Rv1145 (mmpL13a)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: hypothetical protein
- REFSEQ: transmembrane transport protein MmpL13A
- PATRIC: Integral membrane protein
- TUBERCULIST: Probable conserved transmembrane transport protein MmpL13a
- NCBI: Probable conserved transmembrane transport protein MmpL13a
- updated information (H37Rv4):
  - gene name: mmpL13a
  - function:
  - reference:
Type: Conditional
Start: 1272423
End: 1273334
Operon:

Trans-membrane region:
Role: III.A.6 - Efflux proteins
GO terms:
- GO:0016021 - integral component of membrane (Uniprot)
- GO:0016020 - membrane (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:
Search for Homologs in PDB
Top 10 Homologs in PDB (as of Nov 2020): (none with >35% aa id)
Links to additional information on mmpL13a:
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.471 (from Jeremy Rock's lab)

Amino Acid Sequence

MLQRIARLAIAAPRRIIGFAVFVFIAAAVFGVPVADSLSPGGFQDPRSESARAIEVLTDKFGQSGQKMLIVVTAAAGADSPPAREVGTDIVEVLRRSPLV
YNVTSPWTVPPTAAADLLSTDGKSGLIVVNVKGGENDAQNHAQTLSDEVAHDRDGVTVRAGGSAMEYAQINRQNKDDLLVMELIAIPLSFLVLIWVFGGL
LAAGLPMAQAVLAVVGSMAVLRLVTFATEVSTFALNLSTALGLALAIDYTLLIVSRYRDELAEGSDRDEALIRTMALRGARCCFRRSPWRCRCRRLRCSR
CTF

(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)	1.52 (0.24)	2.18 (0.79)
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

Rv1145/mmpL13a, gene len: 911 bp, num TA sites: 11

condition	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	growth advantage	7H9	HMM	fully saturated, 14 TnSeq libraries combined
in-vitro	Sassetti 2003 Mol Micro	non-essential	7H9	TRASH	essential if hybridization ratio<0.2
in-vivo (mice)	Sassetti 2003 PNAS	non-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	non-essential	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	NO (LFC=-0.37)	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	growth advantage	7H9	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice)	Smith 2022 eLife	growth advantage	BL6 mice	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice	Smith 2022 eLife	NO (LFC=0.399)	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=-0.19)	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:
- Rv1423 (whiA) (Direct binding)
- Rv2250c (-) (Direct binding)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv0735 (sigL)
- Rv3416 (whiB3)
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Rv2250c (-)
- Rv3058c (-)

Property	Value	Creator	Evidence	PMID	Comment
Citation	Efflux pump-mediated intrinsic drug resistance in Mycobacterium smegmatis. XZ. Li, L. Zhang et al. Antimicrob. Agents Chemother. 2004	aparna.vchalam	IDA	15215089	In vitro transcription assay
Interaction	Regulatory Rv0735	aparna.vchalam	IDA		In vitro transcription assay XZ. Li, L. Zhang et al. Efflux pump-mediated intrinsic drug resistance in Mycobacterium smegmatis. Antimicrob. Agents Chemother. 2004
Citation	XDR-TB genome sequencing: a glimpse of the microbiology of the future. authors,NJ. Loman,MJ. Pallen Future Microbiol 2008	aparna.vchalam	IDA	18366328	In vitro transcription assay
Interaction	Regulatory Rv0735	aparna.vchalam	IDA		In vitro transcription assay authors,NJ. Loman,MJ. Pallen XDR-TB genome sequencing: a glimpse of the microbiology of the future. Future Microbiol 2008
Citation	[Studies on the action of an anticholinergic agent in combination with a tranquilizer on gastric juice secretion in man]. authors,RR. Scherberger,H. Kaess,S. Brckner Arzneimittelforschung 1975	aparna.vchalam	IDA	26	In vitro transcription assay
Interaction	Regulatory Rv0735	aparna.vchalam	IDA		In vitro transcription assay authors,RR. Scherberger,H. Kaess,S. Brckner [Studies on the action of an anticholinergic agent in combination with a tranquilizer on gastric juice secretion in man]. Arzneimittelforschung 1975
Citation	Posttranslational regulation of Mycobacterium tuberculosis extracytoplasmic-function sigma factor sigma L and roles in virulence and in global regulation of gene expression. E. Dainese, S. Rodrigue et al. Infect. Immun. 2006	aparna.vchalam	IDA	16552079	In vitro transcription assay
Interaction	Regulatory Rv0735	aparna.vchalam	IDA		In vitro transcription assay E. Dainese, S. Rodrigue et al. Posttranslational regulation of Mycobacterium tuberculosis extracytoplasmic-function sigma factor sigma L and roles in virulence and in global regulation of gene expression. Infect. Immun. 2006

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