Rv3137 (-)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: histidinol-phosphatase
- REFSEQ: monophosphatase
- PATRIC: Histidinol-phosphatase [alternative form] (EC 3.1.3.15)
- TUBERCULIST: Probable monophosphatase
- NCBI: Probable monophosphatase
- updated information (H37Rv4):
  - gene name: HolPase
  - function: histidinol phosphate phosphatase
  - reference: Jha (2018) PMID: 29752410
Type: Essential
Start: 3503393
End: 3504175
Operon:

Trans-membrane region:
Role: IV.I - Miscellaneous phosphatases, lyases, and hydrolases
GO terms:
- GO:0046872 - metal ion binding (Uniprot)
- GO:0046854 - phosphatidylinositol phosphorylation (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0016787 - hydrolase activity (Uniprot)
- GO:0016311 - dephosphorylation (Uniprot)
- GO:0010125 - mycothiol biosynthetic process (Uniprot)
- GO:0008934 - inositol monophosphate 1-phosphatase activity (Uniprot)
- GO:0008652 - cellular amino acid biosynthetic process (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0004401 - histidinol-phosphatase activity (Uniprot)
- GO:0000105 - histidine biosynthetic process (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):

PDB	aa ident	species	PDB title
5ZON	100%	Mycobacterium tuberculosis	Histidinol phosphate phosphatase from Mycobacterium tuberculosis
5YHT	100%	Mycobacterium tuberculosis H37Rv	Crystal structure of a phosphatase from Mycobacterium tuberculosis in complex with its substrate
5ESY	50%	Arabidopsis thaliana	Arabidopsis thaliana SAL1
5DJK	38%	Mycobacterium tuberculosis	Structure of M. tuberculosis CysQ, a PAP phosphatase with PO4 and 2Ca bound
5DJJ	38%	Mycobacterium tuberculosis	Structure of M. tuberculosis CysQ, a PAP phosphatase with PO4 and 2Mg bound
5DJI	38%	Mycobacterium tuberculosis	Structure of M. tuberculosis CysQ, a PAP phosphatase with AMP, PO4, and 2Mg bound
5DJH	38%	Mycobacterium tuberculosis	Structure of M. tuberculosis CysQ, a PAP phosphatase with AMP, PO4, and 3Mg bound
5DJG	38%	Mycobacterium tuberculosis	Structure of M. tuberculosis CysQ, a PAP phosphatase with PAP, Mg, and Li bound
5DJF	38%	Mycobacterium tuberculosis	Structure of M. tuberculosis CysQ, a PAP phosphatase - ligand-free structure
4N81	36%	Zymomonas mobilis	Another flexible region at the active site of an inositol monophosphatase from Zymomonas mobilis

Links to additional information on Rv3137:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -6.643 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VSHDDLMLALALADRADELTRVRFGALDLRIDTKPDLTPVTDADRAVESDVRQTLGRDRPGDGVLGEEFGGSTTFTGRQWIVDPIDGTKNFVRGVPVWAS
LIALLEDGVPSVGVVSAPALQRRWWAARGRGAFASVDGARPHRLSVSSVAELHSASLSFSSLSGWARPGLRERFIGLTDTVWRVRAYGDFLSYCLVAEGA
VDIAAEPQVSVWDLAALDIVVREAGGRLTSLDGVAGPHGGSAVATNGLLHDEVLTRLNAG

(Nucleotide sequence available on KEGG)

Additional Information

Jha B, Kumar D, Sharma A, Dwivedy A, Singh R, Biswal
BK. Identification and structural characterization of a histidinol
phosphate phosphatase from Mycobacterium tuberculosis. J Biol
Chem. 2018 Jun 29;293(26):10102-10118. doi: 10.1074/jbc.RA118.002299.
Epub 2018 May 11. PMID: 29752410; PMCID: PMC6028948.

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)	1.03 (0.12)	2.86 (0.99)
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

Rv3137/-, gene len: 782 bp, num TA sites: 9

condition	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	essential	7H9	HMM	fully saturated, 14 TnSeq libraries combined
in-vitro	Sassetti 2003 Mol Micro	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	essential	M9 minimal+glycerol	Gumbel	2 replicates; Padj<0.05
in-vitro (cholesterol)	Griffin 2011 PPath	essential	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	NO (LFC=0.0)	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	essential	7H9	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice)	Smith 2022 eLife	essential	BL6 mice	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice	Smith 2022 eLife	NO (LFC=0.0)	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	essential	minimal medium	HMM
in-vitro (YM rich medium)	Minato 2019 mSys	essential	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, vitamins)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=0.0)	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:
- No bindings to other targets were found.
Bound By:

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0967 (csoR) (Direct binding)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv0576 (-)
- Rv2034 (-)
Downregulates:
- Does not downregulate other genes.
Downregulated by:

Property	Value	Creator	Evidence	Comment
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 Rv3911	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.. S. Raman, X. Puyang et al. Mycobacterium tuberculosis SigM positively regulates Esx secreted protein and nonribosomal peptide synthetase genes and down regulates virulence-associated surface lipid synthesis. J. Bacteriol. 2006
Interaction	RegulatedBy Rv0981	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.. H. He, R. Hovey et al. MprAB is a stress-responsive two-component system that directly regulates expression of sigma factors SigB and SigE in Mycobacterium tuberculosis. J. Bacteriol. 2006
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

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