ID MCM2_HUMAN Reviewed; 904 AA. AC P49736; Q14577; Q15023; Q8N2V1; Q969W7; Q96AE1; Q9BRM7; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 16-JAN-2004, sequence version 4. DT 02-SEP-2026, entry version 249. DE RecName: Full=DNA replication licensing factor MCM2 {ECO:0000305}; DE EC=3.6.4.12 {ECO:0000269|PubMed:32453425}; DE AltName: Full=Minichromosome maintenance protein 2 homolog; DE AltName: Full=Nuclear protein BM28; GN Name=MCM2 {ECO:0000312|HGNC:HGNC:6944}; GN Synonyms=BM28, CCNL1, CDCL1, KIAA0030; 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], FUNCTION, SUBCELLULAR LOCATION, AND VARIANT RP GLN-166. RC TISSUE=Colon carcinoma; RX PubMed=8175912; DOI=10.1242/jcs.107.1.253; RA Todorov I.T., Pepperkok R., Philipova R.N., Kearsey S.E., Ansorge W., RA Werner D.; RT "A human nuclear protein with sequence homology to a family of early S RT phase proteins is required for entry into S phase and for cell division."; RL J. Cell Sci. 107:253-265(1994). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Bone marrow; RX PubMed=7584026; DOI=10.1093/dnares/1.1.27; RA Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., Sato S., RA Nagase T., Seki N., Ishikawa K., Tabata S.; RT "Prediction of the coding sequences of unidentified human genes. I. The RT coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of RT randomly sampled cDNA clones from human immature myeloid cell line KG-1."; RL DNA Res. 1:27-35(1994). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLU-68; PHE-135; THR-396; RP MET-667 AND THR-727. RG NIEHS SNPs program; RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ARG-501 AND THR-727. RC TISSUE=Brain, Lung, Lymph, Muscle, Placenta, and Uterus; 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 [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-904. RC TISSUE=Cervix carcinoma; RA Mimura S., Nishimoto S., Kubota Y., Takisawa H., Nojima H.; RT "Homo sapiens DNA replication licensing factor (huMCM2)."; RL Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 10-904. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP CHROMOSOMAL LOCATION. RX PubMed=8258304; DOI=10.1159/000133647; RA Mincheva A., Todorov I.T., Werner D., Fink T.M., Lichter P.; RT "The human gene for nuclear protein BM28 (CDCL1), a new member of the early RT S-phase family of proteins, maps to chromosome band 3q21."; RL Cytogenet. Cell Genet. 65:276-277(1994). RN [8] RP IDENTIFICATION IN THE MCM2-7 COMPLEX. 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 PHOSPHORYLATION AT SER-108, AND MUTAGENESIS OF SER-108. RX PubMed=15210935; DOI=10.1073/pnas.0403410101; RA Cortez D., Glick G., Elledge S.J.; RT "Minichromosome maintenance proteins are direct targets of the ATM and ATR RT checkpoint kinases."; RL Proc. Natl. Acad. Sci. U.S.A. 101:10078-10083(2004). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [12] RP PHOSPHORYLATION AT SER-27; SER-41; SER-53; SER-108 AND SER-139, MUTAGENESIS RP OF SER-27; SER-41 AND SER-139, IDENTIFICATION IN THE MCM2-7 COMPLEX, AND RP ATPASE ACTIVITY OF THE MCM2-7 COMPLEX. 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 INTERACTION WITH KAT7. RX PubMed=16387653; DOI=10.1016/j.molcel.2005.12.007; RA Doyon Y., Cayrou C., Ullah M., Landry A.-J., Cote V., Selleck W., RA Lane W.S., Tan S., Yang X.-J., Cote J.; RT "ING tumor suppressor proteins are critical regulators of chromatin RT acetylation required for genome expression and perpetuation."; RL Mol. Cell 21:51-64(2006). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27 AND SER-41, 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 [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Prostate cancer; RX PubMed=17487921; DOI=10.1002/elps.200600782; RA Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.; RT "Toward a global characterization of the phosphoproteome in prostate cancer RT cells: identification of phosphoproteins in the LNCaP cell line."; RL Electrophoresis 28:2027-2034(2007). RN [16] RP PHOSPHORYLATION AT SER-40 AND SER-53. RX PubMed=17062569; DOI=10.1074/jbc.m604457200; RA Tenca P., Brotherton D., Montagnoli A., Rainoldi S., Albanese C., RA Santocanale C.; RT "Cdc7 is an active kinase in human cancer cells undergoing replication RT stress."; RL J. Biol. Chem. 282:208-215(2007). RN [17] 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 [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-108, 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 [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=T-cell; RX PubMed=19367720; DOI=10.1021/pr800500r; RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.; RT "Phosphorylation analysis of primary human T lymphocytes using sequential RT IMAC and titanium oxide enrichment."; RL J. Proteome Res. 7:5167-5176(2008). RN [21] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26; THR-39; SER-40; SER-41; RP SER-53 AND SER-139, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [23] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27; THR-59; SER-108 AND RP SER-139, AND 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 [25] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-216, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [26] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-13; SER-27; SER-41; SER-108 AND SER-139, CLEAVAGE OF RP INITIATOR METHIONINE [LARGE SCALE ANALYSIS], 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 [27] 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 [28] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-13; SER-26; SER-27; SER-41; SER-139 AND SER-381, CLEAVAGE RP OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [29] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [30] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [31] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13; THR-25; SER-26; SER-27; RP SER-32; SER-40; SER-41; SER-139 AND SER-484, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE 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 [32] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13; SER-27; TYR-137 AND RP SER-139, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [33] RP PHOSPHORYLATION AT SER-53. RX PubMed=27401717; DOI=10.1038/ncomms12135; RA Yang C.C., Suzuki M., Yamakawa S., Uno S., Ishii A., Yamazaki S., RA Fukatsu R., Fujisawa R., Sakimura K., Tsurimoto T., Masai H.; RT "Claspin recruits Cdc7 kinase for initiation of DNA replication in human RT cells."; RL Nat. Commun. 7:12135-12135(2016). RN [34] RP INTERACTION WITH DONSON. RX PubMed=28191891; DOI=10.1038/ng.3790; RA Reynolds J.J., Bicknell L.S., Carroll P., Higgs M.R., Shaheen R., RA Murray J.E., Papadopoulos D.K., Leitch A., Murina O., Tarnauskaite Z., RA Wessel S.R., Zlatanou A., Vernet A., von Kriegsheim A., Mottram R.M., RA Logan C.V., Bye H., Li Y., Brean A., Maddirevula S., Challis R.C., RA Skouloudaki K., Almoisheer A., Alsaif H.S., Amar A., Prescott N.J., RA Bober M.B., Duker A., Faqeih E., Seidahmed M.Z., Al Tala S., Alswaid A., RA Ahmed S., Al-Aama J.Y., Altmueller J., Al Balwi M., Brady A.F., Chessa L., RA Cox H., Fischetto R., Heller R., Henderson B.D., Hobson E., Nuernberg P., RA Percin E.F., Peron A., Spaccini L., Quigley A.J., Thakur S., Wise C.A., RA Yoon G., Alnemer M., Tomancak P., Yigit G., Taylor A.M., Reijns M.A., RA Simpson M.A., Cortez D., Alkuraya F.S., Mathew C.G., Jackson A.P., RA Stewart G.S.; RT "Mutations in DONSON disrupt replication fork stability and cause RT microcephalic dwarfism."; RL Nat. Genet. 49:537-549(2017). RN [35] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-178, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [36] RP FUNCTION, AND SUBCELLULAR LOCATION. 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 [37] RP INTERACTION WITH AGER. RX PubMed=36807739; DOI=10.1093/nar/gkad085; RA Han Z., Andrs M., Madhavan B.K., Kaymak S., Sulaj A., Kender Z., Kopf S., RA Kihm L., Pepperkok R., Janscak P., Nawroth P., Kumar V.; RT "The importance of nuclear RAGE-Mcm2 axis in diabetes or cancer-associated RT replication stress."; RL Nucleic Acids Res. 51:2298-2318(2023). RN [38] {ECO:0007744|PDB:6XTX, ECO:0007744|PDB:6XTY} RP STRUCTURE BY ELECTRON MICROSCOPY (3.29 ANGSTROMS) IN COMPLEXES WITH ADP IN RP CMG COMPLEX, SUBUNIT, CATALYTIC ACTIVITY, AND FUNCTION. 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 [39] {ECO:0007744|PDB:7CIZ, ECO:0007744|PDB:7CJ0} RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 61-130 IN COMPLEX WITH DNJC9 RP 171-249 MUTANT CYS-243 AND HISTONES H3.3 58-136 AND H4, IDENTIFICATION IN A RP CO-CHAPERONE COMPLEX WITH DNJC9 AND HISTONES H3.3 AND H4, INTERACTION WITH RP DNJC9; H3.1 AND H3.3, AND MUTAGENESIS OF 81-TYR--TYR-90. RX PubMed=33857403; DOI=10.1016/j.molcel.2021.03.041; RA Hammond C.M., Bao H., Hendriks I.A., Carraro M., Garcia-Nieto A., Liu Y., RA Reveron-Gomez N., Spanos C., Chen L., Rappsilber J., Nielsen M.L., RA Patel D.J., Huang H., Groth A.; RT "DNAJC9 integrates heat shock molecular chaperones into the histone RT chaperone network."; RL Mol. Cell 0:0-0(2021). RN [40] {ECO:0007744|PDB:7PFO} RP STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) IN REPLISOME, SUBUNIT, RP AND FUNCTION. 