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Information on EC 7.2.2.12 - P-type Zn2+ transporter and Organism(s) Arabidopsis thaliana and UniProt Accession Q9SZW4
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7.2.2.12 P-type Zn2+ transporterIUBMB Comments
A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. The enzyme, present in prokaryotes and photosynthetic eukaryotes, exports Zn2+ and the related cations Cd2+ and Pb2+.
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Word Map
- 7.2.2.12
- autoantibody
-
islet
- pancreatic
- metallothioneins
- synaptic
-
slc30a8
- children
- vesicular
- mellitus
- autoantigens
- shoot
-
micronutrient
- iaa
-
enteropathica
-
insulinoma-associated
-
zinc-dependent
- beta-cell
-
antigen-2
- c-peptide
-
mossy
- acrodermatitis
- atpases
-
zinc-induced
-
zinc-deficient
-
metal-responsive
- insulinoma
-
autoantibody-positive
-
diabetes-associated
- znuabc
-
hyperaccumulator
-
biofortification
- tpen
- ehlers-danlos
-
phytoremediation
-
root-to-shoot
- cu+
-
dyshomeostasis
-
radiobinding
-
ketoacidosis
-
autometallography
-
islet-specific
-
histidine-rich
The taxonomic range for the selected organisms is: Arabidopsis thaliana
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
zinc transporter, athma4, p1b-type atpase, p1b-atpase, tchma4, zinc transporter 2, npunr4017, heavy metal atpase 2, atpase znta, zn(2+)-atpase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
HMA4
Zn(II)-translocating P-type ATPase
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-
-
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Zn,Cd-transporting P-type ATPase
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-
-
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additional information
additional information
-
HMA1 is a member of the heavy metal-transporting ATPase family
additional information
-
the enzyme is a member of the P1B subfamily of the ATPases
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + H2O + Zn2+[side 1] = ADP + phosphate + Zn2+[side 2]
HMA2 and HMA4 play essential roles in the homeostasis of Zn.
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
transmembrane transport
hydrolysis of phosphoric ester
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-
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transmembrane transport
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-
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SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (P-type, Zn2+-exporting)
A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. The enzyme, present in prokaryotes and photosynthetic eukaryotes, exports Zn2+ and the related cations Cd2+ and Pb2+.
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+/out
97% of the activity with Zn2+
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-
?
ATP + H2O + Co2+/in
ADP + phosphate + Co2+/out
45% of the activity with Zn2+
-
-
?
ATP + H2O + Cu2+/in
ADP + phosphate + Cu2+/out
about 40% of the activity with Zn2+
-
-
?
ATP + H2O + Ni2+/in
ADP + phosphate + Ni2+/out
45% of the activity with Zn2+
-
-
?
ATP + H2O + Pb2+/in
ADP + phosphate + Pb2+/out
about 50% of the activity with Zn2+
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-
?
ATP + H2O + Zn2+/in
ADP + phosphate + Zn2+/out
HMA2 is responsible for Zn2+ efflux from the cells and is required for maintaining low cytoplasmic Zn2+ levels and normal Zn2+ homeostasis
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-
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
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AtHMA4 functions as an efflux pump conferring both Cd and Zn resistance
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-
?
ATP + H2O + Zn2+/in
ADP + phosphate + Zn2+/out
-
AtHMA4 functions as an efflux pump conferring both Cd and Zn resistance
-
-
?
ATP + H2O + Zn2+/in
ADP + phosphate + Zn2+/out
-
overexpression of AtHMA4 improves the root growth in the presence of toxic concentrations of Zn,Cd and Co. A null mutant exhibits a lower translocation of Zn and Cd from the roots to shoot. The AtHMA4 overexpressing lines display an increase in the zinc and cadmium shoot content. AtHMA4 plays a role in metal loading in the xylem
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-
?
ATP + H2O + Zn2+/in
ADP + phosphate + Zn2+/out
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AtHMA1 contributes to the detoxification of excess Zn(II) in Arabidopsis thaliana by reducing the Zn content of Arabidopsis thaliana plastids, regulation, overview
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-
?
ATP + H2O + Zn2+/in
ADP + phosphate + Zn2+/out
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the N-terminal domain of HMA2 is essential for function in planta while the C-terminal domain, although not essential for function, may contain a signal important for the subcellular localization of the protein
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-
?
ATP + H2O + Zn2+/in
ADP + phosphate + Zn2+/out
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HMA2 has N- and C-terminal domains that can bind Zn ions with high affinity
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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 + Zn2+/in
ADP + phosphate + Zn2+/out
HMA2 is responsible for Zn2+ efflux from the cells and is required for maintaining low cytoplasmic Zn2+ levels and normal Zn2+ homeostasis
-
-
?
ATP + H2O + Cd2+/in
ADP + phosphate + Cd2+/out
-
AtHMA4 functions as an efflux pump conferring both Cd and Zn resistance
-
-
?
