Rv2914c (pknI)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: serine/threonine protein kinase
- REFSEQ: transmembrane serine/threonine-protein kinase I
- PATRIC: Transmembrane serine/threonine-protein kinase I PknI (EC 2.7.11.1)
- TUBERCULIST: Probable transmembrane serine/threonine-protein kinase I PknI (protein kinase I) (STPK I) (phosphorylase B kinase kinase) (hydroxyalkyl-protein kinase)
- NCBI: Probable transmembrane serine/threonine-protein kinase I PknI (protein kinase I) (STPK I) (phosphorylase B kinase kinase) (hydroxyalkyl-protein kinase)
- updated information (H37Rv4):
  - gene name: pknI
  - function:
  - reference:
Type: Not Target
Start: 3221767
End: 3223524
Operon:

Trans-membrane region:
Role: I.J.3 - Serine-Threonine protein kinases and phosphoprotein phosphatases
GO terms:
- GO:0046777 - protein autophosphorylation (Uniprot)
- GO:0040009 - regulation of growth rate (Uniprot)
- GO:0030145 - manganese ion binding (Uniprot)
- GO:0018107 - peptidyl-threonine phosphorylation (Uniprot)
- GO:0018105 - peptidyl-serine phosphorylation (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:0009405 - pathogenesis (Uniprot)
- GO:0006468 - protein phosphorylation (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0005737 - cytoplasm (Uniprot)
- GO:0005524 - ATP binding (Uniprot)
- GO:0004674 - protein serine/threonine kinase activity (Uniprot)
- GO:0004672 - protein kinase activity (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
5XLM	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Monomer form of M.tuberculosis PknI sensor domain
5XLL	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Dimer form of M. tuberculosis PknI sensor domain
5XKA	100%	Mycobacterium tuberculosis	Crystal structure of M.tuberculosis PknI kinase domain
5M06	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of Mycobacterium tuberculosis PknI kinase domain
5M07	99%	Mycobacterium tuberculosis H37Rv	Crystal structure of Mycobacterium tuberculosis PknI kinase domain, C20A mutant
5M09	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of Mycobacterium tuberculosis PknI kinase domain, C20A_R136N double mutant
5M08	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of Mycobacterium tuberculosis PknI kinase domain, C20A_R136A double mutant

Links to additional information on pknI:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.214 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MALASGVTFAGYTVVRMLGCSAMGEVYLVQHPGFPGWQALKVLSPAMAADDEFRRRFQRETEVAARLFHPHILEVHDRGEFDGQLWIAMDYVDGIDATQH
MADRFPAVLPVGEVLAIVTAVAGALDYAHQRGLLHRDVNPANVVLTSQSAGDQRILLADFGIASQPSYPAPELSAGADVDGRADQYALALTAIHLFAGAP
PVDRSHTGPLQPPKLSAFRPDLARLDGVLSRALATAPADRFGSCREFADAMNEQAGVAIADQSSGGVDASEVTAAAGEEAYVVDYPAYGWPEAVDCKEPS
ARAPAPAAPTPQRRGSMLQSAAGVLARRLDNFSTATKAPASPTRRRPRRILVGAVAVLLLAGLFAVGIVIGRKTNTTATEVARPPTSGSAVPSAPTTTVA
VTAPVPLDGTYRIEIQRSKQTYDYTPTPQPPDVNTWWAFRTSCTPTECLAAATMLDDNDHTQAKTPPVRPFLMQFGEGQWKSRPETVQFPCVGPNGSPST
QATTQLLALRPQPQGDLVGEMVVTVHSNECGQQGAVIRIPAVASRSGDLPPAVTVPDPATIPDTPDTTSTATLTPPTTTAPGPGR

(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: 0.000400; 7 non-insertions in a row out of 27 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000050; 6 non-insertions in a row out of 27 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000100; 6 non-insertions in a row out of 27 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 27 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 27 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: 0.7
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:

