Alternative titles; symbols
HGNC Approved Gene Symbol: MNAT1
Cytogenetic location: 14q23.1 Genomic coordinates (GRCh38): 14:60,734,761-60,969,965 (from NCBI)
Cyclin-dependent kinases (CDKs), which play an essential role in cell cycle control of eukaryotic cells, are phosphorylated and thus activated by the CDK-activating kinase (CAK). CAK is a multisubunit protein that includes CDK7 (601955), cyclin H (CCNH; 601953), and MAT1. MAT1 (for 'menage a trois-1') is involved in the assembly of the CAK complex.
Yee et al. (1995) isolated a human MAT1 cDNA from a HeLa cell library. The cDNA encoded a 309-amino acid polypeptide with a relative mass of 35.8 kD. The human MAT1 amino acid sequence shares 95%, 79%, and 51% identity with sequences of mouse, frog, and starfish Mat1, respectively. Within the zinc-binding RING finger region, the sequences of all 4 species are nearly identical. Northern blot analysis revealed that the human MAT1 gene expressed varied levels of a 1.6-kb transcript in many tissues and cell lines.
It has been proposed that the CDK7-cyclin H complex functions in cell cycle progression, basal transcription, and DNA repair. Tassan et al. (1995) reported that in vitro reconstitution of an active CDK7-cyclin H complex requires stoichiometric amounts of MNAT1, which they called MAT1. They purified the MAT1 protein and cloned a MAT1 cDNA. The predicted MAT1 protein contains a putative zinc-binding domain, namely a C3HC4 RING finger, in the N terminus; however, this domain was not required for ternary complex formation with CDK7-cyclin H. MAT1 was associated with nuclear CDK7-cyclin H at all stages of the cell cycle in vivo.
Tassan et al. (1995) showed that ternary complexes of CDK7, cyclin H, and MAT1 displayed kinase activity towards substrates mimicking both the T loop in CDKs and the C-terminal domain of RNA polymerase II, regardless of whether they were immunoprecipitated from HeLa cells or reconstituted in a reticulocyte lysate.
Talukder et al. (2003) determined that MAT1 interacts with MTA1 (603526) both in vitro and in vivo. The N-terminal ring finger domain of MAT1 bound to the C-terminal GATA domain and the N-terminal bromodomain of MTA1. MAT1 also interacted with the activation function-2 domain of the estrogen receptor (ER; see 133430), colocalized with ER, and underwent nuclear translocation in a breast cancer cell line upon estrogen activation. Talukder et al. (2003) found that MTA1 deregulation in breast cancer cells led to its interaction with CAK, ER, and HDAC2 (605164). They concluded that the transactivation function of ER might be influenced by the regulatory interactions between CAK and MTA1 in breast cancer cells.
Giglia-Mari et al. (2004) tabulated the 10 subunits of general transcription factor IIH (TFIIH). They referred to MAT1 as the seventh subunit and the homolog of TFB3 in yeast.
Eki et al. (1998) used somatic cell hybrid panels, fluorescence in situ hybridization, and YAC contigs to map the human MAT1 gene to chromosome 14q23.
Eki, T., Okumura, K., Abe, M., Kagotani, K., Taguchi, H., Murakami, Y., Pan, Z.-Q., Hanaoka, F. Mapping of the human genes encoding cyclin H (CCNH) and the CDK-activating kinase (CAK) assembly factor MAT1 (MNAT1) to chromosome bands 5q13.3-q14 and 14q23, respectively. Genomics 47: 115-120, 1998. [PubMed: 9465303] [Full Text: https://doi.org/10.1006/geno.1997.5053]
Giglia-Mari, G., Coin, F., Ranish, J. A., Hoogstraten, D., Theil, A., Wijgers, N., Jaspers, N. G. J., Raams, A., Argentini, M., van der Spek, P. J., Botta, E., Stefanini, M., Egly, J.-M., Aebersold, R., Hoeijmakers, J. H. J., Vermeulen, W. A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A. Nature Genet. 36: 714-719, 2004. [PubMed: 15220921] [Full Text: https://doi.org/10.1038/ng1387]
Talukder, A. H., Mishra, S. K., Mandal, M., Balasenthil, S., Mehta, S., Sahin, A. A., Barnes, C. J., Kumar, R. MTA1 interacts with MAT1, a cyclin-dependent kinase-activating kinase complex ring finger factor, and regulates estrogen receptor transactivation functions. J. Biol. Chem. 278: 11676-11685, 2003. [PubMed: 12527756] [Full Text: https://doi.org/10.1074/jbc.M209570200]
Tassan, J.-P., Jaquenoud, M., Fry, A. M., Frutiger, S., Hughes, G. J., Nigg, E. A. In vitro assembly of a functional human CDK7-cyclin H complex requires MAT1, a novel 36 kDa RING finger protein. EMBO J. 14: 5608-5617, 1995. [PubMed: 8521818] [Full Text: https://doi.org/10.1002/j.1460-2075.1995.tb00248.x]
Yee, A., Nichols, M. A., Wu, L., Hall, F. L., Kobayashi, R., Xiong, Y. Molecular cloning of CDK7-associated human MAT1, a cyclin-dependent kinase-activating kinase (CAK) assembly factor. Cancer Res. 55: 6058-6062, 1995. [PubMed: 8521393]