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PR01662

Identifier
MCMPROTEIN6  [View Relations]  [View Alignment]  
Accession
PR01662
No. of Motifs
5
Creation Date
20-MAR-2002
Title
Mini-chromosome maintenance (MCM) protein 6 signature
Database References
PRINTS; PR01657 MCMFAMILY
Literature References
1. KUBOTA, Y., MIMURA, S., NISHIMOTO, S., MASUDA, T., NOJIMA, H. AND TAKISAWA, H.
Licensing of DNA replication by a multi-protein complex of MCM/P1 proteins in
Xenopus eggs.
EMBO J. 16 3320-3331 (1997).
 
2. STILLMAN, B.
Initiation of chromosomal DNA replication in eukaryotes. Lessons from lambda.
J.BIOL.CHEM. 269 7047-7050 (1994).
 
3. DIFFLEY, J.F.
Once and only once upon a time: specifying and regulating origins of DNA
replication in eukaryotic cells.
GENES DEV. 10 2819-2830 (1996).
 
4. DAHMANN, C., DIFFLEY, J.F. AND NASMYTH, K.A.
S-phase-promoting cyclin-dependent kinases prevent re-replication by
inhibiting the transition of replication origins to a pre-replicative state.
CURR.BIOL. 5 1257-1269 (1995).
 
5. APARACIO, O.M., WEINSTEIN, D.M. AND BELL, S.P.
Components and dynamics of DNA replication complexes in S.cerevisiae:
redistribution of MCM proteins and Cdc45p during S phase.
CELL 91 59-69 (1997).
 
6. MACKAY, J.P. AND CROSSLEY, M.
Zinc fingers are sticking together.
TRENDS BIOCHEM.SCI. 23 1-4 (1998).

Documentation
Mini-chromosome maintenance (MCM) proteins are a family of eukaryotic
replication factors required for the initiation of DNA replication. All
eukaryotes contain six orthologous MCM proteins, designated MCM2-7. Studies 
in Xenopus eggs have showed them to form hexamers, where each class is
present in equal stoichiometry [1]. The initiation of DNA synthesis in
eukaryotes requires the binding of origin recognition complex (ORC) - a
complex of six subunits - to the autonomously replicating sequences (ARS)
of replication origins [2], the recruitment of CDC6 and binding of the MCM
protein complex to the ARS to form the prereplicative complex (pre-RC) [3].
DNA synthesis is subsequently initiated by the activation of pre-RC by CDC7
and CDC28 protein kinases [4].
 
MCM proteins associate with chromatin during G1 phase and dissociate again
during S phase, remaining unbound until the end of mitosis [5]. Periodic
chromatin association of the MCM complex ensures that DNA synthesis from 
replication origins is initiated only once during the cell cycle, avoiding
over-replication of parts of the genome. Elongation of replication forks 
away from individual replication origins results in displacement of the
MCM-containing complex from chromatin. Budding yeast MCM proteins are
translocated in and out of the nucleus during each cell cycle. However,
fission yeast MCMs, like those in metazoans, are constitutively nuclear.
 
The six classes of MCM protein together share a conserved 200 amino acid 
residue domain, while sequences within the same class show more extensive
similarity outside this region. The conserved central domain is similar to
the A motif of the Walker-type NTP-binding domain; it also shares similarity
with ATPase domains of prokaryotic NtrC-related transcription regulators. 
The ATP-binding motif is thought to mediate ATP-dependent opening of double-
stranded DNA at replication origins. In addition to the central region, MCM2,
4, 6 and 7 contain a zinc-finger-type motif thought to have a role in 
mediating protein-protein interactions [6]. Moreover, a conserved alpha-
helical structure in the C-terminal region has been noted; this comprises a
conserved heptad repeat and a putative four-helix bundle. Most of the MCM
proteins contain acidic regions, or alternately repeated clusters of acidic
and basic residues.
 
