P69996 (URE1_HELPY) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Urease subunit beta
EC=3.5.1.5

Alternative name(s):
Urea amidohydrolase subunit beta

Gene names

Name:	ureB
Synonyms:	hpuB
Ordered Locus Names:	HP_0072

Organism

Helicobacter pylori (strain ATCC 700392 / 26695) (Campylobacter pylori)

Taxonomic identifier

85962 [NCBI]

Taxonomic lineage

Bacteria › Proteobacteria › Epsilonproteobacteria › Campylobacterales › Helicobacteraceae › Helicobacter

Protein attributes

Sequence length	569 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Ammonia produced by ureolysis increases the gastric pH thereby providing an environment permissive for colonization of the stomach. Ref.10
Catalytic activity	Urea + H2O = CO2 + 2 NH3. Ref.4 Ref.5 Ref.9
Cofactor	Binds 2 nickel ions per subunit.
Pathway	Nitrogen metabolism; urea degradation; CO(2) and NH(3) from urea (urease route): step 1/1. HAMAP MF_01953
Subunit structure	Heterohexamer of 3 UreA (alpha) and 3 UreB (beta) subunits. Four heterohexamers assemble to form a 16 nm dodecameric complex. Ref.14
Subcellular location	Cytoplasm. Note: Also associates with the outer membrane upon autolysis of neighboring bacteria. Ref.11
Induction	By nickel ions. Ref.12 Ref.13
Post-translational modification	Carbamylation allows a single lysine to coordinate two nickel ions. HAMAP MF_01953
Disruption phenotype	Cells do not express urease. Ref.8
Miscellaneous	The novel dodecameric structure of the enzyme may allow it to remain active at the cell surface at acidic gastric pH. Within this dodecameric structure the 12 active sites are clustered within the interior of the proteinaceous shell. This may allow a high local concentration of ammonia within the enzyme which may protect the nickel-chelating groups from protonation. HAMAP MF_01953
Sequence similarities	Belongs to the urease family. Contains 1 urease domain.
Caution	The orthologous protein is known as the alpha subunit (UreC) in most other bacteria.
Biophysicochemical properties	Kinetic parameters: KM=0.48 mM for urea Ref.4 Ref.5 Vmax=1.1 mmol/min/mg enzyme pH dependence: Optimum pH is 8.0. Active from pH 4.0 to 10.0. In unbuffered solutions, the dodecameric complex is active at pH3.0.

Ontologies

Keywords
Biological process	Virulence
Cellular component	Cytoplasm
Ligand	Metal-binding Nickel
Molecular function	Hydrolase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	pathogenesis Inferred from electronic annotation. Source: UniProtKB-KW urea metabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	nickel cation binding Inferred from electronic annotation. Source: InterPro urease activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 569

569

Urease subunit beta HAMAP MF_01953

PRO_0000067533

Regions

Domain

131 – 569

439

Urease

Sites

Active site

322

1

Proton donor Probable

Metal binding

136

1

Nickel 2

Metal binding

138

1

Nickel 2

Metal binding

219

1

Nickel 1; via carbamate group

Metal binding

219

1

Nickel 2; via carbamate group

Metal binding

248

1

Nickel 1

Metal binding

274

1

Nickel 1

Metal binding

362

1

Nickel 2

Binding site

221

1

Substrate Probable

Amino acid modifications

Modified residue

219

1

N6-carboxylysine HAMAP MF_01953

Experimental info

Sequence conflict

10

1

V → A in CAA34933. Ref.2

Sequence conflict

19

1

D → A Ref.2

Sequence conflict

22

1

R → C AA sequence Ref.4

Sequence conflict

27

1

D → C AA sequence Ref.4

Sequence conflict

104

1

M → T in CAA34933. Ref.2

Sequence conflict

181

1

W → F in CAA34933. Ref.2

Sequence conflict

193

1

L → F in CAA34933. Ref.2

Sequence conflict

218

1

F → L in CAA34933. Ref.2

Sequence conflict

273

1

F → Y in CAA34933. Ref.2

Sequence conflict

540

1

P → S in CAA34933. Ref.2

Sequence conflict

554 – 569

16

SKPAN…LFSIF → LNQPIK in CAA34933. Ref.2

Secondary structure

1

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569

Helix Strand Turn

Details...

Beta strand

3 – 5

3

Helix

6 – 10

5

Beta strand

20 – 22

3

Beta strand

29 – 31

3

Turn

54 – 56

3

Beta strand

67 – 77

11

Beta strand

80 – 89

10

Beta strand

92 – 97

6

Turn

102 – 104

3

Beta strand

105 – 107

3

Helix

110 – 112

3

Beta strand

119 – 122

4

Beta strand

127 – 130

4

Beta strand

132 – 138

7

Helix

144 – 150

7

Beta strand

153 – 159

7

Helix

165 – 169

5

Helix

175 – 186

12

Beta strand

189 – 198

10

Helix

204 – 212

9

Beta strand

216 – 220

5

Helix

222 – 224

3

Helix

228 – 240

13

Beta strand

244 – 247

4

Helix

258 – 265

8

Beta strand

270 – 272

3

Turn

273 – 276

4

Turn

283 – 285

3

Helix

286 – 291

6

Beta strand

295 – 299

5

Helix

301 – 303

3

Helix

310 – 320

11

Turn

321 – 323

3

Helix

329 – 338

10

Helix

341 – 352

12

Helix

372 – 387

16

Beta strand

395 – 397

3

Helix

399 – 406

8

Helix

407 – 409

3

Helix

411 – 416

6

Turn

420 – 422

3

Beta strand

423 – 426

4

Beta strand

434 – 437

4

Turn

439 – 444

6

Beta strand

447 – 451

5

Beta strand

454 – 460

7

Beta strand

465 – 468

4

Beta strand

474 – 477

4

Helix

479 – 481

3

Helix

485 – 489

5

Beta strand

491 – 494

4

Helix

496 – 500

5

Helix

503 – 506

4

Beta strand

511 – 515

5

Helix

524 – 526

3

Beta strand

536 – 538

3

Turn

540 – 542

3

Beta strand

545 – 547

3

Beta strand

561 – 563

3

Turn

564 – 566

3

Sequences

	Sequence		Length	Mass (Da)
	P69996 [UniParc]. Last modified January 4, 2005. Version 1. Checksum: 4C8A6BC6C8295584	FASTA	569	61,684
	10 20 30 40 50 60 MKKISRKEYV SMYGPTTGDK VRLGDTDLIA EVEHDYTIYG EELKFGGGKT LREGMSQSNN 70 80 90 100 110 120 PSKEELDLII TNALIVDYTG IYKADIGIKD GKIAGIGKGG NKDMQDGVKN NLSVGPATEA 130 140 150 160 170 180 LAGEGLIVTA GGIDTHIHFI SPQQIPTAFA SGVTTMIGGG TGPADGTNAT TITPGRRNLK 190 200 210 220 230 240 WMLRAAEEYS MNLGFLAKGN ASNDASLADQ IEAGAIGFKI HEDWGTTPSA INHALDVADK 250 260 270 280 290 300 YDVQVAIHTD TLNEAGCVED TMAAIAGRTM HTFHTEGAGG GHAPDIIKVA GEHNILPAST 310 320 330 340 350 360 NPTIPFTVNT EAEHMDMLMV CHHLDKSIKE DVQFADSRIR PQTIAAEDTL HDMGIFSITS 370 380 390 400 410 420 SDSQAMGRVG EVITRTWQTA DKNKKEFGRL KEEKGDNDNF RIKRYLSKYT INPAIAHGIS 430 440 450 460 470 480 EYVGSVEVGK VADLVLWSPA FFGVKPNMII KGGFIALSQM GDANASIPTP QPVYYREMFA 490 500 510 520 530 540 HHGKAKYDAN ITFVSQAAYD KGIKEELGLE RQVLPVKNCR NITKKDMQFN DTTAHIEVNP 550 560 ETYHVFVDGK EVTSKPANKV SLAQLFSIF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Shuttle cloning and nucleotide sequences of Helicobacter pylori genes responsible for urease activity." Labigne A., Cussac V., Courcoux P. J. Bacteriol. 173:1920-1931(1991) [PubMed: 2001995] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: 85P.
[2]	"Nucleotide sequence of two genes from Helicobacter pylori encoding for urease subunits." Clayton C.L., Pallen M.J., Kleanthous H., Wren B.W., Tabaqchali S. Nucleic Acids Res. 18:362-362(1990) [PubMed: 2326167] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: CPM630.
[3]	"The complete genome sequence of the gastric pathogen Helicobacter pylori." Tomb J.-F., White O., Kerlavage A.R., Clayton R.A., Sutton G.G., Fleischmann R.D., Ketchum K.A., Klenk H.-P., Gill S.R., Dougherty B.A., Nelson K.E., Quackenbush J., Zhou L., Kirkness E.F., Peterson S.N., Loftus B.J., Richardson D.L., Dodson R.J. , Khalak H.G., Glodek A., McKenney K., FitzGerald L.M., Lee N., Adams M.D., Hickey E.K., Berg D.E., Gocayne J.D., Utterback T.R., Peterson J.D., Kelley J.M., Cotton M.D., Weidman J.F., Fujii C., Bowman C., Watthey L., Wallin E., Hayes W.S., Borodovsky M., Karp P.D., Smith H.O., Fraser C.M., Venter J.C. Nature 388:539-547(1997) [PubMed: 9252185] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 700392 / 26695.
[4]	"Characterization of the Helicobacter pylori urease and purification of its subunits." Evans D.J. Jr., Evans D.G., Kirkpatrick S.S., Graham D.Y. Microb. Pathog. 10:15-26(1991) [PubMed: 1857197] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-30, CATALYTIC ACTIVITY, KINETIC PARAMETERS.
[5]	"Purification and characterization of urease from Helicobacter pylori." Dunn B.E., Campbell G.P., Perez-Perez G.I., Blaser M.J. J. Biol. Chem. 265:9464-9469(1990) [PubMed: 2188975] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-20, CATALYTIC ACTIVITY, KINETIC PARAMETERS, INTERACTION WITH UREA.
[6]	"Purification and N-terminal analysis of urease from Helicobacter pylori." Hu L.-T., Mobley H.L.T. Infect. Immun. 58:992-998(1990) [PubMed: 2318539] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-15.
[7]	"Purification and characterization of the urease enzymes of Helicobacter species from humans and animals." Turbett G.R., Hoej P.B., Horne R., Mee B.J. Infect. Immun. 60:5259-5266(1992) [PubMed: 1452359] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-12. Strain: ATCC 43504 / NCTC 11637 / JCM 7653 / RPH 13487.
[8]	"Expression of Helicobacter pylori urease genes in Escherichia coli grown under nitrogen-limiting conditions." Cussac V., Ferrero R.L., Labigne A. J. Bacteriol. 174:2466-2473(1992) [PubMed: 1313413] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 565-569, DISRUPTION PHENOTYPE. Strain: 85P.
[9]	"Purification of recombinant Helicobacter pylori urease apoenzyme encoded by ureA and ureB." Hu L.-T., Foxall P.A., Russell R., Mobley H.L.T. Infect. Immun. 60:2657-2666(1992) [PubMed: 1612735] [Abstract] Cited for: CATALYTIC ACTIVITY.
[10]	"A urease-negative mutant of Helicobacter pylori constructed by allelic exchange mutagenesis lacks the ability to colonize the nude mouse stomach." Tsuda M., Karita M., Morshed M.G., Okita K., Nakazawa T. Infect. Immun. 62:3586-3589(1994) [PubMed: 8039935] [Abstract] Cited for: FUNCTION, ROLE IN VIRULENCE.
[11]	"Surface localization of Helicobacter pylori urease and a heat shock protein homolog requires bacterial autolysis." Phadnis S.H., Parlow M.H., Levy M., Ilver D., Caulkins C.M., Connors J.B., Dunn B.E. Infect. Immun. 64:905-912(1996) [PubMed: 8641799] [Abstract] Cited for: SUBCELLULAR LOCATION.
[12]	"Nickel-responsive induction of urease expression in Helicobacter pylori is mediated at the transcriptional level." van Vliet A.H.M., Kuipers E.J., Waidner B., Davies B.J., de Vries N., Penn C.W., Vandenbroucke-Grauls C.M.J.E., Kist M., Bereswill S., Kusters J.G. Infect. Immun. 69:4891-4897(2001) [PubMed: 11447165] [Abstract] Cited for: INDUCTION.
[13]	"Differential regulation of urease activity in Helicobacter hepaticus and Helicobacter pylori." Belzer C., Stoof J., Beckwith C.S., Kuipers E.J., Kusters J.G., van Vliet A.H.M. Microbiology 151:3989-3995(2005) [PubMed: 16339943] [Abstract] Cited for: INDUCTION.
[14]	"Supramolecular assembly and acid resistance of Helicobacter pylori urease." Ha N.-C., Oh S.-T., Sung J.Y., Cha K.A., Lee M.H., Oh B.-H. Nat. Struct. Biol. 8:505-509(2001) [PubMed: 11373617] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) IN COMPLEX WITH NICKEL IONS, SUBUNIT STRUCTURE, CARBAMYLATION AT LYS-219.
+	Additional computationally mapped references.

Web resources

Protein Spotlight

Going unnoticed - Issue 95 of June 2008

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M60398 Genomic DNA. Translation: AAA25021.1.
X17079 Genomic DNA. Translation: CAA34933.1.
AE000511 Genomic DNA. Translation: AAD07143.1.
M84338 Genomic DNA. No translation available.

PIR

URKCBP. B38537.

RefSeq

NP_206872.1. NC_000915.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1E9Y	X-ray	3.00	B	1-569	[»]
1E9Z	X-ray	3.00	B	1-569	[»]

ProteinModelPortal

P69996.

SMR

P69996. Positions 1-569.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-1567059.

Protein family/group databases

MEROPS

M38.982.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

899104.

GenomeReviews

Gene locus HP_0072 in contig AE000511_GR.

KEGG

hpy:HP0072.

PATRIC

20591347. VBIHelPyl33062_0075.

TIGR

HP_0072.

Phylogenomic databases

HOGENOM

HBG357507.

OMA

MPYTINT.

ProtClustDB

PRK13985.

Family and domain databases

HAMAP

MF_01953. Urease_alpha.
[Tree]

InterPro

IPR006680. Amidohydro_1.
IPR011059. Metal-dep_hydrolase_composite.
IPR011612. Urease_alpha_N.
IPR005848. Urease_asu.
IPR017951. Urease_asu_c.
IPR017950. Urease_asu_CS.
[Graphical view]

KO

K01428.

Pfam

PF01979. Amidohydro_1. 1 hit.
PF00449. Urease_alpha. 1 hit.
[Graphical view]

PRINTS

PR01752. UREASE.

SUPFAM

SSF51338. Metalo_hydrolase. 2 hits.

TIGRFAMs

TIGR01792. Urease_alph. 1 hit.

PROSITE

PS01120. UREASE_1. 1 hit.
PS00145. UREASE_2. 1 hit.
PS51368. UREASE_3. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

URE1_HELPY

Accession

Primary (citable) accession number: P69996
Secondary accession number(s): P14917, Q9R3B3

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 4, 2005
Last sequence update:	January 4, 2005
Last modified:	January 25, 2012
This is version 62 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program