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 [41] {ECO:0007744|PDB:7PLO} RP STRUCTURE BY ELECTRON MICROSCOPY (2.80 ANGSTROMS) IN REPLISOME, SUBUNIT, RP AND FUNCTION. 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 [42] RP INVOLVEMENT IN DFNA70, VARIANT DFNA70 CYS-44, CHARACTERIZATION OF VARIANT RP DFNA70 CYS-44, AND FUNCTION. RX PubMed=26196677; DOI=10.1371/journal.pone.0133522; RA Gao J., Wang Q., Dong C., Chen S., Qi Y., Liu Y.; RT "Whole exome sequencing identified MCM2 as a novel causative gene for RT autosomal dominant nonsyndromic deafness in a chinese family."; RL PLoS ONE 10:E0133522-E0133534(2015). 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). The active ATPase sites in the MCM2-7 ring are formed CC through the interaction surfaces of two neighboring subunits such that CC a critical structure of a conserved arginine finger motif is provided CC in trans relative to the ATP-binding site of the Walker A box of the CC adjacent subunit. The six ATPase active sites, however, are likely to CC contribute differentially to the complex helicase activity CC (PubMed:32453425). Required for the entry in S phase and for cell CC division (PubMed:8175912). Plays a role in terminally differentiated CC hair cells development of the cochlea and induces cells apoptosis CC (PubMed:26196677). {ECO:0000269|PubMed:26196677, CC ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, CC ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, CC ECO:0000269|PubMed:8175912}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + phosphate + H(+); 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:32453425}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066; CC Evidence={ECO:0000269|PubMed:32453425}; 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:32453425, CC PubMed:34694004, PubMed:34700328, PubMed:9305914). Component of the CMG CC helicase complex, a hexameric ring of related MCM2-7 subunits CC stabilized by CDC45 and the tetrameric GINS complex (PubMed:32453425, CC PubMed:34694004, PubMed:34700328). Interacts with DBF4 (By similarity). CC Interacts with KAT7 (PubMed:16387653). May interact with MCM10 CC (PubMed:11095689). Component of the replisome complex composed of at CC least DONSON, MCM2, MCM7, PCNA and TICRR (PubMed:28191891). Forms a co- CC chaperone complex with DNAJC9 and histone H3.3-H4 heterodimers CC (PubMed:33857403). Within the complex, interacts (via N-terminus) with CC DNAJC9 (via C-terminus); the interaction is histone-dependent CC (PubMed:33857403). Interacts with histones H3.1 and H3.3 CC (PubMed:33857403). Interacts with AGER/RAGE; the interaction is CC increased following DNA replication stress and stabilizes the MCM2-7 CC complex at replication forks (PubMed:36807739). CC {ECO:0000250|UniProtKB:P55861, ECO:0000250|UniProtKB:P97310, CC ECO:0000269|PubMed:11095689, ECO:0000269|PubMed:16387653, CC ECO:0000269|PubMed:16899510, ECO:0000269|PubMed:17296731, CC ECO:0000269|PubMed:28191891, ECO:0000269|PubMed:32453425, CC ECO:0000269|PubMed:33857403, ECO:0000269|PubMed:34694004, CC ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:36807739, CC ECO:0000269|PubMed:9305914}. CC -!- INTERACTION: CC P49736; O43823: AKAP8; NbExp=7; IntAct=EBI-374819, EBI-1237481; CC P49736; Q9Y294: ASF1A; NbExp=12; IntAct=EBI-374819, EBI-749553; CC P49736; O75419: CDC45; NbExp=2; IntAct=EBI-374819, EBI-374969; CC P49736; P49450: CENPA; NbExp=3; IntAct=EBI-374819, EBI-1751979; CC P49736; Q9NYP3: DONSON; NbExp=10; IntAct=EBI-374819, EBI-32724208; CC P49736; Q8IYD8: FANCM; NbExp=5; IntAct=EBI-374819, EBI-3957237; CC P49736; Q9BRX5: GINS3; NbExp=2; IntAct=EBI-374819, EBI-2857315; CC P49736; P68431: H3C12; NbExp=8; IntAct=EBI-374819, EBI-79722; CC P49736; P62805: H4C9; NbExp=9; IntAct=EBI-374819, EBI-302023; CC P49736; Q9Y468: L3MBTL1; NbExp=3; IntAct=EBI-374819, EBI-1265089; CC P49736; P25205: MCM3; NbExp=9; IntAct=EBI-374819, EBI-355153; CC P49736; P33992: MCM5; NbExp=5; IntAct=EBI-374819, EBI-359410; CC P49736; Q14566: MCM6; NbExp=18; IntAct=EBI-374819, EBI-374900; CC P49736; P33993: MCM7; NbExp=24; IntAct=EBI-374819, EBI-355924; CC P49736; Q9BTE3: MCMBP; NbExp=5; IntAct=EBI-374819, EBI-749378; CC P49736; P53350: PLK1; NbExp=2; IntAct=EBI-374819, EBI-476768; CC P49736; Q96H20: SNF8; NbExp=8; IntAct=EBI-374819, EBI-747719; CC P49736; Q08945: SSRP1; NbExp=7; IntAct=EBI-374819, EBI-353771; CC P49736; Q9NYB0: TERF2IP; NbExp=2; IntAct=EBI-374819, EBI-750109; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:8175912}. Chromosome CC {ECO:0000305|PubMed:35585232}. Note=Associated with chromatin before CC the formation of nuclei and detaches from it as DNA replication CC progresses. {ECO:0000250|UniProtKB:P55861}. CC -!