Rv2334 (cysK1)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: O-acetylserine sulfhydrylase
- REFSEQ: cysteine synthase A CysK1
- PATRIC: Cysteine synthase (EC 2.5.1.47)
- TUBERCULIST: Cysteine synthase a CysK1 (O-acetylserine sulfhydrylase A) (O-acetylserine (thiol)-lyase A) (CSASE A)
- NCBI: Cysteine synthase a CysK1 (O-acetylserine sulfhydrylase A) (O-acetylserine (thiol)-lyase A) (CSASE A)
- updated information (H37Rv4):
  - gene name: cysK1
  - function:
  - reference:
Type: Not Target
Start: 2608796
End: 2609728
Operon:

Trans-membrane region:
Role: I.D.3 - Serine family
GO terms:
- GO:0080146 - L-cysteine desulfhydrase activity (Uniprot)
- GO:0030170 - pyridoxal phosphate binding (Uniprot)
- GO:0019344 - cysteine biosynthetic process (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0008652 - cellular amino acid biosynthetic process (Uniprot)
- GO:0006535 - cysteine biosynthetic process from serine (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0005737 - cytoplasm (Uniprot)
- GO:0005576 - extracellular region (Uniprot)
- GO:0005515 - protein binding (Uniprot)
- GO:0004124 - cysteine synthase activity (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- H2S[c] + ASER[c] -> AC[c] + CYS[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: 2q3c, 2q3b, 2q3d
Search for Homologs in PDB

Top 10 Homologs in PDB (as of Nov 2020):

PDB	aa ident	species	PDB title
3ZEI	100%	MYCOBACTERIUM TUBERCULOSIS	Structure of the Mycobacterium tuberculosis O-Acetylserine Sulfhydrylase (OASS) CysK1 in complex with a small molecule inhibitor
2Q3D	100%	Mycobacterium tuberculosis	2.2 A Resolution Crystal Structure of O-Acetylserine Sulfhydrylase (OASS) From MYCOBACTERIUM TUBERCULOSIS in Complex with the Reaction Intermediate ALPHA-AMINOACRYLATE
2Q3C	100%	Mycobacterium tuberculosis	2.1 A Resolution Crystal Structure of O-Acetylserine Sulfhydrylase (OASS) Holoenzyme From MYCOBACTERIUM TUBERCULOSIS in Complex with the Inhibitory Peptide DFSI
2Q3B	100%	Mycobacterium tuberculosis	1.8 A Resolution Crystal Structure of O-Acetylserine Sulfhydrylase (OASS) Holoenzyme From MYCOBACTERIUM TUBERCULOSIS
3RR2	85%	Mycobacterium marinum	Structure of a Cysteine synthase (O-Acetylserine Sulfhydrylase (OASS)) from Mycobacterium marinum ATCC BAA-535 / M
4I1Y	84%	Mycobacterium ulcerans	The structure of Cysteine synthase from Mycobacterium ulcerans Agy99
4LMB	66%	Microcystis aeruginosa	Crystal structure analysis of O-acetylserine sulfhydrylase CysK2 complexed with cystine from Microcystis aeruginosa 7806
4LMA	63%	Microcystis aeruginosa	Crystal structure analysis of O-acetylserine sulfhydrylase CysK1 from Microcystis aeruginosa 7806
5XOQ	62%	Planctopirus limnophila (strain ATCC 43296 / DSM 3776 / IFAM 1008 / 290)	Crystal structure of O-Acetylserine Sulfhydrylase with bound Transcription Factor peptide inhibitor from Planctomyces limnophilus
5XA2	62%	Planctopirus limnophila (strain ATCC 43296 / DSM 3776 / IFAM 1008 / 290)	Crystal Structure of O-acetylserine sulfhydrylase from Planctomyces Limnophila

