MTA2

Last updated
MTA2
Identifiers
Aliases MTA2 , MTA1L1, PID, metastasis associated 1 family member 2
External IDs OMIM: 603947 MGI: 1346340 HomoloGene: 3480 GeneCards: MTA2
Orthologs
SpeciesHumanMouse
Entrez

9219

23942

Ensembl

ENSG00000149480

ENSMUSG00000071646

UniProt

O94776

Q9R190

RefSeq (mRNA)

NM_004739
NM_001330292

NM_011842

RefSeq (protein)

NP_001317221
NP_004730

NP_035972

Location (UCSC) Chr 11: 62.59 – 62.6 Mb Chr 19: 8.92 – 8.93 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Metastasis-associated protein MTA2 is a protein that in humans is encoded by the MTA2 gene. [5] [6]

Contents

MTA2 is the second member of the MTA family of genes. [5] [7] [8] MTA2 protein localizes in the nucleus and is a component of the nucleosome remodeling and the deacetylation complex (NuRD). [8] Similar to the founding family member MTA1, MTA2 functions as a chromatin remodeling factor and regulates gene expression. [9] [10] MTA2 is overexpressed in human cancer and its dysregulated level correlates well with cancer invasiveness and aggressive phenotypes. [11]

Discovery

MTA2 was initially recognized as an MTA1 like 1 gene, named MTA1-L1, from a large scale sequencing of randomly selected clones from human cDNA libraries in 1999. [5] Clues about the role of MTA2 in gene expression came from the association of MTA2 polypeptides in the NuRD complex in a proteomic study [7] This was followed by targeted cloning of murine Mta2 in 2001. [12]

Gene and spliced variants

MTA2 is localized on chromosome 11q12-q13.1 in human and on 19B in mice. The 8.6-kb long human MTA2 gene contains 20 exons and seven transcripts inclusive of three protein-coding transcripts but predicted to code for two polypeptides of 688 amino acids and 495 amino acids. [13] The remaining four MTA2 transcripts are non-coding RNA transcripts ranging from 532-bp to 627-bp. The murine Mta2 consists of a 3.1-kb protein-coding transcript to code a protein of 668 amino acids, and five non-coding RNAs transcripts, ranging from 620-bp to 839-bp.

Structure

Amino acid sequence of MTA2 shares 68.2% homology with MTA1’s sequence. MTA2 domains include, a BAH (Bromo-Adjacent Homology), an ELM2 (egl-27 and MTA1 homology), a SANT domain (SWI, ADA2, N-CoR, TFIIIB-B), and a GATA-like zinc finger. [14] [15] [16] MTA2 is acetylated at lysine 152 within the BAH domain [17]

Function

This gene encodes a protein that has been identified as a component of NuRD, a nucleosome remodeling deacetylase complex identified in the nucleus of human cells. It shows a very broad expression pattern and is strongly expressed in many tissues. It may represent one member of a small gene family that encode different but related proteins involved either directly or indirectly in transcriptional regulation. Their indirect effects on transcriptional regulation may include chromatin remodeling. [6]

MTA2 inhibits estrogen receptor-transactivation functions, and participates in the development of hormones independent of breast cancer cells. [11] The MTA2 participate in the circadian rhythm through CLOCK-BMAL1 complex. MTA2 inhibits the expression of target genes owing to its ability to interact with chromatin remodeling complexes, and modulates pathways involved in cellular functions, including invasion, apoptosis, epithelial-to-mesenchymal transition, and growth of normal and cancer cells [9] [11]

Regulation

Expression of MTA2 is stimulated by Sp1 transcription factor [12] [18] and repressed by Kaiso. [19] Growth regulatory activity of MTA2 is modulated through its acetylation by histone acetylase p300 [12]. The expression of MTA2 is inhibited by the Rho GDIa in breast cancer cells [20] and by human β-defensins in colon cancer cells. [21] MicroRNAs-146a and miR-34a also regulate the levels of MTA2 mRNA through post-transcriptional mechanism. [22] [23] [24]

Targets

MTA2 deacetylates the estrogen receptor alpha and p53 and inhibits their transactivation functions. [25] [26] MTA2 represses the expression of E-cadherin in non-small-cell lung cancer cells. [27] but stimulates the expression of IL-11 in gastric cancer cells. [28] The MTA2-containing chromatin remodeling complex targets CLOCK-BMAL1 complex. [29]

Interactions

MTA2 has been shown to interact with:

Notes

Related Research Articles

<span class="mw-page-title-main">HDAC1</span> Protein-coding gene in the species Homo sapiens

Histone deacetylase 1 (HDAC1) is an enzyme that in humans is encoded by the HDAC1 gene.

Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression. Such remodeling is principally carried out by 1) covalent histone modifications by specific enzymes, e.g., histone acetyltransferases (HATs), deacetylases, methyltransferases, and kinases, and 2) ATP-dependent chromatin remodeling complexes which either move, eject or restructure nucleosomes. Besides actively regulating gene expression, dynamic remodeling of chromatin imparts an epigenetic regulatory role in several key biological processes, egg cells DNA replication and repair; apoptosis; chromosome segregation as well as development and pluripotency. Aberrations in chromatin remodeling proteins are found to be associated with human diseases, including cancer. Targeting chromatin remodeling pathways is currently evolving as a major therapeutic strategy in the treatment of several cancers.

<span class="mw-page-title-main">Histone deacetylase 2</span> Protein-coding gene in the species Homo sapiens

Histone deacetylase 2 (HDAC2) is an enzyme that in humans is encoded by the HDAC2 gene. It belongs to the histone deacetylase class of enzymes responsible for the removal of acetyl groups from lysine residues at the N-terminal region of the core histones. As such, it plays an important role in gene expression by facilitating the formation of transcription repressor complexes and for this reason is often considered an important target for cancer therapy.

<span class="mw-page-title-main">SIN3A</span> Protein-coding gene in the species Homo sapiens

Paired amphipathic helix protein Sin3a is a protein that in humans is encoded by the SIN3A gene.

<span class="mw-page-title-main">RBBP4</span> Protein-coding gene in the species Homo sapiens

Histone-binding protein RBBP4 is a protein that in humans is encoded by the RBBP4 gene.

<span class="mw-page-title-main">Methyl-CpG-binding domain protein 2</span> Protein-coding gene in the species Homo sapiens

Methyl-CpG-binding domain protein 2 is a protein that in humans is encoded by the MBD2 gene.

<span class="mw-page-title-main">MTA1</span> Protein-coding gene in the species Homo sapiens

Metastasis-associated protein MTA1 is a protein that in humans is encoded by the MTA1 gene. MTA1 is the founding member of the MTA family of genes. MTA1 is primarily localized in the nucleus but also found to be distributed in the extra-nuclear compartments. MTA1 is a component of several chromatin remodeling complexes including the nucleosome remodeling and deacetylation complex (NuRD). MTA1 regulates gene expression by functioning as a coregulator to integrate DNA-interacting factors to gene activity. MTA1 participates in physiological functions in the normal and cancer cells. MTA1 is one of the most upregulated proteins in human cancer and associates with cancer progression, aggressive phenotypes, and poor prognosis of cancer patients.

<span class="mw-page-title-main">HDAC6</span> Protein-coding gene in the species Homo sapiens

Histone deacetylase 6 is an enzyme that in humans is encoded by the HDAC6 gene. HDAC6 has emerged as a highly promising candidate to selectively inhibit as a therapeutic strategy to combat several types of cancer and neurodegenerative disorders.

<span class="mw-page-title-main">RBBP7</span> Protein-coding gene in the species Homo sapiens

Histone-binding protein RBBP7 is a protein that in humans is encoded by the RBBP7 gene.

<span class="mw-page-title-main">Histone deacetylase 5</span> Protein-coding gene in the species Homo sapiens

Histone deacetylase 5 is an enzyme that in humans is encoded by the HDAC5 gene.

<span class="mw-page-title-main">HDAC9</span> Protein-coding gene in the species Homo sapiens

Histone deacetylase 9 is an enzyme that in humans is encoded by the HDAC9 gene.

<span class="mw-page-title-main">CHD3</span> Protein-coding gene in the species Homo sapiens

Chromodomain-helicase-DNA-binding protein 3 is an enzyme that in humans is encoded by the CHD3 gene.

<span class="mw-page-title-main">MBD3</span> Protein-coding gene in the species Homo sapiens

Methyl-CpG-binding domain protein 3 is a protein that in humans is encoded by the MBD3 gene.

<span class="mw-page-title-main">EIF3A</span> Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 3 subunit A (eIF3a) is a protein that in humans is encoded by the EIF3A gene. It is one of the subunits of Eukaryotic initiation factor 3 (eIF3) a multiprotein complex playing major roles in translation initiation in eukaryotes.

<span class="mw-page-title-main">SAP30</span> Protein-coding gene in the species Homo sapiens

Sin3A-associated protein, 30kDa, also known as SAP30, is a protein which in humans is encoded by the SAP30 gene.

