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P18314 (URE1_ENTAE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Urease subunit alpha

EC=3.5.1.5
Alternative name(s):
Urea amidohydrolase subunit alpha
Gene names
Name:ureC
OrganismEnterobacter aerogenes (Aerobacter aerogenes)
Taxonomic identifier548 [NCBI]
Taxonomic lineageBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEnterobacter

Protein attributes

Sequence length567 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

Urea + H2O = CO2 + 2 NH3. Ref.1 Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10

Cofactor

Binds 2 nickel ions per subunit. Ref.2 Ref.3 Ref.4

Enzyme regulation

The apoenzyme can be activated in vitro in the presence of nickel ions and carbon dioxide, which promotes carbamylation of Lys-217. Ref.7 Ref.8 Ref.9 Ref.10

Pathway

Nitrogen metabolism; urea degradation; CO(2) and NH(3) from urea (urease route): step 1/1. HAMAP-Rule MF_01953

Subunit structure

Heterotrimer of UreA (gamma), UreB (beta) and UreC (alpha) subunits. Three heterotrimers associate to form the active enzyme. The apoenzyme interacts with an accessory complex composed of UreD, UreF and UreG, which is required for the assembly of the nickel containing metallocenter of UreC. The UreE protein may also play a direct role as a metallochaperone in nickel transfer to the urease apoprotein. Ref.5 Ref.6 Ref.8 Ref.9 Ref.12

Subcellular location

Cytoplasm By similarity HAMAP-Rule MF_01953.

Post-translational modification

Carbamylation allows a single lysine to coordinate two nickel ions. HAMAP-Rule MF_01953

Sequence similarities

Belongs to the urease family.

Contains 1 urease domain.

Biophysicochemical properties

Kinetic parameters:

KM=2.3 mM for urea Ref.3 Ref.4 Ref.11 Ref.19

Vmax=1.9 mmol/min/mg enzyme

pH dependence:

Optimum pH is 7.75.

Ontologies

Keywords
   Cellular componentCytoplasm
   LigandMetal-binding
Nickel
   Molecular functionHydrolase
   Technical term3D-structure
Gene Ontology (GO)
   Biological_processurea catabolic process

Inferred from electronic annotation. Source: UniProtKB-UniPathway

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionnickel cation binding

Inferred from electronic annotation. Source: UniProtKB-HAMAP

protein binding

Inferred from physical interaction Ref.18Ref.19PubMed 23582331. Source: IntAct

urease activity

Inferred from electronic annotation. Source: UniProtKB-HAMAP

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ureAP1831611EBI-1028571,EBI-1028581

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 567567Urease subunit alpha HAMAP-Rule MF_01953
PRO_0000067543

Regions

Domain129 – 567439Urease

Sites

Active site3201Proton donor
Metal binding1341Nickel 2
Metal binding1361Nickel 2
Metal binding2171Nickel 1; via carbamate group
Metal binding2171Nickel 2; via carbamate group
Metal binding2461Nickel 1
Metal binding2721Nickel 1
Metal binding3601Nickel 2
Binding site2191Substrate

