PROSITE documentation PDOC51912DMAP1-binding domain profile
The DNA methyltransferase 1 (DNMT1) is a multifunctional protein that is a critical DNA methyltransferase important for chromatin structure and gene silencing as well as methyltransferase-independent transcriptional repression. DNMT1 is composed of multiple functional domains. The N-terminal regulatory region contains conserved domains, including the DNA methyltransferase-associated protein 1 (DMAP1)-binding domain, the PCNA (proliferating cell nuclear antigen) binding domain (PBD) and the replication foci targeting sequence (RFTS) which control the subnuclear localization of DNMT1. In contrast, the C-terminal portion contains a catalytic domain (see <PDOC51555>). The DMAP1-binding domain is a ~120-amino acid protein-protein interaction module that binds notably DMAP1, a transcriptional co-repressor [1,2,3].
In addition to DNMT1, a DMAP1-binding domain is found in the following proteins:
- Animal disco-interacting protein 2 (DIP-2), that maintains morphology of mature neurons. DIP-2 consists of a DMAP1-binding domain and two adenylate- forming domains (AFDs) [4,5,6].
- Animal N-acetylglucosamine-1-phosphotransferase subunits α (GNPTA) and γ (GNPTG), members of a complex that catalyzes the initial step in the formation of the mannose 6-phopsphate targeting signal on newly synthesized lysosomal acid hydrolases. The DMAP1-binding domain mediates the selective binding GlcNAc-1-phosphotranferase to acid hydrolases [7,8].
The DMAP1-binding domain is predicted to adopt a long helix-turn-helix structure that is rich in leucine residues [1].
The profile we developed covers the entire DMAP1-binding domain.
Last update:January 2020 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Yoder J.A. Yen R.-W. Vertino P.M. Bestor T.H. Baylin S.B. |
| Title | New 5' regions of the murine and human genes for DNA (cytosine-5)-methyltransferase. | |
| Source | J. Biol. Chem. 271:31092-31097(1996). | |
| PubMed ID | 8940105 | |
| DOI | 10.1074/jbc.271.49.31092 |
| 2 | Authors | Rountree M.R. Bachman K.E. Baylin S.B. |
| Title | DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci. | |
| Source | Nat. Genet. 25:269-277(2000). | |
| PubMed ID | 10888872 | |
| DOI | 10.1038/77023 |
| 3 | Authors | Misaki T. Yamaguchi L. Sun J. Orii M. Nishiyama A. Nakanishi M. |
| Title | The replication foci targeting sequence (RFTS) of DNMT1 functions as a potent histone H3 binding domain regulated by autoinhibition. | |
| Source | Biochem. Biophys. Res. Commun. 470:741-747(2016). | |
| PubMed ID | 26774338 | |
| DOI | 10.1016/j.bbrc.2016.01.029 |
| 4 | Authors | Winnepenninckx B. Debacker K. Ramsay J. Smeets D. Smits A. FitzPatrick D.R. Kooy R.F. |
| Title | CGG-repeat expansion in the DIP2B gene is associated with the fragile site FRA12A on chromosome 12q13.1. | |
| Source | Am. J. Hum. Genet. 80:221-231(2007). | |
| PubMed ID | 17236128 | |
| DOI | 10.1086/510800 |
| 5 | Authors | Nitta Y. Yamazaki D. Sugie A. Hiroi M. Tabata T. |
| Title | DISCO Interacting Protein 2 regulates axonal bifurcation and guidance of Drosophila mushroom body neurons. | |
| Source | Dev. Biol. 421:233-244(2017). | |
| PubMed ID | 27908785 | |
| DOI | 10.1016/j.ydbio.2016.11.015 |
| 6 | Authors | Noblett N. Wu Z. Ding Z.H. Park S. Roenspies T. Flibotte S. Chisholm A.D. Jin Y. Colavita A. |
| Title | DIP-2 suppresses ectopic neurite sprouting and axonal regeneration in mature neurons. | |
| Source | J. Cell. Biol. 218:125-133(2019). | |
| PubMed ID | 30396999 | |
| DOI | 10.1083/jcb.201804207 |
| 7 | Authors | Qian Y. Flanagan-Steet H. van Meel E. Steet R. Kornfeld S.A. |
| Title | The DMAP interaction domain of UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase is a substrate recognition module. | |
| Source | Proc. Natl. Acad. Sci. U. S. A. 110:10246-10251(2013). | |
| PubMed ID | 23733939 | |
| DOI | 10.1073/pnas.1308453110 |
| 8 | Authors | Qian Y. van Meel E. Flanagan-Steet H. Yox A. Steet R. Kornfeld S. |
| Title | Analysis of mucolipidosis II/III GNPTAB missense mutations identifies domains of UDP-GlcNAc:lysosomal enzyme GlcNAc-1-phosphotransferase involved in catalytic function and lysosomal enzyme recognition. | |
| Source | J. Biol. Chem. 290:3045-3056(2015). | |
| PubMed ID | 25505245 | |
| DOI | 10.1074/jbc.M114.612507 |
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