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Information on EC 7.2.2.2 - ABC-type Cd2+ transporter
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7.2.2.2 ABC-type Cd2+ transporterIUBMB Comments
An ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. Does not undergo phosphorylation during the transport process. A yeast enzyme that exports some heavy metals, especially Cd2+, from the cytosol into the vacuole.
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Word Map
- 7.2.2.2
- vacuolar
-
oshma2
-
osnramp5
-
glutathione-conjugate
-
root-to-shoot
-
tonoplast-localized
-
osirt1
- agriculture
- environmental protection
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
ycf1p, oshma3, yor1p, hmt-1, yeast cadmium factor, yeast cadmium factor 1, cadmium-transporting atpase, hmt1 protein, heavy metal tolerance factor 1, heavy metal-associated atpase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ATP phosphohydrolase (heavy-metal-exporting)
-
-
-
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cadmium-transporting ATPase
cadmium-transporting P1B-type ATPase
EC 3.6.3.46
-
-
formerly
-
heavy metal tolerance factor 1
HMT-1
PCA1
Ycf1
Ycf1p
yeast cadmium factor
-
-
-
-
yeast cadmium factor 1
additional information
cadmium-transporting ATPase
-
-
-
-
additional information
Q0WLU3
the enzyme is a member of the Abc1-like family
additional information
-
the enzyme belongs to the ABCC subfamily of ABC transporters
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + H2O + Cd2+[side 1] = ADP + phosphate + Cd2+[side 2]
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.
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-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
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-
-
-
transmembrane transport
transmembrane transport
-
-
-
-
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SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (ABC-type, heavy-metal-exporting)
An ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. Does not undergo phosphorylation during the transport process. A yeast enzyme that exports some heavy metals, especially Cd2+, from the cytosol into the vacuole.
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CAS REGISTRY NUMBER
COMMENTARY
9000-83-3
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/in
-
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 + Co2+[side 1]
ADP + phosphate + Co2+[side 2]
-
-
-
?
ATP + H2O + estradiol-beta-17-glucuronide [side 1]
ADP + phosphate + estradiol-beta-17-glucuronide [side 2]
-
-
-
-
?
ATP + H2O + leukotriene C4 [side 1]
ADP + phosphate + leukotriene C4 [side 2]
-
-
-
-
?
ATP + H2O + Zn2+[side 1]
ADP + phosphate + Zn2+[side 2]
lowest activity
-
-
?
bilirubin/cytoplasm + ATP + H2O
bilirubin/vacuole + ADP + phosphate
-
unconjugated substrate
-
-
?
Cd x glutathione S2/cytoplasm + ATP + H2O
Cd x glutathione S2/vacuole + phosphate
-
-
-
-
?
diazaborine/cytoplasm + ATP + H2O
diazaborine/vacuole + ADP + phosphate
-
-
-
-
?
glutathione S-conjugated leukotriene C4/cytoplasm + ATP + H2O
glutathione S-conjugated leukotriene C4/vacuole + ADP + phosphate
-
-
-
-
?
glutathione S-conjugates/cytoplasm + ATP + H2O
glutathione S-conjugates/vacuole + ADP + phosphate
-
-
-
-
?
glutathione/cytoplasm + ATP + H2O
glutathione/vacuole + ADP + phosphate
-
-
-
-
?
