| 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).
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| 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.
MCMFAMILY is a 5-element fingerprint that provides a signature for the mini-
chromosome maintenance (MCM) protein family. The fingerprint was derived
from an initial alignment of 12 sequences: the motifs were drawn from
conserved regions spanning the central portion of the alignment - motif 1
encompasses a potential ATP-binding site. Two iterations on SPTR40_18f were
required to reach convergence, at which point a true set comprising 93
sequences was identified. Two partial matches were also found, both family
members that fail to make significant matches with two or more motifs.
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| Sequence Titles | CC19_SCHPO DNA replication licensing factor cdc19 (Cell division control protein 19) - Schizosaccharomyces pombe (Fission yeast).
CC21_SCHPO Cdc21 protein - Schizosaccharomyces pombe (Fission yeast).
CC47_YEAST DNA replication licensing factor CDC47 (Cell division control protein 47) - Saccharomyces cerevisiae (Baker's yeast).
CC54_YEAST Cell division control protein 54 - Saccharomyces cerevisiae (Baker's yeast).
MCM2_DROME DNA replication licensing factor MCM2 - Drosophila melanogaster (Fruit fly).
MCM2_HUMAN DNA replication licensing factor MCM2 (Nuclear protein BM28) - Homo sapiens (Human).
MCM2_MOUSE DNA replication licensing factor MCM2 - Mus musculus (Mouse).
MCM2_XENLA DNA replication licensing factor MCM2 (X.MCM2) - Xenopus laevis (African clawed frog).
MCM2_YEAST DNA replication licensing factor MCM2 (Minichromosome maintenance protein 2) - Saccharomyces cerevisiae (Baker's yeast).
MCM3_ENTHI DNA replication licensing factor MCM3 - Entamoeba histolytica.
MCM3_HUMAN DNA replication licensing factor MCM3 (DNA polymerase alpha holoenzyme-associated protein P1) (RLF beta subunit) (P102 protein) (P1-MCM3) - Homo sapiens (Human).
MCM3_MOUSE DNA replication licensing factor MCM3 (DNA polymerase alpha holoenzyme-associated protein P1) (P1-MCM3) - Mus musculus (Mouse).
MCM3_SCHPO DNA replication licensing factor mcm3 (Minichromosome maintenance protein 3) - Schizosaccharomyces pombe (Fission yeast).
MCM3_XENLA DNA replication licensing factor MCM3 (X.MCM3) (P1 homolog) (P100) - Xenopus laevis (African clawed frog).
MCM3_YEAST DNA replication licensing factor MCM3 (Minichromosome maintenance protein 3) - 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).
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).
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).
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).
MIS5_SCHPO DNA replication licensing factor mis5 - Schizosaccharomyces pombe (Fission yeast).
NDA4_SCHPO DNA replication licensing factor nda4 (Cell division control protein nda4) - Schizosaccharomyces pombe (Fission yeast).
O04721 AGAA.2, PROLIFERA - Arabidopsis thaliana (Mouse-ear cress).
O08971 BM28 HOMOLOGUE - Mus musculus (Mouse).
O16297 F32D1.10 PROTEIN - Caenorhabditis elegans.
O27798 DNA REPLICATION INITIATOR (CDC21/CDC54) - Methanothermobacter thermautotrophicus.
O29733 CELL DIVISION CONTROL PROTEIN 21 (CDC21) - Archaeoglobus fulgidus.
O42588 MCM2P - Xenopus laevis (African clawed frog).
O42589 CDC21P - Xenopus laevis (African clawed frog).
O42590 MIS5P - Xenopus laevis (African clawed frog).
O42591 CDC47P - Xenopus laevis (African clawed frog).
O42592 CDC47-2P - Xenopus laevis (African clawed frog).
O42723 DNA REPLICATION LICENSING FACTOR - Emericella nidulans (Aspergillus nidulans).
O58310 1108AA LONG HYPOTHETICAL CELL DIVISION CONTROL PROTEIN - Pyrococcus horikoshii.
O65400 MCM3 HOMOLOG - Arabidopsis thaliana (Mouse-ear cress).
O73710 ZYGOTIC DNA REPLICATION FACTOR MCM6B - Xenopus laevis (African clawed frog).
O80786 PUTATIVE DNA REPLICATION LICENSING FACTOR, MCM5 - Arabidopsis thaliana (Mouse-ear cress).
O96047 MCM6 - Drosophila melanogaster (Fruit fly).
P87376 B24 PROTEIN - Triturus carnifex (Italian newt).
P91674 MCM7 (MCM HOMOLOG) - Drosophila melanogaster (Fruit fly).
P91675 MCM3 (MCM HOMOLOG) - Drosophila melanogaster (Fruit fly).
P91676 MCM5 HOMOLOG - Drosophila melanogaster (Fruit fly).
PROL_ARATH Prolifera protein - Arabidopsis thaliana (Mouse-ear cress).
