Rv1477 (ripA)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: invasion-associated protein
- REFSEQ: invasion protein
- PATRIC: NLP/P60 family protein
- TUBERCULIST: Peptidoglycan hydrolase
- NCBI: Peptidoglycan hydrolase
- updated information (H37Rv4):
  - gene name: ripA
  - function: activated by MarP during acid stress
  - reference: Botella et al. (2017) PMC5437814; Healy (2020) PMID: 32127458
Type: Not Target
Start: 1666990
End: 1668408
Operon:

Trans-membrane region:
Role: IV.A - Virulence
GO terms:
- GO:0071555 - cell wall organization (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0016787 - hydrolase activity (Uniprot)
- GO:0008745 - N-acetylmuramoyl-L-alanine amidase activity (Uniprot)
- GO:0008234 - cysteine-type peptidase activity (Uniprot)
- GO:0008233 - peptidase activity (Uniprot)
- GO:0006508 - proteolysis (Uniprot)
- GO:0005618 - cell wall (Uniprot)
- GO:0005576 - extracellular region (Uniprot)
- GO:0005515 - protein binding (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: 3s0q, 3ne0, 2xiv, 3pbc
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
6EWY	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	RipA Peptidoglycan hydrolase (Rv1477, Mycobacterium tuberculosis) N-terminal domain
3PBC	100%	Mycobacterium tuberculosis	Peptidase module of the peptidoglycan hydrolase RipA (Rv1477) from Mycobacterium tuberculosis at 1.38 resolution
2XIV	100%	MYCOBACTERIUM TUBERCULOSIS	Structure of Rv1477, hypothetical invasion protein of Mycobacterium tuberculosis
4Q4T	99%	Mycobacterium tuberculosis	Structure of the Resuscitation Promoting Factor Interacting protein RipA mutated at E444
4Q4N	99%	Mycobacterium tuberculosis	Structure of the Resuscitation Promoting Factor Interacting protein RipA mutated at H432
4Q4G	99%	Mycobacterium tuberculosis	Structure of the Resuscitation Promoting Factor Interacting protein RipA mutated at C383
3S0Q	99%	Mycobacterium tuberculosis	Peptidase module of the peptidoglycan hydrolase RipA (Rv1477) from Mycobacterium tuberculosis, catalytic site mutant (Cys383Ala) at 1.45 resolution
3NE0	98%	Mycobacterium tuberculosis	Structure and functional regulation of RipA, a mycobacterial enzyme essential for daughter cell separation
3I86	67%	Mycobacterium avium subsp. paratuberculosis	Crystal structure of the P60 Domain from M. avium subspecies paratuberculosis antigen MAP1204
3PBI	60%	Mycobacterium tuberculosis	Structure of the peptidoglycan hydrolase RipB (Rv1478) from Mycobacterium tuberculosis at 1.6 resolution

Links to additional information on ripA:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -5.701 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MRRNRRGSPARPAARFVRPAIPSALSVALLVCTPGLATADPQTDTIAALIADVAKANQRLQDLSDEVQAEQESVNKAMVDVETARDNAAAAEDDLEVSQR
AVKDANAAIAAAQHRFDTFAAATYMNGPSVSYLSASSPDEIIATVTAAKTLSASSQAVMANLQRARTERVNTESAARLAKQKADKAAADAKASQDAAVAA
LTETRRKFDEQREEVQRLAAERDAAQARLQAARLVAWSSEGGQGAPPFRMWDPGSGPAGGRAWDGLWDPTLPMIPSANIPGDPIAVVNQVLGISATSAQV
TANMGRKFLEQLGILQPTDTGITNAPAGSAQGRIPRVYGRQASEYVIRRGMSQIGVPYSWGGGNAAGPSKGIDSGAGTVGFDCSGLVLYSFAGVGIKLPH
YSGSQYNLGRKIPSSQMRRGDVIFYGPNGSQHVTIYLGNGQMLEAPDVGLKVRVAPVRTAGMTPYVVRYIEY

(Nucleotide sequence available on KEGG)

Additional Information

activated by MarP during acid stress:
Botella et al. (2017). Mycobacterium tuberculosis protease MarP activates a peptidoglycan hydrolase during acid stress. EMBO J. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437814/

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; 23 non-insertions in a row out of 24 sites
Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 1.000000; 23 non-insertions in a row out of 24 sites
Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 1.000000; 23 non-insertions in a row out of 24 sites
Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 1.000000; 23 non-insertions in a row out of 25 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 1.000000; 21 non-insertions in a row out of 25 sites
Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 0.06
Essential-Domain	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:
- Rv1033c (trcR) (Direct binding)
- Rv2034 (-) (Direct binding)
- Rv3246c (mtrA) (Direct binding)
- Rv3830c (-) (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:

