MTA3

MTA3
Identifiers
Aliases	MTA3, metastasis associated 1 family member 3
External IDs	OMIM: 609050; MGI: 2151172; HomoloGene: 14282; GeneCards: MTA3; OMA:MTA3 - orthologs
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2p21 Start 42,494,569 bp[1] End 42,756,947 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17|17 E4 Start 84,013,592 bp[2] End 84,128,945 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right adrenal cortex left adrenal gland left adrenal cortex gonad epithelium of colon oocyte left ovary right ovary ventricular zone secondary oocyte Top expressed in zygote secondary oocyte morula primary oocyte blastocyst lip genital tubercle tail of embryo blood primary visual cortex More reference expression data BioGPS n/a
Gene ontology Molecular function DNA-binding transcription factor activity sequence-specific DNA binding DNA binding zinc ion binding chromatin binding protein binding metal ion binding histone deacetylase activity DNA-binding transcription factor activity, RNA polymerase II-specific protein-containing complex binding transcription coactivator activity transcription corepressor activity histone deacetylase binding Cellular component intracellular membrane-bounded organelle nucleus nucleoplasm cytoplasm NuRD complex Biological process negative regulation of transcription, DNA-templated regulation of transcription, DNA-templated histone deacetylation positive regulation of cell population proliferation positive regulation of G2/M transition of mitotic cell cycle regulation of transcription by RNA polymerase II negative regulation of transcription by RNA polymerase II positive regulation of nucleic acid-templated transcription Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 57504 116871 Ensembl ENSG00000057935 ENSMUSG00000055817 UniProt Q9BTC8 Q924K8 RefSeq (mRNA) NM_001282755 NM_001282756 NM_020744 NM_001330442 NM_001330443 NM_001330444 NM_001171052 NM_001171053 NM_001171054 NM_054082 NM_001379388 NM_001379389 NM_001379390 NM_001379391 NM_001379392 RefSeq (protein) NP_001269684 NP_001269685 NP_001317371 NP_001317372 NP_001317373 NP_065795 NP_001164523 NP_001164524 NP_001164525 NP_473423 NP_001366317 NP_001366318 NP_001366319 NP_001366320 NP_001366321 Location (UCSC) Chr 2: 42.49 – 42.76 Mb Chr 17: 84.01 – 84.13 Mb PubMed search [3] [4]
Wikidata
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Metastasis-associated protein MTA3 is a protein that in humans is encoded by the MTA3 gene.^[5][6][7][8] MTA3 protein localizes in the nucleus as well as in other cellular compartments^[9] MTA3 is a component of the nucleosome remodeling and deacetylate (NuRD) complex and participates in gene expression.^[10][11][12] The expression pattern of MTA3 is opposite to that of MTA1 and MTA2 during mammary gland tumorigenesis.^[13][14] However, MTA3 is also overexpressed in a variety of human cancers.^[15][16][17]

Mouse Mta3 was initially identified as a partial cDNA with open reading frames in screening of a mouse keratinocyte cDNA library with a human MTA1 partial fragment by My G. Mahoney's research team.^[5] The full length Mta3 cDNA was cloned through 5'-RACE methodology using RNA from C57B1/6J mouse skin.^[5] The deduced amino acids and its comparison with the sequences in the GeneBank established MTA3 as the third MTA family member.

The Mta3 is localized on chromosome 12p in mice and MTA3 on 2p21 in human. The human MTA3 gene contains 20 exons, and 19 alternative spliced transcripts. Of these, nine MTA3 transcripts are predicted to code six proteins of 392, 514, 515, 537, 590 and 594 amino acids long, two MTA3 transcripts code 18 amino acids and 91 amino acids polypeptides.^[18] The remaining 10 transcripts are non-coding RNAs. The murine Mta3 gene contains nine transcripts, six of which are predicted to code proteins ranging from 251 amino acids to 591 amino acids while one transcript codes for 40 amino acids polypeptide. The murine Mta3 gene contains two predicted non-coding RNAs.

The overall organization of MTA3 protein domains is similar to the other two family members with a BAH (Bromo-Adjacent Homology), an ELM2 (egl-27 and MTA1 homology), a SANT (SWI, ADA2, N-CoR, TFIIIB-B), a GATA-like zinc finger, and one predicted bipartite nuclear localization signal (NLS).^[5][10][17] The SH3 motif of Mta3 allows it to interact with Fyn and Grb2 – both SH3 containing signaling proteins.^[5]

Functions of MTA3 are believed to be differentially regulated in the context of cancer-types. For example, MTA3 expression is downregulated in breast cancer^[13][14] and endometrioid adenocarcinomas.^[17] MTA3 is overexpressed in non-small cell lung cancer^[15] and human placenta and chorionic carcinoma cells.^[16] In breast cancer, loss of MTA3 promotes EMT and invasiveness of breast cancer cells via upregulating Snail, which in turn represses E-cadherin adhesion molecule.^[19] In the mammary epithelium and breast cancer cells, MTA3 is an estrogen regulated gene and part of a larger regulatory network involving MTA1 and MTAs, all modifiers of hormone response, and participate in the processes involved in growth and differentiation.^{[19][20][21][22]} Accordingly, the MTA3-NuRD complex regulates the expression of Wnt4 in mammary epithelial cells and mice, and controls Wnt4-dependent ductal morphogenesis.^[23]

In contrast to its repressive actions, MTA3 also stimulates the expression of HIF1α as well as its target genes under hypoxic conditions in trophoblasts and is thought to be involved in differentiation during pregnancy.^[24] MTA3-NuRD complex and downstream targets have been shown to participate in primitive hematopoietic and angiogenesis in a zebrafish model system^[11][25] As a part of BCL6 corepressor complex, MTA3 regulates BCL6-dependent repression of target genes, including PRDM1, and modulates the differentiation of B-cells.^[26][27]

The estrogen receptor-stimulates the expression of MTA3 in breast cancer cells.^[19][20][21] The SP1 transcription factor stimulates the transcription of MTA3.^[21] MicroRNA-495 inhibits the level of MTA3 mRNA as well as the growth and migration of non-small cell lung cancer cells.^[28] The β-elemene - a traditional Chinese medicine, upregulates MTA3's expression in breast cancer cells^[29]

The MTA3-NuRD complex represses Snail, a master regulator of epithelial-to-mesenchymal transition (EMT),^[19] Wnt4 expression in mammary epithelial cells,^[23] and BCL6-corepressor target genes^[26][27] The MTA3-NuRD complex interacts with GATA3 to regulate the expression of GATA3 downstream targets.^[14] In addition, MTA3 upregulates HIF1 and its transactivation activity in hypoxic conditions.^[24]

The 2016 version of this article was updated by an external expert under a dual publication model. The corresponding academic peer reviewed article was published in Gene and can be cited as: Rakesh Kumar; Rui-An Wang (15 May 2016). "Structure, expression and functions of MTA genes". Gene. Gene Wiki Review Series. 582 (2): 112–21. doi:10.1016/J.GENE.2016.02.012. ISSN 0378-1119. PMC 4785049. PMID 26869315. Wikidata Q28273245.

• MTA3+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Overview of all the structural information available in the PDB for UniProt: Q924K8 (Mouse Metastasis-associated protein MTA3) at the PDBe-KB.