S-(2,4-dinitrophenyl)glutathione/cytoplasm + ATP + H2O
S-(2,4-dinitrophenyl)glutathione/vacuole + ADP + phosphate
-
-
-
-
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
Q0WLU3
chloroplast envelope membrane protein OSA1, a member of the Abc1-like family, acts as a factor in cadmium and oxidative stress response, playing a role in the balance of oxidative stress
-
-
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
ABC transporter, DmHMT-1, confers tolerance to cadmium. DmHMT-1 and its yeast homolog, SpHMT-1, are not essential for vacuolar phytochelatin sequestration
-
-
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
-
-
-
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
transports glutathione-S-conjugates, like Cd-GS2, from the cytosol into the vacuole
-
-
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
Cd2+ is a toxic environmental contaminant for biological systems, which can form complexes with reduced glutathione, and thus alter the intracellular redox state. In Saccharomyces cerevisiae, bis(glutathionato)cadmium, Cd-[GS]2, complexes can be removed from the cytosol and transported into the vacuole by a glutathione-conjugated pump, Ycf1p, which plays a role in Cd2+ detoxi?cation during respiratory metabolism and is correlated with the glutathione homeostasis, overview
-
-
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
the yeast ABC transporter belongs to the ABCC subfamily of ATP-binding cassette, ABC, transporters that rid cells of toxic endogenous and xenobiotic compounds, negative regulation of Ycf1p by phosphorylation within its N-terminal extension in addition to its ABC core domain and transports substrates in the form of glutathione conjugates
-
-
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
Pca1 is a cadmium transporter, the N-terminal metal-responding degradation signal encompassing amino acids 250-350 functions autonomously in a metal-responsive manner, overview
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-
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
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Ycf1p-dependent transport of [3H]estradiol-beta-17-glucuronide in vitro
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-
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
Pca1 is a cadmium transporter, the N-terminal metal-responding degradation signal encompassing amino acids 250-350 functions autonomously in a metal-responsive manner, overview
-
-
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
Cd2+ is a toxic environmental contaminant for biological systems, which can form complexes with reduced glutathione, and thus alter the intracellular redox state. In Saccharomyces cerevisiae, bis(glutathionato)cadmium, Cd-[GS]2, complexes can be removed from the cytosol and transported into the vacuole by a glutathione-conjugated pump, Ycf1p, which plays a role in Cd2+ detoxi?cation during respiratory metabolism and is correlated with the glutathione homeostasis, overview
-
-
?
ATP + H2O + Cd2+[side 1]
ADP + phosphate + Cd2+[side 2]
highest activity
-
-
?
Cd/cytoplasm + ATP + H2O
Cd/vacuole + ADP + phosphate
-
-
-
-
?
additional information
?
-
Q0WLU3
in the absence of Cd21, an increase in the expression of AtOSA1 is correlated with plant aging. The transcript level of AtOSA1, which is age dependent, is also down-regulated in the night, circadian rhythm dependencies, and senescent leaves
-
-
?
additional information
?
-
-
Pca1, a P1B-type ATPase, plays a critical role in cadmium resistance in Saccharomyces cerevisiae by extruding intracellular cadmium as a cadmium-specific efflux pump, regulation requires cysteine residues within the cytosolic domain. Mechanistic insights into the cadmium-dependent control of Pca1 expression, pathway for Pca1 turnover and the mechanism of cadmium sensing that leads to up-regulation of Pca1, overview. Pca1 degradation is dependent on the proteasome but not vacuolar proteases
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-
?
additional information
?
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enzyme Ycf1p regulates phosphatidylinositol 3-phosphate accumulation at vertex microdomains
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-
?
additional information
?
-
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enzyme Ycf1p regulates phosphatidylinositol 3-phosphate accumulation at vertex microdomains
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-
?
additional information
?
-
-
Pca1, a P1B-type ATPase, plays a critical role in cadmium resistance in Saccharomyces cerevisiae by extruding intracellular cadmium as a cadmium-specific efflux pump, regulation requires cysteine residues within the cytosolic domain. Mechanistic insights into the cadmium-dependent control of Pca1 expression, pathway for Pca1 turnover and the mechanism of cadmium sensing that leads to up-regulation of Pca1, overview. Pca1 degradation is dependent on the proteasome but not vacuolar proteases
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/in
-
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 + Co2+[side 1]
ADP + phosphate + Co2+[side 2]
-
-
-
?
ATP + H2O + Zn2+[side 1]
ADP + phosphate + Zn2+[side 2]
lowest activity
-
-
?
bilirubin/cytoplasm + ATP + H2O
bilirubin/vacuole + ADP + phosphate
-
unconjugated substrate
-
-
?
Cd x glutathione S2/cytoplasm + ATP + H2O
Cd x glutathione S2/vacuole + phosphate
-
-
-
-
?
diazaborine/cytoplasm + ATP + H2O
diazaborine/vacuole + ADP + phosphate
-
-
-
-
?
glutathione S-conjugated leukotriene C4/cytoplasm + ATP + H2O
glutathione S-conjugated leukotriene C4/vacuole + ADP + phosphate
-
-
-
-
?
glutathione S-conjugates/cytoplasm + ATP + H2O
glutathione S-conjugates/vacuole + ADP + phosphate
-
-
-
-
?
glutathione/cytoplasm + ATP + H2O
glutathione/vacuole + ADP + phosphate
-
-
-
-
?
