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    MTDH metadherin [ Homo sapiens (human) ]

    Gene ID: 92140, updated on 3-Nov-2024

    Summary

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    Official Symbol
    MTDHprovided by HGNC
    Official Full Name
    metadherinprovided by HGNC
    Primary source
    HGNC:HGNC:29608
    See related
    Ensembl:ENSG00000147649 MIM:610323; AllianceGenome:HGNC:29608
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    3D3; AEG1; AEG-1; LYRIC; LYRIC/3D3
    Summary
    Enables NF-kappaB binding activity; double-stranded RNA binding activity; and transcription coactivator activity. Involved in several processes, including lipopolysaccharide-mediated signaling pathway; positive regulation of intracellular signal transduction; and regulation of DNA-templated transcription. Located in endoplasmic reticulum; nuclear lumen; and perinuclear region of cytoplasm. Implicated in hepatocellular carcinoma. [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Ubiquitous expression in thyroid (RPKM 24.7), bone marrow (RPKM 21.0) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See MTDH in Genome Data Viewer
    Location:
    8q22.1
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (97644184..97730260)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (98769667..98855740)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (98656412..98742488)

    Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105375657 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27666 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27667 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27668 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27669 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19390 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:98656262-98657242 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:98657243-98658221 Neighboring gene ribosomal protein S2 pseudogene 33 Neighboring gene MPRA-validated peak7115 silencer Neighboring gene uncharacterized LOC124901986 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:98786357-98786856 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:98787884-98788846 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:98788847-98789808 Neighboring gene NANOG hESC enhancer GRCh37_chr8:98789991-98790612 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:98794740-98795248 Neighboring gene lysosomal protein transmembrane 4 beta Neighboring gene TMEM69 pseudogene 1

    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. Uncontrolled inflammation induced by AEG-1 promotes gastric cancer and poor prognosis. Li G, et al. Cancer Res, 2014 Oct 1. PMID 25092897
    2. Astrocyte elevated gene-1(AEG-1) induces epithelial-mesenchymal transition in lung cancer through activating Wnt/β-catenin signaling. He W, et al. BMC Cancer, 2015 Mar 8. PMID 25880337, Free PMC Article
    3. Overexpression of astrocyte elevated gene-1 (AEG-1) in cervical cancer and its correlation with angiogenesis. Yu JQ, et al. Asian Pac J Cancer Prev, 2015. PMID 25824750
    4. Astrocyte elevated gene-1 promotes progression of cervical squamous cell carcinoma by inducing epithelial-mesenchymal transition via Wnt signaling. Song E, et al. Int J Gynecol Cancer, 2015 Mar. PMID 25695541
    5. Repression of metadherin inhibits biological behavior of prostate cancer cells and enhances their sensitivity to cisplatin. Wei YB, et al. Mol Med Rep, 2015 Jul. PMID 25684730, Free PMC Article

