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MTF1 metal regulatory transcription factor 1 [ Homo sapiens (human) ]

Gene ID: 4520, updated on 5-Mar-2024

Summary

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Official Symbol
MTF1provided by HGNC
Official Full Name
metal regulatory transcription factor 1provided by HGNC
Primary source
HGNC:HGNC:7428
See related
Ensembl:ENSG00000188786 MIM:600172; AllianceGenome:HGNC:7428
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
ZRF; MTF-1
Summary
This gene encodes a transcription factor that induces expression of metallothioneins and other genes involved in metal homeostasis in response to heavy metals such as cadmium, zinc, copper, and silver. The protein is a nucleocytoplasmic shuttling protein that accumulates in the nucleus upon heavy metal exposure and binds to promoters containing a metal-responsive element (MRE). [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in bone marrow (RPKM 7.9), testis (RPKM 4.9) and 25 other tissues See more
Orthologs
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Genomic context

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See MTF1 in Genome Data Viewer
Location:
1p34.3
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (37809574..37859592, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (37676462..37726477, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (38275246..38325264, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 679 Neighboring gene mannosidase endo-alpha like Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 680 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 681 Neighboring gene chromosome 1 open reading frame 122 Neighboring gene yrdC N6-threonylcarbamoyltransferase domain containing Neighboring gene ribosomal protein S2 pseudogene 13 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 682 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr1:38330961-38332160 Neighboring gene inositol polyphosphate-5-phosphatase B Neighboring gene RNA, U6 small nuclear 584, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 777 Neighboring gene uncharacterized LOC124904043

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
  • 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. Genomic Redistribution of Metal-Response Transcription Factor-1 (MTF-1) in Cadmium Resistant Cells. Wright GM, et al. Cells, 2023 Mar 21. PMID 36980293, Free PMC Article
  2. Genetic variation in metallothionein and metal-regulatory transcription factor 1 in relation to urinary cadmium, copper, and zinc. Adams SV, et al. Toxicol Appl Pharmacol, 2015 Dec 15. PMID 26529669, Free PMC Article
  3. Metal responsive transcription factor 1 (MTF-1) regulates zinc dependent cellular processes at the molecular level. Grzywacz A, et al. Acta Biochim Pol, 2015. PMID 26336656
  4. Zn-responsive proteome profiling and time-dependent expression of proteins regulated by MTF-1 in A549 cells. Zhao WJ, et al. PLoS One, 2014. PMID 25162517, Free PMC Article
  5. A conserved cysteine cluster, essential for transcriptional activity, mediates homodimerization of human metal-responsive transcription factor-1 (MTF-1). Günther V, et al. Biochim Biophys Acta, 2012 Feb. PMID 22057392

See all (53) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Genomic Redistribution of Metal-Response Transcription Factor-1 (MTF-1) in Cadmium Resistant Cells.
    Title: Genomic Redistribution of Metal-Response Transcription Factor-1 (MTF-1) in Cadmium Resistant Cells.
  2. MTF1 heads a hierarchy of zinc sensors, and through controlling the expression of a raft of metallothioneins and other key proteins involved in controlling intracellular zinc levels (e.g. ZnT1) alters zinc buffering capacity and total cellular zinc content.
    Title: Zinc sensing by metal-responsive transcription factor 1 (MTF1) controls metallothionein and ZnT1 expression to buffer the sensitivity of the transcriptome response to zinc.
  3. MTF-1 has a role in regulating zinc dependent cellular processes at the molecular level [review]
    Title: Metal responsive transcription factor 1 (MTF-1) regulates zinc dependent cellular processes at the molecular level.
  4. Forty-one single nucleotide polymorphisms (SNPs) within the MTF1 gene region.
    Title: Genetic variation in metallothionein and metal-regulatory transcription factor 1 in relation to urinary cadmium, copper, and zinc.
  5. Human ZnT2 expression is regulated by MTF-1.
    Title: Coordinative modulation of human zinc transporter 2 gene expression through active and suppressive regulators.
  6. Zn-responsive proteome profiling and time-dependent expression of proteins are regulated by MTF-1 in human alveolar epithelial cells.
    Title: Zn-responsive proteome profiling and time-dependent expression of proteins regulated by MTF-1 in A549 cells.
  7. The zinc-sensing cytoplasmic transcription factor MTF-1 plays a key role in cellular zinc homoeostasis.
    Title: Zinc-dependent lysosomal enlargement in TRPML1-deficient cells involves MTF-1 transcription factor and ZnT4 (Slc30a4) transporter.
  8. Results identify a cysteine cluster that mediates homodimerization of human MTF-1, and show that dimer formation in vivo is important for basal and especially metal-induced transcriptional activity.
    Title: A conserved cysteine cluster, essential for transcriptional activity, mediates homodimerization of human metal-responsive transcription factor-1 (MTF-1).
  9. Variations in the ability of LAT1/DMT1/MTF1/MT1a to process and transport Hg may not play a significant role in the etiology of autism.
    Title: Lack of association between autism and four heavy metal regulatory genes.
  10. It is concluded that SUMO conjugation and the SIM on MTF-1 do not play a critical role in suppressing transcriptional activity. Instead, MTF-1 forms complexes with cellular factors through SIM and SUMO moiety in the cytoplasm
    Title: The role of small ubiquitin-like modifier-interacting motif in the assembly and regulation of metal-responsive transcription factor 1.
Submit: New GeneRIF Correction See all GeneRIFs (25)

