ID MCM6_HUMAN Reviewed; 821 AA. AC Q14566; B2R6H2; Q13504; Q99859; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 1. DT 27-MAR-2024, entry version 218. DE RecName: Full=DNA replication licensing factor MCM6; DE EC=3.6.4.12 {ECO:0000269|PubMed:25661590}; DE AltName: Full=p105MCM; GN Name=MCM6 {ECO:0000312|HGNC:HGNC:6949}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9286856; DOI=10.1046/j.1365-2443.1997.1290327.x; RA Tsuruga H., Yabuta N., Hosoya S., Tamura K., Endo Y., Nojima H.; RT "HsMCM6: a new member of the human MCM/P1 family encodes a protein RT homologous to fission yeast Mis5."; RL Genes Cells 2:381-399(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9516426; DOI=10.1074/jbc.273.13.7320; RA Holthoff H.P., Baack M., Richter A., Ritzi M., Knippers R.; RT "Human protein MCM6 on HeLa cell chromatin."; RL J. Biol. Chem. 273:7320-7325(1998). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LYS-806. RG NIEHS SNPs program; RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Cervix; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 640-821. RX PubMed=8977093; DOI=10.1016/s0014-5793(96)01189-1; RA Harvey C.B., Wang Y., Darmoul D., Phillips A., Mantei N., Swallow D.M.; RT "Characterisation of a human homologue of a yeast cell division cycle gene, RT MCM6, located adjacent to the 5' end of the lactase gene on chromosome RT 2q21."; RL FEBS Lett. 398:135-140(1996). RN [8] RP IDENTIFICATION IN THE MCM2-7 COMPLEX, AND FUNCTION. RX PubMed=9305914; DOI=10.1074/jbc.272.39.24508; RA Ishimi Y.; RT "A DNA helicase activity is associated with an MCM4, -6, and -7 protein RT complex."; RL J. Biol. Chem. 272:24508-24513(1997). RN [9] RP INTERACTION WITH MCM10. RX PubMed=11095689; DOI=10.1093/nar/28.23.4769; RA Izumi M., Yanagi K., Mizuno T., Yokoi M., Kawasaki Y., Moon K.Y., RA Hurwitz J., Yatagai F., Hanaoka F.; RT "The human homolog of Saccharomyces cerevisiae Mcm10 interacts with RT replication factors and dissociates from nuclease-resistant nuclear RT structures in G(2) phase."; RL Nucleic Acids Res. 28:4769-4777(2000). RN [10] RP INVOLVEMENT IN ADULT-TYPE HYPOLACTASIA. RX PubMed=11788828; DOI=10.1038/ng826; RA Enattah N.S., Sahi T., Savilahti E., Terwilliger J.D., Peltonen L., RA Jaervelae I.; RT "Identification of a variant associated with adult-type hypolactasia."; RL Nat. Genet. 30:233-237(2002). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Lymphoblast; RX PubMed=14654843; DOI=10.1038/nature02166; RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.; RT "Proteomic characterization of the human centrosome by protein correlation RT profiling."; RL Nature 426:570-574(2003). RN [12] RP IDENTIFICATION IN THE MCM2-7 COMPLEX, ATPASE ACTIVITY OF THE MCM2-7 RP COMPLEX, AND SUBCELLULAR LOCATION. RX PubMed=16899510; DOI=10.1091/mbc.e06-03-0241; RA Tsuji T., Ficarro S.B., Jiang W.; RT "Essential role of phosphorylation of MCM2 by Cdc7/Dbf4 in the initiation RT of DNA replication in mammalian cells."; RL Mol. Biol. Cell 17:4459-4472(2006). