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Information on EC 7.2.2.21 - Cd2+-exporting ATPase
for references in articles please use BRENDA:EC7.2.2.21
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EC Tree 7 Translocases
7.2 Catalysing the translocation of inorganic cations
7.2.2 Linked to the hydrolysis of a nucleoside triphosphate
7.2.2.21 Cd2+-exporting ATPase
IUBMB Comments
A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. This enzyme occurs in protozoa, fungi and plants.
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
- 7.2.2.21
-
benzalkonium
- monocytogenes
- listeria
- atpases
- shoots
- arsenic
-
cadmium-resistant
-
serotype
- oshma3
- menkes
-
poland
-
plasmid-borne
-
metal-responsive
- reserpine
-
disinfectant
-
transporter-deficient
-
cation-translocating
-
tonoplast
-
arsenic-resistance
-
metal-transporting
- biotechnology
showSynonyms
cada1, heavy metal atpase 3, heavy metal translocating p-type atpase, cadmium efflux atpase, atp-coupled cd(ii) pump, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ATP-coupled Cd(II) pump
-
-
-
-
CadA
CadA1
Cadmium efflux ATPase
-
-
-
-
cadmium-efflux ATPase
-
-
-
-
cadmium-resistance ATPase
-
-
-
-
cadmium-transporting P1B-type ATPase
EC 3.6.3.3
-
-
formerly
-
heavy metal ATPase
heavy metal ATPase 3
heavy metal translocating P-type ATPase
heavy metal-translocating P-type ATPase 1
HMA3
Hmtp
NTKII
N-terminal binding-domain of 71 amino acids carrying a S71A mutation
OsHMA3
P1B-type ATPase
Pca1,aP1B-type ATPase
ZntA
CadA
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + H2O + Cd2+[side 1] = ADP + phosphate + Cd2+[side 2]
-
-
-
-
ATP + H2O + Cd2+[side 1] = ADP + phosphate + Cd2+[side 2]
ATP forms first a phosphoenzyme which transports the metal across the membrane
-
ATP + H2O + Cd2+[side 1] = ADP + phosphate + Cd2+[side 2]
metal binding environment comprises two conserved Cys residues of the metal binding motif and a Glu in loop 5. function of the N-terminus in the metal specificity of the enzyme
ATP + H2O + Cd2+[side 1] = ADP + phosphate + Cd2+[side 2]
reaction cycle involves two Cd2+ ions
-
ATP + H2O + Cd2+[side 1] = ADP + phosphate + Cd2+[side 2]
Cys14, Cys17 and Glu61 involved in metal binding
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
transmembrane transport
hydrolysis of phosphoric ester
-
-
-
-
transmembrane transport
-
-
-
-
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SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (Cd2+-exporting)
A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. This enzyme occurs in protozoa, fungi and plants.
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CAS REGISTRY NUMBER
COMMENTARY
9000-83-3
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + H2O + Cd2+/out
ADP + phosphate + Cd2+/in
-
Substrates: -
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ATP + H2O + Pb2+/in
ADP + phosphate + Pb2+/out
-
Substrates: -
Products: -
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ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
Substrates: complementation experiments suggest that Pb2+ and Zn2+ are not transported by the enzyme
Products: -
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ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
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Substrates: -
Products: -
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ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
Bacillus subtilis 168 / CU1065
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Substrates: -
Products: -
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ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
Substrates: active transport of Cd2+ out of the cell to maintain metal homeostasis
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ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
Substrates: active transport of Cd2+ out of the cell to maintain metal homeostasis
Products: -
Products: -
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
Substrates: active transport of Cd2+ out of the cell to maintain metal homeostasis
Products: -
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ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
Substrates: -
Products: -
Products: -
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ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
Substrates: active transport of Cd2+ out of the cell to maintain metal homeostasis
Products: -
Products: -
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
Substrates: -
Products: -
Products: -
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ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
Substrates: complementation experiments suggest that Pb2+, Zn2+, Co2+ and Ni2+ are not transported by the enzyme
Products: -
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ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
Substrates: -
Products: -
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ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
Substrates: -
Products: -
Products: -
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ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
Substrates: active transport of Cd2+ out of the cell to maintain metal homeostasis
Products: -
Products: -
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ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
Substrates: Pca1 plays a critical role in cadmium resistance by extruding intracellular cadmium. Yeast cells rapidly enhance expression of Pca1 by a post-transcriptional mechanism. In the absence of cadmium, Pca1 is targeted for degradation before reaching the plasmamembrane
Products: -
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ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
Substrates: the N-terminus of Pca1 contains a metal-responding degradation signal encompassing amino acids 250-350. Seven cysteine residues within the Pca1 regulatory domain are required for metal sensing
Products: -
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ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
Substrates: Pca1 plays a critical role in cadmium resistance by extruding intracellular cadmium. Yeast cells rapidly enhance expression of Pca1 by a post-transcriptional mechanism. In the absence of cadmium, Pca1 is targeted for degradation before reaching the plasmamembrane
Products: -
Products: -
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ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
Substrates: the N-terminus of Pca1 contains a metal-responding degradation signal encompassing amino acids 250-350. Seven cysteine residues within the Pca1 regulatory domain are required for metal sensing
Products: -
Products: -
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ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
Substrates: active transport of Cd2+ out of the cell to maintain metal homeostasis
Products: -
Products: -
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ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
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Substrates: -
Products: -
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ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
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Substrates: -
Products: -
Products: -
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ATP + H2O + Cd2+[side 1]
ADP + phosphate + Cd2+[side 2]
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Substrates: -
Products: -
Products: -
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ATP + H2O + Cd2+[side 1]
ADP + phosphate + Cd2+[side 2]
-
Substrates: -
Products: -
Products: -
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ATP + H2O + Cd2+[side 1]
ADP + phosphate + Cd2+[side 2]
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Substrates: -
Products: -
Products: -
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ATP + H2O + Cd2+[side 1]
ADP + phosphate + Cd2+[side 2]
Substrates: -
Products: -
Products: -
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ATP + H2O + Cd2+[side 1]
ADP + phosphate + Cd2+[side 2]
-
Substrates: -
Products: -
Products: -
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ATP + H2O + Cd2+[side 1]
ADP + phosphate + Cd2+[side 2]
Substrates: -
Products: -
Products: -
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ATP + H2O + Cd2+[side 1]
ADP + phosphate + Cd2+[side 2]
-
Substrates: -
Products: -
Products: -
?