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv3133c (devR) (Direct binding)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv0818 (-)
- Rv3416 (whiB3)
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Rv1219c (-)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Signaling Rv2916c	priti.priety	IDA		Affinity purification (Physical interaction) A. Singh, Y. Singh et al. Protein kinase I of Mycobacterium tuberculosis: cellular localization and expression during infection of macrophage-like cells. Tuberculosis (Edinburgh, Scotland) 2006
Citation	Cloning, overexpression, and characterization of a serine/threonine protein kinase pknI from Mycobacterium tuberculosis H37Rv. R. Gopalaswamy, PR. Narayanan et al. Protein Expr. Purif. 2004	priti.priety	IDA	15177288	Affinity purification (Physical interaction)
Interaction	Signaling Rv2913c	priti.priety	IDA		Affinity purification (Physical interaction) R. Gopalaswamy, PR. Narayanan et al. Cloning, overexpression, and characterization of a serine/threonine protein kinase pknI from Mycobacterium tuberculosis H37Rv. Protein Expr. Purif. 2004
Interaction	Signaling Rv2916c	priti.priety	IDA		Affinity purification (Physical interaction) R. Gopalaswamy, PR. Narayanan et al. Cloning, overexpression, and characterization of a serine/threonine protein kinase pknI from Mycobacterium tuberculosis H37Rv. Protein Expr. Purif. 2004
Citation	The serine/threonine protein kinase PknI controls the growth of Mycobacterium tuberculosis upon infection. R. Gopalaswamy, S. Narayanan et al. FEMS Microbiol. Lett. 2009	priti.priety	IDA	19341393	Affinity purification (Physical interaction)
Interaction	Signaling Rv2913c	priti.priety	IDA		Affinity purification (Physical interaction) R. Gopalaswamy, S. Narayanan et al. The serine/threonine protein kinase PknI controls the growth of Mycobacterium tuberculosis upon infection. FEMS Microbiol. Lett. 2009
Interaction	Signaling Rv2916c	priti.priety	IDA		Affinity purification (Physical interaction) R. Gopalaswamy, S. Narayanan et al. The serine/threonine protein kinase PknI controls the growth of Mycobacterium tuberculosis upon infection. FEMS Microbiol. Lett. 2009
Citation	Protein kinase I of Mycobacterium tuberculosis: cellular localization and expression during infection of macrophage-like cells. A. Singh, Y. Singh et al. Tuberculosis (Edinburgh, Scotland) 2006	priti.priety	IDA	16256441	Affinity purification (Physical interaction)
Interaction	Signaling Rv2913c	priti.priety	IDA		Affinity purification (Physical interaction) A. Singh, Y. Singh et al. Protein kinase I of Mycobacterium tuberculosis: cellular localization and expression during infection of macrophage-like cells. Tuberculosis (Edinburgh, Scotland) 2006
Interaction	Operon Rv2913c	ashwinigbhat	NAS		Co-expression (Functional linkage) authors,A. Zelikovski,J. Abu-Dalu,I. Urca Meso-appendicular testis. Br J Urol 1975
Interaction	Operon Rv2913c	ashwinigbhat	NAS		Co-expression (Functional linkage) Y. Av-Gay,M. Everett The eukaryotic-like Ser/Thr protein kinases of Mycobacterium tuberculosis. Trends Microbiol. 2000
Interaction	Operon Rv2913c	ashwinigbhat	NAS		Co-expression (Functional linkage) R. Gopalaswamy, S. Narayanan et al. The serine/threonine protein kinase PknI controls the growth of Mycobacterium tuberculosis upon infection. FEMS Microbiol. Lett. 2009
Interaction	Operon Rv2913c	ashwinigbhat	NAS		Co-expression (Functional linkage) authors,BM. Altura Role of prostaglandins and histamine in reactive hyperemia: in-vivo studies on single mesenteric arterioles. Prostaglandins Med 1978

TB Genome Annotation Portal