MCM6_HUMAN
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 03-AUG-2022, entry version 209.
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 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).
CC -!- FUNCTION: Acts as component of the MCM2-7 complex (MCM complex) which
CC is the putative replicative helicase essential for 'once per cell
CC cycle' DNA replication initiation and elongation in eukaryotic cells.
CC The active ATPase sites in the MCM2-7 ring are formed through the
CC interaction surfaces of two neighboring subunits such that a critical
CC structure of a conserved arginine finger motif is provided in trans
CC relative to the ATP-binding site of the Walker A box of the adjacent
CC subunit. The six ATPase active sites, however, are likely to contribute
CC differentially to the complex helicase activity.
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). May
CC interact with MCM10 (PubMed:11095689). Interacts with TIPIN
CC (PubMed:17116885). Interacts with CDT1 (PubMed:20202939). Interacts
CC with MCMBP (PubMed:17296731). Interacts with DDI2 (PubMed:29290612).
CC Component of the CMG helicase complex, composed of the MCM2-7 complex,
CC the GINS complex and CDC45 (By similarity).
CC {ECO:0000250|UniProtKB:Q5FWY4, 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: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 detach 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/";
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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 PDBsum; 2KLQ; -.
DR PDBsum; 2LE8; -.
DR PDBsum; 6XTX; -.
DR PDBsum; 6XTY; -.
DR PDBsum; 7PFO; -.
DR PDBsum; 7PLO; -.
DR AlphaFoldDB; Q14566; -.
DR BMRB; Q14566; -.
DR SMR; Q14566; -.
DR BioGRID; 110343; 207.
DR ComplexPortal; CPX-2940; MCM complex.
DR CORUM; Q14566; -.
DR DIP; DIP-31727N; -.
DR IntAct; Q14566; 74.
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 EPD; Q14566; -.
DR jPOST; Q14566; -.
DR MassIVE; Q14566; -.
DR MaxQB; Q14566; -.
DR PaxDb; Q14566; -.
DR PeptideAtlas; Q14566; -.
DR PRIDE; Q14566; -.
DR ProteomicsDB; 60047; -.
DR Antibodypedia; 1416; 366 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 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; KYYIAQI; -.
DR OrthoDB; 266497at2759; -.
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; 751 hits in 1091 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 204 other tissues.
DR Genevisible; Q14566; HS.
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:UniProtKB-EC.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0003697; F:single-stranded DNA binding; IBA:GO_Central.
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; IC:ComplexPortal.
DR Gene3D; 2.40.50.140; -; 1.
DR Gene3D; 3.40.50.300; -; 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; PTHR11630; 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; SSF50249; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00847; MCM_1; 1.
DR PROSITE; PS50051; MCM_2; 1.
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 396..403
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
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:rs3087355)"
FT /id="VAR_014816"
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
