ID PYRH_ECOLI Reviewed; 241 AA. AC P0A7E9; P29464; DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 27-MAR-2024, entry version 146. DE RecName: Full=Uridylate kinase; DE Short=UK; DE EC=2.7.4.22 {ECO:0000269|PubMed:17210578}; DE AltName: Full=Uridine monophosphate kinase; DE Short=UMP kinase; DE Short=UMPK; GN Name=pyrH; Synonyms=smbA; OrderedLocusNames=b0171, JW0166; OS Escherichia coli (strain K12). OC Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales; OC Enterobacteriaceae; Escherichia. OX NCBI_TaxID=83333; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND CHARACTERIZATION. RC STRAIN=K12; RA Smallshaw J.E., Kelln R.A.; RT "Cloning, nucleotide sequence and expression of the Escherichia coli K-12 RT pyrH gene encoding UMP kinase."; RL Life Sci. Adv. (Genet.) 11:59-65(1992). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1447125; DOI=10.1128/jb.174.23.7517-7526.1992; RA Yamanaka K., Ogura T., Niki H., Hiraga S.; RT "Identification and characterization of the smbA gene, a suppressor of the RT mukB null mutant of Escherichia coli."; RL J. Bacteriol. 174:7517-7526(1992). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-8, FUNCTION, RP BIOPHYSICOCHEMICAL PROPERTIES, CHARACTERIZATION, SUBUNIT, AND MUTAGENESIS RP OF ASP-201. RX PubMed=7711027; DOI=10.1021/bi00015a018; RA Serina L., Blondin C., Krin E., Sismeiro O., Danchin A., Sakamoto H., RA Gilles A.-M., Barzu O.; RT "Escherichia coli UMP-kinase, a member of the aspartokinase family, is a RT hexamer regulated by guanine nucleotides and UTP."; RL Biochemistry 34:5066-5074(1995). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911; RX PubMed=8202364; DOI=10.1093/nar/22.9.1637; RA Fujita N., Mori H., Yura T., Ishihama A.; RT "Systematic sequencing of the Escherichia coli genome: analysis of the 2.4- RT 4.1 min (110,917-193,643 bp) region."; RL Nucleic Acids Res. 22:1637-1639(1994). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911; RA Takemoto K., Mori H., Murayama N., Kataoka K., Yano M., Itoh T., RA Yamamoto Y., Inokuchi H., Miki T., Hatada E., Fukuda R., Ichihara S., RA Mizuno T., Makino K., Nakata A., Yura T., Sampei G., Mizobuchi K.; RT "Systematic sequencing of the Escherichia coli genome: analysis of the 4.0 RT - 6.0 min (189,987 - 281,416bp) region."; RL Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / MG1655 / ATCC 47076; RA Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M., RA Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D., RA Namath A., Oefner P., Roberts D., Schramm S., Davis R.W.; RT "Sequence of minutes 4-25 of Escherichia coli."; RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / MG1655 / ATCC 47076; RX PubMed=9278503; DOI=10.1126/science.277.5331.1453; RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., RA Shao Y.; RT "The complete genome sequence of Escherichia coli K-12."; RL Science 277:1453-1462(1997). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911; RX PubMed=16738553; DOI=10.1038/msb4100049; RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.; RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 RT and W3110."; RL Mol. Syst. Biol. 2:E1-E5(2006). RN [9] RP CHARACTERIZATION. RX PubMed=8190075; DOI=10.1007/bf00283870; RA Yamanaka K., Ogura T., Koonin E.V., Niki H., Hiraga S.; RT "Multicopy suppressors, mssA and mssB, of an smbA mutation of Escherichia RT coli."; RL Mol. Gen. Genet. 243:9-16(1994). RN [10] RP SUBCELLULAR LOCATION. RX PubMed=9922246; DOI=10.1128/jb.181.3.833-840.1999; RA Landais S., Gounon P., Laurent-Winter C., Mazie J.