ID:MCM2_HUMAN DESCRIPTION: RecName: Full=DNA replication licensing factor MCM2; EC=3.6.4.12; AltName: Full=Minichromosome maintenance protein 2 homolog; AltName: Full=Nuclear protein BM28; FUNCTION: Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Required for the entry in S phase and for cell division. CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate. SUBUNIT: Component of the MCM2-7 complex. The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6- MCM4-MCM7-MCM3-MCM5 (By simililarity). Interacts with DBF4 (By similarity). Interacts with KAT7. May interact with MCM10. INTERACTION: P62805:HIST2H4B; NbExp=3; IntAct=EBI-374819, EBI-302023; P25205:MCM3; NbExp=4; IntAct=EBI-374819, EBI-355153; P33992:MCM5; NbExp=4; IntAct=EBI-374819, EBI-359410; Q14566:MCM6; NbExp=6; IntAct=EBI-374819, EBI-374900; P33993:MCM7; NbExp=5; IntAct=EBI-374819, EBI-355924; SUBCELLULAR LOCATION: Nucleus. PTM: Phosphorylated on Ser-108 by ATR in proliferating cells. Ser- 108 proliferation is increased by genotoxic agents. Ser-40 is mediated by the CDC7-DBF4 and CDC7-DBF4B complexes, while Ser-53 phosphorylation is only mediated by the CDC7-DBF4 complex. Phosphorylation by the CDC7-DBF4 complex during G1/S phase is required for the initiation of DNA replication. MISCELLANEOUS: Early fractionation of eukaryotic MCM proteins yielded a variety of dimeric, trimeric and tetrameric complexes with unclear biological significance. Specifically a MCM467 subcomplex is shown to have in vitro helicase activity which is inhibited by the MCM2 subunit. The MCM2-7 hexamer is the proposed physiological active complex. SIMILARITY: Belongs to the MCM family. SIMILARITY: Contains 1 MCM domain. SEQUENCE CAUTION: Sequence=BAA04642.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=BAA12177.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=CAA47749.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=CAA47749.1; Type=Frameshift; Positions=115, 124, 127, 129, 154, 158, 773, 811; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/mcm2/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P49736
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000082 G1/S transition of mitotic cell cycle GO:0006260 DNA replication GO:0006268 DNA unwinding involved in DNA replication GO:0006270 DNA replication initiation GO:0006334 nucleosome assembly GO:0006915 apoptotic process GO:0007049 cell cycle GO:0071353 cellular response to interleukin-4 GO:0090102 cochlea development GO:1905775 negative regulation of DNA helicase activity
AK299934 - Homo sapiens cDNA FLJ55651 complete cds, highly similar to DNA replication licensing factor MCM2. AK309335 - Homo sapiens cDNA, FLJ99376. AK128291 - Homo sapiens cDNA FLJ46429 fis, clone THYMU3014372, highly similar to DNA replication licensing factor MCM2. BC014272 - Homo sapiens minichromosome maintenance complex component 2, mRNA (cDNA clone MGC:10606 IMAGE:3938252), complete cds. BC007670 - Homo sapiens minichromosome maintenance complex component 2, mRNA (cDNA clone MGC:2123 IMAGE:3143264), complete cds. AK304204 - Homo sapiens cDNA FLJ53276 complete cds, moderately similar to DNA replication licensing factor MCM2. BC017258 - Homo sapiens minichromosome maintenance complex component 2, mRNA (cDNA clone MGC:29681 IMAGE:3509667), complete cds. D21063 - Homo sapiens KIAA0030 mRNA. BC006165 - Homo sapiens minichromosome maintenance complex component 2, mRNA (cDNA clone MGC:13220 IMAGE:3959276), complete cds. BC007938 - Homo sapiens minichromosome maintenance complex component 2, mRNA (cDNA clone MGC:14281 IMAGE:4131943), complete cds. BC017490 - Homo sapiens minichromosome maintenance complex component 2, mRNA (cDNA clone MGC:16023 IMAGE:3607416), complete cds. CU675751 - Synthetic construct Homo sapiens