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.

ESSENTIALITY

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

TnSeqCorr - genes with correlated TnSeq profiles across >100 conditions *new*

Classification	Condition	Strain	Method	Reference	Notes
Uncertain	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.965500; 8 non-insertions in a row out of 8 sites
Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.995750; 8 non-insertions in a row out of 8 sites
Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.997100; 8 non-insertions in a row out of 8 sites
Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.997350; 9 non-insertions in a row out of 9 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.997100; 9 non-insertions in a row out of 9 sites
Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 0.09
Essential	7H09/7H10 + rich media	H37RvMA	MotifHMM	DeJesus et al. (2017)	Fully saturated (14 reps).

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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