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-271 AND SER-762, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [14] RP INTERACTION WITH TIPIN. RX PubMed=17116885; DOI=10.1073/pnas.0609251103; RA Chou D.M., Elledge S.J.; RT "Tipin and Timeless form a mutually protective complex required for RT genotoxic stress resistance and checkpoint function."; RL Proc. Natl. Acad. Sci. U.S.A. 103:18143-18147(2006). RN [15] RP HELICASE ACTIVITY OF THE MCM2-3 COMPLEX, INTERACTION WITH MCMBP, RP IDENTIFICATION IN THE MCM2-7 COMPLEX, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=17296731; DOI=10.1128/mcb.02384-06; RA Sakwe A.M., Nguyen T., Athanasopoulos V., Shire K., Frappier L.; RT "Identification and characterization of a novel component of the human RT minichromosome maintenance complex."; RL Mol. Cell. Biol. 27:3044-3055(2007). RN [16] RP POLYMORPHISM, AND INVOLVEMENT IN ADULT-TYPE HYPOLACTASIA AND LACTASE RP PERSISTANCE. RX PubMed=17159977; DOI=10.1038/ng1946; RA Tishkoff S.A., Reed F.A., Ranciaro A., Voight B.F., Babbitt C.C., RA Silverman J.S., Powell K., Mortensen H.M., Hirbo J.B., Osman M., RA Ibrahim M., Omar S.A., Lema G., Nyambo T.B., Ghori J., Bumpstead S., RA Pritchard J.K., Wray G.A., Deloukas P.; RT "Convergent adaptation of human lactase persistence in Africa and Europe."; RL Nat. Genet. 39:31-40(2007). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-791, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-271 AND SER-762, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [19] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-271 AND SER-762, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [21] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-13; SER-271 AND SER-762, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [23] RP GLYCOSYLATION. RX PubMed=22967762; DOI=10.1016/j.bbagen.2012.08.024; RA Drougat L., Olivier-Van Stichelen S., Mortuaire M., Foulquier F., RA Lacoste A.S., Michalski J.C., Lefebvre T., Vercoutter-Edouart A.S.; RT "Characterization of O-GlcNAc cycling and proteomic identification of RT differentially O-GlcNAcylated proteins during G1/S transition."; RL Biochim. Biophys. Acta 1820:1839-1848(2012). RN [24] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [25] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13; SER-219; SER-271; THR-278 RP AND SER-762, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [27] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=25661590; DOI=10.1093/jb/mvv015; RA Ishimi Y., Irie D.; RT "G364R mutation of MCM4 detected in human skin cancer cells affects DNA RT helicase activity of MCM4/6/7 complex."; RL J. Biochem. 157:561-569(2015). RN [28] RP INTERACTION WITH DDI2. RX PubMed=29290612; DOI=10.1016/j.molcel.2017.11.035; RA Kottemann M.C., Conti B.A., Lach F.P., Smogorzewska A.; RT "Removal of RTF2 from Stalled Replisomes Promotes Maintenance of Genome RT Integrity."; RL Mol. Cell 69:24-35.E5(2018). RN [29] RP FUNCTION. RX PubMed=35585232; DOI=10.1038/s41586-022-04759-1; RA Baris Y., Taylor M.R.G., Aria V., Yeeles J.T.P.; RT "Fast and efficient DNA replication with purified human proteins."; RL Nature 606:204-210(2022). RN [30] RP