gateway clone IMAGE:100017834 5' read MCM2 mRNA. CU677887 - Synthetic construct Homo sapiens gateway clone IMAGE:100023263 5' read MCM2 mRNA. CU675871 - Synthetic construct Homo sapiens gateway clone IMAGE:100023265 5' read MCM2 mRNA. AB463120 - Synthetic construct DNA, clone: pF1KA0030, Homo sapiens MCM2 gene for minichromosome maintenance complex component 2, without stop codon, in Flexi system. KJ905827 - Synthetic construct Homo sapiens clone ccsbBroadEn_15497 MCM2 gene, encodes complete protein. KJ891592 - Synthetic construct Homo sapiens clone ccsbBroadEn_00986 MCM2 gene, encodes complete protein. KJ897174 - Synthetic construct Homo sapiens clone ccsbBroadEn_06568 MCM2 gene, encodes complete protein. D83987 - Homo sapiens mRNA for DNA replication licensing factor (huMCM2), complete cds. X67334 - H.sapiens BM28 mRNA. BT009734 - Homo sapiens MCM2 minichromosome maintenance deficient 2, mitotin (S. cerevisiae) mRNA, complete cds. BC012756 - Homo sapiens cDNA clone IMAGE:3629543, **** WARNING: chimeric clone ****. BC030131 - Homo sapiens minichromosome maintenance complex component 2, mRNA (cDNA clone IMAGE:4125273), partial cds. BC000300 - Homo sapiens minichromosome maintenance complex component 2, mRNA (cDNA clone IMAGE:2820211), partial cds. JD088636 - Sequence 69660 from Patent EP1572962. JD294687 - Sequence 275711 from Patent EP1572962. JD183049 - Sequence 164073 from Patent EP1572962. JD526870 - Sequence 507894 from Patent EP1572962. JD562352 - Sequence 543376 from Patent EP1572962. JD498373 - Sequence 479397 from Patent EP1572962. JD429345 - Sequence 410369 from Patent EP1572962. JD065315 - Sequence 46339 from Patent EP1572962. JD490125 - Sequence 471149 from Patent EP1572962. JD528360 - Sequence 509384 from Patent EP1572962. JD375376 - Sequence 356400 from Patent EP1572962. JD255045 - Sequence 236069 from Patent EP1572962. JD269867 - Sequence 250891 from Patent EP1572962. JD227524 - Sequence 208548 from Patent EP1572962. JD051869 - Sequence 32893 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_mcmPathway - CDK Regulation of DNA Replication
Reactome (by CSHL, EBI, and GO)
Protein P49736 (Reactome details) participates in the following event(s):
R-HSA-69019 Mcm4,6,7 trimer forms and associates with the replication fork R-HSA-68849 Mcm2-7 associates with the Cdt1:CDC6:ORC:origin complex, forming the pre-replicative complex (preRC) R-HSA-68954 Mcm2-7 is phosphorylated by DDK R-HSA-176942 Multiple proteins are localized at replication fork R-HSA-68919 Mcm10 associates with the pre-replicative complex, stabilizing Mcm2-7 R-HSA-68944 Orc1 is phosphorylated by cyclin A/CDK2 R-HSA-169468 MCM2-7 mediated fork unwinding R-HSA-68940 Cdt1 is displaced from the pre-replicative complex. R-HSA-68918 CDK and DDK associate with the Mcm10:pre-replicative complex R-HSA-68917 Cdc45 associates with the pre-replicative complex at the origin R-HSA-68916 DNA Replication Factor A (RPA) associates with the pre-replicative complex at the origin R-HSA-176318 Loading of claspin onto DNA during replication origin firing R-HSA-176298 Activation of claspin R-HSA-69052 Switching of origins to a post-replicative state R-HSA-68867 Assembly of the pre-replicative complex R-HSA-68962 Activation of the pre-replicative complex R-HSA-176974 Unwinding of DNA R-HSA-69239 Synthesis of DNA R-HSA-68949 Orc1 removal from chromatin R-HSA-69002 DNA Replication Pre-Initiation R-HSA-69206 G1/S Transition R-HSA-69190 DNA strand elongation R-HSA-69242 S Phase R-HSA-69306 DNA Replication R-HSA-68874 M/G1 Transition R-HSA-453279 Mitotic G1-G1/S phases R-HSA-69278 Cell Cycle (Mitotic) R-HSA-1640170 Cell Cycle R-HSA-176187 Activation of ATR in response to replication stress R-HSA-69481 G2/M Checkpoints R-HSA-69620 Cell Cycle Checkpoints