ATP + H2O + Cd2+[side 1]
ADP + phosphate + Cd2+[side 2]
Rossellomorea marisflavi 151-25
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Substrates: -
Products: -
Products: -
?
ATP + H2O + Cd2+[side 1]
ADP + phosphate + Cd2+[side 2]
-
Substrates: -
Products: -
Products: -
?
ATP + H2O + Cd2+[side 1]
ADP + phosphate + Cd2+[side 2]
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Substrates: -
Products: -
Products: -
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ATP + H2O + Zn2+/in
ADP + phosphate + Zn2+/out
-
Substrates: active transport of Cd2+ out of the cell to maintain metal homeostasis
Products: -
Products: -
?
ATP + H2O + Zn2+/in
ADP + phosphate + Zn2+/out
Substrates: active transport of Cd2+ out of the cell to maintain metal homeostasis
Products: -
Products: -
?
ATP + H2O + Zn2+/in
ADP + phosphate + Zn2+/out
-
Substrates: -
Products: -
Products: -
?
additional information
?
-
Substrates: involved in Cd2+, Pb2+, and Zn2+ resistance
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?
additional information
?
-
Substrates: involved in Cd2+, Pb2+, and Zn2+ resistance
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Products: -
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additional information
?
-
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Substrates: mechanism for substrate-mediated control of P1B-type ATPase expression, overview. Dependence of Pca1 degradation through the vacuolar/endosomal pathway
Products: -
Products: -
?
additional information
?
-
-
Substrates: mechanism for substrate-mediated control of P1B-type ATPase expression, overview. Dependence of Pca1 degradation through the vacuolar/endosomal pathway
Products: -
Products: -
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additional information
?
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Substrates: involved in Cd2+, Pb2+, and Zn2+ resistance, not involved in Hg2+ resistance
Products: -
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additional information
?
-
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Substrates: cadmium and zinc lead to the upregulation of genes encoded on the pSymA or pSymB plasmids, expression of the efflux pumps SMc01095, i.e. mexF1, and SMb20345 is enhanced 41fold and 4fold, respectively, overview
Products: -
Products: -
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
Substrates: active transport of Cd2+ out of the cell to maintain metal homeostasis
Products: -
Products: -
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
Substrates: active transport of Cd2+ out of the cell to maintain metal homeostasis
Products: -
Products: -
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
Substrates: active transport of Cd2+ out of the cell to maintain metal homeostasis
Products: -
Products: -
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
Substrates: active transport of Cd2+ out of the cell to maintain metal homeostasis
Products: -
Products: -
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
Substrates: active transport of Cd2+ out of the cell to maintain metal homeostasis
Products: -
Products: -
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
Substrates: Pca1 plays a critical role in cadmium resistance by extruding intracellular cadmium. Yeast cells rapidly enhance expression of Pca1 by a post-transcriptional mechanism. In the absence of cadmium, Pca1 is targeted for degradation before reaching the plasmamembrane
Products: -
Products: -
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
Substrates: Pca1 plays a critical role in cadmium resistance by extruding intracellular cadmium. Yeast cells rapidly enhance expression of Pca1 by a post-transcriptional mechanism. In the absence of cadmium, Pca1 is targeted for degradation before reaching the plasmamembrane
Products: -
Products: -
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
Substrates: active transport of Cd2+ out of the cell to maintain metal homeostasis
Products: -
Products: -
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
Substrates: -
Products: -
Products: -
?
ATP + H2O + Cd2+[side 1]
ADP + phosphate + Cd2+[side 2]
-
Substrates: -
Products: -
Products: -
?
