Rv0821c (phoY2)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: phosphate transporter regulatory protein PhoU
- REFSEQ: phosphate transport regulator
- PATRIC: Phosphate transport system regulatory protein PhoU
- TUBERCULIST: Probable phosphate-transport system transcriptional regulatory protein PhoY2
- NCBI: Probable phosphate-transport system transcriptional regulatory protein PhoY2
- updated information (H37Rv4):
  - gene name: phoY2
  - function:
  - reference: (Namugenyi, 2017)
Type: Not Target
Start: 913558
End: 914199
Operon:

Trans-membrane region:
Role: III.A.4 - Anions
GO terms:
- GO:0045936 - negative regulation of phosphate metabolic process (Uniprot)
- GO:0030643 - cellular phosphate ion homeostasis (Uniprot)
- GO:0022611 - dormancy process (Uniprot)
- GO:0006817 - phosphate ion transport (Uniprot)
- GO:0005737 - cytoplasm (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
Gene Expression Profile (Transcriptional Responses to Drugs; Boshoff et al, 2004)
Gene Modules extracted from cluster analysis of 249 transcriptomic datasets using ICA
Orthologs among selected mycobacteria
Protein structure:
Search for Homologs in PDB
Top 10 Homologs in PDB (as of Nov 2020): (none with >35% aa id)
Links to additional information on phoY2:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.289 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MRTAYHEQLSELSERLGEMCGLAGIAMERATQALLQADLVLAEQVISDHEKIATLSARAEESAFVLLALQAPVAGDLRAIVSAIQMVADIDRMGALALHV
AKIARRRHPQHALPEEVNGYFAEMGRVAVELGNSAQEVVLSHDPEKAAQIREEDDAMDDLHRHLFTVLMDREWKHGVAAAVDVTLLSRFYERFADHAVEV
ARRVIFQATGAFP

(Nucleotide sequence available on KEGG)

Additional Information

Analysis of Positive Selection in Clinical Isolates new

Analysis of dN/dS (omega) in two collections of Mtb clinical isolates using GenomegaMap (Window model) (see description of methods)
- Moldova: 2,057 clinical isolates
- global set: 5,195 clinical isolates from 15 other countries
In the omega plots, the black line shows the mean estimate of omega (dN/dS) at each codon, and the blue lines are the bounds for the 95% credible interval (95%CI, from MCMC sampling).
A gene is under significant positive selection if the lower-bound of the 95%CI of omega (lower blue line) exceeds 1.0 at any codon.

	Moldova (2,057)	global set (5,195)
under significant positive selection?	NO	NO
omega peak height (95%CI lower bound)	0.84 (0.08)	0.85 (0.23)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link

* example format for variants: "D27 (GAC): D27H (CAC,11)" means "Asp27 (native codon GAC) mutated to His (codon CAC) in 11 isolates"

ESSENTIALITY

MtbTnDB - interactive tool for exploring a database of published TnSeq datasets for Mtb

TnSeqCorr - genes with correlated TnSeq profiles across ~100 conditions

Rv0821c/phoY2, gene len: 641 bp, num TA sites: 7

condition	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	growth advantage	7H9	HMM	fully saturated, 14 TnSeq libraries combined
in-vitro	Sassetti 2003 Mol Micro	non-essential	7H9	TRASH	essential if hybridization ratio<0.2
in-vivo (mice)	Sassetti 2003 PNAS	non-essential	BL6 mice	TRASH	essential if hybridization ratio<0.4, min over 4 timepoints (1-8 weeks)
in-vitro (glycerol)	Griffin 2011 PPath	uncertain	M9 minimal+glycerol	Gumbel	2 replicates; Padj<0.05
in-vitro (cholesterol)	Griffin 2011 PPath	non-essential	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	NO (LFC=0.52)	cholesterol vs glycerol	resampling-SR	YES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in cholesterol
in-vitro	Smith 2022 eLife	non-essential	7H9	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice)	Smith 2022 eLife	non-essential	BL6 mice	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice	Smith 2022 eLife	NO (LFC=0.13)	in-vivo vs in-vitro	ZINB	YES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in mice
in-vitro (minimal)	Minato 2019 mSys	non-essential	minimal medium	HMM
in-vitro (YM rich medium)	Minato 2019 mSys	non-essential	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, vitamins)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=-0.06)	YM rich vs minimal medium	resampling

TnSeq Data No data currently available.

No TnSeq data currently available for this Target.

RNASeq Data No data currently available.

No RNA-Seq data currently available for this Target.

Metabolomic Profiles No data currently available.

No Metabolomic data currently available for this Target.

Proteomic Data No data currently available.

No Proteomic data currently available for this Target.

Regulatory Relationships from Systems Biology

BioCyc

Gene interactions based on ChIPSeq and Transcription Factor Over-Expression (TFOE) (Systems Biology)

NOTE: Green edges represent the connected genes being classified as differentially essential as a result of the middle gene being knocked out. These interactions are inferred based on RNASeq.

