PAP_BACSU
ID PAP_BACSU Reviewed; 150 AA.
AC P39155;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Protein-arginine-phosphatase;
DE Short=PAP;
DE EC=3.9.1.2 {ECO:0000269|PubMed:23770242};
DE AltName: Full=Phosphoarginine phosphatase;
GN Name=ywlE; OrderedLocusNames=BSU36930; ORFNames=ipc-31d;
OS Bacillus subtilis (strain 168).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX NCBI_TaxID=224308;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=168;
RX PubMed=7798145; DOI=10.1128/jb.177.1.271-274.1995;
RA Martinussen J., Glaser P., Andersen P.S., Saxild H.H.;
RT "Two genes encoding uracil phosphoribosyltransferase are present in
RT Bacillus subtilis.";
RL J. Bacteriol. 177:271-274(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=168;
RX PubMed=9384377; DOI=10.1038/36786;
RA Kunst F., Ogasawara N., Moszer I., Albertini A.M., Alloni G., Azevedo V.,
RA Bertero M.G., Bessieres P., Bolotin A., Borchert S., Borriss R.,
RA Boursier L., Brans A., Braun M., Brignell S.C., Bron S., Brouillet S.,
RA Bruschi C.V., Caldwell B., Capuano V., Carter N.M., Choi S.-K.,
RA Codani J.-J., Connerton I.F., Cummings N.J., Daniel R.A., Denizot F.,
RA Devine K.M., Duesterhoeft A., Ehrlich S.D., Emmerson P.T., Entian K.-D.,
RA Errington J., Fabret C., Ferrari E., Foulger D., Fritz C., Fujita M.,
RA Fujita Y., Fuma S., Galizzi A., Galleron N., Ghim S.-Y., Glaser P.,
RA Goffeau A., Golightly E.J., Grandi G., Guiseppi G., Guy B.J., Haga K.,
RA Haiech J., Harwood C.R., Henaut A., Hilbert H., Holsappel S., Hosono S.,
RA Hullo M.-F., Itaya M., Jones L.-M., Joris B., Karamata D., Kasahara Y.,
RA Klaerr-Blanchard M., Klein C., Kobayashi Y., Koetter P., Koningstein G.,
RA Krogh S., Kumano M., Kurita K., Lapidus A., Lardinois S., Lauber J.,
RA Lazarevic V., Lee S.-M., Levine A., Liu H., Masuda S., Mauel C.,
RA Medigue C., Medina N., Mellado R.P., Mizuno M., Moestl D., Nakai S.,
RA Noback M., Noone D., O'Reilly M., Ogawa K., Ogiwara A., Oudega B.,
RA Park S.-H., Parro V., Pohl T.M., Portetelle D., Porwollik S.,
RA Prescott A.M., Presecan E., Pujic P., Purnelle B., Rapoport G., Rey M.,
RA Reynolds S., Rieger M., Rivolta C., Rocha E., Roche B., Rose M., Sadaie Y.,
RA Sato T., Scanlan E., Schleich S., Schroeter R., Scoffone F., Sekiguchi J.,
RA Sekowska A., Seror S.J., Serror P., Shin B.-S., Soldo B., Sorokin A.,
RA Tacconi E., Takagi T., Takahashi H., Takemaru K., Takeuchi M.,
RA Tamakoshi A., Tanaka T., Terpstra P., Tognoni A., Tosato V., Uchiyama S.,
RA Vandenbol M., Vannier F., Vassarotti A., Viari A., Wambutt R., Wedler E.,
RA Wedler H., Weitzenegger T., Winters P., Wipat A., Yamamoto H., Yamane K.,
RA Yasumoto K., Yata K., Yoshida K., Yoshikawa H.-F., Zumstein E.,
RA Yoshikawa H., Danchin A.;
RT "The complete genome sequence of the Gram-positive bacterium Bacillus
RT subtilis.";
RL Nature 390:249-256(1997).
RN [3]
RP DISRUPTION PHENOTYPE, INDUCTION, MUTAGENESIS OF CYS-7; ARG-13 AND ASP-118,
RP ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=168 / JH642;
RX PubMed=15995210; DOI=10.1128/jb.187.14.4945-4956.2005;
RA Musumeci L., Bongiorni C., Tautz L., Edwards R.A., Osterman A., Perego M.,
RA Mustelin T., Bottini N.;
RT "Low-molecular-weight protein tyrosine phosphatases of Bacillus subtilis.";
RL J. Bacteriol. 187:4945-4956(2005).