ATP + H2O + Cd2+[side 1]
ADP + phosphate + Cd2+[side 2]
-
Substrates: -
Products: -
Products: -
?
ATP + H2O + Cd2+[side 1]
ADP + phosphate + Cd2+[side 2]
-
Substrates: -
Products: -
Products: -
?
ATP + H2O + Cd2+[side 1]
ADP + phosphate + Cd2+[side 2]
Substrates: -
Products: -
Products: -
?
ATP + H2O + Cd2+[side 1]
ADP + phosphate + Cd2+[side 2]
-
Substrates: -
Products: -
Products: -
?
ATP + H2O + Cd2+[side 1]
ADP + phosphate + Cd2+[side 2]
Substrates: -
Products: -
Products: -
?
ATP + H2O + Cd2+[side 1]
ADP + phosphate + Cd2+[side 2]
-
Substrates: -
Products: -
Products: -
?
ATP + H2O + Cd2+[side 1]
ADP + phosphate + Cd2+[side 2]
Rossellomorea marisflavi 151-25
-
Substrates: -
Products: -
Products: -
?
ATP + H2O + Cd2+[side 1]
ADP + phosphate + Cd2+[side 2]
-
Substrates: -
Products: -
Products: -
?
ATP + H2O + Cd2+[side 1]
ADP + phosphate + Cd2+[side 2]
-
Substrates: -
Products: -
Products: -
?
ATP + H2O + Zn2+/in
ADP + phosphate + Zn2+/out
-
Substrates: active transport of Cd2+ out of the cell to maintain metal homeostasis
Products: -
Products: -
?
ATP + H2O + Zn2+/in
ADP + phosphate + Zn2+/out
Substrates: active transport of Cd2+ out of the cell to maintain metal homeostasis
Products: -
Products: -
?
additional information
?
-
Substrates: involved in Cd2+, Pb2+, and Zn2+ resistance
Products: -
Products: -
?
additional information
?
-
Substrates: involved in Cd2+, Pb2+, and Zn2+ resistance
Products: -
Products: -
?
additional information
?
-
-
Substrates: mechanism for substrate-mediated control of P1B-type ATPase expression, overview. Dependence of Pca1 degradation through the vacuolar/endosomal pathway
Products: -
Products: -
?
additional information
?
-
-
Substrates: mechanism for substrate-mediated control of P1B-type ATPase expression, overview. Dependence of Pca1 degradation through the vacuolar/endosomal pathway
Products: -
Products: -
?
additional information
?
-
Substrates: involved in Cd2+, Pb2+, and Zn2+ resistance, not involved in Hg2+ resistance
Products: -
Products: -
?
additional information
?
-
-
Substrates: cadmium and zinc lead to the upregulation of genes encoded on the pSymA or pSymB plasmids, expression of the efflux pumps SMc01095, i.e. mexF1, and SMb20345 is enhanced 41fold and 4fold, respectively, overview
Products: -
Products: -
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Cd2+
-
enzyme can perform its cycle in the absence of Mg2+, using CdATP2- in the place of MgATP2-
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
N-ethylmaleimide
-
inhibits the formation of the phosphoenzyme, effect can be supressed in presence of Cd2+
orthovanadate
-
Cd2+ uptake by plasma membranes is almost completely reduced in the presence of 1 mM orthovanadate. The relevant process observed in the tonoplasts is strongly reduced by both, 0.1 mM (up to 40% in control and Cd-stressed plants) and 1 mM Na2VO4 (up to 25% and 20% in control plants and stressed plants, respectively)
additional information
-
pre-exposure to either 0.01 or 0.1 mM orthovanadate does not affect the cellular Cd2+ uptake rate. After 60 min efflux, approximately 40% and 20% of accumulated Cd2+ in the enterocytes is lost in the absence and presence of orthovanadate, respectively, when compared to 0 min. Pre-exposure to verapamil or lanthanum does not exhibit any effects on the cellular Cd2+ uptake rate
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ca2+
-
the inducing effect of cadmium on Pca1 expression is independent of epitope or its location
dithiothreitol
-
170% increase of Cd2+ transport across plasma membranes at 5 mM. Cd transport across tonoplasts is stimulated up to 125% by 5 mM dithiothreitol
GSH
-
200% increase of Cd2+ transport across plasma membranes at 5 mM. Cd transport across tonoplasts is stimulated up to 160% by 5 mM GSH
L-cysteine
-
200% increase of Cd2+ transport across plasma membranes at 50 mM. Cd transport across tonoplasts is stimulated up to 120% by 50 mM L-cysteine
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Menkes Kinky Hair Syndrome
Human Menkes X-chromosome disease and the staphylococcal cadmium-resistance ATPase: a remarkable similarity in protein sequences.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
the range of 0.1-10 microM of added CdCl2 corresponds to Cd2+ binding at the transport site of unphosphorylated enzyme which induces the reaction of the enzyme with ATP and impairs the reaction with phosphate. The 0.1-1 mM range of added CdCl2 corresponds to Cd2+ binding to the transport site accessible from the extracellular medium
-
0.00169
Cd2+/out
-
in the presence of 2.5 mM Fe2+, pH and temperature not specified in the publication
0.00193
Cd2+/out
-
in the presence of 0.01 mM Zn2+, pH and temperature not specified in the publication
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
