PYRH_BACSU
ID PYRH_BACSU Reviewed; 240 AA.
AC O31749;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 31-AUG-2004, sequence version 2.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Uridylate kinase;
DE Short=UK;
DE EC=2.7.4.22;
DE AltName: Full=Uridine monophosphate kinase;
DE Short=UMP kinase;
DE Short=UMPK;
GN Name=pyrH; Synonyms=smbA; OrderedLocusNames=BSU16510;
OS Bacillus subtilis (strain 168).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX NCBI_TaxID=224308;
RN [1]
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 [2]
RP SEQUENCE REVISION TO 57-60.
RX PubMed=10568751; DOI=10.1101/gr.9.11.1116;
RA Medigue C., Rose M., Viari A., Danchin A.;
RT "Detecting and analyzing DNA sequencing errors: toward a higher quality of
RT the Bacillus subtilis genome sequence.";
RL Genome Res. 9:1116-1127(1999).
RN [3]
RP FUNCTION, SUBSTRATE SPECIFICITY, ACTIVITY REGULATION, KINETIC PARAMETERS,
RP MASS SPECTROMETRY, AND SUBUNIT.
RC STRAIN=168;
RX PubMed=12869195; DOI=10.1046/j.1432-1033.2003.03702.x;
RA Gagyi C., Bucurenci N., Sirbu O., Labesse G., Ionescu M., Ofiteru A.,
RA Assairi L., Landais S., Danchin A., Barzu O., Gilles A.-M.;
RT "UMP kinase from the Gram-positive bacterium Bacillus subtilis is strongly
RT dependent on GTP for optimal activity.";
RL Eur. J. Biochem. 270:3196-3204(2003).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=168;
RX PubMed=15018105; DOI=10.1007/s00284-003-4117-2;
RA Gagyi C., Ionescu M., Gounon P., Sakamoto H., Rousselle J.-C.,
RA Laurent-Winter C.;
RT "Identification and immunochemical location of UMP kinase from Bacillus
RT subtilis.";
RL Curr. Microbiol. 48:62-67(2004).
RN [5]
RP ACTIVITY REGULATION, KINETIC PARAMETERS, AND MUTAGENESIS OF THR-135 AND
RP ASN-137.
RX PubMed=17210578; DOI=10.1074/jbc.m606963200;
RA Evrin C., Straut M., Slavova-Azmanova N., Bucurenci N., Onu A., Assairi L.,
RA Ionescu M., Palibroda N., Barzu O., Gilles A.-M.;
RT "Regulatory mechanisms differ in UMP kinases from Gram-negative and Gram-
RT positive bacteria.";
RL J. Biol. Chem. 282:7242-7253(2007).
RN [6]
RP INTERACTION WITH BRXC, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=168 / CU1065 {ECO:0000303|PubMed:33722570};
RX PubMed=33722570; DOI=10.1016/j.redox.2021.101935;
RA Gaballa A., Su T.T., Helmann J.D.;
RT "The Bacillus subtilis monothiol bacilliredoxin BrxC (YtxJ) and the Bdr
RT (YpdA) disulfide reductase reduce S-bacillithiolated proteins.";
RL Redox Biol. 42:101935-101935(2021).
CC -!- FUNCTION: Catalyzes the reversible phosphorylation of UMP to UDP, with
CC ATP or dATP as the most efficient phosphate donors. Is also able to
CC phosphorylate 5-fluoro-UMP and 6-aza-UMP. {ECO:0000269|PubMed:12869195,
CC ECO:0000269|PubMed:15018105}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + UMP = ADP + UDP; Xref=Rhea:RHEA:24400,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:57865, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:456216; EC=2.7.4.22;
CC -!- ACTIVITY REGULATION: Allosterically activated by GTP. Can also be
CC activated by dGTP and 3'-anthraniloyl-2'-deoxyguanosine-5'-triphosphate
CC (Ant-dGTP). Inhibited by UTP, 5-bromo-UTP and 5-iodo-UTP.
CC {ECO:0000269|PubMed:12869195, ECO:0000269|PubMed:17210578}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.9 mM for ATP {ECO:0000269|PubMed:12869195,
CC ECO:0000269|PubMed:17210578};
CC KM=8 uM for UMP (in the absence of GTP) {ECO:0000269|PubMed:12869195,
CC ECO:0000269|PubMed:17210578};
CC KM=30 uM for UMP (in the presence of GTP)
CC {ECO:0000269|PubMed:12869195, ECO:0000269|PubMed:17210578};
CC KM=120 uM for 5-fluoro-UMP {ECO:0000269|PubMed:12869195,
CC ECO:0000269|PubMed:17210578};
CC KM=140 uM for 6-aza-UMP {ECO:0000269|PubMed:12869195,
CC ECO:0000269|PubMed:17210578};
CC Vmax=25 umol/min/mg enzyme with UMP as substrate
CC {ECO:0000269|PubMed:12869195, ECO:0000269|PubMed:17210578};
CC Vmax=24 umol/min/mg enzyme with 5-fluoro-UMP as substrate
CC {ECO:0000269|PubMed:12869195, ECO:0000269|PubMed:17210578};
CC Vmax=0.6 umol/min/mg enzyme with 6-aza-UMP as substrate
CC {ECO:0000269|PubMed:12869195, ECO:0000269|PubMed:17210578};
CC Note=In the absence of GTP, the activity is less than 10% of its
CC maximum activity. Is unstable in the absence of UTP. Positive
CC cooperativity is observed with ATP as variable substrate, but it is
CC strongly reduced in the presence of GTP. GTP enhances the affinity
CC for ATP whereas UTP decreases it.;
CC -!- PATHWAY: Pyrimidine metabolism; CTP biosynthesis via de novo pathway;
CC UDP from UMP (UMPK route): step 1/1.