STRUCTURE BY NMR OF 708-821, INTERACTION WITH CDT1, AND MUTAGENESIS OF RP GLU-757; GLU-763 AND LEU-766. RX PubMed=20202939; DOI=10.1074/jbc.c109.094599; RA Wei Z., Liu C., Wu X., Xu N., Zhou B., Liang C., Zhu G.; RT "Characterization and structure determination of the Cdt1 binding domain of RT human minichromosome maintenance (Mcm) 6."; RL J. Biol. Chem. 285:12469-12473(2010). RN [31] {ECO:0007744|PDB:6XTX, ECO:0007744|PDB:6XTY} RP STRUCTURE BY ELECTRON MICROSCOPY (3.29 ANGSTROMS) IN COMPLEXES WITH ADP; RP ATP ANALOG AND WDHD1 IN CMG COMPLEX, AND SUBUNIT. RX PubMed=32453425; DOI=10.1093/nar/gkaa429; RA Rzechorzek N.J., Hardwick S.W., Jatikusumo V.A., Chirgadze D.Y., RA Pellegrini L.; RT "CryoEM structures of human CMG-ATPgammaS-DNA and CMG-AND-1 complexes."; RL Nucleic Acids Res. 48:6980-6995(2020). RN [32] {ECO:0007744|PDB:7PLO} RP STRUCTURE BY ELECTRON MICROSCOPY (2.80 ANGSTROMS) IN REPLISOME, AND RP SUBUNIT. RX PubMed=34700328; DOI=10.1038/s41586-021-04145-3; RA Jenkyn-Bedford M., Jones M.L., Baris Y., Labib K.P.M., Cannone G., RA Yeeles J.T.P., Deegan T.D.; RT "A conserved mechanism for regulating replisome disassembly in RT eukaryotes."; RL Nature 600:743-747(2021). RN [33] {ECO:0007744|PDB:7PFO} RP STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) IN REPLISOME, AND RP SUBUNIT. RX PubMed=34694004; DOI=10.15252/embj.2021108819; RA Jones M.L., Baris Y., Taylor M.R.G., Yeeles J.T.P.; RT "Structure of a human replisome shows the organisation and interactions of RT a DNA replication machine."; RL EMBO J. 40:e108819-e108819(2021). RN [34] RP VARIANTS SER-149; TYR-158; GLY-202 AND SER-239, AND CHARACTERIZATION OF RP VARIANT TYR-158. RX PubMed=37198333; DOI=10.1007/s00439-023-02569-7; RA Smits D.J., Schot R., Popescu C.A., Dias K.R., Ades L., Briere L.C., RA Sweetser D.A., Kushima I., Aleksic B., Khan S., Karageorgou V., Ordonez N., RA Sleutels F.J.G.T., van der Kaay D.C.M., Van Mol C., Van Esch H., RA Bertoli-Avella A.M., Roscioli T., Mancini G.M.S.; RT "De novo MCM6 variants in neurodevelopmental disorders: a recognizable RT phenotype related to zinc binding residues."; RL Hum. Genet. 0:0-0(2023). CC -!- FUNCTION: Acts as a component of the MCM2-7 complex (MCM complex) which CC is the replicative helicase essential for 'once per cell cycle' DNA CC replication initiation and elongation in eukaryotic cells. Core CC component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that CC unwinds template DNA during replication, and around which the replisome CC is built (PubMed:32453425, PubMed:34694004, PubMed:34700328, CC PubMed:35585232, PubMed:16899510, PubMed:9305914). The active ATPase CC sites in the MCM2-7 ring are formed through the interaction surfaces of CC two neighboring subunits such that a critical structure of a conserved CC arginine finger motif is provided in trans relative to the ATP-binding CC site of the Walker A box of the adjacent subunit. The six ATPase active CC sites, however, are likely to contribute differentially to the complex CC helicase activity (PubMed:32453425). {ECO:0000269|PubMed:16899510, CC ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, CC ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, CC ECO:0000269|PubMed:9305914}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12; CC Evidence={ECO:0000269|PubMed:25661590}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066; CC Evidence={ECO:0000269|PubMed:25661590}; CC -!