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FLASH GENE
Symbol MTA1 contributors: mct/ - updated : 18-09-2019
HGNC name metastasis associated 1
HGNC id 7410
Corresponding disease
DEL14QD chromosome 14q terminal deletion
Location 14q32.33      Physical location : 105.886.185 - 105.937.048
Synonym name metastasis associated protein
DNA
TYPE functioning gene
STRUCTURE 50.90 kb     21 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site   HRE
text structure
  • promoter contains two putative TP53 response elements (TP53REs), which were repressed by the TP53-inducing drug 5-fluorouracil (5-FU)
  • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 - 2856 - 715 - 2007 17666527
    21 - 2824 - 430 - 2007 17666527
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivesalivary gland   highly
    Reproductivefemale systemovary  highly
    Visualeye   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    cell lineage
    cell lines virtually all cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • one BAH and one ELM2 domain
  • two DNA binding domains
  • a dimerization domain
  • a domain commonly found in proteins that methylate DNA
  • one SH3 domain-binding motif
  • one GATA type zinc finger domain
  • HOMOLOGY
    interspecies homolog to murine Mta1
    Homologene
    FAMILY
  • NURD complex family
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome,nucleosome
    intracellular,nuclear envelope
    basic FUNCTION
  • nuclear regulatory factor, implicated in cellular transformation, in part through its ability to regulate the epithelial-to-mesenchymal transition and metastasis
  • corepressor of estrogen receptor alpha (ESR1), and transcriptional activator of Breast Cancer Amplified Sequence 3 (BCAS3)
  • playing a role as an upstream modifier of SIX3, a direct stimulator of rhodopsin expression, thus revealing a putative role for the MTA1/SIX3/rhodopsin pathway in vertebrate eye
  • involved in regulating transcription and this may be accomplished by chromatin remodeling
  • may operate as a negative modifier of apoptosis by interacting with TP53 during gametogenesis
  • destabilizes RFWD2 by promoting its autoubiquitination, thus creating a tight feedback loop that regulates both MTA1 and RFWD2 protein stability
  • required for optimum DNA double-strand break repair after ionizing radiation
  • role in DNA double-strand break (DSB) repair, and having an integral role in the nucleosome remodeling and histone-deacetylase (NuRD) complexes
  • required for optimum DNA double-strand break repair after ionizing radiation
  • required for MYD88-dependent stimulation of NFKB signaling and expression of proinflammatory cytokines such as IL1B, MIP2, and TNF1
  • involved in regulation of MYD88 which may constitute at least one of the mechanisms by which MTA1 stimulates LPS-induced NFkB signaling in stimulated macrophages
  • TP53-independent function in DNA damage response via modulation of the CDKN1A-proliferating cell nuclear antigen pathway
  • in addition to its role in the repair of double strand breaks caused by ionizing radiation, MTA1 also participates in the UV-induced ATR-mediated DNA damage checkpoint pathway
  • integral component of the nucleosome remodeling and deacetylase complex, implicated in the ionizing radiation-induced DNA damage response
  • first upstream modifier of GNAI2 gene expression and promotes Ras signalling
  • seems to be an important upstream modifier of GNAI2 expression and, consequently, could influence the activation of the Ras pathway, at least in part
  • master chromatin modifier, regulating the expression of HMMR and, consequently, its function in breast cancer cell motility and invasiveness
  • upstream coactivator of HMMR and is needed for its expression and resulting functions in invasion and migration
  • role for MTA1 in maintenance of circadian rhythmicity through acting on the positive limb of the clock machinery
  • participate in the DNA damage response beyond its well-established roles in gene transcription
  • MTA1 promotes the proliferation of epithelial ovarian cancer cells by enhancing DNA repair
  • MTA1 plays an important role in Epithelial-to-mesenchymal transition (EMT) to promote metastasis via suppressing CDH1 expression, resulting in a poor prognosis in malignant pleural mesothelioma (MPM)
  • critical homeostatic role of MTA1, both as a target and as a component of the neuronal oxidative stress, in the regulation of acute neuronal responses against brain I/R damage
  • cytoplasmic translocation of MTA1 coregulator promotes de-repression of SGK1 transcription in hypoxic cancer cells