- PTM: Phosphorylated on Ser-108 by ATR in proliferating cells. Ser-108 CC proliferation is increased by genotoxic agents. Ser-40 is mediated by CC the CDC7-DBF4 and CDC7-DBF4B complexes, while Ser-53 phosphorylation is CC only mediated by the CDC7-DBF4 complex. Phosphorylation by the CDC7- CC DBF4 complex during G1/S phase is required for the initiation of DNA CC replication. {ECO:0000269|PubMed:15210935, ECO:0000269|PubMed:16899510, CC ECO:0000269|PubMed:17062569}. CC -!- DISEASE: Deafness, autosomal dominant, 70 (DFNA70) [MIM:616968]: A form CC of non-syndromic sensorineural hearing loss. Sensorineural deafness CC results from damage to the neural receptors of the inner ear, the nerve CC pathways to the brain, or the area of the brain that receives sound CC information. DFNA70 is characterized by slowly progressive, postlingual CC hearing impairment. {ECO:0000269|PubMed:26196677}. Note=The disease is CC caused by variants affecting the gene represented in this entry. 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 -!- SIMILARITY: Belongs to the MCM family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA04642.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAA12177.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAA47749.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAA47749.1; Type=Frameshift; Evidence={ECO:0000305}; 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; X67334; CAA47749.1; ALT_SEQ; mRNA. DR EMBL; D21063; BAA04642.1; ALT_INIT; mRNA. DR EMBL; AY675259; AAT70723.1; -; Genomic_DNA. DR EMBL; BC006165; AAH06165.3; -; mRNA. DR EMBL; BC007670; AAH07670.2; -; mRNA. DR EMBL; BC007938; AAH07938.2; -; mRNA. DR EMBL; BC014272; AAH14272.2; -; mRNA. DR EMBL; BC017258; AAH17258.2; -; mRNA. DR EMBL; BC017490; AAH17490.2; -; mRNA. DR EMBL; BC030131; AAH30131.2; -; mRNA. DR EMBL; D83987; BAA12177.1; ALT_INIT; mRNA. DR EMBL; BT009734; AAP88736.1; -; mRNA. DR CCDS; CCDS3043.1; -. DR PIR; S42228; S42228. DR RefSeq; NP_004517.2; NM_004526.4. DR PDB; 4UUZ; X-ray; 2.90 A; C=69-138. DR PDB; 5BNV; X-ray; 2.79 A; C/F=61-130. DR PDB; 5BNX; X-ray; 2.31 A; C=61-130. DR PDB; 5BO0; X-ray; 2.91 A; C=61-130. DR PDB; 5C3I; X-ray; 3.50 A; D/H/L/P/T/X=63-124. DR PDB; 5JA4; X-ray; 2.42 A; C=61-130. DR PDB; 6XTX; EM; 3.29 A; 2=1-904. DR PDB; 6XTY; EM; 6.77 A; 2=1-904. DR PDB; 6YA7; X-ray; 1.67 A; C=33-47. DR PDB; 7CIZ; X-ray; 1.80 A; C/G/K=61-130. DR PDB; 7CJ0; X-ray; 2.50 A; G/H=61-130. DR PDB; 7PFO; EM; 3.20 A; 2=1-904. DR PDB; 7PLO; EM; 2.80 A; 2=1-904. DR PDB; 7W1Y; EM; 2.59 A; 2/A=1-904. DR PDB; 7W68; EM; 4.40 A; A=1-904. DR PDB; 8B9D; EM; 3.40 A; 2=1-904. DR PDB; 8RWV; EM; 6.68 A; 2=1-904. DR PDB; 8S09; EM; 3.10 A; 2/A=1-904. DR PDB; 8S0A; EM; 3.20 A; 2=1-904. DR PDB; 8S0B; EM; 3.60 A; 2=1-904. DR PDB; 8S0D; EM; 3.60 A; 2=1-902. DR PDB; 8S0E; EM; 3.80 A; 2=1-904. DR PDB; 8S0F; EM; 4.10 A; 2=1-904. DR PDB; 8W0E; EM; 3.40 A; 2=1-904. DR PDB; 8W0F; EM; 2.80 A; 2/A=1-904. DR PDB; 8W0G; EM; 3.80 A; 2/A=1-904. DR PDB; 8W0I; EM; 3.50 A; 2=1-904. DR PDB; 8YJF; X-ray; 4.40 A; B=63-154. DR PDB; 8YJM; X-ray; 4.15 A; B=63-154. DR PDB; 9C6G; EM; 4.26 A; 2/8=1-904. DR PDB; 9CAQ; EM; 3.20 A; 2/A=1-904. DR PDB; 9E2Z; EM; 2.60 A; 2=1-904. DR PDB; 9LXD; EM; 3.27 A; 2=1-904. DR PDB; 9LXE; EM; 3.96 A; 2/D=1-904. DR PDB; 9LXF; EM; 3.86 A; 2/D=1-904. DR AlphaFoldDB; P49736; -. DR EMDB; EMD-10619; -. DR EMDB; EMD-10621; -. DR EMDB; EMD-13375; -. DR EMDB; EMD-13494; -. DR EMDB; EMD-19566; -. DR EMDB; EMD-19618; -. DR EMDB; EMD-19619; -. DR EMDB; EMD-19620; -. DR EMDB; EMD-19622; -. DR EMDB; EMD-19623; -. DR EMDB; EMD-19624; -. DR EMDB; EMD-32258; -. DR EMDB; EMD-32326; -. DR EMDB; EMD-43707; -. DR EMDB; EMD-43708; -. DR EMDB; EMD-43709; -. DR EMDB; EMD-43710; -. DR EMDB; EMD-45246; -. DR EMDB; EMD-45400; -. DR EMDB; EMD-47473; -. DR EMDB; EMD-63474; -. DR EMDB; EMD-63475; -. DR EMDB; EMD-63476; -. DR SMR; P49736; -. DR BioGRID; 110339; 1113. DR ComplexPortal; CPX-2940; MCM complex. DR CORUM; P49736; -. DR