Amino acid modifications

Modified residue2171N6-carboxylysine HAMAP-Rule MF_01953

Experimental info

Mutagenesis1341H → A: Abrogates activity and reduces binding to nickel ions. Ref.4
Mutagenesis1361H → A: Abrogates activity and reduces binding to nickel ions. Ref.4
Mutagenesis2171K → A, C or E: Reduces activity 8000-fold and abrogates binding to nickel ions. Ref.17
Mutagenesis2191H → A: Reduces activity 500-fold and increases KM 1000-fold. Resistant to inactivation by diethylpyrocarbonate and iodoacetamide. Ref.4 Ref.19
Mutagenesis2191H → N or Q: Increases KM 100-fold; optimum pH is 6. Ref.4 Ref.19
Mutagenesis2211D → A: Reduces activity 1000-fold and increases KM 10-fold. Ref.19
Mutagenesis2211D → N: Reduces activity 50-fold. Ref.19
Mutagenesis2461H → A: Abrogates activity and reduces binding to nickel ions. Ref.4
Mutagenesis3121H → A: Enhances thermal stability above 50 degrees Celsius.
Mutagenesis3191C → A: Reduces activity 2-fold, but increases KM only 1.7-fold; optimum pH is 6.7. Reduces binding of nickel ions. Resistant to inactivation by iodoacetamide. Ref.3 Ref.18
Mutagenesis3191C → D: Reduces activity 20-fold, but increases KM only 1.9-fold; optimum pH is 5.2. Reduces binding of nickel ions. Resistant to inactivation by iodoacetamide. Ref.3 Ref.18
Mutagenesis3191C → S: Reduces activity 3000-fold, but increases KM only 3.9-fold; optimum pH is 5.2. Reduces binding of nickel ions. Resistant to inactivation by iodoacetamide. Ref.3 Ref.18
Mutagenesis3191C → Y: Abrogates activity. Ref.3 Ref.18
Mutagenesis3201H → A: Reduces activity 100000-fold, but increases KM only 3-fold; optimum pH is 6.75. Resistant to inactivation by diethylpyrocarbonate and iodoacetamide. Ref.4 Ref.19
Mutagenesis3201H → N or Q: Reduces activity 100000-fold, but increases KM only 3-fold. Ref.4 Ref.19
Mutagenesis3361R → Q: Reduces activity 10000-fold, but has no effect on KM. Ref.19

Secondary structure

................................................................................................................................. 567
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P18314 [UniParc].

Last modified November 1, 1990. Version 1.
Checksum: 2ECF3C4268A2E2C7

FASTA56760,305
        10         20         30         40         50         60 
MSNISRQAYA DMFGPTVGDK VRLADTELWI EVEDDLTTYG EEVKFGGGKV IRDGMGQGQM 

        70         80         90        100        110        120 
LAADCVDLVL TNALIVDHWG IVKADIGVKD GRIFAIGKAG NPDIQPNVTI PIGAATEVIA 

       130        140        150        160        170        180 
AEGKIVTAGG IDTHIHWICP QQAEEALVSG VTTMVGGGTG PAAGTHATTC TPGPWYISRM 

       190        200        210        220        230        240 
LQAADSLPVN IGLLGKGNVS QPDALREQVA AGVIGLKIHE DWGATPAAID CALTVADEMD 

       250        260        270        280        290        300 
IQVALHSDTL NESGFVEDTL AAIGGRTIHT FHTEGAGGGH APDIITACAH PNILPSSTNP 

       310        320        330        340        350        360 
TLPYTLNTID EHLDMLMVCH HLDPDIAEDV AFAESRIRRE TIAAEDVLHD LGAFSLTSSD 

       370        380        390        400        410        420 
SQAMGRVGEV ILRTWQVAHR MKVQRGALAE ETGDNDNFRV KRYIAKYTIN PALTHGIAHE 

       430        440        450        460        470        480 
VGSIEVGKLA DLVVWSPAFF GVKPATVIKG GMIAIAPMGD INASIPTPQP VHYRPMFGAL 

       490        500        510        520        530        540 
GSARHHCRLT FLSQAAAANG VAERLNLRSA IAVVKGCRTV QKADMVHNSL QPNITVDAQT 