<span class="mw-page-title-main">CHD4</span> Protein-coding gene in the species Homo sapiens

Chromodomain-helicase-DNA-binding protein 4 is an enzyme that in humans is encoded by the CHD4 gene. CHD4 is the core nucleosome-remodelling component of the Nucleosome Remodelling and Deacetylase (NuRD) complex.

<span class="mw-page-title-main">SALL4</span> Protein-coding gene in the species Homo sapiens

Sal-like protein 4(SALL4) is a transcription factor encoded by a member of the Spalt-like (SALL) gene family, SALL4. The SALL genes were identified based on their sequence homology to Spalt, which is a homeotic gene originally cloned in Drosophila melanogaster that is important for terminal trunk structure formation in embryogenesis and imaginal disc development in the larval stages. There are four human SALL proteins with structural homology and playing diverse roles in embryonic development, kidney function, and cancer. The SALL4 gene encodes at least three isoforms, termed A, B, and C, through alternative splicing, with the A and B forms being the most studied. SALL4 can alter gene expression changes through its interaction with many co-factors and epigenetic complexes. It is also known as a key embryonic stem cell (ESC) factor.

<span class="mw-page-title-main">MTA3</span> Protein-coding gene in the species Homo sapiens

Metastasis-associated protein MTA3 is a protein that in humans is encoded by the MTA3 gene. MTA3 protein localizes in the nucleus as well as in other cellular compartments MTA3 is a component of the nucleosome remodeling and deacetylate (NuRD) complex and participates in gene expression. The expression pattern of MTA3 is opposite to that of MTA1 and MTA2 during mammary gland tumorigenesis. However, MTA3 is also overexpressed in a variety of human cancers.

In the field of molecular biology, the Mi-2/NuRDcomplex, is a group of associated proteins with both ATP-dependent chromatin remodeling and histone deacetylase activities. As of 2007, Mi-2/NuRD was the only known protein complex that couples chromatin remodeling ATPase and chromatin deacetylation enzymatic functions.

<span class="mw-page-title-main">Deficiency of RbAp48 protein and memory loss</span>

