MT3 metallothionein 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: MT3provided by HGNC
Official Full Name: metallothionein 3provided by HGNC
Primary source: HGNC:HGNC:7408
See related: Ensembl:ENSG00000087250 MIM:139255; AllianceGenome:HGNC:7408
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: GIF; GIFB; GRIF; ZnMT3
Summary: This gene is a member of the metallothionein family of genes. Proteins encoded by this gene family are low in molecular weight, are cysteine-rich, lack aromatic residues, and bind divalent heavy metal ions. This gene family member displays tissue-specific expression, and contains a threonine insert near its N-terminus and a glutamate-rich hexapeptide insert near its C-terminus relative to the proteins encoded by other gene family members. It plays an important role in zinc and copper homeostasis, and is induced under hypoxic conditions. The encoded protein is a growth inhibitory factor, and reduced levels of the protein are observed in the brains of individuals with some metal-linked neurodegenerative disorders such as Alzheimer's disease. [provided by RefSeq, Sep 2017]
Annotation information: Note: GIF (Gene ID: 2694) and MT3 (Gene ID: 4504) share the GIF symbol/alias in common. GIF is a widely used alternative name for metallothionein 3 (MT3), which can be confused with the official symbol for GIF (gastric intrinsic factor, GeneID 2694). [01 Jun 2018]
Expression: Biased expression in brain (RPKM 149.3) and adrenal (RPKM 10.1) See more
Orthologs: mouse all
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Genomic context

Location:: 16q13

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (56589528..56591085)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (62384459..62386016)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (56623440..56624997)

Chromosome 16 - NC_000016.10 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?

Apo-metallothionein-3 cooperatively forms tightly compact structures under physiological conditions.
Title: Apo-metallothionein-3 cooperatively forms tightly compact structures under physiological conditions.
Protein interactions with metallothionein-3 promote vectorial active transport in human proximal tubular cells.
Title: Protein interactions with metallothionein-3 promote vectorial active transport in human proximal tubular cells.
Metallothionein-3 is a clinical biomarker for tissue zinc levels in nasal mucosa.
Title: Metallothionein-3 is a clinical biomarker for tissue zinc levels in nasal mucosa.
Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma.
Title: Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma.
miR-325-3p Overexpression Inhibits Proliferation and Metastasis of Bladder Cancer Cells by Regulating MT3.
Title: miR-325-3p Overexpression Inhibits Proliferation and Metastasis of Bladder Cancer Cells by Regulating MT3.
Multistep Protein Unfolding Scenarios from the Rupture of a Complex Metal Cluster Cd3S9.
Title: Multistep Protein Unfolding Scenarios from the Rupture of a Complex Metal Cluster Cd(3)S(9).
We have demonstrated the relationship between MT-3 and senescence-induced oncogene genes and some other genes relevant to cell fate (glutathione S-transferase M3, caspase 4 and DNAJB6) and a significant proportion of MT-3 on cisplatin resistance. High levels of MT-3 in high-risk neuroblastoma could be one of the causes of frequent relapses in this tumor.
Title: [Identifying the Importance of MT-3 Expression for Neuroblastoma Cells].
MT3 is an arsenic- and hypoxia-upregulated oncogene that promotes cell growth and invasion of bladder carcinoma cells via downregulation of NDRG1, NDRG2, and MASPIN expressions.
Title: Metallothionein 3 Is a Hypoxia-Upregulated Oncogene Enhancing Cell Invasion and Tumorigenesis in Human Bladder Carcinoma Cells.
This study suggest that MT3 gene polymorphisms are not associated with autism.
Title: Association Study Between Metallothionein-3 Protein Polymorphisms and Autism.
In recent years, the roles of zinc dynamics and MT3 function in neurodegeneration are slowly emerging. This short review focuses on the recent developments regarding the chemistry and biology of MT3. [review]
Title: Mammalian Metallothionein-3: New Functional and Structural Insights.

Submit: New GeneRIF Correction See all GeneRIFs (51)

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	Microarray analysis indicates HIV-1 Tat upregulates the interferon-responsive gene expression of many proteins, including Metallothionein, in immature dendritic cells, an effect that likely facilitates the expansion of HIV-1 infection	PubMed
Vpr	vpr	Treatment of human primary astrocytes with HIV-1 Vpr downregulates expression of eleven genes, BNIP3, CYGB, DUOX2, DUSP1, FOXM1, GAPDH, HPRT1, MT3, MTL5, PTGS2, and SCARA3	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables antioxidant activity	NAS Non-traceable Author Statement more info	PubMed
enables cadmium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables copper ion binding	IDA Inferred from Direct Assay more info	PubMed
enables copper ion binding	TAS Traceable Author Statement more info	PubMed
enables metal ion binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in activation of protein kinase B activity	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular detoxification	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to cadmium ion	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to copper ion	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to hypoxia	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to oxidative stress	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to reactive oxygen species	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to zinc ion	IBA Inferred from Biological aspect of Ancestor more info
involved_in detoxification of copper ion	IBA Inferred from Biological aspect of Ancestor more info
involved_in energy reserve metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in intracellular monoatomic cation homeostasis	NAS Non-traceable Author Statement more info	PubMed
involved_in intracellular monoatomic cation homeostasis	TAS Traceable Author Statement more info	PubMed
involved_in intracellular zinc ion 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 leptin-mediated signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of axon extension	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell growth	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell growth	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of hydrogen peroxide catabolic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of neuron apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of neuron projection development	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of oxidoreductase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of ERK1 and ERK2 cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of ERK1 and ERK2 cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of ERK1 and ERK2 cascade	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of oxygen metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of vascular endothelial growth factor receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in protein stabilization	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of response to food	ISS Inferred from Sequence or Structural Similarity more info
involved_in removal of superoxide radicals	IDA Inferred from Direct Assay more info	PubMed
involved_in response to hypoxia	IDA Inferred from Direct Assay more info	PubMed
involved_in zinc ion transport	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in astrocyte end-foot	IEA Inferred from Electronic Annotation more info
located_in axon	IEA Inferred from Electronic Annotation more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in dendritic spine	IEA Inferred from Electronic Annotation more info
located_in extracellular space	IEA Inferred from Electronic Annotation more info
located_in inclusion body	IDA Inferred from Direct Assay more info	PubMed
located_in microtubule	IEA Inferred from Electronic Annotation more info
located_in mitochondrial outer membrane	IEA Inferred from Electronic Annotation more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in ribosome	IEA Inferred from Electronic Annotation more info
located_in synaptic vesicle	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: metallothionein-3

Names: growth inhibitory factor; metallothionein 3 (growth inhibitory factor (neurotrophic)); metallothionein-III

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.