       550        560 
YEVRVDGELI TSEPADVLPM AQRYFLF 

« Hide

References

[1]"Sequence of the Klebsiella aerogenes urease genes and evidence for accessory proteins facilitating nickel incorporation."
Mulrooney S.B., Hausinger R.P.
J. Bacteriol. 172:5837-5843(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], CATALYTIC ACTIVITY.
Strain: CG253.
[2]"Klebsiella aerogenes urease gene cluster: sequence of ureD and demonstration that four accessory genes (ureD, ureE, ureF, and ureG) are involved in nickel metallocenter biosynthesis."
Lee M.H., Mulrooney S.B., Renner M.J., Markowicz Y., Hausinger R.P.
J. Bacteriol. 174:4324-4330(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: COFACTOR.
[3]"Site-directed mutagenesis of the active site cysteine in Klebsiella aerogenes urease."
Martin P.R., Hausinger R.P.
J. Biol. Chem. 267:20024-20027(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF CYS-319.
[4]"Site-directed mutagenesis of Klebsiella aerogenes urease: identification of histidine residues that appear to function in nickel ligation, substrate binding, and catalysis."
Park I.-S., Hausinger R.P.
Protein Sci. 2:1034-1041(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF HIS-134; HIS-136; HIS-219; HIS-246; HIS-320 AND HIS-320.
[5]"In vitro activation of urease apoprotein and role of UreD as a chaperone required for nickel metallocenter assembly."
Park I.-S., Carr M.B., Hausinger R.P.
Proc. Natl. Acad. Sci. U.S.A. 91:3233-3237(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, INTERACTION WITH UREA; UREB AND URED.
[6]"Evidence for the presence of urease apoprotein complexes containing UreD, UreF, and UreG in cells that are competent for in vivo enzyme activation."
Park I.-S., Hausinger R.P.
J. Bacteriol. 177:1947-1951(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, INTERACTION WITH UREA; UREB; URED; UREF AND UREG.
[7]"Requirement of carbon dioxide for in vitro assembly of the urease nickel metallocenter."
Park I.-S., Hausinger R.P.
Science 267:1156-1158(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION.
[8]"Purification and activation properties of UreD-UreF-urease apoprotein complexes."
Moncrief M.B.C., Hausinger R.P.
J. Bacteriol. 178:5417-5421(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION, INTERACTION WITH UREA; UREB; URED AND UREF.
[9]"GTP-dependent activation of urease apoprotein in complex with the UreD, UreF, and UreG accessory proteins."
Soriano A., Hausinger R.P.
Proc. Natl. Acad. Sci. U.S.A. 96:11140-11144(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION, INTERACTION WITH UREA; UREB; URED; UREF AND UREG.
[10]"UreE stimulation of GTP-dependent urease activation in the UreD-UreF-UreG-urease apoprotein complex."
Soriano A., Colpas G.J., Hausinger R.P.
Biochemistry 39:12435-12440(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION, ACTIVATION OF THE APOPROTEIN BY UREE.
[11]"Dual effects of ionic strength on Klebsiella aerogenes urease: pH-dependent activation and inhibition."
Mulrooney S.B., Zakharian T., Schaller R.A., Hausinger R.P.
Arch. Biochem. Biophys. 394:280-282(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
[12]"Chemical cross-linking and mass spectrometric identification of sites of interaction for UreD, UreF, and urease."
Chang Z., Kuchar J., Hausinger R.P.
J. Biol. Chem. 279:15305-15313(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UREA; UREB; URED AND UREF, IDENTIFICATION BY MASS SPECTROMETRY.
[13]"The crystal structure of urease from Klebsiella aerogenes."
Jabri E., Carr M.B., Hausinger R.P., Karplus P.A.
Science 268:998-1004(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH UREA; UREB AND NICKEL IONS, CARBAMYLATION AT LYS-217.
[14]"Structures of the Klebsiella aerogenes urease apoenzyme and two active-site mutants."
Jabri E., Karplus P.A.
Biochemistry 35:10616-10626(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF WILD-TYPE AND MUTANTS ALA-219 AND ALA-320 IN COMPLEX WITH UREA; UREB AND NICKEL IONS, CARBAMYLATION AT LYS-217.
