# MTA1

## Overview
MTA1 (metastasis associated 1) is a gene that encodes a protein of the same name, which is a critical component of the nucleosome remodeling and deacetylase (NuRD) complex. This protein plays a pivotal role in chromatin remodeling and transcriptional regulation, influencing various cellular processes such as DNA damage response, circadian rhythm regulation, and inflammatory responses. The MTA1 protein is characterized by several conserved domains, including a bromo-adjacent homology (BAH) domain, an egl-27 and MTA1 homology domain 2 (ELM2), a Swi3, Ada2, NCoR, and TFIIIB domain (SANT), and a GATA-type zinc finger domain, which contribute to its function in transcriptional regulation and chromatin modification (Millard2014Towards; Kumar2016Structure). MTA1 is predominantly nuclear but can also localize in the cytoplasm, where its presence is associated with tumor progression. The gene is notably overexpressed in various cancers, correlating with poor prognosis and aggressive phenotypes, making it a significant focus in cancer research (Toh2008The; Malisetty2017MTA1).

## Structure
The MTA1 protein is a key component of the nucleosome remodeling and deacetylase (NuRD) complex, playing a significant role in chromatin remodeling and transcriptional regulation. It is composed of 715 amino acids and has a molecular weight of approximately 82 kDa in humans (Kumar2016Structure; Nawa2000Tumor). The protein contains several conserved domains, including a bromo-adjacent homology (BAH) domain, an egl-27 and MTA1 homology domain 2 (ELM2), a Swi3, Ada2, NCoR, and TFIIIB domain (SANT), and a GATA-type zinc finger domain (Millard2014Towards; Kumar2016Structure).

The BAH domain is involved in transcriptional regulation, while the ELM2 domain recruits histone deacetylases, forming a stable complex with HDAC1 (Millard2014Towards). The SANT domain is structurally similar to DNA-binding domains and is involved in transcription regulation (Millard2014Towards). The GATA-type zinc finger domain is implicated in DNA binding (Millard2014Towards).

MTA1 can undergo alternative splicing, resulting in multiple isoforms, such as MTA1-short (MTA1s) and ZG29p, which may have distinct roles in cellular processes (Millard2014Towards). The protein is predominantly nuclear but can also localize in the cytoplasm, with its cytoplasmic presence correlating with tumor progression (Kumar2016Structure).

## Function
MTA1 (metastasis associated 1) is a protein involved in various molecular processes in healthy human cells, primarily through its role in chromatin remodeling and transcriptional regulation. It is a component of the Mi2/NuRD complex, which is crucial for modifying chromatin structure and influencing gene expression (Li2014MTA; Sen2014Physiological). MTA1 modulates gene expression by acting as a corepressor or coactivator, depending on the context, and is involved in the regulation of circadian rhythms by interacting with the CLOCK-BMAL1 complex (Sen2014Physiological).

MTA1 is also implicated in DNA damage response, where it stabilizes and activates in response to ionizing radiation, facilitating efficient DNA repair through both p53-dependent and independent pathways (Li2014MTA; Sen2014Physiological). In cell biology, MTA1 influences inflammatory responses and is involved in the regulation of cytokine expression through the NF-κB signaling pathway (Sen2014Physiological). It plays a role in liver regeneration by regulating immuno-modulatory cytokines and affecting Th1 and Th2 responses (Sen2014Physiological).

MTA1 is predominantly located in the nuclear compartment but can also be found in the cytoplasm, where its localization is associated with specific cellular functions and responses (Kumar2016Structure). Its expression is particularly high in the liver, testes, brain, and kidney, suggesting tissue-specific functions (Sen2014Physiological).

## Clinical Significance
MTA1 (metastasis associated 1) is significantly implicated in cancer progression and metastasis. Overexpression of MTA1 is observed in various cancers, including breast, lung, gastric, colorectal, and hepatocellular carcinomas, often correlating with poor prognosis and aggressive cancer phenotypes (Toh2008The; Malisetty2017MTA1). In breast cancer, MTA1 overexpression is linked to higher tumor grades, increased microvessel density, and a higher risk of disease relapse, serving as a potential predictor of aggressive cancer behavior (Toh2008The). 

In colorectal carcinoma, MTA1 overexpression is associated with reduced cell adhesion and influences epithelial-mesenchymal transition (EMT) by regulating markers like E-cadherin and Vimentin (Malisetty2017MTA1). In hepatocellular carcinoma, high MTA1 expression predicts lower disease-free survival and is associated with tumor growth and vascular invasion (Toh2008The). 

MTA1 also plays a role in the regulation of estrogen receptor signaling, with its overexpression linked to ER negativity in breast cancer, indicating a more aggressive phenotype (Malisetty2017MTA1). Additionally, MTA1's interaction with the c-MYC oncoprotein and its involvement in chromatin remodeling further underscore its role in cancer progression (Toh2008The).

