O05871 (PKND_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Gene names

Name:	pknD
Ordered Locus Names:	Rv0931c, MT0958
ORF Names:	MTCY08C9.08

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	664 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Key microbial factor required for central nervous system tuberculosis. Required for invasion of host brain endothelia, but not macrophages, lung epithelia or other endothelia. Phosphorylates the anti-anti-sigma factor homolog Rv0516c, which inhibits binding of Rv0516c to Rv2638, another anti-anti-sigma factor. Can also phosphorylate the FHA domain of Rv1747. Ref.6 Ref.8 Ref.9 Ref.10
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.8 Ref.9
Enzyme regulation	Dimerization activates the kinase domain of unphosphorylated PknD via an allosteric mechanism, triggering autophosphorylation and phosphorylation of target proteins. Phosphorylated PknD is fully active even in the absence of dimerization. Ref.8
Subunit structure	Homodimer. The extracellular domain interacts with host laminin. Ref.8 Ref.10
Subcellular location	Cell membrane; Single-pass membrane protein Potential.
Post-translational modification	Autophosphorylated. Dephosphorylated by PstP. Ref.5 Ref.7
Disruption phenotype	Mutants display defective invasion and reduced survival in brain endothelia. Ref.10
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Contains 6 NHL repeats. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Virulence
Cellular component	Cell membrane Membrane
Domain	Repeat Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to phosphate starvation Inferred from direct assay PubMed 20933472. Source: MTBBASE negative regulation of catalytic activity Inferred from direct assay PubMed 16873379. Source: MTBBASE negative regulation of fatty acid biosynthetic process Inferred from direct assay PubMed 20178986. Source: MTBBASE negative regulation of protein binding Inferred from direct assay Ref.9. Source: MTBBASE pathogenesis Inferred from mutant phenotype PubMed 18956986. Source: MTBBASE positive regulation of catalytic activity Inferred from direct assay PubMed 16873379. Source: MTBBASE
Cellular_component	cell wall Inferred from direct assay PubMed 20825248. Source: MTBBASE cytosol Inferred from direct assay PubMed 15525680. Source: MTBBASE extracellular region Inferred from direct assay PubMed 21148733. Source: MTBBASE integral to plasma membrane Inferred from direct assay PubMed 15952732. Source: MTBBASE
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW manganese ion binding Inferred from direct assay Ref.1. Source: MTBBASE protein serine/threonine kinase activity Inferred from direct assay PubMed 15978616. Source: MTBBASE
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 664

664

Serine/threonine-protein kinase PknD

PRO_0000171209

Regions

Topological domain

1 – 381

381

Cytoplasmic Potential

Transmembrane

382 – 402

21

Helical; Potential

Topological domain

403 – 664

262

Extracellular Potential

Domain

15 – 276

262

Protein kinase

Repeat

414 – 456

43

NHL 1

Repeat

457 – 497

41

NHL 2

Repeat

498 – 539

42

NHL 3

Repeat

540 – 581

42

NHL 4

Repeat

582 – 623

42

NHL 5

Repeat

624 – 664

41

NHL 6

Nucleotide binding

21 – 29

9

ATP By similarity

Sites

Active site

138

1

Proton acceptor By similarity

Binding site

44

1

ATP By similarity

Amino acid modifications

Modified residue

135

1

Phosphothreonine; by autocatalysis Ref.5

Modified residue

169

1

Phosphothreonine; by autocatalysis Ref.5

Modified residue

171

1

Phosphothreonine; by autocatalysis Ref.5

Modified residue

173

1

Phosphothreonine; by autocatalysis Ref.5

Modified residue

209

1

Phosphothreonine; by autocatalysis Ref.5

Experimental info

Mutagenesis

79

1

H → A: Lack of activity. Ref.8

Mutagenesis

81

1

Y → A: Decreases activity and alters substrate specificity. Ref.8

Mutagenesis

138

1

D → N: 2600-fold decrease in activity. Ref.9

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

664

Helix Strand Turn

Details...

