Rv0516c (-)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: anti-anti-sigma factor
- REFSEQ: hypothetical protein
- PATRIC: Anti-sigma F factor antagonist (spoIIAA-2); Anti-sigma B factor antagonist RsbV
- TUBERCULIST: Possible anti-anti-sigma factor
- NCBI: Possible anti-anti-sigma factor
- updated information (H37Rv4):
  - gene name: oprA
  - function: SigF anti-anti穆igma factor; phosphorylated by PknD; osmosensory signaling pathway
  - reference: Greenstein (2007) PMID: 17411339; Hatzios (2013) PMID: 24309377
Type: Not Target
Start: 608059
End: 608535
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0005515 - protein binding (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 Rv0516c:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.475 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MTTTIPTSKSACSVTTRPGNAAVDYGGAQIRAYLHHLATVVTIRGEIDAANVEQISEHVRRFSLGTNPMVLDLSELSHFSGAGISLLCILDEDCRAAGVQ
WALVASPAVVEQLGGRCDQGEHESMFPMARSVHKALHDLADAIDRRRQLVLPLISRSA

(Nucleotide sequence available on KEGG)

Additional Information

Rv0516c - SigF anti-anti–sigma factor (renamed OprA)

phosphorylated by PknD

Greenstein et al (2007). M. tuberculosis Ser/Thr Protein Kinase D Phosphorylates an Anti-Anti–Sigma Factor Homolog. PLOS Pathogens.
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.0030049

Hatzios et al renamed Rv0516c as OprA, due to its involvement in an
osmosensory signaling pathway including PknD and SigF, which regulates
peptidoglycan architecture:

Hatzios, S. K. et al. (2013). Osmosensory signaling in Mycobacterium tuberculosis
mediated by a eukaryotic-like Ser/Thr protein kinase. PNAS 110, E5069-5077.
https://www.pnas.org/content/110/52/E5069

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
Non-Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 9 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 9 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 9 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 0 non-insertions in a row out of 9 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 0 non-insertions in a row out of 9 sites
Non-Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Non-Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 2.79
Growth-Advantage	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:
- Rv0576 (-) (Direct binding)
- Rv0678 (-) (Direct binding)
- Rv2021c (-) (Direct binding)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
Downregulates:
- Does not downregulate other genes.
Downregulated by:

