Curatorial Notes for `phoU` (`A0A0H2MBK2`, `VPARA_10440`) in Variovorax paradoxus TBEA6

1. Gene & Protein Identity

UniProt Accession: A0A0H2MBK2 (A0A0H2MBK2_VARPD)
Gene Symbol: phoU
Locus Tag / EMBL CDS: VPARA_10440 / KLN58032.1 on contig JZWI01000005 (RefSeq:WP_047783561.1)
Protein Length: 233 aa (25,818 Da); cytoplasmic homodimer (PIRNR:PIRNR003107) containing two tandem symmetric three-alpha-helix bundle PhoU domains (Pfam:PF01895 at residues 22–108 and 129–210; InterPro:IPR028366, NCBIfam:TIGR02135 phoU_full, PANTHER:PTHR42930:SF3).
Conserved Metal-Binding & Signaling Motifs:
Conserves the charged metal-coordinating and pocket residues in both three-helix bundles (Glu54, Asn58, Glu96, Asp100 plus conserved Arg97 in bundle 1, and Asp159, Asp163, Glu198, Asp202 plus conserved Arg199 in bundle 2, corresponding to the E. coli PhoU metal ligands D58/N62/E100/D104 and D161/D165/E200/D204 and conserved R101/R201 characterized in PMID:24563032).

Encoded immediately between phoB1 (VPARA_10430, KLN58031.1) and pstB (VPARA_10450, KLN58033.1) within the phoR1-phoB1-phoU-pstB-pstA-pstC-pstS-ppx (VPARA_10420–VPARA_10490) phosphate regulon gene cluster.

PMID:24563032 (Gardner et al. 2014 J Bacteriol): Demonstrates by bacterial two-hybrid, affinity co-elution, gel filtration, ICP-MS, tryptophan fluorescence, and chromosomal integration of phoUQuad mutants that PhoU is a homodimer that binds $\text{Mn}^{2+}$ and $\text{Mg}^{2+}$ (which may be important for localizing PhoU to the inner membrane) and physically bridges the PstB ATPase subunit of PstSCAB to the PAS domain of the PhoR sensor kinase, negatively regulating the Pho regulon and modulating PstSCAB phosphate transport under phosphate-replete conditions.
PMID:3881386 (Surin et al. 1985 J Bacteriol): Nucleotide sequence and organization of phoU at the 3' end of the phoS-pstC-pstA-pstB-phoU operon.

GO:0005737 (cytoplasm, IEA GO_REF:0000044): ACCEPT — core location of soluble PhoU homodimers that peripherally associate with the inner membrane via PstB and PhoR1 (PMID:24563032).
GO:0030643 (intracellular phosphate ion homeostasis, IEA GO_REF:0000002): ACCEPT — PhoU couples PstSCAB transport activity to PhoR1-PhoB1 signaling and prevents toxic hyperaccumulation of inorganic phosphate and polyphosphate (PMID:24563032).
GO:0045936 (negative regulation of phosphate metabolic process, IEA GO_REF:0000002): ACCEPT — PhoU is the essential negative regulator of the PhoR1-PhoB1 phosphate starvation regulon under phosphate-replete conditions (PMID:24563032).
GO:0030145 (manganese ion binding, IC from file:VARPD/phoU/phoU-uniprot.txt): NEW — PhoU coordinates $\text{Mn}^{2+}$ via conserved acidic/arginine pockets (including Glu96/Arg97 and Glu198/Arg199) in each of its two Pfam:PF01895 three-helix bundles (22..108 and 129..210); metal binding may be important for PhoU membrane interactions (PMID:24563032).
GO:0000287 (magnesium ion binding, IC from file:VARPD/phoU/phoU-uniprot.txt): NEW — PhoU also binds $\text{Mg}^{2+}$, which may be important for PhoU membrane interactions (PMID:24563032).