URE23_HELPY
ID URE23_HELPY Reviewed; 238 AA.
AC P14916;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Urease subunit alpha {ECO:0000255|HAMAP-Rule:MF_01955};
DE EC=3.5.1.5 {ECO:0000255|HAMAP-Rule:MF_01955};
DE AltName: Full=Urea amidohydrolase subunit alpha {ECO:0000255|HAMAP-Rule:MF_01955};
GN Name=ureA {ECO:0000255|HAMAP-Rule:MF_01955}; Synonyms=hpuA;
GN OrderedLocusNames=HP_0073;
OS Helicobacter pylori (strain ATCC 700392 / 26695) (Campylobacter pylori).
OC Bacteria; Proteobacteria; Epsilonproteobacteria; Campylobacterales;
OC Helicobacteraceae; Helicobacter.
OX NCBI_TaxID=85962;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=CPM630;
RX PubMed=2326167; DOI=10.1093/nar/18.2.362;
RA Clayton C.L., Pallen M.J., Kleanthous H., Wren B.W., Tabaqchali S.;
RT "Nucleotide sequence of two genes from Helicobacter pylori encoding for
RT urease subunits.";
RL Nucleic Acids Res. 18:362-362(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=85P;
RX PubMed=2001995; DOI=10.1128/jb.173.6.1920-1931.1991;
RA Labigne A., Cussac V., Courcoux P.;
RT "Shuttle cloning and nucleotide sequences of Helicobacter pylori genes
RT responsible for urease activity.";
RL J. Bacteriol. 173:1920-1931(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=HPK5;
RX PubMed=10844692; DOI=10.1046/j.1365-2958.2000.01918.x;
RA Akada J.K., Shirai M., Takeuchi H., Tsuda M., Nakazawa T.;
RT "Identification of the urease operon in Helicobacter pylori and its control
RT by mRNA decay in response to pH.";
RL Mol. Microbiol. 36:1071-1084(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700392 / 26695;
RX PubMed=9252185; DOI=10.1038/41483;
RA Tomb J.-F., White O., Kerlavage A.R., Clayton R.A., Sutton G.G.,
RA Fleischmann R.D., Ketchum K.A., Klenk H.-P., Gill S.R., Dougherty B.A.,
RA Nelson K.E., Quackenbush J., Zhou L., Kirkness E.F., Peterson S.N.,
RA Loftus B.J., Richardson D.L., Dodson R.J., Khalak H.G., Glodek A.,
RA McKenney K., FitzGerald L.M., Lee N., Adams M.D., Hickey E.K., Berg D.E.,
RA Gocayne J.D., Utterback T.R., Peterson J.D., Kelley J.M., Cotton M.D.,
RA Weidman J.F., Fujii C., Bowman C., Watthey L., Wallin E., Hayes W.S.,
RA Borodovsky M., Karp P.D., Smith H.O., Fraser C.M., Venter J.C.;
RT "The complete genome sequence of the gastric pathogen Helicobacter
RT pylori.";
RL Nature 388:539-547(1997).
RN [5]
RP PROTEIN SEQUENCE OF 1-20.
RX PubMed=2318539; DOI=10.1128/iai.58.4.992-998.1990;
RA Hu L.-T., Mobley H.L.T.;
RT "Purification and N-terminal analysis of urease from Helicobacter pylori.";
RL Infect. Immun. 58:992-998(1990).
RN [6]
RP PROTEIN SEQUENCE OF 1-20, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND INTERACTION WITH UREB.
RX PubMed=2188975; DOI=10.1016/s0021-9258(19)38872-6;
RA Dunn B.E., Campbell G.P., Perez-Perez G.I., Blaser M.J.;
RT "Purification and characterization of urease from Helicobacter pylori.";
RL J. Biol. Chem. 265:9464-9469(1990).
RN [7]
RP PROTEIN SEQUENCE OF 1-20.
RC STRAIN=ATCC 43504 / NCTC 11637 / JCM 7653 / RPH 13487;
RX PubMed=1452359; DOI=10.1128/iai.60.12.5259-5266.1992;
RA Turbett G.R., Hoej P.B., Horne R., Mee B.J.;
RT "Purification and characterization of the urease enzymes of Helicobacter
RT species from humans and animals.";
RL Infect. Immun. 60:5259-5266(1992).
