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PR01660

Identifier
MCMPROTEIN4  [View Relations]  [View Alignment]  
Accession
PR01660
No. of Motifs
5
Creation Date
20-MAR-2002
Title
Mini-chromosome maintenance (MCM) protein 4 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).
 
7. HENDRICKSON, M., MADINE, M., DALTON, S. AND GAUTIER, J.
Phosphorylation of MCM4 by cdc2 protein kinase inhibits the activity of the
minichromosome maintenance complex.
PROC.NATL.ACAD.SCI.U.S.A. 93 12223-12228 (1996).

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.
 
MCM4 is thought to play a pivotal role in ensuring DNA replication occurs
only once per cell cycle. Phosphorylation of MCM4 dramatically reduces its
affinity for chromatin - it has been proposed that this cell cycle-dependent
phosphorylation is the mechanism that inactivates the MCM complex from late
S phase through mitosis, thus preventing illegitimate DNA replication during
that period of the cell cycle [7].
 
MCMPROTEIN4 is a 5-element fingerprint that provides a signature for the
mini-chromosome maintenance (MCM) protein 4. 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 MCM4 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 12 sequences was identified.
Summary Information
12 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
51212121212
400000
300000
200000
12345
True Positives
CC21_SCHPO    CC54_YEAST    MCM4_DROME    MCM4_HUMAN    
MCM4_MOUSE MCM4_XENLA O42589 Q9D077
Q9GR06 Q9SIV8 Q9U118 Q9V4M5
Sequence Titles
CC21_SCHPO  Cdc21 protein - Schizosaccharomyces pombe (Fission yeast). 
CC54_YEAST Cell division control protein 54 - Saccharomyces cerevisiae (Baker's yeast).
MCM4_DROME DNA replication licensing factor MCM4 (Disc proliferation abnormal protein) - Drosophila melanogaster (Fruit fly).
MCM4_HUMAN DNA replication licensing factor MCM4 (CDC21 homolog) (P1-CDC21) - Homo sapiens (Human).
MCM4_MOUSE DNA replication licensing factor MCM4 (CDC21 homolog) (P1-CDC21) - Mus musculus (Mouse).
MCM4_XENLA DNA replication licensing factor MCM4 (CDC21 homolog) (P1-CDC21) (X.MCM4) - Xenopus laevis (African clawed frog).
O42589 CDC21P - Xenopus laevis (African clawed frog).
Q9D077 MINI CHROMOSOME MAINTENANCE DEFICIENT 4 HOMOLOG (S. CEREVISIAE) - Mus musculus (Mouse).
Q9GR06 DNA REPLICATION LICENSING FACTOR MCM4 - Plasmodium falciparum.
Q9SIV8 PUTATIVE CDC21 PROTEIN - Arabidopsis thaliana (Mouse-ear cress).
Q9U118 POSSIBLE DNA REPLICATION LICENSING FACTOR MCM4 - Leishmania major.
Q9V4M5 DPA PROTEIN - Drosophila melanogaster (Fruit fly).
Scan History
SPTR40_18f 2  30   NSINGLE    
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
SQIIPEMQEAFFKC MCM4_XENLA 293 293 -
SQLIPEMQEAFFQC MCM4_HUMAN 293 293 -
SQLIPEMQEAFFQC MCM4_MOUSE 292 292 -
SNVIPEMREAFFSC MCM4_DROME 296 296 -
SKIVPEIRVACFQC Q9U118 273 273 -
SNIIPEMTMAAFKC Q9GR06 316 316 -

Motif 2 width=13
Element Seqn Id St Int Rpt
HNRSMFSDKQMIK MCM4_XENLA 341 34 -
HNRSLFSDKQMIK MCM4_HUMAN 341 34 -
HNRSFFSDKQMIK MCM4_MOUSE 340 34 -
HNRSEFTDKQLVK MCM4_DROME 344 34 -
HNLSLYEDKQLIK Q9U118 322 35 -
HNNCCFSSKQLIK Q9GR06 375 45 -

Motif 3 width=12
Element Seqn Id St Int Rpt
EDIKKGILLQLF MCM4_XENLA 474 120 -
EDIKKGILLQLF MCM4_HUMAN 474 120 -
EDIKKGILLQLF MCM4_MOUSE 473 120 -
DDIKKGILLQLF MCM4_DROME 476 119 -
DDVKRGILAQLF Q9U118 486 151 -
GDIKKGLLCQLF Q9GR06 532 144 -

Motif 4 width=18
Element Seqn Id St Int Rpt
SQWNPKKTTIENIQLPHT MCM4_XENLA 622 136 -
SQWNPKKTTIENIQLPHT MCM4_HUMAN 622 136 -
SQWNPKKTTIENIQLPHT MCM4_MOUSE 621 136 -
SQWNKRKNIIDNVQLPHT MCM4_DROME 624 136 -
SQWNAQLNVVENLQIEPT Q9U118 647 149 -
SRYDKNKAVVENINLPPS Q9GR06 678 134 -