DIP; DIP-31732N; -. DR ELM; P49736; -. DR FunCoup; P49736; 2640. DR IntAct; P49736; 123. DR MINT; P49736; -. DR NDEx; IQUERY-CP-MCM2; 11 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000265056; -. DR BindingDB; P49736; -. DR ChEMBL; CHEMBL3308910; -. DR GlyGen; P49736; 4 sites, 1 O-linked glycan (4 sites). DR iPTMnet; P49736; -. DR MetOSite; P49736; -. DR PhosphoSitePlus; P49736; -. DR SwissPalm; P49736; -. DR BioMuta; MCM2; -. DR DMDM; 41019490; -. DR CPTAC; CPTAC-1618; -. DR jPOST; P49736; -. DR MassIVE; P49736; -. DR PaxDb; 9606-ENSP00000265056; -. DR PeptideAtlas; P49736; -. DR ProteomicsDB; 56058; -. DR Pumba; P49736; -. DR Antibodypedia; 4369; 1140 antibodies from 46 providers. DR DNASU; 4171; -. DR Ensembl; ENST00000265056.12; ENSP00000265056.7; ENSG00000073111.16. DR GeneID; 4171; -. DR KEGG; hsa:4171; -. DR MANE-Select; ENST00000265056.12; ENSP00000265056.7; NM_004526.4; NP_004517.2. DR UCSC; uc003ejp.5; human. DR AGR; HGNC:6944; -. DR ClinPGx; PA164742061; -. DR CTD; 4171; -. DR DisGeNET; 4171; -. DR GeneCards; MCM2; -. DR HGNC; HGNC:6944; MCM2. DR HPA; ENSG00000073111; Tissue enhanced (bone marrow, lymphoid tissue). DR MalaCards; MCM2; -. DR MIM; 116945; gene. DR MIM; 616968; phenotype. DR OpenTargets; ENSG00000073111; -. DR Orphanet; 90635; Autosomal dominant non-syndromic genetic deafness. DR VEuPathDB; HostDB:ENSG00000073111; -. DR eggNOG; KOG0477; Eukaryota. DR GeneTree; ENSGT01150000286951; -. DR HOGENOM; CLU_000995_0_1_1; -. DR InParanoid; P49736; -. DR OMA; TYERVTT; -. DR OrthoDB; 844at2759; -. DR PAN-GO; P49736; 7 GO annotations based on evolutionary models. DR PhylomeDB; P49736; -. DR PathwayCommons; P49736; -. 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 Reactome; R-HSA-9825895; Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence. DR SignaLink; P49736; -. DR SIGNOR; P49736; -. DR Agora; ENSG00000073111; -. DR BioGRID-ORCS; 4171; 835 hits in 1177 CRISPR screens. DR CD-CODE; 91857CE7; Nucleolus. DR ChiTaRS; MCM2; human. DR EvolutionaryTrace; P49736; -. DR GeneWiki; MCM2; -. DR GenomeRNAi; 4171; -. DR Pharos; P49736; Tbio. DR PRO; PR:P49736; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; P49736; protein. DR Bgee; ENSG00000073111; Expressed in oocyte and 157 other cell types or tissues. DR ExpressionAtlas; P49736; baseline and differential. DR GO; GO:0000785; C:chromatin; IDA:UniProtKB. DR GO; GO:0000781; C:chromosome, telomeric region; HDA:BHF-UCL. DR GO; GO:0071162; C:CMG complex; IPI:ComplexPortal. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0042555; C:MCM complex; IDA:UniProtKB. DR GO; GO:0005664; C:nuclear origin of replication recognition complex; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0016887; F:ATP hydrolysis activity; EXP:UniProtKB. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0003678; F:DNA helicase activity; IEA:UniProtKB-EC. DR GO; GO:0003688; F:DNA replication origin binding; IEA:Ensembl. DR GO; GO:0019899; F:enzyme binding; IEA:Ensembl. DR GO; GO:0042393; F:histone binding; IPI:DisProt. DR GO; GO:0003697; F:single-stranded DNA binding; IBA:GO_Central. DR GO; GO:0006915; P:apoptotic process; IMP:UniProtKB. DR GO; GO:0090102; P:cochlea development; IMP:UniProtKB. DR GO; GO:0006260; P:DNA replication; IDA:ComplexPortal. DR GO; GO:0006270; P:DNA replication initiation; IMP:UniProtKB. DR GO; GO:0000727; P:double-strand break repair via break-induced replication; IBA:GO_Central. DR GO; GO:1902975; P:mitotic DNA replication initiation; IBA:GO_Central. DR GO; GO:0030174; P:regulation of DNA-templated DNA replication initiation; NAS:ComplexPortal. DR CDD; cd17753; MCM2; 1. DR DisProt; DP01977; -. DR FunFam; 2.20.28.10:FF:000002; DNA helicase; 1. DR FunFam; 3.30.1640.10:FF:000005; DNA helicase; 1. DR FunFam; 3.40.50.300:FF:000138; DNA helicase; 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 IDEAL; IID00715; -. DR InterPro; IPR031327; MCM. DR InterPro; IPR008045; MCM2. DR InterPro; IPR061506; MCM2_N. 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 InterPro; IPR059098; WHD_MCM2. DR PANTHER; PTHR11630; DNA REPLICATION LICENSING FACTOR MCM FAMILY MEMBER; 1. DR PANTHER; PTHR11630:SF44; DNA REPLICATION LICENSING FACTOR MCM2; 1. DR Pfam; PF00493; MCM; 1. DR Pfam; PF12619; MCM2_N; 1. DR Pfam; PF17855; MCM_lid; 1. DR Pfam; PF14551; MCM_N; 1. DR Pfam; PF17207; MCM_OB; 1. DR Pfam; PF23669; WHD_MCM2; 1. DR PRINTS; PR01657; MCMFAMILY. DR PRINTS; PR01658; MCMPROTEIN2. 