P95078 (PKNK_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
Protein kinase K

Gene names

Name:	pknK
Ordered Locus Names:	Rv3080c, MT3165
ORF Names:	MTCY22D7.01, MTV013.01c

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	1110 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Key microbial factor involved in regulation of early and late events in tuberculosis infection, and in host-pathogen interactions. Modulates host immunity during early infection. Slows mycobacterial growth during chronic infection in host and during a variety of stress conditions in vitro. Regulates the expression of a large subset of tRNA genes as a means to facilitate adaptation to changing growth environments. In vitro, directs the inhibition of transcription and translation processes in a phosphorylation-dependent manner. Phosphorylates the transcriptional regulator VirS, thereby increasing the affinity of VirS for the mycobacterial monooxygenase (mymA) promoter. In vitro, can also phosphorylate the mycobacterial monooxygenase operon products Rv3083 (MymA), Rv3084 (LipR), Rv3085 and Rv3088. Ref.3 Ref.4 Ref.5 Ref.6
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.3
Subunit structure	Forms oligomeric complexes in solution. Ref.5
Subcellular location	Cytoplasm. Cell membrane. Secreted › cell wall. Note: Probably attached to the cell membrane through interactions mediated by its C-terminal region. May be secreted during infection. Ref.3 Ref.4
Induction	Induced during early infection in human macrophages. Ref.4 Ref.6
Domain	The C-terminal region exerts intrasteric control that autoregulates kinase activity. Ref.5
Post-translational modification	Can autophosphorylate the carboxyl terminal region in addition to Thr-179 and Thr-181.
Disruption phenotype	Deletion affects cell size and cell wall composition, increases survival during persistent infection in mice, and increases resistance to acidic pH, hypoxia, oxidative and stationary-phase stresses in vitro. Ref.4
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Virulence
Cellular component	Cell membrane Cell wall Cytoplasm Membrane Secreted
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	pathogenesis Inferred from electronic annotation. Source: UniProtKB-KW protein autophosphorylation Inferred from direct assay Ref.3. Source: MTBBASE regulation of sequence-specific DNA binding transcription factor activity Inferred from direct assay Ref.3. Source: MTBBASE
Cellular_component	cell wall Inferred from direct assay PubMed 15525680. Source: MTBBASE cytosol Inferred from direct assay PubMed 15525680. Source: MTBBASE extracellular region Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from direct assay PubMed 15525680Ref.3. Source: MTBBASE
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from direct assay Ref.3. Source: MTBBASE
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		3	EBI-6418825,EBI-6418825

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1110	1110	Serine/threonine-protein kinase PknK		PRO_0000171224
Regions
	Domain	26 – 283	258	Protein kinase
	Nucleotide binding	32 – 40	9	ATP By similarity
Sites
	Active site	149	1	Proton acceptor By similarity
	Metal binding	154	1	Magnesium By similarity
	Metal binding	167	1	Magnesium By similarity
	Binding site	55	1	ATP By similarity
Amino acid modifications
	Modified residue	179	1	Phosphothreonine; by autocatalysis Ref.3
	Modified residue	181	1	Phosphothreonine; by autocatalysis Ref.3
Experimental info
	Mutagenesis	55	1	K → M: Loss of activity. Ref.3
	Mutagenesis	179	1	T → A: Loss of activity; when associated with A-181. Ref.3
	Mutagenesis	181	1	T → A: Loss of activity; when associated with A-179. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P95078 [UniParc]. Last modified August 1, 1998. Version 2. Checksum: 2F81BF18BCD3E472	FASTA	1,110	119,418
	10 20 30 40 50 60 MTDVDPHATR RDLVPNIPAE LLEAGFDNVE EIGRGGFGVV YRCVQPSLDR AVAVKVLSTD 70 80 90 100 110 120 LDRDNLERFL REQRAMGRLS GHPHIVTVLQ VGVLAGGRPF IVMPYHAKNS LETLIRRHGP 130 140 150 160 170 180 LDWRETLSIG VKLAGALEAA HRVGTLHRDV KPGNILLTDY GEPQLTDFGI ARIAGGFETA 190 200 210 220 230 240 TGVIAGSPAF TAPEVLEGAS PTPASDVYSL GATLFCALTG HAAYERRSGE RVIAQFLRIT 250 260 270 280 290 300 SQPIPDLRKQ GLPADVAAAI ERAMARHPAD RPATAADVGE ELRDVQRRNG VSVDEMPLPV 310 320 330 340 350 360 ELGVERRRSP EAHAAHRHTG GGTPTVPTPP TPATKYRPSV PTGSLVTRSR LTDILRAGGR 370 380 390 400 410 420 RRLILIHAPS GFGKSTLAAQ WREELSRDGA AVAWLTIDND DNNEVWFLSH LLESIRRVRP 430 440 450 460 470 480 TLAESLGHVL EEHGDDAGRY VLTSLIDEIH ENDDRIAVVI DDWHRVSDSR TQAALGFLLD 490 500 510 520 530 540 NGCHHLQLIV TSWSRAGLPV GRLRIGDELA EIDSAALRFD TDEAAALLND AGGLRLPRAD 550 560 570 580 590 600 VQALTTSTDG WAAALRLAAL SLRGGGDATQ LLRGLSGASD VIHEFLSENV LDTLEPELRE 610 620 630 640 650 660 FLLVASVTER TCGGLASALA GITNGRAMLE EAEHRGLFLQ RTEDDPNWFR FHQMFADFLH 670 680 690 700 710 720 RRLERGGSHR VAELHRRASA WFAENGYLHE AVDHALAAGD PARAVDLVEQ DETNLPEQSK 730 740 750 760 770 780 MTTLLAIVQK LPTSMVVSRA RLQLAIAWAN ILLQRPAPAT GALNRFETAL GRAELPEATQ 790 800 810 820 830 840 ADLRAEADVL RAVAEVFADR VERVDDLLAE AMSRPDTLPP RVPGTAGNTA ALAAICRFEF 850 860 870 880 890 900 AEVYPLLDWA APYQEMMGPF GTVYAQCLRG MAARNRLDIV AALQNFRTAF EVGTAVGAHS 910 920 930 940 950 960 HAARLAGSLL AELLYETGDL AGAGRLMDES YLLGSEGGAV DYLAARYVIG ARVKAAQGDH 970 980 990 1000 1010 1020 EGAADRLSTG GDTAVQLGLP RLAARINNER IRLGIALPAA VAADLLAPRT IPRDNGIATM 1030 1040 1050 1060 1070 1080 TAELDEDSAV RLLSAGDSAD RDQACQRAGA LAAAIDGTRR PLAALQAQIL HIETLAATGR 1090 1100 1110 ESDARNELAP VATKCAELGL SRLLVDAGLA

