Rv1326c (glgB)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: 14-alpha-glucan-branching enzyme
- REFSEQ: glycogen branching enzyme
- PATRIC: 14-alpha-glucan (glycogen) branching enzyme GH-13-type (EC 2.4.1.18)
- TUBERCULIST: 14-alpha-glucan branching enzyme GlgB (glycogen branching enzyme)
- NCBI: 1,4-alpha-glucan branching enzyme GlgB (glycogen branching enzyme)
- updated information (H37Rv4):
  - gene name: glgB
  - function:
  - reference:
Type: Not Target
Start: 1490117
End: 1492312
Operon:

Trans-membrane region:
Role: II.A.8 - Polysaccharides (cytoplasmic)
GO terms:
- GO:0102752 - 1,4-alpha-glucan branching enzyme activity (using a glucosylated glycogenin as primer for glycogen synthesis) (Uniprot)
- GO:0045227 - capsule polysaccharide biosynthetic process (Uniprot)
- GO:0043169 - cation binding (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0016757 - transferase activity, transferring glycosyl groups (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0009250 - glucan biosynthetic process (Uniprot)
- GO:0005978 - glycogen biosynthetic process (Uniprot)
- GO:0005977 - glycogen metabolic process (Uniprot)
- GO:0005975 - carbohydrate metabolic process (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005515 - protein binding (Uniprot)
- GO:0004553 - hydrolase activity, hydrolyzing O-glycosyl compounds (Uniprot)
- GO:0003844 - 1,4-alpha-glucan branching enzyme activity (Uniprot)
- GO:0003824 - catalytic activity (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- LINEAR-GLUCAN[c] -> GLYCOGEN[c]
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: 3k1d
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
3K1D	100%	Mycobacterium tuberculosis	Crystal structure of glycogen branching enzyme synonym: 1,4-alpha-D-glucan:1,4-alpha-D-GLUCAN 6-glucosyl-transferase from mycobacterium tuberculosis H37RV
6JOY	53%	Rhodothermus marinus	The X-ray Crystallographic Structure of Branching Enzyme from Rhodothermus obamensis STB05
5E70	51%	Escherichia coli O139:H28 (strain E24377A / ETEC)	Crystal structure of Ecoli Branching Enzyme with gamma cyclodextrin
5E6Z	51%	Escherichia coli O139:H28 (strain E24377A / ETEC)	Crystal structure of Ecoli Branching Enzyme with beta cyclodextrin
5E6Y	51%	Escherichia coli O139:H28 (strain E24377A / ETEC)	Crystal structure of E.Coli branching enzyme in complex with alpha cyclodextrin
4LQ1	51%	Escherichia coli	Crystal Structure of E.Coli Branching Enzyme in complex with maltohexaose
4LPC	51%	Escherichia coli	Crystal Structure of E.Coli Branching Enzyme in complex with maltoheptaose
1M7X	51%	Escherichia coli	The X-ray Crystallographic Structure of Branching Enzyme
6KLF	44%	Crocosphaera subtropica ATCC 51142	Crystal structure of branching enzyme D434A mutant from Cyanothece sp. ATCC 51142
5GR6	44%	Cyanothece sp. (strain ATCC 51142)	Crystal structure of branching enzyme Y500A/D501A double mutant from Cyanothece sp. ATCC 51142

Links to additional information on glgB:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -11.661 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology
- Photo of spot titer

Amino Acid Sequence

MSRSEKLTGEHLAPEPAEMARLVAGTHHNPHGILGAHEYDDHTVIRAFRPHAVEVVALVGKDRFSLQHLDSGLFAVALPFVDLIDYRLQVTYEGCEPHTV
ADAYRFLPTLGEVDLHLFAEGRHERLWEVLGAHPRSFTTADGVVSGVSFAVWAPNAKGVSLIGEFNGWNGHEAPMRVLGPSGVWELFWPDFPCDGLYKFR
VHGADGVVTDRADPFAFGTEVPPQTASRVTSSDYTWGDDDWMAGRALRNPVNEAMSTYEVHLGSWRPGLSYRQLARELTDYIVDQGFTHVELLPVAEHPF
AGSWGYQVTSYYAPTSRFGTPDDFRALVDALHQAGIGVIVDWVPAHFPKDAWALGRFDGTPLYEHSDPKRGEQLDWGTYVFDFGRPEVRNFLVANALYWL
QEFHIDGLRVDAVASMLYLDYSRPEGGWTPNVHGGRENLEAVQFLQEMNATAHKVAPGIVTIAEESTPWSGVTRPTNIGGLGFSMKWNMGWMHDTLDYVS
RDPVYRSYHHHEMTFSMLYAFSENYVLPLSHDEVVHGKGTLWGRMPGNNHVKAAGLRSLLAYQWAHPGKQLLFMGQEFGQRAEWSEQRGLDWFQLDENGF
SNGIQRLVRDINDIYRCHPALWSLDTTPEGYSWIDANDSANNVLSFMRYGSDGSVLACVFNFAGAEHRDYRLGLPRAGRWREVLNTDATIYHGSGIGNLG
GVDATDDPWHGRPASAVLVLPPTSALWLTPA

(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)	2.02 (0.38)	1.92 (0.87)
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

