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PR01661

Identifier
MCMPROTEIN5  [View Relations]  [View Alignment]  
Accession
PR01661
No. of Motifs
5
Creation Date
20-MAR-2002
Title
Mini-chromosome maintenance (MCM) protein 5 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. DAFONSECA, C.J., SHU, F. AND ZHANG, J.J.
Identification of two residues in MCM5 critical for the assembly of MCM
complexes and Stat1-mediated transcription activation in response to
IFN-gamma.
PROC.NATL.ACAD.SCI.U.S.A. 98 3034-3039 (2001).

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.
 
The human MCM5 gene has been localised to chromosome region 22q13.1-q13.2. 
It has been shown that MCM5 protein containing mutations of R732/K734 fails
to form complexes with other MCM proteins in vivo, suggesting that these two
residues are important for protein-protein interactions. MCM5 directly 
interacts with the Stat1 protein (signal transducer and activator of 
transcription) to enhance Stat1-mediated transcription activation [7].
 
MCMPROTEIN5 is a 5-element fingerrpint that provides a signature for the
mini-chromosome maintenance (MCM) protein 5. The fingerrpint was derived 
from an initial alignment of 5 sequences: the motifs were drawn from 
conserved regions spanning the full alignment length, focusing on those
sections that characterise the MCM5 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 11 sequences was identified.
A single partial match was also found, an MCM5 protein from Entamoeba
histolytica that fails to make significant matches with motifs 2, 3 and 5.
Summary Information
  11 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
51111111111
400000
300000
210010
12345
True Positives
MCM5_CAEEL    MCM5_HUMAN    MCM5_MOUSE    MCM5_XENLA    
MCM5_YEAST NDA4_SCHPO O80786 P91676
Q9BTJ4 Q9BWL8 Q9VGW6
True Positive Partials
Codes involving 2 elements
Q9U3X1
Sequence Titles
MCM5_CAEEL  DNA replication licensing factor MCM5 homolog - Caenorhabditis elegans. 
MCM5_HUMAN DNA replication licensing factor MCM5 (CDC46 homolog) (P1-CDC46) - Homo sapiens (Human).
MCM5_MOUSE DNA replication licensing factor MCM5 (CDC46 homolog) (P1-CDC46) - Mus musculus (Mouse).
MCM5_XENLA DNA replication licensing factor MCM5 (CDC46 homolog) (X.CDC46) - Xenopus laevis (African clawed frog).
MCM5_YEAST Minichromosome maintenance protein 5 (Cell division control protein 46) - Saccharomyces cerevisiae (Baker's yeast).
NDA4_SCHPO DNA replication licensing factor nda4 (Cell division control protein nda4) - Schizosaccharomyces pombe (Fission yeast).
O80786 PUTATIVE DNA REPLICATION LICENSING FACTOR, MCM5 - Arabidopsis thaliana (Mouse-ear cress).
P91676 MCM5 HOMOLOG - Drosophila melanogaster (Fruit fly).
Q9BTJ4 MINICHROMOSOME MAINTENANCE DEFICIENT (S. CEREVISIAE) 5 (CELL DIVISION CYCLE 46) - Homo sapiens (Human).
Q9BWL8 MINICHROMOSOME MAINTENANCE DEFICIENT (S. CEREVISIAE) 5 (CELL DIVISION CYCLE 46) - Homo sapiens (Human).
Q9VGW6 MCM5 PROTEIN - Drosophila melanogaster (Fruit fly).

Q9U3X1 MINICHROMOSOME MAINTENANCE 5 PROTEIN - Entamoeba histolytica.
Scan History
SPTR40_18f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
RSLKSDMMSHLVKIPG MCM5_HUMAN 138 138 -
RSLKSEQMSHLVKIPG MCM5_XENLA 139 139 -
RILKSDMMSHLVKIPG MCM5_MOUSE 138 138 -
RDLDSEHVSKIVRLSG MCM5_YEAST 149 149 -
RQVKSAQVSQVVKISG MCM5_CAEEL 138 138 -

Motif 2 width=13
Element Seqn Id St Int Rpt
KATRISIQCRSCR MCM5_HUMAN 164 10 -
KATKISIQCRSCR MCM5_XENLA 165 10 -
KATRISIQCRSCH MCM5_MOUSE 164 10 -
RATYLSIMCRNCR MCM5_YEAST 175 10 -
KATKVTLQCRQCK MCM5_CAEEL 164 10 -

Motif 3 width=13
Element Seqn Id St Int Rpt
RSSYIRVLGIQVD MCM5_HUMAN 290 113 -
RSSYIRVVGIQVD MCM5_XENLA 291 113 -
RSSYIRVLGIQVD MCM5_MOUSE 289 112 -
RTPYIKILGIQSD MCM5_YEAST 324 136 -
RTPYLRVLGIHME MCM5_CAEEL 289 112 -

