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

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
Non-Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 14 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 14 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 14 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 15 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 0 non-insertions in a row out of 15 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: 2.54
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.

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.

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