## Interactions
MTA1 (metastasis associated 1) is a key component of the nucleosome remodeling and deacetylase (NuRD) complex, where it acts as a scaffold protein, assembling enzymatic activity and nucleosome targeting proteins. Within the NuRD complex, MTA1 interacts directly with histone deacetylase 1 (HDAC1), RBBP4, and CHD4, enhancing and directing the activity of HDAC1 to modify chromatin (Millard2014Towards). The ELM2 domain of MTA1 is crucial for recruiting HDAC1 and HDAC2 to corepressor complexes, forming a stable complex with HDAC1 that allows for potential targeting of multiple nucleosomes simultaneously (Millard2014Towards).

MTA1 also interacts with various proteins and influences gene expression through post-translational modifications and protein-protein interactions. It is known to inhibit ERα transactivation activity, affecting hormone-independent phenotypes in breast cancer cells. MTA1 regulates the transcription of several genes, including PTEN and p21 WAF1, and represses BCL11B during T-cell leukemia (Kumar2016Structure). The protein's interactions within the NuRD complex and its regulatory roles highlight its significance in cancer biology, particularly in processes like DNA damage response, metastasis, and therapeutic resistance (Kumar2016Structure).


## References


[1. (Toh2008The) Yasushi Toh and Garth L. Nicolson. The role of the mta family and their encoded proteins in human cancers: molecular functions and clinical implications. Clinical & Experimental Metastasis, 26(3):215–227, December 2008. URL: http://dx.doi.org/10.1007/s10585-008-9233-8, doi:10.1007/s10585-008-9233-8. This article has 161 citations.](https://doi.org/10.1007/s10585-008-9233-8)

[2. (Kumar2016Structure) Rakesh Kumar and Rui-An Wang. Structure, expression and functions of mta genes. Gene, 582(2):112–121, May 2016. URL: http://dx.doi.org/10.1016/j.gene.2016.02.012, doi:10.1016/j.gene.2016.02.012. This article has 53 citations and is from a peer-reviewed journal.](https://doi.org/10.1016/j.gene.2016.02.012)

[3. (Malisetty2017MTA1) Vijaya Lakshmi Malisetty, Vasudevarao Penugurti, Prashanth Panta, Suresh Kumar Chitta, and Bramanandam Manavathi. Mta1 expression in human cancers – clinical and pharmacological significance. Biomedicine & Pharmacotherapy, 95:956–964, November 2017. URL: http://dx.doi.org/10.1016/j.biopha.2017.09.025, doi:10.1016/j.biopha.2017.09.025. This article has 21 citations.](https://doi.org/10.1016/j.biopha.2017.09.025)

[4. (Sen2014Physiological) Nirmalya Sen, Bin Gui, and Rakesh Kumar. Physiological functions of mta family of proteins. Cancer and Metastasis Reviews, 33(4):869–877, October 2014. URL: http://dx.doi.org/10.1007/s10555-014-9514-4, doi:10.1007/s10555-014-9514-4. This article has 32 citations and is from a peer-reviewed journal.](https://doi.org/10.1007/s10555-014-9514-4)

[5. (Nawa2000Tumor) Akihiro Nawa, Katsuhiko Nishimori, Paul Lin, Yoshiyuki Maki, Kennsuke Moue, Hidetomo Sawada, Yasushi Toh, Kikkawa Fumitaka, and Garth L. Nicolson. Tumor metastasis-associated humanmta1 gene: its deduced protein sequence, localization, and association with breast cancer cell proliferation using antisense phosphorothioate oligonucleotides. Journal of Cellular Biochemistry, 79(2):202–212, 2000. URL: http://dx.doi.org/10.1002/1097-4644(20001101)79:2<202::AID-JCB40>3.0.CO;2-L, doi:10.1002/1097-4644(20001101)79:2<202::aid-jcb40>3.0.co;2-l. This article has 132 citations and is from a peer-reviewed journal.](https://doi.org/10.1002/1097-4644(20001101)79:2)

[6. (Millard2014Towards) Christopher J. Millard, Louise Fairall, and John W. R. Schwabe. Towards an understanding of the structure and function of mta1. Cancer and Metastasis Reviews, 33(4):857–867, October 2014. URL: http://dx.doi.org/10.1007/s10555-014-9513-5, doi:10.1007/s10555-014-9513-5. This article has 33 citations and is from a peer-reviewed journal.](https://doi.org/10.1007/s10555-014-9513-5)

[7. (Li2014MTA) Da-Qiang Li, Yinlong Yang, and Rakesh Kumar. Mta family of proteins in dna damage response: mechanistic insights and potential applications. Cancer and Metastasis Reviews, 33(4):993–1000, October 2014. URL: http://dx.doi.org/10.1007/s10555-014-9524-2, doi:10.1007/s10555-014-9524-2. This article has 9 citations and is from a peer-reviewed journal.](https://doi.org/10.1007/s10555-014-9524-2)