Rv2429 (ahpD)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: alkyl hydroperoxide reductase AhpD
- REFSEQ: alkyl hydroperoxide reductase subunit D
- PATRIC: Alkylhydroperoxidase protein D
- TUBERCULIST: Alkyl hydroperoxide reductase D protein AhpD (alkyl hydroperoxidase D)
- NCBI: Alkyl hydroperoxide reductase D protein AhpD (alkyl hydroperoxidase D)
- updated information (H37Rv4):
  - gene name: ahpD
  - function:
  - reference:
Type: Not Target
Start: 2726806
End: 2727339
Operon:

Trans-membrane region:
Role: III.F - Detoxification
GO terms:
- GO:0098869 - cellular oxidant detoxification (Uniprot)
- GO:0055114 - oxidation-reduction process (Uniprot)
- GO:0051920 - peroxiredoxin activity (Uniprot)
- GO:0045454 - cell redox homeostasis (Uniprot)
- GO:0032843 - hydroperoxide reductase activity (Uniprot)
- GO:0016491 - oxidoreductase activity (Uniprot)
- GO:0016209 - antioxidant activity (Uniprot)
- GO:0015036 - disulfide oxidoreductase activity (Uniprot)
- GO:0006979 - response to oxidative stress (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0005515 - protein binding (Uniprot)
- GO:0004601 - peroxidase activity (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: 1gu9, 1knc, 1me5, 1lw1
Search for Homologs in PDB

Top 10 Homologs in PDB (as of Nov 2020):

PDB	aa ident	species	PDB title
1KNC	100%	Mycobacterium tuberculosis	Structure of AhpD from Mycobacterium tuberculosis, a novel enzyme with thioredoxin-like activity.
1GU9	100%	MYCOBACTERIUM TUBERCULOSIS	Crystal Structure of Mycobacterium tuberculosis Alkylperoxidase AhpD
1ME5	99%	Mycobacterium tuberculosis	Crystal Structure of Mycobacterium Tuberculosis Alkylperoxidase AhpD H132Q Mutant
1LW1	99%	Mycobacterium tuberculosis	Crystal Structure Of Mycobacterium Tuberculosis Alkylperoxidase Ahpd H137F mutant

Links to additional information on ahpD:
- 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 = 0.671 (from Jeremy Rock's lab)

Amino Acid Sequence

MSIEKLKAALPEYAKDIKLNLSSITRSSVLDQEQLWGTLLASAAATRNPQVLADIGAEATDHLSAAARHAALGAAAIMGMNNVFYRGRGFLEGRYDDLRP
GLRMNIIANPGIPKANFELWSFAVSAINGCSHCLVAHEHTLRTVGVDREAIFEALKAAAIVSGVAQALATIEALSPS

(Nucleotide sequence available on KEGG)

Additional Information

ESSENTIALITY

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

TnSeqCorr - genes with correlated TnSeq profiles across >100 conditions *new*

Classification	Condition	Strain	Method	Reference	Notes
Non-Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 13 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 13 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 13 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 14 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 14 sites
Non-Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Non-Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 1.19
Non-Essential	7H09/7H10 + rich media	H37RvMA	MotifHMM	DeJesus et al. (2017)	Fully saturated (14 reps).

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:
- Rv0047c (-) (Upstream of operon)
- Rv0324 (-) (Upstream of operon)
- Rv3597c (lsr2) (Upstream of operon)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv0023 (-)
- Rv0081 (-)
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Rv0260c (-)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Activation Rv2428	singhpankaj2116	IDA		Structural analysis BG. Guimares, H. Souchon et al. Structure and mechanism of the alkyl hydroperoxidase AhpC, a key element of the Mycobacterium tuberculosis defense system against oxidative stress. J. Biol. Chem. 2005
Citation	Structure and mechanism of the alkyl hydroperoxidase AhpC, a key element of the Mycobacterium tuberculosis defense system against oxidative stress. BG. Guimares, H. Souchon et al. J. Biol. Chem. 2005	singhpankaj2116	IDA	15886207	Structural analysis
Interaction	Activation Rv2428	singhpankaj2116	IDA		Structural analysis BG. Guimares, H. Souchon et al. Structure and mechanism of the alkyl hydroperoxidase AhpC, a key element of the Mycobacterium tuberculosis defense system against oxidative stress. J. Biol. Chem. 2005
Interaction	Regulatory Rv0616c	akankshajain.21	IEP		Co-expression (Functional linkage) T. Parish, DA. Smith et al. The senX3-regX3 two-component regulatory system of Mycobacterium tuberculosis is required for virulence. Microbiology (Reading, Engl.) 2003
Interaction	PhysicalInteraction Rv0462	sourish10	ISO		Gene Neighbourhood (Functional Linkage) A. Argyrou & JS. Blanchard Mycobacterium tuberculosis lipoamide dehydrogenase is encoded by Rv0462 and not by the lpdA or lpdB genes. Biochemistry 2001
Interaction	PhysicalInteraction Rv0462	sourish10	ISO		Gene Neighbourhood (Functional Linkage) R. Bryk, CD. Lima et al. Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein. Science 2002
Interaction	PhysicalInteraction Rv0462	ahal4789	ISO		Gene Neighbourhood (Functional Linkage) A. Argyrou & JS. Blanchard Mycobacterium tuberculosis lipoamide dehydrogenase is encoded by Rv0462 and not by the lpdA or lpdB genes. Biochemistry 2001
Interaction	PhysicalInteraction Rv0462	ahal4789	ISO		Gene Neighbourhood (Functional Linkage) R. Bryk, CD. Lima et al. Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein. Science 2002
Interaction	RegulatedBy Rv0981	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.. H. He, R. Hovey et al. MprAB is a stress-responsive two-component system that directly regulates expression of sigma factors SigB and SigE in Mycobacterium tuberculosis. J. Bacteriol. 2006
Interaction	RegulatedBy Rv2711	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.. GM. Rodriguez, MI. Voskuil et al. ideR, An essential gene in mycobacterium tuberculosis: role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response. Infect. Immun. 2002
Interaction	RegulatedBy Rv0491	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.. T. Parish, DA. Smith et al. The senX3-regX3 two-component regulatory system of Mycobacterium tuberculosis is required for virulence. Microbiology (Reading, Engl.) 2003

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