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 27-MAR-2024, entry version 157. 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; Bacillota; 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 phosphotyrosine 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, 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, PubMed:23770242). CC {ECO:0000305|PubMed:15995210}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 224308-BSU36930; -. 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 OrthoDB; 9784339at2; -. DR PhylomeDB; P39155; -. DR BioCyc; BSUB:BSU36930-MONOMER; -. DR BioCyc; MetaCyc:BSU36930-MONOMER; -. 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 CDD; cd16344; LMWPAP; 1. DR Gene3D; 3.40.50.2300; -; 1. DR InterPro; IPR023485; Ptyr_pPase. DR InterPro; IPR036196; Ptyr_pPase_sf. DR InterPro; IPR017867; Tyr_phospatase_low_mol_wt. DR PANTHER; PTHR11717; LOW MOLECULAR WEIGHT PROTEIN TYROSINE PHOSPHATASE; 1. DR PANTHER; PTHR11717:SF31; LOW MOLECULAR WEIGHT PROTEIN-TYROSINE-PHOSPHATASE PTPB; 1. DR Pfam; PF01451; LMWPc; 1. DR PRINTS; PR00719; LMWPTPASE. DR SMART; SM00226; LMWPc; 1. DR SUPFAM; SSF52788; Phosphotyrosine protein phosphatases I; 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 //