HMA4 heavy metal atpase 4 [Arabidopsis thaliana (thale cress)] - Gene

Summary

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Official Symbol: HMA4
Official Full Name: heavy metal atpase 4
Primary source: TAIR:AT2G19110
Locus tag: AT2G19110
See related: Araport:AT2G19110
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Arabidopsis thaliana (ecotype: Columbia)
Lineage: Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta; Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae; rosids; malvids; Brassicales; Brassicaceae; Camelineae; Arabidopsis
Also known as: ARABIDOPSIS HEAVY METAL ATPASE 4; ATHMA4; heavy metal atpase 4; T20K24.12; T20K24_12
Summary: Encodes a protein with similarity to Zn ATPase. Can rescue Zn deficiency in yeast and Cd resistance, suggesting a role in Zn and Cd transport.
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Genomic context

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See HMA4 in Genome Data Viewer

Location:: chromosome: 2

Exon count:: 10

Sequence:: Chromosome: 2; NC_003071.7 (8278789..8286561)

Chromosome 2 - NC_003071.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_003071.7

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Arabidopsis thaliana Zn2+-efflux ATPases HMA2 and HMA4 are required for resistance to the necrotrophic fungus Plectosphaerella cucumerina BMM.
Title: Arabidopsis thaliana Zn2+-efflux ATPases HMA2 and HMA4 are required for resistance to the necrotrophic fungus Plectosphaerella cucumerina BMM.
Homology modeling of the HMA4 transmembrane region based on the crystal structure of a ZntA bacterial homolog highlighted amino acids forming a metal permeation pathway. Although the zinc pathway displayed overall conservation among the two proteins, significant differences were observed, especially in the entrance area with altered electronegativity and the presence of a ionic interaction/hydrogen bond network.
Title: Homology modeling and in vivo functional characterization of the zinc permeation pathway in a heavy metal P-type ATPase.
di-Cys motifs, but not the His-stretch, contribute to high affinity zinc binding and function in planta. We suggest that the HMA4 C-terminal extension is at least partly responsible for protein targeting to the plasma membrane.
Title: di-Cysteine motifs in the C-terminus of plant HMA4 proteins confer nanomolar affinity for zinc and are essential for HMA4 function in vivo.
To test whether developing Arabidopsis seeds depend on AtHMA2 and AtHMA4 for proper zinc unloading from the seed coat, the authors analysed the amount of zinc present in the maternal and filial parts of the seed, respectively, in wild-type and mutant seeds lacking functional AtHMA2, AtHMA4, or both.
Title: Mother-plant-mediated pumping of zinc into the developing seed.
overexpression modulates the ratio of Zn to Cd supply as a determinant of metal-homeostasis gene expression in tobacco
Title: The ratio of Zn to Cd supply as a determinant of metal-homeostasis gene expression in tobacco and its modulation by overexpressing the metal exporter AtHMA4.
These studies evaluated the the function and structure of the N-terminal cytoplasmic metal-binding domain of HMA4.
Title: Metal binding to the N-terminal cytoplasmic domain of the PIB ATPase HMA4 is required for metal transport in Arabidopsis.
Due to ectopic expression of 35S::AtHMA4, the physical apoplastic barrier within the external cell layer developed, which is likely to be responsible for the reduction of Cd uptake/accumulation.
Title: HMA4 expression in tobacco reduces Cd accumulation due to the induction of the apoplastic barrier.
Ectopically expressing AtHMA4 in tobacco results in overloading the root and leaf apoplast with zinc.
Title: Development of Zn-related necrosis in tobacco is enhanced by expressing AtHMA4 and depends on the apoplastic Zn levels.
the C-terminal domain of AtHMA4 serves a dual role as Zn(2+) and Cd(2+) chelator (sensor) and as a regulator of the efficiency of Zn(2+) and Cd(2+) export.
Title: A combined zinc/cadmium sensor and zinc/cadmium export regulator in a heavy metal pump.
The binding affinities of HMA2 and HMA4 for zinc are higher than that of HMA7 by a factor of 20-30, but the relative affinities for copper are inverted by a factor of 30-50.
Title: Metal binding affinities of Arabidopsis zinc and copper transporters: selectivities match the relative, but not the absolute, affinities of their amino-terminal domains.

