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

Summary

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: mouse all
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Genomic context

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_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D1S1423 (e-PCR)
- UniSTS:149619

D16S325 (e-PCR)
- UniSTS:147089

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

NG_012234.3 RefSeqGene

Range

5000..9430

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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

NC_000008.11 Reference GRCh38.p14 Primary Assembly

Range

144412414..144416844 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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