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_CTD; 1. DR PDBsum; 4UUZ; -. DR PDBsum; 5BNV; -. DR PDBsum; 5BNX; -. DR PDBsum; 5BO0; -. DR PDBsum; 5C3I; -. DR PDBsum; 5JA4; -. DR PDBsum; 6XTX; -. DR PDBsum; 6XTY; -. DR PDBsum; 6YA7; -. DR PDBsum; 7CIZ; -. DR PDBsum; 7CJ0; -. DR PDBsum; 7PFO; -. DR PDBsum; 7PLO; -. DR PDBsum; 7W1Y; -. DR PDBsum; 7W68; -. DR PDBsum; 8B9D; -. DR PDBsum; 8RWV; -. DR PDBsum; 8S09; -. DR PDBsum; 8S0A; -. DR PDBsum; 8S0B; -. DR PDBsum; 8S0D; -. DR PDBsum; 8S0E; -. DR PDBsum; 8S0F; -. DR PDBsum; 8W0E; -. DR PDBsum; 8W0F; -. DR PDBsum; 8W0G; -. DR PDBsum; 8W0I; -. DR PDBsum; 8YJF; -. DR PDBsum; 8YJM; -. DR PDBsum; 9C6G; -. DR PDBsum; 9CAQ; -. DR PDBsum; 9E2Z; -. DR PDBsum; 9LXD; -. DR PDBsum; 9LXE; -. DR PDBsum; 9LXF; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; ATP-binding; Cell cycle; Chromosome; Deafness; KW Disease variant; DNA replication; DNA-binding; Helicase; Hydrolase; KW Isopeptide bond; Metal-binding; Non-syndromic deafness; Nucleotide-binding; KW Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; KW Ubl conjugation; Zinc; Zinc-finger. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT CHAIN 2..904 FT /note="DNA replication licensing factor MCM2" FT /id="PRO_0000194087" FT DOMAIN 456..808 FT /note="MCM C-terminal AAA(+) ATPase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01410" FT ZN_FING 329..355 FT /note="C4-type" FT /evidence="ECO:0000255" FT REGION 1..80 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2..257 FT /note="Interaction with KAT7" FT /evidence="ECO:0000250" FT REGION 61..130 FT /note="Interaction with DNJC9" FT /evidence="ECO:0000269|PubMed:33857403" FT REGION 109..167 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 686..705 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 523..530 FT /note="Walker A" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01410" FT MOTIF 587..590 FT /note="Walker B" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01410" FT COMPBIAS 1..15 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 62..73 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 111..125 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 530 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /ligand_note="ligand shared with MCM6" FT /evidence="ECO:0000269|PubMed:32453425, FT ECO:0007744|PDB:6XTX" FT BINDING 531 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /ligand_note="ligand shared with MCM6" FT /evidence="ECO:0000269|PubMed:32453425, FT ECO:0007744|PDB:6XTX" FT SITE 656 FT /note="Arginine finger" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01410" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT MOD_RES 12 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P97310" FT MOD_RES 13 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 25 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 26 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 27 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:16899510, FT ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 32 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 39 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 40 FT /note="Phosphoserine; by CDC7" FT /evidence="ECO:0000269|PubMed:17062569, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163" FT MOD_RES 41 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:16899510, FT ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 53 FT /note="Phosphoserine; by CDC7" FT /evidence="ECO:0000269|PubMed:16899510, FT ECO:0000269|PubMed:17062569, ECO:0000269|PubMed:27401717, FT ECO:0007744|PubMed:18669648" FT MOD_RES 59 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 108 FT /note="Phosphoserine; by ATR" FT /evidence="ECO:0000269|PubMed:15210935, FT ECO:0000269|PubMed:16899510, ECO:0007744|PubMed:17525332, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231" FT MOD_RES 137 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 139 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:16899510, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 216 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 381 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 484 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CROSSLNK 178 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VARIANT 44 FT /note="R -> C (in DFNA70; increases the apoptotic process; FT no effect on cell proliferation and cell cycle phase; FT dbSNP:rs375851208)" FT /evidence="ECO:0000269|PubMed:26196677" FT /id="VAR_077049" FT VARIANT 68 FT /note="D -> E (in dbSNP:rs3087452)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_021111" FT VARIANT 135 FT /note="L -> F (in dbSNP:rs2307314)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_021112" FT VARIANT 166 FT /note="E -> Q (in dbSNP:rs1048225)" FT /evidence="ECO:0000269|PubMed:8175912" FT /id="VAR_033298" FT VARIANT 396 FT /note="A -> T (in dbSNP:rs3087450)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_016137" FT VARIANT 501 FT /note="G -> R (in dbSNP:rs13087457)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_033299" FT VARIANT 667 FT /note="V -> M (in dbSNP:rs2307311)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_016138" FT VARIANT 727 FT /note="A -> T (in dbSNP:rs2307313)" FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3" FT /id="VAR_016139" FT MUTAGEN 27 FT /note="S->A: Impairs ATPase activity of the MCM-2-7 complex FT and reduces phosphorylation by the CDC7-DBF4 complex; when FT associated with A-41 and A-139." FT /evidence="ECO:0000269|PubMed:16899510" FT MUTAGEN 41 FT /note="S->A: Impairs ATPase activity of the MCM-2-7 complex FT and reduces phosphorylation by the CDC7-DBF4 complex; when FT associated with A-27 and A-139." FT /evidence="ECO:0000269|PubMed:16899510" FT MUTAGEN 81..90 FT /note="YRAIPELDAY->ARAIPELDAA: Loss of interaction with FT DNAJC9." FT /evidence="ECO:0000269|PubMed:33857403" FT MUTAGEN 108 FT /note="S->A: Reduces phosphorylation by ATR." FT /evidence="ECO:0000269|PubMed:15210935" FT MUTAGEN 139 FT /note="S->A: Impairs ATPase activity of the MCM-2-7 complex FT and reduces phosphorylation by the CDC7-DBF4 complex; when FT associated with A-27 and A-41." FT /evidence="ECO:0000269|PubMed:16899510" FT CONFLICT 1 FT /note="M -> S (in Ref. 1; CAA47749)" FT /evidence="ECO:0000305" FT CONFLICT 109 FT /note="Q -> R (in Ref. 1; CAA47749)" FT /evidence="ECO:0000305" FT CONFLICT 388 FT /note="G -> R (in Ref. 1; CAA47749)" FT /evidence="ECO:0000305" FT CONFLICT 407..408 FT /note="KP -> NA (in Ref. 1; CAA47749 and 5; BAA12177)" FT /evidence="ECO:0000305" FT CONFLICT 495 FT /note="L -> P (in Ref. 1; CAA47749)" FT /evidence="ECO:0000305" FT CONFLICT 555..556 FT /note="GL -> AV (in Ref. 1; CAA47749)" FT /evidence="ECO:0000305" FT HELIX 39..41 FT /evidence="ECO:0007829|PDB:6YA7" FT STRAND 69..74 FT /evidence="ECO:0007829|PDB:7CIZ" FT HELIX 77..81 FT /evidence="ECO:0007829|PDB:7CIZ" FT TURN 85..87 FT /evidence="ECO:0007829|PDB:7CIZ" FT STRAND 98..100 FT /evidence="ECO:0007829|PDB:5BO0" FT HELIX 103..106 FT /evidence="ECO:0007829|PDB:7CIZ" FT HELIX 107..124 FT /evidence="ECO:0007829|PDB:7CIZ" FT HELIX 170..172 FT /evidence="ECO:0007829|PDB:7PFO" FT HELIX 182..187 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 189..205 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 209..211 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 214..224 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 229..233 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 234..240 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 242..250 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 252..270 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 272..276 FT /evidence="ECO:0007829|PDB:7W1Y" FT TURN 277..279 FT /evidence="ECO:0007829|PDB:8W0F" FT STRAND 282..286 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 289..292 FT /evidence="ECO:0007829|PDB:8S09" FT HELIX 294..296 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 299..301 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 304..315 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 316..318 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 319..329 FT /evidence="ECO:0007829|PDB:7W1Y" FT TURN 330..332 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 335..340 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 343..345 FT /evidence="ECO:0007829|PDB:9E2Z" FT HELIX 346..348 FT /evidence="ECO:0007829|PDB:7PLO" FT TURN 353..355 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 361..379 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 382..384 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 387..389 FT /evidence="ECO:0007829|PDB:7PFO" FT HELIX 390..392 FT /evidence="ECO:0007829|PDB:9E2Z" FT STRAND 393..399 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 400..402 FT /evidence="ECO:0007829|PDB:9E2Z" FT STRAND 403..405 FT /evidence="ECO:0007829|PDB:6XTX" FT STRAND 411..419 