Rv2869c (rip)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: RIP metalloprotease RseP
- REFSEQ: transmembrane protein
- PATRIC: Intramembrane protease RasP/YluC implicated in cell division based on FtsL cleavage
- TUBERCULIST: Membrane bound metalloprotease
- NCBI: Membrane bound metalloprotease
- updated information (H37Rv4):
  - gene name: rip1
  - function: site-2-protease, cleaves anti-sigma factors (anti-sigD)
  - reference: Scheider (2014) PMID: 24816608
Type: Essential
Start: 3180548
End: 3181762
Operon:

Trans-membrane region:
Role: II.C.5 - Other membrane proteins
GO terms:
- GO:0046872 - metal ion binding (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0016787 - hydrolase activity (Uniprot)
- GO:0016021 - integral component of membrane (Uniprot)
- GO:0016020 - membrane (Uniprot)
- GO:0008237 - metallopeptidase activity (Uniprot)
- GO:0008233 - peptidase activity (Uniprot)
- GO:0006508 - proteolysis (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0004222 - metalloendopeptidase activity (Uniprot)
- GO:0043022 - ribosome binding (FLUTE) (FLUTE 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): (none with >35% aa id)
Links to additional information on rip:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -1.591 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Pubmed - Glickman 2013 paper
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MMFVTGIVLFALAILISVALHECGHMWVARRTGMKVRRYFVGFGPTLWSTRRGETEYGVKAVPLGGFCDIAGMTPVEELDPDERDRAMYKQATWKRVAVL
FAGPGMNLAICLVLIYAIALVWGLPNLHPPTRAVIGETGCVAQEVSQGKLEQCTGPGPAALAGIRSGDVVVKVGDTPVSSFDEMAAAVRKSHGSVPIVVE
RDGTAIVTYVDIESTQRWIPNGQGGELQPATVGAIGVGAARVGPVRYGVFSAMPATFAVTGDLTVEVGKALAALPTKVGALVRAIGGGQRDPQTPISVVG
ASIIGGDTVDHGLWVAFWFFLAQLNLILAAINLLPLLPFDGGHIAVAVFERIRNMVRSARGKVAAAPVNYLKLLPATYVVLVLVVGYMLLTVTADLVNPI
RLFQ

(Nucleotide sequence available on KEGG)

Additional Information

Rip1; S2P protease
site-2-protease, cleaves anti-sigma factors
Schneider JS, Reddy SP, E HY, Evans HW, Glickman MS. 2013. Site-2 protease substrate specificity and coupling in trans by a PDZ-substrate adapter protein. https://www.ncbi.nlm.nih.gov/pubmed/24218594
Sklar et al, 2010, Mol Micro. http://www.ncbi.nlm.nih.gov/pubmed/20545848

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
Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 1.000000; 20 non-insertions in a row out of 21 sites
Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 1.000000; 21 non-insertions in a row out of 21 sites
Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 1.000000; 21 non-insertions in a row out of 21 sites
Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 1.000000; 19 non-insertions in a row out of 22 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.999650; 13 non-insertions in a row out of 22 sites
Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 0.15
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.

data collected by: Sassetti lab (2014)
reference strain: Erdman
strains were grown in 7H10+glycerol with and without phenanthroline
RPKMs: Rv2869c-RNA-Seq-RPKMs.csv
DeSeq analysis: delta_Rv2869c_vs_Erdman_in_glycerol-deseq.csv (DEGs are those with padj<0.05)
DeSeq analysis: delta_Rv2869c_vs_Erdman_in_phenanthroline-deseq.csv (DEGs are those with padj<0.05)

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)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Inhibition Rv3912	sourish10	IPI		Affinity purification (Physical interaction) authors,JG. Sklar,H. Makinoshima,JS. Schneider,MS. Glickman M. tuberculosis intramembrane protease Rip1 controls transcription through three anti-sigma factor substrates. Mol. Microbiol. 2010
Interaction	Regulatory Rv1124	ashwinigbhat	IEP		Microarrary Analysis H. Makinoshima & MS. Glickman Regulation of Mycobacterium tuberculosis cell envelope composition and virulence by intramembrane proteolysis. Nature 2005

TB Genome Annotation Portal

Rv2869c (rip)

Amino Acid Sequence

Additional Information

Gene interactions based on ChIPSeq and Transcription Factor Over-Expression (TFOE) (Systems Biology)

Interactions based on ChIPSeq data

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

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

TBCAP

Comments