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SLC39A4 solute carrier family 39 member 4 [ Homo sapiens (human) ]

Gene ID: 55630, updated on 28-Oct-2024

Summary

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Official Symbol
SLC39A4provided by HGNC
Official Full Name
solute carrier family 39 member 4provided by HGNC
Primary source
HGNC:HGNC:17129
See related
Ensembl:ENSG00000147804 MIM:607059; AllianceGenome:HGNC:17129
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
AEZ; ZIP4; AWMS2
Summary
This gene encodes a member of the zinc/iron-regulated transporter-like protein (ZIP) family. The encoded protein localizes to cell membranes and is required for zinc uptake in the intestine. Mutations in this gene result in acrodermatitis enteropathica. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]
Expression
Biased expression in duodenum (RPKM 47.9), small intestine (RPKM 33.9) and 3 other tissues See more
Orthologs
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Genomic context

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See SLC39A4 in Genome Data Viewer
Location:
8q24.3
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (144412414..144416844, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (145582227..145586657, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (145637798..145642228, complement)

Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene cleavage and polyadenylation specific factor 1 Neighboring gene microRNA 1234 Neighboring gene microRNA 6849 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28097 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19681 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19682 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28098 Neighboring gene ReSE screen-validated silencer GRCh37_chr8:145638844-145639041 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:145639267-145640084 Neighboring gene uncharacterized LOC124902041 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:145647393-145648164 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:145648165-145648934 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:145651263-145652026 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19684 Neighboring gene VPS28 subunit of ESCRT-I Neighboring gene tonsoku like, DNA repair protein Neighboring gene TONSL antisense RNA 1 Neighboring gene microRNA 6893

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. A new genetic isolate of acrodermatitis enteropathica with a novel mutation. Vardi A, et al. Br J Dermatol, 2009 Jun. PMID 19416242
  2. Computation and Functional Studies Provide a Model for the Structure of the Zinc Transporter hZIP4. Antala S, et al. J Biol Chem, 2015 Jul 17. PMID 25971965, Free PMC Article
  3. The large intracellular loop of hZIP4 is an intrinsically disordered zinc binding domain. Bafaro EM, et al. Metallomics, 2015 Sep. PMID 25882556, Free PMC Article
  4. SLC39A4 mutation in zinc deficiency patients. Limpongsanurak W, et al. J Med Assoc Thai, 2014 Jun. PMID 25391167
  5. Extreme population differences in the human zinc transporter ZIP4 (SLC39A4) are explained by positive selection in Sub-Saharan Africa. Engelken J, et al. PLoS Genet, 2014 Feb. PMID 24586184, Free PMC Article

See all (82) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. ZIP4 upregulation aggravates nucleus pulposus cell degradation by promoting inflammation and oxidative stress by mediating the HDAC4-FoxO3a axis.
    Title: ZIP4 upregulation aggravates nucleus pulposus cell degradation by promoting inflammation and oxidative stress by mediating the HDAC4-FoxO3a axis.
  2. GREM1, LRPPRC and SLC39A4 as potential biomarkers of intervertebral disc degeneration: a bioinformatics analysis based on multiple microarray and single-cell sequencing data.
    Title: GREM1, LRPPRC and SLC39A4 as potential biomarkers of intervertebral disc degeneration: a bioinformatics analysis based on multiple microarray and single-cell sequencing data.
  3. The transmembrane domains mediate oligomerization of the human ZIP4 transporter in vivo.
    Title: The transmembrane domains mediate oligomerization of the human ZIP4 transporter in vivo.
  4. Increased expression of zinc transporter ZIP4, ZIP11, ZnT1, and ZnT6 predicts poor prognosis in pancreatic cancer.
    Title: Increased expression of zinc transporter ZIP4, ZIP11, ZnT1, and ZnT6 predicts poor prognosis in pancreatic cancer.
  5. Elucidating the H(+) Coupled Zn(2+) Transport Mechanism of ZIP4; Implications in Acrodermatitis Enteropathica.
    Title: Elucidating the H(+) Coupled Zn(2+) Transport Mechanism of ZIP4; Implications in Acrodermatitis Enteropathica.
  6. Analysis of the relationship between the mutation site of the SLC39A4 gene and acrodermatitis enteropathica by reporting a rare Chinese twin: a case report and review of the literature.
    Title: Analysis of the relationship between the mutation site of the SLC39A4 gene and acrodermatitis enteropathica by reporting a rare Chinese twin: a case report and review of the literature.
  7. High ZIP4 expression was associated with metastasis and poor prognosis in human nasopharyngeal carcinoma patients. Elevated ZIP4 expression induced the EMT in C666-1 cells by activating the PI3K/Akt pathway. Downregulation of ZIP4 expression enhanced the radiosensitivity of C666-1 cells and inhibited metastasis.
    Title: Inhibition of ZIP4 reverses epithelial-to-mesenchymal transition and enhances the radiosensitivity in human nasopharyngeal carcinoma cells.
  8. This work provides important insights into the transport mechanism of the ZIPs broadly involved in transition metal homeostasis and signaling, and also a paradigm on a novel function of metal cluster in metalloproteins.
    Title: Asymmetric functions of a binuclear metal center within the transport pathway of a human zinc transporter ZIP4.
  9. We found that ZIP4 overexpression enhanced cell growth and chemoresistance in pancreatic cancer cells, whereas knockdown of ZIP4 reduced metastasis and sensitized pancreatic cancer cells to chemotherapy. We also found that ZIP4 increases expression of the transcription factor ZEB1, which activates expression of ITGA3 and ITGB1.
    Title: ZIP4 Increases Expression of Transcription Factor ZEB1 to Promote Integrin α3β1 Signaling and Inhibit Expression of the Gemcitabine Transporter ENT1 in Pancreatic Cancer Cells.
  10. Results demonstrate that the hZIP4 ICL2 domain is conformationally heterogeneous in the apo- and metal-bound states. No signi fi cant structural differences between the apo- and zinc-bound protein forms were discernable. The histidine-rich region in the apoprotein makes transient tertiary contacts with predicted post-translational modification sites.
    Title: Concomitant disorder and high-affinity zinc binding in the human zinc- and iron-regulated transport protein 4 intracellular loop.
Submit: New GeneRIF Correction See all GeneRIFs (53)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Hereditary acrodermatitis enteropathica
MedGen: C0221036 OMIM: 201100 GeneReviews: Not available
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

