Rv2068c (blaC)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: beta-lactamase
- REFSEQ: class A BETA-lactamase BLAC
- PATRIC: Beta-lactamase class A
- TUBERCULIST: Class a beta-lactamase BlaC
- NCBI: Class a beta-lactamase BlaC
- updated information (H37Rv4):
  - gene name: blaC
  - function:
  - reference:
Type: Not Target
Start: 2325886
End: 2326809
Operon:

Trans-membrane region:
Role: IV.D - Antibiotic production and resistance
GO terms:
- GO:0046677 - response to antibiotic (Uniprot)
- GO:0042597 - periplasmic space (Uniprot)
- GO:0033251 - cephalosporinase activity (Uniprot)
- GO:0033250 - penicillinase activity (Uniprot)
- GO:0030655 - beta-lactam antibiotic catabolic process (Uniprot)
- GO:0016787 - hydrolase activity (Uniprot)
- GO:0016020 - membrane (Uniprot)
- GO:0008800 - beta-lactamase activity (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005576 - extracellular region (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: 3dwz, 3nck, 4ebl, 4ebn, 4ebp, 3ny4, 3n6i, 2gdn, 3ndg, 3n8l, 3nbl, 3nc8, 3vfh, 3cg5, 3vff, 3nde, 3n8r, 3n8s, 4df6, 3m6h, 3m6b, 3iqa, 3n7w
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
6H2K	100%	Mycobacterium tuberculosis	Structure of BlaC from Mycobacterium tuberculosis bound to the trans-enamine adduct of sulbactam.
6H2I	100%	Mycobacterium tuberculosis	Structure of BlaC from Mycobacterium tuberculosis bound to the trans-enamine adduct of tazobactam.
6H2H	100%	Mycobacterium tuberculosis	Structure of BlaC from Mycobacterium tuberculosis covalently bound to avibactam.
6H2G	100%	Mycobacterium tuberculosis	Structure of BlaC from Mycobacterium tuberculosis bound to the propionaldehyde ester adduct of clavulanic acid.
6H2C	100%	Mycobacterium tuberculosis	Structure of BlaC from Mycobacterium tuberculosis bound to the trans-enamine adduct derived from clavulanic acid.
6B6F	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Beta-Lactamase, mixed with Ceftriaxone, needles crystal form, 2sec
6B6E	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Beta-Lactamase, mixed with Ceftriaxone, needles crystal form, 500ms
6B6D	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Beta-Lactamase, mixed with Ceftriaxone, needles crystal form, 100ms
6B6C	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Beta-Lactamase, mixed with Ceftriaxone, needles crystal form, 30ms
6B6B	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Beta-Lactamase, unmixed needles crystal form

Links to additional information on blaC:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.726 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MRNRGFGRRELLVAMAMLVSVTGCARHASGARPASTTLPAGADLADRFAELERRYDARLGVYVPATGTTAAIEYRADERFAFCSTFKAPLVAAVLHQNPL
THLDKLITYTSDDIRSISPVAQQHVQTGMTIGQLCDAAIRYSDGTAANLLLADLGGPGGGTAAFTGYLRSLGDTVSRLDAEEPELNRDPPGDERDTTTPH
AIALVLQQLVLGNALPPDKRALLTDWMARNTTGAKRIRAGFPADWKVIDKTGTGDYGRANDIAVVWSPTGVPYVVAVMSDRAGGGYDAEPREALLAEAAT
CVAGVLA

(Nucleotide sequence available on KEGG)

Additional Information

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)	1.49 (0.36)	1.37 (0.52)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link

* example format for variants: "D27 (GAC): D27H (CAC,11)" means "Asp27 (native codon GAC) mutated to His (codon CAC) in 11 isolates"

ESSENTIALITY

MtbTnDB - interactive tool for exploring a database of published TnSeq datasets for Mtb

TnSeqCorr - genes with correlated TnSeq profiles across ~100 conditions

Rv2068c/blaC, gene len: 923 bp, num TA sites: 15

condition	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	non-essential	7H9	HMM	fully saturated, 14 TnSeq libraries combined
in-vitro	Sassetti 2003 Mol Micro	non-essential	7H9	TRASH	essential if hybridization ratio<0.2
in-vivo (mice)	Sassetti 2003 PNAS	non-essential	BL6 mice	TRASH	essential if hybridization ratio<0.4, min over 4 timepoints (1-8 weeks)
in-vitro (glycerol)	Griffin 2011 PPath	non-essential	M9 minimal+glycerol	Gumbel	2 replicates; Padj<0.05
in-vitro (cholesterol)	Griffin 2011 PPath	non-essential	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	NO (LFC=-0.09)	cholesterol vs glycerol	resampling-SR	YES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in cholesterol
in-vitro	Smith 2022 eLife	non-essential	7H9	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice)	Smith 2022 eLife	non-essential	BL6 mice	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice	Smith 2022 eLife	NO (LFC=-0.003)	in-vivo vs in-vitro	ZINB	YES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in mice
in-vitro (minimal)	Minato 2019 mSys	non-essential	minimal medium	HMM
in-vitro (YM rich medium)	Minato 2019 mSys	non-essential	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, vitamins)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=-0.51)	YM rich vs minimal medium	resampling

