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PR01663

Identifier
MCMPROTEIN7  [View Relations]  [View Alignment]  
Accession
PR01663
No. of Motifs
5
Creation Date
21-MAR-2002
Title
Mini-chromosome maintenance (MCM) protein 7 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. SHOHET, J.M., HICKS, M.J., PLON, S.E., BURLINGAME, S.M., STUART, S.,
CHEN, S.Y., BRENNER, M.K. AND NUCHTERN, J.G.
Minichromosome maintenance protein MCM7 is a direct target of the MYCN
transcription factor in neuroblastoma.
CANCER RES. 62 1123-1128 (2002).
 
8. STERNER, J.M., DEW-KNIGHT, S., MUSAHL, C., KORNBLUTH, S. AND HOROWITZ, J.M.
Negative regulation of DNA replication by the retinoblastoma protein is
mediated by its association with MCM7.
MOL.CELL BIOL. 18 2748-2757 (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 MCM7 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. The human MCM7 gene
has been localised to chromosome 7q21.3-q22.1. Increased expression of MCM7
RNA and protein in MYCN-amplified neuroblastoma tumour and cell lines has
been reported [7]. Furthermore, The MCM7 protein has been shown to form
complexes with the retinoblastoma protein [8]. These findings suggest MCM7-
directed DNA replication contributes to neoplastic transformation.
 
MCMPROTEIN7 is a 5-element fingerprint that provides a signature for the
mini-chromosome maintenance (MCM) protein 7. The fingerprint 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 MCM7 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. 
Two partial matches were also found, both of which are putative family
members that fail to make significant matches with motifs 2, 3 and 5. 
Summary Information
  12 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
2 codes involving 2 elements
Composite Feature Index
51212121212
400000
300000
220020
12345
True Positives
CC47_YEAST    MCM7_HUMAN    MCM7_MOUSE    MCM7_SCHPO    
MCM7_XENLA O04721 O16297 O42591
O42592 P91674 PROL_ARATH Q9XYU0
True Positive Partials
Codes involving 2 elements
Q9U1E0 Q9U9L0
Sequence Titles
CC47_YEAST  DNA replication licensing factor CDC47 (Cell division control protein 47) - Saccharomyces cerevisiae (Baker's yeast). 
MCM7_HUMAN DNA replication licensing factor MCM7 (CDC47 homolog) (P1.1-MCM3) - Homo sapiens (Human).
MCM7_MOUSE DNA replication licensing factor MCM7 (CDC47 homolog) - Mus musculus (Mouse).
MCM7_SCHPO DNA replication licensing factor mcm7 (Minichromosome maintenance protein 7) - Schizosaccharomyces pombe (Fission yeast).
MCM7_XENLA DNA replication licensing factor MCM7 (CDC47 homolog) (X.MCM7) - Xenopus laevis (African clawed frog).
O04721 AGAA.2, PROLIFERA - Arabidopsis thaliana (Mouse-ear cress).
O16297 F32D1.10 PROTEIN - Caenorhabditis elegans.
O42591 CDC47P - Xenopus laevis (African clawed frog).
O42592 CDC47-2P - Xenopus laevis (African clawed frog).
P91674 MCM7 (MCM HOMOLOG) - Drosophila melanogaster (Fruit fly).
PROL_ARATH Prolifera protein - Arabidopsis thaliana (Mouse-ear cress).
Q9XYU0 MCM7 PROTEIN - Drosophila melanogaster (Fruit fly).

Q9U1E0 DNA REPLICATION LICENSING FACTOR (CDC47 HOMOLOG) - Leishmania major.
Q9U9L0 PUTATIVE DNA REPLICATION PROTEIN CDC47 - Trypanosoma brucei.
Scan History
SPTR40_18f 2  150  NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
YPSELMRRFELYF MCM7_MOUSE 126 126 -
YPPELMRRFELYF MCM7_XENLA 125 125 -
YPAELMRRFELYF MCM7_HUMAN 126 126 -
FPPELTRGYDLYF MCM7_SCHPO 146 146 -
YPPQLLQRFEVYF O16297 139 139 -

Motif 2 width=12
Element Seqn Id St Int Rpt
RGIVTRVSEVKP MCM7_MOUSE 164 25 -
RGIVTRVTEVKP MCM7_XENLA 163 25 -
RGIVTRVSEVKP MCM7_HUMAN 164 25 -
RGIVTRTSDVKP MCM7_SCHPO 185 26 -
KGVVIRATEVKP O16297 177 25 -

Motif 3 width=12
Element Seqn Id St Int Rpt
YTCDQCGAETYQ MCM7_MOUSE 182 6 -
YTCDQCGAETYQ MCM7_XENLA 181 6 -
YTCDQCGAETYQ MCM7_HUMAN 182 6 -
YTCDRCGYEVFQ MCM7_SCHPO 203 6 -
YTCDTCAAEVYQ O16297 195 6 -