- SUBUNIT: Component of the MCM2-7 complex (PubMed:16899510, CC PubMed:17296731, PubMed:9305914). The complex forms a toroidal CC hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7- CC MCM3-MCM5 (PubMed:16899510, PubMed:17296731, PubMed:9305914, CC PubMed:32453425, PubMed:34700328, PubMed:34694004). Component of the CC CMG helicase complex, a hexameric ring of related MCM2-7 subunits CC stabilized by CDC45 and the tetrameric GINS complex (PubMed:34700328, CC PubMed:34694004, PubMed:32453425). May interact with MCM10 CC (PubMed:11095689). Interacts with TIPIN (PubMed:17116885). Interacts CC with CDT1 (PubMed:20202939). Interacts with MCMBP (PubMed:17296731). CC Interacts with DDI2 (PubMed:29290612). {ECO:0000269|PubMed:11095689, CC ECO:0000269|PubMed:16899510, ECO:0000269|PubMed:17116885, CC ECO:0000269|PubMed:17296731, ECO:0000269|PubMed:20202939, CC ECO:0000269|PubMed:29290612, ECO:0000269|PubMed:32453425, CC ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, CC ECO:0000269|PubMed:9305914}. CC -!- INTERACTION: CC Q14566; P42771: CDKN2A; NbExp=4; IntAct=EBI-374900, EBI-375053; CC Q14566; Q9H211: CDT1; NbExp=4; IntAct=EBI-374900, EBI-456953; CC Q14566; Q3B820: FAM161A; NbExp=3; IntAct=EBI-374900, EBI-719941; CC Q14566; Q7L590: MCM10; NbExp=2; IntAct=EBI-374900, EBI-374912; CC Q14566; Q7L590-2: MCM10; NbExp=4; IntAct=EBI-374900, EBI-10233517; CC Q14566; P49736: MCM2; NbExp=16; IntAct=EBI-374900, EBI-374819; CC Q14566; P25205: MCM3; NbExp=4; IntAct=EBI-374900, EBI-355153; CC Q14566; Q14566: MCM6; NbExp=2; IntAct=EBI-374900, EBI-374900; CC Q14566; P33993: MCM7; NbExp=6; IntAct=EBI-374900, EBI-355924; CC Q14566; Q9BTE3: MCMBP; NbExp=15; IntAct=EBI-374900, EBI-749378; CC Q14566; P50583: NUDT2; NbExp=3; IntAct=EBI-374900, EBI-10096247; CC Q14566; P08579: SNRPB2; NbExp=3; IntAct=EBI-374900, EBI-1053651; CC Q14566; Q08945: SSRP1; NbExp=3; IntAct=EBI-374900, EBI-353771; CC Q14566; Q05086: UBE3A; NbExp=6; IntAct=EBI-374900, EBI-954357; CC Q14566; Q05086-2: UBE3A; NbExp=3; IntAct=EBI-374900, EBI-10175863; CC Q14566; Q96C00: ZBTB9; NbExp=3; IntAct=EBI-374900, EBI-395708; CC Q14566; Q76353; Xeno; NbExp=2; IntAct=EBI-374900, EBI-6248077; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16899510}. Chromosome CC {ECO:0000269|PubMed:16899510}. Note=Binds to chromatin during G1 and CC detaches from it during S phase. {ECO:0000269|PubMed:16899510}. CC -!- PTM: O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner. CC {ECO:0000269|PubMed:22967762}. CC -!