-C., Danchin A., RA Barzu O., Sakamoto H.; RT "Immunochemical analysis of UMP kinase from Escherichia coli."; RL J. Bacteriol. 181:833-840(1999). RN [11] RP MUTAGENESIS OF ARG-62; ASP-77; ASP-146; ASP-159; ASP-174 AND ASP-201. RX PubMed=9457846; DOI=10.1128/jb.180.3.473-477.1998; RA Bucurenci N., Serina L., Zaharia C., Landais S., Danchin A., Barzu O.; RT "Mutational analysis of UMP kinase from Escherichia coli."; RL J. Bacteriol. 180:473-477(1998). RN [12] RP ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, AND RP PATHWAY. 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 [13] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANT ASN-159 IN COMPLEX WITH RP UMP; UDP AND UTP, ACTIVITY REGULATION, AND MUTAGENESIS OF THR-138 AND RP ASN-140. RX PubMed=15857829; DOI=10.1074/jbc.m501849200; RA Briozzo P., Evrin C., Meyer P., Assairi L., Joly N., Barzu O., RA Gilles A.-M.; RT "Structure of Escherichia coli UMP kinase differs from that of other RT nucleoside monophosphate kinases and sheds new light on enzyme RT regulation."; RL J. Biol. Chem. 280:25533-25540(2005). RN [14] RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) IN COMPLEX WITH GTP, ACTIVITY RP REGULATION, AND MUTAGENESIS OF ASP-93 AND ASN-140. RX PubMed=18945668; DOI=10.1074/jbc.m802614200; RA Meyer P., Evrin C., Briozzo P., Joly N., Barzu O., Gilles A.-M.; RT "Structural and functional characterization of Escherichia coli UMP kinase RT in complex with its allosteric regulator GTP."; RL J. Biol. Chem. 283:36011-36018(2008). CC -!- FUNCTION: Catalyzes the reversible phosphorylation of UMP to UDP, with CC ATP as the most efficient phosphate donor. CC {ECO:0000269|PubMed:7711027}. 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 Evidence={ECO:0000269|PubMed:17210578}; CC -!- ACTIVITY REGULATION: Allosterically activated by GTP. Competitively CC inhibited by magnesium-free UTP. Magnesium-bound UTP is unable to CC inhibit enzyme activity. {ECO:0000269|PubMed:15857829, CC ECO:0000269|PubMed:17210578, ECO:0000269|PubMed:18945668}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=210 uM for ATP (in the presence of 0.3 mM UMP) CC {ECO:0000269|PubMed:17210578}; CC KM=50 uM for UMP (in the presence of 0.2 mM ATP) CC {ECO:0000269|PubMed:17210578}; CC Vmax=62.4 umol/min/mg enzyme with ATP as substrate (in the presence CC of 0.3 mM UMP) {ECO:0000269|PubMed:17210578}; CC Vmax=46.1 umol/min/mg enzyme with UMP as substrate (in the presence CC of 0.2 mM ATP) {ECO:0000269|PubMed:17210578}; CC -!- PATHWAY: Pyrimidine metabolism; CTP biosynthesis via de novo pathway; CC UDP from UMP (UMPK route): step 1/1. {ECO:0000269|PubMed:17210578}. CC -!- SUBUNIT: Homohexamer. {ECO:0000269|PubMed:15857829, CC ECO:0000269|PubMed:7711027}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9922246}. Note=Is CC predominantly localized near the bacterial membranes. CC -!- MISCELLANEOUS: The peripheral distribution of PyrH is related most CC probably to its role in the synthesis of membrane sugar components. CC -!- SIMILARITY: Belongs to the UMP kinase family. {ECO:0000305}. 