RN [8]
RP DISRUPTION PHENOTYPE.
RC STRAIN=85P;
RX PubMed=1313413; DOI=10.1128/jb.174.8.2466-2473.1992;
RA Cussac V., Ferrero R.L., Labigne A.;
RT "Expression of Helicobacter pylori urease genes in Escherichia coli grown
RT under nitrogen-limiting conditions.";
RL J. Bacteriol. 174:2466-2473(1992).
RN [9]
RP CATALYTIC ACTIVITY.
RX PubMed=1612735; DOI=10.1128/iai.60.7.2657-2666.1992;
RA Hu L.-T., Foxall P.A., Russell R., Mobley H.L.T.;
RT "Purification of recombinant Helicobacter pylori urease apoenzyme encoded
RT by ureA and ureB.";
RL Infect. Immun. 60:2657-2666(1992).
RN [10]
RP FUNCTION.
RX PubMed=8039935; DOI=10.1128/iai.62.8.3586-3589.1994;
RA Tsuda M., Karita M., Morshed M.G., Okita K., Nakazawa T.;
RT "A urease-negative mutant of Helicobacter pylori constructed by allelic
RT exchange mutagenesis lacks the ability to colonize the nude mouse
RT stomach.";
RL Infect. Immun. 62:3586-3589(1994).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=8641799; DOI=10.1128/iai.64.3.905-912.1996;
RA Phadnis S.H., Parlow M.H., Levy M., Ilver D., Caulkins C.M., Connors J.B.,
RA Dunn B.E.;
RT "Surface localization of Helicobacter pylori urease and a heat shock
RT protein homolog requires bacterial autolysis.";
RL Infect. Immun. 64:905-912(1996).
RN [12]
RP INDUCTION.
RX PubMed=11447165; DOI=10.1128/iai.69.8.4891-4897.2001;
RA van Vliet A.H.M., Kuipers E.J., Waidner B., Davies B.J., de Vries N.,
RA Penn C.W., Vandenbroucke-Grauls C.M.J.E., Kist M., Bereswill S.,
RA Kusters J.G.;
RT "Nickel-responsive induction of urease expression in Helicobacter pylori is
RT mediated at the transcriptional level.";
RL Infect. Immun. 69:4891-4897(2001).
RN [13]
RP REVIEW ON VIRULENCE OF H.PYLORI.
RX PubMed=17313591; DOI=10.1111/j.1574-6968.2007.00648.x;
RA Clyne M., Dolan B., Reeves E.P.;
RT "Bacterial factors that mediate colonization of the stomach and virulence
RT of Helicobacter pylori.";
RL FEMS Microbiol. Lett. 268:135-143(2007).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS), SUBUNIT STRUCTURE, AND PH
RP DEPENDENCE.
RX PubMed=11373617; DOI=10.1038/88563;
RA Ha N.-C., Oh S.-T., Sung J.Y., Cha K.A., Lee M.H., Oh B.-H.;
RT "Supramolecular assembly and acid resistance of Helicobacter pylori
RT urease.";
RL Nat. Struct. Biol. 8:505-509(2001).
CC -!- FUNCTION: Ammonia produced by ureolysis increases the gastric pH
CC thereby providing an environment permissive for colonization of the
CC stomach. {ECO:0000269|PubMed:8039935}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H(+) + H2O + urea = CO2 + 2 NH4(+); Xref=Rhea:RHEA:20557,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16199,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:28938; EC=3.5.1.5;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01955,
CC ECO:0000269|PubMed:1612735, ECO:0000269|PubMed:2188975};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.48 mM for urea {ECO:0000269|PubMed:2188975};
CC Vmax=1.1 mmol/min/mg enzyme {ECO:0000269|PubMed:2188975};
CC pH dependence:
CC Optimum pH is 8.0. Active from pH 4.0 to 10.0. In unbuffered
CC solutions, the dodecameric complex is active at pH 3.0.
CC {ECO:0000269|PubMed:11373617, ECO:0000269|PubMed:2188975};
CC -!- PATHWAY: Nitrogen metabolism; urea degradation; CO(2) and NH(3) from
CC urea (urease route): step 1/1. {ECO:0000255|HAMAP-Rule:MF_01955}.
