TB Genome Annotation Portal

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

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/

Analysis of Positive Selection in Clinical Isolates *new*

• Analysis of dN/dS (omega) in two collections of Mtb clinical isolates using GenomegaMap (Window model) (see description of methods)
  • Moldova: 2,057 clinical isolates
  • global set: 5,195 clinical isolates from 15 other countries
• In the omega plots, the black line shows the mean estimate of omega (dN/dS) at each codon, and the blue lines are the bounds for the 95% credible interval (95%CI, from MCMC sampling).
• A gene is under significant positive selection if the lower-bound of the 95%CI of omega (lower blue line) exceeds 1.0 at any codon.

	Moldova (2,057)	global set (5,195)
under significant positive selection?	NO	NO
omega peak height (95%CI lower bound)	1.76 (0.36)	0.89 (0.38)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link