Information on EC 3.6.3.46 - cadmium-transporting ATPase

Word Map on EC 3.6.3.46
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
3.6.3.46
-
RECOMMENDED NAME
GeneOntology No.
cadmium-transporting ATPase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + H2O = ADP + phosphate
show the reaction diagram
ABC-type (ATP-binding cassette) ATPase, characterized by the presence of two similar ATP-binding domains. Does not undergo phosphorylation during the transport process. A yeast enzyme that exports some heavy metals, especially Cd2+, from the cytosol into the vacuole.
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
transmembrane transport
SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (heavy-metal-exporting)
ABC-type (ATP-binding cassette-type) ATPase, characterized by the presence of two similar ATP-binding domains. Does not undergo phosphorylation during the transport process. A yeast enzyme that exports some heavy metals, especially Cd2+, from the cytosol into the vacuole.
CAS REGISTRY NUMBER
COMMENTARY hide
9000-83-3
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
no activity in Arabidopsis thaliana ecotype Columbia
-
-
-
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
strain BY4741, gene YCF1
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + H2O + Cd/in
ADP + phosphate + Cd/out
show the reaction diagram
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/in
show the reaction diagram
-
ABC transporter, HMT-1, confers tolerance to cadmium. HMT-1 is not essential for vacuolar phytochelatin sequestration. HMT-1 either does not transport Cd-PC complexes or is not the principal Cd-PC/apoPC transporter
-
-
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
show the reaction diagram
bilirubin/cytoplasm + ATP + H2O
bilirubin/vacuole + ADP + phosphate
show the reaction diagram
-
unconjugated substrate
-
-
?
Cd x glutathione S2/cytoplasm + ATP + H2O
Cd x glutathione S2/vacuole + phosphate
show the reaction diagram
-
-
-
-
?
Cd/cytoplasm + ATP + H2O
Cd/vacuole + ADP + phosphate
show the reaction diagram
Cd2+/cytoplasm + ATP + H2O
Cd2+/vacuole + ADP + phosphate
show the reaction diagram
-
-
-
-
?
diazaborine/cytoplasm + ATP + H2O
diazaborine/vacuole + ADP + phosphate
show the reaction diagram
-
-
-
-
?
glutathione S-conjugated leukotriene C4/cytoplasm + ATP + H2O
glutathione S-conjugated leukotriene C4/vacuole + ADP + phosphate
show the reaction diagram
glutathione S-conjugates/cytoplasm + ATP + H2O
glutathione S-conjugates/vacuole + ADP + phosphate
show the reaction diagram
-
-
-
-
?
glutathione/cytoplasm + ATP + H2O
glutathione/vacuole + ADP + phosphate
show the reaction diagram
-
-
-
-
?
S-(2,4-dinitrophenyl)glutathione/cytoplasm + ATP + H2O
S-(2,4-dinitrophenyl)glutathione/vacuole + ADP + phosphate
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + H2O + Cd/in
ADP + phosphate + Cd/out
show the reaction diagram
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/in
show the reaction diagram
-
ABC transporter, HMT-1, confers tolerance to cadmium. HMT-1 is not essential for vacuolar phytochelatin sequestration. HMT-1 either does not transport Cd-PC complexes or is not the principal Cd-PC/apoPC transporter
-
-
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
show the reaction diagram
bilirubin/cytoplasm + ATP + H2O
bilirubin/vacuole + ADP + phosphate
show the reaction diagram
-
unconjugated substrate
-
-
?
Cd x glutathione S2/cytoplasm + ATP + H2O
Cd x glutathione S2/vacuole + phosphate
show the reaction diagram
-
-
-
-
?
Cd/cytoplasm + ATP + H2O
Cd/vacuole + ADP + phosphate
show the reaction diagram
diazaborine/cytoplasm + ATP + H2O
diazaborine/vacuole + ADP + phosphate
show the reaction diagram
-
-
-
-
?
glutathione S-conjugated leukotriene C4/cytoplasm + ATP + H2O
glutathione S-conjugated leukotriene C4/vacuole + ADP + phosphate
show the reaction diagram
-
-
-
-
?
glutathione S-conjugates/cytoplasm + ATP + H2O
glutathione S-conjugates/vacuole + ADP + phosphate
show the reaction diagram
-
-
-
-
?
glutathione/cytoplasm + ATP + H2O
glutathione/vacuole + ADP + phosphate
show the reaction diagram
-
-
-
-
?
