Rv2865 (relF)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: antitoxin
- REFSEQ: hypothetical protein
- PATRIC: Antitoxin of toxin-antitoxin stability system
- TUBERCULIST: Antitoxin RelF
- NCBI: Antitoxin RelF
- updated information (H37Rv4):
  - gene name: relF
  - function:
  - reference:
Type: Not Target
Start: 3177537
End: 3177818
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0097351 - toxin-antitoxin pair type II binding (Uniprot)
- GO:0045927 - positive regulation of growth (Uniprot)
- GO:0006355 - regulation of transcription, DNA-templated (Uniprot)
- GO:0006351 - transcription, DNA-templated (Uniprot)
- GO:0005515 - protein binding (Uniprot)
- GO:0003677 - DNA 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: 3g5o
Search for Homologs in PDB
Top 10 Homologs in PDB (as of Nov 2020):

PDB aa ident species PDB title

3G5O 100% Mycobacterium tuberculosis The crystal structure of the toxin-antitoxin complex RelBE2 (Rv2865-2866) from Mycobacterium tuberculosis
Links to additional information on relF:
- Mycobrowser
- PATRIC
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.504 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- BioCyc
- Systems Biology

PDB	aa ident	species	PDB title
3G5O	100%	Mycobacterium tuberculosis	The crystal structure of the toxin-antitoxin complex RelBE2 (Rv2865-2866) from Mycobacterium tuberculosis

Amino Acid Sequence

MRILPISTIKGKLNEFVDAVSSTQDQITITKNGAPAAVLVGADEWESLQETLYWLAQPGIRESIAEADADIASGRTYGEDEIRAEFGVPRRPH

(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
Non-Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 3 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 0 non-insertions in a row out of 3 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 3 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 3 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 3 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: 2.16
Non-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:
- Rv0653c (-) (Direct binding)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv0023 (-)
Downregulates:
- Does not downregulate other genes.
Downregulated by:

