Rv2193 (ctaE)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: cytochrome c oxidase subunit III
- REFSEQ: cytochrome C oxidase subunit III
- PATRIC: Cytochrome c oxidase polypeptide III (EC 1.9.3.1)
- TUBERCULIST: Probable cytochrome C oxidase (subunit III) CtaE
- NCBI: Probable cytochrome C oxidase (subunit III) CtaE
- updated information (H37Rv4):
  - gene name: ctaE
  - function:
  - reference:
Type: Not Target
Start: 2456901
End: 2457512
Operon:

Trans-membrane region:
Role: I.B.6.a - aerobic
GO terms:
- GO:1902600 - proton transmembrane transport (Uniprot)
- GO:0055114 - oxidation-reduction process (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0022904 - respiratory electron transport chain (Uniprot)
- GO:0019646 - aerobic electron transport chain (Uniprot)
- GO:0016491 - oxidoreductase activity (Uniprot)
- GO:0016021 - integral component of membrane (Uniprot)
- GO:0016020 - membrane (Uniprot)
- GO:0015002 - heme-copper terminal oxidase activity (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0004129 - cytochrome-c oxidase activity (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- 0.5 O2[c] + 2 HEME_FE2[c] -> 6 H[c] + 2 HEME_FE3[c]
- MKH2[c] + 2 HEME_FE3[c] <=> MK[c] + 2 HEME_FE2[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):

PDB	aa ident	species	PDB title
6HWH	87%	Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)	Structure of a functional obligate respiratory supercomplex from Mycobacterium smegmatis
6ADQ	87%	Mycobacterium smegmatis MC2 51	Respiratory Complex CIII2CIV2SOD2 from Mycobacterium smegmatis
5Z62	39%	Homo sapiens	Structure of human cytochrome c oxidase
6NMP	36%	Bos taurus	SFX structure of oxidized cytochrome c oxidase at room temperature
6NMF	36%	Bos taurus	SFX structure of reduced cytochrome c oxidase at room temperature
6NKN	36%	Bos taurus	Time-resolved SFX structure of the PR intermediate of cytochrome c oxidase at room temperature
6JY4	36%	Bos taurus	Monomeric Form of Bovine Heart Cytochrome c Oxidase in the Fully Reduced State
6JY3	36%	Bos taurus	Monomeric Form of Bovine Heart Cytochrome c Oxidase in the Fully Oxidized State
6JUW	36%	Bos taurus	BOVINE HEART CYTOCHROME C OXIDASE IN CATALITIC INTERMEDIATES AT 1.80 ANGSTROM RESOLUTION
6J8M	36%	Bos taurus	Low-dose structure of bovine heart cytochrome c oxidase in the fully oxidized state determined using 30 keV X-ray

Links to additional information on ctaE:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -8.948 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VTSAVGTSGTAITSRVHSLNRPNMVSVGTIVWLSSELMFFAGLFAFYFSARAQAGGNWPPPPTELNLYQAVPVTLVLIASSFTCQMGVFAAERGDIFGLR
RWYVITFLMGLFFVLGQAYEYRNLMSHGTSIPSSAYGSVFYLATGFHGLHVTGGLIAFIFLLVRTGMSKFTPAQATASIVVSYYWHFVDIVWIALFTVIY
FIR

(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)	1.57 (0.32)	0.88 (0.19)
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

Rv2193/ctaE, gene len: 611 bp, num TA sites: 17

condition	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	growth defect	7H9	HMM	fully saturated, 14 TnSeq libraries combined
in-vitro	Sassetti 2003 Mol Micro	essential	7H9	TRASH	essential if hybridization ratio<0.2
in-vivo (mice)	Sassetti 2003 PNAS	no data	BL6 mice	TRASH	essential if hybridization ratio<0.4, min over 4 timepoints (1-8 weeks)
in-vitro (glycerol)	Griffin 2011 PPath	essential	M9 minimal+glycerol	Gumbel	2 replicates; Padj<0.05
in-vitro (cholesterol)	Griffin 2011 PPath	essential	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	NO (LFC=-0.23)	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	essential	7H9	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice)	Smith 2022 eLife	essential	BL6 mice	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice	Smith 2022 eLife	NO (LFC=0.0)	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	essential	minimal medium	HMM
in-vitro (YM rich medium)	Minato 2019 mSys	essential	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, vitamins)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=-4.39)	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:
- Rv0324 (-)

Interactions based on ChIPSeq data (Minch et al. 2014)

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0081 (-) (Direct binding)
- Rv0324 (-) (Direct binding)
- Rv2034 (-) (Direct binding)

