Q11053 (PKNH_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase PknH
EC=2.7.11.1

Gene names

Name:	pknH
Ordered Locus Names:	Rv1266c, MT1304
ORF Names:	MTCY50.16

Organism

Mycobacterium tuberculosis [Reference proteome] [HAMAP]

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Actinobacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Corynebacterineae › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex

Protein attributes

Sequence length	626 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May regulate bacterial growth in response to external signals to facilitate adaptation to the host environment. In vitro, phosphorylates several substates such as EmbR, DevR (DosR), DacB1 and Rv0681. Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.9 Ref.10
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.3 Ref.4 Ref.7 Ref.9 Ref.10
Cofactor	Divalent metal ions. Ref.4
Enzyme regulation	Inhibited by the kinase inhibitors staurosporine and H-7. Ref.4
Subcellular location	Cell membrane; Single-pass membrane protein Ref.4.
Induction	Repressed by low pH and heat shock. Up-regulated inside the host macrophages. Ref.4 Ref.7
Post-translational modification	Autophosphorylated on threonine and serine residues. Dephosphorylated by PstP. Ref.3 Ref.4 Ref.6 Ref.8
Disruption phenotype	Deletion causes hypervirulence during the chronic phase of infection in BALB/c mice. Mutant displays increased resistance to acidified nitrite stress. Does not affect sensitivity to ethambutol. Ref.5
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Contains 1 protein kinase domain.
Biophysicochemical properties	Kinetic parameters: KM=0.597 µM for EmbR Ref.9 KM=1.59 µM for DacB1 KM=19.82 µM for Rv0681

Ontologies

Keywords
Biological process	Stress response
Cellular component	Cell membrane Membrane
Domain	Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Disulfide bond Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of catalytic activity Inferred from direct assay PubMed 16873379. Source: MTBBASE negative regulation of growth Inferred from mutant phenotype Ref.5. Source: MTBBASE positive regulation of DNA binding Inferred from direct assay Ref.7Ref.6. Source: MTBBASE positive regulation of catalytic activity Inferred from direct assay PubMed 16873379. Source: MTBBASE positive regulation of transcription, DNA-dependent Inferred from mutant phenotype Ref.7. Source: MTBBASE protein autophosphorylation Inferred from direct assay Ref.3. Source: MTBBASE regulation of lipid biosynthetic process Inferred from mutant phenotype Ref.7. Source: MTBBASE response to host immune response Inferred from expression pattern Ref.7. Source: MTBBASE response to stress Inferred from expression pattern Ref.4. Source: MTBBASE
Cellular_component	cell wall Inferred from direct assay PubMed 20825248. Source: MTBBASE integral to plasma membrane Inferred from direct assay Ref.4. Source: MTBBASE
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from direct assay Ref.3Ref.4. Source: MTBBASE
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 626

626

Serine/threonine-protein kinase PknH

PRO_0000171218

Regions

Topological domain

1 – 403

403

Cytoplasmic Potential

Transmembrane

404 – 424

21

Helical; Potential

Topological domain

425 – 626

202

Extracellular Potential

Domain

16 – 276

261

Protein kinase

Nucleotide binding

22 – 30

9

ATP By similarity

Compositional bias

297 – 403

107

Pro-rich

Sites

Active site

139

1

Proton acceptor By similarity

Binding site

45

1

ATP By similarity

Amino acid modifications

Modified residue

170

1

Phosphothreonine Probable

Disulfide bond

482 ↔ 545

Ref.11

Disulfide bond

587 ↔ 604

Ref.11

Experimental info

Mutagenesis

45

1

K → M: Abolished kinase activity. Ref.3 Ref.4

Mutagenesis

170

1

T → A: Abolished autophosphorylation. Ref.3

Sequence conflict

607

1

R → Q in AAK45563. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

626

Helix Strand Turn

Details...