S-(2,4-dinitrophenyl)glutathione/cytoplasm + ATP + H2O
S-(2,4-dinitrophenyl)glutathione/vacuole + ADP + phosphate
show the reaction diagram
-
-
-
-
?
additional information
?
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4',4'-diisothiocyanatostilbene-2',2'-disulfonic acid
-
uptake of S-(2,4-dinitrophenyl)glutathione inhibited
N-ethylmaleimide
-
inhibition of phosphorylation, Cd2+ protects
PAK-104P
-
42% inhibition at 0.1 mM
probenecid
-
uptake of S-(2,4-dinitrophenyl)glutathione inhibited
sulfinpyrazone
-
uptake of S-(2,4-dinitrophenyl)glutathione inhibited
vanadate
verapamil
-
IC50: 0.2 mM
vinblastine
-
IC50: 0.08 mM
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Tus1p
-
a guanine nucleotide exchange factor, stimulates the enzyme
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.05 - 1.71
ATP
0.0000168 - 0.0000237
bilirubin
0.187 - 0.548
estradiol-beta-17-glucuronide
-
15
glutathione
-
in vesicles
0.000758 - 0.00082
leukotriene C4
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.18
vanadate
Saccharomyces cerevisiae
-
IC50: 0.18 mM
0.2
verapamil
Saccharomyces cerevisiae
-
IC50: 0.2 mM
0.08
vinblastine
Saccharomyces cerevisiae
-
IC50: 0.08 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
measurement of growth inhibition by cadmium in wild-type and mutant strains, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
; phytochelatin synthase pcs-1 and hmt-1 are co-expressed in coelomocytes. Coelomocytes are essential mainly for detoxification of heavy metals, but not of oxidative stress, a by-product of heavy metal toxicity
Manually annotated by BRENDA team
high expression level
Manually annotated by BRENDA team
low expression level
Manually annotated by BRENDA team
additional information
poor expression in roots
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
the N terminus of Pca1 contains a targeting signal for ERAD. Degradation of Pca1 and cadmium sensing occur at the endoplasmic reticulum
Manually annotated by BRENDA team
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
77000
-
x * 77000, SDS-PAGE
120000
140000
-
SDS-PAGE
160000 - 170000
-
SDS-PAGE
170000
171000
-
nucleotide sequence
185000 - 200000
-
SDS-PAGE
additional information
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
additional information
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
Pca1 is a short-lived proteinwith t1?2 below 5 min and is subject to ubiquitination when cells are growing in media lacking cadmium
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-85°C, vacuolar membrane preparations
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
construction of an integrated membrane yeast two-hybrid, iMYTH, screen and identification of two kinase genes, CKA1 and HAL5, deletion of which increases Ycf1p function
-
expressed in Sf21 insect cells
-
expression in Schizosaccharomyces pombe
gene YCF1, semiquantitative expression analysis in absence and presence of Cd2+, overview
-
OSA1 expression analysis, and phylogenetic analysis, overview. No complementation of Saccharomyces cerevisiae mutant strain W303-1A abc1THIS3 by the wild-type enzyme
Pca1 expression analysis
-
phylogenetic analysis
-
the pYES2 plasmid is used for overexpression of EGFP-N2, YCF1, or YCF-EGFP-N2 in different Saccharomyces cerevisiae strains
-
transgenic expression of wild-type and mutant enzymes in Arabidopsis thaliana Col-0 ecotype, which is sensitive to Cd. EGFP-tagged mutant OsMA3-C788 is bombarded into onion epidermal cell, the green fluorescence of the OsHMA3-C788 fusion protein is observed as an outline of the cell shape and is also delineated the nucleus
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
endoplasmic reticulum-associated degradation (ERAD) system is responsible for the regulation of Pca1 expression by cadmium. Direct cadmium sensing at the endoplasmic reticulum by a degron in Pca1 leads to an escape of Pca1 from endoplasmic reticulum-associated degradation
-
in the absence of its cadmium substrate, Pca1 is rapidly degraded through the endoplasmic reticulum-associated degradation pathway
-
the expression of gene YFC1 is downregulated in presence of Cd2+, which affects the YFC1 promoter
