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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q6P5W5: Variant p.Gly526Arg

Zinc transporter ZIP4
Gene: SLC39A4
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Variant information Variant position: help 526 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Glycine (G) to Arginine (R) at position 526 (G526R, p.Gly526Arg). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Change from glycine (G) to large size and basic (R) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page
Variant description: help In AEZ. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 526 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 647 The length of the canonical sequence.
Location on the sequence: help VHNFADGLAVGAAFASSWKT G LATSLAVFCHELPHELGDFA The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         VHNFADGLAVGAAFASSWKTGLATSLAVFCHELPHELGDFA

Mouse                         VHNFADGLAVGAAFSSSWKTGLATSLAVFCHELPHELGDFA

Rat                           VHNFADGLAVGAAFSSTWKTGLATSLAVFCHELPHELGDFA

Bovine                        VHNFADGLAVGAAFLSSWKTGLATSLAVFCHEVPHELGDFA
Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 23 – 647 Zinc transporter ZIP4
Topological domain 519 – 526 Extracellular
Binding site 507 – 507 M1 metal binding site
Binding site 508 – 508 M2 metal binding site
Binding site 511 – 511 M1 metal binding site
Binding site 511 – 511 M2 metal binding site
Binding site 536 – 536 M1 metal binding site
Binding site 537 – 537 M2 metal binding site
Binding site 540 – 540 M1 metal binding site
Site 511 – 511 Essential role in Zn(2+) sensing
Mutagenesis 507 – 507 H -> A. Moderately reduces zinc transport activity. Completely abrogated zinc transport activity; when associated with A-536 and A-540.
Mutagenesis 507 – 507 H -> R. Abolishes zinc transport activity.
Mutagenesis 508 – 508 N -> A. Moderately Reduces zinc transport activity. Reduced zinc transmembrane transporter activity; when associated with A-537. Does not affect substrate specificity; when associated with A-537. Exhibits a zinc transport activity dependent on pH; when associated with A-537.
Mutagenesis 508 – 508 N -> R. Reduces zinc transport activity by 60%.
Mutagenesis 508 – 508 N -> S. Strong reduction of zinc transport activity; when associated with K-537.
Mutagenesis 511 – 511 D -> A. Strongly reduced zinc transport activity. Loss of zinc-sensing function; endocytosis of this mutant becomes a zinc-independent process.
Mutagenesis 536 – 536 H -> A. Moderately reduces zinc transport activity. Completely abrogates zinc transport activity; when associated with A-507 and A-540.
Mutagenesis 536 – 536 H -> R. Abolishes zinc transport activity.
Mutagenesis 537 – 537 E -> A. Moderately reduces zinc transport activity. Reduces zinc transmembrane transporter activity; when associated with A-508. Does not affect substrate specificity; when associated with A-508. Exhibits a zinc transport activity dependent on pH; when associated with A-508.
Mutagenesis 537 – 537 E -> K. Strong reduction of zinc transport activity; when associated with S-537.
Mutagenesis 537 – 537 E -> R. Abolishes zinc transport activity.
Mutagenesis 540 – 540 H -> A. Increases zinc transport activity. Reduces affinity toward zinc. No defect in endocytosis or zinc sensing. Completely abrogated zinc transport activity; when associated with A-507 and A-536.
Mutagenesis 540 – 540 H -> R. Does not affect zinc transport activity.



Literature citations
Identification of SLC39A4, a gene involved in acrodermatitis enteropathica.
Kuery S.; Dreno B.; Bezieau S.; Giraudet S.; Kharfi M.; Kamoun R.; Moisan J.-P.;
Nat. Genet. 31:239-240(2002)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2); TISSUE SPECIFICITY; VARIANTS AEZ LEU-200; ARG-374 AND ARG-526;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.