S-(2,4-dinitrophenyl)glutathione/cytoplasm + ATP + H2O
S-(2,4-dinitrophenyl)glutathione/vacuole + ADP + phosphate
-
-
-
-
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
Q0WLU3
chloroplast envelope membrane protein OSA1, a member of the Abc1-like family, acts as a factor in cadmium and oxidative stress response, playing a role in the balance of oxidative stress
-
-
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
ABC transporter, DmHMT-1, confers tolerance to cadmium. DmHMT-1 and its yeast homolog, SpHMT-1, are not essential for vacuolar phytochelatin sequestration
-
-
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
transports glutathione-S-conjugates, like Cd-GS2, from the cytosol into the vacuole
-
-
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
Cd2+ is a toxic environmental contaminant for biological systems, which can form complexes with reduced glutathione, and thus alter the intracellular redox state. In Saccharomyces cerevisiae, bis(glutathionato)cadmium, Cd-[GS]2, complexes can be removed from the cytosol and transported into the vacuole by a glutathione-conjugated pump, Ycf1p, which plays a role in Cd2+ detoxi?cation during respiratory metabolism and is correlated with the glutathione homeostasis, overview
-
-
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
the yeast ABC transporter belongs to the ABCC subfamily of ATP-binding cassette, ABC, transporters that rid cells of toxic endogenous and xenobiotic compounds, negative regulation of Ycf1p by phosphorylation within its N-terminal extension in addition to its ABC core domain and transports substrates in the form of glutathione conjugates
-
-
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
Cd2+ is a toxic environmental contaminant for biological systems, which can form complexes with reduced glutathione, and thus alter the intracellular redox state. In Saccharomyces cerevisiae, bis(glutathionato)cadmium, Cd-[GS]2, complexes can be removed from the cytosol and transported into the vacuole by a glutathione-conjugated pump, Ycf1p, which plays a role in Cd2+ detoxi?cation during respiratory metabolism and is correlated with the glutathione homeostasis, overview
-
-
?
ATP + H2O + Cd2+[side 1]
ADP + phosphate + Cd2+[side 2]
highest activity
-
-
?
Cd/cytoplasm + ATP + H2O
Cd/vacuole + ADP + phosphate
-
-
-
-
?
additional information
?
-
Q0WLU3
in the absence of Cd21, an increase in the expression of AtOSA1 is correlated with plant aging. The transcript level of AtOSA1, which is age dependent, is also down-regulated in the night, circadian rhythm dependencies, and senescent leaves
-
-
?
additional information
?
-
-
Pca1, a P1B-type ATPase, plays a critical role in cadmium resistance in Saccharomyces cerevisiae by extruding intracellular cadmium as a cadmium-specific efflux pump, regulation requires cysteine residues within the cytosolic domain. Mechanistic insights into the cadmium-dependent control of Pca1 expression, pathway for Pca1 turnover and the mechanism of cadmium sensing that leads to up-regulation of Pca1, overview. Pca1 degradation is dependent on the proteasome but not vacuolar proteases
-
-
?
additional information
?
-
enzyme Ycf1p regulates phosphatidylinositol 3-phosphate accumulation at vertex microdomains
-
-
?
additional information
?
-
-
enzyme Ycf1p regulates phosphatidylinositol 3-phosphate accumulation at vertex microdomains
-
-
?
additional information
?
-
-
Pca1, a P1B-type ATPase, plays a critical role in cadmium resistance in Saccharomyces cerevisiae by extruding intracellular cadmium as a cadmium-specific efflux pump, regulation requires cysteine residues within the cytosolic domain. Mechanistic insights into the cadmium-dependent control of Pca1 expression, pathway for Pca1 turnover and the mechanism of cadmium sensing that leads to up-regulation of Pca1, overview. Pca1 degradation is dependent on the proteasome but not vacuolar proteases
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4',4'-diisothiocyanatostilbene-2',2'-disulfonic acid
-
uptake of S-(2,4-dinitrophenyl)glutathione inhibited
sulfinpyrazone
-
uptake of S-(2,4-dinitrophenyl)glutathione inhibited
additional information
-
phosphorylation of Ser251 in the Ycf1p N-terminal extension negatively regulates activity
-
additional information
-
Pca1 degradation is dependent on the proteasome but not vacuolar proteases
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Tus1p
-
a guanine nucleotide exchange factor, stimulates the enzyme
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additional information
-
in response to cadmium, yeast cells rapidly enhance expression of Pca1 by a post-transcriptional mechanism
-
additional information
-
N-acetylcysteine, a precursor of glutathione, induces the enzyme expression, restoring the expression in presence of Cd2+
-
additional information
-
the enzyme is activated by phosphorylation in its ABC core domain at residues Ser908 and Thr911
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Cystic Fibrosis
A yeast metal resistance protein similar to human cystic fibrosis transmembrane conductance regulator (CFTR) and multidrug resistance-associated protein.
