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PR01659

Identifier
MCMPROTEIN3  [View Relations]  [View Alignment]  
Accession
PR01659
No. of Motifs
5
Creation Date
15-MAR-2002
Title
Mini-chromosome maintenance (MCM) protein 3 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. THOMMES, P., FETT, R., SCHRAY, B., BURKHART, R., BARNES, M., KENNEDY, C.,
BROWN, N.C. AND  KNIPPERS, R.
Properties of the nuclear P1 protein, a mammalian homologue of the yeast
Mcm3 replication protein.
NUCLEIC ACIDS RES. 20 1069-1074 (1992).
 
8. HOFMANN, Y., BECKER, J., WRIGHT, F., AVNER, E.D., MRUG, M.,
GUAY-WOODFORD, L.M., SOMLO, S., ZERRES, K., GERMINO, G.G. AND ONUCHIC, L.F.
Genomic structure of the gene for the human P1 protein (MCM3) and its
exclusion as a candidate for autosomal recessive polycystic kidney disease.
EUR.J.HUM.GENET. 8 163-166 (2000).

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.
 
Members of the MCM3 class have been isolated from a number of organisms. 
Human MCM3 was first described as a protein associated with DNA polymerase
alpha-primase [7], although subsequent analysis failed to show a direct
interaction between the them. The gene encoding human MCM3 has been
localised to chromosome 6p21.1-p12 [8]. In S.cerevisiae, MCM3 is a phospho-
protein that exists in multiple isoforms; distinct isoforms can be detected
at specific stages of the cell cycle. MCM3 has been implicated in limb 
development in Xenopus; identification of maternal and zygotic proteins 
suggests that specific forms may be used at different developmental stages.
The MCM3 protein contains a nuclear localisation signal, which is necessary
for its translocation into the nucleus.
 
MCMPROTEIN3 is a 5-element fingerprint that provides a signature for the
mini-chromosome maintenance (MCM) protein 3. 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 MCM3 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 15 sequences was identified.
Summary Information
15 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
51515151515
400000
300000
200000
12345
True Positives
MCM3_ENTHI    MCM3_HUMAN    MCM3_MOUSE    MCM3_SCHPO    
MCM3_XENLA MCM3_YEAST O65400 P87376
P91675 Q9FL33 Q9NUE7 Q9SX03
Q9SX04 Q9XVR7 Q9XYU1
Sequence Titles
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).
O65400 MCM3 HOMOLOG - Arabidopsis thaliana (Mouse-ear cress).
P87376 B24 PROTEIN - Triturus carnifex (Italian newt).
P91675 MCM3 (MCM HOMOLOG) - Drosophila melanogaster (Fruit fly).
Q9FL33 MCM3 HOMOLOG - Arabidopsis thaliana (Mouse-ear cress).
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).
Q9SX03 REPLICATION ORIGIN ACTIVATOR 3 - Zea mays (Maize).
Q9SX04 REPLICATION ORIGIN ACTIVATOR 2 - Zea mays (Maize).
Q9XVR7 C25D7.6 PROTEIN - Caenorhabditis elegans.
Q9XYU1 MCM3 PROTEIN - Drosophila melanogaster (Fruit fly).
Scan History
SPTR40_18f 2  50   NSINGLE    
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
TEYGLSVYKDHQTIT MCM3_HUMAN 186 186 -
TEYGLSTYKDHQTLS MCM3_XENLA 186 186 -
TEYGLSVYKDHQTIT MCM3_MOUSE 186 186 -
TEYGYSTFIDHQRIT MCM3_YEAST 243 243 -
IEFGFSTFRDHQSIS MCM3_SCHPO 191 191 -
LEPGLSTYKDFQTLV MCM3_ENTHI 77 77 -

Motif 2 width=13
Element Seqn Id St Int Rpt
QLPRSVDVILDDD MCM3_HUMAN 212 11 -
QLPRSVDIIADDD MCM3_XENLA 212 11 -
QLPRSVDVILDDD MCM3_MOUSE 212 11 -
QLPRSIDVILDDD MCM3_YEAST 269 11 -
QLPRSIDILLDDD MCM3_SCHPO 217 11 -
QMPRSVIVILLDQ MCM3_ENTHI 103 11 -

Motif 3 width=11
Element Seqn Id St Int Rpt
TPMENIGLQDS MCM3_HUMAN 464 239 -
TPMENIGLQDS MCM3_XENLA 464 239 -
TPMENIGLQDS MCM3_MOUSE 464 239 -
DPHQNIALPDS MCM3_YEAST 528 246 -
DPHQNIALPDS MCM3_SCHPO 475 245 -
SPMENLYFPES MCM3_ENTHI 348 232 -

Motif 4 width=11
Element Seqn Id St Int Rpt
ISDHVLRMHRY MCM3_HUMAN 497 22 -
IADHVLRMHRY MCM3_XENLA 497 22 -
ISDHVLRMHQY MCM3_MOUSE 497 22 -
ISEHVLRTHRY MCM3_YEAST 561 22 -
LSEHVLRMHRY MCM3_SCHPO 508 22 -
LSQHVLKMHRH MCM3_ENTHI 381 22 -

