Rv0451c (mmpS4)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: membrane protein mmpS4
- REFSEQ: membrane protein
- PATRIC: membrane protein MmpS family
- TUBERCULIST: Probable conserved membrane protein MmpS4
- NCBI: Probable conserved membrane protein MmpS4
- updated information (H37Rv4):
  - gene name: mmpS4
  - function: mycobactin export
  - reference: Wells 2013; PMC3561183
Type: Not Target
Start: 541488
End: 541910
Operon:

Trans-membrane region:
Role: II.C.4 - Conserved membrane proteins
GO terms:
- GO:0016021 - integral component of membrane (Uniprot)
- GO:0016020 - membrane (Uniprot)
- GO:0009405 - pathogenesis (Uniprot)
- GO:0005886 - plasma membrane (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: 2lw3
Search for Homologs in PDB
Top 10 Homologs in PDB (as of Nov 2020):

PDB aa ident species PDB title

2LW3 100% Mycobacterium tuberculosis Solution structure of the soluble domain of MmpS4 from Mycobacterium tuberculosis
Links to additional information on mmpS4:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.583 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

PDB	aa ident	species	PDB title
2LW3	100%	Mycobacterium tuberculosis	Solution structure of the soluble domain of MmpS4 from Mycobacterium tuberculosis

Amino Acid Sequence

VLMRTWIPLVILVVVIVGGFTVHRIRGFFGSENRPSYSDTNLENSKPFNPKHLTYEIFGPPGTVADISYFDVNSEPQRVDGAVLPWSLHITTNDAAVMGN
IVAQGNSDSIGCRITVDGKVRAERVSNEVNAYTYCLVKSA

(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: 0.000050; 8 non-insertions in a row out of 15 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 15 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 15 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000050; 6 non-insertions in a row out of 15 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.999900; 14 non-insertions in a row out of 15 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: 0.46
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:
- Rv0353 (hspR)
- Rv3849 (espR)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0135c (-) (Direct binding)
- Rv0678 (-) (Direct binding)
- Rv1049 (-) (Direct binding)
- Rv2250c (-) (Direct binding)
- Rv3676 (crp) (Direct binding)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Not upregulated by other genes.
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Rv0353 (hspR)
- Rv3849 (espR)

Property	Value	Creator	Evidence	PMID	Comment
Citation	Computational prediction and experimental verification of novel IdeR binding sites in the upstream sequences of Mycobacterium tuberculosis open reading frames. P. Prakash, S. Yellaboina et al. Bioinformatics 2005	priyadarshinipriyanka2001	IEP	15746274	None
Interaction	Regulatory Rv2711	priyadarshinipriyanka2001	IEP		P. Prakash, S. Yellaboina et al. Computational prediction and experimental verification of novel IdeR binding sites in the upstream sequences of Mycobacterium tuberculosis open reading frames. Bioinformatics 2005
Citation	The Mycobacterium tuberculosis IdeR is a dual functional regulator that controls transcription of genes involved in iron acquisition, iron storage and survival in macrophages. B. Gold, GM. Rodriguez et al. Mol. Microbiol. 2001	priyadarshinipriyanka2001	IEP	11722747	None
Interaction	Regulatory Rv2711	priyadarshinipriyanka2001	IEP		B. Gold, GM. Rodriguez et al. The Mycobacterium tuberculosis IdeR is a dual functional regulator that controls transcription of genes involved in iron acquisition, iron storage and survival in macrophages. Mol. Microbiol. 2001
Citation	ideR, An essential gene in mycobacterium tuberculosis: role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response. GM. Rodriguez, MI. Voskuil et al. Infect. Immun. 2002	priyadarshinipriyanka2001	IEP	12065475	None
Interaction	Regulatory Rv2711	priyadarshinipriyanka2001	IEP		GM. Rodriguez, MI. Voskuil et al. ideR, An essential gene in mycobacterium tuberculosis: role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response. Infect. Immun. 2002
Interaction	RegulatedBy Rv3676	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 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
Interaction	RegulatedBy Rv2711	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.. GM. Rodriguez, MI. Voskuil et al. ideR, An essential gene in mycobacterium tuberculosis: role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response. Infect. Immun. 2002

TB Genome Annotation Portal