Memory is commonly referred to as the ability to encode, store, retain and subsequently recall information and past experiences in the human brain. This process involves many proteins, one of which is the Histone-binding protein RbAp48, encoded by the RBBP4 gene in humans.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000149480 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000071646 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 3 Futamura M, Nishimori H, Shiratsuchi T, Saji S, Nakamura Y, Tokino T (1999). "Molecular cloning, mapping, and characterization of a novel human gene, MTA1-L1, showing homology to a metastasis-associated gene, MTA1". Journal of Human Genetics. 44 (1): 52–6. doi: 10.1007/s100380050107 . PMID   9929979.
  6. 1 2 "Entrez Gene: MTA2 metastasis associated 1 family, member 2".
  7. 1 2 Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D (Aug 1999). "Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation". Genes & Development. 13 (15): 1924–35. doi:10.1101/gad.13.15.1924. PMC   316920 . PMID   10444591.
  8. 1 2 Li DQ, Kumar R (2015). Unravelling the Complexity and Functions of MTA Coregulators in Human Cancer. Vol. 127. pp. 1–47. doi:10.1016/bs.acr.2015.04.005. ISBN   9780128029206. PMID   26093897.{{cite book}}: |journal= ignored (help)
  9. 1 2 Sen N, Gui B, Kumar R (Dec 2014). "Physiological functions of MTA family of proteins". Cancer and Metastasis Reviews. 33 (4): 869–77. doi:10.1007/s10555-014-9514-4. PMC   4245464 . PMID   25344801.
  10. ↑ Kumar R (Dec 2014). "Functions and clinical relevance of MTA proteins in human cancer. Preface". Cancer and Metastasis Reviews. 33 (4): 835. doi:10.1007/s10555-014-9509-1. PMC   4245326 . PMID   25348751.
  11. 1 2 3 Covington KR, Fuqua SA (Dec 2014). "Role of MTA2 in human cancer". Cancer and Metastasis Reviews. 33 (4): 921–8. doi:10.1007/s10555-014-9518-0. PMC   4425804 . PMID   25394532.
  12. 1 2 Xia L, Zhang Y (May 2001). "Sp1 and ETS family transcription factors regulate the mouse Mta2 gene expression". Gene. 268 (1–2): 77–85. doi:10.1016/s0378-1119(01)00429-2. PMID   11368903. S2CID   20705099.
  13. ↑ Kumar R, Wang RA (May 2016). "Structure, expression and functions of MTA genes". Gene. 582 (2): 112–21. doi:10.1016/j.gene.2016.02.012. PMC   4785049 . PMID   26869315.
  14. ↑ Millard CJ, Watson PJ, Celardo I, Gordiyenko Y, Cowley SM, Robinson CV, Fairall L, Schwabe JW (Jul 2013). "Class I HDACs share a common mechanism of regulation by inositol phosphates". Molecular Cell. 51 (1): 57–67. doi:10.1016/j.molcel.2013.05.020. PMC   3710971 . PMID   23791785.
  15. ↑ Alqarni SS, Murthy A, Zhang W, Przewloka MR, Silva AP, Watson AA, Lejon S, Pei XY, Smits AH, Kloet SL, Wang H, Shepherd NE, Stokes PH, Blobel GA, Vermeulen M, Glover DM, Mackay JP, Laue ED (Aug 2014). "Insight into the architecture of the NuRD complex: structure of the RbAp48-MTA1 subcomplex". The Journal of Biological Chemistry. 289 (32): 21844–55. doi: 10.1074/jbc.M114.558940 . PMC   4139204 . PMID   24920672.
  16. ↑ Millard CJ, Fairall L, Schwabe JW (Dec 2014). "Towards an understanding of the structure and function of MTA1". Cancer and Metastasis Reviews. 33 (4): 857–67. doi:10.1007/s10555-014-9513-5. PMC   4244562 . PMID   25352341.
  17. ↑ Zhou J, Zhan S, Tan W, Cheng R, Gong H, Zhu Q (Feb 2014). "P300 binds to and acetylates MTA2 to promote colorectal cancer cells growth". Biochemical and Biophysical Research Communications. 444 (3): 387–90. doi:10.1016/j.bbrc.2014.01.062. PMID   24468085.
  18. ↑ Zhou C, Ji J, Cai Q, Shi M, Chen X, Yu Y, Liu B, Zhu Z, Zhang J (8 September 2013). "MTA2 promotes gastric cancer cells invasion and is transcriptionally regulated by Sp1". Molecular Cancer. 12 (1): 102. doi: 10.1186/1476-4598-12-102 . PMC   3851872 . PMID   24010737.
  19. ↑ Yoon HG, Chan DW, Reynolds AB, Qin J, Wong J (Sep 2003). "N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso". Molecular Cell. 12 (3): 723–34. doi: 10.1016/j.molcel.2003.08.008 . PMID   14527417.
  20. ↑ Barone I, Brusco L, Gu G, Selever J, Beyer A, Covington KR, Tsimelzon A, Wang T, Hilsenbeck SG, Chamness GC, Andò S, Fuqua SA (Apr 2011). "Loss of Rho GDIα and resistance to tamoxifen via effects on estrogen receptor α". Journal of the National Cancer Institute. 103 (7): 538–52. doi:10.1093/jnci/djr058. PMC   3071355 . PMID   21447808.