CC -!- SUBUNIT: Heterohexamer of 3 UreA (alpha) and 3 UreB (beta) subunits.
CC Four heterohexamers assemble to form a 16 nm dodecameric complex.
CC {ECO:0000255|HAMAP-Rule:MF_01955, ECO:0000269|PubMed:11373617}.
CC -!- INTERACTION:
CC P14916; P69996: ureB; NbExp=2; IntAct=EBI-7737170, EBI-7566591;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01955,
CC ECO:0000269|PubMed:8641799}. Note=Also associates with the outer
CC membrane upon autolysis of neighboring bacteria.
CC -!- INDUCTION: By nickel ions. {ECO:0000269|PubMed:11447165}.
CC -!- DISRUPTION PHENOTYPE: Cells do not express urease.
CC {ECO:0000269|PubMed:1313413}.
CC -!- MISCELLANEOUS: The novel dodecameric structure of the enzyme may allow
CC it to remain active at the cell surface at acidic gastric pH. Within
CC this dodecameric structure the 12 active sites are clustered within the
CC interior of the proteinaceous shell. This may allow a high local
CC concentration of ammonia within the enzyme which may protect the
CC nickel-chelating groups from protonation.
CC -!- SIMILARITY: In the N-terminal section; belongs to the urease gamma
CC subunit family. {ECO:0000255|HAMAP-Rule:MF_01955}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the urease beta
CC subunit family. {ECO:0000255|HAMAP-Rule:MF_01955}.
CC -!- CAUTION: The orthologous protein is known as the gamma/beta subunit
CC (UreAB) in most other bacteria. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Going unnoticed - Issue 95
CC of June 2008;
CC URL="https://web.expasy.org/spotlight/back_issues/095";
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DR EMBL; X17079; CAA34932.1; -; Genomic_DNA.
DR EMBL; M60398; AAA25020.1; -; Genomic_DNA.
DR EMBL; AB032429; BAA84532.1; -; Genomic_DNA.
DR EMBL; AE000511; AAD07144.1; -; Genomic_DNA.
DR PIR; A38537; URKCAP.
DR RefSeq; NP_206873.1; NC_000915.1.
DR RefSeq; WP_000779223.1; NC_018939.1.
DR PDB; 1E9Y; X-ray; 3.00 A; A=1-238.
DR PDB; 1E9Z; X-ray; 3.00 A; A=1-238.
DR PDB; 6QSU; EM; 2.40 A; A/C/E/G/I/K/M/O/Q/S/U/W=1-238.
DR PDB; 6ZJA; EM; 2.00 A; A/C/E/G/I/K/M/O/Q/S/U/W=1-238.
DR PDBsum; 1E9Y; -.
DR PDBsum; 1E9Z; -.
DR PDBsum; 6QSU; -.
DR PDBsum; 6ZJA; -.
DR AlphaFoldDB; P14916; -.
DR SMR; P14916; -.
DR DIP; DIP-3146N; -.
DR IntAct; P14916; 7.
DR MINT; P14916; -.
DR STRING; 85962.C694_00355; -.
DR BindingDB; P14916; -.
DR ChEMBL; CHEMBL3885651; -.
DR PaxDb; P14916; -.
DR DNASU; 900171; -.
DR EnsemblBacteria; AAD07144; AAD07144; HP_0073.
DR KEGG; hpy:HP_0073; -.
DR PATRIC; fig|85962.47.peg.77; -.
DR eggNOG; COG0831; Bacteria.
DR eggNOG; COG0832; Bacteria.
DR OMA; DNTGDRP; -.
DR PhylomeDB; P14916; -.
DR BioCyc; MetaCyc:HP_RS00370-MON; -.
DR BRENDA; 3.5.1.5; 2604.
DR SABIO-RK; P14916; -.
DR UniPathway; UPA00258; UER00370.
DR EvolutionaryTrace; P14916; -.
DR PHI-base; PHI:7264; -.
DR Proteomes; UP000000429; Chromosome.
DR GO; GO:0035550; C:urease complex; IEA:InterPro.
DR GO; GO:0016151; F:nickel cation binding; IEA:InterPro.