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:
- Rv0324 (-)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Operon Rv2200c	harsharohiratruefriend	TAS		BD. Kana, EA. Weinstein et al. Characterization of the cydAB-encoded cytochrome bd oxidase from Mycobacterium smegmatis. J. Bacteriol. 2001
Interaction	PhysicalInteraction Rv2196	ashwinigbhat	TAS		BD. Kana, EA. Weinstein et al. Characterization of the cydAB-encoded cytochrome bd oxidase from Mycobacterium smegmatis. J. Bacteriol. 2001
Interaction	PhysicalInteraction Rv2195	ashwinigbhat	TAS		BD. Kana, EA. Weinstein et al. Characterization of the cydAB-encoded cytochrome bd oxidase from Mycobacterium smegmatis. J. Bacteriol. 2001
Interaction	PhysicalInteraction Rv2196	priti.priety	TAS		BD. Kana, EA. Weinstein et al. Characterization of the cydAB-encoded cytochrome bd oxidase from Mycobacterium smegmatis. J. Bacteriol. 2001
Interaction	PhysicalInteraction Rv2195	priti.priety	TAS		BD. Kana, EA. Weinstein et al. Characterization of the cydAB-encoded cytochrome bd oxidase from Mycobacterium smegmatis. J. Bacteriol. 2001
Interaction	PhysicalInteraction Rv2194	priti.priety	TAS		BD. Kana, EA. Weinstein et al. Characterization of the cydAB-encoded cytochrome bd oxidase from Mycobacterium smegmatis. J. Bacteriol. 2001
Interaction	PhysicalInteraction Rv2194	ashwinigbhat	TAS		BD. Kana, EA. Weinstein et al. Characterization of the cydAB-encoded cytochrome bd oxidase from Mycobacterium smegmatis. J. Bacteriol. 2001
Interaction	PhysicalInteraction Rv2196	priti.priety	TAS		Coexpression BD. Kana, EA. Weinstein et al. Characterization of the cydAB-encoded cytochrome bd oxidase from Mycobacterium smegmatis. J. Bacteriol. 2001
Citation	Characterization of the cydAB-encoded cytochrome bd oxidase from Mycobacterium smegmatis. BD. Kana, EA. Weinstein et al. J. Bacteriol. 2001	ashwinigbhat	TAS	11717265	Coexpression
Interaction	PhysicalInteraction Rv2194	ashwinigbhat	TAS		Coexpression BD. Kana, EA. Weinstein et al. Characterization of the cydAB-encoded cytochrome bd oxidase from Mycobacterium smegmatis. J. Bacteriol. 2001
Interaction	PhysicalInteraction Rv2195	ashwinigbhat	TAS		Coexpression BD. Kana, EA. Weinstein et al. Characterization of the cydAB-encoded cytochrome bd oxidase from Mycobacterium smegmatis. J. Bacteriol. 2001
Interaction	PhysicalInteraction Rv2196	ashwinigbhat	TAS		Coexpression BD. Kana, EA. Weinstein et al. Characterization of the cydAB-encoded cytochrome bd oxidase from Mycobacterium smegmatis. J. Bacteriol. 2001
Citation	Characterization of the cydAB-encoded cytochrome bd oxidase from Mycobacterium smegmatis. BD. Kana, EA. Weinstein et al. J. Bacteriol. 2001	harsharohiratruefriend	TAS	11717265	None
Interaction	Operon Rv2200c	harsharohiratruefriend	TAS		BD. Kana, EA. Weinstein et al. Characterization of the cydAB-encoded cytochrome bd oxidase from Mycobacterium smegmatis. J. Bacteriol. 2001
Interaction	Operon Rv3043c	harsharohiratruefriend	TAS		BD. Kana, EA. Weinstein et al. Characterization of the cydAB-encoded cytochrome bd oxidase from Mycobacterium smegmatis. J. Bacteriol. 2001
Citation	Characterization of the cydAB-encoded cytochrome bd oxidase from Mycobacterium smegmatis. BD. Kana, EA. Weinstein et al. J. Bacteriol. 2001	priti.priety	TAS	11717265	Coexpression
Interaction	PhysicalInteraction Rv2194	priti.priety	TAS		Coexpression BD. Kana, EA. Weinstein et al. Characterization of the cydAB-encoded cytochrome bd oxidase from Mycobacterium smegmatis. J. Bacteriol. 2001
Interaction	PhysicalInteraction Rv2195	priti.priety	TAS		Coexpression BD. Kana, EA. Weinstein et al. Characterization of the cydAB-encoded cytochrome bd oxidase from Mycobacterium smegmatis. J. Bacteriol. 2001
Interaction	PhysicalInteraction Rv1451	ashwinigbhat	ISA		Co-occurrence (Functional linkage) authors,M. Strong,TG. Graeber,M. Beeby,M. Pellegrini,MJ. Thompson,TO. Yeates,D. Eisenberg Visualization and interpretation of protein networks in Mycobacterium tuberculosis based on hierarchical clustering of genome-wide functional linkage maps. Nucleic Acids Res. 2003
Interaction	PhysicalInteraction Rv1451	priti.priety	ISA		Co-occurrence (Functional linkage) authors,M. Strong,TG. Graeber,M. Beeby,M. Pellegrini,MJ. Thompson,TO. Yeates,D. Eisenberg Visualization and interpretation of protein networks in Mycobacterium tuberculosis based on hierarchical clustering of genome-wide functional linkage maps. Nucleic Acids Res. 2003
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 Rv1221	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.. R. Manganelli, MI. Voskuil et al. The Mycobacterium tuberculosis ECF sigma factor sigmaE: role in global gene expression and survival in macrophages. Mol. Microbiol. 2001

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