Description: Homo sapiens minichromosome maintenance complex component 6 (MCM6), mRNA. RefSeq Summary (NM_005915): The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by the MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. The MCM complex consisting of this protein and MCM2, 4 and 7 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. The phosphorylation of the complex by CDC2 kinase reduces the helicase activity, suggesting a role in the regulation of DNA replication. Single nucleotide polymorphisms in the intron regions of this gene are associated with differential transcriptional activation of the promoter of the neighboring lactase gene and, thereby, influence lactose intolerance in early adulthood. [provided by RefSeq, May 2012]. Transcript (Including UTRs) Position: hg19 chr2:136,597,196-136,634,047 Size: 36,852 Total Exon Count: 17 Strand: - Coding Region Position: hg19 chr2:136,598,405-136,633,935 Size: 35,531 Coding Exon Count: 17
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
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa03030 - DNA replication hsa04110 - Cell cycle
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 