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; X78809; CAA55388.1; -; Genomic_DNA. DR EMBL; D13334; BAA02598.1; -; Genomic_DNA. DR EMBL; U70214; AAB08600.1; -; Genomic_DNA. DR EMBL; U00096; AAC73282.1; -; Genomic_DNA. DR EMBL; AP009048; BAB96747.1; -; Genomic_DNA. DR PIR; B45269; B45269. DR RefSeq; NP_414713.1; NC_000913.3. DR RefSeq; WP_000224573.1; NZ_STEB01000032.1. DR PDB; 2BND; X-ray; 2.60 A; A/B=1-241. DR PDB; 2BNE; X-ray; 2.30 A; A/B=1-241. DR PDB; 2BNF; X-ray; 2.45 A; A/B=1-241. DR PDB; 2V4Y; X-ray; 2.80 A; A/B/C/D/E/F=1-241. DR PDBsum; 2BND; -. DR PDBsum; 2BNE; -. DR PDBsum; 2BNF; -. DR PDBsum; 2V4Y; -. DR AlphaFoldDB; P0A7E9; -. DR SMR; P0A7E9; -. DR BioGRID; 4262225; 29. DR BioGRID; 849386; 1. DR DIP; DIP-31830N; -. DR IntAct; P0A7E9; 54. DR STRING; 511145.b0171; -. DR ChEMBL; CHEMBL4523176; -. DR MoonProt; P0A7E9; -. DR jPOST; P0A7E9; -. DR PaxDb; 511145-b0171; -. DR EnsemblBacteria; AAC73282; AAC73282; b0171. DR GeneID; 83577891; -. DR GeneID; 944989; -. DR KEGG; ecj:JW0166; -. DR KEGG; eco:b0171; -. DR PATRIC; fig|1411691.4.peg.2109; -. DR EchoBASE; EB1501; -. DR eggNOG; COG0528; Bacteria. DR HOGENOM; CLU_033861_0_0_6; -. DR InParanoid; P0A7E9; -. DR OMA; RRAIRHM; -. DR OrthoDB; 9807458at2; -. DR PhylomeDB; P0A7E9; -. DR BioCyc; EcoCyc:UMPKI-MONOMER; -. DR BioCyc; MetaCyc:UMPKI-MONOMER; -. DR BRENDA; 2.7.4.22; 2026. DR SABIO-RK; P0A7E9; -. DR UniPathway; UPA00159; UER00275. DR EvolutionaryTrace; P0A7E9; -. DR PRO; PR:P0A7E9; -. DR Proteomes; UP000000318; Chromosome. DR Proteomes; UP000000625; Chromosome. DR GO; GO:0005829; C:cytosol; IDA:EcoCyc. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; IDA:EcoCyc. DR GO; GO:0033862; F:UMP kinase activity; IDA:EcoCyc. 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:0006221; P:pyrimidine nucleotide biosynthetic process; IDA:EcoCyc. 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; Acetylglutamate kinase-like; 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 NCBIfam; TIGR02075; pyrH_bact; 1. DR PANTHER; PTHR42833; URIDYLATE KINASE; 1. DR PANTHER; PTHR42833:SF4; URIDYLATE KINASE PUMPKIN, CHLOROPLASTIC; 1. DR Pfam; PF00696; AA_kinase; 1. DR PIRSF; PIRSF005650; Uridylate_kin; 1. DR SUPFAM; SSF53633; Carbamate kinase-like; 1. PE 1: Evidence at protein level; KW 3D-structure; Allosteric enzyme; ATP-binding; Cytoplasm; KW Direct protein sequencing; Kinase; Nucleotide-binding; KW Pyrimidine biosynthesis; Reference proteome; Transferase. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:7711027" FT CHAIN 2..241 FT /note="Uridylate kinase" FT /id="PRO_0000143842" FT REGION 23..28 FT /note="Involved in allosteric activation by GTP" FT /evidence="ECO:0000255" FT BINDING 15..18 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:15857829, FT ECO:0000269|PubMed:18945668, ECO:0007744|PDB:2BND, FT ECO:0007744|PDB:2BNF, ECO:0007744|PDB:2V4Y" FT BINDING 57 FT /ligand="UMP" FT /ligand_id="ChEBI:CHEBI:57865" FT /evidence="ECO:0000269|PubMed:15857829, FT ECO:0000269|PubMed:18945668, ECO:0007744|PDB:2BND, FT ECO:0007744|PDB:2BNF, ECO:0007744|PDB:2V4Y" FT BINDING 58 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:15857829, FT ECO:0000269|PubMed:18945668, ECO:0007744|PDB:2BND, FT ECO:0007744|PDB:2BNF, ECO:0007744|PDB:2V4Y" FT BINDING 62 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:15857829, FT ECO:0007744|PDB:2BND, ECO:0007744|PDB:2BNE, FT ECO:0007744|PDB:2BNF" FT BINDING 77 FT /ligand="UMP" FT /ligand_id="ChEBI:CHEBI:57865" FT /evidence="ECO:0000269|PubMed:15857829, FT ECO:0000269|PubMed:18945668, ECO:0007744|PDB:2BNE, FT ECO:0007744|PDB:2BNF, ECO:0007744|PDB:2V4Y" FT BINDING 92..96 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:18945668, FT ECO:0007744|PDB:2V4Y" FT BINDING 101..103 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:18945668, FT ECO:0007744|PDB:2V4Y" FT BINDING 138..145 FT /ligand="UMP" FT /ligand_id="ChEBI:CHEBI:57865" FT /evidence="ECO:0000269|PubMed:15857829, FT ECO:0000269|PubMed:18945668, ECO:0007744|PDB:2BND, FT ECO:0007744|PDB:2BNE, ECO:0007744|PDB:2BNF, FT ECO:0007744|PDB:2V4Y" FT BINDING 165 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 171 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 174 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT VARIANT 62 FT /note="R -> H (in Smba9)" FT VARIANT 201 FT /note="D -> N (in Smba2)" FT MUTAGEN 62 FT /note="R->H: Loss of activation by GTP and decreased FT affinity for UTP." FT /evidence="ECO:0000269|PubMed:9457846" FT MUTAGEN 77 FT /note="D->N: Loss of activation by GTP and decreased FT affinity for UTP." FT /evidence="ECO:0000269|PubMed:9457846" FT MUTAGEN 93 FT /note="D->A: Loss of activation by GTP and of inhibition by FT UTP." FT /evidence="ECO:0000269|PubMed:18945668" FT MUTAGEN 138 FT /note="T->A: Loss of activation by GTP. Moderate loss of FT sensitivity to UTP inhibition. 4-fold and 2-fold decrease FT in affinity for UMP and ATP, respectively." FT /evidence="ECO:0000269|PubMed:15857829" FT MUTAGEN 140 FT /note="N->A: Loss of activation by GTP. Moderate loss of FT sensitivity to UTP inhibition." FT /evidence="ECO:0000269|PubMed:15857829, FT ECO:0000269|PubMed:18945668" FT MUTAGEN 146 FT /note="D->N: Drastically reduced activity." FT /evidence="ECO:0000269|PubMed:9457846" FT MUTAGEN 159 FT /note="D->N: Increased solubility at neutral pH. Nearly no FT change in kinetic properties and stability." FT /evidence="ECO:0000269|PubMed:9457846" FT MUTAGEN 174 FT /note="D->N: Reduced UMP-binding affinity." FT /evidence="ECO:0000269|PubMed:9457846" FT MUTAGEN 201 FT /note="D->N: Loss of activation by GTP." FT /evidence="ECO:0000269|PubMed:7711027, FT ECO:0000269|PubMed:9457846" FT CONFLICT 64..69 FT /note="AGLAKA -> RWSGET (in Ref. 1; CAA55388)" FT /evidence="ECO:0000305" FT STRAND 10..16 FT /evidence="ECO:0007829|PDB:2BNE" FT HELIX 18..21 FT /evidence="ECO:0007829|PDB:2BNE" FT STRAND 26..28 FT /evidence="ECO:0007829|PDB:2BNE" FT HELIX 31..46 FT /evidence="ECO:0007829|PDB:2BNE" FT STRAND 50..55 FT /evidence="ECO:0007829|PDB:2BNE" FT TURN 58..60 FT /evidence="ECO:0007829|PDB:2BNE" FT HELIX 63..68 FT /evidence="ECO:0007829|PDB:2BNE" FT HELIX 73..97 FT /evidence="ECO:0007829|PDB:2BNE" FT STRAND 102..108 FT /evidence="ECO:0007829|PDB:2BNE" FT TURN 111..113 FT /evidence="ECO:0007829|PDB:2BNE" FT STRAND 114..116 FT /evidence="ECO:0007829|PDB:2BNE" FT HELIX 119..127 FT /evidence="ECO:0007829|PDB:2BNE" FT STRAND 131..136 FT /evidence="ECO:0007829|PDB:2BNE" FT STRAND 139..142 FT /evidence="ECO:0007829|PDB:2BNF" FT HELIX 145..155 FT /evidence="ECO:0007829|PDB:2BNE" FT STRAND 159..169 FT /evidence="ECO:0007829|PDB:2BNE" FT STRAND 171..173 FT /evidence="ECO:0007829|PDB:2BNE" FT TURN 175..177 FT /evidence="ECO:0007829|PDB:2BND" FT STRAND 185..188 FT /evidence="ECO:0007829|PDB:2BNE" FT HELIX 189..194 FT /evidence="ECO:0007829|PDB:2BNE" FT HELIX 202..210 FT /evidence="ECO:0007829|PDB:2BNE" FT STRAND 215..219 FT /evidence="ECO:0007829|PDB:2BNE" FT HELIX 225..230 FT /evidence="ECO:0007829|PDB:2BNE" FT STRAND 236..240 FT /evidence="ECO:0007829|PDB:2BNE" SQ SEQUENCE 241 AA; 25970 MW; 82EFA75F7226E201 CRC64; MATNAKPVYK RILLKLSGEA LQGTEGFGID ASILDRMAQE IKELVELGIQ VGVVIGGGNL FRGAGLAKAG MNRVVGDHMG MLATVMNGLA MRDALHRAYV NARLMSAIPL NGVCDSYSWA EAISLLRNNR VVILSAGTGN PFFTTDSAAC LRGIEIEADV VLKATKVDGV FTADPAKDPT ATMYEQLTYS EVLEKELKVM DLAAFTLARD HKLPIRVFNM NKPGALRRVV MGEKEGTLIT E //