MTA1 (metastasis-associated gene 1)

2005-04-01   Yasushi Toh , Garth L Nicolson 

Department of Gastroenterological Surgery National Kyushu Cancer, Center Fukuoka, 811-1395, Japan

Identity

HGNC
LOCATION
14q32.33
LOCUSID
ALIAS
-
FUSION GENES

DNA/RNA

Transcription

About 2.7 k mRNA; Protein coding region of 714 amino acid residues.

Proteins

Atlas Image
Motifs in putative amino acid sequence of MTA1.
A leucine zipper motif and a GATA-type zinc finger motif are found near the mid-portion of the protein. Between them, a SANT domain is found which is homologous to the DNA binding domain of the myb oncogene family. In the amino terminal 200 amino acid residues, there are two highly acidic regions characteristic of the acidic activation domains of many transcription factors. At the carboxyl-terminus is a proline rich stretch whose sequence matches the consensus sequence of the src-homology 3-binding motif. Three putative nuclear localization signals are also present in the sequence.

Description

715 amino acids; about 80 kDa.

Expression

Found in almost all tissues; most abundantly expressed in testis.

Localisation

Nucleus.

Function

MTA1 protein physically interacts with histone deacetylase 1 and is included in a protein nucleosome remodeling complex, NuRD (nucleosome remodeling and histone deacetylation). This protein complex, containing histone deacetylase, plays an important role in histone deacetylation, alteration of chromatin structure and transcriptional control.

Homology

Implicated in

Disease
Cancer invasion and metastasis as follows:
  • Overexpression of MTA1 mRNA is correlated with the depth of invasion and lymph node metastasis in gastric and colorectal carcinomas as well as in esophageal carcinomas. The correlation of overexpression of this gene is also reported in lung cancer, thymoma and prostate cancer.
  • Overexpression of MTA1 protein might be a useful predictor for poor prognosis of human esophageal squamous cell carcinomas.
  • Forced expression of the MTA1 protein in breast cancer cell line MCF-7 is accompanied by enhancement of the ability of cells to invade an artificial matrix and to grow in an anchorage-independent manner.
  • Increasing MTA1 expression enhances migration, invasion and anchorage-independent survival of immortalized human keratinocytes.
  • Bibliography

    Pubmed IDLast YearTitleAuthors
    114742002001Assignment of the human metastasis-associated gene 1 (MTA1) to human chromosome band 14q32.3 by fluorescence in situ hybridization.Cui Q et al
    127058692003MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer.Fujita N et al
    148718072004The role of metastasis-associated protein 1 in prostate cancer progression.Hofer MD et al
    146130242003Emerging roles of MTA family members in human cancers.Kumar R et al
    119483992002Metastasis-associated protein (MTA)1 enhances migration, invasion, and anchorage-independent survival of immortalized human keratinocytes.Mahoney MG et al
    111466232001Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor.Mazumdar A et al
    109675482000Tumor metastasis-associated human MTA1 gene: its deduced protein sequence, localization, and association with breast cancer cell proliferation using antisense phosphorothioate oligonucleotides.Nawa A et al
    118046872002Expression of the MTA1 mRNA in advanced lung cancer.Sasaki H et al
    116892912001Expression of the MTA1 mRNA in thymoma patients.Sasaki H et al
    108409442000Molecular analysis of a candidate metastasis-associated gene, MTA1: possible interaction with histone deacetylase 1.Toh Y et al
    102062831999Overexpression of metastasis-associated MTA1 mRNA in invasive oesophageal carcinomas.Toh Y et al
    150953002004Expression of the metastasis-associated MTA1 protein and its relationship to deacetylation of the histone H4 in esophageal squamous cell carcinomas.Toh Y et al
    92914401997Overexpression of the MTA1 gene in gastrointestinal carcinomas: correlation with invasion and metastasis.Toh Y et al
    80831951994A novel candidate metastasis-associated gene, mta1, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA cloning, expression, and protein analyses.Toh Y et al
    98855721998NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities.Xue Y et al

