Rv3792 (aftA)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: arabinofuranosyltransferase AftA
- REFSEQ: transmembrane protein
- PATRIC: putative membrane protein
- TUBERCULIST: Arabinofuranosyltransferase AftA
- NCBI: Arabinofuranosyltransferase AftA
- updated information (H37Rv4):
  - gene name: aftA
  - function:
  - reference:
Type: Essential
Start: 4237932
End: 4239863
Operon:

Trans-membrane region:
Role: II.C.5 - Other membrane proteins
GO terms:
- GO:0071769 - mycolate cell wall layer assembly (Uniprot)
- GO:0071555 - cell wall organization (Uniprot)
- GO:0045227 - capsule polysaccharide biosynthetic process (Uniprot)
- GO:0044038 - cell wall macromolecule biosynthetic process (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0035250 - UDP-galactosyltransferase activity (Uniprot)
- GO:0016757 - transferase activity, transferring glycosyl groups (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0016021 - integral component of membrane (Uniprot)
- GO:0016020 - membrane (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005618 - cell wall (Uniprot)
- GO:0043022 - ribosome binding (FLUTE) (FLUTE Assigned!)
Reaction(s) (based on iSM810 metabolic model):
- ARAFDPP[c] + GALACTANDPP[c] <=> DPP[c] + ARA_91_1_93_GALACTANDPP[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:
Search for Homologs in PDB
Top 10 Homologs in PDB (as of Nov 2020): (none with >35% aa id)
Links to additional information on aftA:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -5.973 (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

MPSRRKSPQFGHEMGAFTSARAREVLVALGQLAAAVVVAVGVAVVSLLAIARVEWPAFPSSNQLHALTTVGQVGCLAGLVGIGWLWRHGRFRRLARLGGL
VLVSAFTVVTLGMPLGATKLYLFGISVDQQFRTEYLTRLTDTAALRDMTYIGLPPFYPPGWFWIGGRAAALTGTPAWEMFKPWAITSMAIAVAVALVLWW
RMIRFEYALLVTVATAAVMLAYSSPEPYAAMITVLLPPMLVLTWSGLGARDRQGWAAVVGAGVFLGFAATWYTLLVAYGAFTVVLMALLLAGSRLQSGIK
AAVDPLCRLAVVGAIAAAIGSTTWLPYLLRAARDPVSDTGSAQHYLPADGAALTFPMLQFSLLGAICLLGTLWLVMRARSSAPAGALAIGVLAVYLWSLL
SMLATLARTTLLSFRLQPTLSVLLVAAGAFGFVEAVQALGKRGRGVIPMAAAIGLAGAIAFSQDIPDVLRPDLTIAYTDTDGYGQRGDRRPPGSEKYYPA
IDAAIRRVTGKRRDRTVVLTADYSFLSYYPYWGFQGLTPHYANPLAQFDKRATQIDSWSGLSTADEFIAALDKLPWQPPTVFLMRHGAHNSYTLRLAQDV
YPNQPNVRRYTVDLRTALFADPRFVVEDIGPFVLAIRKPQESA

(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)	1.58 (0.26)	1.64 (0.62)
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

Rv3792/aftA, gene len: 1931 bp, num TA sites: 33

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=-1.03)	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=0.015)	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, vitamins)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=0.92)	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:
- Rv0023 (-)
- Rv3286c (sigF)

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

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

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:
- Rv0023 (-)