TBCAP

Tubculosis Community Annotation Project (

Slayden et al., 2013

Rv2865 (relF)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	InhibitedBy Rv2866	akvsangli	IDA		Spectrophotometric assay SB. Korch, H. Contreras et al. Three Mycobacterium tuberculosis Rel toxin:antitoxin modules inhibit mycobacterial growth and are expressed in human-infected macrophages. J. Bacteriol. 2008
Citation	Three Mycobacterium tuberculosis Rel toxin:antitoxin modules inhibit mycobacterial growth and are expressed in human-infected macrophages. SB. Korch, H. Contreras et al. J. Bacteriol. 2008	akvsangli	IDA	19114484	Spectrophotometric assay
Interaction	InhibitedBy Rv2866	akvsangli	IDA		Spectrophotometric assay SB. Korch, H. Contreras et al. Three Mycobacterium tuberculosis Rel toxin:antitoxin modules inhibit mycobacterial growth and are expressed in human-infected macrophages. J. Bacteriol. 2008
Interaction	RegulatedBy Rv2711	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
Citation	The three RelE homologs of Mycobacterium tuberculosis have individual, drug-specific effects on bacterial antibiotic tolerance. authors,R. Singh,CE. Barry,HI. Boshoff J. Bacteriol. 2010	jlew		20061486	Each toxin individually arrests growth of both M. tuberculosis and E. coli, an effect that is neutralized by coexpression of the cognate antitoxin.
Symbol	relF	jlew			Each pair shows interaction by two-hybrid and GST pulldown. F and B each interact with E, G, K, and itself. authors,M. Yang,C. Gao,Y. Wang,H. Zhang,ZG. He Characterization of the interaction and cross-regulation of three Mycobacterium tuberculosis RelBE modules. PLoS ONE 2010
Citation	Characterization of the interaction and cross-regulation of three Mycobacterium tuberculosis RelBE modules. authors,M. Yang,C. Gao,Y. Wang,H. Zhang,ZG. He PLoS ONE 2010	jlew		20498855	Each pair shows interaction by two-hybrid and GST pulldown. F and B each interact with E, G, K, and itself.
Symbol	relB2	jlew			Each toxin individually arrests growth of both M. tuberculosis and E. coli, an effect that is neutralized by coexpression of the cognate antitoxin. authors,R. Singh,CE. Barry,HI. Boshoff The three RelE homologs of Mycobacterium tuberculosis have individual, drug-specific effects on bacterial antibiotic tolerance. J. Bacteriol. 2010
Symbol	relF	jlew			Overexpression of Mtb relE, relG and relK induces growth arrest in Msmeg; reversed by expression of relB, relF and relJ SB. Korch, H. Contreras et al. Three Mycobacterium tuberculosis Rel toxin:antitoxin modules inhibit mycobacterial growth and are expressed in human-infected macrophages. J. Bacteriol. 2008
Citation	Three Mycobacterium tuberculosis Rel toxin:antitoxin modules inhibit mycobacterial growth and are expressed in human-infected macrophages. SB. Korch, H. Contreras et al. J. Bacteriol. 2008	jlew		19114484	Overexpression of Mtb relE, relG and relK induces growth arrest in Msmeg; reversed by expression of relB, relF and relJ
Symbol	RelB2	jlew			We report the heterologous toxicity of these TA loci in Escherichia coli and show that only a few of the M. tuberculosis-encoded toxins can inhibit E. coli growth and have a killing effect. This killing effect can be suppressed by coexpression of the cognate antitoxin. authors,A. Gupta Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. FEMS Microbiol. Lett. 2009
Citation	Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. authors,A. Gupta FEMS Microbiol. Lett. 2009	jlew		19016878	We report the heterologous toxicity of these TA loci in Escherichia coli and show that only a few of the M. tuberculosis-encoded toxins can inhibit E. coli growth and have a killing effect. This killing effect can be suppressed by coexpression of the cognate antitoxin.
Other	start:3177537	rslayden			YR54_SYNY3
Other	stop:3177818	rslayden			YR54_SYNY3
Other	strand:+	rslayden			YR54_SYNY3
Symbol	rel BE-2	rslayden			SSR2754 HYPOTHETICAL 9.7 KDA PROTEIN from Synechocystis sp. strain PCC 6803 (87 aa), FASTA scores: opt: 134, E(): 0.007, (30.65% identity in 75 aa overlap); BAB58570
Other	start:3177537	rslayden			SSR2754 HYPOTHETICAL 9.7 KDA PROTEIN from Synechocystis sp. strain PCC 6803 (87 aa), FASTA scores: opt: 134, E(): 0.007, (30.65% identity in 75 aa overlap); BAB58570
Other	stop:3177818	rslayden			SSR2754 HYPOTHETICAL 9.7 KDA PROTEIN from Synechocystis sp. strain PCC 6803 (87 aa), FASTA scores: opt: 134, E(): 0.007, (30.65% identity in 75 aa overlap); BAB58570
Other	strand:+	rslayden			SSR2754 HYPOTHETICAL 9.7 KDA PROTEIN from Synechocystis sp. strain PCC 6803 (87 aa), FASTA scores: opt: 134, E(): 0.007, (30.65% identity in 75 aa overlap); BAB58570
Symbol	rel BE-2	rslayden			SAV2408 CONSERvED HYPOTHETICAL PROTEIN from Staphylococcus aureus subsp. aureus Mu50 (83 aa), FASTA scores: opt: 124, E(): 0.037, (27.5% identity in 80 aa overlap). Also similar to Rv1247
Other	start:3177537	rslayden			SAV2408 CONSERvED HYPOTHETICAL PROTEIN from Staphylococcus aureus subsp. aureus Mu50 (83 aa), FASTA scores: opt: 124, E(): 0.037, (27.5% identity in 80 aa overlap). Also similar to Rv1247
Other	stop:3177818	rslayden			SAV2408 CONSERvED HYPOTHETICAL PROTEIN from Staphylococcus aureus subsp. aureus Mu50 (83 aa), FASTA scores: opt: 124, E(): 0.037, (27.5% identity in 80 aa overlap). Also similar to Rv1247
Other	strand:+	rslayden			SAV2408 CONSERvED HYPOTHETICAL PROTEIN from Staphylococcus aureus subsp. aureus Mu50 (83 aa), FASTA scores: opt: 124, E(): 0.037, (27.5% identity in 80 aa overlap). Also similar to Rv1247
Symbol	rel BE-2	rslayden			MTV006.19c HYPOTHETICAL 9.8 KDA PROTEIN from Mycobacterium tuberculosis (89 aa), FASTA scores: opt: 249, E(): 2.6e-11, (44.2% identity in 86 aa overlap)
Other	start:3177537	rslayden			MTV006.19c HYPOTHETICAL 9.8 KDA PROTEIN from Mycobacterium tuberculosis (89 aa), FASTA scores: opt: 249, E(): 2.6e-11, (44.2% identity in 86 aa overlap)
Other	stop:3177818	rslayden			MTV006.19c HYPOTHETICAL 9.8 KDA PROTEIN from Mycobacterium tuberculosis (89 aa), FASTA scores: opt: 249, E(): 2.6e-11, (44.2% identity in 86 aa overlap)
Other	strand:+	rslayden			MTV006.19c HYPOTHETICAL 9.8 KDA PROTEIN from Mycobacterium tuberculosis (89 aa), FASTA scores: opt: 249, E(): 2.6e-11, (44.2% identity in 86 aa overlap)
Symbol	rel BE-2	rslayden			Conserved hypothetical protein, showing weak similarity with P58235
Other	start:3177537	rslayden			Conserved hypothetical protein, showing weak similarity with P58235
Other	stop:3177818	rslayden			Conserved hypothetical protein, showing weak similarity with P58235
Other	strand:+	rslayden			Conserved hypothetical protein, showing weak similarity with P58235
Symbol	rel BE-2	rslayden			YR54_SYNY3

