Slc39a4 solute carrier family 39 (zinc transporter), member 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Slc39a4provided by MGI
Official Full Name: solute carrier family 39 (zinc transporter), member 4provided by MGI
Primary source: MGI:MGI:1919277
See related: Ensembl:ENSMUSG00000063354 AllianceGenome:MGI:1919277
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: ZIP4; AWMS2; 1600025H15Rik
Summary: Enables zinc ion transmembrane transporter activity. Acts upstream of or within cellular response to zinc ion starvation; cellular zinc ion homeostasis; and zinc ion transport. Located in apical plasma membrane and endosome. Is expressed in several structures, including alimentary system; early embryo; extraembryonic component; genitourinary system; and integumental system. Used to study acrodermatitis enteropathica. Human ortholog(s) of this gene implicated in acrodermatitis enteropathica. Orthologous to human SLC39A4 (solute carrier family 39 member 4). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in duodenum adult (RPKM 110.1), small intestine adult (RPKM 81.8) and 10 other tissues See more
Orthologs: human all
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Genomic context

Location:: 15 D3; 15 36.16 cM

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	15	NC_000081.7 (76496583..76501579, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	15	NC_000081.6 (76612383..76618506, complement)

Chromosome 15 - NC_000081.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Slc39a4 in the small intestine predicts zinc absorption and utilization: a comprehensive analysis of zinc transporter expression in response to diets of varied zinc content in young mice.
Title: Slc39a4 in the small intestine predicts zinc absorption and utilization: a comprehensive analysis of zinc transporter expression in response to diets of varied zinc content in young mice.
While Zip4 was not found to be essential for proper glucose homeostasis and insulin secretion in vivo in mice, this study found that Zip4 mediates increases in cytoplasmic and granular zinc pools and stimulates glucose dependent insulin secretion in-vitro
Title: Zip4 mediated zinc influx stimulates insulin secretion in pancreatic beta cells.
These studies strongly suggest that wasting and lethality in acrodermatitis enteropathica patients reflects the loss-of-function of the intestine zinc transporter ZIP4, which leads to abnormal Paneth cell gene expression
Title: A mouse model of acrodermatitis enteropathica: loss of intestine zinc transporter ZIP4 (Slc39a4) disrupts the stem cell niche and intestine integrity.
Cell migration assays revealed that RNAi knockdown of Zip4 in Hepa cells depressed in vitro migration whereas forced over-expression in Hepa cells and MCF-7 cells enhanced in vitro migration
Title: Zip4 (Slc39a4) expression is activated in hepatocellular carcinomas and functions to repress apoptosis, enhance cell cycle and increase migration.
ZIP4 physically interacts with tPA, correlating with an increased intracellular zinc influx and lysosomal sequestration after excitotoxin stimulation. Changes in prosurvival signals support the idea that this sequestration results in neuroprotection.
Title: Tissue plasminogen activator alters intracellular sequestration of zinc through interaction with the transporter ZIP4.
KLF4 is induced during zinc restriction and is a transcription factor involved in adaptive regulation of the zinc transporter ZIP4
Title: Krüppel-like factor 4 regulates adaptive expression of the zinc transporter Zip4 in mouse small intestine.
The processing of ZIP4 may represent a significant regulatory mechanism controlling its function.
Title: Novel proteolytic processing of the ectodomain of the zinc transporter ZIP4 (SLC39A4) during zinc deficiency is inhibited by acrodermatitis enteropathica mutations.
ZIP4 is induced by zinc deficiency in cultured mouse Hepa cells and is rapidly degraded in response to added zinc
Title: Novel zinc-responsive post-transcriptional mechanisms reciprocally regulate expression of the mouse Slc39a4 and Slc39a5 zinc transporters (Zip4 and Zip5).
that heterozygous mutations in the acrodermatitis gene Zip4 (Slc39a4) may be associated with a wider range of developmental defects than was previously appreciated, particularly when dietary zinc is limiting.
Title: The mouse acrodermatitis enteropathica gene Slc39a4 (Zip4) is essential for early development and heterozygosity causes hypersensitivity to zinc deficiency.
ZIP4 and ZIP5 have roles in the adaptive response to dietary zinc in mice
Title: The adaptive response to dietary zinc in mice involves the differential cellular localization and zinc regulation of the zinc transporters ZIP4 and ZIP5.

Submit: New GeneRIF Correction See all GeneRIFs (12)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (2)
Targeted (4) 1 citation

General gene information

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Markers

Slc39a4 (e-PCR), detects polymorphism
- UniSTS:547106

AU041686 (e-PCR)
- UniSTS:160468

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables identical protein binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables metal ion binding	ISO Inferred from Sequence Orthology more info
enables metal ion transmembrane transporter activity	IEA Inferred from Electronic Annotation more info
enables monoatomic cation:bicarbonate symporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables zinc ion binding	ISO Inferred from Sequence Orthology more info
enables zinc ion sensor activity	ISO Inferred from Sequence Orthology more info
enables zinc ion sequestering activity	ISO Inferred from Sequence Orthology more info
enables zinc ion transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables zinc ion transmembrane transporter activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within cellular response to zinc ion starvation	IDA Inferred from Direct Assay more info	PubMed
involved_in intracellular monoatomic cation homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular zinc ion homeostasis	IDA Inferred from Direct Assay more info	PubMed
involved_in metal ion transport	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within monoatomic ion transport	IEA Inferred from Electronic Annotation more info
involved_in transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in zinc ion import across plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
involved_in zinc ion transmembrane transport	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic vesicle	ISO Inferred from Sequence Orthology more info
located_in membrane	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in recycling endosome membrane	IDA Inferred from Direct Assay more info	PubMed
located_in recycling endosome membrane	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: zinc transporter ZIP4

Names: activated in W/Wv mouse stomach 2; zrt- and Irt-like protein 4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_028064.3 → NP_082340.1 zinc transporter ZIP4 precursor

See identical proteins and their annotated locations for NP_082340.1

Status: VALIDATED

Source sequence(s)

AC157566

Consensus CDS

CCDS27578.1

UniProtKB/Swiss-Prot

Q78IQ7, Q8CHL4

UniProtKB/TrEMBL

Q3U263

Related

ENSMUSP00000155442.2, ENSMUST00000230977.2

Conserved Domains (1) summary

pfam02535
Location:338 → 651

Zip; ZIP Zinc transporter

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000081.7 Reference GRCm39 C57BL/6J

Range

76496583..76501579 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006521427.3 → XP_006521490.1 zinc transporter ZIP4 isoform X1

UniProtKB/TrEMBL

Q3U263

Conserved Domains (2) summary

pfam02535
Location:243 → 556

Zip; ZIP Zinc transporter

pfam18292
Location:27 → 101

ZIP4_domain; Zinc transporter ZIP4 domain