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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Markers

Homology

Clone Names

  • FLJ20327, MGC74741

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables identical protein binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables metal ion binding EXP
Inferred from Experiment
more info
 PubMed 
enables monoatomic cation:bicarbonate symporter activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables zinc ion binding IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables zinc ion sensor activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables zinc ion sequestering activity EXP
Inferred from Experiment
more info
 PubMed 
enables zinc ion sequestering activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables zinc ion transmembrane transporter activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables zinc ion transmembrane transporter activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables zinc ion transmembrane transporter activity TAS
Traceable Author Statement
more info
  
Process Evidence Code Pubs
involved_in bicarbonate transport IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to zinc ion starvation IEA
Inferred from Electronic Annotation
more info
  
involved_in intracellular monoatomic cation homeostasis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in intracellular zinc ion homeostasis ISS
Inferred from Sequence or Structural Similarity
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 IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in zinc ion transmembrane transport TAS
Traceable Author Statement
more info
  
Component Evidence Code Pubs
located_in apical plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in cytoplasmic vesicle IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  
located_in recycling endosome membrane IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
zinc transporter ZIP4
Names
ZRT/IRT-like protein 4
solute carrier family 39 (zinc transporter), member 4
zinc transporter 4
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.

Genomic

  1. NG_012234.3 RefSeqGene

    Range
    5000..9430
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001280557.2 → NP_001267486.1  zinc transporter ZIP4 isoform 3

    See identical proteins and their annotated locations for NP_001267486.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and lacks multiple 5' exons, compared to variant 2. It initiates translation at a downstream in-frame start codon. The encoded isoform (3) has a shorter N-terminus, compared to isoform 2.
    Source sequence(s)
    AK000489
    UniProtKB/TrEMBL
    Q9NX22
    Related
    ENST00000532718.5
    Conserved Domains (1) summary
    cl00437
    Location:1 → 140
    Zip; ZIP Zinc transporter

  2. NM_001374839.1 → NP_001361768.1  zinc transporter ZIP4 isoform 4 precursor

    Status: REVIEWED

    Source sequence(s)
    AC233992
    UniProtKB/TrEMBL
    A0A0S2Z5G2
    Conserved Domains (2) summary
    pfam02535
    Location:234 → 544
    Zip; ZIP Zinc transporter
    pfam18292
    Location:28 → 102
    ZIP4_domain; Zinc transporter ZIP4 domain

  3. NM_017767.3 → NP_060237.3  zinc transporter ZIP4 isoform 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 2. The encoded isoform (1) is shorter and has a distinct N-terminus, compared to isoform 2.
    Source sequence(s)
    AC233992
    Consensus CDS
    CCDS43782.1
    UniProtKB/TrEMBL
    A0AAG2TIE2
    Related
    ENSP00000276833.5, ENST00000276833.9
    Conserved Domains (2) summary
    pfam02535
    Location:303 → 613
    Zip; ZIP Zinc transporter
    pfam18292
    Location:37 → 171
    ZIP4_domain; Zinc transporter ZIP4 domain

  4. NM_130849.4 → NP_570901.3  zinc transporter ZIP4 isoform 2 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) encodes the longest isoform (2).
    Source sequence(s)
    AC233992
    Consensus CDS
    CCDS6424.1
    UniProtKB/Swiss-Prot
    Q6P5W5, Q7L5S5, Q9H6T8, Q9NXC4
    UniProtKB/TrEMBL
    A0A0S2Z5G8
    Related
    ENSP00000301305.4, ENST00000301305.8
    Conserved Domains (2) summary
    pfam02535
    Location:328 → 638
    Zip; ZIP Zinc transporter
    pfam18292
    Location:46 → 196
    ZIP4_domain; Zinc transporter ZIP4 domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000008.11 Reference GRCh38.p14 Primary Assembly

    Range
    144412414..144416844 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_024447189.2 → XP_024302957.1  zinc transporter ZIP4 isoform X1

    UniProtKB/TrEMBL
    A0A0S2Z5G2
    Conserved Domains (1) summary
    cl00437
    Location:234 → 493
    Zip; ZIP Zinc transporter

Reference GRCh38.p14 PATCHES

Genomic

  1. NW_018654716.1 Reference GRCh38.p14 PATCHES

    Range
    143017..147447 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054332202.1 → XP_054188177.1  zinc transporter ZIP4 isoform X2

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060932.1 Alternate T2T-CHM13v2.0

    Range
    145582227..145586657 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054360773.1 → XP_054216748.1  zinc transporter ZIP4 isoform X3

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q6P5W5.4 GenPept UniProtKB/Swiss-Prot:Q6P5W5

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