Property	Value	Creator	Evidence	PMID	Comment
Interaction	PhysicalInteraction Rv2450c	singhpankaj2116	IMP		Co-expression (Functional linkage) BD. Kana, BG. Gordhan et al. The resuscitation-promoting factors of Mycobacterium tuberculosis are required for virulence and resuscitation from dormancy but are collectively dispensable for growth in vitro. Mol. Microbiol. 2008
Interaction	PhysicalInteraction Rv2450c	singhpankaj2116	IMP		Co-expression (Functional linkage) EC. Hett, MC. Chao et al. A partner for the resuscitation-promoting factors of Mycobacterium tuberculosis. Mol. Microbiol. 2007
Interaction	PhysicalInteraction Rv2450c	singhpankaj2116	IMP		Co-expression (Functional linkage) authors,GV. Mukamolova,AS. Kaprelyants,DI. Young,M. Young,DB. Kell A bacterial cytokine. Proc. Natl. Acad. Sci. U.S.A. 1998
Interaction	PhysicalInteraction Rv2450c	richasinha4u	IDA		Yeast two-hybrid (Physical interaction) KJ. Downing, JC. Betts et al. Global expression profiling of strains harbouring null mutations reveals that the five rpf-like genes of Mycobacterium tuberculosis show functional redundancy. Tuberculosis (Edinburgh, Scotland) 2004
Interaction	PhysicalInteraction Rv2450c	richasinha4u	IDA		Yeast two-hybrid (Physical interaction) BD. Kana, BG. Gordhan et al. The resuscitation-promoting factors of Mycobacterium tuberculosis are required for virulence and resuscitation from dormancy but are collectively dispensable for growth in vitro. Mol. Microbiol. 2008
Interaction	PhysicalInteraction Rv2450c	richasinha4u	IDA		Yeast two-hybrid (Physical interaction) authors,JM. Tufariello,WR. Jacobs,J. Chan Individual Mycobacterium tuberculosis resuscitation-promoting factor homologues are dispensable for growth in vitro and in vivo. Infect. Immun. 2004
Interaction	PhysicalInteraction Rv2450c	richasinha4u	IDA		Yeast two-hybrid (Physical interaction) EC. Hett, MC. Chao et al. A partner for the resuscitation-promoting factors of Mycobacterium tuberculosis. Mol. Microbiol. 2007
Citation	A partner for the resuscitation-promoting factors of Mycobacterium tuberculosis. EC. Hett, MC. Chao et al. Mol. Microbiol. 2007	vijayachitra	IPI	17919286	Yeast two-hybrid (Physical interaction)
Interaction	Activates Rv1009	vijayachitra	IPI		Yeast two-hybrid (Physical interaction) EC. Hett, MC. Chao et al. A partner for the resuscitation-promoting factors of Mycobacterium tuberculosis. Mol. Microbiol. 2007
Interaction	Activates Rv2450c	vijayachitra	IPI		Yeast two-hybrid (Physical interaction) EC. Hett, MC. Chao et al. A partner for the resuscitation-promoting factors of Mycobacterium tuberculosis. Mol. Microbiol. 2007
Interaction	PhysicalInteraction Rv1009	harsharohiratruefriend	IPI		yeast two hybrid EC. Hett, MC. Chao et al. A partner for the resuscitation-promoting factors of Mycobacterium tuberculosis. Mol. Microbiol. 2007
Interaction	PhysicalInteraction Rv1009	harsharohiratruefriend	IPI		yeast two hybrid BD. Kana, BG. Gordhan et al. The resuscitation-promoting factors of Mycobacterium tuberculosis are required for virulence and resuscitation from dormancy but are collectively dispensable for growth in vitro. Mol. Microbiol. 2008
Interaction	PhysicalInteraction Rv1009	harsharohiratruefriend	IPI		yeast two hybrid JM. Tufariello, K. Mi et al. Deletion of the Mycobacterium tuberculosis resuscitation-promoting factor Rv1009 gene results in delayed reactivation from chronic tuberculosis. Infect. Immun. 2006
Interaction	PhysicalInteraction Rv1009	harsharohiratruefriend	IPI		yeast two hybrid KJ. Downing, VV. Mischenko et al. Mutants of Mycobacterium tuberculosis lacking three of the five rpf-like genes are defective for growth in vivo and for resuscitation in vitro. Infect. Immun. 2005
Interaction	PhysicalInteraction Rv0867c	girishgene07	IPI		Affinity purification (Physical interaction) BD. Kana, BG. Gordhan et al. The resuscitation-promoting factors of Mycobacterium tuberculosis are required for virulence and resuscitation from dormancy but are collectively dispensable for growth in vitro. Mol. Microbiol. 2008
Interaction	PhysicalInteraction Rv0867c	girishgene07	IPI		Affinity purification (Physical interaction) EC. Hett, MC. Chao et al. A mycobacterial enzyme essential for cell division synergizes with resuscitation-promoting factor. PLoS Pathog. 2008
Interaction	PhysicalInteraction Rv0867c	girishgene07	IPI		Affinity purification (Physical interaction) S. Bardarov, S. Bardarov Jr et al. Specialized transduction: an efficient method for generating marked and unmarked targeted gene disruptions in Mycobacterium tuberculosis, M. bovis BCG and M. smegmatis. Microbiology (Reading, Engl.) 2002
Symbol	ripA	mjackson	IDA		Peptidoglycan turnover
Name	Peptidoglycan hydrolase (L,D-peptidase, NLP/P60 family member)	mjackson	IDA		Peptidoglycan turnover

TB Genome Annotation Portal