Rv0950c (-)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: hypothetical protein
- REFSEQ: hypothetical protein
- PATRIC: Phage peptidoglycan binding endopeptidase
- TUBERCULIST: Conserved hypothetical protein
- NCBI: hypothetical protein
- updated information (H37Rv4):
  - gene name: -
  - function:
  - reference:
Type: Conditional
Start: 1060656
End: 1061654
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0009405 - pathogenesis (FLUTE) (FLUTE Assigned!)
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):

PDB	aa ident	species	PDB title
5J1M	47%	Helicobacter pylori	Crystal structure of Csd1-Csd2 dimer II
5J1L	47%	Helicobacter pylori	Crystal structure of Csd1-Csd2 dimer I
6MUK	43%	Neisseria gonorrhoeae	1.93 Angstrom Resolution Crystal Structure of Peptidase M23 from Neisseria gonorrhoeae.
3SLU	43%	Neisseria meningitidis	Crystal structure of NMB0315
2GU1	41%	Vibrio cholerae	Crystal structure of a zinc containing peptidase from vibrio cholerae
4ZYB	40%	Staphylococcus aureus subsp. aureus NCTC 8325	High resolution structure of M23 peptidase LytM with substrate analogue
2B44	40%	Staphylococcus aureus	Truncated S. aureus LytM, P 32 2 1 crystal form
2B13	40%	Staphylococcus aureus	Truncated S. aureus LytM, P41 crystal form
2B0P	40%	Staphylococcus aureus	truncated S. aureus LytM, P212121 crystal form
1QWY	40%	Staphylococcus aureus subsp. aureus NCTC 8325	Latent LytM at 1.3 A resolution

Links to additional information on Rv0950c:
- KEGG - nucleotide and amino acid sequences of gene
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -0.12 (from Jeremy Rock's lab)
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MAAIRTPRDRWPHHHRNEVTEIIPLDGFLDGLALYDELDFAELDDLDLGDDCVFDYEAQLLAAPELDDLDDADDLAPEWLVAPTVVLTPEVTPVSRRVGQ
HRKQPIGAARGRLLISAMAAGAAAAAAHTAIQQSETPRTETVLTAHASALNEGSGSNPPRGVQVIAAQPAASAAVHNAEFARGVAFAEERAEREARLQRP
LYVMPTKGIFTSSFGYRWGVLHAGIDLANAIGTPIYAVSDGVVIDAGPTAGYGMWVKLLHADGTVTLYGHVNTTLVSVGERVMAGDQIATMGSRGFSTGP
HLHFEVLLGGTERVDPVPWLAKRGLSVGNYTG

(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)	1.39 (0.25)	1.12 (0.38)
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

Rv0950c/-, gene len: 998 bp, num TA sites: 21

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	non-essential	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	uncertain	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=1.49)	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=-1.78)	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	growth defect	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, cofactors)
differentially essential in YM rich medium	Minato 2019 mSys	YES (LFC=-3.34)	YM rich vs minimal medium	resampling

TnSeq Data

collected by: Rebecca Audette/Hesper Rego (Rubin lab) (5/3/2016)
SRA accession: PRJNA377978
counts: TnSeq_Mtb_Rv0950ko.wig
reference: TnSeq_H37Rv_CB.wig
resampling:resampling_H37Rv_Rv0950_day0_s10000_pc0.00.xlsx

RNASeq Data No data currently available.

collected by: Shoko Wakabayashi (Rubin lab) 2019
counts/RPKMs: RNAseq_Rv0950c_KO-1.expr, RNAseq_Rv0950c_KO-2.expr, RNAseq_Rv0950c_KO-3.expr
reference datasets: RNAseq_H37Rv_WT-1.expr, RNAseq_H37Rv_WT-2.expr, RNAseq_H37Rv_WT-3.expr
DeSeq analysis: DESeq_Rv0950c_KO.txt (differentially expressed genes, qval<0.05, marked in yellow)
BioProject accession: PRJNA511742

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:
- Rv0324 (-) (Direct binding)
- Rv0678 (-) (Direct binding)
- Rv1255c (-) (Direct binding)
- Rv3246c (mtrA) (Direct binding)
- Rv3416 (whiB3) (Direct binding)
- Rv3597c (lsr2) (Direct binding)

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

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

Property	Value	Creator	Evidence	PMID	Comment
Citation	The Mycobacterium bovis BCG cyclic AMP receptor-like protein is a functional DNA binding protein in vitro and in vivo, but its activity differs from that of its M. tuberculosis ortholog, Rv3676. G. Bai, MA. Gazdik et al. Infect. Immun. 2007	sourish10	IPI	17785469	ChIP (Physical interaction)
Interaction	Transcription Rv3676	sourish10	IPI		ChIP (Physical interaction) G. Bai, MA. Gazdik et al. The Mycobacterium bovis BCG cyclic AMP receptor-like protein is a functional DNA binding protein in vitro and in vivo, but its activity differs from that of its M. tuberculosis ortholog, Rv3676. Infect. Immun. 2007
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

TB Genome Annotation Portal