Rv2246 (kasB)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: 3-oxoacyl-[acyl-carrier-protein] synthase 2
- REFSEQ: 3-oxoacyl-(acyl carrier protein) synthase II
- PATRIC: 3-oxoacyl-[acyl-carrier-protein] synthase KASII (EC 2.3.1.41)
- TUBERCULIST: 3-oxoacyl-[acyl-carrier protein] synthase 2 KasB (beta-ketoacyl-ACP synthase) (KAS I)
- NCBI: 3-oxoacyl-[acyl-carrier protein] synthase 2 KasB (beta-ketoacyl-ACP synthase) (KAS I)
- updated information (H37Rv4):
  - gene name: kasB
  - function:
  - reference:
Type: Not Target
Start: 2519396
End: 2520712
Operon:

Trans-membrane region:
Role: I.H.1 - Synthesis of fatty and mycolic acids
GO terms:
- GO:0071768 - mycolic acid biosynthetic process (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0030497 - fatty acid elongation (Uniprot)
- GO:0016746 - transferase activity, transferring acyl groups (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0008152 - metabolic process (Uniprot)
- GO:0006633 - fatty acid biosynthetic process (Uniprot)
- GO:0006631 - fatty acid metabolic process (Uniprot)
- GO:0006629 - lipid metabolic process (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005737 - cytoplasm (Uniprot)
- GO:0005618 - cell wall (Uniprot)
- GO:0005515 - protein binding (Uniprot)
- GO:0004315 - 3-oxoacyl-[acyl-carrier-protein] synthase activity (Uniprot)
- GO:0003824 - catalytic activity (Uniprot)
- GO:0001666 - response to hypoxia (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: 2gp6
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
2GP6	99%	Mycobacterium tuberculosis	X-ray crystal structure of Mycobacterium tuberculosis beta-ketoacyl acyl carrier protein synthase II (mtKasB)
6P9M	66%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of Mycobacterium tuberculosis KasA in complex with O6J
6P9L	66%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of Mycobacterium tuberculosis KasA in complex with JFX
6P9K	66%	Mycobacterium tuberculosis	Crystal structure of Mycobacterium tuberculosis KasA in complex with O6G
5W2S	66%	Mycobacterium tuberculosis (strain ATCC 35801 / TMC 107 / Erdman)	Crystal Structure of Mycobacterium Tuberculosis KasA in complex with KMG
5W2Q	66%	Mycobacterium tuberculosis	Crystal structure of Mycobacterium tuberculosis KasA in complex with 6U5
5W2P	66%	Mycobacterium tuberculosis (strain ATCC 35801 / TMC 107 / Erdman)	Crystal structure of Mycobacterium tuberculosis KasA in complex with 6U5
5W2O	66%	Mycobacterium tuberculosis (strain ATCC 35801 / TMC 107 / Erdman)	Crystal structure of Mycobacterium tuberculosis KasA
4C6V	66%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of M. tuberculosis KasA in complex with TLM5 (Soak for 5 min)
4C6U	66%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of M. tuberculosis KasA in complex with TLM5

Links to additional information on kasB:
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -7.491 (from Jeremy Rock's lab)
- BioCyc
- Systems Biology

Amino Acid Sequence

VGVPPLAGASRTDMEGTFARPMTELVTGKAFPYVVVTGIAMTTALATDAETTWKLLLDRQSGIRTLDDPFVEEFDLPVRIGGHLLEEFDHQLTRIELRRM
GYLQRMSTVLSRRLWENAGSPEVDTNRLMVSIGTGLGSAEELVFSYDDMRARGMKAVSPLTVQKYMPNGAAAAVGLERHAKAGVMTPVSACASGAEAIAR
AWQQIVLGEADAAICGGVETRIEAVPIAGFAQMRIVMSTNNDDPAGACRPFDRDRDGFVFGEGGALLLIETEEHAKARGANILARIMGASITSDGFHMVA
PDPNGERAGHAITRAIQLAGLAPGDIDHVNAHATGTQVGDLAEGRAINNALGGNRPAVYAPKSALGHSVGAVGAVESILTVLALRDQVIPPTLNLVNLDP
EIDLDVVAGEPRPGNYRYAINNSFGFGGHNVAIAFGRY

(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)	1.36 (0.19)	0.73 (0.2)
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

Rv2246/kasB, gene len: 1316 bp, num TA sites: 19

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	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	growth defect	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, cofactors)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=-1.46)	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:

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0302 (-) (Direct binding)
- Rv0967 (csoR) (Direct binding)
- Rv1033c (trcR) (Upstream of operon)

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:

Property	Value	Creator	Evidence	PMID	Comment
Interaction	RegulatedBy Rv3911	yamir.moreno	IEP		Microarrays. mRNA levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using microarray (or macroarray) experiments.. S. Raman, X. Puyang et al. Mycobacterium tuberculosis SigM positively regulates Esx secreted protein and nonribosomal peptide synthetase genes and down regulates virulence-associated surface lipid synthesis. J. Bacteriol. 2006
Name	#NAME?	mjackson	IDA		FAS-II
Citation	Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. K. Takayama, C. Wang et al. Clin. Microbiol. Rev. 2005	jjmcfadden		15653820	Inferred from direct assay
Term	EC:2.1.1.- Transferases. Transferring one-carbon groups. Methyltransferases. - NR	jjmcfadden	NR		Inferred from direct assay K. Takayama, C. Wang et al. Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. Clin. Microbiol. Rev. 2005
Term	EC:2.3.1.41 Beta-ketoacyl-acyl-carrier-protein synthase I. - NR	jjmcfadden	NR		Inferred from direct assay K. Takayama, C. Wang et al. Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. Clin. Microbiol. Rev. 2005
Citation	Deletion of kasB in Mycobacterium tuberculosis causes loss of acid-fastness and subclinical latent tuberculosis in immunocompetent mice. A. Bhatt, N. Fujiwara et al. Proc. Natl. Acad. Sci. U.S.A. 2007	extern:JZUCKER		17360388	Reaction blocked in mutant
Term	EC:2.3.1.179 Beta-ketoacyl-acyl-carrier-protein synthase II. - NR	extern:JZUCKER	NR		Reaction blocked in mutant A. Bhatt, N. Fujiwara et al. Deletion of kasB in Mycobacterium tuberculosis causes loss of acid-fastness and subclinical latent tuberculosis in immunocompetent mice. Proc. Natl. Acad. Sci. U.S.A. 2007
Term	EC:2.3.1.41 Beta-ketoacyl-acyl-carrier-protein synthase I. - NR	extern:JZUCKER	NR		Reaction blocked in mutant A. Bhatt, N. Fujiwara et al. Deletion of kasB in Mycobacterium tuberculosis causes loss of acid-fastness and subclinical latent tuberculosis in immunocompetent mice. Proc. Natl. Acad. Sci. U.S.A. 2007

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