Rv1183 (mmpL10)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: transmembrane transporter mmpL10
- REFSEQ: transmembrane transport protein MmpL10
- PATRIC: membrane protein MmpL family putative
- TUBERCULIST: Probable conserved transmembrane transport protein MmpL10
- NCBI: Probable conserved transmembrane transport protein MmpL10
- updated information (H37Rv4):
  - gene name: mmpL10
  - function:
  - reference:
Type: Not Target
Start: 1321520
End: 1324528
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:0006869 - lipid transport (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0005618 - cell wall (Uniprot)
- GO:0005576 - extracellular region (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- 4 NADPH[c] + OCTADECANOYL_COA[c] + 3 RMMALONYLACP[c] -> 4 NADP[c] + 3 CO2[c] + COA[c] + 2 ACP[c] + MYCOLIPDIENOYL_ACP[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 mmpL10:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.809 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VVGCWVALALVLPMAVPSLAEMAQRHPVAVLPADAPSSVAVRQMAEAFHESGSENILVVLLTDEKGLGAADENVYHTLVDRLRNDAKDVVMLQDFLTTPP
LREVLGSKDGKAWILPIGLAGDLGTPKSYHAYTDVERIVKRTVAGTTLTANVTGPAATVADLTDAGARDRASIELAIAVMLLVILMVIYRNPVTMLLPLV
TIGASLMTAQALVAGVSLVGGLAVSNQAIVLLSAMIAGAGTDYAVFLISRYHEYVRLGEHPERAVQRAMMSVGKVIAASAATVGITFLGMRFAKLGVFST
VGPALAIGIAVSFLAAVTLLPAILVLASPRGWVAPRGERMATFWRRAGTRIVRRPKAYLGASLIGLVALASCASLAHFNYDDRKQLPPSDPSSVGYAAME
HHFSVNQTIPEYLIIHSAHDLRTPRGLADLEQLAQRVSQIPGVAMVRGVTRPNGETLEQARATYQAGQVGNRLGGASRMIDERTGDLNRLASGANLLADN
LGDVRGQVSRAVAGVRSLVDALAYIQNQFGGNKTFNEIDNAARLVSNIHALGDALQVNFDGIANSFDWLDSVVAALDTSPVCDSNPMCGNARVQFHKLQT
ARDNGTLDKVVGLARQLQSTRSPQTVSAVVNDLGRSLNSVVRSLKSLGLDNPDAARARLISMQNGANDLASAGRQVADGVQMLVDQTKNMGIGLNQASAF
LMAMGNDASQPSMAGFNVPPQVLKSEEFKKVAQAFISPDGHTVRYFIQTDLNPFSTAAMDQVNTIIDTAKGAQPNTSLADASISMSGYPVMLRDIRDYYE
RDMRLIVAVTVVVVILILMALLRAIVAPLYLVGSVVISYMSAIGLGVVVFQVFLGQELHWSVPGLAFVVLVAVGADYNMLLASRLRDESALGVRSSVIRT
VRCTGGVITAAGLIFAASMSGLLFSSIGTVVQGGFIIGVGILIDTFVVRTITVPAMATLLGRASWWPGHPWQRCAPEEGQMSARMSARTKTVFQAVADGS
KR

(Nucleotide sequence available on KEGG)

Additional Information

Analysis of Positive Selection in Clinical Isolates new

Analysis of dN/dS (omega) in two collections of Mtb clinical isolates using GenomegaMap (Window model) (see description of methods)
- Moldova: 2,057 clinical isolates
- global set: 5,195 clinical isolates from 15 other countries
In the omega plots, the black line shows the mean estimate of omega (dN/dS) at each codon, and the blue lines are the bounds for the 95% credible interval (95%CI, from MCMC sampling).
A gene is under significant positive selection if the lower-bound of the 95%CI of omega (lower blue line) exceeds 1.0 at any codon.

	Moldova (2,057)	global set (5,195)
under significant positive selection?	NO	NO
omega peak height (95%CI lower bound)	1.59 (0.25)	1.39 (0.67)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link

* example format for variants: "D27 (GAC): D27H (CAC,11)" means "Asp27 (native codon GAC) mutated to His (codon CAC) in 11 isolates"

ESSENTIALITY

MtbTnDB - interactive tool for exploring a database of published TnSeq datasets for Mtb

TnSeqCorr - genes with correlated TnSeq profiles across ~100 conditions

Rv1183/mmpL10, gene len: 3008 bp, num TA sites: 53

condition	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	non-essential	7H9	HMM	fully saturated, 14 TnSeq libraries combined
in-vitro	Sassetti 2003 Mol Micro	no data	7H9	TRASH	essential if hybridization ratio<0.2
in-vivo (mice)	Sassetti 2003 PNAS	essential	BL6 mice	TRASH	essential if hybridization ratio<0.4, min over 4 timepoints (1-8 weeks)
in-vitro (glycerol)	Griffin 2011 PPath	non-essential	M9 minimal+glycerol	Gumbel	2 replicates; Padj<0.05
in-vitro (cholesterol)	Griffin 2011 PPath	uncertain	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	YES (LFC=-2.84)	cholesterol vs glycerol	resampling-SR	YES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in cholesterol
in-vitro	Smith 2022 eLife	non-essential	7H9	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice)	Smith 2022 eLife	non-essential	BL6 mice	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice	Smith 2022 eLife	YES (LFC=-0.8)	in-vivo vs in-vitro	ZINB	YES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in mice
in-vitro (minimal)	Minato 2019 mSys	non-essential	minimal medium	HMM
in-vitro (YM rich medium)	Minato 2019 mSys	non-essential	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, cofactors)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=-0.5)	YM rich vs minimal medium	resampling

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:
- Rv1353c (-) (Direct binding)
- Rv3249c (-) (Direct binding)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Rv0023 (-)
- Rv0081 (-)

Property	Value	Creator	Evidence	PMID	Comment
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
Other	EC:	jjmcfadden			Inferred from direct assay VS. Dubey, TD. Sirakova et al. Disruption of msl3 abolishes the synthesis of mycolipanoic and mycolipenic acids required for polyacyltrehalose synthesis in Mycobacterium tuberculosis H37Rv and causes cell aggregation. Mol. Microbiol. 2002
Citation	Disruption of msl3 abolishes the synthesis of mycolipanoic and mycolipenic acids required for polyacyltrehalose synthesis in Mycobacterium tuberculosis H37Rv and causes cell aggregation. VS. Dubey, TD. Sirakova et al. Mol. Microbiol. 2002	jjmcfadden		12207710	Inferred from direct assay

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