Rv0903c (prrA)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: transcriptional regulatory protein prrA
- REFSEQ: two component response transcriptional regulatory protein PRRA
- PATRIC: DNA-binding response regulator
- TUBERCULIST: Two component response transcriptional regulatory protein PrrA
- NCBI: Two component response transcriptional regulatory protein PrrA
- updated information (H37Rv4):
  - gene name: prrA
  - function:
  - reference:
Type: Not Target
Start: 1005852
End: 1006562
Operon:

Trans-membrane region:
Role: I.J.2 - Two component systems
GO terms:
- GO:0044110 - growth involved in symbiotic interaction (Uniprot)
- GO:0006355 - regulation of transcription, DNA-templated (Uniprot)
- GO:0006351 - transcription, DNA-templated (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0005737 - cytoplasm (Uniprot)
- GO:0005509 - calcium ion binding (Uniprot)
- GO:0003677 - DNA binding (Uniprot)
- GO:0000287 - magnesium ion binding (Uniprot)
- GO:0000160 - phosphorelay signal transduction system (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: 1ys6, 1ys7
Search for Homologs in PDB

Top 10 Homologs in PDB (as of Nov 2020):

PDB	aa ident	species	PDB title
1YS7	100%	Mycobacterium tuberculosis	Crystal structure of the response regulator protein prrA complexed with Mg2+
1YS6	100%	Mycobacterium tuberculosis	Crystal structure of the response regulatory protein PrrA from Mycobacterium Tuberculosis
3F6P	49%	Bacillus subtilis	Crystal Structure of unphosphorelated receiver domain of YycF
2ZWM	49%	Bacillus subtilis	Crystal structure of YycF receiver domain from Bacillus subtilis
3NHZ	48%	Mycobacterium tuberculosis	Structure of N-terminal Domain of MtrA
3RJP	47%	Streptococcus pyogenes	Crystal structure of the DNA binding domain of CovR from Streptococcus pyogenes
1MVO	47%	Bacillus subtilis	Crystal structure of the PhoP receiver domain from Bacillus subtilis
6KYX	46%	Staphylococcus aureus	Crystal Structure of Staphylococcus aureus response regulator ArlR DNA binding domain with His tag cleaved
6IS4	46%	Staphylococcus aureus	Crystal Structure of Staphylococcus aureus response regulator ArlR DNA binding domain
6IJU	46%	Staphylococcus aureus	The DNA binding domain of a response regulator ArlR from Staphylococcus aureus

Links to additional information on prrA:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -10.959 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MGGMDTGVTSPRVLVVDDDSDVLASLERGLRLSGFEVATAVDGAEALRSATENRPDAIVLDINMPVLDGVSVVTALRAMDNDVPVCVLSARSSVDDRVAG
LEAGADDYLVKPFVLAELVARVKALLRRRGSTATSSSETITVGPLEVDIPGRRARVNGVDVDLTKREFDLLAVLAEHKTAVLSRAQLLELVWGYDFAADT
NVVDVFIGYLRRKLEAGGGPRLLHTVRGVGFVLRMQ

(Nucleotide sequence available on KEGG)

Additional Information

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: 0.977500; 9 non-insertions in a row out of 10 sites
Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.997850; 9 non-insertions in a row out of 10 sites
Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.998600; 9 non-insertions in a row out of 10 sites
Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.996300; 9 non-insertions in a row out of 10 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.996400; 9 non-insertions in a row out of 10 sites
No-Data	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Too-Short	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: -1
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

RNA processing and modification

Energy production and conversion

Chromatin structure and dynamics

Amino acid transport and metabolism

Cell cycle control, cell division, chromosome partitioning

Carbohydrate transport and metabolism

Nucleotide transport and metabolism

Lipid transport and metabolism

Coenzyme transport and metabolism

Transcription

Translation, ribosomal structure and biogenesis

Cell wall/membrane/envelope biogenesis

Replication, recombination and repair

Posttranslational modification, protein turnover, chaperones

Cell motility

Secondary metabolites biosynthesis, transport and catabolism

Inorganic ion transport and metabolism

Function unknown

General function prediction only

Intracellular trafficking, secretion, and vesicular transport

Signal transduction mechanisms

Extracellular structures

Defense mechanisms

Nuclear structure

Cytoskeleton

BioCyc Co-regulated genes based on gene expression profiling (Systems Biology, Inferelator Network)

Differentially expressed as result of RNASeq in glycerol environment (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

Conditionally essential as result of TNSeq (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

BioCyc Transcription factor binding based on ChIP-Seq (Systems Biology)

Binds To:
Bound By:
- No bindings from other targets were found.

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0767c (-) (Direct binding)

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

Upregulates:
- Rv0903c (prrA)
Upregulated by:
- Rv0903c (prrA)
Downregulates:
- Rv1331 (-)
- Rv3656c (-)
Downregulated by:
- Rv0767c (-)

Property	Value	Creator	Evidence	PMID	Comment
Citation	The structural basis of signal transduction for the response regulator PrrA from Mycobacterium tuberculosis. E. Nowak, S. Panjikar et al. J. Biol. Chem. 2006	ahal4789	IDA	16434396	Structural Analysis
Interaction	Regulatory Rv0902c	ahal4789	IDA		Structural Analysis E. Nowak, S. Panjikar et al. The structural basis of signal transduction for the response regulator PrrA from Mycobacterium tuberculosis. J. Biol. Chem. 2006
Citation	Transient requirement of the PrrA-PrrB two-component system for early intracellular multiplication of Mycobacterium tuberculosis. F. Ewann, M. Jackson et al. Infect. Immun. 2002	ahal4789	IDA	11953357	Structural Analysis
Interaction	Regulatory Rv0902c	ahal4789	IDA		Structural Analysis F. Ewann, M. Jackson et al. Transient requirement of the PrrA-PrrB two-component system for early intracellular multiplication of Mycobacterium tuberculosis. Infect. Immun. 2002

TB Genome Annotation Portal