serovar Typhimurium, use of wild type and a cadmium senitive zntA-knockout mutant, expression of cadA gene from Geobacillus stearothermophilus LV in wild type yields a cadmium hypersensitive phenotype, when the zntA-knockout mutant is used cadmium sensitivity is reverted
SwissProt
brenda
harboring plasmid pGN114 containing the cadmium resistance determinant
-
-
brenda
the plasmid pLm74 confers resistance to Cd2+, it does not confer zinc resistance
-
-
brenda
different laboratory (S288c, BY4741, DTY1, EG103, SKY9, and YPH98) and wild type strains (RM11-1a and Fleischmanns), PCA1 allele in all laboratory yeast strains examined carries a missense mutation in a conserved residue resulting in loss of function, wild-type PCA1 allele confers cadmium resistance by an Cd2+ efflux mechanism
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
found in all tissues, with highest levels in roots and cauline leaves
brenda
-
variation in the BrHMA3 promoter sequence has little effect on Cd translocation. Variation in the BrHMA3 coding sequence is a key determinant of Cd translocation to and accumulation in the leaves of Brassica rapa
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
recombinant enzyme in Saccharomyces cerevisiae
brenda
-
G970R mutation affects correct trafficking of the protein
brenda
-
Pca1 contains a cytosolic cysteine-rich N-terminal extension of nearly 400 residue
brenda
-
Pca1 contains a cytosolic cysteine-rich N-terminal extension of nearly 400 residue
-
brenda
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
-
the root cell cytoplasm of Cd-overaccumulating rice plants has more Cd available for loading into the xylem as a result of the lack of HMA3-mediated transportation of Cd to the vacuoles
malfunction
-
compared to the wild type strain, 20% more Cd2+ accumulate in DELTAzntA strain
malfunction
-
compared to the wild type strain, 20% more Cd2+ accumulate in DELTAzntA strain
-
physiological function
-
metal ATPase 3 controls root-to-shoot Cd2+ translocation rates
physiological function
expression of Hmtp in Escherichia coli increases the tolerance to cadmium and zinc
physiological function
a CadA-deleted strain fails to grow at high zinc concentrations (2 mM) and its growth is delayed at lower zinc concentrations. CadA is specifically induced in a dose-dependent manner by zinc and cadmium in in vitro conditions and into Anthyllis vulneraria nodules after Zn stress. Metal induction sensitivity is increased in the strain where CadA gene is deleted. Heterlogous expression in Escherichia coli confers resistance to Cd2+ to the clone
physiological function
HMA3-RNAi lines are hypersensitive to Cd but not to Zn, with the growth of shoots and young leaves being severely inhibited by Cd. Overexpressing HMA3 in the nonhyperaccumulating ecotype of Sedum alfredii greatly increases its tolerance to and accumulation of Cd, but not Zn. Expression of HMA3 in Saccharomyces cerevisiae results in Cd-specific transport activity
physiological function
-
Orf4802 (ATPase transporter) and Orf4803 (transcriptional regulator) on plasmid p25 are major contributors to Cd2+ resistance of Bacillus marisflavi 151-25
physiological function
-
the enzyme (HMA1) is involved in chloroplast Cd detoxification
physiological function
-
the enzyme (HMA2) contributes to the translocation of Cd during the xylem loading process
physiological function
-
the enzyme (HMA3) is associated with high Cd accumulation in root vacuoles
physiological function
-
down-regulation of HMA3 (heavy metal ATPase 3) and up-regulation of HMA2 (heavy metal ATPase 2) might play roles in reducing Cd toxicity in roots
physiological function
-
root to shoot translocation of Cd is a critical step controlling Cd accumulation in the above-ground tissues of Brassica rapa. BrHMA3 is a key gene controlling Cd translocation to and accumulation in the edible parts of Brassica rapa vegetables. BrHMA3 is responsible for the sequestration of Cd into the root vacuoles
physiological function
-
Orf4802 (ATPase transporter) and Orf4803 (transcriptional regulator) on plasmid p25 are major contributors to Cd2+ resistance of Bacillus marisflavi 151-25
physiological function
ZntA confers resistance to wild-type Escherichia coli strains against toxic levels of Pb2+, Cd2+, and Zn2+ in the growth medium
physiological function
-
the enzyme (OsHMA3) allows vacuolar sequestration of Cd2+ in the root
physiological function
-
expression of Hmtp in Escherichia coli increases the tolerance to cadmium and zinc
-
physiological function
-
ZntA confers resistance to wild-type Escherichia coli strains against toxic levels of Pb2+, Cd2+, and Zn2+ in the growth medium
-
physiological function
Mesorhizobium metallidurans STM 2683T
-