Motif 4 width=13
Element Seqn Id St Int Rpt
TFMPLIMCPSQEC MCM7_MOUSE 199 5 -
TFMPLIMCPSREC MCM7_XENLA 198 5 -
TFMPLIMCPSQEC MCM7_HUMAN 199 5 -
TFLPMSECPSDEC MCM7_SCHPO 220 5 -
QFTPPVNCPNKEC O16297 212 5 -

Motif 5 width=11
Element Seqn Id St Int Rpt
GLLSETYLEAH MCM7_MOUSE 291 79 -
GLLSETYLECH MCM7_XENLA 290 79 -
GLLSETYLEAH MCM7_HUMAN 291 79 -
GLLTDTYLECH MCM7_SCHPO 312 79 -
GLVADTYLEAH O16297 303 78 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
YPSELMRRFELYF MCM7_MOUSE 126 126 -
YPPELMRRFELYF MCM7_XENLA 125 125 -
YPPELMRRFELYF O42591 125 125 -
YPAELMRRFELYF MCM7_HUMAN 126 126 -
YPPELMRRFELYF O42592 125 125 -
FPSELMKRFEVGF P91674 126 126 -
FPSELMKRFEVGF Q9XYU0 126 126 -
FPPELTRGYDLYF MCM7_SCHPO 146 146 -
FPPNLTRRYFLYF CC47_YEAST 192 192 -
IPSEIKRYYEVYF O04721 120 120 -
IPSEIKRYYEVYF PROL_ARATH 120 120 -
YPPQLLQRFEVYF O16297 139 139 -

Motif 2 width=12
Element Seqn Id St Int Rpt
RGIVTRVSEVKP MCM7_MOUSE 164 25 -
RGIVTRVTEVKP MCM7_XENLA 163 25 -
RGIVTRVTEVKP O42591 163 25 -
RGIVTRVSEVKP MCM7_HUMAN 164 25 -
RGIVTRVTEVKP O42592 163 25 -
RGIVTRCTEVKP P91674 164 25 -
RGIVTRCTEVKP Q9XYU0 164 25 -
RGIVTRTSDVKP MCM7_SCHPO 185 26 -
RGIITRVSDVKP CC47_YEAST 242 37 -
SGIVTRCSDVKP O04721 158 25 -
SGIVTRCSDVKP PROL_ARATH 158 25 -
KGVVIRATEVKP O16297 177 25 -

Motif 3 width=12
Element Seqn Id St Int Rpt
YTCDQCGAETYQ MCM7_MOUSE 182 6 -
YTCDQCGAETYQ MCM7_XENLA 181 6 -
YTCDQCGAETYQ O42591 181 6 -
YTCDQCGAETYQ MCM7_HUMAN 182 6 -
YTCDQCGAETYQ O42592 181 6 -
YTCDRCGSETYQ P91674 182 6 -
YTCDRCGSETYQ Q9XYU0 182 6 -
YTCDRCGYEVFQ MCM7_SCHPO 203 6 -
YTCDQCGYEVFQ CC47_YEAST 260 6 -
YTCEDCGHEIYQ O04721 176 6 -
YTCEDCGHEIYQ PROL_ARATH 176 6 -
YTCDTCAAEVYQ O16297 195 6 -

Motif 4 width=13
Element Seqn Id St Int Rpt
TFMPLIMCPSQEC MCM7_MOUSE 199 5 -
TFMPLIMCPSREC MCM7_XENLA 198 5 -
TFMPLIMCPSREC O42591 198 5 -
TFMPLIMCPSQEC MCM7_HUMAN 199 5 -
TFMPLIMCPSREC O42592 198 5 -
SFTPVHDCPSDDC P91674 199 5 -
SFTPVHDCPSDDC Q9XYU0 199 5 -
TFLPMSECPSDEC MCM7_SCHPO 220 5 -
TFTPLSECTSEEC CC47_YEAST 277 5 -
VFMPLFKCPSSRC O04721 193 5 -
VFMPLFKCPSSRC PROL_ARATH 193 5 -
QFTPPVNCPNKEC O16297 212 5 -

Motif 5 width=11
Element Seqn Id St Int Rpt
GLLSETYLEAH MCM7_MOUSE 291 79 -
GLLSETYLECH MCM7_XENLA 290 79 -
GLLSETYLECH O42591 290 79 -
GLLSETYLEAH MCM7_HUMAN 291 79 -
GLLSETYLESH O42592 290 79 -
GLLSETFLQAH P91674 289 77 -
GLLSETFLQAH Q9XYU0 291 79 -
GLLTDTYLECH MCM7_SCHPO 312 79 -
GLLTETYLEAQ CC47_YEAST 369 79 -
GLVADTYLEAT O04721 285 79 -
GLVADTYLEAT PROL_ARATH 285 79 -
GLVADTYLEAH O16297 303 78 -