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

    Gene ID: 4520, updated on 10-Dec-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
    mouse all
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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_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (37809574..37859592, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (37676462..37726477, complement)
    RS_2024_09 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

    Bibliography

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    Related articles in PubMed

    1. Cloning, chromosomal mapping and characterization of the human metal-regulatory transcription factor MTF-1. Brugnera E, et al. Nucleic Acids Res, 1994 Aug 11. PMID 8065932, Free PMC Article
    2. 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
    3. MRE-Binding transcription factor-1: weak zinc-binding finger domains 5 and 6 modulate the structure, affinity, and specificity of the metal-response element complex. Chen X, et al. Biochemistry, 1999 Sep 28. PMID 10504263
    4. Novel responses of ZRF, a variant of human MTF-1, to in vivo treatment with heavy metals. Otsuka F, et al. Biochim Biophys Acta, 2000 Jul 24. PMID 11004505
    5. Nucleo-cytoplasmic trafficking of metal-regulatory transcription factor 1 is regulated by diverse stress signals. Saydam N, et al. J Biol Chem, 2001 Jul 6. PMID 11306562

    See all (55) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. MTF1 genetic variants are associated with lung cancer risk in the Chinese Han population.
      Title: MTF1 genetic variants are associated with lung cancer risk in the Chinese Han population.
    2. Knocking-down long non-coding RNA LINC01094 prohibits chondrocyte apoptosis via regulating microRNA-577/metal-regulatory transcription factor 1 axis.
      Title: Knocking-down long non-coding RNA LINC01094 prohibits chondrocyte apoptosis via regulating microRNA-577/metal-regulatory transcription factor 1 axis.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. Human ZnT2 expression is regulated by MTF-1.
      Title: Coordinative modulation of human zinc transporter 2 gene expression through active and suppressive regulators.
    8. 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.
    9. 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.
    10. 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).
    Submit: New GeneRIF Correction See all GeneRIFs (27)

    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)

    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_2024_08

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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