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Protein

Serine/threonine-protein kinase PknB

Gene

pknB

Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Protein kinase that regulates many aspects of mycobacterial physiology, and is critical for growth in vitro and survival of the pathogen in the host (PubMed:24706757). Is a key component of a signal transduction pathway that regulates cell growth, cell shape and cell division via phosphorylation of target proteins such as GarA, GlmU, PapA5, PbpA, FhaB (Rv0019c), FhaA (Rv0020c), MviN, PstP, EmbR, Rv1422, Rv1747 and RseA (PubMed:15978616, PubMed:15985609, PubMed:15987910, PubMed:16436437, PubMed:16817899, PubMed:16980473, PubMed:19121323, PubMed:19826007, PubMed:20025669, PubMed:21423706, PubMed:22275220). Also catalyzes the phosphorylation of the core proteasome alpha-subunit (PrcA), and thereby regulates the proteolytic activity of the proteasome (PubMed:25224505). Is a major regulator of the oxygen-dependent replication switch since PknB activity is necessary for reactivation of cells from the hypoxic state (PubMed:24409094). Shows a strong preference for Thr versus Ser as the phosphoacceptor. Overexpression of PknB alters cell morphology and leads to cell death (PubMed:24706757) (PubMed:24409094).14 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.7 Publications

Enzyme regulationi

Interaction of the PASTA domains with peptidoglycan leads to septal and polar localization of PknB, and dimerization of the intracellular kinase domain. Dimerization activates the kinase domain via an allosteric mechanism, triggering autophosphorylation and phosphorylation of target proteins. Inhibited by mitoxantrone. Inhibition prevents mycobacterial growth.4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei40ATPPROSITE-ProRule annotation2 Publications1
Active sitei138Proton acceptor1
Metal bindingi143Magnesium1
Metal bindingi156Magnesium1
Binding sitei156ATPPROSITE-ProRule annotation2 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi17 – 25ATPPROSITE-ProRule annotation2 Publications9
Nucleotide bindingi93 – 95ATPPROSITE-ProRule annotation2 Publications3
Nucleotide bindingi140 – 143ATPPROSITE-ProRule annotation2 Publications4

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • manganese ion binding Source: MTBBASE
  • protein kinase activity Source: MTBBASE
  • protein serine/threonine kinase activity Source: MTBBASE

GO - Biological processi

  • growth Source: MTBBASE
  • negative regulation of catalytic activity Source: MTBBASE
  • negative regulation of fatty acid biosynthetic process Source: MTBBASE
  • negative regulation of protein binding Source: MTBBASE
  • pathogenesis Source: UniProtKB-KW
  • positive regulation of catalytic activity Source: MTBBASE
  • positive regulation of DNA binding Source: MTBBASE
  • protein autophosphorylation Source: MTBBASE
  • regulation of cell shape Source: MTBBASE
  • regulation of transferase activity Source: MTBBASE
  • response to host immune response Source: MTBBASE
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Virulence

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMTBH37RV:G185E-4127-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase PknB (EC:2.7.11.1)
Gene namesi
Name:pknB
Ordered Locus Names:Rv0014c
ORF Names:MTCY10H4.14c
OrganismiMycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Taxonomic identifieri83332 [NCBI]
Taxonomic lineageiBacteriaActinobacteriaCorynebacterialesMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex
Proteomesi
  • UP000001584 Componenti: Chromosome

Organism-specific databases

TubercuListiRv0014c.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini2 – 332CytoplasmicSequence analysisAdd BLAST331
Transmembranei333 – 353HelicalSequence analysisAdd BLAST21
Topological domaini354 – 626ExtracellularSequence analysisAdd BLAST273

GO - Cellular componenti

  • cell wall Source: MTBBASE
  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Essential for growth, it cannot be disrupted (PubMed:16980473). PknB depletion in M.tuberculosis results in cell death and aberrant cell morphology, and leads to complete clearance of the pathogen from the host tissues using the murine infection model (PubMed:24706757).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi10R → A: Impairs kinase activity. 1 Publication1
Mutagenesisi33L → D: Impairs kinase activity. 1 Publication1
Mutagenesisi40K → M: Lack of autophosphorylation. Decreases affinity for FhaB. 2 Publications1
Mutagenesisi76D → A: Impairs kinase activity. 1 Publication1
Mutagenesisi138D → N: Impairs kinase activity. 1 Publication1
Mutagenesisi171T → A: Reduces activity and autophosphorylation. Decreases interaction with GarA. 3 Publications1
Mutagenesisi173T → A: Reduces activity and autophosphorylation. Decreases interaction with GarA. 3 Publications1
Mutagenesisi294T → A: Does not affect activity. 1 Publication1
Mutagenesisi309T → A: Does not affect activity. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL1908385.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001712082 – 626Serine/threonine-protein kinase PknBAdd BLAST625

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylthreonineCombined sources1
Modified residuei166Phosphoserine; by autocatalysis2 Publications1
Modified residuei169Phosphoserine; by autocatalysis1 Publication1
Modified residuei171Phosphothreonine; by autocatalysis5 Publications1
Modified residuei173Phosphothreonine; by autocatalysis4 Publications1
Modified residuei294Phosphothreonine; by autocatalysis2 Publications1
Modified residuei295Phosphoserine; by autocatalysis1 Publication1
Modified residuei309Phosphothreonine; by autocatalysis1 Publication1

Post-translational modificationi

Autophosphorylated. Dephosphorylated by PstP.5 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiP9WI81.