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:
- Rv1353c (-)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- 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:
- Rv1353c (-)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	PhysicalInteraction Rv2094c	ashwinigbhat	IDA		Spectrophotometric Analysis JA. McDonough, KE. Hacker et al. The twin-arginine translocation pathway of Mycobacterium smegmatis is functional and required for the export of mycobacterial beta-lactamases. J. Bacteriol. 2005
Interaction	PhysicalInteraction Rv2093c	ashwinigbhat	IDA		Spectrophotometric Analysis JA. McDonough, KE. Hacker et al. The twin-arginine translocation pathway of Mycobacterium smegmatis is functional and required for the export of mycobacterial beta-lactamases. J. Bacteriol. 2005
Interaction	PhysicalInteraction Rv2094c	priti.priety	IDA		Spectrophotometric Analysis JE. Posey, TM. Shinnick et al. Characterization of the twin-arginine translocase secretion system of Mycobacterium smegmatis. J. Bacteriol. 2006
Interaction	PhysicalInteraction Rv2094c	priti.priety	IDA		Spectrophotometric Analysis JA. McDonough, KE. Hacker et al. The twin-arginine translocation pathway of Mycobacterium smegmatis is functional and required for the export of mycobacterial beta-lactamases. J. Bacteriol. 2005
Interaction	PhysicalInteraction Rv2094c	ashwinigbhat	IDA		Spectrophotometric Analysis JE. Posey, TM. Shinnick et al. Characterization of the twin-arginine translocase secretion system of Mycobacterium smegmatis. J. Bacteriol. 2006
Interaction	PhysicalInteraction Rv2093c	priti.priety	IDA		Spectrophotometric Analysis JE. Posey, TM. Shinnick et al. Characterization of the twin-arginine translocase secretion system of Mycobacterium smegmatis. J. Bacteriol. 2006
Interaction	PhysicalInteraction Rv2093c	priti.priety	IDA		Spectrophotometric Analysis JA. McDonough, KE. Hacker et al. The twin-arginine translocation pathway of Mycobacterium smegmatis is functional and required for the export of mycobacterial beta-lactamases. J. Bacteriol. 2005
Interaction	PhysicalInteraction Rv2093c	ashwinigbhat	IDA		Spectrophotometric Analysis JE. Posey, TM. Shinnick et al. Characterization of the twin-arginine translocase secretion system of Mycobacterium smegmatis. J. Bacteriol. 2006
Interaction	PhysicalInteraction Rv1224	gaat3s	IDA		Spectrophotometric Analysis JA. McDonough, KE. Hacker et al. The twin-arginine translocation pathway of Mycobacterium smegmatis is functional and required for the export of mycobacterial beta-lactamases. J. Bacteriol. 2005
Interaction	PhysicalInteraction Rv1224	gaat3s	IDA		Spectrophotometric Analysis JE. Posey, TM. Shinnick et al. Characterization of the twin-arginine translocase secretion system of Mycobacterium smegmatis. J. Bacteriol. 2006
Interaction	PhysicalInteraction Rv1224	gaat3s	IDA		Spectrophotometric Analysis authors,BC. Berks,F. Sargent,T. Palmer The Tat protein export pathway. Mol. Microbiol. 2000
Interaction	PhysicalInteraction Rv0552	priyadarshinipriyanka2001	ISA		Spectrophotometric Analysis JA. McDonough, KE. Hacker et al. The twin-arginine translocation pathway of Mycobacterium smegmatis is functional and required for the export of mycobacterial beta-lactamases. J. Bacteriol. 2005
Name	Major beta-lactamase	mjackson	IMP		Beta-lactamases/esterases/peptidases
Name	Major beta-lactamase	mjackson	IDA		Beta-lactamases/esterases/peptidases
Symbol	BlaC	jlew			Contains a functional tat sequence. Test for functional tat sequences using a BlaC reporter. 13 identified. JA. McDonough, JR. McCann et al. Identification of functional Tat signal sequences in Mycobacterium tuberculosis proteins. J. Bacteriol. 2008
Citation	Identification of functional Tat signal sequences in Mycobacterium tuberculosis proteins. JA. McDonough, JR. McCann et al. J. Bacteriol. 2008	jlew		18658266	Contains a functional tat sequence. Test for functional tat sequences using a BlaC reporter. 13 identified.
Citation	The twin-arginine translocation pathway of Mycobacterium smegmatis is functional and required for the export of mycobacterial beta-lactamases. JA. McDonough, KE. Hacker et al. J. Bacteriol. 2005	jlew		16267291	MS needs tatA to export Mtb BlaC; BlaC(KK) mutant is not exported. We describe phenotypic analyses of tatA and tatC deletion mutants of M. smegmatis, which demonstrated that tatA and tatC encode components of a functional Tat system.

TB Genome Annotation Portal