a CadA-deleted strain fails to grow at high zinc concentrations (2 mM) and its growth is delayed at lower zinc concentrations. CadA is specifically induced in a dose-dependent manner by zinc and cadmium in in vitro conditions and into Anthyllis vulneraria nodules after Zn stress. Metal induction sensitivity is increased in the strain where CadA gene is deleted. Heterlogous expression in Escherichia coli confers resistance to Cd2+ to the clone
-
physiological function
-
Orf4802 (ATPase transporter) and Orf4803 (transcriptional regulator) on plasmid p25 are major contributors to Cd2+ resistance of Bacillus marisflavi 151-25
-
physiological function
Rossellomorea marisflavi 151-25
-
Orf4802 (ATPase transporter) and Orf4803 (transcriptional regulator) on plasmid p25 are major contributors to Cd2+ resistance of Bacillus marisflavi 151-25
-
physiological function
Oryza sativa Indica Group MTU 7029
-
the enzyme (OsHMA3) allows vacuolar sequestration of Cd2+ in the root
-
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
dimer
the first four transmembrane helices in ZntA and P1B-type ATPases play an important role in maintaining the correct dimer structure
dimer
-
the first four transmembrane helices in ZntA and P1B-type ATPases play an important role in maintaining the correct dimer structure
-
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
structural analysis of N-terminal enzyme domain, soluble monomeric protein of 71 amino acids, by NMR and X-ray absorption spectroscopy
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C392A
mutant DELTA231-ZntA(C392A), binds Pb2+ and Zn2+ with a stoichiometry of 0.5 and with similar or slightly higher affinity than DELTA231-ZntA. Cd2+ does not bind to the mutant enzyme
C394A
mutant DELTA231-ZntA(C394A), binds Pb2+ and Zn2+ with a stoichiometry of 0.5 and with similar or slightly higher affinity than DELTA231-ZntA. The mutant enzyme binds Cd2+ with unchanged affinity and with a stoichiometry of 0.5
D714A
mutant DELTA231-ZntA(D714A), binds Pb2+ and Zn2+ with a stoichiometry of 0.5 and with similar or slightly higher affinity than DELTA231-ZntA. Cd2+ does not bind to the mutant enzyme
C354A
-
transmembrane segment 6, participation in Cd2+ binding, inactive in transport of Cd2+, no ATPase activity
C356A
-
transmembrane segment 6, participation in Cd2+ binding, inactive in transport of Cd2+
D692A
-
transmembrane segment 8, participation in Cd2+ binding, inactive in transport of Cd2+, no ATPase activity
M149A
-
transmembrane segment 3, participation in Cd2+ binding, reduced ATPase activity
C298A/C300A
-
site-directed mutation of the CXC motif abolishes copper resistance but not cadmium resistance
C311A/C312A
-
site-directed mutation of the CC motif abolishes cadmium resistance yet retains the ability to confer copper resistance
G970R
-
naturally occurring missense mutation presented in a number of yeast laboratory strains, loss of function, mutation is not found in wild type strains
C298A/C300A
-
site-directed mutation of the CXC motif abolishes copper resistance but not cadmium resistance
-
C311A/C312A
-
site-directed mutation of the CC motif abolishes cadmium resistance yet retains the ability to confer copper resistance
-
additional information
additional information
DELTA231-ZntA has no in vivo and greatly reduced in vitro activity. It binds one metal ion per dimer at the transmembrane site, with a 15-19000-fold higher binding affinity, indicating highly significant changes in the dimer structure of DELTA231-ZntA relative to that of ZntA. Cd2+ has the highest affinity for DELTA231-ZntA, in contrast to ZntA, which has the highest affinity for Pb2+. DELTA231-ZntA is unable to confer resistance to Pb2+, Zn2+, and Cd2+ salts in LMG194(zntA::cat) and behaves like the zntA deletion strain
additional information
-
DELTA231-ZntA has no in vivo and greatly reduced in vitro activity. It binds one metal ion per dimer at the transmembrane site, with a 15-19000-fold higher binding affinity, indicating highly significant changes in the dimer structure of DELTA231-ZntA relative to that of ZntA. Cd2+ has the highest affinity for DELTA231-ZntA, in contrast to ZntA, which has the highest affinity for Pb2+. DELTA231-ZntA is unable to confer resistance to Pb2+, Zn2+, and Cd2+ salts in LMG194(zntA::cat) and behaves like the zntA deletion strain
-
additional information
construction of a C-terminal fragment that contains heavy metal-binding domains
additional information
-
site-directed mutagenesis of conserved amino acids among P1B-type ATPases, including the CXXC motif (C421, C424), the CPX motif (C859), and the phosphorylation site (Asp-903), completely abolished cadmium resistance
additional information
-
deletion of the N-terminal extension domain results in constitutive expression of Pca1 at the cell surface even in the absence of cadmium. Pca1 is not stabilized in a yeast strain defective in endocytosis, GFP-Pca1 does not accumulate in the vacuole of the DELTApep4 strain
