Rv0868c (moaD2)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: molybdenum cofactor biosynthesis protein D 2 moaD2
- REFSEQ: molybdenum cofactor biosynthesis protein D
- PATRIC: Molybdenum cofactor biosynthesis protein MoaD
- TUBERCULIST: Probable molybdenum cofactor biosynthesis protein D 2 MoaD2 (molybdopterin converting factor small subunit) (molybdopterin [MPT] converting factor subunit 1)
- NCBI: Probable molybdenum cofactor biosynthesis protein D 2 MoaD2 (molybdopterin converting factor small subunit) (molybdopterin [MPT] converting factor, subunit 1)
- updated information (H37Rv4):
  - gene name: moaD2
  - function:
  - reference:
Type: Not Target
Start: 965983
End: 966261
Operon:

Trans-membrane region:
Role: I.G.4 - Molybdopterin
GO terms:
- No terms 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
6JBZ	98%	Mycobacterium tuberculosis	Structural analysis of molybdopterin synthases from two mycobacteria pathogens
6JC0	56%	Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)	Structural analysis of molybdopterin synthases from two mycobacteria pathogens

Links to additional information on moaD2:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.971 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VTQVSDESAGIQVTVRYFAAARAAAGAGSEKVTLRSGATVAELIDGLSVRDVRLATVLSRCSYLRDGIVVRDDAVALSAGDTIDVLPPFAGG

(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)	1.07 (0.2)	2.49 (0.89)
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

Rv0868c/moaD2, gene len: 278 bp, num TA sites: 7

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	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=0.99)	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	NO (LFC=-0.028)	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, vitamins)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=0.87)	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:
- No bindings to other targets were found.

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv0818 (-)
- Rv3416 (whiB3)
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Rv2595 (vapB40)
- Rv3167c (-)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	ActivatedBy Rv3323c	shahanup86	RCA		Domain Fusion(Functional-linkage) authors,MS. Cortese,AB. Caplan,RL. Crawford Structural, functional, and evolutionary analysis of moeZ, a gene encoding an enzyme required for the synthesis of the Pseudomonas metabolite, pyridine-2,6-bis(thiocarboxylic acid). BMC Evol. Biol. 2002
Interaction	ActivatedBy Rv3323c	vashishtrv	RCA		Domain Fusion(Functional-linkage) authors,MS. Cortese,AB. Caplan,RL. Crawford Structural, functional, and evolutionary analysis of moeZ, a gene encoding an enzyme required for the synthesis of the Pseudomonas metabolite, pyridine-2,6-bis(thiocarboxylic acid). BMC Evol. Biol. 2002
Interaction	PhysicalInteraction Rv3116	kaveri.verma	ISS		Structural Analysis CT. Jurgenson, KE. Burns et al. Crystal structure of a sulfur carrier protein complex found in the cysteine biosynthetic pathway of Mycobacterium tuberculosis. Biochemistry 2008
Citation	IscS functions as a primary sulfur-donating enzyme by interacting specifically with MoeB and MoaD in the biosynthesis of molybdopterin in Escherichia coli. authors,W. Zhang,A. Urban,H. Mihara,S. Leimkhler,T. Kurihara,N. Esaki J. Biol. Chem. 2010	girishgene07	ISO	19946146	co-occurrence (functional linkage)
Interaction	Activation Rv3206c	girishgene07	ISO		co-occurrence (functional linkage) authors,W. Zhang,A. Urban,H. Mihara,S. Leimkhler,T. Kurihara,N. Esaki IscS functions as a primary sulfur-donating enzyme by interacting specifically with MoeB and MoaD in the biosynthesis of molybdopterin in Escherichia coli. J. Biol. Chem. 2010
Interaction	Activation Rv3025c	girishgene07	ISO		co-occurrence (functional linkage) authors,W. Zhang,A. Urban,H. Mihara,S. Leimkhler,T. Kurihara,N. Esaki IscS functions as a primary sulfur-donating enzyme by interacting specifically with MoeB and MoaD in the biosynthesis of molybdopterin in Escherichia coli. J. Biol. Chem. 2010
Citation	[Digestive tract disease in the surgical department and acute abdomen]. authors,K. Mieno Kango Gijutsu 1979	girishgene07	ISO	259713	co-occurrence (functional linkage)
Interaction	Activation Rv3206c	girishgene07	ISO		co-occurrence (functional linkage) authors,K. Mieno [Digestive tract disease in the surgical department and acute abdomen]. Kango Gijutsu 1979
Interaction	Activation Rv3025c	girishgene07	ISO		co-occurrence (functional linkage) authors,K. Mieno [Digestive tract disease in the surgical department and acute abdomen]. Kango Gijutsu 1979
Citation	The iscS gene in Escherichia coli is required for the biosynthesis of 4-thiouridine, thiamin, and NAD. authors,CT. Lauhon,R. Kambampati J. Biol. Chem. 2000	girishgene07	ISO	10781607	co-occurrence (functional linkage)
Interaction	Activation Rv3206c	girishgene07	ISO		co-occurrence (functional linkage) authors,CT. Lauhon,R. Kambampati The iscS gene in Escherichia coli is required for the biosynthesis of 4-thiouridine, thiamin, and NAD. J. Biol. Chem. 2000
Interaction	Activation Rv3025c	girishgene07	ISO		co-occurrence (functional linkage) authors,CT. Lauhon,R. Kambampati The iscS gene in Escherichia coli is required for the biosynthesis of 4-thiouridine, thiamin, and NAD. J. Biol. Chem. 2000
Interaction	PhysicalInteraction Rv0866	sourish10	ISS		authors,R. Sanishvili,S. Beasley,T. Skarina,D. Glesne,A. Joachimiak,A. Edwards,A. Savchenko The crystal structure of Escherichia coli MoaB suggests a probable role in molybdenum cofactor synthesis. J. Biol. Chem. 2004
Interaction	PhysicalInteraction Rv0866	sourish10	ISS		EP. Williams, JH. Lee et al. Mycobacterium tuberculosis SigF regulates genes encoding cell wall-associated proteins and directly regulates the transcriptional regulatory gene phoY1. J. Bacteriol. 2007
Interaction	PhysicalInteraction Rv0866	ahal4789	ISS		authors,R. Sanishvili,S. Beasley,T. Skarina,D. Glesne,A. Joachimiak,A. Edwards,A. Savchenko The crystal structure of Escherichia coli MoaB suggests a probable role in molybdenum cofactor synthesis. J. Biol. Chem. 2004
Interaction	PhysicalInteraction Rv0866	ahal4789	ISS		EP. Williams, JH. Lee et al. Mycobacterium tuberculosis SigF regulates genes encoding cell wall-associated proteins and directly regulates the transcriptional regulatory gene phoY1. J. Bacteriol. 2007
Citation	Functional analysis of molybdopterin biosynthesis in mycobacteria identifies a fused molybdopterin synthase in Mycobacterium tuberculosis. authors,MJ. Williams,BD. Kana,V. Mizrahi J. Bacteriol. 2011	mwilliams		20971904	Deletion in M. tuberculosis results in reduced MoCo biosynthesis
Citation	Functional analysis of molybdopterin biosynthesis in mycobacteria identifies a fused molybdopterin synthase in Mycobacterium tuberculosis. authors,MJ. Williams,BD. Kana,V. Mizrahi J. Bacteriol. 2011	mwilliams		20971904	Expression in M. smegmatis moaD mutant restores MoCo biosynthesis

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