- POLYMORPHISM: Intronic variations in MCM6 upstream from the LCT gene CC are associated with adult-type hypolactasia [MIM:223100] leading to CC lactose intolerance, or with lactase persistance. Lactose intolerance CC is a normal physiological phenomenon caused by developmental down- CC regulation of lactase activity during childhood or early adulthood. A CC non-coding variation in MCM6 affects the transcriptional regulation of CC the LCT gene resulting in down-regulation of lactase activity. However, CC the majority of Northern Europeans and some African populations have CC the ability to maintain lactase activity and digest lactose throughout CC life (lactase persistence). {ECO:0000269|PubMed:17159977}. CC -!- MISCELLANEOUS: Early fractionation of eukaryotic MCM proteins yielded a CC variety of dimeric, trimeric and tetrameric complexes with unclear CC biological significance. Specifically a MCM467 subcomplex is shown to CC have in vitro helicase activity which is inhibited by the MCM2 subunit. CC The MCM2-7 hexamer is the proposed physiological active complex. CC {ECO:0000250|UniProtKB:P97311}. CC -!- SIMILARITY: Belongs to the MCM family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/mcm6/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D84557; BAA12699.1; -; mRNA. DR EMBL; U46838; AAC50766.1; -; mRNA. DR EMBL; AY220757; AAO26043.1; -; Genomic_DNA. DR EMBL; AK312575; BAG35469.1; -; mRNA. DR EMBL; CH471058; EAX11621.1; -; Genomic_DNA. DR EMBL; BC032374; AAH32374.1; -; mRNA. DR EMBL; AH005100; AAB48165.1; -; Genomic_DNA. DR CCDS; CCDS2179.1; -. DR RefSeq; NP_005906.2; NM_005915.5. DR PDB; 2KLQ; NMR; -; A=708-821. DR PDB; 2LE8; NMR; -; A=708-821. DR PDB; 6XTX; EM; 3.29 A; 6=1-821. DR PDB; 6XTY; EM; 6.77 A; 6=1-821. DR PDB; 7PFO; EM; 3.20 A; 6=1-821. DR PDB; 7PLO; EM; 2.80 A; 6=1-821. DR PDB; 7W1Y; EM; 2.59 A; 6/E=1-821. DR PDB; 7W68; EM; 4.40 A; E=1-821. DR PDB; 8B9D; EM; 3.40 A; 6=1-821. DR PDBsum; 2KLQ; -. DR PDBsum; 2LE8; -. DR PDBsum; 6XTX; -. DR PDBsum; 6XTY; -. DR PDBsum; 7PFO; -. DR PDBsum; 7PLO; -. DR PDBsum; 7W1Y; -. DR PDBsum; 7W68; -. DR PDBsum; 8B9D; -. DR AlphaFoldDB; Q14566; -. DR BMRB; Q14566; -. DR EMDB; EMD-10619; -. DR EMDB; EMD-10621; -. DR EMDB; EMD-13375; -. DR EMDB; EMD-13494; -. DR EMDB; EMD-32258; -. DR EMDB; EMD-32326; -. DR SMR; Q14566; -. DR BioGRID; 110343; 284. DR ComplexPortal; CPX-2940; MCM complex. DR CORUM; Q14566; -. DR DIP; DIP-31727N; -. DR IntAct; Q14566; 75. DR MINT; Q14566; -. DR STRING; 9606.ENSP00000264156; -. DR ChEMBL; CHEMBL4296011; -. DR GlyGen; Q14566; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q14566; -. DR MetOSite; Q14566; -. DR PhosphoSitePlus; Q14566; -. DR SwissPalm; Q14566; -. DR BioMuta; MCM6; -. DR DMDM; 2497824; -. DR CPTAC; CPTAC-5918; -. DR CPTAC; CPTAC-5919; -. DR EPD; Q14566; -. DR jPOST; Q14566; -. DR MassIVE; Q14566; -. DR MaxQB; Q14566; -. DR PaxDb; 9606-ENSP00000264156; -. DR PeptideAtlas; Q14566; -. DR ProteomicsDB; 60047; -. DR Pumba; Q14566; -. DR Antibodypedia; 1416; 425 antibodies from 35 providers. DR CPTC; Q14566; 1 antibody. DR DNASU; 4175; -. DR Ensembl; ENST00000264156.3; ENSP00000264156.2; ENSG00000076003.5. DR GeneID; 4175; -. DR KEGG; hsa:4175; -. DR MANE-Select; ENST00000264156.3; ENSP00000264156.2; NM_005915.6; NP_005906.2. DR UCSC; uc002tuw.5; human. DR AGR; HGNC:6949; -. DR CTD; 4175; -. DR