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

    Gene ID: 816428, updated on 18-Sep-2024

    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_003071.7Genomic Context describing neighboring genes Neighboring gene pseudo Neighboring gene ncRNA Neighboring gene P-loop containing nucleoside triphosphate hydrolases superfamily protein Neighboring gene S-locus lectin protein kinase family protein

    Genomic regions, transcripts, and products

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    Genomic Sequence:
    NC_003071.7

    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. Homology modeling and in vivo functional characterization of the zinc permeation pathway in a heavy metal P-type ATPase. Lekeux G, et al. J Exp Bot, 2019 Jan 1. PMID 30418580, Free PMC Article
    2. Overexpression of AtHMA4 enhances root-to-shoot translocation of zinc and cadmium and plant metal tolerance. Verret F, et al. FEBS Lett, 2004 Oct 22. PMID 15498553
    3. The plant P1B-type ATPase AtHMA4 transports Zn and Cd and plays a role in detoxification of transition metals supplied at elevated levels. Mills RF, et al. FEBS Lett, 2005 Jan 31. PMID 15670847
    4. Heavy metal transport by AtHMA4 involves the N-terminal degenerated metal binding domain and the C-terminal His11 stretch. Verret F, et al. FEBS Lett, 2005 Feb 28. PMID 15733866
    5. A major quantitative trait locus for cadmium tolerance in Arabidopsis halleri colocalizes with HMA4, a gene encoding a heavy metal ATPase. Courbot M, et al. Plant Physiol, 2007 Jun. PMID 17434989, Free PMC Article

    See all (19) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (13)

    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

    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 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

    1. NC_003071.7 Reference assembly

      Range
      8278789..8286561
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. 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

    2. 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

    3. 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
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O64474.2

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