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D398A
-
non-phosphorylatable protein, no stimulation by Cd2+ but rather inhibition at high Cd2+ concentrations
A910G
-
mutants more sensitive to Cd2+ than wild type strain, higher activity for glutathione S-conjugated leukotriene C4
D777N/A1003V
-
intragenic suppressor of mutation D777N
D777N/A1021T
-
intragenic suppressor of mutation D777N, functionally important residue
D777N/A1021V
-
intragenic suppressor of mutation D777N, functionally important residue
D777N/F565L
-
intragenic suppressor of mutation D777N, involved in determination of substrate specificity
D777N/G1207D
-
intragenic suppressor of mutation D777N, functionally important residue
D777N/G1207S
-
intragenic suppressor of mutation D777N, functionally important residue
D777N/N1027D
-
intragenic suppressor of mutation D777N
D777N/Q1107R
-
intragenic suppressor of mutation D777N, involved in determination of substrate specificity
D777N/R1415G
-
intragenic suppressor of mutation D777N, functionally important residue
D777N/S1212L
-
intragenic suppressor of mutation D777N, functionally important residue
D777N/S674L
-
intragenic suppressor of mutation D777N
D777N/V543I
-
intragenic suppressor of mutation D777N, involved in determination of substrate specificity
D777N/W1225C
-
intragenic suppressor of mutation D777N, involved in determination of substrate specificity
D821G
-
mutants with Ycf1p in vivo activity as wild type strain
E709Q
-
mutants with Ycf1p in vivo activity as wild type strain
E927K
-
mutants exhibit a Cd2+ hypersensitive phenotype
G1306E
-
mutants exhibit a Cd2+ hypersensitive phenotype, abolished transport activity for glutathione S-conjugated leukotriene C4
G1311R
-
mutants exhibit a Cd2+ hypersensitive phenotype, abolished transport activity for glutathione S-conjugated leukotriene C4
G1413D
-
mutants exhibit a Cd2+ hypersensitive phenotype
G663V
-
mutants exhibit a Cd2+ hypersensitive phenotype, abolished transport activity for glutathione S-conjugated leukotriene C4
G756S
-
substitution mutation, unable to complement the cadmium hypersensitivity of the introduced strain
G835R
-
mutants more sensitive to Cd2+ than wild type strain, partially reduced transport activity for glutathione S-conjugated leukotriene C4
I711S
-
mutants exhibit a Cd2+ hypersensitive phenotype
I840P
-
mutants more sensitive to Cd2+ than wild type strain, partially reduced transport activity for glutathione S-conjugated leukotriene C4
L817S
-
mutants more sensitive to Cd2+ than wild type strain
L825T
-
mutants more sensitive to Cd2+ than wild type strain
L826S
-
mutants more sensitive to Cd2+ than wild type strain, partially reduced transport activity for glutathione S-conjugated leukotriene C4
N1366K
-
mutants exhibit a Cd2+ hypersensitive phenotype, partially reduced transport activity for glutathione S-conjugated leukotriene C4
Q1148P
-
mutants more sensitive to Cd2+ than wild type strain
R1143C
-
mutants more sensitive to Cd2+ than wild type strain, partially reduced transport activity for glutathione S-conjugated leukotriene C4
S251A
-
the site-directed mutation inhibits phosphorylation, the mutant exhibits increased resistance to cadmium in vivo and increased Ycf1p-dependent transport of [3H]estradiol-beta-17-glucuronide in vitro as compared with wild-type Ycf1p
S251E
-
the site-directed mutation mimics phosphorylation, activity is restored to the wild-type level for mutant Ycf1-S251E
S908A
-
replacement of Ser908 by alanine
S908A/T911A
-
the mutant shows a 50% diminished expression of Ycf1p compared to the wild-type enzyme
S908D
-
replacement of Ser908 by aspartate
S908E
-
replacement of Ser908 by glutamate
S908T
-
replacement of Ser908 by threonine
Y855L
-
mutants more sensitive to Cd2+ than wild type strain, higher activity for glutathione S-conjugated leukotriene C4
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
agriculture
-
improvement of heavy metal, salt or xenobiotic chemical tolerance in plants
environmental protection
-
overexpression of this fungal transporter in plants can be useful for phytoremediation of lead and cadmium polluted soils