  21. ↑ Uraki S, Sugimoto K, Shiraki K, Tameda M, Inagaki Y, Ogura S, Kasai C, Nojiri K, Yoneda M, Yamamoto N, Takei Y, Nobori T, Ito M (Sep 2014). "Human β-defensin-3 inhibits migration of colon cancer cells via downregulation of metastasis-associated 1 family, member 2 expression". International Journal of Oncology. 45 (3): 1059–64. doi: 10.3892/ijo.2014.2507 . PMID   24969834.
  22. ↑ Li Y, Vandenboom TG, Wang Z, Kong D, Ali S, Philip PA, Sarkar FH (Feb 2010). "miR-146a suppresses invasion of pancreatic cancer cells". Cancer Research. 70 (4): 1486–95. doi:10.1158/0008-5472.CAN-09-2792. PMC   2978025 . PMID   20124483.
  23. ↑ Kaller M, Liffers ST, Oeljeklaus S, Kuhlmann K, Röh S, Hoffmann R, Warscheid B, Hermeking H (Aug 2011). "Genome-wide characterization of miR-34a induced changes in protein and mRNA expression by a combined pulsed SILAC and microarray analysis". Molecular & Cellular Proteomics. 10 (8): M111.010462. doi: 10.1074/mcp.M111.010462 . PMC   3149097 . PMID   21566225.
  24. ↑ Zhang Y, Wang XF (Dec 2014). "Post-transcriptional regulation of MTA family by microRNAs in the context of cancer". Cancer and Metastasis Reviews. 33 (4): 1011–6. doi:10.1007/s10555-014-9526-0. PMC   4245459 . PMID   25332146.
  25. ↑ Cui Y, Niu A, Pestell R, Kumar R, Curran EM, Liu Y, Fuqua SA (Sep 2006). "Metastasis-associated protein 2 is a repressor of estrogen receptor alpha whose overexpression leads to estrogen-independent growth of human breast cancer cells". Molecular Endocrinology. 20 (9): 2020–35. doi:10.1210/me.2005-0063. PMC   4484605 . PMID   16645043.
  26. ↑ Luo J, Su F, Chen D, Shiloh A, Gu W (Nov 2000). "Deacetylation of p53 modulates its effect on cell growth and apoptosis". Nature. 408 (6810): 377–81. Bibcode:2000Natur.408..377L. doi:10.1038/35042612. PMID   11099047. S2CID   4300392.
  27. ↑ Lu X, Kovalev GI, Chang H, Kallin E, Knudsen G, Xia L, Mishra N, Ruiz P, Li E, Su L, Zhang Y (May 2008). "Inactivation of NuRD component Mta2 causes abnormal T cell activation and lupus-like autoimmune disease in mice". The Journal of Biological Chemistry. 283 (20): 13825–33. doi: 10.1074/jbc.M801275200 . PMC   2376246 . PMID   18353770.
  28. ↑ Zhou C, Ji J, Cai Q, Shi M, Chen X, Yu Y, Zhu Z, Zhang J (2 May 2015). "MTA2 enhances colony formation and tumor growth of gastric cancer cells through IL-11". BMC Cancer. 15: 343. doi: 10.1186/s12885-015-1366-y . PMC   4419442 . PMID   25929737.
  29. ↑ Kim JY, Kwak PB, Weitz CJ (Dec 2014). "Specificity in circadian clock feedback from targeted reconstitution of the NuRD corepressor". Molecular Cell. 56 (6): 738–48. doi: 10.1016/j.molcel.2014.10.017 . PMID   25453762.
  30. 1 2 3 4 5 6 Yao YL, Yang WM (Oct 2003). "The metastasis-associated proteins 1 and 2 form distinct protein complexes with histone deacetylase activity". The Journal of Biological Chemistry. 278 (43): 42560–8. doi: 10.1074/jbc.M302955200 . PMID   12920132.
  31. ↑ You A, Tong JK, Grozinger CM, Schreiber SL (Feb 2001). "CoREST is an integral component of the CoREST- human histone deacetylase complex". Proceedings of the National Academy of Sciences of the United States of America. 98 (4): 1454–8. Bibcode:2001PNAS...98.1454Y. doi: 10.1073/pnas.98.4.1454 . PMC   29278 . PMID   11171972.
  32. 1 2 3 4 5 Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D (Aug 1999). "Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation". Genes & Development. 13 (15): 1924–35. doi:10.1101/gad.13.15.1924. PMC   316920 . PMID   10444591.
  33. 1 2 Yasui D, Miyano M, Cai S, Varga-Weisz P, Kohwi-Shigematsu T (Oct 2002). "SATB1 targets chromatin remodelling to regulate genes over long distances". Nature. 419 (6907): 641–5. Bibcode:2002Natur.419..641Y. doi:10.1038/nature01084. PMID   12374985. S2CID   25822700.
  34. ↑ Hakimi MA, Dong Y, Lane WS, Speicher DW, Shiekhattar R (Feb 2003). "A candidate X-linked mental retardation gene is a component of a new family of histone deacetylase-containing complexes". The Journal of Biological Chemistry. 278 (9): 7234–9. doi: 10.1074/jbc.M208992200 . PMID   12493763.
  35. ↑ Sakai H, Urano T, Ookata K, Kim MH, Hirai Y, Saito M, Nojima Y, Ishikawa F (Dec 2002). "MBD3 and HDAC1, two components of the NuRD complex, are localized at Aurora-A-positive centrosomes in M phase". The Journal of Biological Chemistry. 277 (50): 48714–23. doi: 10.1074/jbc.M208461200 . PMID   12354758.
  36. ↑ Saito M, Ishikawa F (Sep 2002). "The mCpG-binding domain of human MBD3 does not bind to mCpG but interacts with NuRD/Mi2 components HDAC1 and MTA2". The Journal of Biological Chemistry. 277 (38): 35434–9. doi: 10.1074/jbc.M203455200 . PMID   12124384.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.