additional information
-
deletion of the N-terminal extension domain results in constitutive expression of Pca1 at the cell surface even in the absence of cadmium. Pca1 is not stabilized in a yeast strain defective in endocytosis, GFP-Pca1 does not accumulate in the vacuole of the DELTApep4 strain
-
additional information
-
construction of mutant strains containing mini-Tn5 transposons, analysis of mutation effects on protein expression levels in presence of high concentrations of cadmium or zinc
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
complementation studies by expression in Saccharomyces cerevisiae
expression in Saccharomyces cerevisiae for a complementation screening
expression in Saccharomyces cerevisiae, expression in the Cd-sensitive yeast strain Y04069 complements the mutation
expression in Sf9 cells of the native enzyme and a truncated peptide lacking the metal-binding domain
-
expression of a mutant protein in Bacillus subtilis, the resulting strain shows higher sensitivity to Cd2+, Zn2+ and Co2+ than the wild type
-
expression of gene in Salmonella enterica serovar Typhimurium yields a cadmium hypersensitive phenotype, when a zntA-knockout mutant of Salmonella enterica (cadmium senitive) is used cadmium sensitivity is reverted
generation of transgenic tobacco plants expressing the rice heavy metal P-type ATPase 3 gene (OsHMA3) in the roots under the control of a root-specific promoter from a tobacco root extensin-like protein-coding gene (NtREL1). Transgenic plants showed significantly reduced Cd accumulation in the shoots
N-terminal binding-domain of 71 amino acids carrying a S71A mutation expressed in Escherichia coli M15
when expressed in yeast and Arabidopsis thaliana, full-length BrHMA3 shows activity consistent with a Cd transport function, whereas truncated BrHMA3 does not
-
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
genes encoding HMA2 (BjuA003596, BjuB040613) are significantly upregulated in roots, and BjuB040613 also shows higher expression levels in leaves, when plants are under Cd30 treatment
-
genes encoding HMA3 (BjuO011640, BjuA042408) are down-regulated in roots when plants are under Cd30 treatment
-
no significant difference in HMA3 expression is observed after Cd treatment
organic acid supply enhances carboxylic speciation of Cd which in turn favors vacuolar sequestration of Cd in the root along with the overexpression of OsHMA3
organic acid supply enhances carboxylic speciation of Cd which in turn favors vacuolar sequestration of Cd in the root along with the overexpression of OsHMA3
-
organic acid supply enhances carboxylic speciation of Cd which in turn favors vacuolar sequestration of Cd in the root along with the overexpression of OsHMA3
Oryza sativa Indica Group MTU 7029
-
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
agriculture
OsHMA3 can be expressed in tobacco plants and may be useful for developing tobacco varieties with a reduced capacity to accumulate Cd in the shoots, potentially reducing the risk of Cd exposure for smoking people
biotechnology
-
expression of enzyme in Saccharomyces cerevisiae strikingly decreases Cd2+ tolerance of yeast cells. Yeast expressing the non-functional mutant D398A can grow on selective medium containing up to 0.1 mM Cd2+, while those expressing the intact enzyme cannot grow in presence of 0.001 mM Cd2+. Enzyme is localized in the endoplasmic reticulum, so hypersensitivity to Cd2+ is due to Cd2+ accumulation in the reticulum lumen. Zn2+ does not protect cells against Cd2+ poisoning
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Silver, S.; Nucifora, G.; Phung, L.T.
Human Menkes X-chromosome disease and the staphylococcal cadmium-resistance ATPase: a remarkable similarity in protein sequences
Mol. Microbiol.
10
7-12
1993
Staphylococcus aureus
brenda
Lebrun, M.; Audurier, A.; Cossart, P.
Plasmid-borne cadmium resistance genes in Listeria monocytogenes are similar to cadA and cadC of Staphylococcus aureus and are induced by cadmium
J. Bacteriol.
176
3040-3048
1994
Listeria monocytogenes
brenda
Tsai, K.J.; Yoon, K.P.; Lynn, A.R.
ATP-dependent cadmium transport by the cadA cadmium resistance determinat in everted membrane vesicles of Bacillus subtilis
J. Bacteriol.
174
116-121
1992
Bacillus subtilis
brenda
Nucifora, G.; Chu, L.; Misra, T.K.; Silver, S.
Cadmium resistance from Staphylococcus aureus plasmid pI258 cadA gene results from a cadmium-efflux ATPase
Proc. Natl. Acad. Sci. USA
86
3544-3548
1989
Staphylococcus aureus
brenda
Rensing, C.; Sun, Y.; Mitra, B.; Rosen, B.P.
Pb(II)-translocating P-type ATPase
J. Biol. Chem.
273
32614-32617
1998
Staphylococcus aureus
brenda
Lee, S.W.; Glickmann, E.; Cooksey, D.A.