Q979U9 DNA REPLICATION INITIATOR - Thermoplasma volcanium.
Q9BRM7 SIMILAR TO MINI CHROMOSOME MAINTENANCE DEFICIENT 2 (S. CEREVISIAE) - Homo sapiens (Human).
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).
Q9CWV1 5730432L01RIK PROTEIN - Mus musculus (Mouse).
Q9D077 MINI CHROMOSOME MAINTENANCE DEFICIENT 4 HOMOLOG (S. CEREVISIAE) - Mus musculus (Mouse).
Q9FL33 MCM3 HOMOLOG - Arabidopsis thaliana (Mouse-ear cress).
Q9GR05 DNA REPLICATION LICENSING FACTOR MCM2 - Plasmodium falciparum.
Q9GR06 DNA REPLICATION LICENSING FACTOR MCM4 - Plasmodium falciparum.
Q9H4N9 CLONE CDABP0042 MRNA SEQUENCE - Homo sapiens (Human).
Q9HK10 DNA REPLICATION LICENSING FACTOR MCM RELATED PROTEIN - Thermoplasma acidophilum.
Q9HNA5 MCM / CELL DIVISION CONTROL PROTEIN 21 - Halobacterium sp. (strain NRC-1).
Q9LPD9 T12C22.19 PROTEIN - Arabidopsis thaliana (Mouse-ear cress).
Q9NE40 POSSIBLE MINICHROMOSOME MAINTENANCE PROTEIN - Leishmania major.
Q9NUE7 DJ108C2.1 (MINICHROMOSOME MAINTENANCE DEFICIENT (S. CEREVISIAE) 3 (DNA REPLICATION LICENSING FACTOR, DNA POLYMERASE ALPHA HOLOENZYME- ASSOCIATED PROTEIN P1, RLF BETA SUBUNIT)) - Homo sapiens (Human).
Q9SF37 PUTATIVE MINICHROMOSOME MAINTENANCE (MCM) PROTEIN - Arabidopsis thaliana (Mouse-ear cress).
Q9SIV8 PUTATIVE CDC21 PROTEIN - Arabidopsis thaliana (Mouse-ear cress).
Q9SX03 REPLICATION ORIGIN ACTIVATOR 3 - Zea mays (Maize).
Q9SX04 REPLICATION ORIGIN ACTIVATOR 2 - Zea mays (Maize).
Q9U118 POSSIBLE DNA REPLICATION LICENSING FACTOR MCM4 - Leishmania major.
Q9U1E0 DNA REPLICATION LICENSING FACTOR (CDC47 HOMOLOG) - Leishmania major.
Q9U3X1 MINICHROMOSOME MAINTENANCE 5 PROTEIN - Entamoeba histolytica.
Q9U446 MINICHROMOSOME MAINTENANCE PROTEIN 2 HOMOLOG - Entamoeba histolytica.
Q9U9L0 PUTATIVE DNA REPLICATION PROTEIN CDC47 - Trypanosoma brucei.
Q9UJA3 DJ967N21.5 (NOVEL MCM2/3/5 FAMILY MEMBER) - Homo sapiens (Human).
Q9UXG1 MINICHROMOSOME MAINTENANCE (MCM) PROTEIN (MINICHROMOSOME MAINTENANCE PROTEIN MCM) - Sulfolobus solfataricus.
Q9UYR7 CELL DIVISION CONTROL PROTEIN - Pyrococcus abyssi.
Q9V461 MCM6 PROTEIN - Drosophila melanogaster (Fruit fly).
Q9V4M5 DPA PROTEIN - Drosophila melanogaster (Fruit fly).
Q9VGW6 MCM5 PROTEIN - Drosophila melanogaster (Fruit fly).
Q9XVR7 C25D7.6 PROTEIN - Caenorhabditis elegans.
Q9XXI9 Y17G7B.5 PROTEIN - Caenorhabditis elegans.
Q9XYU0 MCM7 PROTEIN - Drosophila melanogaster (Fruit fly).
Q9XYU1 MCM3 PROTEIN - Drosophila melanogaster (Fruit fly).
Q9YFR1 699AA LONG HYPOTHETICAL DNA REPLICATION LICENSING FACTOR MCM - Aeropyrum pernix.
Y363_METJA Hypothetical MCM-type protein MJ0363 - Methanococcus jannaschii.
Y961_METJA Hypothetical MCM-type protein MJ0961 - Methanococcus jannaschii.
YE89_METJA Hypothetical MCM-type protein MJ1489 - Methanococcus jannaschii.
Q9ZPT4 PUTATIVE DNA REPLICATION LICENSING FACTOR WITH AN MCM FAMILY DOMAIN (PROSITE:PDOC00662) - Arabidopsis thaliana (Mouse-ear cress).
Q9VF30 CG4828 PROTEIN - Drosophila melanogaster (Fruit fly).
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