Rv3823c (mmpL8)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: membrane transporter mmpL8
- REFSEQ: integral membrane transport protein
- PATRIC: membrane protein MmpL family putative
- TUBERCULIST: Conserved integral membrane transport protein MmpL8
- NCBI: Conserved integral membrane transport protein MmpL8
- updated information (H37Rv4):
  - gene name: mmpL8
  - function: sulfolipid-1 synthesis
  - reference: Seeliger (2012) PMID: 22194604
Type: Not Target
Start: 4288260
End: 4291529
Operon:

Trans-membrane region:
Role: II.C.4 - Conserved membrane proteins
GO terms:
- GO:0071555 - cell wall organization (Uniprot)
- GO:0046506 - sulfolipid biosynthetic process (Uniprot)
- GO:0016021 - integral component of membrane (Uniprot)
- GO:0016020 - membrane (Uniprot)
- GO:0006869 - lipid transport (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0005618 - cell wall (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- SL1278_CYTO[c] -> SL1278_WALL[c]
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 mmpL8:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.609 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MCDVLMQPVRTPRPSTNLRSKPLRPTGDGGVFPRLGRLIVRRPWVVIAFWVALAGLLAPTVPSLDAISQRHPVAILPSDAPVLVSTRQMTAAFREAGLQS
VAVVVLSDAKGLGAADERSYKELVDALRRDTRDVVMLQDFVTTPPLRELMTSKDNQAWILPVGLPGDLGSTQSKQAYARVADIVEHQVAGSTLTANLTGP
AATVADLNLTGQRDRSRIEFAITILLLVILLIIYGNPITMVLPLITIGMSVVVAQRLVAIAGLAGLGIANQSIIFMSGMMVGAGTDYAVFLISRYHDYLR
QGADSDQAVKKALTSIGKVIAASAATVAITFLGMVFTQLGILKTVGPMLGISVAVVFFAAVTLLPALMVLTGRRGWIAPRRDLTRRFWRSSGVHIVRRPK
THLLASALVLVILAGCAGLARYNYDDRKTLPASVESSIGYAALDKHFPSNLIIPEYLFIQSSTDLRTPKALADLEQMVQRVSQVPGVAMVRGITRPAGRS
LEQARTSWQAGEVGSKLDEGSKQIAVHTGDIDKLAGGANLMASKLGDVRAQVNRAISTVGGLIDALAYLQDLLGGNRVLGELEGAEKLIGSMRALGDTID
ADASFVANNTEWASPVLGALDSSPMCTADPACASARTELQRLVTARDDGTLAKISELARQLQATRAVQTLAATVSGLRGALATVIRAMGSLGMSSPGGVR
SKINLVNKGVNDLADGSRQLAEGVQLLVDQVKKMGFGLGEASAFLLAMKDTATTPAMAGFYIPPELLSYATGESVKAETMPSEYRDLLGGLNVDQLKKVA
AAFISPDGHSIRYLIQTDLNPFSTAAMDQIDAITAAARGAQPNTALADAKVSVVGLPVVLKDTRDYSDHDLRLIIAMTVCIVLLILIVLLRAIVAPLYLI
GSVIVSYLAALGIGVIVFQFLLGQEMHWSIPGLTFVILVAVGADYNMLLISRLREEAVLGVRSGVIRTVASTGGVITAAGLIMAASMYGLVFASLGSVVQ
GAFVLGTGLLLDTFLVRTVTVPAIAVLVGQANWWLPSSWRPATWWPLGRRRGRAQRTKRKPLLPKEEEEQSPPDDDDLIGLWLHDGLRL

(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; 8 non-insertions in a row out of 78 sites
Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.999650; 15 non-insertions in a row out of 78 sites
Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.999150; 14 non-insertions in a row out of 78 sites
Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 1.000000; 19 non-insertions in a row out of 79 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 1.000000; 19 non-insertions in a row out of 79 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: 3.01
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:
- No bindings to other targets were found.

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv0324 (-)
- Rv0757 (phoP)
Downregulates:
- Does not downregulate other genes.
Downregulated by:

Property	Value	Creator	Evidence	PMID	Comment
Citation	The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. SB. Walters, E. Dubnau et al. Mol. Microbiol. 2006	sourish10	IEP	16573683	Co-expression (Functional linkage)
Interaction	Transcription Rv0757	sourish10	IEP		Co-expression (Functional linkage) SB. Walters, E. Dubnau et al. The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol. Microbiol. 2006
Interaction	RegulatedBy Rv0348	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.. B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009
Interaction	RegulatedBy Rv0757	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.. qRT-PCR. mRNA expression levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using qRT-PCR technique. SB. Walters, E. Dubnau et al. The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol. Microbiol. 2006
Interaction	RegulatedBy Rv0757	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.. qRT-PCR. mRNA expression levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using qRT-PCR technique. SB. Walters, E. Dubnau et al. The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol. Microbiol. 2006
Name	RND superfamily inner membrane transporter thought to be involved in the translocation of a diacylated precursor of sulfolipid I across the plasma membrane	mjackson	IMP		Polymethyl-branched acyltrehaloses
Citation	The role of MmpL8 in sulfatide biogenesis and virulence of Mycobacterium tuberculosis. P. Domenech, MB. Reed et al. J. Biol. Chem. 2004	mjackson		15001577	RND superfamily inner membrane transporter thought to be involved in the translocation of a diacylated precursor of sulfolipid I across the plasma membrane (phenotypic [mycobacterial recombinant strains])
Other	TBPWY:Polymethyl-branched acyltrehaloses	mjackson			RND superfamily inner membrane transporter thought to be involved in the translocation of a diacylated precursor of sulfolipid I across the plasma membrane (phenotypic [mycobacterial recombinant strains]) P. Domenech, MB. Reed et al. The role of MmpL8 in sulfatide biogenesis and virulence of Mycobacterium tuberculosis. J. Biol. Chem. 2004
Citation	MmpL8 is required for sulfolipid-1 biosynthesis and Mycobacterium tuberculosis virulence. SE. Converse, JD. Mougous et al. Proc. Natl. Acad. Sci. U.S.A. 2003	mjackson		12724526	RND superfamily inner membrane transporter thought to be involved in the translocation of a diacylated precursor of sulfolipid I across the plasma membrane (phenotypic [mycobacterial recombinant strains])
Other	TBPWY:Polymethyl-branched acyltrehaloses	mjackson			RND superfamily inner membrane transporter thought to be involved in the translocation of a diacylated precursor of sulfolipid I across the plasma membrane (phenotypic [mycobacterial recombinant strains]) SE. Converse, JD. Mougous et al. MmpL8 is required for sulfolipid-1 biosynthesis and Mycobacterium tuberculosis virulence. Proc. Natl. Acad. Sci. U.S.A. 2003
Citation	MmpL8 is required for sulfolipid-1 biosynthesis and Mycobacterium tuberculosis virulence. SE. Converse, JD. Mougous et al. Proc. Natl. Acad. Sci. U.S.A. 2003	jjmcfadden		12724526	Inferred from direct assay
Other	EC:	jjmcfadden			Inferred from direct assay SE. Converse, JD. Mougous et al. MmpL8 is required for sulfolipid-1 biosynthesis and Mycobacterium tuberculosis virulence. Proc. Natl. Acad. Sci. U.S.A. 2003

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