Rv0983 (pepD)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: serine protease PepD
- REFSEQ: serine protease PepD
- PATRIC: Heat shock protein HtrA
- TUBERCULIST: Probable serine protease PepD (serine proteinase) (MTB32B)
- NCBI: Probable serine protease PepD (serine proteinase) (MTB32B)
- updated information (H37Rv4):
  - gene name: htrA2/pepD
  - function:
  - reference: Mohamedmohaideen (2008) PMID: 18479146
Type: Not Target
Start: 1099066
End: 1100460
Operon:

Trans-membrane region:
Role: II.B.3 - Proteins, peptides and glycopeptides
GO terms:
- GO:0071236 - cellular response to antibiotic (Uniprot)
- GO:0030163 - protein catabolic process (Uniprot)
- GO:0016021 - integral component of membrane (Uniprot)
- GO:0016020 - membrane (Uniprot)
- GO:0009405 - pathogenesis (Uniprot)
- GO:0008236 - serine-type peptidase activity (Uniprot)
- GO:0008233 - peptidase activity (Uniprot)
- GO:0006508 - proteolysis (Uniprot)
- GO:0005576 - extracellular region (Uniprot)
- GO:0004252 - serine-type endopeptidase 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: 2z9i, 1y8t
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
2Z9I	100%	Mycobacterium tuberculosis	Crystal structure of RV0983 from Mycobacterium tuberculosis- Proteolytically active form
1Y8T	100%	Mycobacterium tuberculosis	Crystal Structure of RV0983 from Mycobacterium tuberculosis- Proteolytically active form
6IEO	46%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of Mycobacterium tuberculosis HtrA1 (Rv1223) in regulated conformation
5ZVJ	46%	Mycobacterium tuberculosis	Crystal structure of HtrA1 from Mycobacterium tuberculosis
3STI	43%	Escherichia coli	Crystal structure of the protease domain of DegQ from Escherichia coli
3MH6	39%	Escherichia coli	HtrA proteases are activated by a conserved mechanism that can be triggered by distinct molecular cues
3MH5	39%	Escherichia coli	HtrA proteases are activated by a conserved mechanism that can be triggered by distinct molecular cues
2ZLE	39%	Escherichia coli	Cryo-EM structure of DegP12/OMP
6JJO	39%	Escherichia coli K-12	Crystal structure of the DegP dodecamer with a modulator
6JJL	39%	Escherichia coli K-12	Crystal structure of the DegP dodecamer with a modulator

Links to additional information on pepD:
- Mycobrowser
- PATRIC
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -0.448 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- BioCyc
- Systems Biology

Amino Acid Sequence

MAKLARVVGLVQEEQPSDMTNHPRYSPPPQQPGTPGYAQGQQQTYSQQFDWRYPPSPPPQPTQYRQPYEALGGTRPGLIPGVIPTMTPPPGMVRQRPRAG
MLAIGAVTIAVVSAGIGGAAASLVGFNRAPAGPSGGPVAASAAPSIPAANMPPGSVEQVAAKVVPSVVMLETDLGRQSEEGSGIILSAEGLILTNNHVIA
AAAKPPLGSPPPKTTVTFSDGRTAPFTVVGADPTSDIAVVRVQGVSGLTPISLGSSSDLRVGQPVLAIGSPLGLEGTVTTGIVSALNRPVSTTGEAGNQN
TVLDAIQTDAAINPGNSGGALVNMNAQLVGVNSAIATLGADSADAQSGSIGLGFAIPVDQAKRIADELISTGKASHASLGVQVTNDKDTLGAKIVEVVAG
GAAANAGVPKGVVVTKVDDRPINSADALVAAVRSKAPGATVALTFQDPSGGSRTVQVTLGKAEQ

(Nucleotide sequence available on KEGG)

Additional Information

HtrA2
(Mohamedmohaideen et al., 2008, Biochemistry) http://www.ncbi.nlm.nih.gov/pubmed/18479146

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
Uncertain	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.700650; 7 non-insertions in a row out of 19 sites
Uncertain	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.224800; 4 non-insertions in a row out of 19 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 19 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 19 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 4 non-insertions in a row out of 19 sites
No-Data	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Too-Short	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: -1
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

RNA processing and modification

Energy production and conversion

Chromatin structure and dynamics

Amino acid transport and metabolism

Cell cycle control, cell division, chromosome partitioning

Carbohydrate transport and metabolism

Nucleotide transport and metabolism

Lipid transport and metabolism

Coenzyme transport and metabolism

Transcription

Translation, ribosomal structure and biogenesis

Cell wall/membrane/envelope biogenesis

Replication, recombination and repair

Posttranslational modification, protein turnover, chaperones

Cell motility

Secondary metabolites biosynthesis, transport and catabolism

Inorganic ion transport and metabolism

Function unknown

General function prediction only

Intracellular trafficking, secretion, and vesicular transport

Signal transduction mechanisms

Extracellular structures

Defense mechanisms

Nuclear structure

Cytoskeleton

BioCyc Co-regulated genes based on gene expression profiling (Systems Biology, Inferelator Network)

Differentially expressed as result of RNASeq in glycerol environment (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

Conditionally essential as result of TNSeq (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

BioCyc Transcription factor binding based on ChIP-Seq (Systems Biology)

Binds To:
- No bindings to other targets were found.
Bound By:
- No bindings from other targets were found.

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0678 (-) (Direct binding)
- Rv1049 (-) (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:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Regulatory Rv0981	ahal4789	IMP		Affinity purification(physical interaction) H. He & TC. Zahrt Identification and characterization of a regulatory sequence recognized by Mycobacterium tuberculosis persistence regulator MprA. J. Bacteriol. 2005
Citation	PepD participates in the mycobacterial stress response mediated through MprAB and SigE. MJ. White, H. He et al. J. Bacteriol. 2010	ahal4789	IDA	20061478	Band shift
Interaction	Regulatory Rv0981	ahal4789	IDA		Band shift MJ. White, H. He et al. PepD participates in the mycobacterial stress response mediated through MprAB and SigE. J. Bacteriol. 2010
Citation	Identification and characterization of a regulatory sequence recognized by Mycobacterium tuberculosis persistence regulator MprA. H. He & TC. Zahrt J. Bacteriol. 2005	ahal4789	IDA	15601704	Band shift
Interaction	Regulatory Rv0981	ahal4789	IDA		Band shift H. He & TC. Zahrt Identification and characterization of a regulatory sequence recognized by Mycobacterium tuberculosis persistence regulator MprA. J. Bacteriol. 2005
Interaction	Regulatory Rv0981	ahal4789	IMP		Affinity purification(physical interaction) TC. Zahrt, C. Wozniak et al. Functional analysis of the Mycobacterium tuberculosis MprAB two-component signal transduction system. Infect. Immun. 2003
Interaction	Regulatory Rv0981	ahal4789	IMP		Affinity purification(physical interaction) 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 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
Interaction	RegulatedBy Rv0981	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

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