    See all (434) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. A Study on the Binding Mechanism and the Impact of Key Residue Mutations between SND1 and MTDH Peptide through Molecular Dynamics Simulations.
      Title: A Study on the Binding Mechanism and the Impact of Key Residue Mutations between SND1 and MTDH Peptide through Molecular Dynamics Simulations.
    2. Linc00239 Promotes Colorectal Cancer Development via MicroRNA-182-5p/Metadherin Axis.
      Title: Linc00239 Promotes Colorectal Cancer Development via MicroRNA-182-5p/Metadherin Axis.
    3. Metadherin inhibits chemosensitivity of triple-negative breast cancer to paclitaxel via activation of AKT/GSK-3beta signaling pathway.
      Title: Metadherin inhibits chemosensitivity of triple-negative breast cancer to paclitaxel via activation of AKT/GSK-3β signaling pathway.
    4. Plasma metadherin mRNA expression in bladder cancer.
      Title: Plasma metadherin mRNA expression in bladder cancer.
    5. USP7 promotes cervical cancer progression by stabilizing MTDH expression through deubiquitination.
      Title: USP7 promotes cervical cancer progression by stabilizing MTDH expression through deubiquitination.
    6. HIV-1 gp120 amplifies astrocyte elevated gene-1 activity to compromise the integrity of the outer blood-retinal barrier.
      Title: HIV-1 gp120 amplifies astrocyte elevated gene-1 activity to compromise the integrity of the outer blood-retinal barrier.
    7. Metadherin promotes stem cell phenotypes and correlated with immune infiltration in hepatocellular carcinoma.
      Title: Metadherin promotes stem cell phenotypes and correlated with immune infiltration in hepatocellular carcinoma.
    8. Metadherin orchestrates PKA and PKM2 to activate beta-catenin signaling in podocytes during proteinuric chronic kidney disease.
      Title: Metadherin orchestrates PKA and PKM2 to activate β-catenin signaling in podocytes during proteinuric chronic kidney disease.
    9. Using the metabolite alterations monitoring the AEG-1 expression level and cell biological behaviour of U251 cell in vitro.
      Title: Using the metabolite alterations monitoring the AEG-1 expression level and cell biological behaviour of U251 cell in vitro.
    10. Expression patterns of AEG-1 in the normal brain.
      Title: Expression patterns of AEG-1 in the normal brain.
    Submit: New GeneRIF Correction See all GeneRIFs (285)

    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
    Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1.
    EBI GWAS Catalog

    Variation

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    See Variation Viewer (GRCh37.p13)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Astrocyte elevated gene (AEG)-1 expression is increased in astrocytes infected with HIV-1 or treated with HIV-1 gp120; AEG-1 inhibits excitatory amino acid transporter 2 (EAAT2) promoter activity with the potential to promote glutamate excito-toxicity PubMed
    Envelope transmembrane glycoprotein gp41 env Lyric decreases HIV-1 gp41 expression compared to control cells PubMed
    Pr55(Gag) gag HIV-1 Gag interacts with MTDH as demonstrated by proximity dependent biotinylation proteomics PubMed
    gag Cellular biotinylated metadherin (MTDH, Lyric, AEG-1) protein is incorporated into HIV-1 Gag virus-like particles PubMed
    gag Interaction of HIV-1 Gag with metadherin (MTDH, Lyric) is identified in a series of six affinity purification/mass spectrometry screens PubMed
    gag HIV-1 Gag multimerization is a prerequisite for the interaction with Lyric PubMed
    gag MA and NC domains of HIV-1 Gag are required for the interaction with Lyric. The Lyric region between amino acids 107 and 204 is essential for the interaction PubMed
    Tat tat AEG-1 expression is upregulated in the CNS of HIV-1-infected individuals and corelates with the expression of HIV-1 Tat protein in the brain PubMed
    Vpr vpr A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies upregulation of metadherin (Lyric) expression by HIV-1 Vpr in Vpr transduced macrophages PubMed
    retropepsin gag-pol Lyric is incorporated into viral particles and cleaved at its C-terminus by HIV-1 PR PubMed

    Go to the HIV-1, Human Interaction Database

    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables NF-kappaB binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables NF-kappaB binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables RNA binding HDA PubMed 
    enables RNA polymerase II-specific DNA-binding transcription factor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables double-stranded RNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transcription coactivator activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables transcription coregulator activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in lipopolysaccharide-mediated signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of DNA-templated transcription IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of NF-kappaB transcription factor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of angiogenesis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of autophagy IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of canonical NF-kappaB signal transduction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in apical plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in bicellular tight junction ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endoplasmic reticulum membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in fibrillar center IDA
    Inferred from Direct Assay
    more info
    		  
    located_in intercellular canaliculus ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in nuclear body IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nuclear membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in perinuclear region of cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    protein LYRIC
    Names
    3D3/LYRIC
    astrocyte elevated gene 1
    astrocyte elevated gene-1 protein
    lysine-rich CEACAM1 co-isolated protein
    metastasis adhesion protein

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_001363136.1 → NP_001350065.1  protein LYRIC isoform 2