TBCAP

Tubculosis Community Annotation Project (

Slayden et al., 2013

Rv0516c (-)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Regulatory Rv3286c	hibeeluck	IDA		Co-expression (Functional linkage) authors,J. Beaucher,S. Rodrigue,PE. Jacques,I. Smith,R. Brzezinski,L. Gaudreau Novel Mycobacterium tuberculosis anti-sigma factor antagonists control sigmaF activity by distinct mechanisms. Mol. Microbiol. 2002
Interaction	Transcription Rv3286c	hibeeluck	IDA		Co-expression (Functional linkage) authors,J. Beaucher,S. Rodrigue,PE. Jacques,I. Smith,R. Brzezinski,L. Gaudreau Novel Mycobacterium tuberculosis anti-sigma factor antagonists control sigmaF activity by distinct mechanisms. Mol. Microbiol. 2002
Interaction	Regulatory Rv3286c	hibeeluck	IDA		Co-expression (Functional linkage) EP. Williams, JH. Lee et al. Mycobacterium tuberculosis SigF regulates genes encoding cell wall-associated proteins and directly regulates the transcriptional regulatory gene phoY1. J. Bacteriol. 2007
Interaction	Transcription Rv3286c	hibeeluck	IDA		Co-expression (Functional linkage) EP. Williams, JH. Lee et al. Mycobacterium tuberculosis SigF regulates genes encoding cell wall-associated proteins and directly regulates the transcriptional regulatory gene phoY1. J. Bacteriol. 2007
Interaction	Regulatory Rv3286c	hibeeluck	IDA		Co-expression (Functional linkage) S. Dhandayuthapani Stress response of genes encoding putative stress signaling molecules of Mycobacterium tuberculosis. Front. Biosci. 2007
Interaction	Transcription Rv3286c	hibeeluck	IDA		Co-expression (Functional linkage) S. Dhandayuthapani Stress response of genes encoding putative stress signaling molecules of Mycobacterium tuberculosis. Front. Biosci. 2007
Interaction	Signaling Rv0931c	priyadarshinipriyanka2001	IDA		spectrophotometric Analysis AE. Greenstein, JA. MacGurn et al. M. tuberculosis Ser/Thr protein kinase D phosphorylates an anti-anti-sigma factor homolog. PLoS Pathog. 2007
Interaction	Regulatory Rv3287c	yashabhasin	IPI		Yeast two-hybrid (Physical interaction) AE. Greenstein, JA. MacGurn et al. M. tuberculosis Ser/Thr protein kinase D phosphorylates an anti-anti-sigma factor homolog. PLoS Pathog. 2007
Citation	Interactions of anti-sigma factor antagonists of Mycobacterium tuberculosis in the yeast two-hybrid system. BK. Parida, T. Douglas et al. Tuberculosis (Edinburgh, Scotland) null	yashabhasin	IPI	16263329	Yeast two-hybrid (Physical interaction)
Interaction	Regulatory Rv2638	yashabhasin	IPI		Yeast two-hybrid (Physical interaction) BK. Parida, T. Douglas et al. Interactions of anti-sigma factor antagonists of Mycobacterium tuberculosis in the yeast two-hybrid system. Tuberculosis (Edinburgh, Scotland) null
Interaction	Regulatory Rv3687c	yashabhasin	IPI		Yeast two-hybrid (Physical interaction) BK. Parida, T. Douglas et al. Interactions of anti-sigma factor antagonists of Mycobacterium tuberculosis in the yeast two-hybrid system. Tuberculosis (Edinburgh, Scotland) null
Interaction	Regulatory Rv3286c	yashabhasin	IPI		Yeast two-hybrid (Physical interaction) BK. Parida, T. Douglas et al. Interactions of anti-sigma factor antagonists of Mycobacterium tuberculosis in the yeast two-hybrid system. Tuberculosis (Edinburgh, Scotland) null
Interaction	Regulatory Rv3287c	yashabhasin	IPI		Yeast two-hybrid (Physical interaction) BK. Parida, T. Douglas et al. Interactions of anti-sigma factor antagonists of Mycobacterium tuberculosis in the yeast two-hybrid system. Tuberculosis (Edinburgh, Scotland) null
Citation	M. tuberculosis Ser/Thr protein kinase D phosphorylates an anti-anti-sigma factor homolog. AE. Greenstein, JA. MacGurn et al. PLoS Pathog. 2007	shahanup86	IDA	17411339	Affinity purification (Physical interaction)
Interaction	Regulatory Rv0931c	shahanup86	IDA		Affinity purification (Physical interaction) AE. Greenstein, JA. MacGurn et al. M. tuberculosis Ser/Thr protein kinase D phosphorylates an anti-anti-sigma factor homolog. PLoS Pathog. 2007
Interaction	Regulatory Rv2638	yashabhasin	IPI		Yeast two-hybrid (Physical interaction) S. Dhandayuthapani Stress response of genes encoding putative stress signaling molecules of Mycobacterium tuberculosis. Front. Biosci. 2007
Interaction	Regulatory Rv3687c	yashabhasin	IPI		Yeast two-hybrid (Physical interaction) S. Dhandayuthapani Stress response of genes encoding putative stress signaling molecules of Mycobacterium tuberculosis. Front. Biosci. 2007
Interaction	Regulatory Rv3286c	yashabhasin	IPI		Yeast two-hybrid (Physical interaction) S. Dhandayuthapani Stress response of genes encoding putative stress signaling molecules of Mycobacterium tuberculosis. Front. Biosci. 2007
Interaction	Regulatory Rv3287c	yashabhasin	IPI		Yeast two-hybrid (Physical interaction) S. Dhandayuthapani Stress response of genes encoding putative stress signaling molecules of Mycobacterium tuberculosis. Front. Biosci. 2007
Citation	M. tuberculosis Ser/Thr protein kinase D phosphorylates an anti-anti-sigma factor homolog. AE. Greenstein, JA. MacGurn et al. PLoS Pathog. 2007	yashabhasin	IPI	17411339	Yeast two-hybrid (Physical interaction)
Interaction	Regulatory Rv2638	yashabhasin	IPI		Yeast two-hybrid (Physical interaction) AE. Greenstein, JA. MacGurn et al. M. tuberculosis Ser/Thr protein kinase D phosphorylates an anti-anti-sigma factor homolog. PLoS Pathog. 2007
Interaction	Regulatory Rv3687c	yashabhasin	IPI		Yeast two-hybrid (Physical interaction) AE. Greenstein, JA. MacGurn et al. M. tuberculosis Ser/Thr protein kinase D phosphorylates an anti-anti-sigma factor homolog. PLoS Pathog. 2007
Interaction	Regulatory Rv3286c	yashabhasin	IPI		Yeast two-hybrid (Physical interaction) AE. Greenstein, JA. MacGurn et al. M. tuberculosis Ser/Thr protein kinase D phosphorylates an anti-anti-sigma factor homolog. PLoS Pathog. 2007
Citation	Stress response of genes encoding putative stress signaling molecules of Mycobacterium tuberculosis. S. Dhandayuthapani Front. Biosci. 2007	yashabhasin	IPI	17485404	Yeast two-hybrid (Physical interaction)
Interaction	RegulatedBy Rv3286c	yamir.moreno	TAS		Literature previously reported link (from Balazsi et al. 2008). Traceable author statement to experimental support. 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	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.. T. Parish, DA. Smith et al. The senX3-regX3 two-component regulatory system of Mycobacterium tuberculosis is required for virulence. Microbiology (Reading, Engl.) 2003

