REF:0000002 		TOO GENERAL
Summary: True but uninformative parent molecular function already entailed by GO:0000155 (phosphorelay sensor kinase activity).
Reason: GO:0016772 is an ancestor of GO:0000155 (phosphorelay sensor kinase activity) already accepted in this review.
Supporting Evidence:
file:VARPD/phoR1/phoR1-uniprot.txt
FT DOMAIN 216..436 FT /note="Histidine kinase" FT /evidence="ECO:0000259|PROSITE:PS50109"

Core Functions

Inner-membrane phosphorelay sensor histidine kinase that autophosphorylates at His219 and transfers the phosphoryl group to Asp54 of PhoB1 when extracellular inorganic phosphate is limiting, initiating the cellular response to phosphate starvation.

Molecular Function:
phosphorelay sensor kinase activity
Directly Involved In:
phosphorelay signal transduction system cellular response to phosphate starvation
Cellular Locations:
plasma membrane
Supporting Evidence:
  • file:VARPD/phoR1/phoR1-uniprot.txt
    FT TRANSMEM 29..45 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT DOMAIN 216..436 FT /note="Histidine kinase" FT /evidence="ECO:0000259|PROSITE:PS50109"
  • PMID:24563032
    PhoR is the bifunctional histidine autokinase/phospho-PhoB phosphatase that donates a phosphoryl group to PhoB when environmental P i is limiting and removes the phosphoryl group from phosphorylated PhoB (PhoB∼P) when environmental P i is abundant ( 11 , 12 ).

Dephosphorylates phospho-PhoB1 under phosphate-replete conditions when its cytoplasmic PAS domain interacts with PhoU in the active PstSCAB-PhoU signaling complex.

Molecular Function:
phosphoprotein phosphatase activity
Directly Involved In:
phosphorelay signal transduction system
Cellular Locations:
plasma membrane
Supporting Evidence:
  • PMID:24563032
    When external P i levels are above ∼4 μM, the transporter exists in a high-activity state that stimulates the phospho-PhoB phosphatase activity of PhoR ( 5 ).

References

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Suggested Questions for Experts

Q: How does binding of PhoU (VPARA_10440) to the cytoplasmic PAS domain of PhoR1 (VPARA_10420) reorient the HisKA (DHp) and HATPase_c (CA) domains around His219 to switch PhoR1 from autokinase to phospho-PhoB1 phosphatase activity?

Suggested experts: McCleary WR

Suggested Experiments

Experiment: Reconstitute the cytoplasmic PAS-DHp-CA fragment of Variovorax paradoxus PhoR1 (A0A0H2MMT2) with phosphorylated PhoB1 (A0A0H2M7F4) and PhoU (A0A0H2MBK2) in vitro to measure autophosphorylation at His219, phosphotransfer to PhoB1 Asp54, and PhoU-stimulated phospho-PhoB1 dephosphorylation.

Hypothesis: PhoR1 exhibits His219 autokinase and PhoB1 phosphotransfer activity in the absence of PstB-PhoU, and shifts toward phospho-PhoB1 phosphatase activity when bound by the PhoU-PstB complex (PMID:24563032).

πŸ“š Additional Documentation

Notes

(phoR1-notes.md)

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