{PDOC51912}
{PS51912; DMAP1_BIND}
{BEGIN}
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* DMAP1-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 alpha (GNPTA) and
   gamma (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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: January 2020 / First entry.

[ 1] Yoder J.A., Yen R.-W., Vertino P.M., Bestor T.H., Baylin S.B.
     "New 5' regions of the murine and human genes for DNA
     (cytosine-5)-methyltransferase."
     J. Biol. Chem. 271:31092-31097(1996).
     PubMed=8940105; DOI=10.1074/jbc.271.49.31092
[ 2] Rountree M.R., Bachman K.E., Baylin S.B.
     "DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at
     replication foci."
     Nat. Genet. 25:269-277(2000).
     PubMed=10888872; DOI=10.1038/77023
[ 3] Misaki T., Yamaguchi L., Sun J., Orii M., Nishiyama A., Nakanishi M.
     "The replication foci targeting sequence (RFTS) of DNMT1 functions as
     a potent histone H3 binding domain regulated by autoinhibition."
     Biochem. Biophys. Res. Commun. 470:741-747(2016).
     PubMed=26774338; DOI=10.1016/j.bbrc.2016.01.029
[ 4] Winnepenninckx B., Debacker K., Ramsay J., Smeets D., Smits A.,
     FitzPatrick D.R., Kooy R.F.
     "CGG-repeat expansion in the DIP2B gene is associated with the fragile
     site FRA12A on chromosome 12q13.1."
     Am. J. Hum. Genet. 80:221-231(2007).
     PubMed=17236128; DOI=10.1086/510800
[ 5] Nitta Y., Yamazaki D., Sugie A., Hiroi M., Tabata T.
     "DISCO Interacting Protein 2 regulates axonal bifurcation and guidance
     of Drosophila mushroom body neurons."
     Dev. Biol. 421:233-244(2017).
     PubMed=27908785; DOI=10.1016/j.ydbio.2016.11.015
[ 6] Noblett N., Wu Z., Ding Z.H., Park S., Roenspies T., Flibotte S.,
     Chisholm A.D., Jin Y., Colavita A.
     "DIP-2 suppresses ectopic neurite sprouting and axonal regeneration in
     mature neurons."
     J. Cell. Biol. 218:125-133(2019).
     PubMed=30396999; DOI=10.1083/jcb.201804207
[ 7] Qian Y., Flanagan-Steet H., van Meel E., Steet R., Kornfeld S.A.
     "The DMAP interaction domain of UDP-GlcNAc:lysosomal enzyme
     N-acetylglucosamine-1-phosphotransferase is a substrate recognition
     module."
     Proc. Natl. Acad. Sci. U. S. A. 110:10246-10251(2013).
     PubMed=23733939; DOI=10.1073/pnas.1308453110
[ 8] Qian Y., van Meel E., Flanagan-Steet H., Yox A., Steet R.,
     Kornfeld S.
     "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."
     J. Biol. Chem. 290:3045-3056(2015).
     PubMed=25505245; DOI=10.1074/jbc.M114.612507

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