Rv1539 (lspA)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: lipoprotein signal peptidase
- REFSEQ: lipoprotein signal peptidase
- PATRIC: Lipoprotein signal peptidase (EC 3.4.23.36)
- TUBERCULIST: Probable lipoprotein signal peptidase LspA
- NCBI: Probable lipoprotein signal peptidase LspA
- updated information (H37Rv4):
  - gene name: lspA
  - function:
  - reference:
Type: Not Target
Start: 1742244
End: 1742852
Operon:

Trans-membrane region:
Role: III.D - Protein and peptide secretion
GO terms:
- GO:0040007 - growth (Uniprot)
- GO:0016787 - hydrolase activity (Uniprot)
- GO:0016021 - integral component of membrane (Uniprot)
- GO:0016020 - membrane (Uniprot)
- GO:0009405 - pathogenesis (Uniprot)
- GO:0008233 - peptidase activity (Uniprot)
- GO:0006508 - proteolysis (Uniprot)
- GO:0006497 - protein lipidation (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0004190 - aspartic-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:
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
6FMS	37%	Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)	IMISX-EP of Se-LspA
5DIR	37%	Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)	membrane protein at 2.8 Angstroms

Links to additional information on lspA:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -2.064 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VPDEPTGSADPLTSTEEAGGAGEPNAPAPPRRLRMLLSVAVVVLTLDIVTKVVAVQLLPPGQPVSIIGDTVTWTLVRNSGAAFSMATGYTWVLTLIATGV
VVGIFWMGRRLVSPWWALGLGMILGGAMGNLVDRFFRAPGPLRGHVVDFLSVGWWPVFNVADPSVVGGAILLVILSIFGFDFDTVGRRHADGDTVGRRKA
DG

(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
Uncertain	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.985550; 9 non-insertions in a row out of 9 sites
Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.993950; 8 non-insertions in a row out of 9 sites
Uncertain	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.986450; 7 non-insertions in a row out of 9 sites
Uncertain	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.975450; 7 non-insertions in a row out of 9 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.992650; 8 non-insertions in a row out of 9 sites
Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 0.13
Growth-Defect	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:
- Rv0967 (csoR) (Direct binding)
- Rv1353c (-) (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
Citation	Signal peptidases and signal peptide hydrolases. authors,IK. Dev,PH. Ray J. Bioenerg. Biomembr. 1990	shahanup86	IMP	2202720	None
Interaction	Regulatory Rv2873	shahanup86	IMP		authors,IK. Dev,PH. Ray Signal peptidases and signal peptide hydrolases. J. Bioenerg. Biomembr. 1990
Citation	Lipoprotein processing is required for virulence of Mycobacterium tuberculosis. P. Sander, M. Rezwan et al. Mol. Microbiol. 2004	shahanup86	IMP	15186407	None
Interaction	Regulatory Rv2873	shahanup86	IMP		P. Sander, M. Rezwan et al. Lipoprotein processing is required for virulence of Mycobacterium tuberculosis. Mol. Microbiol. 2004

TB Genome Annotation Portal