RN [4]
RP FUNCTION AS AN ARGININE PHOSPHATASE, IDENTIFICATION OF SUBSTRATES, AND
RP DISRUPTION PHENOTYPE.
RC STRAIN=168;
RX PubMed=22517742; DOI=10.1073/pnas.1117483109;
RA Elsholz A.K., Turgay K., Michalik S., Hessling B., Gronau K., Oertel D.,
RA Mader U., Bernhardt J., Becher D., Hecker M., Gerth U.;
RT "Global impact of protein arginine phosphorylation on the physiology of
RT Bacillus subtilis.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:7451-7456(2012).
RN [5]
RP FUNCTION, IDENTIFICATION OF SUBSTRATES, AND DISRUPTION PHENOTYPE.
RC STRAIN=168;
RX PubMed=24263382; DOI=10.1074/mcp.m113.032292;
RA Schmidt A., Trentini D.B., Spiess S., Fuhrmann J., Ammerer G., Mechtler K.,
RA Clausen T.;
RT "Quantitative phosphoproteomics reveals the role of protein arginine
RT phosphorylation in the bacterial stress response.";
RL Mol. Cell. Proteomics 13:537-550(2014).
RN [6]
RP STRUCTURE BY NMR, AND KINETIC PARAMETERS.
RX PubMed=16452434; DOI=10.1128/jb.188.4.1509-1517.2006;
RA Xu H., Xia B., Jin C.;
RT "Solution structure of a low-molecular-weight protein tyrosine phosphatase
RT from Bacillus subtilis.";
RL J. Bacteriol. 188:1509-1517(2006).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS).
RA Cao X.F.;
RT "Crystal Structure of YwlE from Bacillus subtilis.";
RL Submitted (APR-2012) to the PDB data bank.
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.10 ANGSTROMS) OF MUTANT SER-12 IN COMPLEX WITH
RP PHOSPHATE.
RA Cao X.F., Su X.D.;
RT "Crystal structure of YwlE mutant from Bacillus subtilis.";
RL Submitted (APR-2012) to the PDB data bank.
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF WILD-TYPE IN COMPLEX WITH
RP PHOSPHATE AND MUTANT PHOSPHO-SER-7, FUNCTION AS AN ARGININE PHOSPHATASE,
RP CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, KINETIC PARAMETERS, DISRUPTION
RP PHENOTYPE, SUBSTRATE DISCRIMINATION SITE, REACTION MECHANISM, ACTIVE SITES,
RP AND MUTAGENESIS OF THR-11; ASP-118 AND PHE-120.
RC STRAIN=168;
RX PubMed=23770242; DOI=10.1016/j.celrep.2013.05.023;
RA Fuhrmann J., Mierzwa B., Trentini D.B., Spiess S., Lehner A.,
RA Charpentier E., Clausen T.;
RT "Structural basis for recognizing phosphoarginine and evolving residue-
RT specific protein phosphatases in gram-positive bacteria.";
RL Cell Rep. 3:1832-1839(2013).