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]	"The Mycobacterium tuberculosis protein kinase K modulates activation of transcription from the promoter of mycobacterial monooxygenase operon through phosphorylation of the transcriptional regulator VirS." Kumar P., Kumar D., Parikh A., Rananaware D., Gupta M., Singh Y., Nandicoori V.K. J. Biol. Chem. 284:11090-11099(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-179 AND THR-181, MUTAGENESIS OF LYS-55; THR-179 AND THR-181. Strain: ATCC 25618 / H37Rv.
[4]	"Mycobacterium tuberculosis protein kinase K confers survival advantage during early infection in mice and regulates growth in culture and during persistent infection: implications for immune modulation." Malhotra V., Arteaga-Cortes L.T., Clay G., Clark-Curtiss J.E. Microbiology 156:2829-2841(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INDUCTION, DISRUPTION PHENOTYPE. Strain: ATCC 25618 / H37Rv.
[5]	"Mycobacterium tuberculosis protein kinase K enables growth adaptation through translation control." Malhotra V., Okon B.P., Clark-Curtiss J.E. J. Bacteriol. 194:4184-4196(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, DOMAIN. Strain: ATCC 25618 / H37Rv.
[6]	"Functional characterization delineates that a Mycobacterium tuberculosis specific protein kinase (Rv3080c) is responsible for the growth, phagocytosis and intracellular survival of avirulent mycobacteria." Kumari R., Singh S.K., Singh D.K., Singh P.K., Chaurasiya S.K., Srivastava K.K. Mol. Cell. Biochem. 369:67-74(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AE000516 Genomic DNA. Translation: AAK47501.1. AL123456 Genomic DNA. Translation: CCP45889.1.
PIR	A70652.
RefSeq	NP_217596.1. NC_000962.3. NP_337687.1. NC_002755.2. YP_006516541.1. NC_018143.1.
3D structure databases
ProteinModelPortal	P95078.
SMR	P95078. Positions 30-339.
ModBase	Search...
Protein-protein interaction databases
STRING	83332.Rv3080c.
Proteomic databases
PRIDE	P95078.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblBacteria	AAK47501; AAK47501; MT3165.
GeneID	13317885. 888659. 926679.
KEGG	mtc:MT3165. mtu:Rv3080c.
PATRIC	18128722. VBIMycTub22151_3458.
Organism-specific databases
TubercuList	Rv3080c.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000074403.
KO	K13419.
OMA	RPYIVMQ.
ProtClustDB	CLSK792267.
Family and domain databases
Gene3D	1.25.40.10. 1 hit.
InterPro	IPR011009. Kinase-like_dom. IPR027417. P-loop_NTPase. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR016236. Ser/Thr_kinase_PknK_prd. IPR011990. TPR-like_helical. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
PIRSF	PIRSF000574. Ser/Thr_PK_PknK_prd. 1 hit.
SUPFAM	SSF56112. Kinase_like. 1 hit. SSF52540. SSF52540. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. False negative. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

PKNK_MYCTU

Accession

Primary (citable) accession number: P95078
Secondary accession number(s): L0TEA2

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	August 1, 1998
Last modified:	May 29, 2013
This is version 103 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program