Motif 4 width=16
Element Seqn Id St Int Rpt
CRVKCGPRLSAEAAEK MCM5_HUMAN 566 263 -
CRAKCGPRLSAEAAEK MCM5_XENLA 567 263 -
CRARCGPRLSAEAAEK MCM5_MOUSE 565 263 -
CRLKCAPRLSPQAAEK MCM5_YEAST 606 269 -
ARLNCGPRLTPQASEK MCM5_CAEEL 586 284 -

Motif 5 width=18
Element Seqn Id St Int Rpt
RLFQVSTLDAALSGTLSG MCM5_HUMAN 642 60 -
RLFQVSTLDAAMSGSLSG MCM5_XENLA 643 60 -
RLFQVSTLDAALSGNLSG MCM5_MOUSE 641 60 -
RLFQASTMDAASQDPIGG MCM5_YEAST 682 60 -
RLFRVSTIEAAATGNLAG MCM5_CAEEL 666 64 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
RSLKSDMMSHLVKIPG MCM5_HUMAN 138 138 -
RSLKSDMMSHLVKIPG Q9BTJ4 138 138 -
RSLKSDMMSHLVKIPG Q9BWL8 138 138 -
RSLKSEQMSHLVKIPG MCM5_XENLA 139 139 -
RILKSDMMSHLVKIPG MCM5_MOUSE 138 138 -
RQLKSDCVSKLVKIAG P91676 132 132 -
RQLKSDCVSKLVKIAG Q9VGW6 133 133 -
RDLDSEHVSKIVRLSG MCM5_YEAST 149 149 -
RQVKSAQVSQVVKISG MCM5_CAEEL 138 138 -
RNLTASHISKLVRVPG NDA4_SCHPO 133 133 -
RLLGAQYISKLVKISG O80786 135 135 -

Motif 2 width=13
Element Seqn Id St Int Rpt
KATRISIQCRSCR MCM5_HUMAN 164 10 -
KATRISIQCRSCR Q9BTJ4 164 10 -
KATRISIQCRSCR Q9BWL8 164 10 -
KATKISIQCRSCR MCM5_XENLA 165 10 -
KATRISIQCRSCH MCM5_MOUSE 164 10 -
KATRMSIQCLSCS P91676 158 10 -
KATRMSIQCLSCS Q9VGW6 159 10 -
RATYLSIMCRNCR MCM5_YEAST 175 10 -
KATKVTLQCRQCK MCM5_CAEEL 164 10 -
RATALHLVCRNCR NDA4_SCHPO 159 10 -
KATYVFLVCKNCK O80786 161 10 -

Motif 3 width=13
Element Seqn Id St Int Rpt
RSSYIRVLGIQVD MCM5_HUMAN 290 113 -
RSSYIRVLGIQVD Q9BTJ4 290 113 -
RSSYIRVLGIQVD Q9BWL8 290 113 -
RSSYIRVVGIQVD MCM5_XENLA 291 113 -
RSSYIRVLGIQVD MCM5_MOUSE 289 112 -
RAPYMRVVGITVD P91676 285 114 -
RAPYMRVVGITVD Q9VGW6 286 114 -
RTPYIKILGIQSD MCM5_YEAST 324 136 -
RTPYLRVLGIHME MCM5_CAEEL 289 112 -
RNPYIRVVGIQMD NDA4_SCHPO 282 110 -
RQPYIRVVGLEDT O80786 285 111 -

Motif 4 width=16
Element Seqn Id St Int Rpt
CRVKCGPRLSAEAAEK MCM5_HUMAN 566 263 -
CRVKCGPRLSAEAAEK Q9BTJ4 566 263 -
CRVKCGPRLSAEAAEK Q9BWL8 566 263 -
CRAKCGPRLSAEAAEK MCM5_XENLA 567 263 -
CRARCGPRLSAEAAEK MCM5_MOUSE 565 263 -
CRTHCGPRLSEAAGEK P91676 564 266 -
CRTHCGPRLSEAAGEK Q9VGW6 565 266 -
CRLKCAPRLSPQAAEK MCM5_YEAST 606 269 -
ARLNCGPRLTPQASEK MCM5_CAEEL 586 284 -
CRHKCAPNLDAEAAEK NDA4_SCHPO 559 264 -
CRARCHPRLSKDAAEN O80786 561 263 -

Motif 5 width=18
Element Seqn Id St Int Rpt
RLFQVSTLDAALSGTLSG MCM5_HUMAN 642 60 -
RLFQVSTLDAALSGTLSG Q9BTJ4 642 60 -
RLFQVSTLDAALSGTLSG Q9BWL8 642 60 -
RLFQVSTLDAAMSGSLSG MCM5_XENLA 643 60 -
RLFQVSTLDAALSGNLSG MCM5_MOUSE 641 60 -
RLFQVSTLDAAMTGSLAG P91676 640 60 -
RLFQVSTLDAAMTGSLAG Q9VGW6 641 60 -
RLFQASTMDAASQDPIGG MCM5_YEAST 682 60 -
RLFRVSTIEAAATGNLAG MCM5_CAEEL 666 64 -
RLFLTSTLAAATQSSPEV NDA4_SCHPO 635 60 -
KLFDTSTMDAARSGINQQ O80786 637 60 -