ATP + H2O + Zn2+/in
ADP + phosphate + Zn2+/out
-
AtHMA4 functions as an efflux pump conferring both Cd and Zn resistance
-
-
?
ATP + H2O + Zn2+/in
ADP + phosphate + Zn2+/out
-
overexpression of AtHMA4 improves the root growth in the presence of toxic concentrations of Zn,Cd and Co. A null mutant exhibits a lower translocation of Zn and Cd from the roots to shoot. The AtHMA4 overexpressing lines display an increase in the zinc and cadmium shoot content. AtHMA4 plays a role in metal loading in the xylem
-
-
?
ATP + H2O + Zn2+/in
ADP + phosphate + Zn2+/out
-
AtHMA1 contributes to the detoxification of excess Zn(II) in Arabidopsis thaliana by reducing the Zn content of Arabidopsis thaliana plastids, regulation, overview
-
-
?
ATP + H2O + Zn2+/in
ADP + phosphate + Zn2+/out
-
the N-terminal domain of HMA2 is essential for function in planta while the C-terminal domain, although not essential for function, may contain a signal important for the subcellular localization of the protein
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
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expression pattern of HMA1 invarious tissues of wild-type plants, HMA1 is expressed preferentially in shoots, including rosette leaves, cauline leaves, ?owers and stems, but little expression is observed in the roots, overview
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AtHMA4 is expressed in tissues surrounding the root vascular vessels
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
the enzyme is involved in Zn2+ and Cd2+ transport. Expression of HMA4 in tobacco (Nicotiana tabacum var. Xanthi) enhances Zn2+ translocation to the shoots only at 0.01 mM but not at 0.0005, 0.1 and 0.2 mM Zn2+. HMA4-expressing plants also show a decrease in cadmium uptake when exposed to 0.00025 and 0.005 mM Cd2+
physiological function
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the enzyme is responsible for zinc and cadmium translocation from roots to shoots in Arabidopsis thaliana
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). HMA2_ARATH
951
6
101990
Swiss-Prot
Secretory Pathway (Reliability: 4)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
HMA1 contains poly-His motifs that are commonly found in Zn(II)-binding proteins, but lacks some amino acids that are typical for this class of transporters
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D149A
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the mutant shows about 135% of wild type Zn2+-transporting activity
D313A
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the mutant shows about 130% of wild type Zn2+-transporting activity
D688A
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the mutant shows about 20% of wild type Zn2+-transporting activity
DELTAN-HMA2
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mutant, lacking the N-terminal first 75 amino acids, 56% decrease in Vmax
DELTANC-HMA2
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mutant, lacking the N-terminal first 75 amino acids and the 244 C-terminal amino acids
E169A
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the mutant shows about 25% of wild type Zn2+-transporting activity
F177A
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the mutant shows about 95% of wild type Zn2+-transporting activity
F177L
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the mutant shows about 40% of wild type Zn2+-transporting activity and reduced Cd2+-transporting activity (about 20%) compared to the wild type enzyme
G360A
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the mutant shows about 75% of wild type Zn2+-transporting activity
K138A
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the mutant shows about 110% of wild type Zn2+-transporting activity
K667A
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the mutant shows about 30% of wild type Zn2+-transporting activity
N151A
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the mutant shows about 70% of wild type Zn2+-transporting activity
P366L
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the mutant shows about 15% of wild type Zn2+-transporting activity
V154A
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the mutant shows about 60% of wild type Zn2+-transporting activity
V154S
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the mutant shows about 60% of wild type Zn2+-transporting activity
additional information
additional information
-
AtHMA4 and a truncated form lacking the last 457 amino acids both confer Cd and Zn resistance to yeast
additional information
-
expression of mutant derivatives, with and without a C-terminal GFP tag, from the HMA2 promoter in transgenic hma2,hma4, Zn-deficient plants. The deletion mutant lacking the C-terminal 244 amino acids rescues most of the hma2,hma4 Zn-deficiency phenotypes with the exception of embryo or seed development. Root-to-shoot Cd translocation is fully rescued. The GFP-tagged derivative is partially mislocalized in the root pericycle cells in which it is expressed. Deletion derivatives lacking the C-terminal 121 and 21 amino acids rescue all phenotypes and localize normally. N-terminal domain mutants localize normally but fail to complement the hma2,hma4 phenotypes, overview
additional information
-
sensitivity of Saccharomyces cerevisiae to high concentrations of Zn2+ is altered by the expression of AtHMA1 lacking its N-terminal chloroplast-targeting signal. Construction of HMA knockout plants showing as more pronounced sensitivity in the presence of high Zn2+ concentrations, and increased accumulation of Zn in the chloroplast of T-DNA insertional mutants of AtHMA1 compared to the wild-type, overview. The Zn2+-sensitive phenotype of AtHMA1 knock-out plants is complemented by the expression of AtHMA1 under the control of its own promoter. No organ-specific differences in the Zn content of hma1-1 mutants
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80°C, 100 mM Tris-HCl, pH 8.0, 150 mM NaCl, 1 mM Tris(2-carboxyethyl)phosphine hydrochoride
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
membranes from yeast are prepared, purification of the HMA2 C-terminal metal binding domain is performed using a Strep-Tactin Superflow column
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purification of the HMA2 N-terminal metal binding domain is performed using Strep-tag affinity chromatography, membranes from HMA2 expressing yeasts are prepared
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
Arabidopsis thaliana HMA2 and truncated forms of the protein are prepared using the bacterial expression vector pPRIBA1 and the yeast expression vector pYES2/CT
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expression of wild-type HMA2 and mutant derivatives in transgenic hma2,hma4, Zn-deficient plants from the HMA2 promoter, quantitative realtime PCR expression analysis
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HMA1 DNA and amino acid sequence determination and analysis, phylogenetic analysis, quantitative realtime RT-PCR expression analysis, expression in Saccharomyces cerevisiae
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identification of two independent mutant alleles for both genes, HMA2 and HMA4. The hma2-2 mutant is indistinguishable from the wild-type, whereas the hma4-1 and the double mutant hma2-2,hma4-1 accumulate approximately 2fold and 4fold less Zn, respectively, than the wild type.