Property

Value

Creator

Evidence

PMID

Comment

Interaction

Regulatory Rv3286c

hibeeluck

IDA

Co-expression (Functional linkage)
authors,J. Beaucher,S. Rodrigue,PE. Jacques,I. Smith,R. Brzezinski,L. Gaudreau Novel Mycobacterium tuberculosis anti-sigma factor antagonists control sigmaF activity by distinct mechanisms. Mol. Microbiol. 2002

Interaction

Transcription Rv3286c

hibeeluck

IDA

Interaction

Regulatory Rv3286c

hibeeluck

IDA

Co-expression (Functional linkage)
EP. Williams, JH. Lee et al. Mycobacterium tuberculosis SigF regulates genes encoding cell wall-associated proteins and directly regulates the transcriptional regulatory gene phoY1. J. Bacteriol. 2007

Interaction

Transcription Rv3286c

hibeeluck

IDA

Interaction

Regulatory Rv3286c

hibeeluck

IDA

Co-expression (Functional linkage)
S. Dhandayuthapani Stress response of genes encoding putative stress signaling molecules of Mycobacterium tuberculosis. Front. Biosci. 2007

Interaction

Transcription Rv3286c

hibeeluck

IDA

Co-expression (Functional linkage)
S. Dhandayuthapani Stress response of genes encoding putative stress signaling molecules of Mycobacterium tuberculosis. Front. Biosci. 2007

Interaction

Signaling Rv0931c

priyadarshinipriyanka2001

IDA

spectrophotometric Analysis
AE. Greenstein, JA. MacGurn et al. M. tuberculosis Ser/Thr protein kinase D phosphorylates an anti-anti-sigma factor homolog. PLoS Pathog. 2007

Interaction

Regulatory Rv3287c

yashabhasin

IPI

Yeast two-hybrid (Physical interaction)
AE. Greenstein, JA. MacGurn et al. M. tuberculosis Ser/Thr protein kinase D phosphorylates an anti-anti-sigma factor homolog. PLoS Pathog. 2007

Citation

Interactions of anti-sigma factor antagonists of Mycobacterium tuberculosis in the yeast two-hybrid system. BK. Parida, T. Douglas et al. Tuberculosis (Edinburgh, Scotland) null

yashabhasin

IPI

16263329

Yeast two-hybrid (Physical interaction)