Motif 5 width=16
Element Seqn Id St Int Rpt
DAEEAVELVQYAYFKK MCM3_HUMAN 641 133 -
DAETALELVQFAYFKK MCM3_XENLA 641 133 -
DAEEAVELVQYAYFKK MCM3_MOUSE 641 133 -
DAKVAANLLRFALLGE MCM3_YEAST 725 153 -
DAKAAEKILRYALFRE MCM3_SCHPO 658 139 -
DAQVAVQLILMKIWEG MCM3_ENTHI 518 126 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
TEYGLSVYKDHQTIT MCM3_HUMAN 186 186 -
TEYGLSVYKDHQTIT Q9NUE7 186 186 -
TEYGLCTYKDHQTLT P87376 186 186 -
TEYGLSTYKDHQTLS MCM3_XENLA 186 186 -
TEYGLSVYKDHQTIT MCM3_MOUSE 186 186 -
TEYGLSVYKDHQTLT Q9XYU1 183 183 -
TEYGLSVYKDDQTLT P91675 183 183 -
TEYGLCKYKDHQTLS O65400 177 177 -
TEYGLCKYKDHQTLS Q9FL33 177 177 -
TEYGMCEYKDHQTLS Q9SX03 182 182 -
TEYGMCEYKDHQTLS Q9SX04 182 182 -
TEYGYSTFIDHQRIT MCM3_YEAST 243 243 -
IEFGFSTFRDHQSIS MCM3_SCHPO 191 191 -
TEFGHSVYKDHQTFT Q9XVR7 191 191 -
LEPGLSTYKDFQTLV MCM3_ENTHI 77 77 -

Motif 2 width=13
Element Seqn Id St Int Rpt
QLPRSVDVILDDD MCM3_HUMAN 212 11 -
QLPRSVDVILDDD Q9NUE7 212 11 -
QLPRSIDIIADDD P87376 212 11 -
QLPRSVDIIADDD MCM3_XENLA 212 11 -
QLPRSVDVILDDD MCM3_MOUSE 212 11 -
QLPRSVDIVCDDD Q9XYU1 209 11 -
QLPRSVDIVCDDD P91675 209 11 -
QLPRSVDVIAEDD O65400 203 11 -
QLPRSVDVIAEDD Q9FL33 203 11 -
QLPRTVDVIVEDD Q9SX03 208 11 -
QLPRTVDVIVEDD Q9SX04 208 11 -
QLPRSIDVILDDD MCM3_YEAST 269 11 -
QLPRSIDILLDDD MCM3_SCHPO 217 11 -
QLPRAVDCVADLD Q9XVR7 217 11 -
QMPRSVIVILLDQ MCM3_ENTHI 103 11 -

Motif 3 width=11
Element Seqn Id St Int Rpt
TPMENIGLQDS MCM3_HUMAN 464 239 -
TPMENIGLQDS Q9NUE7 464 239 -
TPMENIGLQDS P87376 465 240 -
TPMENIGLQDS MCM3_XENLA 464 239 -
TPMENIGLQDS MCM3_MOUSE 464 239 -
TPMENIGLQDS Q9XYU1 459 237 -
TPMENIGLQDS P91675 459 237 -
TPTKNIGLPDS O65400 454 238 -
TPTKNIGLPDS Q9FL33 454 238 -
TPTKNIGLPDS Q9SX03 459 238 -
TPTKNIGLPDS Q9SX04 459 238 -
DPHQNIALPDS MCM3_YEAST 528 246 -
DPHQNIALPDS MCM3_SCHPO 475 245 -
SPMENIGMQDS Q9XVR7 467 237 -
SPMENLYFPES MCM3_ENTHI 348 232 -

Motif 4 width=11
Element Seqn Id St Int Rpt
ISDHVLRMHRY MCM3_HUMAN 497 22 -
ISDHVLRMHRY Q9NUE7 497 22 -
ISDHVLRMHRY P87376 498 22 -
IADHVLRMHRY MCM3_XENLA 497 22 -
ISDHVLRMHQY MCM3_MOUSE 497 22 -
ISDHVVRMHRY Q9XYU1 492 22 -
ISDHVVRMHRY P91675 492 22 -
ISEHVLRMHRY O65400 487 22 -
ISEHVLRMHRY Q9FL33 487 22 -
ISEHVARMHRY Q9SX03 492 22 -
ISEHVARMHRY Q9SX04 492 22 -
ISEHVLRTHRY MCM3_YEAST 561 22 -
LSEHVLRMHRY MCM3_SCHPO 508 22 -
VAEHVLKLHTY Q9XVR7 500 22 -
LSQHVLKMHRH MCM3_ENTHI 381 22 -

Motif 5 width=16
Element Seqn Id St Int Rpt
DAEEAVELVQYAYFKK MCM3_HUMAN 641 133 -
DAEEAVELVQYAYFKK Q9NUE7 641 133 -
DAEVALELVQFAYFKK P87376 642 133 -
DAETALELVQFAYFKK MCM3_XENLA 641 133 -
DAEEAVELVQYAYFKK MCM3_MOUSE 641 133 -
DAHAAIELVQFAYFKK Q9XYU1 635 132 -
DAHAAIELVQFAYFKK P91675 635 132 -
DAEAALKLMNFAIYHQ O65400 622 124 -
DAEAALKLMNFAIYHQ Q9FL33 622 124 -
DVEAALQVLNFAIYHK Q9SX03 632 129 -
DVEAALQVLNFAIYHK Q9SX04 632 129 -
DAKVAANLLRFALLGE MCM3_YEAST 725 153 -
DAKAAEKILRYALFRE MCM3_SCHPO 658 139 -
DTEKAYNLLHFACFKE Q9XVR7 638 127 -
DAQVAVQLILMKIWEG MCM3_ENTHI 518 126 -