DisGeNET; 4175; -. DR GeneCards; MCM6; -. DR HGNC; HGNC:6949; MCM6. DR HPA; ENSG00000076003; Tissue enhanced (lymphoid). DR MalaCards; MCM6; -. DR MIM; 223100; phenotype. DR MIM; 601806; gene. DR neXtProt; NX_Q14566; -. DR OpenTargets; ENSG00000076003; -. DR Orphanet; 319681; NON RARE IN EUROPE: Lactase non-persistence in adulthood. DR PharmGKB; PA30696; -. DR VEuPathDB; HostDB:ENSG00000076003; -. DR eggNOG; KOG0480; Eukaryota. DR GeneTree; ENSGT01050000244824; -. DR HOGENOM; CLU_000995_3_2_1; -. DR InParanoid; Q14566; -. DR OMA; CQTEIRN; -. DR OrthoDB; 5476523at2759; -. DR PhylomeDB; Q14566; -. DR TreeFam; TF105646; -. DR PathwayCommons; Q14566; -. DR Reactome; R-HSA-176187; Activation of ATR in response to replication stress. DR Reactome; R-HSA-176974; Unwinding of DNA. DR Reactome; R-HSA-68867; Assembly of the pre-replicative complex. DR Reactome; R-HSA-68949; Orc1 removal from chromatin. DR Reactome; R-HSA-68962; Activation of the pre-replicative complex. DR Reactome; R-HSA-69052; Switching of origins to a post-replicative state. DR SignaLink; Q14566; -. DR SIGNOR; Q14566; -. DR BioGRID-ORCS; 4175; 787 hits in 1172 CRISPR screens. DR ChiTaRS; MCM6; human. DR EvolutionaryTrace; Q14566; -. DR GeneWiki; MCM6; -. DR GenomeRNAi; 4175; -. DR Pharos; Q14566; Tbio. DR PRO; PR:Q14566; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q14566; Protein. DR Bgee; ENSG00000076003; Expressed in ventricular zone and 205 other cell types or tissues. DR GO; GO:0000781; C:chromosome, telomeric region; HDA:BHF-UCL. DR GO; GO:0071162; C:CMG complex; IPI:ComplexPortal. DR GO; GO:0042555; C:MCM complex; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; NAS:UniProtKB. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA. DR GO; GO:0003678; F:DNA helicase activity; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0003697; F:single-stranded DNA binding; IEA:Ensembl. DR GO; GO:0006260; P:DNA replication; NAS:UniProtKB. DR GO; GO:0006270; P:DNA replication initiation; IEA:InterPro. DR GO; GO:0006268; P:DNA unwinding involved in DNA replication; IDA:ComplexPortal. DR GO; GO:0000727; P:double-strand break repair via break-induced replication; IBA:GO_Central. DR GO; GO:1902969; P:mitotic DNA replication; IBA:GO_Central. DR GO; GO:0030174; P:regulation of DNA-templated DNA replication initiation; NAS:ComplexPortal. DR CDD; cd17757; MCM6; 1. DR Gene3D; 1.20.58.870; -; 1. DR Gene3D; 2.20.28.10; -; 1. DR Gene3D; 3.30.1640.10; mini-chromosome maintenance (MCM) complex, chain A, domain 1; 1. DR Gene3D; 2.40.50.140; Nucleic acid-binding proteins; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR031327; MCM. DR InterPro; IPR008049; MCM6. DR InterPro; IPR041024; Mcm6_C. DR InterPro; IPR018525; MCM_CS. DR InterPro; IPR001208; MCM_dom. DR InterPro; IPR041562; MCM_lid. DR InterPro; IPR027925; MCM_N. DR InterPro; IPR033762; MCM_OB. DR InterPro; IPR012340; NA-bd_OB-fold. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR11630; DNA REPLICATION LICENSING FACTOR MCM FAMILY MEMBER; 1. DR PANTHER; PTHR11630:SF73; DNA REPLICATION LICENSING FACTOR MCM6; 1. DR Pfam; PF00493; MCM; 1. DR Pfam; PF18263; MCM6_C; 1. DR Pfam; PF17855; MCM_lid; 1. DR Pfam; PF14551; MCM_N; 1. DR Pfam; PF17207; MCM_OB; 1. DR PRINTS; PR01657; MCMFAMILY. DR PRINTS; PR01662; MCMPROTEIN6. DR SMART; SM00350; MCM; 1. DR SUPFAM; SSF50249; Nucleic acid-binding proteins; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS00847; MCM_1; 1. DR PROSITE; PS50051; MCM_2; 1. DR Genevisible; Q14566; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; ATP-binding; Cell cycle; Chromosome; KW DNA replication; DNA-binding; Glycoprotein; Helicase; Hydrolase; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome. FT CHAIN 1..821 FT /note="DNA replication licensing factor MCM6" FT /id="PRO_0000194113" FT DOMAIN 346..553 FT /note="MCM" FT MOTIF 528..531 FT /note="Arginine finger" FT BINDING 359 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="ligand shared with MCM4" FT /evidence="ECO:0000305|PubMed:32453425, FT ECO:0007744|PDB:6XTX" FT BINDING 399 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="ligand shared with MCM4" FT /evidence="ECO:0000305|PubMed:32453425, FT ECO:0007744|PDB:6XTX" FT BINDING 400 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="ligand shared with MCM4" FT /evidence="ECO:0000305|PubMed:32453425, FT ECO:0007744|PDB:6XTX" FT BINDING 401 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="ligand shared with MCM4" FT /evidence="ECO:0000305|PubMed:32453425, FT ECO:0007744|PDB:6XTX" FT BINDING 402 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="ligand shared with MCM4" FT /evidence="ECO:0000305|PubMed:32453425, FT ECO:0007744|PDB:6XTX" FT BINDING 403 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="ligand shared with MCM4" FT /evidence="ECO:0000305|PubMed:32453425, FT ECO:0007744|PDB:6XTX" FT BINDING 504 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="ligand shared with MCM4" FT /evidence="ECO:0000305|PubMed:32453425, FT ECO:0007744|PDB:6XTX" FT BINDING 619 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /ligand_note="ligand shared with MCM2" FT /evidence="ECO:0000305|PubMed:32453425, FT ECO:0007744|PDB:6XTX" FT BINDING 622 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /ligand_note="ligand shared with MCM2" FT /evidence="ECO:0000305|PubMed:32453425, FT ECO:0007744|PDB:6XTX" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:22223895, FT ECO:0007744|PubMed:22814378" FT MOD_RES 13 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 219 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 271 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 278 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 643 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P97311" FT MOD_RES 689 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P97311" FT MOD_RES 762 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 791 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:17525332" FT VARIANT 35 FT /note="E -> V (in dbSNP:rs796879083)" FT /id="VAR_014816" FT VARIANT 149 FT /note="P -> S (found in a patient with mild developmental FT delay and autism spectrum disorder; uncertain