Interaction

Regulatory Rv2638

yashabhasin

IPI

Yeast two-hybrid (Physical interaction)
BK. Parida, T. Douglas et al. Interactions of anti-sigma factor antagonists of Mycobacterium tuberculosis in the yeast two-hybrid system. Tuberculosis (Edinburgh, Scotland) null

Interaction

Regulatory Rv3687c

yashabhasin

IPI

Interaction

Regulatory Rv3286c

yashabhasin

IPI

Interaction

Regulatory Rv3287c

yashabhasin

IPI

Citation

M. tuberculosis Ser/Thr protein kinase D phosphorylates an anti-anti-sigma factor homolog. AE. Greenstein, JA. MacGurn et al. PLoS Pathog. 2007

shahanup86

IDA

17411339

Affinity purification (Physical interaction)

Interaction

Regulatory Rv0931c

shahanup86

IDA

Affinity purification (Physical interaction)
AE. Greenstein, JA. MacGurn et al. M. tuberculosis Ser/Thr protein kinase D phosphorylates an anti-anti-sigma factor homolog. PLoS Pathog. 2007

Interaction

Regulatory Rv2638

yashabhasin

IPI

Yeast two-hybrid (Physical interaction)
S. Dhandayuthapani Stress response of genes encoding putative stress signaling molecules of Mycobacterium tuberculosis. Front. Biosci. 2007

Interaction

Regulatory Rv3687c

yashabhasin

IPI

Yeast two-hybrid (Physical interaction)
S. Dhandayuthapani Stress response of genes encoding putative stress signaling molecules of Mycobacterium tuberculosis. Front. Biosci. 2007

Interaction

Regulatory Rv3286c

yashabhasin

IPI

Yeast two-hybrid (Physical interaction)
S. Dhandayuthapani Stress response of genes encoding putative stress signaling molecules of Mycobacterium tuberculosis. Front. Biosci. 2007

Interaction

Regulatory Rv3287c

yashabhasin

IPI

Yeast two-hybrid (Physical interaction)
S. Dhandayuthapani Stress response of genes encoding putative stress signaling molecules of Mycobacterium tuberculosis. Front. Biosci. 2007

Citation

M. tuberculosis Ser/Thr protein kinase D phosphorylates an anti-anti-sigma factor homolog. AE. Greenstein, JA. MacGurn et al. PLoS Pathog. 2007

yashabhasin

IPI

17411339

Yeast two-hybrid (Physical interaction)

Interaction

Regulatory Rv2638

yashabhasin

IPI

Yeast two-hybrid (Physical interaction)
AE. Greenstein, JA. MacGurn et al. M. tuberculosis Ser/Thr protein kinase D phosphorylates an anti-anti-sigma factor homolog. PLoS Pathog. 2007

Interaction

Regulatory Rv3687c

yashabhasin

IPI

Yeast two-hybrid (Physical interaction)
AE. Greenstein, JA. MacGurn et al. M. tuberculosis Ser/Thr protein kinase D phosphorylates an anti-anti-sigma factor homolog. PLoS Pathog. 2007

Interaction

Regulatory Rv3286c

yashabhasin

IPI

Yeast two-hybrid (Physical interaction)
AE. Greenstein, JA. MacGurn et al. M. tuberculosis Ser/Thr protein kinase D phosphorylates an anti-anti-sigma factor homolog. PLoS Pathog. 2007

Citation

Stress response of genes encoding putative stress signaling molecules of Mycobacterium tuberculosis. S. Dhandayuthapani Front. Biosci. 2007

yashabhasin

IPI

17485404

Yeast two-hybrid (Physical interaction)

Interaction

RegulatedBy Rv3286c

yamir.moreno

TAS

Literature previously reported link (from Balazsi et al. 2008). Traceable author statement to experimental support.
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

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..
T. Parish, DA. Smith et al. The senX3-regX3 two-component regulatory system of Mycobacterium tuberculosis is required for virulence. Microbiology (Reading, Engl.) 2003

Comments