In addition to its role as a replication factor, the MCM6 protein has DNA
helicase activity when complexed as a hexamer (containing two molecules each
of MCM4, MCM6 and MCM7), suggesting that this complex is involved in the
initiation of DNA replication as a DNA-unwinding enzyme. Xenopus MCM6
exists in two forms, maternal and zygotic, suggesting that specific
forms of MCM6 may be used at different developmental stages.
 
MCMPROTEIN6 is a 5-element fingerprint that provides a signature for the
mini-chromosome maintenance (MCM) protein 6. The fingerprint was derived 
from an initial alignment of 6 sequences: the motifs were drawn from 
conserved regions spanning the full alignment length, focusing on those
sections that characterise the MCM6 proteins but distinguish them from the
rest of the MCM family. Two iterations on SPTR40_18f were required to reach
convergence, at which point a true set comprising 9 sequences was identified.
Summary Information
9 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
599999
400000
300000
200000
12345
True Positives
MCM6_CAEEL    MCM6_HUMAN    MCM6_MOUSE    MCM6_YEAST    
MIS5_SCHPO O42590 O73710 O96047
Q9V461
Sequence Titles
MCM6_CAEEL  DNA replication licensing factor MCM6 homolog - Caenorhabditis elegans. 
MCM6_HUMAN DNA replication licensing factor MCM6 (P105MCM) - Homo sapiens (Human).
MCM6_MOUSE DNA replication licensing factor MCM6 (Mis5 homolog) - Mus musculus (Mouse).
MCM6_YEAST DNA replication licensing factor MCM6 (Minichromosome maintenance protein 6) - Saccharomyces cerevisiae (Baker's yeast).
MIS5_SCHPO DNA replication licensing factor mis5 - Schizosaccharomyces pombe (Fission yeast).
O42590 MIS5P - Xenopus laevis (African clawed frog).
O73710 ZYGOTIC DNA REPLICATION FACTOR MCM6B - Xenopus laevis (African clawed frog).
O96047 MCM6 - Drosophila melanogaster (Fruit fly).
Q9V461 MCM6 PROTEIN - Drosophila melanogaster (Fruit fly).
Scan History
SPTR40_18f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
FYRVYPYLCRALK MCM6_HUMAN 83 83 -
FYRVYPYLCRALK MCM6_MOUSE 83 83 -
FYRVYPYLCRAVK O73710 84 84 -
YYHIYPFLCQSVS O96047 77 77 -
YYRVYPFMCEALH MCM6_CAEEL 77 77 -
YYRFLAFLQKGLR MCM6_YEAST 174 174 -

Motif 2 width=13
Element Seqn Id St Int Rpt
RHKIRELTSSRIG MCM6_HUMAN 120 24 -
RHKIRELTSSRIG MCM6_MOUSE 120 24 -
RHKIRELTTPRIG O73710 121 24 -
RHKVRDLTTSKIG O96047 114 24 -
KTKVRELSADKVG MCM6_CAEEL 119 29 -
VHRIRDIRSEKIG MCM6_YEAST 273 86 -

Motif 3 width=18
Element Seqn Id St Int Rpt
QQFKYTQPNICRNPVCAN MCM6_HUMAN 170 37 -
QQFKYTQPNICRNPVCAN MCM6_MOUSE 170 37 -
QQFKYTQPSICRNPVCAN O73710 171 37 -
QQFKFTNPTICRNPVCSN O96047 164 37 -
QQFRYTQPTKCANPQCMN MCM6_CAEEL 169 37 -
QSFKYTEPTFCPNPSCEN MCM6_YEAST 323 37 -

Motif 4 width=12
Element Seqn Id St Int Rpt
SLEVILRAEAVE MCM6_HUMAN 223 35 -
SLEVILRAEAVE MCM6_MOUSE 223 35 -
SVEVILRAEAVE O73710 224 35 -
AVEIILRSELVE O96047 217 35 -
TVDVIVRGEMVE MCM6_CAEEL 222 35 -
TLDVILRGDSVE MCM6_YEAST 376 35 -