significance; FT dbSNP:rs774059991)" FT /evidence="ECO:0000269|PubMed:37198333" FT /id="VAR_088369" FT VARIANT 158 FT /note="C -> Y (found in patients with microcephaly, FT developmental delay, typical facial characteristics, FT endocrine disorders, feeding difficulties and urogenital FT anomalies; uncertain significance; impairs cell FT proliferation and ciliogenesis)" FT /evidence="ECO:0000269|PubMed:37198333" FT /id="VAR_088370" FT VARIANT 202 FT /note="D -> G (found in a patient with intra-uterine growth FT restriction, developmental delay and autism spectrum FT disorder; uncertain significance)" FT /evidence="ECO:0000269|PubMed:37198333" FT /id="VAR_088371" FT VARIANT 239 FT /note="G -> S (found in a patient with endocrine disorders, FT developmental regression, autism spectrum disorder and FT epilepsy; uncertain significance)" FT /evidence="ECO:0000269|PubMed:37198333" FT /id="VAR_088372" FT VARIANT 806 FT /note="E -> K (in dbSNP:rs4988283)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_016340" FT MUTAGEN 757 FT /note="E->A,D: Impairs interaction with CTD1." FT /evidence="ECO:0000269|PubMed:20202939" FT MUTAGEN 763 FT /note="E->A,D: Impairs interaction with CTD1." FT /evidence="ECO:0000269|PubMed:20202939" FT MUTAGEN 766 FT /note="L->A: Impairs interaction with CTD1." FT /evidence="ECO:0000269|PubMed:20202939" FT CONFLICT 377..387 FT /note="PKTTGEGTSLR -> SKDNRRRDLSS (in Ref. 2; AAC50766)" FT /evidence="ECO:0000305" FT CONFLICT 495 FT /note="A -> T (in Ref. 2; AAC50766)" FT /evidence="ECO:0000305" FT CONFLICT 738 FT /note="Missing (in Ref. 7; AAB48165)" FT /evidence="ECO:0000305" FT CONFLICT 790 FT /note="L -> P (in Ref. 2; AAC50766)" FT /evidence="ECO:0000305" FT HELIX 709..711 FT /evidence="ECO:0007829|PDB:2LE8" FT STRAND 714..716 FT /evidence="ECO:0007829|PDB:2LE8" FT HELIX 718..737 FT /evidence="ECO:0007829|PDB:2KLQ" FT STRAND 739..741 FT /evidence="ECO:0007829|PDB:2KLQ" FT HELIX 745..756 FT /evidence="ECO:0007829|PDB:2KLQ" FT TURN 757..759 FT /evidence="ECO:0007829|PDB:2KLQ" FT HELIX 763..782 FT /evidence="ECO:0007829|PDB:2KLQ" FT HELIX 793..796 FT /evidence="ECO:0007829|PDB:2KLQ" SQ SEQUENCE 821 AA; 92889 MW; F94968EB25A3E501 CRC64; MDLAAAAEPG AGSQHLEVRD EVAEKCQKLF LDFLEEFQSS DGEIKYLQLA EELIRPERNT LVVSFVDLEQ FNQQLSTTIQ EEFYRVYPYL CRALKTFVKD RKEIPLAKDF YVAFQDLPTR HKIRELTSSR IGLLTRISGQ VVRTHPVHPE LVSGTFLCLD CQTVIRDVEQ QFKYTQPNIC RNPVCANRRR FLLDTNKSRF VDFQKVRIQE TQAELPRGSI PRSLEVILRA EAVESAQAGD KCDFTGTLIV VPDVSKLSTP GARAETNSRV SGVDGYETEG IRGLRALGVR DLSYRLVFLA CCVAPTNPRF GGKELRDEEQ TAESIKNQMT VKEWEKVFEM SQDKNLYHNL CTSLFPTIHG NDEVKRGVLL MLFGGVPKTT GEGTSLRGDI NVCIVGDPST AKSQFLKHVE EFSPRAVYTS GKASSAAGLT AAVVRDEESH EFVIEAGALM LADNGVCCID EFDKMDVRDQ VAIHEAMEQQ TISITKAGVK ATLNARTSIL AAANPISGHY DRSKSLKQNI NLSAPIMSRF DLFFILVDEC NEVTDYAIAR RIVDLHSRIE ESIDRVYSLD DIRRYLLFAR QFKPKISKES EDFIVEQYKH LRQRDGSGVT KSSWRITVRQ LESMIRLSEA MARMHCCDEV QPKHVKEAFR LLNKSIIRVE TPDVNLDQEE EIQMEVDEGA GGINGHADSP APVNGINGYN EDINQESAPK ASLRLGFSEY CRISNLIVLH LRKVEEEEDE SALKRSELVN WYLKEIESEI DSEEELINKK RIIEKVIHRL THYDHVLIEL TQAGLKGSTE GSESYEEDPY LVVNPNYLLE D //