Rv0127 (mak)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: hypothetical protein
- REFSEQ: hypothetical protein
- PATRIC: Uncharacterized protein probably involved in trehalose biosynthesis [Carbohydrate transport and metabolism]
- TUBERCULIST: Maltokinase Mak
- NCBI: Maltokinase Mak
- updated information (H37Rv4):
  - gene name: mak
  - function:
  - reference: Fraga (2015) PMID: 25619172
Type: Essential
Start: 154232
End: 155599
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0046835 - carbohydrate phosphorylation (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0016310 - phosphorylation (Uniprot)
- GO:0016301 - kinase activity (Uniprot)
- GO:0005992 - trehalose 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:0005829 - cytosol (Uniprot)
- GO:0005524 - ATP binding (Uniprot)
- GO:0000166 - nucleotide binding (Uniprot)
- GO:0009252 - peptidoglycan biosynthetic process (FLUTE) (FLUTE Assigned!)
Reaction(s) (based on iSM810 metabolic model):
- ATP[c] + MLT[c] -> ADP[c] + MLT1P[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
4O7P	100%	Mycobacterium tuberculosis	Crystal structure of Mycobacterium tuberculosis maltose kinase MaK complexed with maltose
4O7O	100%	Mycobacterium tuberculosis	Crystal structure of Mycobacterium tuberculosis maltose kinase MaK
5JY7	65%	Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)	Complex of Mycobacterium smegmatis trehalose synthase with maltokinase
4WZY	59%	Mycobacterium vanbaalenii	Structure of mycobacterial maltokinase, the missing link in the essential GlgE-pathway (ATP complex)
4U98	59%	Mycobacterium vanbaalenii	Structure of mycobacterial maltokinase, the missing link in the essential GlgE-pathway (AppCp complex)
4U94	59%	Mycobacterium vanbaalenii	Structure of mycobacterial maltokinase, the missing link in the essential GlgE-pathway

Links to additional information on mak:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.279 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MTRSDTLATKLPWSDWLSRQRWYAGRNRELATVKPGVVVALRHNLDLVLVDVTYTDGATERYQVLVGWDFEPASEYGTKAAIGVADDRTGFDALYDVAGP
QFLLSLIVSSAVCGTSTGEVTFTREPDVELPFAAQPRVCDAEQSNTSVIFDRRAILKVFRRVSSGINPDIELNRVLTRAGNPHVARLLGAYQFGRPNRSP
TDALAYALGMVTEYEANAAEGWAMATASVRDLFAEGDLYAHEVGGDFAGESYRLGEAVASVHATLADSLGTAQATFPVDRMLARLSSTVAVVPELREYAP
TIEQQFQKLAAEAITVQRVHGDLHLGQVLRTPESWLLIDFEGEPGQPLDERRAPDSPLRDVAGVLRSFEYAAYGPLVDQATDKQLAARAREWVERNRAAF
CDGYAVASGIDPRDSALLLGAYELDKAVYETGYETRHRPGWLPIPLRSIARLTAS

(Nucleotide sequence available on KEGG)

Additional Information

pep2

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
Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.999850; 19 non-insertions in a row out of 30 sites
Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 1.000000; 18 non-insertions in a row out of 30 sites
Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 1.000000; 30 non-insertions in a row out of 30 sites
Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 1.000000; 29 non-insertions in a row out of 30 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 1.000000; 30 non-insertions in a row out of 30 sites
Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 0.2
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

RNA processing and modification

Energy production and conversion

Chromatin structure and dynamics

Amino acid transport and metabolism

Cell cycle control, cell division, chromosome partitioning

Carbohydrate transport and metabolism

Nucleotide transport and metabolism

Lipid transport and metabolism

Coenzyme transport and metabolism

Transcription

Translation, ribosomal structure and biogenesis

Cell wall/membrane/envelope biogenesis

Replication, recombination and repair

Posttranslational modification, protein turnover, chaperones

Cell motility

Secondary metabolites biosynthesis, transport and catabolism

Inorganic ion transport and metabolism

Function unknown

General function prediction only

Intracellular trafficking, secretion, and vesicular transport

Signal transduction mechanisms

Extracellular structures

Defense mechanisms

Nuclear structure

Cytoskeleton

BioCyc Co-regulated genes based on gene expression profiling (Systems Biology, Inferelator Network)

Differentially expressed as result of RNASeq in glycerol environment (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

Conditionally essential as result of TNSeq (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

BioCyc Transcription factor binding based on ChIP-Seq (Systems Biology)

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

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv1816 (-) (Direct binding)
- Rv2250c (-) (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:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Symbol	pep2	mjackson	IMP		Other (lipo)polysaccharides [Methylglucose lipolysaccharides, glycogen and capsular alpha-1,4 glucan]
Name	Maltokinase	mjackson	IMP		Other (lipo)polysaccharides [Methylglucose lipolysaccharides, glycogen and capsular alpha-1,4 glucan]
Symbol	pep2	mjackson	IDA		Other (lipo)polysaccharides [Methylglucose lipolysaccharides, glycogen and capsular alpha-1,4 glucan]
Name	Maltokinase	mjackson	IDA		Other (lipo)polysaccharides [Methylglucose lipolysaccharides, glycogen and capsular alpha-1,4 glucan]
Symbol	pep2	mjackson			Maltokinase (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
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	Maltokinase (phenotypic [mycobacterial recombinant strains]; enzymatic)
Other	TBPWY:(MGLP and alpha-1,4 glucans)	mjackson			Maltokinase (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
Symbol	pep2	mjackson			Maltokinase (phenotypic [mycobacterial recombinant strains]; enzymatic) authors,V. Mendes,A. Maranha,P. Lamosa,MS. da Costa,N. Empadinhas Biochemical characterization of the maltokinase from Mycobacterium bovis BCG. BMC Biochem. 2010
Citation	Biochemical characterization of the maltokinase from Mycobacterium bovis BCG. authors,V. Mendes,A. Maranha,P. Lamosa,MS. da Costa,N. Empadinhas BMC Biochem. 2010	mjackson		20507595	Maltokinase (phenotypic [mycobacterial recombinant strains]; enzymatic)
Other	TBPWY:(MGLP and alpha-1,4 glucans)	mjackson			Maltokinase (phenotypic [mycobacterial recombinant strains]; enzymatic) authors,V. Mendes,A. Maranha,P. Lamosa,MS. da Costa,N. Empadinhas Biochemical characterization of the maltokinase from Mycobacterium bovis BCG. BMC Biochem. 2010

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