PTM databases

iPTMnetiP9WI81.

Expressioni

Inductioni

Expressed predominantly in exponential phase (PubMed:15985609). PknB levels are regulated in response to hypoxia; its expression is down-regulated during hypoxia and recovers to aerated levels upon reaeration (at mRNA and protein level) (PubMed:24409094).2 Publications

Interactioni

Subunit structurei

Homodimer. Interacts with the FHA domain of GarA, FhaB and FhaA.8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself9EBI-2946037,EBI-2946037
garAP9WJA92EBI-2946037,EBI-6405522

Protein-protein interaction databases

IntActiP9WI81. 3 interactors.
STRINGi83332.Rv0014c.

Chemistry databases

BindingDBiP9WI81.

Structurei

Secondary structure

1626
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 7Combined sources3
Turni8 – 10Combined sources3
Beta strandi11 – 19Combined sources9
Beta strandi21 – 30Combined sources10
Turni31 – 34Combined sources4
Beta strandi35 – 42Combined sources8
Helixi44 – 46Combined sources3
Helixi50 – 60Combined sources11
Beta strandi74 – 82Combined sources9
Beta strandi85 – 93Combined sources9
Beta strandi97 – 99Combined sources3
Helixi100 – 107Combined sources8
Helixi112 – 131Combined sources20
Helixi141 – 143Combined sources3
Beta strandi144 – 147Combined sources4
Beta strandi152 – 154Combined sources3
Beta strandi167 – 169Combined sources3
Helixi185 – 189Combined sources5
Helixi195 – 211Combined sources17
Helixi221 – 230Combined sources10
Helixi236 – 239Combined sources4
Beta strandi240 – 242Combined sources3
Helixi245 – 254Combined sources10
Helixi259 – 261Combined sources3
Helixi266 – 277Combined sources12
Beta strandi358 – 361Combined sources4
Helixi370 – 379Combined sources10
Beta strandi383 – 389Combined sources7
Beta strandi392 – 394Combined sources3
Beta strandi398 – 404Combined sources7
Beta strandi408 – 410Combined sources3
Beta strandi415 – 421Combined sources7
Beta strandi426 – 428Combined sources3
Helixi433 – 435Combined sources3
Helixi437 – 446Combined sources10
Beta strandi452 – 458Combined sources7
Helixi461 – 463Combined sources3
Beta strandi466 – 472Combined sources7
Beta strandi477 – 479Combined sources3
Beta strandi484 – 490Combined sources7
Beta strandi494 – 496Combined sources3
Beta strandi502 – 504Combined sources3
Helixi505 – 513Combined sources9
Turni514 – 516Combined sources3
Beta strandi519 – 525Combined sources7
Beta strandi533 – 539Combined sources7
Beta strandi544 – 546Combined sources3
Beta strandi549 – 556Combined sources8
Beta strandi560 – 562Combined sources3
Helixi571 – 580Combined sources10
Beta strandi587 – 589Combined sources3
Helixi597 – 599Combined sources3
Beta strandi602 – 608Combined sources7
Beta strandi612 – 615Combined sources4
Beta strandi620 – 625Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1MRUX-ray3.00A/B1-308[»]
1O6YX-ray2.20A1-279[»]
2FUMX-ray2.89A/B/C/D1-279[»]
2KUDNMR-A355-491[»]
2KUENMR-A423-557[»]
2KUFNMR-A491-626[»]
2KUINMR-A355-626[»]
3F61X-ray1.80A1-308[»]
3F69X-ray2.80A/B1-308[»]
5E0YX-ray2.00A558-626[»]
5E0ZX-ray2.00A491-626[»]
5E10X-ray1.80A360-491[»]
5E12X-ray2.21A/B423-626[»]
ProteinModelPortaliP9WI81.
SMRiP9WI81.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini11 – 274Protein kinasePROSITE-ProRule annotationAdd BLAST264
Domaini356 – 422PASTA 1PROSITE-ProRule annotationAdd BLAST67
Domaini423 – 490PASTA 2PROSITE-ProRule annotationAdd BLAST68
Domaini491 – 557PASTA 3PROSITE-ProRule annotationAdd BLAST67
Domaini558 – 626PASTA 4PROSITE-ProRule annotationAdd BLAST69

Domaini

The intracellular kinase domain and all four extracytoplasmic PASTA domains are essential for PknB function and cell survival (PubMed:24706757). The PASTA domains interact with peptidoglycans and are required for PknB localization (PubMed:21829358).2 Publications