      Status: VALIDATED

      Source sequence(s)
      AF411226, AP003357, AY082966, BC045642, DA213697, DW426198
      UniProtKB/TrEMBL
      E5RJU9
      Conserved Domains (1) summary
      pfam15686
      Location:6 → 400
      LYRIC; Lysine-rich CEACAM1 co-isolated protein family

    2. NM_001363137.1 → NP_001350066.1  protein LYRIC isoform 3

      Status: VALIDATED

      Source sequence(s)
      AF411226, AP003357, AY082966, BC045642
      UniProtKB/TrEMBL
      E5RJU9
      Conserved Domains (1) summary
      pfam15686
      Location:6 → 452
      LYRIC; Lysine-rich CEACAM1 co-isolated protein family

    3. NM_001363138.1 → NP_001350067.1  protein LYRIC isoform 4

      Status: VALIDATED

      Source sequence(s)
      AF411226, AK308030, AP003357, AY082966, BC045642
      UniProtKB/TrEMBL
      E5RJU9
      Related
      ENSP00000428168.1, ENST00000519934.5
      Conserved Domains (1) summary
      pfam15686
      Location:6 → 389
      LYRIC; Lysine-rich CEACAM1 co-isolated protein family

    4. NM_001363139.1 → NP_001350068.1  protein LYRIC isoform 5

      Status: VALIDATED

      Source sequence(s)
      AF411226, AK308030, AP003357, AY082966, BC045642, DW426198
      UniProtKB/TrEMBL
      E5RJU9
      Conserved Domains (1) summary
      pfam15686
      Location:6 → 367
      LYRIC; Lysine-rich CEACAM1 co-isolated protein family

    5. NM_178812.4 → NP_848927.2  protein LYRIC isoform 1

      Status: VALIDATED

      Source sequence(s)
      AF411226, AP003357, AY082966, BC045642
      Consensus CDS
      CCDS6274.1
      UniProtKB/Swiss-Prot
      Q05DH2, Q52QU9, Q6PK07, Q86UE4, Q8TCX3
      UniProtKB/TrEMBL
      E5RJU9
      Related
      ENSP00000338235.3, ENST00000336273.8
      Conserved Domains (1) summary
      pfam15686
      Location:6 → 422
      LYRIC; Lysine-rich CEACAM1 co-isolated protein family

    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
      97644184..97730260
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011517369.4 → XP_011515671.1  protein LYRIC isoform X2

      UniProtKB/TrEMBL
      E5RJU9
      Conserved Domains (1) summary
      pfam15686
      Location:6 → 452
      LYRIC; Lysine-rich CEACAM1 co-isolated protein family

    2. XM_011517370.4 → XP_011515672.1  protein LYRIC isoform X3

      UniProtKB/TrEMBL
      E5RJU9
      Conserved Domains (1) summary
      pfam15686
      Location:6 → 422
      LYRIC; Lysine-rich CEACAM1 co-isolated protein family

    3. XM_017013968.3 → XP_016869457.1  protein LYRIC isoform X5

      UniProtKB/TrEMBL
      E5RJU9

    4. XM_011517368.3 → XP_011515670.1  protein LYRIC isoform X1

      UniProtKB/TrEMBL
      E5RJU9
      Conserved Domains (1) summary
      pfam15686
      Location:6 → 430
      LYRIC; Lysine-rich CEACAM1 co-isolated protein family

    5. XM_047422418.1 → XP_047278374.1  protein LYRIC isoform X4

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060932.1 Alternate T2T-CHM13v2.0

      Range
      98769667..98855740
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054361501.1 → XP_054217476.1  protein LYRIC isoform X2

    2. XM_054361502.1 → XP_054217477.1  protein LYRIC isoform X3

    3. XM_054361504.1 → XP_054217479.1  protein LYRIC isoform X5

    4. XM_054361500.1 → XP_054217475.1  protein LYRIC isoform X1

    5. XM_054361503.1 → XP_054217478.1  protein LYRIC isoform X4

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q86UE4.2 GenPept UniProtKB/Swiss-Prot:Q86UE4

    Gene LinkOut

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

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