Reviewed, UniProtKB/Swiss-Prot P71588 (PSTP_MYCTU)

Names and origin

Protein names

Recommended name:
    PP2C-family Ser/Thr phosphatase
    EC=3.1.3.16
Alternative name(s):
    Mycobacterial Ser/Thr phosphatase
      Short name=Mstp
    Possible serine/threonine phosphatase Ppp

Gene names

Name:	pstP
Synonyms:	mstp, ppp
Ordered Locus Names:	Rv0018c, MT0021

Organism

Mycobacterium tuberculosis [Complete proteome] [HAMAP]

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	514 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	The only predicted protein phosphatase in M.tuberculosis, it dephosphorylates at least 5 protein kinases (pknA, pknB, pknD, pknE and pknF) and the penicillin-binding protein PBPA. Ref.3 Ref.4 Ref.5 Ref.6
Catalytic activity	A phosphoprotein + H2O = a protein + phosphate. Ref.3 Ref.4
Cofactor	Bind 3 Mn2+ ions per subunit. Ref.3
Enzyme regulation	Inhibited partially by NaF and cyclosporine.
Subcellular location	Cell membrane; Single-pass membrane protein Potential. Note: May be localized to the outside of the cell.
Miscellaneous	Was identified as a high-confidence drug target.
Sequence similarities	Contains 1 PP2C-like domain.
Caution	It is uncertain whether Met-1 or Val-4 is the initiator.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Domain	Transmembrane
Ligand	Manganese Metal-binding
Molecular function	Hydrolase Protein phosphatase
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	manganese ion binding Inferred from electronic annotation. Source: UniProtKB-KW phosphoprotein phosphatase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

4 – 514

511

PP2C-family Ser/Thr phosphatase

PRO_0000344805

Regions

Topological domain

4 – 302

299

Cytoplasmic Potential

Transmembrane

303 – 323

21

Potential

Topological domain

324 – 514

191

Extracellular Potential

Domain

9 – 231

223

PP2C-like

Compositional bias

422 – 506

85

Pro-rich

Sites

Metal binding

38

1

Manganese 1

Metal binding

38

1

Manganese 2

Metal binding

39

1

Manganese 1; via carbonyl oxygen

Metal binding

118

1

Manganese 3

Metal binding

160

1

Manganese 3; via carbonyl oxygen

Metal binding

191

1

Manganese 2

Metal binding

191

1

Manganese 3

Metal binding

229

1

Manganese 2

Experimental info

Mutagenesis

118

1

D → N: Decreases affinity for Mn3 by 4-fold, no effect on hydrolysis of p-nitrophenyl phosphate. Ref.8

Mutagenesis

160

1

S → A: No change in affinity for Mn3, no effect on hydrolysis of p-nitrophenyl phosphate. Ref.8

Sequence conflict

463

1

P → S in AAK44243. Ref.2

Secondary structure

1

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514

Helix Strand Turn

Details...

Beta strand

7 – 15

9

Beta strand

25 – 29

5

Beta strand

31 – 40

10

Helix

46 – 57

12

Helix

59 – 62

4

Helix

69 – 90

22

Helix

92 – 94

3

Beta strand

101 – 107

7

Beta strand

110 – 118

9

Beta strand

120 – 125

6

Beta strand

128 – 131

4

Helix

138 – 144

7

Turn

150 – 153

4

Beta strand

166 – 169

4

Beta strand

174 – 179

6

Beta strand

185 – 189

5

Helix

191 – 194

4

Helix

199 – 205

7

Helix

211 – 224

14

Beta strand

231 – 239

9

Sequences

	Sequence		Length	Mass (Da)
	P71588-1 [UniParc]. Last modified July 1, 1997. Version 2. Checksum: DD78F54D2FC19D95	FASTA	514	53,812
	10 20 30 40 50 60 MARVTLVLRY AARSDRGLVR ANNEDSVYAG ARLLALADGM GGHAAGEVAS QLVIAALAHL 70 80 90 100 110 120 DDDEPGGDLL AKLDAAVRAG NSAIAAQVEM EPDLEGMGTT LTAILFAGNR LGLVHIGDSR 130 140 150 160 170 180 GYLLRDGELT QITKDDTFVQ TLVDEGRITP EEAHSHPQRS LIMRALTGHE VEPTLTMREA 190 200 210 220 230 240 RAGDRYLLCS DGLSDPVSDE TILEALQIPE VAESAHRLIE LALRGGGPDN VTVVVADVVD 250 260 270 280 290 300 YDYGQTQPIL AGAVSGDDDQ LTLPNTAAGR ASAISQRKEI VKRVPPQADT FSRPRWSGRR 310 320 330 340 350 360 LAFVVALVTV LMTAGLLIGR AIIRSNYYVA DYAGSVSIMR GIQGSLLGMS LHQPYLMGCL 370 380 390 400 410 420 SPRNELSQIS YGQSGGPLDC HLMKLEDLRP PERAQVRAGL PAGTLDDAIG QLRELAANSL 430 440 450 460 470 480 LPPCPAPRAT SPPGRPAPPT TSETTEPNVT SSPASPSPTT SAPAPTGTTP AIPTSASPAA 490 500 510 PASPPTPWPV TSSPTMAALP PPPPQPGIDC RAAA