    Other Information

    Locus ID:

    NCBI: 9112
    MIM: 603526
    HGNC: 7410
    Ensembl: ENSG00000182979

    Variants:

    dbSNP: 9112
    ClinVar: 9112
    TCGA: ENSG00000182979
    COSMIC: MTA1

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000182979ENST00000331320Q13330
    ENSG00000182979ENST00000405646Q13330
    ENSG00000182979ENST00000406191E7ESY4
    ENSG00000182979ENST00000424723H7C3F3
    ENSG00000182979ENST00000434050H0Y4T7
    ENSG00000182979ENST00000435036F8W9Y9
    ENSG00000182979ENST00000438610Q13330
    ENSG00000182979ENST00000551236H0YIT0

    Expression (GTEx)

    0
    50
    100
    150

    Pathways

    PathwaySourceExternal ID
    Metabolism of proteinsREACTOMER-HSA-392499
    Post-translational protein modificationREACTOMER-HSA-597592
    SUMOylationREACTOMER-HSA-2990846
    SUMO E3 ligases SUMOylate target proteinsREACTOMER-HSA-3108232
    Gene ExpressionREACTOMER-HSA-74160
    RNA Polymerase I, RNA Polymerase III, and Mitochondrial TranscriptionREACTOMER-HSA-504046
    RNA Polymerase I TranscriptionREACTOMER-HSA-73864
    RNA Polymerase I Promoter ClearanceREACTOMER-HSA-73854
    RNA Polymerase I Transcription InitiationREACTOMER-HSA-73762
    Epigenetic regulation of gene expressionREACTOMER-HSA-212165
    Chromatin organizationREACTOMER-HSA-4839726
    Chromatin modifying enzymesREACTOMER-HSA-3247509
    HDACs deacetylate histonesREACTOMER-HSA-3214815
    SUMOylation of transcription factorsREACTOMER-HSA-3232118
    Positive epigenetic regulation of rRNA expressionREACTOMER-HSA-5250913
    ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expressionREACTOMER-HSA-427389

    Protein levels (Protein atlas)

    Not detected
    Low
    Medium
    High

    References

    Pubmed IDYearTitleCitations
    237917852013Class I HDACs share a common mechanism of regulation by inositol phosphates.95
    121678652002A naturally occurring MTA1 variant sequesters oestrogen receptor-alpha in the cytoplasm.69
    222703592012Leptin-induced epithelial-mesenchymal transition in breast cancer cells requires β-catenin activation via Akt/GSK3- and MTA1/Wnt1 protein-dependent pathways.67
    218134702012Overexpression of EIF5A2 promotes colorectal carcinoma cell aggressiveness by upregulating MTA1 through C-myc to induce epithelial-mesenchymaltransition.65
    161723992005Metastasis-associated protein 1 (MTA1) is an essential downstream effector of the c-MYC oncoprotein.54
    129201322003The metastasis-associated proteins 1 and 2 form distinct protein complexes with histone deacetylase activity.51
    166171022006MTA1, a transcriptional activator of breast cancer amplified sequence 3.51
    179220352008Heat shock factor 1 represses estrogen-dependent transcription through association with MTA1.49
    183628312008Expression of hypoxia-inducible factor-1alpha, histone deacetylase 1, and metastasis-associated protein 1 in pancreatic carcinoma: correlation with poor prognosis with possible regulation.47
    210477982011Insights into association of the NuRD complex with FOG-1 from the crystal structure of an RbAp48·FOG-1 complex.45

    Citation

    Yasushi Toh ; Garth L Nicolson

    MTA1 (metastasis-associated gene 1)

    Atlas Genet Cytogenet Oncol Haematol. 2005-04-01

    Online version: http://atlasgeneticsoncology.org/gene/41443/mta1id41443ch14q32