Rv1746 (pknF)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: serine/threonine-protein kinase pknF
- REFSEQ: anchored-membrane serine/threonine-protein kinase PKNF (protein kinase F) (STPK F)
- PATRIC: Probable serine/threonine-protein kinase pknF (EC 2.7.11.1)
- TUBERCULIST: Anchored-membrane serine/threonine-protein kinase PknF (protein kinase F) (STPK F)
- NCBI: Anchored-membrane serine/threonine-protein kinase PknF (protein kinase F) (STPK F)
- updated information (H37Rv4):
  - gene name: pknF
  - function:
  - reference:
Type: Not Target
Start: 1972138
End: 1973568
Operon:

Trans-membrane region:
Role: I.J.3 - Serine-Threonine protein kinases and phosphoprotein phosphatases
GO terms:
- GO:0051055 - negative regulation of lipid biosynthetic process (Uniprot)
- GO:0043086 - negative regulation of catalytic activity (Uniprot)
- GO:0043085 - positive regulation of catalytic activity (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0016310 - phosphorylation (Uniprot)
- GO:0016301 - kinase activity (Uniprot)
- GO:0016021 - integral component of membrane (Uniprot)
- GO:0016020 - membrane (Uniprot)
- GO:0010827 - regulation of glucose transmembrane transport (Uniprot)
- GO:0006468 - protein phosphorylation (Uniprot)
- GO:0005887 - integral component of plasma membrane (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0005524 - ATP binding (Uniprot)
- GO:0005515 - protein binding (Uniprot)
- GO:0004674 - protein serine/threonine kinase activity (Uniprot)
- GO:0004672 - protein kinase activity (Uniprot)
- GO:0001558 - regulation of cell growth (Uniprot)
- GO:0000921 - septin ring assembly (Uniprot)
- GO:0000166 - nucleotide 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
5XKA	50%	Mycobacterium tuberculosis	Crystal structure of M.tuberculosis PknI kinase domain
5M07	50%	Mycobacterium tuberculosis H37Rv	Crystal structure of Mycobacterium tuberculosis PknI kinase domain, C20A mutant
5M06	50%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of Mycobacterium tuberculosis PknI kinase domain
5M09	49%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of Mycobacterium tuberculosis PknI kinase domain, C20A_R136N double mutant
5M08	49%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of Mycobacterium tuberculosis PknI kinase domain, C20A_R136A double mutant
6B2P	41%	Mycobacterium tuberculosis	Dual Inhibition of the Essential Protein Kinases A and B in Mycobacterium tuberculosis
5U94	41%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of the Mycobacterium tuberculosis PASTA kinase PknB in complex with the potential theraputic kinase inhibitor GSK690693.
2FUM	41%	Mycobacterium tuberculosis H37Rv	Catalytic domain of protein kinase PknB from Mycobacterium tuberculosis in complex with mitoxantrone
1O6Y	41%	MYCOBACTERIUM TUBERCULOSIS	Catalytic domain of PknB kinase from Mycobacterium tuberculosis
6I2P	41%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of the Mycobacterium tuberculosis PknB kinase domain (L33E mutant) in complex with its substrate GarA

Links to additional information on pknF:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.034 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MPLAEGSTFAGFTIVRQLGSGGMGEVYLARHPRLPRQDALKVLRADVSADGEYRARFNREADAAASLWHPHIVAVHDRGEFDGQLWIDMDFVDGTDTVSL
LRDRYPNGMPGPEVTEIITAVAEALDYAHERRLLHRDVKPANILIANPDSPDRRIMLADFGIAGWVDDPSGLTATNMTVGTVSYAAPEQLMGNELDGRAD
QYALAATAFHLLTGSPPFQHANPAVVISQHLSASPPAIGDRVPELTPLDPVFAKALAKQPKDRYQRCVDFARALGHRLGGAGDPDDTRVSQPVAVAAPAK
RSLLRTAVIVPAVLAMLLVMAVAVAVREFQRADDERAAQPARTRTTTSAGTTTSVAPASTTRPAPTTPTTTGAADTATASPTAAVVAIGALCFPLGSTGT
TKTGATAYCSTLQGTNTTIWSLTEDTVASPTVTATADPTEAPLPIEQESPIRVCMQQTGQTRRECREEIRRSNGWP

