Rv2224c (caeA)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: hypothetical protein
- REFSEQ: exported protease
- PATRIC: Probable exported protease [EC:3.4.-.-]
- TUBERCULIST: Probable carboxylesterase CaeA
- NCBI: Probable carboxylesterase CaeA
- updated information (H37Rv4):
  - gene name: caeA
  - function: cell-wall-associated carboxylesterase; essential in vitro and required for virulence
  - reference: Lun and Bishai (2007) PMID 17428787
Type: Conditional
Start: 2495461
End: 2497023
Operon:

Trans-membrane region:
Role: II.C.2 - Surface polysaccharides, lipopolysaccharides, proteins and antigens
GO terms:
- GO:0052689 - carboxylic ester hydrolase activity (Uniprot)
- GO:0052572 - response to host immune response (Uniprot)
- GO:0043687 - post-translational protein modification (Uniprot)
- GO:0016787 - hydrolase activity (Uniprot)
- GO:0016020 - membrane (Uniprot)
- GO:0009405 - pathogenesis (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0005576 - extracellular region (Uniprot)
- GO:0016042 - lipid catabolic process (FLUTE) (FLUTE Assigned!)
- GO:0009252 - peptidoglycan biosynthetic process (FLUTE) (FLUTE Assigned!Y2 report, Kieser et al.)
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
5UNO	98%	Mycobacterium tuberculosis	Crystal Structure of Hip1 (Rv2224c)
5UGQ	98%	Mycobacterium tuberculosis	Crystal Structure of Hip1 (Rv2224c)
5UOH	98%	Mycobacterium tuberculosis	Crystal Structure of Hip1 (Rv2224c) T466A mutant

Links to additional information on caeA:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -1.336 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VGMRLSRRDKIARMLLIWAALAAVALVLVGCIRVVGGRARMAEPKLGQPVEWTPCRSSNPQVKIPGGALCGKLAVPVDYDRPDGDVAALALIRFPATGDK
IGSLVINPGGPGESGIEAALGVFQTLPKRVHERFDLVGFDPRGVASSRPAIWCNSDADNDRLRAEPQVDYSREGVAHIENETKQFVGRCVDKMGKNFLAH
VGTVNVAKDLDAIRAALGDDKLTYLGYSYGTRIGSAYAEEFPQRVRAMILDGAVDPNADPIEAELRQAKGFQDAFNNYAADCAKNAGCPLGADPAKAVEV
YHSLVDPLVDPDNPRISRPARTKDPRGLSYSDAIVGTIMALYSPNLWQHLTDGLSELVDNRGDTLLALADMYMRRDSHGRYNNSGDARVAINCVDQPPVT
DRDKVIDEDRRAREIAPFMSYGKFTGDAPLGTCAFWPVPPTSQPHAVSAPGLVPTVVVSTTHDPATPYKAGVDLANQLRGSLLTFDGTQHTVVFQGDSCI
DEYVTAYLIGGTTPPSGAKC

(Nucleotide sequence available on KEGG)

Additional Information

CaeA - cell-wall-associated carboxylesterase
Lun and Bishai (2007). JBC. http://www.ncbi.nlm.nih.gov/pubmed/17428787
essential in vitro, required for virulence in vivo

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: 0.898650; 10 non-insertions in a row out of 29 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 29 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 29 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 30 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 30 sites
Non-Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Non-Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 1.85
Growth-Advantage	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:
- Rv1049 (-) (Direct binding)
- Rv1990c (-) (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 Rv2223c	shahanup86	TAS		Operon (Functional linkage) AR. Flores, LM. Parsons et al. Characterization of novel Mycobacterium tuberculosis and Mycobacterium smegmatis mutants hypersusceptible to beta-lactam antibiotics. J. Bacteriol. 2005
Citation	Mycobacterium tuberculosis Rv2224c modulates innate immune responses. J. Rengarajan, E. Murphy et al. Proc. Natl. Acad. Sci. U.S.A. 2008	priti.priety	IPI	18172199	Affinity purification (Physical interaction)
Interaction	Degradation Rv0440	priti.priety	IPI		Affinity purification (Physical interaction) J. Rengarajan, E. Murphy et al. Mycobacterium tuberculosis Rv2224c modulates innate immune responses. Proc. Natl. Acad. Sci. U.S.A. 2008
Citation	Characterization of novel Mycobacterium tuberculosis and Mycobacterium smegmatis mutants hypersusceptible to beta-lactam antibiotics. AR. Flores, LM. Parsons et al. J. Bacteriol. 2005	priti.priety	IPI	15743935	Affinity purification (Physical interaction)
Interaction	Degradation Rv0440	priti.priety	IPI		Affinity purification (Physical interaction) AR. Flores, LM. Parsons et al. Characterization of novel Mycobacterium tuberculosis and Mycobacterium smegmatis mutants hypersusceptible to beta-lactam antibiotics. J. Bacteriol. 2005
Interaction	Regulatory Rv2223c	shahanup86	TAS		Operon (Functional linkage) J. Rengarajan, E. Murphy et al. Mycobacterium tuberculosis Rv2224c modulates innate immune responses. Proc. Natl. Acad. Sci. U.S.A. 2008
Interaction	Regulatory Rv2223c	shahanup86	TAS		Operon (Functional linkage) AR. Flores, LM. Parsons et al. Characterization of novel Mycobacterium tuberculosis and Mycobacterium smegmatis mutants hypersusceptible to beta-lactam antibiotics. J. Bacteriol. 2005
Citation	Mycobacterium tuberculosis Rv2224c modulates innate immune responses. J. Rengarajan, E. Murphy et al. Proc. Natl. Acad. Sci. U.S.A. 2008	shahanup86	TAS	18172199	Operon (Functional linkage)
Interaction	Regulatory Rv2223c	shahanup86	TAS		Operon (Functional linkage) J. Rengarajan, E. Murphy et al. Mycobacterium tuberculosis Rv2224c modulates innate immune responses. Proc. Natl. Acad. Sci. U.S.A. 2008
Citation	Characterization of novel Mycobacterium tuberculosis and Mycobacterium smegmatis mutants hypersusceptible to beta-lactam antibiotics. AR. Flores, LM. Parsons et al. J. Bacteriol. 2005	shahanup86	TAS	15743935	Operon (Functional linkage)

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