Motif 5 width=10
Element Seqn Id St Int Rpt
KQSATDPRTG MCM4_XENLA 770 130 -
KQSATDPRTG MCM4_HUMAN 770 130 -
KQSATDPRTG MCM4_MOUSE 769 130 -
KQSATDPLSG MCM4_DROME 772 130 -
KKAATDPTTG Q9U118 880 215 -
FQSLIDPLSG Q9GR06 909 213 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
SQIIPEMQEAFFKC MCM4_XENLA 293 293 -
SQLIPEMQEAFFQC MCM4_HUMAN 293 293 -
SQLIPEMQEAFFQC MCM4_MOUSE 292 292 -
SQLIPEMQEAFFQC Q9D077 292 292 -
SQIIPEMQESFFKC O42589 288 288 -
SNVIPEMREAFFSC MCM4_DROME 296 296 -
SNVIPEMREAFFSC Q9V4M5 296 296 -
TPVIPDMKVAFFKC CC54_YEAST 336 336 -
TPVIPDMKQAFFRC CC21_SCHPO 313 313 -
SSIIPEIREAVFRC Q9SIV8 161 161 -
SKIVPEIRVACFQC Q9U118 273 273 -
SNIIPEMTMAAFKC Q9GR06 316 316 -

Motif 2 width=13
Element Seqn Id St Int Rpt
HNRSMFSDKQMIK MCM4_XENLA 341 34 -
HNRSLFSDKQMIK MCM4_HUMAN 341 34 -
HNRSFFSDKQMIK MCM4_MOUSE 340 34 -
HNRSFFSDKQMIK Q9D077 340 34 -
HNRSMFSDKQMIK O42589 336 34 -
HNRSEFTDKQLVK MCM4_DROME 344 34 -
HNRSEFTDKQLVK Q9V4M5 344 34 -
HNRCSFADKQVIK CC54_YEAST 386 36 -
HNRSEFADKQVIK CC21_SCHPO 363 36 -
HNRCRFADKQIVR Q9SIV8 212 37 -
HNLSLYEDKQLIK Q9U118 322 35 -
HNNCCFSSKQLIK Q9GR06 375 45 -

Motif 3 width=12
Element Seqn Id St Int Rpt
EDIKKGILLQLF MCM4_XENLA 474 120 -
EDIKKGILLQLF MCM4_HUMAN 474 120 -
EDIKKGILLQLF MCM4_MOUSE 473 120 -
EDIKKGILLQLF Q9D077 473 120 -
EDIKKGILLQLF O42589 469 120 -
DDIKKGILLQLF MCM4_DROME 476 119 -
DDIKKGILLQLF Q9V4M5 476 119 -
EDVKKGILLQLF CC54_YEAST 534 135 -
DDVKKGLLLQLF CC21_SCHPO 509 133 -
DDVKKGLLCQLF Q9SIV8 347 122 -
DDVKRGILAQLF Q9U118 486 151 -
GDIKKGLLCQLF Q9GR06 532 144 -

Motif 4 width=18
Element Seqn Id St Int Rpt
SQWNPKKTTIENIQLPHT MCM4_XENLA 622 136 -
SQWNPKKTTIENIQLPHT MCM4_HUMAN 622 136 -
SQWNPKKTTIENIQLPHT MCM4_MOUSE 621 136 -
SQWNPKKTTIENIQLPHT Q9D077 621 136 -
SQWNPKKTTIENIQLPHT O42589 617 136 -
SQWNKRKNIIDNVQLPHT MCM4_DROME 624 136 -
SQWNKRKNIIDNVQLPHT Q9V4M5 624 136 -
SRYNPNLPVTENIDLPPP CC54_YEAST 680 134 -
SKYNPDLPVTKNIDLPPT CC21_SCHPO 657 136 -
SRYNPRLSVIENIHLPPT Q9SIV8 493 134 -
SQWNAQLNVVENLQIEPT Q9U118 647 149 -
SRYDKNKAVVENINLPPS Q9GR06 678 134 -

Motif 5 width=10
Element Seqn Id St Int Rpt
KQSATDPRTG MCM4_XENLA 770 130 -
KQSATDPRTG MCM4_HUMAN 770 130 -
KQSATDPRTG MCM4_MOUSE 769 130 -
KQSATDPRTG Q9D077 769 130 -
KQSATDPRTG O42589 765 130 -
KQSATDPLSG MCM4_DROME 772 130 -
KQSATDPLSG Q9V4M5 772 130 -
KDYATDPKTG CC54_YEAST 834 136 -
KDYATDPATG CC21_SCHPO 811 136 -
QQSATDHATG Q9SIV8 645 134 -
KKAATDPTTG Q9U118 880 215 -
FQSLIDPLSG Q9GR06 909 213 -