(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; 1 non-insertions in a row out of 13 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 13 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 13 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 13 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 13 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: 0.45
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:
- Rv0967 (csoR) (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	Signaling Rv1747	aparna.vchalam	IPI		Yeast two-hybrid (Physical interaction) JM. Curry, R. Whalan et al. An ABC transporter containing a forkhead-associated domain interacts with a serine-threonine protein kinase and is required for growth of Mycobacterium tuberculosis in mice. Infect. Immun. 2005
Interaction	Signaling Rv1747	aparna.vchalam	IPI		Yeast two-hybrid (Physical interaction) V. Molle, D. Soulat et al. Two FHA domains on an ABC transporter, Rv1747, mediate its phosphorylation by PknF, a Ser/Thr protein kinase from Mycobacterium tuberculosis. FEMS Microbiol. Lett. 2004
Citation	Two FHA domains on an ABC transporter, Rv1747, mediate its phosphorylation by PknF, a Ser/Thr protein kinase from Mycobacterium tuberculosis. V. Molle, D. Soulat et al. FEMS Microbiol. Lett. 2004	aparna.vchalam	IPI	15135525	Yeast two-hybrid (Physical interaction)
Interaction	Signaling Rv1747	aparna.vchalam	IPI		Yeast two-hybrid (Physical interaction) V. Molle, D. Soulat et al. Two FHA domains on an ABC transporter, Rv1747, mediate its phosphorylation by PknF, a Ser/Thr protein kinase from Mycobacterium tuberculosis. FEMS Microbiol. Lett. 2004
Citation	Role of Mycobacterium tuberculosis Ser/Thr kinase PknF: implications in glucose transport and cell division. P. Deol, R. Vohra et al. J. Bacteriol. 2005	aparna.vchalam	IPI	15866927	Yeast two-hybrid (Physical interaction)
Interaction	Signaling Rv1747	aparna.vchalam	IPI		Yeast two-hybrid (Physical interaction) P. Deol, R. Vohra et al. Role of Mycobacterium tuberculosis Ser/Thr kinase PknF: implications in glucose transport and cell division. J. Bacteriol. 2005
Interaction	Signaling Rv1747	priyadarshinipriyanka2001	IPI		Yeast two-hybrid (Physical interaction) JM. Curry, R. Whalan et al. An ABC transporter containing a forkhead-associated domain interacts with a serine-threonine protein kinase and is required for growth of Mycobacterium tuberculosis in mice. Infect. Immun. 2005
Interaction	Signaling Rv1747	priyadarshinipriyanka2001	IPI		Yeast two-hybrid (Physical interaction) V. Molle, D. Soulat et al. Two FHA domains on an ABC transporter, Rv1747, mediate its phosphorylation by PknF, a Ser/Thr protein kinase from Mycobacterium tuberculosis. FEMS Microbiol. Lett. 2004
Citation	Two FHA domains on an ABC transporter, Rv1747, mediate its phosphorylation by PknF, a Ser/Thr protein kinase from Mycobacterium tuberculosis. V. Molle, D. Soulat et al. FEMS Microbiol. Lett. 2004	priyadarshinipriyanka2001	IPI	15135525	Yeast two-hybrid (Physical interaction)
Interaction	Signaling Rv1747	priyadarshinipriyanka2001	IPI		Yeast two-hybrid (Physical interaction) V. Molle, D. Soulat et al. Two FHA domains on an ABC transporter, Rv1747, mediate its phosphorylation by PknF, a Ser/Thr protein kinase from Mycobacterium tuberculosis. FEMS Microbiol. Lett. 2004
Citation	Role of Mycobacterium tuberculosis Ser/Thr kinase PknF: implications in glucose transport and cell division. P. Deol, R. Vohra et al. J. Bacteriol. 2005	priyadarshinipriyanka2001	IPI	15866927	Yeast two-hybrid (Physical interaction)
Interaction	Signaling Rv1747	priyadarshinipriyanka2001	IPI		Yeast two-hybrid (Physical interaction) P. Deol, R. Vohra et al. Role of Mycobacterium tuberculosis Ser/Thr kinase PknF: implications in glucose transport and cell division. J. Bacteriol. 2005
Interaction	Signaling Rv0020c	vmevada102	IEP		Affinity purification (Physical interaction) C. Grundner, LM. Gay et al. Mycobacterium tuberculosis serine/threonine kinases PknB, PknD, PknE, and PknF phosphorylate multiple FHA domains. Protein Sci. 2005
Name	TRANSMEMBRANE SERINE/THREONINE-PROTEIN KINASE, known to phosphorylate FabH, and InhA (not as well as PknA and PknB), KasA, KasB	mjackson	IDA		Regulatory proteins

TB Genome Annotation Portal