Chromosomal locus for cadmium resistance in Pseudomonas putida consisting of a cadmium-transporting ATPase and a MerR family response regulator
Appl. Environ. Microbiol.
67
1437-1444
2001
Pseudomonas putida (Q93TP6), Pseudomonas putida 6909 (Q93TP6)
brenda
Bal, N.; Wu, C.C.; Catty, P.; Guillain, F.; Mintz, E.
Cd2+ and the N-terminal metal-binding domain protect the putative membranous CPC motif of the Cd2+-ATPase of Listeria monocytogenes
Biochem. J.
369
681-685
2003
Listeria monocytogenes
brenda
Gaballa, A.; Helmann, J.D.
Bacillus subtilis CPx-type ATPases: Characterization of Cd, Zn, Co and Cu efflux systems
BioMetals
16
497-505
2003
Bacillus subtilis, Bacillus subtilis 168 / CU1065
brenda
Gravot, A.; Lieutaud, A.; Verret, F.; Auroy, P.; Vavasseur, A.; Richaud, P.
AtHMA3, a plant P1B-ATPase, functions as a Cd/Pb transporter in yeast
FEBS Lett.
561
22-28
2004
Arabidopsis thaliana (P0CW78)
brenda
Bernard, C.; Roosens, N.; Czernic, P.; Lebrun, M.; Verbruggen, N.
A novel CPx-ATPase from the cadmium hyperaccumulator Thlaspi caerulescens
FEBS Lett.
569
140-148
2004
Noccaea caerulescens (Q70LF4)
brenda
Papoyan, A.; Kochian, L.V.
Identification of Thlaspi caerulescens genes that may be involved in heavy metal hyperaccumulation and tolerance - characterization of a novel heavy metal transporting ATPase
Plant Physiol.
136
3814-3823
2004
Noccaea caerulescens (Q69AX6)
brenda
Wu, C.C.; Bal, N.; Perard, J.; Lowe, J.; Boscheron, C.; Mintz, E.; Catty, P.
A cloned prokaryotic Cd2+ P-type ATPase increases yeast sensitivity to Cd2+
Biochem. Biophys. Res. Commun.
324
1034-1040
2004
Listeria monocytogenes
brenda
Wu, C.C.; Gardarin, A.; Catty, P.; Guillain, F.; Mintz, E.
CadA, the Cd(2+)-ATPase from Listeria monocytogenes, can use Cd(2+) as co-substrate
Biochimie
88
1687-1692
2006
Listeria monocytogenes
brenda
Wu, C.C.; Gardarin, A.; Martel, A.; Mintz, E.; Guillain, F.; Catty, P.
The cadmium transport sites of CadA, the Cd(2+)-ATPase from Listeria monocytogenes
J. Biol. Chem.
281
29533-29541
2006
Listeria monocytogenes
brenda
Banci, L.; Bertini, I.; Ciofi-Baffoni, S.; Su, X.C.; Miras, R.; Bal, N.; Mintz, E.; Catty, P.; Shokes, J.E.; Scott, R.A.
Structural basis for metal binding specificity: the N-terminal cadmium binding domain of the P1-type ATPase CadA
J. Mol. Biol.
356
638-650
2006
Listeria monocytogenes (Q60048), Escherichia coli
brenda
Perez, J.M.; Pradenas, G.A.; Navarro, C.A.; Henriquez, D.R.; Pichuantes, S.E.; Vasquez, C.C.
Geobacillus stearothermophilus LV cadA gene mediates resistance to cadmium, lead and zinc in zntA mutants of Salmonella enterica serovar Typhimurium
Biol. Res.
39
661-668
2006
Geobacillus stearothermophilus (Q93GJ9), Salmonella enterica (Q8ZLE5), Geobacillus stearothermophilus LV (Q93GJ9)
brenda
Adle, D.J.; Sinani, D.; Kim, H.; Lee, J.
A cadmium-transporting P1B-type ATPase in yeast Saccharomyces cerevisiae
J. Biol. Chem.
282
947-955
2007
Saccharomyces cerevisiae
brenda
Rossbach, S.; Mai, D.J.; Carter, E.L.; Sauviac, L.; Capela, D.; Bruand, C.; de Bruijn, F.J.
Response of Sinorhizobium meliloti to elevated concentrations of cadmium and zinc
Appl. Environ. Microbiol.
74
4218-4221
2008
Sinorhizobium meliloti
brenda
Adle, D.J.; Lee, J.
Expressional control of a cadmium-transporting P1B-type ATPase by a metal sensing degradation signal
J. Biol. Chem.
283
31460-31468
2008
Saccharomyces cerevisiae, Saccharomyces cerevisiae BY4741
brenda
Kwong, R.W.; Niyogi, S.
Cadmium transport in isolated enterocytes of freshwater rainbow trout: interactions with zinc and iron, effects of complexation with cysteine, and an ATPase-coupled efflux
Comp. Biochem. Physiol. C
155
238-246
2012
Oncorhynchus mykiss
brenda
Migocka, M.; Papierniak, A.; Kosatka, E.; Klobus, G.
