Rv0450c (mmpL4)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: transmembrane transporter mmpL4
- REFSEQ: transmembrane transport protein MmpL4
- PATRIC: Transmembrane transport protein MmpL4
- TUBERCULIST: Probable conserved transmembrane transport protein MmpL4
- NCBI: Probable conserved transmembrane transport protein MmpL4
- updated information (H37Rv4):
  - gene name: mmpL4
  - function: mycobactin export
  - reference: Wells 2013; PMC3561183
Type: Essential
Start: 538588
End: 541491
Operon:

Trans-membrane region:
Role: II.C.4 - Conserved membrane proteins
GO terms:
- GO:0044119 - growth of symbiont in host cell (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0016021 - integral component of membrane (Uniprot)
- GO:0016020 - membrane (Uniprot)
- GO:0009405 - pathogenesis (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005618 - cell wall (Uniprot)
- GO:0005576 - extracellular region (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 mmpL4:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.423 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VSTKFANDSNTNARPEKPFIARMIHAFAVPIILGWLAVCVVVTVFVPSLEAVGQERSVSLSPKDAPSFEAMGRIGMVFKEGDSDSFAMVIIEGNQPLGDA
AHKYYDGLVAQLRADKKHVQSVQDLWGDPLTAAGVQSNDGKAAYVQLSLAGNQGTPLANESVEAVRSIVESTPAPPGIKAYVTGPSALAADMHHSGDRSM
ARITMVTVAVIFIMLLLVYRSIITVVLLLITVGVELTAARGVVAVLGHSGAIGLTTFAVSLLTSLAIAAGTDYGIFIIGRYQEARQAGEDKEAAYYTMYR
GTAHVILGSGLTIAGATFCLSFARMPYFQTLGIPCAVGMLVAVAVALTLGPAVLHVGSRFGLFDPKRLLKVRGWRRVGTVVVRWPLPVLVATCAIALVGL
LALPGYKTSYNDRDYLPDFIPANQGYAAADRHFSQARMKPEILMIESDHDMRNPADFLVLDKLAKGIFRVPGISRVQAITRPEGTTMDHTSIPFQISMQN
AGQLQTIKYQRDRANDMLKQADEMATTIAVLTRMHSLMAEMASTTHRMVGDTEEMKEITEELRDHVADFDDFWRPIRSYFYWEKHCYGIPICWSFRSIFD
ALDGIDKLSEQIGVLLGDLREMDRLMPQMVAQIPPQIEAMENMRTMILTMHSTMTGIFDQMLEMSDNATAMGKAFDAAKNDDSFYLPPEVFKNKDFQRAM
KSFLSSDGHAARFIILHRGDPQSPEGIKSIDAIRTAAEESLKGTPLEDAKIYLAGTAAVFHDISEGAQWDLLIAAISSLCLIFIIMLIITRAFIAAAVIV
GTVALSLGASFGLSVLLWQHILAIHLHWLVLAMSVIVLLAVGSDYNLLLVSRFKQEIGAGLKTGIIRSMGGTGKVVTNAGLVFAVTMASMAVSDLRVIGQ
VGTTIGLGLLFDTLIVRSFMTPSIAALLGRWFWWPLRVRSRPARTPTVPSETQPAGRPLAMSSDRLG

(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: 0.972900; 15 non-insertions in a row out of 84 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 6 non-insertions in a row out of 84 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 5 non-insertions in a row out of 84 sites
Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.998250; 14 non-insertions in a row out of 84 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.999900; 18 non-insertions in a row out of 84 sites
Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 0.08
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:
- Rv0023 (-)
- 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)
- Rv1776c (-) (Direct binding)
- Rv0678 (-) (Upstream of operon)
- Rv1049 (-) (Upstream of operon)
- Rv2250c (-) (Upstream of operon)
- Rv3676 (crp) (Upstream of operon)

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:
- Rv0023 (-)
- Rv3849 (espR)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Regulatory Rv2711	priyadarshinipriyanka2001	IEP		G. Lamichhane, S. Tyagi et al. Designer arrays for defined mutant analysis to detect genes essential for survival of Mycobacterium tuberculosis in mouse lungs. Infect. Immun. 2005
Citation	Identification of a virulence gene cluster of Mycobacterium tuberculosis by signature-tagged transposon mutagenesis. authors,LR. Camacho,D. Ensergueix,E. Perez,B. Gicquel,C. Guilhot Mol. Microbiol. 1999	priyadarshinipriyanka2001	IEP	10564470	None
Interaction	Regulatory Rv2711	priyadarshinipriyanka2001	IEP		authors,LR. Camacho,D. Ensergueix,E. Perez,B. Gicquel,C. Guilhot Identification of a virulence gene cluster of Mycobacterium tuberculosis by signature-tagged transposon mutagenesis. Mol. Microbiol. 1999
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
Citation	Contribution of the Mycobacterium tuberculosis MmpL protein family to virulence and drug resistance. P. Domenech, MB. Reed et al. Infect. Immun. 2005	priyadarshinipriyanka2001	IEP	15908378	None
Interaction	Regulatory Rv2711	priyadarshinipriyanka2001	IEP		P. Domenech, MB. Reed et al. Contribution of the Mycobacterium tuberculosis MmpL protein family to virulence and drug resistance. Infect. Immun. 2005
Citation	Designer arrays for defined mutant analysis to detect genes essential for survival of Mycobacterium tuberculosis in mouse lungs. G. Lamichhane, S. Tyagi et al. Infect. Immun. 2005	priyadarshinipriyanka2001	IEP	15784600	None
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

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