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Pathways from PubChem

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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NM_001335621.1

Supported by ESTs:

Gene Ontology Provided by TAIR

Function	Evidence Code	Pubs
enables ABC-type cadmium transporter activity	ISS Inferred from Sequence or Structural Similarity more info
enables ATP hydrolysis activity	IEA Inferred from Electronic Annotation more info
enables P-type cadmium transporter activity	IEA Inferred from Electronic Annotation more info
enables P-type zinc transporter activity	IEA Inferred from Electronic Annotation more info
enables cadmium ion transmembrane transporter activity	IGI Inferred from Genetic Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables zinc ion transmembrane transporter activity	IGI Inferred from Genetic Interaction more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within cadmium ion transport	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within intracellular zinc ion homeostasis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within metal ion transport	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to cadmium ion	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to cobalt ion	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to metal ion	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to zinc ion	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within zinc ion transport	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in plasma membrane	ISM Inferred from Sequence Model more info
located_in plasma membrane	TAS Traceable Author Statement more info	PubMed
located_in plasmodesma	HDA more info	PubMed

General protein information

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Preferred Names: heavy metal atpase 4

NP_001318247.1

heavy metal atpase 4 (HMA4); FUNCTIONS IN: zinc ion transmembrane transporter activity, protein binding, cadmium ion transmembrane transporter activity, cadmium-transporting ATPase activity; INVOLVED IN: in 8 processes; LOCATED IN: plasma membrane; EXPRESSED IN: 30 plant structures; EXPRESSED DURING: 7 growth stages; CONTAINS InterPro DOMAIN/s: ATPase, P-type copper-transporter (InterPro:IPR001756), Heavy metal transport/detoxification protein (InterPro:IPR006121), ATPase, P-type, ATPase-associated domain (InterPro:IPR008250), ATPase, P-type, heavy metal-(Cd/Co/Hg/Pb/Zn)-translocating (InterPro:IPR006404), Haloacid dehalogenase-like hydrolase (InterPro:IPR005834), ATPase, P-type, K/Mg/Cd/Cu/Zn/Na/Ca/Na/H-transporter (InterPro:IPR001757), ATPase, P-type, heavy metal translocating (InterPro:IPR006416), ATPase, P-type phosphorylation site (InterPro:IPR018303); BEST Arabidopsis thaliana protein match is: heavy metal atpase 2 (TAIR:AT4G30110.1); Has 40067 Blast hits to 31648 proteins in 3107 species: Archae - 784; Bacteria - 26302; Metazoa - 4194; Fungi - 2461; Plants - 1970; Viruses - 7; Other Eukaryotes - 4349 (source: NCBI BLink).

NCBI Reference Sequences (RefSeq)

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Genome Annotation

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference assembly

Genomic

NC_003071.7 Reference assembly

Range

8278789..8286561

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001335622.1 → NP_001324425.1 heavy metal atpase 4 [Arabidopsis thaliana]

Status: REVIEWED

UniProtKB/Swiss-Prot

O64474

UniProtKB/TrEMBL

A0A178VWP5, A0A384L331, A0A5S9WZ72, Q0WUP4

Conserved Domains (2) summary

COG2608
Location:16 → 85

CopZ; Copper chaperone CopZ [Inorganic ion transport and metabolism]

cd02079
Location:100 → 701

P-type_ATPase_HM; P-type heavy metal-transporting ATPase
NM_127468.5 → NP_179501.1 heavy metal atpase 4 [Arabidopsis thaliana]

See identical proteins and their annotated locations for NP_179501.1

Status: REVIEWED

UniProtKB/Swiss-Prot

O64474

UniProtKB/TrEMBL

A0A178VWP5, A0A384L331, A0A5S9WZ72, Q0WUP4

Conserved Domains (2) summary

COG2608
Location:16 → 85

CopZ; Copper chaperone CopZ [Inorganic ion transport and metabolism]

cd02079
Location:100 → 701

P-type_ATPase_HM; P-type heavy metal-transporting ATPase
NM_001335621.1 → NP_001318247.1 heavy metal atpase 4 [Arabidopsis thaliana]

Status: REVIEWED

UniProtKB/Swiss-Prot

O64474

UniProtKB/TrEMBL

A0A178VWP5, A0A384L331, A0A5S9WZ72, Q0WUP4

Conserved Domains (2) summary

COG2608
Location:16 → 85

CopZ; Copper chaperone CopZ [Inorganic ion transport and metabolism]

cd02079
Location:100 → 701

P-type_ATPase_HM; P-type heavy metal-transporting ATPase