Rv1326c/glgB, gene len: 2195 bp, num TA sites: 43

condition	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	essential	7H9	HMM	fully saturated, 14 TnSeq libraries combined
in-vitro	Sassetti 2003 Mol Micro	essential	7H9	TRASH	essential if hybridization ratio<0.2
in-vivo (mice)	Sassetti 2003 PNAS	no data	BL6 mice	TRASH	essential if hybridization ratio<0.4, min over 4 timepoints (1-8 weeks)
in-vitro (glycerol)	Griffin 2011 PPath	essential	M9 minimal+glycerol	Gumbel	2 replicates; Padj<0.05
in-vitro (cholesterol)	Griffin 2011 PPath	essential	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	NO (LFC=0.0)	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	essential	7H9	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice)	Smith 2022 eLife	essential	BL6 mice	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice	Smith 2022 eLife	NO (LFC=0.0)	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	essential	minimal medium	HMM
in-vitro (YM rich medium)	Minato 2019 mSys	essential	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, cofactors)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=0.0)	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:
- Rv3286c (sigF)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0023 (-) (Direct binding)
- Rv0302 (-) (Upstream of operon)

Interactions based on TFOE data (Rustad et al. 2014)

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv3286c (sigF)
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Citation	Redox Biology of Mycobacterium tuberculosis H37Rv: protein-protein interaction between GlgB and WhiB1 involves exchange of thiol-disulfide. SK. Garg, MS. Alam et al. BMC Biochem. 2009	ahal4789	IPI	19121228	Yeast two-hybrid (Physical interaction)
Interaction	PhysicalInteraction Rv3219	ahal4789	IPI		Yeast two-hybrid (Physical interaction) SK. Garg, MS. Alam et al. Redox Biology of Mycobacterium tuberculosis H37Rv: protein-protein interaction between GlgB and WhiB1 involves exchange of thiol-disulfide. BMC Biochem. 2009
Citation	Redox Biology of Mycobacterium tuberculosis H37Rv: protein-protein interaction between GlgB and WhiB1 involves exchange of thiol-disulfide. SK. Garg, MS. Alam et al. BMC Biochem. 2009	sourish10	IPI	19121228	Yeast two-hybrid (Physical interaction)
Interaction	PhysicalInteraction Rv3219	sourish10	IPI		Yeast two-hybrid (Physical interaction) SK. Garg, MS. Alam et al. Redox Biology of Mycobacterium tuberculosis H37Rv: protein-protein interaction between GlgB and WhiB1 involves exchange of thiol-disulfide. BMC Biochem. 2009
Name	alpha-1,4-glucan branching enzyme	mjackson	IMP		Other (lipo)polysaccharides [Methylglucose lipolysaccharides, glycogen and capsular alpha-1,4 glucan]
Name	alpha-1,4-glucan branching enzyme	mjackson	IDA		Other (lipo)polysaccharides [Methylglucose lipolysaccharides, glycogen and capsular alpha-1,4 glucan]
Citation	Expression and characterization of alpha-(1,4)-glucan branching enzyme Rv1326c of Mycobacterium tuberculosis H37Rv. SK. Garg, MS. Alam et al. Protein Expr. Purif. 2007	mjackson		17005418	alpha-1,4-glucan branching enzyme (phenotypic [mycobacterial recombinant strains]; enzymatic)
Other	TBPWY:(MGLP and alpha-1,4 glucans)	mjackson			alpha-1,4-glucan branching enzyme (phenotypic [mycobacterial recombinant strains]; enzymatic) SK. Garg, MS. Alam et al. Expression and characterization of alpha-(1,4)-glucan branching enzyme Rv1326c of Mycobacterium tuberculosis H37Rv. Protein Expr. Purif. 2007
Citation	Capsular glucan and intracellular glycogen of Mycobacterium tuberculosis: biosynthesis and impact on the persistence in mice. T. Sambou, P. Dinadayala et al. Mol. Microbiol. 2008	mjackson		18808383	alpha-1,4-glucan branching enzyme (phenotypic [mycobacterial recombinant strains]; enzymatic)
Other	TBPWY:(MGLP and alpha-1,4 glucans)	mjackson			alpha-1,4-glucan branching enzyme (phenotypic [mycobacterial recombinant strains]; enzymatic) T. Sambou, P. Dinadayala et al. Capsular glucan and intracellular glycogen of Mycobacterium tuberculosis: biosynthesis and impact on the persistence in mice. Mol. Microbiol. 2008
Citation	Self-poisoning of Mycobacterium tuberculosis by targeting GlgE in an alpha-glucan pathway. R. Kalscheuer,K. Syson,U. Veeraraghavan,B. Weinrick,KE. Biermann,Z. Liu,JC. Sacchettini,G. Besra,S. Bornemann,WR. Jacobs Nature chemical biology 2010	mjackson		20305657	alpha-1,4-glucan branching enzyme (phenotypic [mycobacterial recombinant strains]; enzymatic)
Other	TBPWY:(MGLP and alpha-1,4 glucans)	mjackson			alpha-1,4-glucan branching enzyme (phenotypic [mycobacterial recombinant strains]; enzymatic) R. Kalscheuer,K. Syson,U. Veeraraghavan,B. Weinrick,KE. Biermann,Z. Liu,JC. Sacchettini,G. Besra,S. Bornemann,WR. Jacobs Self-poisoning of Mycobacterium tuberculosis by targeting GlgE in an alpha-glucan pathway. Nature chemical biology 2010

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