Links to additional information on cysK1:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -1.151 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MSIAEDITQLIGRTPLVRLRRVTDGAVADIVAKLEFFNPANSVKDRIGVAMLQAAEQAGLIKPDTIILEPTSGNTGIALAMVCAARGYRCVLTMPETMSL
ERRMLLRAYGAELILTPGADGMSGAIAKAEELAKTDQRYFVPQQFENPANPAIHRVTTAEEVWRDTDGKVDIVVAGVGTGGTITGVAQVIKERKPSARFV
AVEPAASPVLSGGQKGPHPIQGIGAGFVPPVLDQDLVDEIITVGNEDALNVARRLAREEGLLVGISSGAATVAALQVARRPENAGKLIVVVLPDFGERYL
STPLFADVAD

(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: 0.000000; 5 non-insertions in a row out of 14 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 14 sites
Uncertain	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.990650; 8 non-insertions in a row out of 14 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 5 non-insertions in a row out of 15 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 15 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: 0.6
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:
- Rv1353c (-) (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
Interaction	Inhibits Rv2335	akankshajain.21	IDA		Spectrophotometric Assay D. Gren, R. Schnell et al. The C-terminal of CysM from Mycobacterium tuberculosis protects the aminoacrylate intermediate and is involved in sulfur donor selectivity. FEBS Lett. 2008
Citation	Structural insights into catalysis and inhibition of O-acetylserine sulfhydrylase from Mycobacterium tuberculosis. Crystal structures of the enzyme alpha-aminoacrylate intermediate and an enzyme-inhibitor complex. R. Schnell, W. Oehlmann et al. J. Biol. Chem. 2007	akankshajain.21	IDA	17567578	Structural Analysis
Interaction	Inhibits Rv2335	akankshajain.21	IDA		Structural Analysis R. Schnell, W. Oehlmann et al. Structural insights into catalysis and inhibition of O-acetylserine sulfhydrylase from Mycobacterium tuberculosis. Crystal structures of the enzyme alpha-aminoacrylate intermediate and an enzyme-inhibitor complex. J. Biol. Chem. 2007
Citation	The C-terminal of CysM from Mycobacterium tuberculosis protects the aminoacrylate intermediate and is involved in sulfur donor selectivity. D. Gren, R. Schnell et al. FEBS Lett. 2008	akankshajain.21	IDA	19101553	Structural Analysis
Interaction	Inhibits Rv2335	akankshajain.21	IDA		Structural Analysis D. Gren, R. Schnell et al. The C-terminal of CysM from Mycobacterium tuberculosis protects the aminoacrylate intermediate and is involved in sulfur donor selectivity. FEBS Lett. 2008
Interaction	Inhibits Rv2335	akankshajain.21	IMP		Functional Linkage(Coexpression) D. Gren, R. Schnell et al. The C-terminal of CysM from Mycobacterium tuberculosis protects the aminoacrylate intermediate and is involved in sulfur donor selectivity. FEBS Lett. 2008
Citation	Structural insights into catalysis and inhibition of O-acetylserine sulfhydrylase from Mycobacterium tuberculosis. Crystal structures of the enzyme alpha-aminoacrylate intermediate and an enzyme-inhibitor complex. R. Schnell, W. Oehlmann et al. J. Biol. Chem. 2007	akankshajain.21	IDA	17567578	Spectrophotometric Assay
Interaction	Inhibits Rv2335	akankshajain.21	IDA		Spectrophotometric Assay R. Schnell, W. Oehlmann et al. Structural insights into catalysis and inhibition of O-acetylserine sulfhydrylase from Mycobacterium tuberculosis. Crystal structures of the enzyme alpha-aminoacrylate intermediate and an enzyme-inhibitor complex. J. Biol. Chem. 2007
Citation	The C-terminal of CysM from Mycobacterium tuberculosis protects the aminoacrylate intermediate and is involved in sulfur donor selectivity. D. Gren, R. Schnell et al. FEBS Lett. 2008	akankshajain.21	IDA	19101553	Spectrophotometric Assay

TB Genome Annotation Portal