Rv1563c (treY)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: malto-oligosyltrehalose synthase
- REFSEQ: maltooligosyltrehalose synthase TreY
- PATRIC: Malto-oligosyltrehalose synthase (EC 5.4.99.15)
- TUBERCULIST: Maltooligosyltrehalose synthase TreY
- NCBI: Maltooligosyltrehalose synthase TreY
- updated information (H37Rv4):
  - gene name: treY
  - function:
  - reference:
Type: Not Target
Start: 1767135
End: 1769432
Operon:

Trans-membrane region:
Role: II.A.8 - Polysaccharides (cytoplasmic)
GO terms:
- GO:0047470 - (1,4)-alpha-D-glucan 1-alpha-D-glucosylmutase activity (Uniprot)
- GO:0030980 - alpha-glucan catabolic process (Uniprot)
- GO:0016853 - isomerase activity (Uniprot)
- GO:0005992 - trehalose biosynthetic process (Uniprot)
- GO:0005975 - carbohydrate metabolic process (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0003824 - catalytic activity (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- MALTODEXTRIN[c] -> MALTOOLIGOSYL-TREHALOSE[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):

PDB	aa ident	species	PDB title
3EDK	41%	Flavobacterium sp. 92	Structural base for cyclodextrin hydrolysis
3EDJ	41%	Flavobacterium sp. 92	Structural base for cyclodextrin hydrolysis
3EDF	41%	Flavobacterium sp. 92	Structural base for cyclodextrin hydrolysis
3EDE	41%	Flavobacterium sp. 92	Structural base for cyclodextrin hydrolysis
3EDD	41%	Flavobacterium sp. 92	Structural base for cyclodextrin hydrolysis
1H3G	41%	Flavobacterium sp. 92	Cyclomaltodextrinase from Flavobacterium sp. No. 92: from DNA sequence to protein structure
3UER	40%	Deinococcus geothermalis	Crystal structure of amylosucrase from Deinococcus geothermalis in complex with turanose
3UCQ	40%	Deinococcus geothermalis	Crystal structure of amylosucrase from Deinococcus geothermalis
2AAA	39%	Aspergillus niger	CALCIUM BINDING IN ALPHA-AMYLASES: AN X-RAY DIFFRACTION STUDY AT 2.1 ANGSTROMS RESOLUTION OF TWO ENZYMES FROM ASPERGILLUS
5OT1	37%	Thermococcus kodakarensis	The type III pullulan hydrolase from Thermococcus kodakarensis

Links to additional information on treY:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.598 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MAFPVISTYRVQMRGRSNGFGFTFADAENLLDYLDDLGVSHLYLSPILTAVGGSTHGYDVTDPTTVSPELGGSDGLARLSAAARSRGMGLIVDIVPSHVG
VGKPEQNAWWWDVLKFGRSSAYAEFFDIDWELGDGRIILPLLGSDSDVANLRVDGDLLRLGDLALPVAPGSGDGTGPAVHDRQHYRLVGWRHGLCGYRRF
FSITSLAGLRQEDRAVFDASHAEVARWFTEGLVDGVRVDHLDGLSDPSGYLAQLRELLGPNAWIVVEKILAVDEALEPTLPVDGSTGYDVLREIGGVLVD
PQGESPLTALVESAGVDYQEMPAMLADLKVHAAVHTLASELRRLRRCIAAAAGADHPLLPAAVAALLRHIGRYRCDYPGQAAVLPCALAETHSTTPQLAP
GLQLIAAAVARGGEPAVRLQQLCGAVSAKAVEDCMFYRDARLVSLNEVGGEPRRFGVGAAEFHHRAATRARLWPRSMTTLSTHDTKRGEDVRARIGVLSQ
VPWLWAKFIGHAQAIAPAPDAVTGQFLWQNVFGVWPVSGEVSAALRGRLHTYAEKAIREAAWHTSWHNPNRAFEDDVHGWLDLVLDGPLASELTGLVAHL
NSHAESDALAAKLLALTVPGVPDVYQGSELWDDSLVDPDNRRPVDYGTRRVALKALQHPKIRVLAAALRLRRTHPESFLGGAYHPVFAAGPAADHVVAFR
RGDDILVAVTRWTVRLQQTGWDHTVLPLPDGSWTDALTGFTASGHTPAVELFADLPVVLLVRDNA

(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)	2.07 (0.5)	1.82 (0.83)
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

Rv1563c/treY, gene len: 2297 bp, num TA sites: 36

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	no data	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	uncertain	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=0.25)	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=0.306)	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=0.68)	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:
- Rv1353c (-) (Direct binding)
- Rv2887 (-) (Upstream of operon)
- Rv3249c (-) (Upstream of operon)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv3416 (whiB3)
Downregulates:
- Does not downregulate other genes.
Downregulated by:

Property	Value	Creator	Evidence	PMID	Comment
Term	TBRXN:MOTS maltooligosyltrehalose synthase - IDA	njamshidi	IDA	10658666	PMID: 10658666 describes 3 pathways for tre synthesis in Mtb KA. De Smet, A. Weston et al. Three pathways for trehalose biosynthesis in mycobacteria. Microbiology (Reading, Engl.) 2000
Citation	Three pathways for trehalose biosynthesis in mycobacteria. KA. De Smet, A. Weston et al. Microbiology (Reading, Engl.) 2000	njamshidi	ISS	10658666	PMID: 10658666 describes 3 pathways for tre synthesis in Mtb
Term	TBRXN:MOTS maltooligosyltrehalose synthase - ISS	njamshidi	ISS	10658666	PMID: 10658666 describes 3 pathways for tre synthesis in Mtb KA. De Smet, A. Weston et al. Three pathways for trehalose biosynthesis in mycobacteria. Microbiology (Reading, Engl.) 2000
Citation	Three pathways for trehalose biosynthesis in mycobacteria. KA. De Smet, A. Weston et al. Microbiology (Reading, Engl.) 2000	njamshidi	IDA	10658666	PMID: 10658666 describes 3 pathways for tre synthesis in Mtb
Symbol	TreY	mjackson	ISS		Trehalose biosynthesis
Name	MALTOOLIGOSYLTREHALOSE SYNTHASE: INVOLVED IN TREHALOSE BIOSYNTHESIS FROM GLYCOGEN-LIKE ALPHA(1-->4)-LINKED GLUCOSE POLYMERS	mjackson	ISS		Trehalose biosynthesis
Symbol	TreY	mjackson	IMP		Trehalose biosynthesis
Name	MALTOOLIGOSYLTREHALOSE SYNTHASE: INVOLVED IN TREHALOSE BIOSYNTHESIS FROM GLYCOGEN-LIKE ALPHA(1-->4)-LINKED GLUCOSE POLYMERS	mjackson	IMP		Trehalose biosynthesis

TB Genome Annotation Portal