Rv2756c (hsdM)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: type I restriction enzyme M protein
- REFSEQ: type I restriction/modification system DNA methylase HsdM
- PATRIC: Type I restriction-modification system DNA-methyltransferase subunit M (EC 2.1.1.72)
- TUBERCULIST: Possible type I restriction/modification system DNA methylase HsdM (M protein) (DNA methyltransferase)
- NCBI: Possible type I restriction/modification system DNA methylase HsdM (M protein) (DNA methyltransferase)
- updated information (H37Rv4):
  - gene name: hsdM
  - function: DNA methylase
  - reference: Zhu (2016) PMID: 26704977; Chu (2021) PMID: 34943756
Type: Not Target
Start: 3068461
End: 3070083
Operon:

Trans-membrane region:
Role: II.A.5 - DNA replication, repair, recombination and restriction/modification
GO terms:
- GO:0032259 - methylation (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0008170 - N-methyltransferase activity (Uniprot)
- GO:0008168 - methyltransferase activity (Uniprot)
- GO:0006306 - DNA methylation (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005618 - cell wall (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):

PDB aa ident species PDB title

3KHK 45% Methanosarcina mazei Crystal structure of type-I restriction-modification system methylation subunit (MM_0429) from Methanosarchina mazei.
Links to additional information on hsdM:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.988 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

PDB	aa ident	species	PDB title
3KHK	45%	Methanosarcina mazei	Crystal structure of type-I restriction-modification system methylation subunit (MM_0429) from Methanosarchina mazei.

Amino Acid Sequence

MPPRKKQAPQAPSTMKELKDTLWKAADKLRGSLSASQYKDVILGLVFLKYVSDAYDERREAIRAELAAEGMEESQIEDLIDDPEQYQGYGVFVVPVSARW
KFLAENTKGKPAVGGEPAKNIGQLIDEAMDAVMKANPTLGGTLPRLYNKDNIDQRRLGELIDLFNSARFSRQGEHRARDLMGEVYEYFLGNFARAEGKRG
GEFFTPPSVVKVIVEVLEPSSGRVYDPCCGSGGMFVQTEKFIYEHDGDPKDVSIYGQESIEETWRMAKMNLAIHGIDNKGLGARWSDTFARDQHPDVQMD
YVMANLPFNIKDWARNEEDPRWRFGVPPANNANYAWIQHILYKLAPGGRAGVVMANGSMSSNSNGEGDIRAQIVEADLVSCMVALPTQLFRSTGIPVCLW
FFAKDKAAGKQGSIDRCGQVLFIDARELGDLVDRAERALTNEEIVRIGDTFHAWRGSKSAAVKGIMYEDVPGFCKSATLAEIKATDYALTPGRYVGTPAV
EDDGEPIDEKMARLSKALLEAFDESARLERVVREQLGRLR

(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
Uncertain	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.692850; 9 non-insertions in a row out of 37 sites
Uncertain	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.152150; 7 non-insertions in a row out of 37 sites
Uncertain	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.206450; 7 non-insertions in a row out of 37 sites
Uncertain	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.933500; 9 non-insertions in a row out of 37 sites
Uncertain	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.931600; 9 non-insertions in a row out of 37 sites
Non-Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Non-Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 0.39
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:
- Rv0023 (-)
- Rv2760c (vapB42)

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:
- Rv2760c (vapB42)
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Rv0023 (-)

Property	Value	Creator	Evidence	PMID	Comment
Citation	Specificity of restriction endonucleases and DNA modification methyltransferases a review (Edition 3). authors,C. Kessler,V. Manta Gene 1990	vizhi.gurusamy	ISA	2172084	Affinity purification (Physical interaction)
Interaction	PhysicalInteraction Rv2761c	vizhi.gurusamy	ISA		Affinity purification (Physical interaction) authors,C. Kessler,V. Manta Specificity of restriction endonucleases and DNA modification methyltransferases a review (Edition 3). Gene 1990
Citation	Biology of DNA restriction. authors,TA. Bickle,DH. Krger Microbiol. Rev. 1993	vizhi.gurusamy	ISA	8336674	Affinity purification (Physical interaction)
Interaction	PhysicalInteraction Rv2761c	vizhi.gurusamy	ISA		Affinity purification (Physical interaction) authors,TA. Bickle,DH. Krger Biology of DNA restriction. Microbiol. Rev. 1993
Citation	The DNA recognition subunit of the type IB restriction-modification enzyme EcoAI tolerates circular permutions of its polypeptide chain. authors,P. Janscak,TA. Bickle J. Mol. Biol. 1998	vizhi.gurusamy	ISA	9837717	Affinity purification (Physical interaction)
Interaction	PhysicalInteraction Rv2761c	vizhi.gurusamy	ISA		Affinity purification (Physical interaction) authors,P. Janscak,TA. Bickle The DNA recognition subunit of the type IB restriction-modification enzyme EcoAI tolerates circular permutions of its polypeptide chain. J. Mol. Biol. 1998

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