Rv0937c (mku)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: Ku protein
- REFSEQ: hypothetical protein
- PATRIC: Ku domain protein
- TUBERCULIST: DNA end-binding protein Mku
- NCBI: DNA end-binding protein, Mku
- updated information (H37Rv4):
  - gene name: mku
  - function:
  - reference:
Type: Not Target
Start: 1045199
End: 1046020
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0051351 - positive regulation of ligase activity (Uniprot)
- GO:0006974 - cellular response to DNA damage stimulus (Uniprot)
- GO:0006310 - DNA recombination (Uniprot)
- GO:0006303 - double-strand break repair via nonhomologous end joining (Uniprot)
- GO:0006281 - DNA repair (Uniprot)
- GO:0003690 - double-stranded DNA binding (Uniprot)
- GO:0003677 - DNA binding (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:
Search for Homologs in PDB
Top 10 Homologs in PDB (as of Nov 2020): (none with >35% aa id)
Links to additional information on mku:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -0.242 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MRAIWTGSIAFGLVNVPVKVYSATADHDIRFHQVHAKDNGRIRYKRVCEACGEVVDYRDLARAYESGDGQMVAITDDDIASLPEERSREIEVLEFVPAAD
VDPMMFDRSYFLEPDSKSSKSYVLLAKTLAETDRMAIVHFTLRNKTRLAALRVKDFGKREVMMVHTLLWPDEIRDPDFPVLDQKVEIKPAELKMAGQVVD
SMADDFNPDRYHDTYQEQLQELIDTKLEGGQAFTAEDQPRLLDEPEDVSDLLAKLEASVKARSKANSNVPTPP

(Nucleotide sequence available on KEGG)

Additional Information

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
Non-Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.016100; 5 non-insertions in a row out of 12 sites
Uncertain	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.039150; 5 non-insertions in a row out of 12 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 12 sites
Uncertain	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.284100; 4 non-insertions in a row out of 12 sites
Uncertain	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.870750; 6 non-insertions in a row out of 12 sites
No-Data	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Too-Short	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: -1
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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0022c (whiB5)
- Rv0818 (-)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv2250c (-) (Direct binding)
- Rv3574 (kstR) (Direct binding)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv0022c (whiB5)
- Rv0818 (-)
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Interaction	PhysicalInteraction Rv0938	aparna.vchalam	IDA		Yeast two-hybrid (Physical interaction) KM. Sinha, NC. Stephanou et al. Mycobacterial UvrD1 is a Ku-dependent DNA helicase that plays a role in multiple DNA repair events, including double-strand break repair. J. Biol. Chem. 2007
Interaction	PhysicalInteraction Rv0938	aparna.vchalam	IDA		Yeast two-hybrid (Physical interaction) authors,RS. Pitcher,LM. Tonkin,AJ. Green,AJ. Doherty Domain structure of a NHEJ DNA repair ligase from Mycobacterium tuberculosis. J. Mol. Biol. 2005
Interaction	PhysicalInteraction Rv0938	aparna.vchalam	IDA		Yeast two-hybrid (Physical interaction) authors,C. Gong,P. Bongiorno,A. Martins,NC. Stephanou,H. Zhu,S. Shuman,MS. Glickman Mechanism of nonhomologous end-joining in mycobacteria: a low-fidelity repair system driven by Ku, ligase D and ligase C. Nat. Struct. Mol. Biol. 2005
Citation	Mycobacterial UvrD1 is a Ku-dependent DNA helicase that plays a role in multiple DNA repair events, including double-strand break repair. KM. Sinha, NC. Stephanou et al. J. Biol. Chem. 2007	aparna.vchalam	IDA	17376770	Yeast two-hybrid (Physical interaction)
Interaction	PhysicalInteraction Rv0938	aparna.vchalam	IDA		Yeast two-hybrid (Physical interaction) KM. Sinha, NC. Stephanou et al. Mycobacterial UvrD1 is a Ku-dependent DNA helicase that plays a role in multiple DNA repair events, including double-strand break repair. J. Biol. Chem. 2007
Citation	Domain structure of a NHEJ DNA repair ligase from Mycobacterium tuberculosis. authors,RS. Pitcher,LM. Tonkin,AJ. Green,AJ. Doherty J. Mol. Biol. 2005	aparna.vchalam	IDA	16023671	Yeast two-hybrid (Physical interaction)
Interaction	PhysicalInteraction Rv0938	aparna.vchalam	IDA		Yeast two-hybrid (Physical interaction) authors,RS. Pitcher,LM. Tonkin,AJ. Green,AJ. Doherty Domain structure of a NHEJ DNA repair ligase from Mycobacterium tuberculosis. J. Mol. Biol. 2005
Citation	Mechanism of nonhomologous end-joining in mycobacteria: a low-fidelity repair system driven by Ku, ligase D and ligase C. authors,C. Gong,P. Bongiorno,A. Martins,NC. Stephanou,H. Zhu,S. Shuman,MS. Glickman Nat. Struct. Mol. Biol. 2005	aparna.vchalam	IDA	15778718	Yeast two-hybrid (Physical interaction)
Interaction	PhysicalInteraction Rv0938	aparna.vchalam	IDA		Yeast two-hybrid (Physical interaction) authors,C. Gong,P. Bongiorno,A. Martins,NC. Stephanou,H. Zhu,S. Shuman,MS. Glickman Mechanism of nonhomologous end-joining in mycobacteria: a low-fidelity repair system driven by Ku, ligase D and ligase C. Nat. Struct. Mol. Biol. 2005
Interaction	PhysicalInteraction Rv0938	aparna.vchalam	IDA		Yeast two-hybrid (Physical interaction) authors,D. Akey,A. Martins,J. Aniukwu,MS. Glickman,S. Shuman,JM. Berger Crystal structure and nonhomologous end-joining function of the ligase component of Mycobacterium DNA ligase D. J. Biol. Chem. 2006
Citation	Mycobacteriophage exploit NHEJ to facilitate genome circularization. authors,RS. Pitcher,LM. Tonkin,JM. Daley,PL. Palmbos,AJ. Green,TL. Velting,A. Brzostek,M. Korycka-Machala,S. Cresawn,J. Dziadek,GF. Hatfull,TE. Wilson,AJ. Doherty Mol. Cell 2006	aparna.vchalam	IDA	16949369	Yeast two-hybrid (Physical interaction)
Interaction	PhysicalInteraction Rv0938	aparna.vchalam	IDA		Yeast two-hybrid (Physical interaction) authors,RS. Pitcher,LM. Tonkin,JM. Daley,PL. Palmbos,AJ. Green,TL. Velting,A. Brzostek,M. Korycka-Machala,S. Cresawn,J. Dziadek,GF. Hatfull,TE. Wilson,AJ. Doherty Mycobacteriophage exploit NHEJ to facilitate genome circularization. Mol. Cell 2006
Symbol	ku	vmizrahi			LigD consists of a C-terminal ATP-dependent ligase domain fused to upstream polymerase and phosphoesterase modules. Catalyses DSB repair via non-homologous end-joining (NHEJ) with DNA ligase D (LigD)
Other	TBPWY:Non-homologous end-joining	vmizrahi			LigD consists of a C-terminal ATP-dependent ligase domain fused to upstream polymerase and phosphoesterase modules. Catalyses DSB repair via non-homologous end-joining (NHEJ) with DNA ligase D (LigD)

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