CC -!- FUNCTION: Catalyzes the specific dephosphorylation of phosphoarginine
CC residues in a large number of proteins. Counteracts the protein
CC arginine kinase McsB in vivo. Can dephosphorylate CtsR-P; thus, can
CC restore the DNA-binding ability of the CtsR repressor by reversing the
CC McsB-mediated phosphorylation. Is the only active pArg phosphatase
CC present in B.subtilis. Exhibits almost no activity against pSer, pThr,
CC or pTyr peptides. Appears to play a role in B.subtilis stress
CC resistance. Protein arginine phosphorylation has a physiologically
CC important role and is involved in the regulation of many critical
CC cellular processes, such as protein homeostasis, motility, competence,
CC and stringent and stress responses, by regulating gene expression and
CC protein activity. {ECO:0000269|PubMed:22517742,
CC ECO:0000269|PubMed:23770242, ECO:0000269|PubMed:24263382}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(omega)-phospho-L-arginyl-[protein] = L-arginyl-
CC [protein] + phosphate; Xref=Rhea:RHEA:43380, Rhea:RHEA-COMP:10532,
CC Rhea:RHEA-COMP:10533, ChEBI:CHEBI:15377, ChEBI:CHEBI:29965,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:83226; EC=3.9.1.2;
CC Evidence={ECO:0000269|PubMed:23770242};
CC -!- ACTIVITY REGULATION: Efficiently inhibited by Cu(2+) ion, Zn(2+) ion,
CC sodium pyrophosphate and N-ethylmaleimide, while the addition of
CC Mg(2+), Ca(2+) or Fe(3+) ions has minimal effect. Inhibited in a
CC competitive manner by vanadate. {ECO:0000269|PubMed:15995210}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.157 mM for p-nitrophenyl-phosphate (at 37 degrees Celsius and pH
CC 5.5) {ECO:0000269|PubMed:15995210};
CC KM=28 mM for p-nitrophenyl-phosphate (at 55 degrees Celsius)
CC {ECO:0000269|PubMed:16452434};
CC KM=61.41 mM for p-nitrophenyl-phosphate (at 40 degrees Celsius and pH
CC 8.0) {ECO:0000269|PubMed:23770242};
CC Note=kcat is 0.010 sec(-1) with pNPP as substrate (at 37 degrees
CC Celsius and pH 5.5) (PubMed:15995210). kcat is 0.13 sec(-1) with pNPP
CC as substrate (at 40 degrees Celsius and pH 8.0) (PubMed:23770242).
CC pNPP is a phospho-tyrosine mimicking compound.
CC {ECO:0000269|PubMed:15995210, ECO:0000269|PubMed:23770242};
CC pH dependence:
CC Optimum pH is 5.5 with pNPP as substrate.
CC {ECO:0000269|PubMed:15995210};
CC -!- INDUCTION: Expression is up-regulated in the exponential phase of
CC growth, followed by a significant and gradual reduction in the
CC stationary/sporulation phase. Is not up-regulated during ethanol
CC stress. {ECO:0000269|PubMed:15995210}.
CC -!- DISRUPTION PHENOTYPE: Cellular protein arginine phosphorylation is only
CC detectable in a ywlE mutant and not in the wild-type strain, and global
CC gene expression is significantly impacted in the mutant strain
CC (PubMed:22517742 and PubMed:24263382). Cells lacking this gene are
CC impaired in dephosphorylating McsB-P (PubMed:23770242). They also show
CC a reduced resistance to ethanol stress (PubMed:15995210).
CC {ECO:0000269|PubMed:15995210, ECO:0000269|PubMed:22517742,
CC ECO:0000269|PubMed:23770242, ECO:0000269|PubMed:24263382}.
CC -!- SIMILARITY: Belongs to the low molecular weight phosphotyrosine protein
CC phosphatase family. {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be a protein-tyrosine-phosphatase
CC (PubMed:15995210). Was later shown to function as an arginine
CC phosphatase in vivo and in vitro (PubMed:22517742 and PubMed:23770242).
CC {ECO:0000305|PubMed:15995210}.
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DR EMBL; Z38002; CAA86107.1; -; Genomic_DNA.
DR EMBL; AL009126; CAB15710.1; -; Genomic_DNA.
DR PIR; I40479; S49360.
DR RefSeq; NP_391574.1; NC_000964.3.
DR RefSeq; WP_003227664.1; NZ_JNCM01000034.1.
DR PDB; 1ZGG; NMR; -; A=1-150.
DR PDB; 4ETI; X-ray; 1.80 A; A=1-150.
DR PDB; 4ETN; X-ray; 1.10 A; A=1-150.
DR PDB; 4KK3; X-ray; 1.70 A; A=1-150.
DR PDB; 4KK4; X-ray; 1.80 A; A=1-150.
DR PDBsum; 1ZGG; -.
DR PDBsum; 4ETI; -.
DR PDBsum; 4ETN; -.
DR PDBsum; 4KK3; -.
DR PDBsum; 4KK4; -.
DR AlphaFoldDB; P39155; -.
DR BMRB; P39155; -.
DR SMR; P39155; -.
DR MINT; P39155; -.
DR STRING; 224308.BSU36930; -.
DR PaxDb; P39155; -.
DR PRIDE; P39155; -.
DR EnsemblBacteria; CAB15710; CAB15710; BSU_36930.
DR GeneID; 937021; -.
DR KEGG; bsu:BSU36930; -.
DR PATRIC; fig|224308.179.peg.4000; -.
DR eggNOG; COG0394; Bacteria.
DR InParanoid; P39155; -.