CC -!- SUBUNIT: Homohexamer (PubMed:12869195). Interacts with BrxC
CC (PubMed:33722570). {ECO:0000269|PubMed:12869195,
CC ECO:0000269|PubMed:33722570}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15018105}. Note=Is
CC predominantly localized near the bacterial membranes.
CC -!- MASS SPECTROMETRY: Mass=26084.2; Mass_error=1.5; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:12869195};
CC -!- MISCELLANEOUS: The peripheral distribution of PyrH is related most
CC probably to its role in the synthesis of membrane sugar components and
CC its putative role in cell division.
CC -!- SIMILARITY: Belongs to the UMP kinase family. {ECO:0000305}.
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DR EMBL; AL009126; CAB13524.2; -; Genomic_DNA.
DR PIR; F69708; F69708.
DR RefSeq; NP_389533.2; NC_000964.3.
DR RefSeq; WP_003220923.1; NZ_JNCM01000035.1.
DR AlphaFoldDB; O31749; -.
DR SMR; O31749; -.
DR STRING; 224308.BSU16510; -.
DR jPOST; O31749; -.
DR PaxDb; O31749; -.
DR PRIDE; O31749; -.
DR EnsemblBacteria; CAB13524; CAB13524; BSU_16510.
DR GeneID; 64303544; -.
DR GeneID; 939602; -.
DR KEGG; bsu:BSU16510; -.
DR PATRIC; fig|224308.179.peg.1792; -.
DR eggNOG; COG0528; Bacteria.
DR InParanoid; O31749; -.
DR OMA; PIIVFDM; -.
DR PhylomeDB; O31749; -.
DR BioCyc; BSUB:BSU16510-MON; -.
DR BRENDA; 2.7.4.22; 658.
DR SABIO-RK; O31749; -.
DR UniPathway; UPA00159; UER00275.
DR PRO; PR:O31749; -.
DR Proteomes; UP000001570; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0033862; F:UMP kinase activity; IBA:GO_Central.
DR GO; GO:0044210; P:'de novo' CTP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0006225; P:UDP biosynthetic process; IBA:GO_Central.
DR CDD; cd04254; AAK_UMPK-PyrH-Ec; 1.
DR Gene3D; 3.40.1160.10; -; 1.
DR HAMAP; MF_01220_B; PyrH_B; 1.
DR InterPro; IPR036393; AceGlu_kinase-like_sf.
DR InterPro; IPR001048; Asp/Glu/Uridylate_kinase.
DR InterPro; IPR011817; Uridylate_kinase.
DR InterPro; IPR015963; Uridylate_kinase_bac.
DR Pfam; PF00696; AA_kinase; 1.
DR PIRSF; PIRSF005650; Uridylate_kin; 1.
DR SUPFAM; SSF53633; SSF53633; 1.
DR TIGRFAMs; TIGR02075; pyrH_bact; 1.
PE 1: Evidence at protein level;
KW Allosteric enzyme; ATP-binding; Cytoplasm; Kinase; Nucleotide-binding;
KW Pyrimidine biosynthesis; Reference proteome; Transferase.
FT CHAIN 1..240
FT /note="Uridylate kinase"
FT /id="PRO_0000143825"
FT REGION 20..25
FT /note="Involved in allosteric activation by GTP"
FT /evidence="ECO:0000255"
FT BINDING 12..15
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 54
FT /ligand="UMP"
FT /ligand_id="ChEBI:CHEBI:57865"
FT /evidence="ECO:0000250"
FT BINDING 55
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 59
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 74
FT /ligand="UMP"
FT /ligand_id="ChEBI:CHEBI:57865"
FT /evidence="ECO:0000250"
FT BINDING 135..142
FT /ligand="UMP"
FT /ligand_id="ChEBI:CHEBI:57865"
FT /evidence="ECO:0000250"
FT BINDING 163
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 169
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 172
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MUTAGEN 135
FT /note="T->A: Loss of cooperativity with ATP. 5-fold
FT decrease in affinity for UMP. Increased sensitivity to
FT activation by GTP."
FT /evidence="ECO:0000269|PubMed:17210578"
FT MUTAGEN 137
FT /note="N->A: Loss of cooperativity with ATP. Increased
FT sensitivity to activation by GTP."
FT /evidence="ECO:0000269|PubMed:17210578"
SQ SEQUENCE 240 AA; 26083 MW; 4B374BF1D4FAA14A CRC64;
MEKPKYKRIV LKLSGEALAG EQGNGINPTV IQSIAKQVKE IAELEVEVAV VVGGGNLWRG
KTGSDLGMDR ATADYMGMLA TVMNSLALQD SLETLGIQSR VQTSIEMRQV AEPYIRRKAI
RHLEKKRVVI FAAGTGNPYF STDTTAALRA AEIEADVILM AKNNVDGVYN ADPRKDESAV
KYESLSYLDV LKDGLEVMDS TASSLCMDND IPLIVFSIME EGNIKRAVIG ESIGTIVRGK