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: 9634230] [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: 12218036] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: CDC 1551 / Oshkosh.
[3]	"Phosphoprotein phosphatase of Mycobacterium tuberculosis dephosphorylates serine-threonine kinases PknA and PknB." Chopra P., Singh B., Singh R., Vohra R., Koul A., Meena L.S., Koduri H., Ghildiyal M., Deol P., Das T.K., Tyagi A.K., Singh Y. Biochem. Biophys. Res. Commun. 311:112-120(2003) [PubMed: 14575702] [Abstract] Cited for: ENZYMATIC ACTIVITY, COFACTOR, ENZYME INHIBITION, FUNCTION IN THE DEPHOSPHORYLATION OF PKNA AND PKNB. Strain: ATCC 25618 / H37Rv.
[4]	"PknB kinase activity is regulated by phosphorylation in two Thr residues and dephosphorylation by PstP, the cognate phospho-Ser/Thr phosphatase, in Mycobacterium tuberculosis." Boitel B., Ortiz-Lombardia M., Duran R., Pompeo F., Cole S.T., Cervenansky C., Alzari P.M. Mol. Microbiol. 49:1493-1508(2003) [PubMed: 12950916] [Abstract] Cited for: ENZYMATIC ACTIVITY, DIVALENT CATION-DEPENDENCE, FUNCTION IN THE DEPHOSPHORYLATION OF PKNB. Strain: ATCC 25618 / H37Rv.
[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: 15967413] [Abstract] Cited for: FUNCTION IN THE DEPHOSPHORYLATION OF PKNB; PKND; PKNE AND PKNF. Strain: ATCC 25618 / H37Rv.
[6]	"The serine/threonine kinase PknB of Mycobacterium tuberculosis phosphorylates PBPA, a penicillin-binding protein required for cell division." Dasgupta A., Datta P., Kundu M., Basu J. Microbiology 152:493-504(2006) [PubMed: 16436437] [Abstract] Cited for: FUNCTION IN THE DEPHOSPHORYLATION OF PBPA. Strain: ATCC 25618 / H37Rv.
[7]	"targetTB: a target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis." Raman K., Yeturu K., Chandra N. BMC Syst. Biol. 2:109-109(2008) [PubMed: 19099550] [Abstract] Cited for: IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
[8]	"An alternate conformation and a third metal in PstP/Ppp, the M. tuberculosis PP2C-Family Ser/Thr protein phosphatase." Pullen K.E., Ng H.-L., Sung P.-Y., Good M.C., Smith S.M., Alber T. Structure 12:1947-1954(2004) [PubMed: 15530359] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 5-237, MUTAGENESIS OF ASP-118 AND SER-160. Strain: ATCC 25618 / H37Rv.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

BX842572 Genomic DNA. Translation: CAB02438.1.
AE000516 Genomic DNA. Translation: AAK44243.1. Different initiation.

PIR

H70699.

RefSeq

NP_214532.1.
NP_334429.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TXO	X-ray	1.95	A/B	5-237	[»]
2CM1	X-ray	2.00	A	1-240	[»]

ModBase

Search...

Protein family/group databases

PptaseDB

P3D0410141.

Genome annotation databases

GeneID

887070.
922470.

GenomeReviews

Gene locus MT0021 in contig AE000516_GR.

KEGG

mtc:MT0021.
mtu:Rv0018c.

TIGR

MT0021.

Organism-specific databases

TubercuList

Rv0018c.

Phylogenomic databases

HOGENOM

HBG688775.

OMA

SNNEDSV.

Family and domain databases

InterPro

IPR015655. PP2C.
IPR001932. PP2C-related.
IPR014045. PP2C_N.
[Graphical view]

Gene3D

G3DSA:3.60.40.10. PP2C-related. 1 hit.

PANTHER

PTHR13832. PP2C. 1 hit.

Pfam

PF00481. PP2C. 1 hit.
[Graphical view]

SMART

SM00331. PP2C_SIG. 1 hit.
SM00332. PP2Cc. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

PSTP_MYCTU

Accession

Primary (citable) accession number: P71588
Secondary accession number(s): Q8VKT2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 22, 2008
Last sequence update:	July 1, 1997
Last modified:	February 9, 2010
This is version 60 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HAMAP (High-quality Automated and Manual Annotation of microbial Proteomes)