{PDOC52065}
{PS52065; MCM10_ID}
{PS52066; MCM10_CTD}
{BEGIN}
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* MCM10 internal and C-terminal domains (MCM-ID and MCM-CTD) profiles *
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Eukaryotic DNA  replication is carried out by large multiprotein machines that
coordinate DNA unwinding and synthesis at the replication fork. Minichromosome
Maintenance protein  10 (MCM10) is exclusive to eukaryotes and is essential to
both initiation  and  elongation  phases of chromosomal DNA replication. MCM10
works as  scaffold  protein  that can interact with many proteins, such as DNA
polymerase alpha  (pol  alpha) and DNA primase, some subunits of Cdc45-Mcm2-7-
GINS helicase  (CMG)  complex, and PCNA. In addition, MCM10 binds both single-
stranded (ss)  and  double-stranded (ds) DNA. MCM10 does not have a preference
for particular  DNA  sequences or topological structures, but its affinity for
ssDNA is higher than for dsDNA [1,2,3,4,5].

MCM10 is  composed  of three domains, the N-terminal (NTD), internal (ID), and
C-terminal (CTD) domains, each containing distinct functional regions involved
in DNA binding and/or protein-protein contacts. The structural integrity of ID
and CTD is dependent on the presence of bound zinc [1,2,3,4,5].

The NTD  is  common  among  MCM10  proteins  from  yeast to humans, but is not
essential and  less  well conserved than the central ID. Functionally, the NTD
contributes to   self-oligomerization   and  partner  protein  interaction.  A
conserved coiled-coil  (CC)  within  the  NTD  is  responsible for MCM10 self-
interaction [4].

The ID is the most highly conserved region of MCM10 and mediates both protein-
DNA and   protein-protein   interactions.  The  MCM10-ID  is  composed  of  an
oligonucleotide/oligosaccharide binding  (OB)-fold  followed  in  tandem  by a
variant and  highly  basic  CCCH-type zinc finger (ZnF1), which form a unified
DNA binding  platform  capable  of binding ss- and dsDNA (see <PDB:3EBE>). DNA
spans both  the  hydrophobic beta barrel of the OB-fold and the electrostatic,
extended loop  of  the  zinc finger. In addition to DNA binding motifs, the ID
contains specific   sites  that  contact  Pol  alpha,  PCNA  and  MCM2-7  (see
<PDOC00662>). Association with Pol alpha occurs via a hydrophobic patch termed
the heat  shock  protein  10  (Hsp10)-like  motif,  whereas  PCNA  binds  to a
noncanonical PCNA interacting peptide (PIP) box, QxxM/I/LxxF/YF/Y [2,4].

The MCM10-CTD, although not present in unicellular eukaryotes and land plants,
is conserved  among  metazoan  species from nematodes to humans. Functionally,
the CTD  is similar to the ID, specifically in mediating interactions with DNA
and Pol  alpha.  It contains a winged helix domain (WH) and two zinc chelating
motifs, a   CCCH   zinc-finger  (ZnF2)  and  a  CCCC  zinc-ribbon  (ZnR)  (see
<PDB:2KWQ>). ZnF2 is required for the CTD to bind DNA, but the function of the
ZnR has  not  been  clearly defined, although it shares homology with the ZnRs
found in archaeal and vertebrate MCM helicases [3,4].

The profiles  we  developed  cover  respectively the entire MCM-ID and MCM-CTD
domains.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: June 2025 / First entry.

[ 1] Robertson P.D., Warren E.M., Zhang H., Friedman D.B., Lary J.W.,
     Cole J.L., Tutter A.V., Walter J.C., Fanning E., Eichman B.F.
     "Domain architecture and biochemical characterization of vertebrate
     Mcm10."
     J. Biol. Chem. 283:3338-3348(2008).
     PubMed=18065420; DOI=10.1074/jbc.M706267200
[ 2] Warren E.M., Vaithiyalingam S., Haworth J., Greer B., Bielinsky A.-K.,
     Chazin W.J., Eichman B.F.
     "Structural basis for DNA binding by replication initiator Mcm10."
     Structure 16:1892-1901(2008).
     PubMed=19081065; DOI=10.1016/j.str.2008.10.005
[ 3] Robertson P.D., Chagot B., Chazin W.J., Eichman B.F.
     "Solution NMR structure of the C-terminal DNA binding domain of Mcm10
     reveals a  conserved MCM motif."
     J. Biol. Chem. 285:22942-22949(2010).
     PubMed=20489205; DOI=10.1074/jbc.M110.131276
[ 4] Baxley R.M., Bielinsky A.K.
     "Mcm10: A Dynamic Scaffold at Eukaryotic Replication Forks."
     Genes. (Basel). 8:0-0(2017).
     PubMed=28218679; DOI=10.3390/genes8020073
[ 5] Zhao X., Wang J., Jin D., Cheng J., Chen H., Li Z., Wang Y., Lou H.,
     Zhu J.-K., Du X., Gong Z.
     "AtMCM10 promotes DNA replication-coupled nucleosome assembly in
     Arabidopsis."
     J. Integr. Plant. Biol. 65:203-222(2023).
     PubMed=36541721; DOI=10.1111/jipb.13438

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