DR GO; GO:0009039; F:urease activity; IEA:UniProtKB-UniRule.
DR GO; GO:0043419; P:urea catabolic process; IMP:CACAO.
DR CDD; cd00407; Urease_beta; 1.
DR CDD; cd00390; Urease_gamma; 1.
DR Gene3D; 2.10.150.10; -; 1.
DR Gene3D; 3.30.280.10; -; 1.
DR HAMAP; MF_01954; Urease_beta; 1.
DR HAMAP; MF_01955; Urease_beta_gamma; 1.
DR InterPro; IPR002019; Urease_beta.
DR InterPro; IPR036461; Urease_betasu_sf.
DR InterPro; IPR008223; Urease_gamma-beta_su.
DR InterPro; IPR002026; Urease_gamma/gamma-beta_su.
DR InterPro; IPR036463; Urease_gamma_sf.
DR Pfam; PF00699; Urease_beta; 1.
DR Pfam; PF00547; Urease_gamma; 1.
DR PIRSF; PIRSF001225; Urease_gammabeta; 1.
DR SUPFAM; SSF51278; SSF51278; 1.
DR SUPFAM; SSF54111; SSF54111; 1.
DR TIGRFAMs; TIGR00192; urease_beta; 1.
DR TIGRFAMs; TIGR00193; urease_gam; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Direct protein sequencing; Hydrolase;
KW Reference proteome; Virulence.
FT CHAIN 1..238
FT /note="Urease subunit alpha"
FT /id="PRO_0000098075"
FT REGION 1..102
FT /note="Urease gamma"
FT REGION 103..238
FT /note="Urease beta"
FT CONFLICT 14
FT /note="H -> S (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 37
FT /note="A -> R (in Ref. 1; CAA34932)"
FT /evidence="ECO:0000305"
FT CONFLICT 49
FT /note="A -> R (in Ref. 1; CAA34932)"
FT /evidence="ECO:0000305"
FT CONFLICT 132..133
FT /note="KN -> PP (in Ref. 1; CAA34932)"
FT /evidence="ECO:0000305"
FT HELIX 5..25
FT /evidence="ECO:0007829|PDB:6ZJA"
FT HELIX 32..49
FT /evidence="ECO:0007829|PDB:6ZJA"
FT HELIX 54..60
FT /evidence="ECO:0007829|PDB:6ZJA"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:6ZJA"
FT HELIX 67..69
FT /evidence="ECO:0007829|PDB:6ZJA"
FT HELIX 74..77
FT /evidence="ECO:0007829|PDB:6ZJA"
FT STRAND 79..87
FT /evidence="ECO:0007829|PDB:6ZJA"
FT STRAND 90..97
FT /evidence="ECO:0007829|PDB:6ZJA"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:6ZJA"
FT STRAND 127..133
FT /evidence="ECO:0007829|PDB:6ZJA"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:6ZJA"
FT STRAND 139..142
FT /evidence="ECO:0007829|PDB:6ZJA"
FT HELIX 147..149
FT /evidence="ECO:0007829|PDB:6ZJA"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:6ZJA"
FT HELIX 158..161
FT /evidence="ECO:0007829|PDB:6ZJA"
FT STRAND 164..166
FT /evidence="ECO:0007829|PDB:6ZJA"
FT STRAND 173..176
FT /evidence="ECO:0007829|PDB:6ZJA"
FT STRAND 181..188
FT /evidence="ECO:0007829|PDB:6ZJA"
FT HELIX 208..220
FT /evidence="ECO:0007829|PDB:6ZJA"
SQ SEQUENCE 238 AA; 26540 MW; 4E77328669CD9A2D CRC64;
MKLTPKELDK LMLHYAGELA KKRKEKGIKL NYVEAVALIS AHIMEEARAG KKTAAELMQE
GRTLLKPDDV MDGVASMIHE VGIEAMFPDG TKLVTVHTPI EANGKLVPGE LFLKNEDITI
NEGKKAVSVK VKNVGDRPVQ IGSHFHFFEV NRCLDFDREK TFGKRLDIAS GTAVRFEPGE
EKSVELIDIG GNRRIFGFNA LVDRQADNES KKIALHRAKE RGFHGAKSDD NYVKTIKE