Motif 5 width=22
Element Seqn Id St Int Rpt
GIRGLRALGVRDLSYRLVFLAC MCM6_HUMAN 280 45 -
GIRGLRALGVRDLSYRLVFLAC MCM6_MOUSE 280 45 -
GVQGLRALGVRDLSYKLVFLAC O73710 281 45 -
GVTGLKALGMRELNYRMAFLAC O96047 272 43 -
GITGLKALGVRDLTYKMAFLAC MCM6_CAEEL 279 45 -
GVTGLRSLGVRDLTYKISFLAC MCM6_YEAST 436 48 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
FYRVYPYLCRALK MCM6_HUMAN 83 83 -
FYRVYPYLCRALK MCM6_MOUSE 83 83 -
FYRVYPYLCRAVK O73710 84 84 -
YYRVYPHLCRAVR O42590 85 85 -
YYHIYPFLCQSVS O96047 77 77 -
YYHIYPFLCQSVS Q9V461 77 77 -
YYRFSPFLLRALQ MIS5_SCHPO 140 140 -
YYRVYPFMCEALH MCM6_CAEEL 77 77 -
YYRFLAFLQKGLR MCM6_YEAST 174 174 -

Motif 2 width=13
Element Seqn Id St Int Rpt
RHKIRELTSSRIG MCM6_HUMAN 120 24 -
RHKIRELTSSRIG MCM6_MOUSE 120 24 -
RHKIRELTTPRIG O73710 121 24 -
RQKIRELSSAKIG O42590 122 24 -
RHKVRDLTTSKIG O96047 114 24 -
RHKVRDLTTSKIG Q9V461 114 24 -
RSTIRDLRTDRIG MIS5_SCHPO 195 42 -
KTKVRELSADKVG MCM6_CAEEL 119 29 -
VHRIRDIRSEKIG MCM6_YEAST 273 86 -

Motif 3 width=18
Element Seqn Id St Int Rpt
QQFKYTQPNICRNPVCAN MCM6_HUMAN 170 37 -
QQFKYTQPNICRNPVCAN MCM6_MOUSE 170 37 -
QQFKYTQPSICRNPVCAN O73710 171 37 -
QQFRYTQPTICKNPVCAN O42590 172 37 -
QQFKFTNPTICRNPVCSN O96047 164 37 -
QQFKFTNPTICRNPVCSN Q9V461 164 37 -
QAFRYTEPTQCPNELCAN MIS5_SCHPO 245 37 -
QQFRYTQPTKCANPQCMN MCM6_CAEEL 169 37 -
QSFKYTEPTFCPNPSCEN MCM6_YEAST 323 37 -

Motif 4 width=12
Element Seqn Id St Int Rpt
SLEVILRAEAVE MCM6_HUMAN 223 35 -
SLEVILRAEAVE MCM6_MOUSE 223 35 -
SVEVILRAEAVE O73710 224 35 -
SVEIILRAEAVE O42590 225 35 -
AVEIILRSELVE O96047 217 35 -
AVEIILRSELVE Q9V461 217 35 -
TLDVILRGDIVE MIS5_SCHPO 298 35 -
TVDVIVRGEMVE MCM6_CAEEL 222 35 -
TLDVILRGDSVE MCM6_YEAST 376 35 -

Motif 5 width=22
Element Seqn Id St Int Rpt
GIRGLRALGVRDLSYRLVFLAC MCM6_HUMAN 280 45 -
GIRGLRALGVRDLSYRLVFLAC MCM6_MOUSE 280 45 -
GVQGLRALGVRDLSYKLVFLAC O73710 281 45 -
GVQGLKALGVRDLSYRLAFLAC O42590 282 45 -
GVTGLKALGMRELNYRMAFLAC O96047 272 43 -
GVTGLKALGMRELNYRMAFLAC Q9V461 272 43 -
GVTGLKSLGVRDLTYKLSFLAC MIS5_SCHPO 355 45 -
GITGLKALGVRDLTYKMAFLAC MCM6_CAEEL 279 45 -
GVTGLRSLGVRDLTYKISFLAC MCM6_YEAST 436 48 -