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

EBI GWAS Catalog

Description
Genetics of rheumatoid arthritis contributes to biology and drug discovery.
EBI GWAS Catalog
Novel associations for hypothyroidism include known autoimmune risk loci.
EBI GWAS Catalog

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

  • MGC23036

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables DNA binding TAS
Traceable Author Statement
more info
 PubMed 
enables DNA-binding transcription activator activity, RNA polymerase II-specific IBA
Inferred from Biological aspect of Ancestor
more info
  
enables DNA-binding transcription activator activity, RNA polymerase II-specific IDA
Inferred from Direct Assay
more info
 PubMed 
enables DNA-binding transcription factor activity TAS
Traceable Author Statement
more info
  
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables cis-regulatory region sequence-specific DNA binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables histone acetyltransferase binding IEA
Inferred from Electronic Annotation
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables sequence-specific double-stranded DNA binding IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in DNA-templated transcription IEA
Inferred from Electronic Annotation
more info
  
involved_in cartilage homeostasis IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to zinc ion IEA
Inferred from Electronic Annotation
more info
  
involved_in central nervous system development IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of transcription by RNA polymerase II TAS
Traceable Author Statement
more info
  
involved_in response to cadmium ion IEA
Inferred from Electronic Annotation
more info
  
involved_in response to metal ion TAS
Traceable Author Statement
more info
 PubMed 
involved_in response to oxidative stress IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in cytoplasm IEA
Inferred from Electronic Annotation
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleus TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
metal regulatory transcription factor 1
Names
MRE-binding transcription factor
MRE-binding transcription factor-1
metal-responsive transcription factor 1
transcription factor MTF-1
zinc regulatory factor

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)

  1. NM_005955.3 → NP_005946.2  metal regulatory transcription factor 1

    See identical proteins and their annotated locations for NP_005946.2

    Status: REVIEWED

    Source sequence(s)
    AI915521, AL929472, BC014454, X78710
    Consensus CDS
    CCDS30676.1
    UniProtKB/Swiss-Prot
    B2RAK6, Q14872, Q96CB1
    Related
    ENSP00000362127.3, ENST00000373036.5
    Conserved Domains (4) summary
    COG5048
    Location:93 → 291
    COG5048; FOG: Zn-finger [General function prediction only]
    sd00017
    Location:234 → 253
    ZF_C2H2; C2H2 Zn finger [structural motif]
    pfam13465
    Location:245 → 271
    zf-H2C2_2; Zinc-finger double domain
    pfam15909
    Location:231 → 319
    zf-C2H2_8; C2H2-type zinc ribbon

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    37809574..37859592 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047421170.1 → XP_047277126.1  metal regulatory transcription factor 1 isoform X1

    UniProtKB/Swiss-Prot
    B2RAK6, Q14872, Q96CB1

  2. XM_011541491.3 → XP_011539793.1  metal regulatory transcription factor 1 isoform X1

    See identical proteins and their annotated locations for XP_011539793.1

    UniProtKB/Swiss-Prot
    B2RAK6, Q14872, Q96CB1
    Conserved Domains (4) summary
    COG5048
    Location:93 → 291
    COG5048; FOG: Zn-finger [General function prediction only]
    sd00017
    Location:234 → 253
    ZF_C2H2; C2H2 Zn finger [structural motif]
    pfam13465
    Location:245 → 271
    zf-H2C2_2; Zinc-finger double domain
    pfam15909
    Location:231 → 319
    zf-C2H2_8; C2H2-type zinc ribbon

  3. XM_047421173.1 → XP_047277129.1  metal regulatory transcription factor 1 isoform X3

  4. XM_011541493.4 → XP_011539795.1  metal regulatory transcription factor 1 isoform X2

    Conserved Domains (4) summary
    COG5048
    Location:93 → 291
    COG5048; FOG: Zn-finger [General function prediction only]
    sd00017
    Location:234 → 253
    ZF_C2H2; C2H2 Zn finger [structural motif]
    pfam13465
    Location:245 → 271
    zf-H2C2_2; Zinc-finger double domain
    pfam15909
    Location:231 → 319
    zf-C2H2_8; C2H2-type zinc ribbon

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    37676462..37726477 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054336697.1 → XP_054192672.1  metal regulatory transcription factor 1 isoform X1

    UniProtKB/Swiss-Prot
    B2RAK6, Q14872, Q96CB1

  2. XM_054336699.1 → XP_054192674.1  metal regulatory transcription factor 1 isoform X3

  3. XM_054336698.1 → XP_054192673.1  metal regulatory transcription factor 1 isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q14872.2 GenPept UniProtKB/Swiss-Prot:Q14872

Gene LinkOut

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