Cystic Fibrosis
Domain interactions in the yeast ATP binding cassette transporter Ycf1p: intragenic suppressor analysis of mutations in the nucleotide binding domains.
Cystic Fibrosis
Expression of an ATP-binding cassette transporter-encoding gene (YOR1) is required for oligomycin resistance in Saccharomyces cerevisiae.
Cystic Fibrosis
Inhibiting endoplasmic reticulum (ER)-associated degradation of misfolded Yor1p does not permit ER export despite the presence of a diacidic sorting signal.
Cystic Fibrosis
Mutational analysis of the Saccharomyces cerevisiae ATP-binding cassette transporter protein Ycf1p.
Cystic Fibrosis
Structure and expression of the messenger RNA encoding the murine multidrug resistance protein, an ATP-binding cassette transporter.
Cystic Fibrosis
Substitution of Yor1p NBD1 residues improves the thermal stability of Human Cystic Fibrosis Transmembrane Conductance Regulator.
Hypersensitivity
Drosophila ABC transporter, DmHMT-1, confers tolerance to cadmium. DmHMT-1 and its yeast homolog, SpHMT-1, are not essential for vacuolar phytochelatin sequestration.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
measurement of growth inhibition by cadmium in wild-type and mutant strains, overview
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
formerly named Alcaligenes eutrophus and Ralstonia metallidurans
UniProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
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
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
the N terminus of Pca1 contains a targeting signal for ERAD. Degradation of Pca1 and cadmium sensing occur at the endoplasmic reticulum
brenda
-
in the absence of cadmium, Pca1 is targeted for degradation before reaching the plasma membrane
brenda
-
in the absence of cadmium, Pca1 is targeted for degradation before reaching the plasma membrane
-
brenda
-
detected by indirect immunofluorescence, fractionation technique
-
brenda
additional information
-
Pca1 contains a cytosolic cysteine-rich N-terminal extension of nearly 400 residues
-
brenda
additional information
-
Pca1 contains a cytosolic cysteine-rich N-terminal extension of nearly 400 residues
-
-
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
physiological function
evolution
enzyme OsHMA3 is a vacuolar cadmium transporter belonging to the P1B-ATPase family, it has a long (273aa) C-terminal region
evolution
the enzyme belongs to the ATP-binding cassette class C (ABCC) transporter family
malfunction
hmt-1 deletion alleles of Caenorhabditis elegans are hypersensitive to Cd
malfunction
deletion of YCF1 attenuates in vitro vacuole fusion by up to 40% relative to wild-type vacuoles, plasmid-expressed wild-type Ycf1p rescues the deletion phenotype. Ycf1p containing a mutation of the conserved Lys669 to Met in the Walker A box of the first nucleotide-binding domain (Ycf1pK669M) is unable to complement the fusion defect of DELTAycf1 vacuoles. Also, deleting YCF1 causes a striking decrease in vacuolar levels of the soluble SNARE Vam7p, whereas total cellular levels are not altered. The attenuated fusion of DELTAycf1 vacuoles is rescued by the addition of recombinant Vam7p to in vitro experiments, exogenous Vam7p restores Ca2+ efflux in DELTAycf1 vacuoles. Phenotypes, overview
physiological function
functional in vivo assays show that HMT-1 from Caenorhabditis elegans, functions distinctly from its Schizosaccharomyces pombe counterpart in that in addition to Cd it confers tolerance to arsenic and copper while acting independently of phytochelatin synthase
physiological function
in addition to Cd, HMT-1 confers tolerance to arsenic and copper while acting independently of phytochelatin synthase pcs-1
physiological function
the enzyme Ycf1p is a Cd2+ transporter, it regulates the transport of cadmium, mercury, and other toxins into the vacuole lumen to detoxify the cytoplasm. The ATPase activity of Ycf1p is required for its function in regulating fusion. The enzyme physically interacts with a wide array of proteins, including factors that regulate vacuole homeostasis. Role of Ycf1p and other ABCC transporters in the regulation of vacuole homotypic fusion, overview. Ycf1p contributes in the recruitment of Vam7p to the vacuole for efficient membrane fusion
physiological function
-
the enzyme sequesters cadmium to the root endoplasmic reticulum to limit translocation to the stems in soybean
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). YOR1_YEAST
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
1477
11
166728
Swiss-Prot
other Location (Reliability: 1)
YCFI_YEAST
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
1515
14
171121
Swiss-Prot
other Location