Interactions based on ChIPSeq data

Binds To:
Bound By:
- Rv0757 (phoP)

Interactions based on ChIPSeq data (Minch et al. 2014)

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0081 (-) (Direct binding)
- Rv0678 (-) (Direct binding)
- Rv0757 (phoP) (Direct binding)

Interactions based on TFOE data (Rustad et al. 2014)

Upregulates:
- Rv0821c (phoY2)
Upregulated by:
- Rv0757 (phoP)
- Rv0821c (phoY2)
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Regulatory Rv0928	diponlove	NAS		W. Shi,Y. Zhang PhoY2 but not PhoY1 is the PhoU homologue involved in persisters in Mycobacterium tuberculosis. The Journal of antimicrobial chemotherapy 2010
Interaction	Regulatory Rv0929	diponlove	NAS		W. Shi,Y. Zhang PhoY2 but not PhoY1 is the PhoU homologue involved in persisters in Mycobacterium tuberculosis. The Journal of antimicrobial chemotherapy 2010
Interaction	Regulatory Rv0930	diponlove	NAS		W. Shi,Y. Zhang PhoY2 but not PhoY1 is the PhoU homologue involved in persisters in Mycobacterium tuberculosis. The Journal of antimicrobial chemotherapy 2010
Interaction	Regulatory Rv0932c	diponlove	NAS		W. Shi,Y. Zhang PhoY2 but not PhoY1 is the PhoU homologue involved in persisters in Mycobacterium tuberculosis. The Journal of antimicrobial chemotherapy 2010
Interaction	Regulatory Rv0933	diponlove	NAS		W. Shi,Y. Zhang PhoY2 but not PhoY1 is the PhoU homologue involved in persisters in Mycobacterium tuberculosis. The Journal of antimicrobial chemotherapy 2010
Interaction	Regulatory Rv0934	diponlove	NAS		W. Shi,Y. Zhang PhoY2 but not PhoY1 is the PhoU homologue involved in persisters in Mycobacterium tuberculosis. The Journal of antimicrobial chemotherapy 2010
Interaction	Regulatory Rv0935	diponlove	NAS		W. Shi,Y. Zhang PhoY2 but not PhoY1 is the PhoU homologue involved in persisters in Mycobacterium tuberculosis. The Journal of antimicrobial chemotherapy 2010
Interaction	Regulatory Rv0936	diponlove	NAS		W. Shi,Y. Zhang PhoY2 but not PhoY1 is the PhoU homologue involved in persisters in Mycobacterium tuberculosis. The Journal of antimicrobial chemotherapy 2010
Citation	PhoY2 but not PhoY1 is the PhoU homologue involved in persisters in Mycobacterium tuberculosis. W. Shi,Y. Zhang The Journal of antimicrobial chemotherapy 2010	diponlove	NAS	20360062	None
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) ML. Chesne-Seck, N. Barilone et al. A point mutation in the two-component regulator PhoP-PhoR accounts for the absence of polyketide-derived acyltrehaloses but not that of phthiocerol dimycocerosates in Mycobacterium tuberculosis H37Ra. J. Bacteriol. 2008
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) authors,A. Sola-Landa,RS. Moura,JF. Martn The two-component PhoR-PhoP system controls both primary metabolism and secondary metabolite biosynthesis in Streptomyces lividans. Proc. Natl. Acad. Sci. U.S.A. 2003
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) J. Gonzalo Asensio, C. Maia et al. The virulence-associated two-component PhoP-PhoR system controls the biosynthesis of polyketide-derived lipids in Mycobacterium tuberculosis. J. Biol. Chem. 2006
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) J. Gonzalo-Asensio, CY. Soto et al. The Mycobacterium tuberculosis phoPR operon is positively autoregulated in the virulent strain H37Rv. J. Bacteriol. 2008
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) A. Sinha, S. Gupta et al. PhoP-PhoP interaction at adjacent PhoP binding sites is influenced by protein phosphorylation. J. Bacteriol. 2008
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) J. Gonzalo Asensio, C. Maia et al. The virulence-associated two-component PhoP-PhoR system controls the biosynthesis of polyketide-derived lipids in Mycobacterium tuberculosis. J. Biol. Chem. 2006
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) M. Ryndak, S. Wang et al. PhoP, a key player in Mycobacterium tuberculosis virulence. Trends Microbiol. 2008
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) JA. Asensio, A. Arbus et al. Live tuberculosis vaccines based on phoP mutants: a step towards clinical trials. Expert opinion on biological therapy 2008
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) SB. Walters, E. Dubnau et al. The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol. Microbiol. 2006
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) J. Gonzalo-Asensio, S. Mostowy et al. PhoP: a missing piece in the intricate puzzle of Mycobacterium tuberculosis virulence. PLoS ONE 2008
Interaction	RegulatedBy Rv0757	yamir.moreno	IEP		Microarrays. mRNA levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using microarray (or macroarray) experiments.. J. Gonzalo Asensio, C. Maia et al. The virulence-associated two-component PhoP-PhoR system controls the biosynthesis of polyketide-derived lipids in Mycobacterium tuberculosis. J. Biol. Chem. 2006
Interaction	RegulatedBy Rv0491	yamir.moreno	ISO		E.coli orthology based inference. Orthologous pair regulator-target found in E.coli. G. Balzsi, AP. Heath et al. The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest. Mol. Syst. Biol. 2008
Interaction	RegulatedBy Rv0491	yamir.moreno	ISO		E.coli orthology based inference. Orthologous pair regulator-target found in E.coli. authors,M. Madan Babu,SA. Teichmann,L. Aravind Evolutionary dynamics of prokaryotic transcriptional regulatory networks. J. Mol. Biol. 2006

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