DR OMA; AFFPQKA; -.
DR PhylomeDB; P39155; -.
DR BioCyc; BSUB:BSU36930-MON; -.
DR BioCyc; MetaCyc:BSU36930-MON; -.
DR BRENDA; 3.1.3.48; 658.
DR BRENDA; 3.9.1.2; 658.
DR SABIO-RK; P39155; -.
DR EvolutionaryTrace; P39155; -.
DR Proteomes; UP000001570; Chromosome.
DR GO; GO:0098627; F:protein arginine phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IBA:GO_Central.
DR GO; GO:0006470; P:protein dephosphorylation; IEA:InterPro.
DR InterPro; IPR023485; Ptyr_pPase.
DR InterPro; IPR036196; Ptyr_pPase_sf.
DR InterPro; IPR017867; Tyr_phospatase_low_mol_wt.
DR Pfam; PF01451; LMWPc; 1.
DR PRINTS; PR00719; LMWPTPASE.
DR SMART; SM00226; LMWPc; 1.
DR SUPFAM; SSF52788; SSF52788; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Protein phosphatase; Reference proteome.
FT CHAIN 1..150
FT /note="Protein-arginine-phosphatase"
FT /id="PRO_0000046579"
FT ACT_SITE 7
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:23770242"
FT ACT_SITE 13
FT /evidence="ECO:0000250|UniProtKB:P11064"
FT ACT_SITE 118
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000269|PubMed:23770242"
FT BINDING 8..13
FT /ligand="substrate"
FT SITE 11
FT /note="Important for substrate discrimination"
FT MUTAGEN 7
FT /note="C->S: Complete loss of phosphatase activity."
FT /evidence="ECO:0000269|PubMed:15995210"
FT MUTAGEN 11
FT /note="T->I: 18-fold reduction in p-Arg phosphatase
FT activity and 22-fold increase in p-Tyr phosphatase
FT activity."
FT /evidence="ECO:0000269|PubMed:23770242"
FT MUTAGEN 11
FT /note="T->V: 18-fold reduction in p-Arg phosphatase
FT activity and 11-fold increase in p-Tyr phosphatase
FT activity."
FT /evidence="ECO:0000269|PubMed:23770242"
FT MUTAGEN 13
FT /note="R->K: Completely loss of phosphatase activity."
FT /evidence="ECO:0000269|PubMed:15995210"
FT MUTAGEN 118
FT /note="D->A: Completely loss of phosphatase activity."
FT /evidence="ECO:0000269|PubMed:15995210,
FT ECO:0000269|PubMed:23770242"
FT MUTAGEN 120
FT /note="F->A: 60-fold reduction in p-Arg phosphatase
FT activity and 4-fold reduction in p-Tyr phosphatase
FT activity."
FT /evidence="ECO:0000269|PubMed:23770242"
FT STRAND 1..12
FT /evidence="ECO:0007829|PDB:4ETN"
FT HELIX 13..28
FT /evidence="ECO:0007829|PDB:4ETN"
FT STRAND 32..38
FT /evidence="ECO:0007829|PDB:4ETN"
FT HELIX 49..57
FT /evidence="ECO:0007829|PDB:4ETN"
FT HELIX 71..76
FT /evidence="ECO:0007829|PDB:4ETN"
FT STRAND 78..84
FT /evidence="ECO:0007829|PDB:4ETN"
FT HELIX 85..94
FT /evidence="ECO:0007829|PDB:4ETN"
FT HELIX 96..101
FT /evidence="ECO:0007829|PDB:4ETN"
FT STRAND 102..104
FT /evidence="ECO:0007829|PDB:4ETN"
FT HELIX 105..110
FT /evidence="ECO:0007829|PDB:4ETN"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:1ZGG"
FT HELIX 124..145
FT /evidence="ECO:0007829|PDB:4ETN"
FT TURN 146..148
FT /evidence="ECO:0007829|PDB:1ZGG"
SQ SEQUENCE 150 AA; 16785 MW; E1BD5EA5231DED2C CRC64;
MDIIFVCTGN TCRSPMAEAL FKSIAEREGL NVNVRSAGVF ASPNGKATPH AVEALFEKHI
ALNHVSSPLT EELMESADLV LAMTHQHKQI IASQFGRYRD KVFTLKEYVT GSHGDVLDPF
GGSIDIYKQT RDELEELLRQ LAKQLKKDRR