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the yeast expression vector pYES2/CT carrying Arabidopsis thaliana HMA2 containing a C-terminal Strep-tag is prepared, the HMA2 N-terminal metal binding domain is cloned into the pPRIBA1 vector for expression in Escherichia coli BL21DE3pLysS cells
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hussain, D.; Haydon, M.J.; Wang, Y.; Wong, E.; Sherson, S.M.; Young, J.; Camakaris, J.; Harper, J.F.; Cobbett, C.S.
P-type ATPase heavy metal transporters with roles in essential zinc homeostasis in Arabidopsis
Plant Cell
16
1327-1339
2004
Arabidopsis thaliana
Verret, F.; Gravot, A.; Auroy, P.; Leonhardt, N.; David, P.; Nussaume, L.; Vavasseur, A.; Richaud, P.
Overexpression of AtHMA4 enhances root-to-shoot translocation of zinc and cadmium and plant metal tolerance
FEBS Lett.
576
306-312
2004
Arabidopsis thaliana
Mills, R.F.; Francini, A.; Ferreira da Rocha, P.S.; Baccarini, P.J.; Aylett, M.; Krijger, G.C.; Williams, L.E.
The plant P1B-type ATPase AtHMA4 transports Zn and Cd and plays a role in detoxification of transition metals supplied at elevated levels
FEBS Lett.
579
783-791
2005
Arabidopsis thaliana
Eren, E.; Argueello, J.M.
Arabidopsis HMA2, a divalent heavy metal-transporting PIB-type ATPase, is involved in cytoplasmic Zn2+ homeostasis
Plant Physiol.
136
3712-3723
2004
Arabidopsis thaliana (Q9SZW4)
Eren, E.; Gonzalez-Guerrero, M.; Kaufman, B.M.; Argueello, J.M.
Novel Zn2+ coordination by the regulatory N-terminus metal binding domain of Arabidopsis thaliana Zn(2+)-ATPase HMA2
Biochemistry
46
7754-7764
2007
Arabidopsis thaliana
Eren, E.; Kennedy, D.C.; Maroney, M.J.; Argueello, J.M.
A novel regulatory metal binding domain is present in the C terminus of Arabidopsis Zn2+-ATPase HMA2
J. Biol. Chem.
281
33881-33891
2006
Arabidopsis thaliana
Wong, C.K.; Cobbett, C.S.
HMA P-type ATPases are the major mechanism for root-to-shoot Cd translocation in Arabidopsis thaliana
New Phytol.
181
71-78
2009
Arabidopsis thaliana
Kim, Y.Y.; Choi, H.; Segami, S.; Cho, H.T.; Martinoia, E.; Maeshima, M.; Lee, Y.
AtHMA1 contributes to the detoxification of excess Zn(II) in Arabidopsis
Plant J.
58
737-753
2009
Arabidopsis thaliana
Siemianowski, O.; Mills, R.F.; Williams, L.E.; Antosiewicz, D.M.
Expression of the P1B-type ATPase AtHMA4 in tobacco modifies Zn and Cd root to shoot partitioning and metal tolerance
Plant Biotechnol. J.
9
64-74
2011
Arabidopsis thaliana (P12265)
Lekeux, G.; Crowet, J.M.; Nouet, C.; Joris, M.; Jadoul, A.; Bosman, B.; Carnol, M.; Motte, P.; Lins, L.; Galleni, M.; Hanikenne, M.
Homology modeling and in vivo functional characterization of the zinc permeation pathway in a heavy metal P-type ATPase
J. Exp. Bot.
70
329-341
2019
Arabidopsis thaliana
EXTERNAL LINKS (specific for EC-Number 7.2.2.12)
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.3.6.2, 3.A.3.6.10
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