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PR01658

Identifier
MCMPROTEIN2  [View Relations]  [View Alignment]  
Accession
PR01658
No. of Motifs
5
Creation Date
27-MAR-2002
Title
Mini-chromosome maintenance (MCM) protein 2 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. ISHIMI, Y., KOMAMURA-KOHNO, Y., ARAI, K. AND MASAI, H.
Biochemical activities associated with mouse Mcm2 protein.
J.BIOL.CHEM. 276 44-52 (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.
 
In addition to its role in initiation of DNA replication, MCM2 is able to
inhibit the MCM4,6,7 helicase. Studies on murine MCM2 indicate that its
C-terminus is required for interaction with MCM4, as well as for inhibition
of the DNA helicase activity of the MCM4,6,7 complex. The N-terminal region,
which contains an H3-binding domain and a region required for nuclear
localisation, is required for the phosphorylation by CDC7 kinase [7].
 
MCMPROTEIN2 is a 5-element fingerprint that provides a signature for the 
mini-chromosome maintenance (MCM) protein 2. 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 MCM2 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 14 sequences was identified.
Summary Information
14 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
51414141414
400000
300000
200000
12345
True Positives
CC19_SCHPO    MCM2_DROME    MCM2_HUMAN    MCM2_MOUSE    
MCM2_XENLA MCM2_YEAST O08971 O42588
O42723 Q9BRM7 Q9GR05 Q9LPD9
Q9U446 Q9XXI9
Sequence Titles
CC19_SCHPO  DNA replication licensing factor cdc19 (Cell division control protein 19) - Schizosaccharomyces pombe (Fission 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).
O08971 BM28 HOMOLOGUE - Mus musculus (Mouse).
O42588 MCM2P - Xenopus laevis (African clawed frog).
O42723 DNA REPLICATION LICENSING FACTOR - Emericella nidulans (Aspergillus nidulans).
Q9BRM7 SIMILAR TO MINI CHROMOSOME MAINTENANCE DEFICIENT 2 (S. CEREVISIAE) - Homo sapiens (Human).
Q9GR05 DNA REPLICATION LICENSING FACTOR MCM2 - Plasmodium falciparum.
Q9LPD9 T12C22.19 PROTEIN - Arabidopsis thaliana (Mouse-ear cress).
Q9U446 MINICHROMOSOME MAINTENANCE PROTEIN 2 HOMOLOG - Entamoeba histolytica.
Q9XXI9 Y17G7B.5 PROTEIN - Caenorhabditis elegans.
Scan History
SPTR40_18f 2  200  NSINGLE    
Initial Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
NQLIRTSGVVTCCTGVLP MCM2_XENLA 288 288 -
NQLIRTSGVVTSCTGVLP MCM2_MOUSE 303 303 -
NQLVRTLGVVTATTGVLP MCM2_DROME 288 288 -
NQLIRTSGVVTSCTGVLP MCM2_HUMAN 294 294 -
SSLVRVTGVVTRRTGVFP MCM2_YEAST 315 315 -
NTLIKVTGVCIKRGYVLP Q9GR05 315 315 -

Motif 2 width=13
Element Seqn Id St Int Rpt
KYNCNKCNFVLGP MCM2_HUMAN 317 5 -
KYNCNKCNFILGP MCM2_XENLA 311 5 -
KYNCSKCNFVLGP MCM2_MOUSE 326 5 -
KYDCVKCGYVLGP MCM2_DROME 311 5 -
KFNCLKCGSILGP MCM2_YEAST 338 5 -
YLKCNSCDTTLSE Q9GR05 338 5 -

Motif 3 width=15
Element Seqn Id St Int Rpt
FRVNGEKTVYRNYQR MCM2_YEAST 373 22 -
FEVNMEETIYQNYQR MCM2_HUMAN 352 22 -
FEINMEETVYQNYQR MCM2_XENLA 346 22 -
FEINMEETIYQNYQR MCM2_MOUSE 361 22 -
FSINMEQTLYRNYQK MCM2_DROME 346 22 -
FSVDRIKTAYTDYQK Q9GR05 375 24 -

Motif 4 width=12
Element Seqn Id St Int Rpt
YDGSLNTANGFP MCM2_HUMAN 413 46 -
YDGSLNTANGFP MCM2_XENLA 407 46 -
YDGSLNTANGFP MCM2_MOUSE 422 46 -
YDGSLNTDQGFP MCM2_DROME 407 46 -
YDGNLNAKNGFP MCM2_YEAST 434 46 -
YDIGLNIKYGFP Q9GR05 436 46 -