Property

Value

Creator

Evidence

PMID

Comment

Interaction

InhibitedBy Rv2866

akvsangli

IDA

Spectrophotometric assay
SB. Korch, H. Contreras et al. Three Mycobacterium tuberculosis Rel toxin:antitoxin modules inhibit mycobacterial growth and are expressed in human-infected macrophages. J. Bacteriol. 2008

Citation

Three Mycobacterium tuberculosis Rel toxin:antitoxin modules inhibit mycobacterial growth and are expressed in human-infected macrophages. SB. Korch, H. Contreras et al. J. Bacteriol. 2008

akvsangli

IDA

19114484

Spectrophotometric assay

Interaction

InhibitedBy Rv2866

akvsangli

IDA

Interaction

RegulatedBy Rv2711

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

Citation

The three RelE homologs of Mycobacterium tuberculosis have individual, drug-specific effects on bacterial antibiotic tolerance. authors,R. Singh,CE. Barry,HI. Boshoff J. Bacteriol. 2010

jlew

20061486

Each toxin individually arrests growth of both M. tuberculosis and E. coli, an effect that is neutralized by coexpression of the cognate antitoxin.

Symbol

relF

jlew

Each pair shows interaction by two-hybrid and GST pulldown. F and B each interact with E, G, K, and itself.
authors,M. Yang,C. Gao,Y. Wang,H. Zhang,ZG. He Characterization of the interaction and cross-regulation of three Mycobacterium tuberculosis RelBE modules. PLoS ONE 2010

Citation

Characterization of the interaction and cross-regulation of three Mycobacterium tuberculosis RelBE modules. authors,M. Yang,C. Gao,Y. Wang,H. Zhang,ZG. He PLoS ONE 2010

jlew

20498855

Each pair shows interaction by two-hybrid and GST pulldown. F and B each interact with E, G, K, and itself.

Symbol

relB2

jlew

Each toxin individually arrests growth of both M. tuberculosis and E. coli, an effect that is neutralized by coexpression of the cognate antitoxin.
authors,R. Singh,CE. Barry,HI. Boshoff The three RelE homologs of Mycobacterium tuberculosis have individual, drug-specific effects on bacterial antibiotic tolerance. J. Bacteriol. 2010

Symbol

relF

jlew

Overexpression of Mtb relE, relG and relK induces growth arrest in Msmeg; reversed by expression of relB, relF and relJ
SB. Korch, H. Contreras et al. Three Mycobacterium tuberculosis Rel toxin:antitoxin modules inhibit mycobacterial growth and are expressed in human-infected macrophages. J. Bacteriol. 2008

Citation

Three Mycobacterium tuberculosis Rel toxin:antitoxin modules inhibit mycobacterial growth and are expressed in human-infected macrophages. SB. Korch, H. Contreras et al. J. Bacteriol. 2008

jlew

19114484

Overexpression of Mtb relE, relG and relK induces growth arrest in Msmeg; reversed by expression of relB, relF and relJ

Symbol

RelB2

jlew

We report the heterologous toxicity of these TA loci in Escherichia coli and show that only a few of the M. tuberculosis-encoded toxins can inhibit E. coli growth and have a killing effect. This killing effect can be suppressed by coexpression of the cognate antitoxin.
authors,A. Gupta Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. FEMS Microbiol. Lett. 2009