  • MTA1 potentially promoted pancreatic cancer metastasis via HIF1A/VEGF pathway
  • MTA1-S100A4-MYH9 axis exists in endothelial cells as a novel pathway in promoting tumor vascular formation
  • is a chromatin modifier and its expression is significantly associated with prognosis of many cancers
  • MTA1 coregulator regulates LDHA expression and function in breast cancer
  • CELLULAR PROCESS cell life, proliferation/growth
    nucleotide, chromatin organization, remodeling
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    text proliferation and growth of cancer cells; regulator of transcription (by chromatin remodeling)
    PATHWAY
    metabolism
    signaling
  • important role for MTA1-BCAS3 pathway in promoting cancerous phenotypes in breast tumor cells
  • putative role for the MTA1/SIX3/rhodopsin pathway in vertebrate eye
  • a component
  • component of the Mi-2/nucleosome remodeling and deacetylating (NURD) complex that contains both histone deacetylase and nucleosome remodeling activity
  • complexing with histone deacetylase to plays an important role in histone deacetylation, alteration of chromatin structure and transcriptional control
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • target of MYC
  • target of ITGB3BP (regulatory interactions between MTA1 and ITGB3BP might be important in modulating the sensitivity of breast cancer cells to estrogen)
  • interacting with SIX3 ( physically interacts with the SIX3 chromatin in a histone deacetylase-dependent manner, leading to transcriptional suppression of the SIX3 gene)
  • interacting with TP53 (controls the stability of TP53 protein and consequently may constitute a new upstream regulator of TP53 protein)
  • interacts directly with histone deacetylase 1 (HDAC1) and HDAC2
  • behaves as a co-repressor of the GNAI2 gene
  • role for MTA1 as an upstream coactivator of TH
  • transcriptionally stimulates expression of the hyaluronan-mediated motility receptor (HMMR) and consequently regulates cancer invasion and migratory function
  • target of TP53-mediated transrepression
  • novel function for poly(ADP-ribose)ylation of TP53 in the gene-specific regulation of the transcriptional mode of TP53 on the promoter of MTA1
  • RBBP4-MTA1 interaction is essential for the integration of RBBP7/RBBP4 into the NuRD complex
  • histone chaperone protein RBBP4, bind to the C-terminal tail of MTA1, and MTA1 recruits a second copy of RBBP4
  • MTA1 is a novel corepressor of serum and glucocorticoid-inducible kinase 1 (SGK1)
  • PRKD1 is an upstream regulatory kinase of MTA1
  • associations of SPEN with MTA1 (metastasis-associated 1), a member of the nucleosome remodeling complex with histone deacetylase activity, which might contribute to interactions of SPEN with chromatin
  • TRIM25 is the E3 ligase that interacts with and degrades MTA1 protein in normal liver cells, and TRIM25 ubiquitinates MTA1 at lysine 98 and degrades it normal liver cells
  • cytoplasmic MTA1, but not nuclear MTA1, was colocalized with S100A4, suggesting bthe involvement of MTA1 in S100A4 stability
  • interaction of MTA1 with MYC and recruitment of MTA1-MYC complex on to the LDHA promoter to regulate its transcription
  • cell & other
    REGULATION
    Other regulated by MYC
    ASSOCIATED DISORDERS
    corresponding disease(s) DEL14QD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    overexpression and acetylation level of histone H4 protein, closely related, are predictors of malignant potential of esophageal squamous cell carcinomas
    tumoral     --over  
    in cancer cell lines (metastatic), closely associated with higher tumor grade and increased tumor angiogenesis
    tumoral   deletion    
    in breast cancer without metastasis
    tumoral     --over  
    in majority of invasive breast carcinomas
    Susceptibility
    Variant & Polymorphism
    Candidate gene for ID in del14qter
    Marker
  • positive expression of MTA1 predicts higher disease-free survival (DFS) and overall survival (OS) rates in laryngeal squamous cell carcinoma
  • MTA1 level may be used as a new indicator to predict the progression of endometriosis
  • MTA1 is a novel biomarker and indicative of a poor prognosis in malignant pleural mesothelioma (MPM) patients
  • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivepancreas
    may be an effective therapy target in pancreatic cancer
    cancerreproductivebreast
    possible target molecule for anti-angiogenic drugs in breast cancer treatment
    cancer  
    potential therapeutic target that could be used to enhance the effectiveness of IR or DNA-damaging anticancer agents in cancer cells by targeting MTA1 expression
    ANIMAL & CELL MODELS