Motif 5 width=12
Element Seqn Id St Int Rpt
TVILANHVAKKD MCM2_HUMAN 428 3 -
TVILANHITKKD MCM2_XENLA 422 3 -
TIILANHVAKKD MCM2_MOUSE 437 3 -
TVIIANHVVVKD MCM2_DROME 422 3 -
TIIEANSIKRRE MCM2_YEAST 449 3 -
TEIEANNIERKE Q9GR05 451 3 -
Final Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
NQLIRTSGVVTSCTGVLP Q9BRM7 294 294 -
NQLIRTSGVVTCCTGVLP MCM2_XENLA 288 288 -
NQLIRTSGVVTCCTGVLP O42588 288 288 -
NQLIRTSGVVTSCTGVLP MCM2_MOUSE 303 303 -
NQLIRTSGVVTSCTGVLP O08971 303 303 -
NQLIRTSGVVTSCTGVLP MCM2_HUMAN 294 294 -
NQLVRTLGVVTATTGVLP MCM2_DROME 288 288 -
NTMIRIGGVVTRRSGVFP Q9LPD9 329 329 -
NCLVRVSGVVTRRTGLFP CC19_SCHPO 308 308 -
NMLIRTAGVVTIASGILP Q9XXI9 279 279 -
SSLVRVTGVVTRRTGVFP MCM2_YEAST 315 315 -
NCLVRVSGVVTRRTGVFP O42723 312 312 -
NTLIRVVGIVTRVTAIFP Q9U446 364 364 -
NTLIKVTGVCIKRGYVLP Q9GR05 315 315 -

Motif 2 width=13
Element Seqn Id St Int Rpt
KYNCNKCNFVLGP MCM2_HUMAN 317 5 -
KYNCNKCNFVLGP Q9BRM7 317 5 -
KYNCNKCNFILGP MCM2_XENLA 311 5 -
KYNCNKCNFILGP O42588 311 5 -
KYNCSKCNFVLGP MCM2_MOUSE 326 5 -
KYNCSKCNFVLGP O08971 326 5 -
KYDCVKCGYVLGP MCM2_DROME 311 5 -
KYDCNKCGAVLGP Q9LPD9 352 5 -
RFTCTKCGATLGP CC19_SCHPO 331 5 -
KYDCVACGYLLGP Q9XXI9 302 5 -
KFNCLKCGSILGP MCM2_YEAST 338 5 -
MFICQKCNMTLGP O42723 335 5 -
KYICSVCQARLGP Q9U446 387 5 -
YLKCNSCDTTLSE Q9GR05 338 5 -

Motif 3 width=15
Element Seqn Id St Int Rpt
FSINMEQTLYRNYQK MCM2_DROME 346 22 -
FEVNMEETIYQNYQR MCM2_HUMAN 352 22 -
FEVNMEETIYQNYQR Q9BRM7 352 22 -
FEINMEETVYQNYQR MCM2_XENLA 346 22 -
FEINMEETVYQNYQR O42588 346 22 -
FEINMEETIYQNYQR MCM2_MOUSE 361 22 -
FEINMEETIYQNYQR O08971 361 22 -
FTVNVEQTIYRNYQK Q9LPD9 387 22 -
FVINSERTVYNNYQR CC19_SCHPO 366 22 -
FELNVENTVYHNYQR Q9XXI9 337 22 -
FRVNGEKTVYRNYQR MCM2_YEAST 373 22 -
FTVSSEKTVYRNYQK O42723 370 22 -
FSIDVQNTIYQNYQK Q9U446 424 24 -
FSVDRIKTAYTDYQK Q9GR05 375 24 -

Motif 4 width=12
Element Seqn Id St Int Rpt
YDGSLNTANGFP Q9BRM7 413 46 -
YDGSLNTANGFP MCM2_XENLA 407 46 -
YDGSLNTANGFP O42588 407 46 -
YDGSLNTANGFP MCM2_MOUSE 422 46 -
YDGSLNTANGFP O08971 422 46 -
YDGSLNTDQGFP MCM2_DROME 407 46 -
FDLSLNTKNGFP Q9LPD9 448 46 -
YDGSLNTANGFP MCM2_HUMAN 413 46 -
FDASLNTKNGFP CC19_SCHPO 427 46 -
FDGSLNYKQGFP Q9XXI9 398 46 -
YDGNLNAKNGFP MCM2_YEAST 434 46 -
YDAQLNNKNGFP O42723 431 46 -
YETGLNRNFGFP Q9U446 485 46 -
YDIGLNIKYGFP Q9GR05 436 46 -

Motif 5 width=12
Element Seqn Id St Int Rpt
TVIEVNTIEKRS Q9U446 500 3 -
TVILANHVAKKD MCM2_HUMAN 428 3 -
TVILANHVAKKD Q9BRM7 428 3 -
TVILANHITKKD MCM2_XENLA 422 3 -
TVILANHITKKD O42588 422 3 -
TIILANHVAKKD MCM2_MOUSE 437 3 -
TIILANHVAKKD O08971 437 3 -
TVIIANHVVVKD MCM2_DROME 422 3 -
TVVEANYVTKKQ Q9LPD9 463 3 -
TIIEANHISQLD CC19_SCHPO 442 3 -
TLIHANHITNKD Q9XXI9 413 3 -
TIIEANSIKRRE MCM2_YEAST 449 3 -
TIIEANHVIKSH O42723 446 3 -
TEIEANNIERKE Q9GR05 451 3 -