ID:MCM6_HUMAN DESCRIPTION: RecName: Full=DNA replication licensing factor MCM6; EC=3.6.4.12; AltName: Full=p105MCM; 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. 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). May interact with MCM10. Interacts with TIPIN. Interacts with CDT1. Interacts with MCMBP. INTERACTION: Self; NbExp=2; IntAct=EBI-374900, EBI-374900; Q76353:- (xeno); NbExp=2; IntAct=EBI-374900, EBI-6248077; P42771:CDKN2A; NbExp=4; IntAct=EBI-374900, EBI-375053; Q9H211:CDT1; NbExp=3; IntAct=EBI-374900, EBI-456953; Q7L590:MCM10; NbExp=2; IntAct=EBI-374900, EBI-374912; P49736:MCM2; NbExp=6; IntAct=EBI-374900, EBI-374819; P25205:MCM3; NbExp=2; IntAct=EBI-374900, EBI-355153; P33993:MCM7; NbExp=4; IntAct=EBI-374900, EBI-355924; SUBCELLULAR LOCATION: Nucleus. Note=Binds to chromatin during G1 and detach from it during S phase. PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. POLYMORPHISM: Intronic variations in MCM6 upstream from the LCT gene are associated with adult-type hypolactasia [MIM:223100] leading to lactose intolerance, or with lactase persistance. Lactose intolerance is a normal physiological phenomenon caused by developmental down-regulation of lactase activity during childhood or early adulthood. A non-coding variation in MCM6 affects the transcriptional regulation of the LCT gene resulting in down- regulation of lactase activity. However, the majority of Northern Europeans and some African populations have the ability to maintain lactase activity and digest lactose throughout life (lactase persistence). 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. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/mcm6/";
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 Q14566
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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:0007049 cell cycle
BC032374 - Homo sapiens minichromosome maintenance complex component 6, mRNA (cDNA clone MGC:40308 IMAGE:5122786), complete cds. JD510582 - Sequence 491606 from Patent EP1572962. JD292111 - Sequence 273135 from Patent EP1572962. JD083725 - Sequence 64749 from Patent EP1572962. JD379944 - Sequence 360968 from Patent EP1572962. JD299446 - Sequence 280470 from Patent EP1572962. JD093636 - Sequence 74660 from Patent EP1572962. JD400679 - Sequence 381703 from Patent EP1572962. JD503726 - Sequence 484750 from Patent EP1572962. JD251510 - Sequence 232534 from Patent EP1572962. BC020268 - Homo sapiens minichromosome maintenance complex component 6, mRNA (cDNA clone IMAGE:5094951). U46838 - Human p105MCM mRNA, complete cds. D84557 - Homo sapiens mRNA for HsMcm6, complete cds. JD090606 - Sequence 71630 from Patent EP1572962. JD432962 - Sequence 413986 from Patent EP1572962. JD288270 - Sequence 269294 from Patent EP1572962. JD521168 - Sequence 502192 from Patent EP1572962. JD081050 - Sequence 62074 from Patent EP1572962. JD311510 - Sequence 292534 from Patent EP1572962. JD290891 - Sequence 271915 from Patent EP1572962. JD158005 - Sequence 139029 from Patent EP1572962. JD532811 - Sequence 513835 from Patent EP1572962. AK312575 - Homo sapiens cDNA, FLJ92950, Homo sapiens MCM6 minichromosome maintenance deficient 6 (MIS5 homolog, S. pombe) (S. cerevisiae) (MCM6), mRNA. KJ897177 - Synthetic construct Homo sapiens clone ccsbBroadEn_06571 MCM6 gene, encodes complete protein. AK299236 - Homo sapiens cDNA FLJ51591 partial cds, highly similar to DNA replication licensing factor MCM6. BC008774 - Homo sapiens MCM6 minichromosome maintenance deficient 6 (MIS5 homolog, S. pombe) (S. cerevisiae), mRNA (cDNA clone IMAGE:3140421), with apparent retained intron. AK303455 - Homo sapiens cDNA FLJ51590 complete cds, moderately similar to DNA replication licensing factor MCM6. CU689360 - Synthetic construct Homo sapiens gateway clone IMAGE:100017823 5' read MCM6 mRNA.
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 Q14566 (Reactome details) participates in the following event(s):
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-69019 Mcm4,6,7 trimer forms and associates with the replication fork 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-68867 Assembly of the pre-replicative complex R-HSA-68962 Activation of the pre-replicative complex R-HSA-69052 Switching of origins to a post-replicative state R-HSA-176974 Unwinding of DNA R-HSA-68949 Orc1 removal from chromatin R-HSA-69002 DNA Replication Pre-Initiation R-HSA-69206 G1/S Transition R-HSA-69239 Synthesis of DNA R-HSA-69190 DNA strand elongation R-HSA-68874 M/G1 Transition R-HSA-453279 Mitotic G1-G1/S phases R-HSA-69242 S Phase R-HSA-69306 DNA Replication R-HSA-69278 Cell Cycle (Mitotic) R-HSA-176187 Activation of ATR in response to replication stress R-HSA-1640170 Cell Cycle R-HSA-69481 G2/M Checkpoints R-HSA-69620 Cell Cycle Checkpoints
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