Property	Value	Creator	Evidence	PMID	Comment
Citation	Identification of a novel arabinofuranosyltransferase (AftA) involved in cell wall arabinan biosynthesis in Mycobacterium tuberculosis. LJ. Alderwick, M. Seidel et al. J. Biol. Chem. 2006	njamshidi	IDA	16595677	see PMID: 16595677 and cole et al text (Tuberculosis and the tubercle bacillus) for more details. Priming reaction for subsequent addition of arabinan
Term	TBRXN:AFTA arabinofuranosyl transferase (M tb) - IDA	njamshidi	IDA	16595677	see PMID: 16595677 and cole et al text (Tuberculosis and the tubercle bacillus) for more details. Priming reaction for subsequent addition of arabinan LJ. Alderwick, M. Seidel et al. Identification of a novel arabinofuranosyltransferase (AftA) involved in cell wall arabinan biosynthesis in Mycobacterium tuberculosis. J. Biol. Chem. 2006
Citation	Identification of a novel arabinofuranosyltransferase (AftA) involved in cell wall arabinan biosynthesis in Mycobacterium tuberculosis. LJ. Alderwick, M. Seidel et al. J. Biol. Chem. 2006	njamshidi	ISS	16595677	see PMID: 16595677 and cole et al text (Tuberculosis and the tubercle bacillus) for more details. Priming reaction for subsequent addition of arabinan
Term	TBRXN:AFTA arabinofuranosyl transferase (M tb) - ISS	njamshidi	ISS	16595677	see PMID: 16595677 and cole et al text (Tuberculosis and the tubercle bacillus) for more details. Priming reaction for subsequent addition of arabinan LJ. Alderwick, M. Seidel et al. Identification of a novel arabinofuranosyltransferase (AftA) involved in cell wall arabinan biosynthesis in Mycobacterium tuberculosis. J. Biol. Chem. 2006
Name	Decaprenol phosphoarabinose-dependent arabinosyltransferase that transfers the first arabinosyl residue to the galactan backbone	mjackson	IDA		Arabinosyltransferases
Symbol	aftC	mjackson	IMP		Arabinosyltransferases
Name	Decaprenol phosphoarabinose-dependent arabinosyltransferase which transfers an arabinosyl unit to the 3 position of an arabinosyl residue	mjackson	IMP		Arabinosyltransferases
Symbol	aftC	mjackson	IDA		Arabinosyltransferases
Name	Decaprenol phosphoarabinose-dependent arabinosyltransferase which transfers an arabinosyl unit to the 3 position of an arabinosyl residue	mjackson	IDA		Arabinosyltransferases
Symbol	aftA	mjackson	IMP		Arabinosyltransferases
Name	Decaprenol phosphoarabinose-dependent arabinosyltransferase that transfers the first arabinosyl residue to the galactan backbone	mjackson	IMP		Arabinosyltransferases
Symbol	aftA	mjackson	IDA		Arabinosyltransferases
Symbol	aftC	mmcneil			Decaprenol phosphoarabinose-dependent arabinosyltransferase which transferase an arabinosyl unit to the 3 position of an arabinosyl residue HL. Birch, LJ. Alderwick et al. Biosynthesis of mycobacterial arabinogalactan: identification of a novel alpha(1-->3) arabinofuranosyltransferase. Mol. Microbiol. 2008
Citation	Biosynthesis of mycobacterial arabinogalactan: identification of a novel alpha(1-->3) arabinofuranosyltransferase. HL. Birch, LJ. Alderwick et al. Mol. Microbiol. 2008	mmcneil		18627460	Decaprenol phosphoarabinose-dependent arabinosyltransferase which transferase an arabinosyl unit to the 3 position of an arabinosyl residue
Term	GO:0052636 arabinosyltransferase activity - NR	mmcneil	NR		Decaprenol phosphoarabinose-dependent arabinosyltransferase which transferase an arabinosyl unit to the 3 position of an arabinosyl residue HL. Birch, LJ. Alderwick et al. Biosynthesis of mycobacterial arabinogalactan: identification of a novel alpha(1-->3) arabinofuranosyltransferase. Mol. Microbiol. 2008
Symbol	afTA	mmcneil			Decaprenol phosphoarabinose-dependent arabinosyltransferase that transferase the first arabinosyl residue to the galactan backbone LJ. Alderwick, M. Seidel et al. Identification of a novel arabinofuranosyltransferase (AftA) involved in cell wall arabinan biosynthesis in Mycobacterium tuberculosis. J. Biol. Chem. 2006
Citation	Identification of a novel arabinofuranosyltransferase (AftA) involved in cell wall arabinan biosynthesis in Mycobacterium tuberculosis. LJ. Alderwick, M. Seidel et al. J. Biol. Chem. 2006	mmcneil		16595677	Decaprenol phosphoarabinose-dependent arabinosyltransferase that transferase the first arabinosyl residue to the galactan backbone
Term	GO:0052636 arabinosyltransferase activity - NR	mmcneil	NR		Decaprenol phosphoarabinose-dependent arabinosyltransferase that transferase the first arabinosyl residue to the galactan backbone LJ. Alderwick, M. Seidel et al. Identification of a novel arabinofuranosyltransferase (AftA) involved in cell wall arabinan biosynthesis in Mycobacterium tuberculosis. J. Biol. Chem. 2006
Citation	Roles of conserved proline and glycosyltransferase motifs of EmbC in biosynthesis of lipoarabinomannan. S. Berg, J. Starbuck et al. J. Biol. Chem. 2005	jjmcfadden		15546869	Inferred from direct assay
Term	EC:2.4.2.34 Indolylacetylinositol arabinosyltransferase. - NR	jjmcfadden	NR		Inferred from direct assay S. Berg, J. Starbuck et al. Roles of conserved proline and glycosyltransferase motifs of EmbC in biosynthesis of lipoarabinomannan. J. Biol. Chem. 2005
Citation	Roles of conserved proline and glycosyltransferase motifs of EmbC in biosynthesis of lipoarabinomannan. S. Berg, J. Starbuck et al. J. Biol. Chem. 2005	extern:JZUCKER		15546869	Inferred from direct assay
Term	EC:2.4.2.34 Indolylacetylinositol arabinosyltransferase. - NR	extern:JZUCKER	NR		Inferred from direct assay S. Berg, J. Starbuck et al. Roles of conserved proline and glycosyltransferase motifs of EmbC in biosynthesis of lipoarabinomannan. J. Biol. Chem. 2005

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