Beta strand

428 – 433

6

Beta strand

439 – 443

5

Beta strand

445 – 447

3

Beta strand

449 – 453

5

Beta strand

460 – 462

3

Beta strand

474 – 476

3

Beta strand

482 – 486

5

Turn

487 – 489

3

Beta strand

490 – 494

5

Beta strand

510 – 517

8

Beta strand

523 – 527

5

Helix

528 – 530

3

Beta strand

532 – 536

5

Beta strand

557 – 559

3

Beta strand

565 – 569

5

Helix

570 – 572

3

Beta strand

574 – 578

5

Turn

580 – 582

3

Beta strand

585 – 587

3

Beta strand

595 – 601

7

Beta strand

607 – 611

5

Turn

612 – 614

3

Beta strand

617 – 620

4

Beta strand

638 – 643

6

Beta strand

649 – 653

5

Helix

654 – 656

3

Beta strand

658 – 662

5

Sequences

	Sequence		Length	Mass (Da)
	O05871 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: FE39716825A41CC1	FASTA	664	69,545
	10 20 30 40 50 60 MSDAVPQVGS QFGPYQLLRL LGRGGMGEVY EAEDTRKHRV VALKLISPQY SDNAVFRARM 70 80 90 100 110 120 QREADTAGRL TEPHIVPIHD YGEINGQFFV EMRMIDGTSL RALLKQYGPL TPARAVAIVR 130 140 150 160 170 180 QIAAALDAAH ANGVTHRDVK PENILVTASD FAYLVDFGIA RAASDPGLTQ TGTAVGTYNY 190 200 210 220 230 240 MAPERFTGDE VTYRADIYAL ACVLGECLTG APPYRADSVE RLIAAHLMDP APQPSQLRPG 250 260 270 280 290 300 RVPPALDQVI AKGMAKNPAE RFMSAGDLAI AAHDALTTSE QHQATTILRR GDNATLLATP 310 320 330 340 350 360 ADTGLSQSES GIAGAGTGPP TPGAARWSPG DSATVAGPLA ADSRGGNWPS QTGHSPAVPN 370 380 390 400 410 420 ALQASLGHAV PPAGNKRKVW AVVGAAAIVL VAIVAAAGYL VLRPSWSPTQ ASGQTVLPFT 430 440 450 460 470 480 GIDFRLSPSG VAVDSAGNVY VTSEGMYGRV VKLATGSTGT TVLPFNGLYQ PQGLAVDGAG 490 500 510 520 530 540 TVYVTDFNNR VVTLAAGSNN QTVLPFDGLN YPEGLAVDTQ GAVYVADRGN NRVVKLAAGS 550 560 570 580 590 600 KTQTVLPFTG LNDPDGVAVD NSGNVYVTDT DNNRVVKLEA ESNNQVVLPF TDITAPWGIA 610 620 630 640 650 660 VDEAGTVYVT EHNTNQVVKL LAGSTTSTVL PFTGLNTPLA VAVDSDRTVY VADRGNDRVV KLTS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A serine/threonine protein kinase from Mycobacterium tuberculosis." Peirs P., De Wit L., Braibant M., Huygen K., Content J. Eur. J. Biochem. 244:604-612(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 35801 / TMC 107 / Erdman.
[2]	Content J. Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION. Strain: ATCC 35801 / TMC 107 / Erdman.
[3]	"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.
[4]	"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.
[5]	"Conserved autophosphorylation pattern in activation loops and juxtamembrane regions of Mycobacterium tuberculosis Ser/Thr protein kinases." Duran R., Villarino A., Bellinzoni M., Wehenkel A., Fernandez P., Boitel B., Cole S.T., Alzari P.M., Cervenansky C. Biochem. Biophys. Res. Commun. 333:858-867(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-135; THR-169; THR-171; THR-173 AND THR-209, MASS SPECTROMETRY.
[6]	"Mycobacterium tuberculosis serine/threonine kinases PknB, PknD, PknE, and PknF phosphorylate multiple FHA domains." Grundner C., Gay L.M., Alber T. Protein Sci. 14:1918-1921(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"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.
[8]	"Allosteric activation by dimerization of the PknD receptor Ser/Thr protein kinase from Mycobacterium tuberculosis." Greenstein A.E., Echols N., Lombana T.N., King D.S., Alber T. J. Biol. Chem. 282:11427-11435(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, SUBUNIT, MUTAGENESIS OF HIS-79 AND TYR-81.
[9]	"M. tuberculosis Ser/Thr protein kinase D phosphorylates an anti-anti-sigma factor homolog." Greenstein A.E., MacGurn J.A., Baer C.E., Falick A.M., Cox J.S., Alber T. PLoS Pathog. 3:E49-E49(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ASP-138.
[10]	"Role of Mycobacterium tuberculosis pknD in the pathogenesis of central nervous system tuberculosis." Be N.A., Bishai W.R., Jain S.K. BMC Microbiol. 12:7-7(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN VIRULENCE, INTERACTION WITH HOST LAMININ, DISRUPTION PHENOTYPE. Strain: CDC 1551 / Oshkosh.
[11]	"Sensor domain of the Mycobacterium tuberculosis receptor Ser/Thr protein kinase, PknD, forms a highly symmetric beta propeller." Good M.C., Greenstein A.E., Young T.A., Ng H.L., Alber T. J. Mol. Biol. 339:459-469(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 403-664.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X99618 Genomic DNA. Translation: CAA67929.2.
AE000516 Genomic DNA. Translation: AAK45205.1.
AL123456 Genomic DNA. Translation: CCP43679.1.

PIR

C70584.

RefSeq

NP_215446.1. NC_000962.3.
NP_335391.1. NC_002755.2.
YP_006514287.1. NC_018143.1.
YP_007609515.1. NC_020559.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1RWI	X-ray	1.80	A/B	403-664	[»]
1RWL	X-ray	1.90	A	403-664	[»]

ProteinModelPortal

O05871.

SMR

O05871. Positions 13-296, 413-664.

ModBase

Search...

Protein-protein interaction databases

IntAct

O05871. 2 interactions.

STRING

83332.Rv0931c.

PTM databases

PhosSite

P0603130.

Proteomic databases

PaxDb

O05871.

PRIDE

O05871.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAK45205; AAK45205; MT0958.

GeneID

13318839.
14963745.
885607.
926274.

KEGG

mtc:MT0958.
mtu:Rv0931c.

PATRIC

18123850. VBIMycTub22151_1048.

Organism-specific databases

TubercuList

Rv0931c.

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000050426.

KO

K08884.

OMA

RIDTHGI.

ProtClustDB

CLSK790840.

Enzyme and pathway databases

BRENDA

2.7.11.1. 3445.

Family and domain databases

Gene3D

2.120.10.30. 1 hit.

InterPro

IPR011042. 6-blade_b-propeller_TolB-like.
IPR011009. Kinase-like_dom.
IPR001258. NHL_repeat.
IPR013017. NHL_repeat_subgr.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF01436. NHL. 6 hits.
PF00069. Pkinase. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS51125. NHL. 6 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O05871.

Entry information

Entry name

PKND_MYCTU

Accession

Primary (citable) accession number: O05871
Secondary accession number(s): L0T6U6, P95308

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	July 1, 1997
Last modified:	May 29, 2013
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program