[15]"Characterization of the mononickel metallocenter in H134A mutant urease."
Park I.-S., Michel L.O., Pearson M.A., Jabri E., Karplus P.A., Wang S., Dong J., Scott R.A., Koehler B.P., Johnson M.K., Hausinger R.P.
J. Biol. Chem. 271:18632-18637(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF MUTANT ALA-134 IN COMPLEX WITH UREA; UREB AND NICKEL IONS, MAGNETIC CIRCULAR DICHROISM, ABSORPTION SPECTROSCOPY, CARBAMYLATION AT LYS-217.
[16]"Structures of Cys319 variants and acetohydroxamate-inhibited Klebsiella aerogenes urease."
Pearson M.A., Michel L.O., Hausinger R.P., Karplus P.A.
Biochemistry 36:8164-8172(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF MUTANTS ALA/ASP/SER/TYR-319 IN COMPLEX WITH UREA; UREB; NICKEL IONS AND ACETOHYDROXAMIC ACID.
[17]"Chemical rescue of Klebsiella aerogenes urease variants lacking the carbamylated-lysine nickel ligand."
Pearson M.A., Schaller R.A., Michel L.O., Karplus P.A., Hausinger R.P.
Biochemistry 37:6214-6220(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF MUTANTS ALA/CYS/GLU-217 IN COMPLEX WITH UREA; UREB AND FORMATE, MUTAGENESIS OF LYS-217.
[18]"Characterization of metal-substituted Klebsiella aerogenes urease."
Yamaguchi K., Cosper N.J., Staalhandske C., Scott R.A., Pearson M.A., Karplus P.A., Hausinger R.P.
J. Biol. Inorg. Chem. 4:468-477(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH UREA; UREB AND MANGANESE IONS, ABSORPTION SPECTROSCOPY, MUTAGENESIS OF CYS-319.
[19]"Kinetic and structural characterization of urease active site variants."
Pearson M.A., Park I.-S., Schaller R.A., Michel L.O., Karplus P.A., Hausinger R.P.
Biochemistry 39:8575-8584(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF WILD-TYPE AND MUTANTS ASN/GLN-219; ALA-221 AND ASN/GLN-320 IN COMPLEX WITH UREA; UREB AND NICKEL IONS, CARBAMYLATION AT LYS-217, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF HIS-219; ASP-221; HIS-320 AND ARG-336.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M36068 Genomic DNA. Translation: AAA25151.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1A5KX-ray2.20C2-567[»]
1A5LX-ray2.20C2-567[»]
1A5MX-ray2.00C2-567[»]
1A5NX-ray2.40C2-567[»]
1A5OX-ray2.50C2-567[»]
1EF2X-ray2.50A2-567[»]
1EJRX-ray2.00C1-567[»]
1EJSX-ray2.00C1-567[»]
1EJTX-ray2.00C1-567[»]
1EJUX-ray2.00C1-567[»]
1EJVX-ray2.40C1-567[»]
1EJWX-ray1.90C1-567[»]
1EJXX-ray1.60C1-567[»]
1FWAX-ray2.00C1-567[»]
1FWBX-ray2.00C1-567[»]
1FWCX-ray2.00C1-567[»]
1FWDX-ray2.00C1-567[»]
1FWEX-ray2.00C1-567[»]
1FWFX-ray2.00C1-567[»]
1FWGX-ray2.00C1-567[»]
1FWHX-ray2.00C1-567[»]
1FWIX-ray2.00C1-567[»]
1FWJX-ray2.20C1-567[»]
1KRAX-ray2.30C1-567[»]
1KRBX-ray2.50C1-567[»]
1KRCX-ray2.50C1-567[»]
2KAUX-ray2.00C1-567[»]
4EP8X-ray1.55C2-567[»]
4EPBX-ray1.75C2-567[»]
4EPDX-ray1.70C2-567[»]
4EPEX-ray2.05C2-567[»]
ProteinModelPortalP18314.
SMRP18314. Positions 2-567.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP18314. 3 interactions.

Chemistry

DrugBankDB00551. Acetohydroxamic Acid.

Protein family/group databases

MEROPSM38.982.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Enzyme and pathway databases

SABIO-RKP18314.
UniPathwayUPA00258; UER00370.

Family and domain databases

Gene3D2.30.40.10. 1 hit.
HAMAPMF_01953. Urease_alpha.
InterProIPR006680. Amidohydro_1.
IPR011059. Metal-dep_hydrolase_composite.
IPR011612. Urease_alpha_N.
IPR005848. Urease_asu.
IPR017951. Urease_asu_c.
IPR017950. Urease_asu_CS.
[Graphical view]
PfamPF01979. Amidohydro_1. 1 hit.
PF00449. Urease_alpha. 1 hit.
[Graphical view]
PRINTSPR01752. UREASE.
SUPFAMSSF51338. SSF51338. 2 hits.
TIGRFAMsTIGR01792. urease_alph. 1 hit.
PROSITEPS01120. UREASE_1. 1 hit.
PS00145. UREASE_2. 1 hit.
PS51368. UREASE_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP18314.

Entry information

Entry nameURE1_ENTAE
AccessionPrimary (citable) accession number: P18314
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: November 1, 1990
Last modified: July 9, 2014
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways