Nickel-dependent urease biogenesis and urea hydrolysis

Urease is a nickel metalloenzyme that hydrolyzes urea to ammonia and carbamate, which decomposes to a second ammonia and bicarbonate. Its catalytic unit (the alpha chain or alpha region) is assembled first as an inactive apoprotein. The apoprotein is built from three chains (UreA gamma, UreB beta, UreC alpha) in most bacteria, from two chains in Helicobacter (a fused gamma-beta UreA plus a UreB alpha chain), and from a single chain in plants and fungi. The active site, two nickel ions bridged by a carbamylated lysine, is installed after assembly. That activation is carried out by conserved accessory proteins: UreD (UreH in Helicobacter) binds the apoprotein and, with UreF, recruits the SIMIBI-class GTPase UreG. In bacteria, the nickel metallochaperone UreE supplies nickel to UreG, and GTP hydrolysis by UreG releases nickel into the active site. Plants and fungi use UreD, UreF and UreG but have no UreE. The mature enzyme then hydrolyzes urea. The module does not include nickel uptake or homeostasis, urea transport, regulation of urease gene expression, or assimilation of the released ammonia.

MODULE:urease_biogenesis_urea_hydrolysisCOMPLETECONCRETEBiological Processmodules/urease_biogenesis_urea_hydrolysis.yaml
urea catabolic processGO:0043419
PMID:7909161
In vitro activation of urease apoprotein and role of UreD as a chaperone required for nickel metallocenter assembly
Establishes the UreABC apoprotein and the requirement for UreD, UreE, UreF, and UreG in functional metallocenter assembly.
The formation of active urease in Klebsiella aerogenes requires the presence of three structural genes for the apoprotein (ureA, ureB, and ureC), as well as four accessory genes (ureD, ureE, ureF, and ureG) that are involved in functional assembly of the metallocenter in this nickel-containing enzyme.
PMID:10500143
GTP-dependent activation of urease apoprotein in complex with the UreD, UreF, and UreG accessory proteins
Establishes that UreG-dependent GTP hydrolysis activates the UreD-UreF-UreG-apourease complex at physiological bicarbonate.
Based on studies involving a nonhydrolyzable analog of GTP, we conclude that nucleotide hydrolysis, not just binding, is required for this process.
PMID:8318889
Purification and characterization of Klebsiella aerogenes UreE protein - a nickel-binding protein that functions in urease metallocenter assembly
Establishes UreE as a cytoplasmic nickel-binding donor for urease maturation.
We hypothesize that UreE binds intracellular nickel ion and functions as a nickel donor during metallocenter assembly into the urease apoprotein.
PMID:24115911
Structure of UreG/UreF/UreH complex reveals how urease accessory proteins facilitate maturation of Helicobacter pylori urease
Extends the activation mechanism to the two-chain Helicobacter urease: UreF and UreH recruit UreG, and a nickel-charged UreG dimer releases nickel to urease upon GTP hydrolysis.
UreF and UreH form a complex to recruit UreG, which is a SIMIBI class GTPase, to the preactivation complex.
PMID:16244137
Identification of three urease accessory proteins that are required for urease activation in Arabidopsis
Extends the module to plants: single-chain plant urease needs UreD, UreF and UreG (no UreE), and the three are sufficient to activate plant urease when co-expressed in E. coli.
urease activity was observed only when all three plant accessory genes were coexpressed together with the plant urease gene
PMID:28710280
The assembly of the plant urease activation complex and the essential role of the urease accessory protein G (UreG) in delivery of nickel to urease
Shows that a urease-UreD-UreF-UreG activation complex assembles stepwise in plants and that UreG delivers nickel.
we demonstrate that a urease-UreD-UreF-UreG complex exists in plants and show its stepwise assembly.
file:VARPS/ureC/ureC-ai-review.yaml
Variovorax paradoxus S110 ureC gene review
C5CY00 (Vapar_4243) encodes the catalytic alpha subunit of three-chain bacterial urease in Variovorax paradoxus S110.
Nickel-dependent hydrolysis of urea into hydrogencarbonate (carbonate) and ammonium ions by the catalytic alpha subunit of the cytosolic (UreABC)3 urease complex.
file:VARPS/ureA/ureA-ai-review.yaml
Variovorax paradoxus S110 ureA gene review
C5CXZ7 (Vapar_4240) encodes the 100-residue gamma structural subunit of the three-chain bacterial urease complex in Variovorax paradoxus S110.
Cytoplasmic gamma structural subunit of the (UreABC)3 urease complex that stabilizes the trimer-of-heterotrimers assembly and contributes to urease-catalyzed urea hydrolysis.
file:VARPS/ureB/ureB-ai-review.yaml
Variovorax paradoxus S110 ureB gene review
C5CXZ9 (Vapar_4242) encodes the 101-residue beta structural subunit of the three-chain bacterial urease complex in Variovorax paradoxus S110.
Cytoplasmic beta structural subunit of the (UreABC)3 urease complex that contributes to urease-catalyzed urea hydrolysis.
file:VARPS/ureD/ureD-ai-review.yaml
Variovorax paradoxus S110 ureD gene review
C5CVT2 (Vapar_3971) encodes the 276-residue cytoplasmic urease accessory protein UreD in Variovorax paradoxus S110.
Cytoplasmic urease activator that binds the (UreABC)3 apoprotein, recruits UreF and UreG, and promotes nickel incorporation into the UreC active site.
file:VARPD/ureE/ureE-ai-review.yaml
Variovorax paradoxus ureE gene review
A0A0H2LU38 (VPARA_50940) encodes the 200-residue cytoplasmic nickel metallochaperone UreE in Variovorax paradoxus.
Cytoplasmic nickel-binding metallochaperone that binds intracellular Ni(2+) and transfers it to the UreD-UreF-UreG activation machinery for urease active-site maturation and urea catabolism.
file:VARPD/ureF/ureF-ai-review.yaml
Variovorax paradoxus ureF gene review
A0A0H2LZ72 (VPARA_50930) encodes the 223-residue cytoplasmic urease accessory protein UreF in Variovorax paradoxus.
Cytoplasmic urease activator that docks UreG onto the UreD-apourease scaffold to promote nickel incorporation into the UreC active site.
file:VARPS/ureG/ureG-ai-review.yaml
Variovorax paradoxus S110 ureG gene review
C5CY05 (Vapar_4248) encodes the 216-residue cytoplasmic SIMIBI-class G3E GTPase and nickel metallochaperone UreG in Variovorax paradoxus S110.
Cytoplasmic SIMIBI-class G3E GTPase that couples GTP hydrolysis to productive insertion of the dinickel metallocenter into the UreC active site for urea catabolism.

Scope and generalization. Nickel urease and its UreD/UreF/UreG activation machinery are conserved across bacteria, archaea, plants and fungi, so the module is written species-neutrally. Concrete exemplars come from the classic experimental systems: Klebsiella aerogenes (three-chain biochemistry and structure), Helicobacter pylori (two-chain enzyme; UreG/UreF/UreH structure) and Arabidopsis thaliana (single-chain enzyme; UreD/UreF/UreG genetics and in-planta complex). Pseudomonas putida KT2440 is kept as a genomic exemplar, and Nitrososphaera viennensis ureC1 as an archaeal catalytic exemplar. scope is CONCRETE because every leaf is grounded to representative proteins; the lineage differences are modelled as variants of the structural part and as an optional UreE part, not as separate modules. Family grounding. The catalytic chain and the three accessory proteins are grounded to single-subfamily PANTHER families (PTHR43440:SF1, PTHR33643:SF1, PTHR33620:SF1, PTHR31715:SF0), each with a family review. The gamma and beta structural chains are left without a PANTHER id: PANTHER's PTHR33569 lumps them with fungal single-chain urease, which does not identify the role. UreE has no PANTHER family. The InterPro accessions for these roles are given in the descriptors' descriptions. Boundary. Nickel import (for example NikR-regulated transporters), urea transport (Helicobacter UreI), hydrogenase-shared nickel chaperones (HypA/HypB, which also feed urease in Helicobacter), regulation of urease expression, and assimilation of the released ammonia are inputs or consequences, not module parts. Fungal accessory-protein homologues (S. pombe UreD/UreF/UreG-like proteins) are PAINT seeds for the accessory families but are not grounded here. For Variovorax paradoxus, reviewed Swiss-Prot/TrEMBL entries from strain S110 (VARPS) represent UreA (C5CXZ7), UreB (C5CXZ9), UreC (C5CY00), UreD (C5CVT2), and UreG (C5CY05), while strain TBEA6 (VARPD) entries represent UreE (A0A0H2LU38) and UreF (A0A0H2LZ72), as the corresponding S110 proteins are indexed in UniProtKB only by locus tag rather than standard ureE/ureF gene symbols.

10Nodes
6Parts
1Variant Sets
3Variants
8Annotons
4Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:urease_biogenesis_urea_hydrolysis deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

25 gene-function check(s) reflected in core functions · 0 conflict(s) · 1 evidence or coverage gap(s) (30 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
ured_urease_scaffold ureD (PSEPK)
UniProtKB:Q88J07
Family Representative 		urease activator activity
GO:0018237 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ured_urease_scaffold ureD (KLEAE)
UniProtKB:Q09063
Family Representative 		urease activator activity
GO:0018237 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ured_urease_scaffold ureH (HELPY)
UniProtKB:Q09067
Family Representative 		urease activator activity
GO:0018237 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ured_urease_scaffold URED (ARATH)
UniProtKB:Q7Y0S0
Family Representative 		urease activator activity
GO:0018237 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ured_urease_scaffold ureD (VARPS)
UniProtKB:C5CVT2
Family Representative 		urease activator activity
GO:0018237 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
uref_activation_checkpoint ureF (PSEPK)
UniProtKB:Q88J01
Family Representative 		urease activator activity
GO:0018237 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
uref_activation_checkpoint ureF (KLEAE)
UniProtKB:P18318
Family Representative 		urease activator activity
GO:0018237 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
uref_activation_checkpoint ureF (HELPY)
UniProtKB:Q09065
Family Representative 		urease activator activity
GO:0018237 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
uref_activation_checkpoint UREF (ARATH)
UniProtKB:Q9XHZ3
Family Representative 		urease activator activity
GO:0018237 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
uref_activation_checkpoint ureF (VARPD)
UniProtKB:A0A0H2LZ72
Family Representative 		urease activator activity
GO:0018237 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
uree_nickel_metallochaperone ureE (PSEPK)
UniProtKB:Q88J03
Family Representative 		nickel cation binding
GO:0016151 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
uree_nickel_metallochaperone ureE (KLEAE)
UniProtKB:P18317
Family Representative 		nickel cation binding
GO:0016151 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
uree_nickel_metallochaperone ureE (HELPY)
UniProtKB:Q09064
Family Representative 		nickel cation binding
GO:0016151 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
uree_nickel_metallochaperone ureE (VARPD)
UniProtKB:A0A0H2LU38
Family Representative 		nickel cation binding
GO:0016151 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ureg_gtpase_metallochaperone ureG (PSEPK)
UniProtKB:Q88J00
Family Representative 		GTPase activity
GO:0003924 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ureg_gtpase_metallochaperone ureG (KLEAE)
UniProtKB:P18319
Family Representative 		GTPase activity
GO:0003924 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ureg_gtpase_metallochaperone ureG (HELPY)
UniProtKB:Q09066
Family Representative 		GTPase activity
GO:0003924 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ureg_gtpase_metallochaperone UREG (ARATH)
UniProtKB:O64700
Family Representative 		GTPase activity
GO:0003924 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ureg_gtpase_metallochaperone ureG (VARPS)
UniProtKB:C5CY05
Family Representative 		GTPase activity
GO:0003924 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mature_urease_activity ureC (PSEPK)
UniProtKB:Q88J04
Family Representative 		urease activity
GO:0009039 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mature_urease_activity ureC (KLEAE)
UniProtKB:P18314
Family Representative 		urease activity
GO:0009039 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mature_urease_activity ureB (HELPY)
UniProtKB:P69996
Family Representative 		urease activity
GO:0009039 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mature_urease_activity URE (ARATH)
UniProtKB:Q9SR52
Family Representative 		urease activity
GO:0009039 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mature_urease_activity ureC1 (9ARCH)
UniProtKB:A0A060HK93
Family Representative 		urease activity
GO:0009039 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mature_urease_activity ureC (VARPS)
UniProtKB:C5CY00
Family Representative 		urease activity
GO:0009039 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ured_urease_scaffold urease accessory protein UreD/UreH
PANTHER:PTHR33643:SF1
Family 		urease activator activity
GO:0018237 		Family Supported
Family review supports GO:0018237 FAMILY_WIDE. Required for urease activation in bacteria (K. aerogenes) and plants (Arabidopsis), placed at the family node by PAINT, and no member is known to have another role.
uref_activation_checkpoint urease accessory protein UreF
PANTHER:PTHR33620:SF1
Family 		urease activator activity
GO:0018237 		Family Supported
Family review supports GO:0018237 FAMILY_WIDE. Shared by bacterial, Helicobacter and plant members, and placed at the family node by PAINT.
uree_nickel_metallochaperone urease accessory protein UreE
Family 		nickel cation binding
GO:0016151 		Family Id Missing
The family has no identifier linking it to a curated family review.
ureg_gtpase_metallochaperone urease accessory protein UreG (SIMIBI GTPase)
PANTHER:PTHR31715:SF0
Family 		GTPase activity
GO:0003924 		Family Supported
Family review supports GO:0003924 FAMILY_WIDE. SIMIBI-class P-loop GTPase fold with a conserved GxxGxGK(S/T) Walker A motif (at 8-15 in H. pylori UreG). K. aerogenes activation needs nucleotide hydrolysis localized to UreG, and in H. pylori GTP hydrolysis releases nickel to urease. PAINT has not placed this term on a node; it is a family-level judgment for this review.
mature_urease_activity urease catalytic alpha chain or region
PANTHER:PTHR43440:SF1
Family 		urease activity
GO:0009039 		Family Supported
Family review supports GO:0009039 FAMILY_WIDE. Ancestral at the family root node, the dinickel ligand set is conserved, and no reviewed member lacks the activity. In multi-chain ureases the alpha chain is the catalytic unit, so the term is correctly enabled by members of this family; the gamma/beta (or fused gamma-beta) chains only contribute.

Gene-review completeness (33/33 grounded genes reviewed)

33 complete review(s) · 2 with deep research · 0 missing review · 31 reviewed but lacking deep research

Gene Review Complete Deep research
URE Q9SR52 ✓ ✓ ✗
ure1 O00084 ✓ ✓ ✗
ureA C5CXZ7 ✓ ✓ ✗
ureA P14916 ✓ ✓ ✗
ureA P18316 ✓ ✓ ✗
ureA Q88J06 ✓ ✓ ✗
ureB C5CXZ9 ✓ ✓ ✗
ureB P18315 ✓ ✓ ✗
ureB P69996 ✓ ✓ ✗
ureB Q88J05 ✓ ✓ ✗
ureC C5CY00 ✓ ✓ ✗
ureC P18314 ✓ ✓ ✗
ureC Q88J04 ✓ ✓ ✗
ureC1 A0A060HK93 ✓ ✓ ✓
ureD C5CVT2 ✓ ✓ ✗
ureD Q09063 ✓ ✓ ✗
URED Q7Y0S0 ✓ ✓ ✗
ureD Q88J07 ✓ ✓ ✗
ureE A0A0H2LU38 ✓ ✓ ✗
ureE P18317 ✓ ✓ ✗
ureE Q09064 ✓ ✓ ✗
ureE Q88J03 ✓ ✓ ✗
ureF A0A0H2LZ72 ✓ ✓ ✗
ureF P18318 ✓ ✓ ✗
ureF Q09065 ✓ ✓ ✗
ureF Q88J01 ✓ ✓ ✓
UREF Q9XHZ3 ✓ ✓ ✗
ureG C5CY05 ✓ ✓ ✗
UREG O64700 ✓ ✓ ✗
ureG P18319 ✓ ✓ ✗
ureG Q09066 ✓ ✓ ✗
ureG Q88J00 ✓ ✓ ✗
ureH Q09067 ✓ ✓ ✗

Details

Nickel-dependent urease biogenesis and urea hydrolysisBiological Processurease_biogenesis_urea_hydrolysis

Assembly of the urease apoprotein (three-chain, two-chain or single-chain), UreD/UreF/UreG-dependent installation of the carbamylated dinickel site (with UreE nickel supply in bacteria), and hydrolysis of urea by the mature enzyme.

urea catabolic processGO:0043419

Connections

The assembled apoprotein is what the UreD/UreF/UreG activation machinery acts on.
Carbamylation and dinickel-site assembly convert apo-urease into the catalytically competent enzyme.
Part 1: apo-urease structural assembly
Apo-urease structural assemblyCellular Componentapo_urease_assembly

The structural chains associate into the inactive, preorganized apoprotein before the active site is loaded with carbamate and nickel. The number of chains differs between lineages; the catalytic alpha chain or region is conserved in all of them.

Variant set: Urease chain architecture by subunit architecture (taxon-associated) (Exactly One)

Each urease is built on exactly one of these architectures. They differ only in how the gamma, beta and alpha regions are split across polypeptides; the catalytic alpha region and its dinickel ligands are the same in all three.

Three-chain (UreA-UreB-UreC) apo-ureaseProtein Complexthree_chain_apourease

Most bacteria and archaea, including Klebsiella aerogenes and Pseudomonas putida, make an (alpha-beta-gamma)3 urease.

Annotons

Three-chain apo-urease complex
apo_urease_three_chain_complex
Participant: Protein Complex: three-chain apo-urease complex
Protein Complex:
three-chain apo-urease complexGO:0035550 Inactive UreABC complex lacking the carbamylated dinickel active site, built as an (alpha-beta-gamma)3 trimer (unit stoichiometry 3 each). The GO complex term covers both apo and mature assemblies.
Active units:
UreA gamma structural subunit3
Participant: Family: urease gamma subunit (UreA)
Family:
urease gamma subunit (UreA) InterPro IPR002026 (urease gamma/gamma-beta subunit). PANTHER puts the gamma and beta chains together with fungal single-chain urease in PTHR33569, which is too broad to identify this role, so no PANTHER id is asserted.
Representative Members: ureA (PSEPK)UniProtKB:Q88J06 ureA (KLEAE)UniProtKB:P18316 ureA (VARPS)UniProtKB:C5CXZ7
Role: Structural gamma chain that contributes to the assembled complex but does not catalyze urea hydrolysis on its own.
PMID:7909161
ureA is one of the three structural genes for the K. aerogenes apoprotein.
UreB beta structural subunit3
Participant: Family: urease beta subunit (UreB)
Family:
urease beta subunit (UreB) InterPro IPR002019 (urease beta subunit). PANTHER PTHR33569 is too broad for this role (see the gamma subunit), so no PANTHER id is asserted.
Representative Members: ureB (PSEPK)UniProtKB:Q88J05 ureB (KLEAE)UniProtKB:P18315 ureB (VARPS)UniProtKB:C5CXZ9
Role: Structural beta chain that contributes to the assembled complex but does not catalyze urea hydrolysis on its own.
PMID:7909161
ureB is one of the three structural genes for the K. aerogenes apoprotein.
UreC alpha catalytic subunit3
Participant: Family: urease alpha subunit (UreC)
Family:
urease alpha subunit (UreC)PANTHER:PTHR43440:SF1
Representative Members: ureC (PSEPK)UniProtKB:Q88J04 ureC (KLEAE)UniProtKB:P18314 ureC (VARPS)UniProtKB:C5CY00
Role: Catalytic alpha chain that supplies the carbamylated lysine and the ligands of the dinickel active site after maturation.
PMID:8718850
Structural analysis places the binickel active center in the alpha subunit.

Builds the preorganized UreABC apoprotein that the activation machinery acts on.

PMID:8718850
The apoenzyme keeps the UreABC architecture but lacks carbamate and nickel at the active site.
With the exception of the active site, in which a water molecule takes the place of the missing carbamate and nickel atoms, the structure of the apoenzyme is nearly identical to that of the holoenzyme, suggesting a high degree of preorganization which helps explain the tight binding of nickel.
Two-chain (fused gamma-beta UreA plus UreB alpha) apo-ureaseProtein Complextwo_chain_apourease

Helicobacter and related epsilonproteobacteria fuse the gamma and beta regions into one chain, named UreA (UniProt "urease subunit alpha"), and name the catalytic alpha chain UreB (UniProt "urease subunit beta"). The names are swapped relative to the three-chain enzyme; the catalytic chain is still the PTHR43440 member.

Annotons

Two-chain apo-urease complex
apo_urease_two_chain_complex
Participant: Protein Complex: two-chain apo-urease complex
Protein Complex:
two-chain apo-urease complexGO:0035550 Spherical ((UreA-UreB)3)4 assembly of 12 catalytic units (unit stoichiometry 12 each).
Active units:
Fused gamma-beta structural subunit (Helicobacter UreA)12
Participant: Family: fused urease gamma-beta subunit
Family:
fused urease gamma-beta subunit InterPro IPR002026 (urease gamma/gamma-beta subunit) family member that also carries the beta region. No PANTHER id is asserted, for the same reason as for the three-chain gamma subunit.
Representative Members: ureA (HELPY)UniProtKB:P14916
Role: Structural chain combining the gamma and beta regions; it contributes to the complex but does not catalyze urea hydrolysis.
Catalytic alpha chain (Helicobacter UreB)12
Participant: Family: urease alpha chain (Helicobacter UreB)
Family:
urease alpha chain (Helicobacter UreB)PANTHER:PTHR43440:SF1
Representative Members: ureB (HELPY)UniProtKB:P69996
Role: Catalytic chain carrying the dinickel site, with the carbamylated lysine at Lys219.
PMID:24115911
H. pylori urease maturation carbamylates Lys219 and inserts two nickel ions.
Maturation of urease involves carbamylation of Lys219 and insertion of two nickel ions at its active site.

Builds the two-chain apoprotein that the Helicobacter UreF/UreH/UreG machinery acts on.

Single-chain apo-urease (plants and fungi)Protein Complexsingle_chain_apourease

Plant and fungal ureases are one polypeptide carrying the gamma, beta and alpha regions in that order, assembled into homo-oligomers.

Annotons

Single-chain apo-urease
single_chain_apourease_chain
Participant: Protein Complex: single-chain apo-urease homo-oligomer
Protein Complex:
single-chain apo-urease homo-oligomerGO:0035550 Homo-oligomer of a single polypeptide that carries the gamma, beta and alpha regions in that order.
Active units:
Single-chain urease polypeptide
Participant: Family: single-chain urease
Family:
single-chain urease PANTHER splits this architecture by lineage: plant single-chain ureases fall in PTHR43440:SF1 with the bacterial alpha subunits, and fungal ones, such as S. pombe ure1, in PTHR33569:SF1 with the bacterial gamma and beta subunits.
Representative Members: URE (ARATH)UniProtKB:Q9SR52 ure1 (SCHPO)UniProtKB:O00084
Role: Supplies the structural regions and the catalytic dinickel region of the apoprotein in one chain.

Single polypeptide that supplies both the structural regions and the catalytic dinickel region of the apoprotein that the UreD/UreF/UreG machinery acts on.

PMID:16244137
Arabidopsis has one structural urease gene, whose insertion mutants lack urease activity.
Part 2: nickel delivery and GTP-dependent urease activation
Nickel delivery and GTP-dependent urease activationBiological Processurease_metallocenter_activation

UreD (UreH) and UreF form an activation platform on apo-urease that recruits UreG. UreG binds nickel, supplied in bacteria by UreE, and its GTP hydrolysis releases the nickel into the carbamylated active site.

Connections

The UreD-UreF scaffold recruits UreG to the apoprotein and gates its nucleotide turnover.
In bacteria, UreE-bound nickel is transferred to UreG.
Part 1: activation-complex recruitment to apo-urease
UreD-UreF activation scaffold formationProtein Complexuredf_activation_scaffold

Annotons

UreD/UreH apo-urease activation scaffold
ured_urease_scaffold
Participant: Family: urease accessory protein UreD/UreH
Family:
urease accessory protein UreD/UreHPANTHER:PTHR33643:SF1
Representative Members: ureD (PSEPK)UniProtKB:Q88J07 ureD (KLEAE)UniProtKB:Q09063 ureH (HELPY)UniProtKB:Q09067 URED (ARATH)UniProtKB:Q7Y0S0 ureD (VARPS)UniProtKB:C5CVT2

Function

urease activator activityGO:0018237

Binds apo-urease and scaffolds recruitment of UreF and UreG, promoting nickel incorporation into the active site.

PMID:7909161
UreD binds urease apoprotein and is required for nickel incorporation.
The UreD-urease apoprotein complexes are competent for activation by nickel
UreF activation-complex component
uref_activation_checkpoint
Participant: Family: urease accessory protein UreF
Family:
urease accessory protein UreFPANTHER:PTHR33620:SF1
Representative Members: ureF (PSEPK)UniProtKB:Q88J01 ureF (KLEAE)UniProtKB:P18318 ureF (HELPY)UniProtKB:Q09065 UREF (ARATH)UniProtKB:Q9XHZ3 ureF (VARPD)UniProtKB:A0A0H2LZ72

Function

urease activator activityGO:0018237

Docks UreG onto the UreD-apourease platform and couples UreG nucleotide turnover to faithful, rather than adventitious, metal incorporation.

PMID:22369361
UreF interaction with UreG gates GTPase activity and maturation fidelity.
Part 2: nickel supply by UreE (bacteria) (optional)

Optional because plants and fungi have no UreE. In bacteria UreE raises the efficiency of nickel delivery; in K. aerogenes, deleting ureE reduces activation in cell extracts but does not abolish it.

UreE nickel supplyBiological Processuree_nickel_supply

Annotons

UreE nickel metallochaperone
uree_nickel_metallochaperone
Participant: Family: urease accessory protein UreE
Family:
urease accessory protein UreE InterPro IPR012406 (UreE urease accessory protein). PANTHER has no UreE family, so no PANTHER id is asserted.
Representative Members: ureE (PSEPK)UniProtKB:Q88J03 ureE (KLEAE)UniProtKB:P18317 ureE (HELPY)UniProtKB:Q09064 ureE (VARPD)UniProtKB:A0A0H2LU38

Function

nickel cation bindingGO:0016151

Binds cytoplasmic nickel and supplies it to UreG in the activation machinery.

PMID:8318889
Purified UreE binds nickel and was proposed to donate it during metallocenter assembly.
Part 3: UreG nickel loading and GTP-dependent release
UreG GTP-dependent nickel deliveryBiological Processureg_nickel_delivery

Annotons

UreG GTPase metallochaperone
ureg_gtpase_metallochaperone
Participant: Family: urease accessory protein UreG (SIMIBI GTPase)
Family:
urease accessory protein UreG (SIMIBI GTPase)PANTHER:PTHR31715:SF0
Representative Members: ureG (PSEPK)UniProtKB:Q88J00 ureG (KLEAE)UniProtKB:P18319 ureG (HELPY)UniProtKB:Q09066 UREG (ARATH)UniProtKB:O64700 ureG (VARPS)UniProtKB:C5CY05

Function

GTPase activityGO:0003924
Substrates: GTP water
Products: GDP phosphate

Forms a nickel-loaded dimer at its invariant Cys-Pro-His motif and hydrolyzes GTP to release the nickel into the urease active site.

PMID:10500143
A UreG nucleotide-site variant localized the GTP-hydrolysis requirement to UreG.
PMID:24115911
GTP hydrolysis returns the nickel-charged UreG dimer to monomer and releases nickel to urease.
the nickel-charged UreG dimer, upon GTP hydrolysis, reverts to its monomeric form and releases nickel to urease
Part 3: urea hydrolysis by mature urease
Urea hydrolysis by mature ureaseReactionmature_urease_hydrolysis

Annotons

Mature dinickel urease activity
mature_urease_activity
Participant: Family: urease catalytic alpha chain or region
Family:
urease catalytic alpha chain or regionPANTHER:PTHR43440:SF1 The catalytic unit is the alpha chain (UreC; Helicobacter UreB) or the alpha region of a single-chain urease. It acts within the assembled urease complex (GO:0035550) from part 1, where the gamma and beta chains or regions contribute structurally but do not catalyze.
Representative Members: ureC (PSEPK)UniProtKB:Q88J04 ureC (KLEAE)UniProtKB:P18314 ureB (HELPY)UniProtKB:P69996 URE (ARATH)UniProtKB:Q9SR52 ureC1 (9ARCH)UniProtKB:A0A060HK93 ureC (VARPS)UniProtKB:C5CY00

Function

urease activityGO:0009039
Substrates: ureaCHEBI:16199 waterCHEBI:15377 hydronCHEBI:15378
Products: hydrogencarbonateCHEBI:17544 ammoniumCHEBI:28938
Cofactors: two nickel(II) ions carbamylated active-site lysine

Processes

urea catabolic processGO:0043419

Hydrolyzes urea after UreD/UreF/UreG-dependent metallocenter activation. Balanced reaction (RHEA:20557): urea + 2 H2O + H+ = hydrogencarbonate + 2 NH4+; the substrate and product lists name each participant once and leave the stoichiometry to this statement.

RHEA:20557
Urease reaction
Rhea 20557 defines the EC 3.5.1.5 urea hydrolysis reaction.
PMID:8718850
Each alpha subunit carries a binickel active center.
is an (alpha beta gamma)3 trimer with each alpha-subunit having an (alpha beta)8-barrel domain containing a binickel active center