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.PROSITE-ProRule annotation
Contains 4 PASTA domains.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG4105D9P. Bacteria.
COG0515. LUCA.
COG2815. LUCA.
KOiK12132.
OMAiIRMYIND.
PhylomeDBiP9WI81.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR005543. PASTA_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF03793. PASTA. 4 hits.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00740. PASTA. 4 hits.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51178. PASTA. 4 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P9WI81-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTTPSHLSDR YELGEILGFG GMSEVHLARD LRLHRDVAVK VLRADLARDP
60 70 80 90 100
SFYLRFRREA QNAAALNHPA IVAVYDTGEA ETPAGPLPYI VMEYVDGVTL
110 120 130 140 150
RDIVHTEGPM TPKRAIEVIA DACQALNFSH QNGIIHRDVK PANIMISATN
160 170 180 190 200
AVKVMDFGIA RAIADSGNSV TQTAAVIGTA QYLSPEQARG DSVDARSDVY
210 220 230 240 250
SLGCVLYEVL TGEPPFTGDS PVSVAYQHVR EDPIPPSARH EGLSADLDAV
260 270 280 290 300
VLKALAKNPE NRYQTAAEMR ADLVRVHNGE PPEAPKVLTD AERTSLLSSA
310 320 330 340 350
AGNLSGPRTD PLPRQDLDDT DRDRSIGSVG RWVAVVAVLA VLTVVVTIAI
360 370 380 390 400
NTFGGITRDV QVPDVRGQSS ADAIATLQNR GFKIRTLQKP DSTIPPDHVI
410 420 430 440 450
GTDPAANTSV SAGDEITVNV STGPEQREIP DVSTLTYAEA VKKLTAAGFG
460 470 480 490 500
RFKQANSPST PELVGKVIGT NPPANQTSAI TNVVIIIVGS GPATKDIPDV
510 520 530 540 550
AGQTVDVAQK NLNVYGFTKF SQASVDSPRP AGEVTGTNPP AGTTVPVDSV
560 570 580 590 600
IELQVSKGNQ FVMPDLSGMF WVDAEPRLRA LGWTGMLDKG ADVDAGGSQH
610 620
NRVVYQNPPA GTGVNRDGII TLRFGQ
Length:626
Mass (Da):66,510
Last modified:April 16, 2014 - v1
Checksum:i6C27EEBE9D5A453B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL123456 Genomic DNA. Translation: CCP42736.1.
PIRiD70699.
RefSeqiNP_214528.1. NC_000962.3.
WP_003400356.1. NZ_KK339370.1.

Genome annotation databases

EnsemblBacteriaiCCP42736; CCP42736; Rv0014c.
GeneIDi887072.
KEGGimtu:Rv0014c.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL123456 Genomic DNA. Translation: CCP42736.1.
PIRiD70699.
RefSeqiNP_214528.1. NC_000962.3.
WP_003400356.1. NZ_KK339370.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1MRUX-ray3.00A/B1-308[»]
1O6YX-ray2.20A1-279[»]
2FUMX-ray2.89A/B/C/D1-279[»]
2KUDNMR-A355-491[»]
2KUENMR-A423-557[»]
2KUFNMR-A491-626[»]
2KUINMR-A355-626[»]
3F61X-ray1.80A1-308[»]
3F69X-ray2.80A/B1-308[»]
5E0YX-ray2.00A558-626[»]
5E0ZX-ray2.00A491-626[»]
5E10X-ray1.80A360-491[»]
5E12X-ray2.21A/B423-626[»]
ProteinModelPortaliP9WI81.
SMRiP9WI81.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP9WI81. 3 interactors.
STRINGi83332.Rv0014c.

Chemistry databases

BindingDBiP9WI81.
ChEMBLiCHEMBL1908385.

PTM databases

iPTMnetiP9WI81.

Proteomic databases

PaxDbiP9WI81.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiCCP42736; CCP42736; Rv0014c.
GeneIDi887072.
KEGGimtu:Rv0014c.

Organism-specific databases

TubercuListiRv0014c.

Phylogenomic databases

eggNOGiENOG4105D9P. Bacteria.
COG0515. LUCA.
COG2815. LUCA.
KOiK12132.
OMAiIRMYIND.
PhylomeDBiP9WI81.

Enzyme and pathway databases

BioCyciMTBH37RV:G185E-4127-MONOMER.

Miscellaneous databases

PROiP9WI81.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR005543. PASTA_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF03793. PASTA. 4 hits.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00740. PASTA. 4 hits.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51178. PASTA. 4 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPKNB_MYCTU
AccessioniPrimary (citable) accession number: P9WI81
Secondary accession number(s): L0T5F6, P0A5S4, P71584
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 16, 2014
Last sequence update: April 16, 2014
Last modified: November 30, 2016
This is version 27 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

Overexpression causes major growth and morphological changes that indicate defects in cell wall synthesis and possibly in cell division.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh
    Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: entries and gene names
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.