Helix

439 – 445

7

Helix

449 – 456

8

Beta strand

476 – 479

4

Helix

480 – 482

3

Helix

483 – 486

4

Beta strand

488 – 490

3

Helix

491 – 494

4

Beta strand

501 – 508

8

Beta strand

515 – 524

10

Helix

528 – 543

16

Turn

544 – 547

4

Beta strand

549 – 554

6

Beta strand

557 – 563

7

Beta strand

573 – 581

9

Beta strand

586 – 594

9

Beta strand

597 – 607

11

Helix

611 – 624

14

Sequences

	Sequence		Length	Mass (Da)
	Q11053 [UniParc]. Last modified July 15, 1999. Version 2. Checksum: 927C5D0A58605757	FASTA	626	66,754
	10 20 30 40 50 60 MSDAQDSRVG SMFGPYHLKR LLGRGGMGEV YEAEHTVKEW TVAVKLMTAE FSKDPVFRER 70 80 90 100 110 120 MKREARIAGR LQEPHVVPIH DYGEVDGQMF LEMRLVEGTD LDSVLKRFGP LTPPRAVAII 130 140 150 160 170 180 TQIASALDAA HADGVMHRDV KPQNILITRD DFAYLVDFGI ASATTDEKLT QLGTAVGTWK 190 200 210 220 230 240 YMAPERFSND EVTYRADIYA LACVLHECLT GAPPYRADSA GTLVSSHLMG PIPQPSAIRP 250 260 270 280 290 300 GIPKAFDAVV ARGMAKKPED RYASAGDLAL AAHEALSDPD QDHAADILRR SQESTLPAPP 310 320 330 340 350 360 KPVPPPTMPA TAMAPRQPPA PPVTPPGVQP APKPSYTPPA QPGPAGQRPG PTGQPSWAPN 370 380 390 400 410 420 SGPMPASGPT PTPQYYQGGG WGAPPSGGPS PWAQTPRKTN PWPLVAGAAA VVLVLVLGAI 430 440 450 460 470 480 GIWIAIRPKP VQPPQPVAEE RLSALLLNSS EVNAVMGSSS MQPGKPITSM DSSPVTVSLP 490 500 510 520 530 540 DCQGALYTSQ DPVYAGTGYT AINGLISSEP GDNYEHWVNQ AVVAFPTADK ARAFVQTSAD 550 560 570 580 590 600 KWKNCAGKTV TVTNKAKTYR WTFADVKGSP PTITVIDTQE GAEGWECQRA MSVANNVVVD 610 620 VNACGYRITN QAGQIAAKIV DKVNKE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence." Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K. , Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J., Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S., Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S., Barrell B.G. Nature 393:537-544(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 25618 / H37Rv.
[2]	"Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains." Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O., Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K., Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L., Delcher A., Utterback T.R. , Weidman J.F., Khouri H.M., Gill J., Mikula A., Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M. J. Bacteriol. 184:5479-5490(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: CDC 1551 / Oshkosh.
[3]	"An FHA phosphoprotein recognition domain mediates protein EmbR phosphorylation by PknH, a Ser/Thr protein kinase from Mycobacterium tuberculosis." Molle V., Kremer L., Girard-Blanc C., Besra G.S., Cozzone A.J., Prost J.F. Biochemistry 42:15300-15309(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, PHOSPHORYLATION AT THR-170, MUTAGENESIS OF LYS-45 AND THR-170.
[4]	"PknH, a transmembrane Hank's type serine/threonine kinase from Mycobacterium tuberculosis is differentially expressed under stress conditions." Sharma K., Chandra H., Gupta P.K., Pathak M., Narayan A., Meena L.S., D'Souza R.C., Chopra P., Ramachandran S., Singh Y. FEMS Microbiol. Lett. 233:107-113(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ENZYME REGULATION, SUBCELLULAR LOCATION, INDUCTION, AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-45.
[5]	"Deletion of the Mycobacterium tuberculosis pknH gene confers a higher bacillary load during the chronic phase of infection in BALB/c mice." Papavinasasundaram K.G., Chan B., Chung J.H., Colston M.J., Davis E.O., Av-Gay Y. J. Bacteriol. 187:5751-5760(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[6]	"EmbR, a regulatory protein with ATPase activity, is a substrate of multiple serine/threonine kinases and phosphatase in Mycobacterium tuberculosis." Sharma K., Gupta M., Krupa A., Srinivasan N., Singh Y. FEBS J. 273:2711-2721(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS A KINASE WITH EMBR AS SUBSTRATE, DEPHOSPHORYLATION BY PSTP.
[7]	"Transcriptional control of the mycobacterial embCAB operon by PknH through a regulatory protein, EmbR, in vivo." Sharma K., Gupta M., Pathak M., Gupta N., Koul A., Sarangi S., Baweja R., Singh Y. J. Bacteriol. 188:2936-2944(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, INDUCTION.
[8]	"Characterization of the phosphorylation sites of Mycobacterium tuberculosis serine/threonine protein kinases, PknA, PknD, PknE, and PknH by mass spectrometry." Molle V., Zanella-Cleon I., Robin J.P., Mallejac S., Cozzone A.J., Becchi M. Proteomics 6:3754-3766(2006) [PubMed] [Europe PMC] [Abstract] Cited for: AUTOPHOSPHORYLATION, MASS SPECTROMETRY. Strain: ATCC 25618 / H37Rv.
[9]	"Novel substrates of Mycobacterium tuberculosis PknH Ser/Thr kinase." Zheng X., Papavinasasundaram K.G., Av-Gay Y. Biochem. Biophys. Res. Commun. 355:162-168(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES. Strain: ATCC 25618 / H37Rv.
[10]	"Convergence of Ser/Thr and two-component signaling to coordinate expression of the dormancy regulon in Mycobacterium tuberculosis." Chao J.D., Papavinasasundaram K.G., Zheng X., Chavez-Steenbock A., Wang X., Lee G.Q., Av-Gay Y. J. Biol. Chem. 285:29239-29246(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY. Strain: ATCC 25618 / H37Rv.
[11]	"Structure of the sensor domain of Mycobacterium tuberculosis PknH receptor kinase reveals a conserved binding cleft." Cavazos A., Prigozhin D.M., Alber T. J. Mol. Biol. 422:488-494(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 435-626, DISULFIDE BONDS. Strain: ATCC 25618 / H37Rv.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

BX842576 Genomic DNA. Translation: CAB00914.1.
AE000516 Genomic DNA. Translation: AAK45563.1.
AL123456 Genomic DNA. Translation: CCP44022.1.

PIR

B70754.

RefSeq

NP_215782.1. NC_000962.3.
NP_335749.1. NC_002755.2.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4ESQ	X-ray	1.70	A	435-626	[»]

ProteinModelPortal

Q11053.

SMR

Q11053. Positions 14-310, 435-626.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q11053. 1 interaction.

STRING

83332.Rv1266c.

PTM databases

PhosSite

P0603153.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAK45563; AAK45563; MT1304.

GeneID

887023.
924768.

KEGG

mtc:MT1304.
mtu:Rv1266c.

PATRIC

18124632. VBIMycTub22151_1435.

Organism-specific databases

TubercuList

Rv1266c.

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000050426.

KO

K08884.

OMA

REETYYG.

ProtClustDB

CLSK791062.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR026954. PknH-like_Extracell.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
PF14032. PknH_C. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

PKNH_MYCTU

Accession

Primary (citable) accession number: Q11053
Secondary accession number(s): L0T6C9

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	July 15, 1999
Last modified:	May 1, 2013
This is version 98 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program