MTA1

This gene encodes a protein that was identified in a screen for genes expressed in metastatic cells, specifically, mammary adenocarcinoma cell lines. Expression of this gene has been correlated with the metastatic potential of at least two types of carcinomas although it is also expressed in many normal tissues. The role it plays in metastasis is unclear. It was initially thought to be the 70kD component of a nucleosome remodeling deacetylase complex, NuRD, but it is more likely that this component is a different but very similar protein. These two proteins are so closely related, though, that they share the same types of domains. These domains include two DNA binding domains, a dimerization domain, and a domain commonly found in proteins that methylate DNA. The profile and activity of this gene product suggest that it is involved in regulating transcription and that this may be accomplished by chromatin remodeling. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]

Metastasis Associated 1

Transcriptional coregulator which can act as both a transcriptional corepressor and coactivator. As a part of the histone-deacetylase multiprotein complex (NuRD), regulates transcription of its targets by modifying the acetylation status of the target chromatin and cofactor accessibility to the target DNA. In conjunction with other components of NuRD, acts as a transcriptional corepressor of BRCA1, ESR1, TFF1 and CDKN1A. Acts as a transcriptional coactivator of BCAS3, PAX5 and SUMO2, independent of the NuRD complex. Stimulates the expression of WNT1 by inhibiting the expression of its transcriptional corepressor SIX3. Regulates p53-dependent and -independent DNA repair processes following genotoxic stress. Regulates the stability and function of p53/TP53 by inhibiting its ubiquitination by COP1 and MDM2 thereby regulating the p53-dependent DNA repair. Plays an important role in tumorigenesis, tumor invasion, and metastasis. Involved in the epigenetic regulation of ESR1 expression in breast cancer in a TFAP2C, IFI16 and HDAC4/5/6-dependent manner. Plays a role in the regulation of the circadian clock and is essential for the generation and maintenance of circadian rhythms under constant light and for normal entrainment of behavior to light-dark (LD) cycles. Positively regulates the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of its own transcription and the transcription of CRY1. Regulates deacetylation of ARNTL/BMAL1 by regulating SIRT1 expression, resulting in derepressing CRY1-mediated transcription repression. Isoform Short binds to ESR1 and sequesters it in the cytoplasm and enhances its non-genomic responses. With TFCP2L1, promotes establishment and maintenance of pluripotency in embryonic stem cells (ESCs) and inhibits endoderm differentiation (By similarity).

Chromatin remodeling Source: ComplexPortal
Circadian regulation of gene expression Source: UniProtKB
Double-strand break repair Source: UniProtKB
Entrainment of circadian clock by photoperiod Source: UniProtKB
Histone deacetylation Source: ComplexPortal
Locomotor rhythm Source: UniProtKB
Negative regulation of transcription, DNA-templated Source: ComplexPortal
Negative regulation of transcription by RNA polymerase II Source: GO_Central
Positive regulation of protein autoubiquitination Source: UniProtKB
Positive regulation of transcription, DNA-templated Source: ComplexPortal
Proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
Regulation of cell fate specification Source: ComplexPortal
Regulation of gene expression, epigenetic Source: UniProtKB
Regulation of stem cell differentiation Source: ComplexPortal
Response to ionizing radiation Source: UniProtKB
Signal transduction Source: ProtInc

Isoform Short:
Cytoplasm
Isoform Long:
Cytoskeleton
Cytoplasm
Nucleus
Nucleus envelope
Note: Associated with microtubules. Localization at the nuclear envelope is TPR-dependent.

Phosphorylation by CSNK1G2/CK1 triggered by estrogen enhances corepression of estrogen receptor (ER).
Acetylation is essential for its transcriptional coactivator activity.3 Publications
Sumoylation positively regulates its transcriptional corepressor activity but does not affect the protein stability. preferentially by SUMO2 or SUMO3 than SUMO1. Sumoylation is enhanced by PIAS1/3/4 and preferentially sumoylated by SUMO2 in the presence of PIAS1/3/4. Desumoylated by SENP1.
Ubiquitinated by COP1, which leads to proteasomal degradation.