Citation

Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. authors,A. Gupta FEMS Microbiol. Lett. 2009

jlew

19016878

Other

start:3177537

rslayden

YR54_SYNY3

Other

stop:3177818

rslayden

YR54_SYNY3

Other

strand:+

rslayden

YR54_SYNY3

Symbol

rel BE-2

rslayden

SSR2754 HYPOTHETICAL 9.7 KDA PROTEIN from Synechocystis sp. strain PCC 6803 (87 aa), FASTA scores: opt: 134, E(): 0.007, (30.65% identity in 75 aa overlap); BAB58570

Other

start:3177537

rslayden

SSR2754 HYPOTHETICAL 9.7 KDA PROTEIN from Synechocystis sp. strain PCC 6803 (87 aa), FASTA scores: opt: 134, E(): 0.007, (30.65% identity in 75 aa overlap); BAB58570

Other

stop:3177818

rslayden

SSR2754 HYPOTHETICAL 9.7 KDA PROTEIN from Synechocystis sp. strain PCC 6803 (87 aa), FASTA scores: opt: 134, E(): 0.007, (30.65% identity in 75 aa overlap); BAB58570

Other

strand:+

rslayden

SSR2754 HYPOTHETICAL 9.7 KDA PROTEIN from Synechocystis sp. strain PCC 6803 (87 aa), FASTA scores: opt: 134, E(): 0.007, (30.65% identity in 75 aa overlap); BAB58570

Symbol

rel BE-2

rslayden

SAV2408 CONSERvED HYPOTHETICAL PROTEIN from Staphylococcus aureus subsp. aureus Mu50 (83 aa), FASTA scores: opt: 124, E(): 0.037, (27.5% identity in 80 aa overlap). Also similar to Rv1247

Other

start:3177537

rslayden

SAV2408 CONSERvED HYPOTHETICAL PROTEIN from Staphylococcus aureus subsp. aureus Mu50 (83 aa), FASTA scores: opt: 124, E(): 0.037, (27.5% identity in 80 aa overlap). Also similar to Rv1247

Other

stop:3177818

rslayden

SAV2408 CONSERvED HYPOTHETICAL PROTEIN from Staphylococcus aureus subsp. aureus Mu50 (83 aa), FASTA scores: opt: 124, E(): 0.037, (27.5% identity in 80 aa overlap). Also similar to Rv1247

Other

strand:+

rslayden

SAV2408 CONSERvED HYPOTHETICAL PROTEIN from Staphylococcus aureus subsp. aureus Mu50 (83 aa), FASTA scores: opt: 124, E(): 0.037, (27.5% identity in 80 aa overlap). Also similar to Rv1247

Symbol

rel BE-2

rslayden

MTV006.19c HYPOTHETICAL 9.8 KDA PROTEIN from Mycobacterium tuberculosis (89 aa), FASTA scores: opt: 249, E(): 2.6e-11, (44.2% identity in 86 aa overlap)

Other

start:3177537

rslayden

MTV006.19c HYPOTHETICAL 9.8 KDA PROTEIN from Mycobacterium tuberculosis (89 aa), FASTA scores: opt: 249, E(): 2.6e-11, (44.2% identity in 86 aa overlap)

Other

stop:3177818

rslayden

MTV006.19c HYPOTHETICAL 9.8 KDA PROTEIN from Mycobacterium tuberculosis (89 aa), FASTA scores: opt: 249, E(): 2.6e-11, (44.2% identity in 86 aa overlap)

Other

strand:+

rslayden

MTV006.19c HYPOTHETICAL 9.8 KDA PROTEIN from Mycobacterium tuberculosis (89 aa), FASTA scores: opt: 249, E(): 2.6e-11, (44.2% identity in 86 aa overlap)

Symbol

rel BE-2

rslayden

Conserved hypothetical protein, showing weak similarity with P58235

Other

start:3177537

rslayden

Conserved hypothetical protein, showing weak similarity with P58235

Other

stop:3177818

rslayden

Conserved hypothetical protein, showing weak similarity with P58235

Other

strand:+

rslayden

Conserved hypothetical protein, showing weak similarity with P58235

Symbol

rel BE-2

rslayden

YR54_SYNY3

Comments