Rv1092c (coaA)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: pantothenate kinase
- REFSEQ: pantothenate kinase
- PATRIC: Pantothenate kinase (EC 2.7.1.33)
- TUBERCULIST: Probable pantothenate kinase CoaA (pantothenic acid kinase)
- NCBI: Probable pantothenate kinase CoaA (pantothenic acid kinase)
- updated information (H37Rv4):
  - gene name: coaA/panK
  - function:
  - reference: Evans (2016) PMID: 27676316
Type: Not Target
Start: 1219248
End: 1220186
Operon:

Trans-membrane region:
Role: I.G.5 - Pantothenate
GO terms:
- GO:0040007 - growth (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0016310 - phosphorylation (Uniprot)
- GO:0016301 - kinase activity (Uniprot)
- GO:0015937 - coenzyme A biosynthetic process (Uniprot)
- GO:0008152 - metabolic process (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0005737 - cytoplasm (Uniprot)
- GO:0005524 - ATP binding (Uniprot)
- GO:0005515 - protein binding (Uniprot)
- GO:0004594 - pantothenate kinase activity (Uniprot)
- GO:0000166 - nucleotide binding (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- ATP[c] + PNTO[c] -> ADP[c] + 4PPNTO[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: 3avo, 3avq, 3avp, 3af1, 3af0, 3af3, 3af2, 3af4, 3aez, 2zs9, 2zs7, 4bfz, 4bfy, 4bfx, 4bfw, 4bfv, 4bfu, 4bft, 4bfs, 2zs8, 2ges, 2geu, 2get, 2gev, 2zsf, 2zsd, 2zse, 2zsb, 2zsa
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
4BFZ	100%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of Mycobacterium tuberculosis PanK in complex with a biaryl inhibitory compound (2b) and phosphate
4BFY	100%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of Mycobacterium tuberculosis PanK in complex with a biaryl inhibitory compound (2a) and phosphate
4BFX	100%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of Mycobacterium tuberculosis PanK in complex with a triazole inhibitory compound (1f) and phosphate
4BFW	100%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of Mycobacterium tuberculosis PanK in complex with a triazole inhibitory compound (1e) and phosphate
4BFV	100%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of Mycobacterium tuberculosis PanK in complex with a triazole inhibitory compound (1d) and phosphate
4BFU	100%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of Mycobacterium tuberculosis PanK in complex with a triazole inhibitory compound (1c) and phosphate
4BFT	100%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of Mycobacterium tuberculosis PanK in complex with a triazole inhibitory compound (1b) and phosphate
4BFS	100%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of Mycobacterium tuberculosis PanK in complex with a triazole inhibitory compound (1a)
3AVQ	100%	Mycobacterium tuberculosis	Pantothenate kinase from Mycobacterium tuberculosis (MtPanK) in complex with N9-Pan
3AVP	100%	Mycobacterium tuberculosis	Pantothenate kinase from Mycobacterium tuberculosis (MtPanK) in complex with Pantothenol

Links to additional information on coaA:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -2.786 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MSRLSEPSPYVEFDRRQWRALRMSTPLALTEEELVGLRGLGEQIDLLEVEEVYLPLARLIHLQVAARQRLFAATAEFLGEPQQNPDRPVPFIIGVAGSVA
VGKSTTARVLQALLARWDHHPRVDLVTTDGFLYPNAELQRRNLMHRKGFPESYNRRALMRFVTSVKSGSDYACAPVYSHLHYDIIPGAEQVVRHPDILIL
EGLNVLQTGPTLMVSDLFDFSLYVDARIEDIEQWYVSRFLAMRTTAFADPESHFHHYAAFSDSQAVVAAREIWRTINRPNLVENILPTRPRATLVLRKDA
DHSINRLRLRKL

(Nucleotide sequence available on KEGG)

Additional Information

CoaA/PanK

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)	1.87 (0.28)	1.27 (0.51)
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

Rv1092c/coaA, gene len: 938 bp, num TA sites: 20

condition	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	essential	7H9	HMM	fully saturated, 14 TnSeq libraries combined
in-vitro	Sassetti 2003 Mol Micro	essential	7H9	TRASH	essential if hybridization ratio<0.2
in-vivo (mice)	Sassetti 2003 PNAS	essential	BL6 mice	TRASH	essential if hybridization ratio<0.4, min over 4 timepoints (1-8 weeks)
in-vitro (glycerol)	Griffin 2011 PPath	essential	M9 minimal+glycerol	Gumbel	2 replicates; Padj<0.05
in-vitro (cholesterol)	Griffin 2011 PPath	essential	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	NO (LFC=0.83)	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	essential	7H9	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice)	Smith 2022 eLife	essential	BL6 mice	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice	Smith 2022 eLife	NO (LFC=0.036)	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	essential	minimal medium	HMM
in-vitro (YM rich medium)	Minato 2019 mSys	essential	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, cofactors)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=-1.78)	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:
- No bindings to other targets were found.

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:

Property	Value	Creator	Evidence	PMID	Comment
Interaction	RegulatedBy Rv3676	yamir.moreno	TAS		Literature previously reported link (from Balazsi et al. 2008). Traceable author statement to experimental support. G. Balzsi, AP. Heath et al. The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest. Mol. Syst. Biol. 2008
Interaction	RegulatedBy Rv3286c	yamir.moreno	TAS		Literature previously reported link (from Balazsi et al. 2008). Traceable author statement to experimental support. G. Balzsi, AP. Heath et al. The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest. Mol. Syst. Biol. 2008
Citation	Location and conformation of pantothenate and its derivatives in Mycobacterium tuberculosis pantothenate kinase: insights into enzyme action. authors,B. Chetnani,P. Kumar,KV. Abhinav,M. Chhibber,A. Surolia,M. Vijayan Acta Crystallogr. D Biol. Crystallogr. 2011	jevans		21904030	Determination of structural interactions between Mtb CoaA and pantothenate in binary and ternary complexes.
Citation	Essentiality and functional analysis of type I and type III pantothenate kinases of Mycobacterium tuberculosis. authors,D. Awasthy,A. Ambady,J. Bhat,G. Sheikh,S. Ravishankar,V. Subbulakshmi,K. Mukherjee,V. Sambandamurthy,UK. Sharma Microbiology (Reading, England) 2010	jevans		20576686	Can only be inactivated in the presence of another functional copy of the gene - essential pantothenate kinase in Mtb
Citation	Screening, Identification, and Characterization of Mechanistically Diverse Inhibitors of the Mycobacterium Tuberculosis Enzyme, Pantothenate Kinase (CoaA). authors,J. Venkatraman,J. Bhat,SM. Solapure,J. Sandesh,D. Sarkar,S. Aishwarya,K. Mukherjee,S. Datta,K. Malolanarasimhan,B. Bandodkar,KS. Das J Biomol Screen 2012	jevans		22086722	Inhibitors occupy overlapping positions with coenzyme A.
Citation	Invariance and variability in bacterial PanK: a study based on the crystal structure of Mycobacterium tuberculosis PanK. S. Das,P. Kumar,V. Bhor,A. Surolia,M. Vijayan Acta Crystallogr. D Biol. Crystallogr. 2006	jevans		16699190	Crystal structure of Mtb CoaA in complex with a CoA derivative.

TB Genome Annotation Portal