Comparative study of the active cadmium efflux systems operating at the plasma membrane and tonoplast of cucumber root cells
J. Exp. Bot.
62
4903-4916
2011
Cucumis sativus
brenda
Miyadate, H.; Adachi, S.; Hiraizumi, A.; Tezuka, K.; Nakazawa, N.; Kawamoto, T.; Katou, K.; Kodama, I.; Sakurai, K.; Takahashi, H.; Satoh-Nagasawa, N.; Watanabe, A.; Fujimura, T.; Akagi, H.
OsHMA3, a P1B-type of ATPase affects root-to-shoot cadmium translocation in rice by mediating efflux into vacuoles
New Phytol.
189
190-199
2011
Oryza sativa
brenda
Chien, C.; Huang, C.; Lin, Y.
Characterization of a heavy metal translocating P-type ATPase gene from an environmental heavy metal resistance Enterobacter sp. isolate
Appl. Biochem. Biotechnol.
169
1837-1846
2013
Enterobacter sp. (M9NX10), Enterobacter sp. CD01 (M9NX10)
brenda
Liu, H.; Zhao, H.; Wu, L.; Liu, A.; Zhao, F.J.; Xu, W.
Heavy metal ATPase 3 (HMA3) confers cadmium hypertolerance on the cadmium/zinc hyperaccumulator Sedum plumbizincicola
New Phytol.
215
687-698
2017
Sedum plumbizincicola (A0A1W6EUG1), Sedum plumbizincicola
brenda
Maynaud, G.; Brunel, B.; Yashiro, E.; Mergeay, M.; Cleyet-Marel, J.C.; Le Quere, A.
CadA of Mesorhizobium metallidurans isolated from a zinc-rich mining soil is a P(IB-2)-type ATPase involved in cadmium and zinc resistance
Res. Microbiol.
165
175-189
2014
Mesorhizobium metallidurans (I4IY19), Mesorhizobium metallidurans STM 2683T (I4IY19)
brenda
Roberts, C.; Muralidharan, S.; Ni, F.; Mitra, B.
Structural role of the first four transmembrane helices in ZntA, a P1B-Type ATPase from Escherichia coli
Biochemistry
59
4488-4498
2020
Escherichia coli (P37617), Escherichia coli K12 (P37617)
brenda
Yu, X.; Ding, Z.; Ji, Y.; Zhao, J.; Liu, X.; Tian, J.; Wu, N.; Fan, Y.
An operon consisting of a P-type ATPase gene and a transcriptional regulator gene responsible for cadmium resistances in Bacillus vietamensis 151-6 and Bacillus marisflavi 151-25
BMC Microbiol.
20
18
2020
Rossellomorea marisflavi, Rossellomorea marisflavi 151-25, Rossellomorea vietnamensis, Rossellomorea vietnamensis 151-6
brenda
Sebastian, A.; Prasad, M.N.V.
Exogenous citrate and malate alleviate cadmium stress in Oryza sativa L. Probing role of cadmium localization and iron nutrition
Ecotoxicol. Environ. Saf.
166
215-222
2018
Oryza sativa Indica Group, Oryza sativa Indica Group MTU 7029
brenda
Zhang, D.; Du, Y.; He, D.; Zhou, D.; Wu, J.; Peng, J.; Liu, L.; Liu, Z.; Yan, M.
Use of comparative transcriptomics combined with physiological analyses to identify key factors underlying cadmium accumulation in Brassica juncea L
Front. Genet.
12
655885
2021
Brassica juncea
brenda
Zhang, L.; Wu, J.; Tang, Z.; Huang, X.Y.; Wang, X.; Salt, D.E.; Zhao, F.J.
Variation in the BrHMA3 coding region controls natural variation in cadmium accumulation in Brassica rapa vegetables
J. Exp. Bot.
70
5865-5878
2019
Brassica rapa
brenda
Zhu, T.; Tian, L.; Yu, S.; Yu, H.
Roles of cation efflux pump in biomineralization of cadmium into quantum dots in Escherichia coli
J. Hazard. Mater.
412
125248
2021
Escherichia coli, Escherichia coli JM109
brenda
Cai, H.; Xie, P.; Zeng, W.; Zhai, Z.; Zhou, W.; Tang, Z.
Root-specific expression of rice OsHMA3 reduces shoot cadmium accumulation in transgenic tobacco
Mol. Breed.
39
49
2019
Oryza sativa Japonica Group (Q8H384)
-
brenda
EXTERNAL LINKS (specific for EC-Number 7.2.2.21)
Transporter Classification Database (TCDB): 3.A.3.6.6, 3.A.3.6.7, 3.A.3.6.19, 3.A.3.6.20, 3.A.3.6.17, 3.A.3.6.18, 3.A.3.6.3, 3.A.3.5.14, 3.A.3.6.2, 3.A.3.6.1, 3.A.3.6.10, 3.A.3.6.8
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