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 428..432 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 438..446 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 448..450 FT /evidence="ECO:0007829|PDB:8W0I" FT TURN 453..455 FT /evidence="ECO:0007829|PDB:9E2Z" FT HELIX 461..468 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 473..479 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 481..485 FT /evidence="ECO:0007829|PDB:6XTX" FT HELIX 489..500 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 507..509 FT /evidence="ECO:0007829|PDB:7PLO" FT STRAND 519..523 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 525..528 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 529..539 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 540..550 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 552..554 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 559..562 FT /evidence="ECO:0007829|PDB:7W1Y" FT TURN 564..566 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 569..572 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 575..578 FT /evidence="ECO:0007829|PDB:7W1Y" FT TURN 579..581 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 582..588 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 589..591 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 594..606 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 607..615 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 617..621 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 625..630 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 633..635 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 639..641 FT /evidence="ECO:0007829|PDB:9CAQ" FT HELIX 643..645 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 646..648 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 651..654 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 658..663 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 669..685 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 688..690 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 709..712 FT /evidence="ECO:0007829|PDB:8S0A" FT STRAND 713..715 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 720..728 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 734..736 FT /evidence="ECO:0007829|PDB:7PLO" FT STRAND 737..739 FT /evidence="ECO:0007829|PDB:6XTX" FT HELIX 741..756 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 757..759 FT /evidence="ECO:0007829|PDB:6XTX" FT HELIX 760..762 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 764..780 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 784..786 FT /evidence="ECO:0007829|PDB:7PLO" FT HELIX 788..804 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 808..817 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 819..822 FT /evidence="ECO:0007829|PDB:7W1Y" FT TURN 823..825 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 828..850 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 851..853 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 856..861 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 862..871 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 878..882 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 884..888 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 891..894 FT /evidence="ECO:0007829|PDB:7W1Y" FT TURN 895..898 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 899..902 FT /evidence="ECO:0007829|PDB:7W1Y" SQ SEQUENCE 904 AA; 101896 MW; 52C6DC61F128B404 CRC64; MAESSESFTM ASSPAQRRRG NDPLTSSPGR SSRRTDALTS SPGRDLPPFE DESEGLLGTE GPLEEEEDGE ELIGDGMERD YRAIPELDAY EAEGLALDDE DVEELTASQR EAAERAMRQR DREAGRGLGR MRRGLLYDSD EEDEERPARK RRQVERATED GEEDEEMIES IENLEDLKGH SVREWVSMAG PRLEIHHRFK NFLRTHVDSH GHNVFKERIS DMCKENRESL VVNYEDLAAR EHVLAYFLPE APAELLQIFD EAALEVVLAM YPKYDRITNH IHVRISHLPL VEELRSLRQL HLNQLIRTSG VVTSCTGVLP QLSMVKYNCN KCNFVLGPFC QSQNQEVKPG SCPECQSAGP FEVNMEETIY QNYQRIRIQE SPGKVAAGRL PRSKDAILLA DLVDSCKPGD EIELTGIYHN NYDGSLNTAN GFPVFATVIL ANHVAKKDNK VAVGELTDED VKMITSLSKD QQIGEKIFAS IAPSIYGHED IKRGLALALF GGEPKNPGGK HKVRGDINVL LCGDPGTAKS QFLKYIEKVS SRAIFTTGQG ASAVGLTAYV QRHPVSREWT LEAGALVLAD RGVCLIDEFD KMNDQDRTSI HEAMEQQSIS ISKAGIVTSL QARCTVIAAA NPIGGRYDPS LTFSENVDLT EPIISRFDIL CVVRDTVDPV QDEMLARFVV GSHVRHHPSN KEEEGLANGS AAEPAMPNTY GVEPLPQEVL KKYIIYAKER VHPKLNQMDQ DKVAKMYSDL RKESMATGSI PITVRHIESM IRMAEAHARI HLRDYVIEDD VNMAIRVMLE SFIDTQKFSV MRSMRKTFAR YLSFRRDNNE LLLFILKQLV AEQVTYQRNR FGAQQDTIEV PEKDLVDKAR QINIHNLSAF YDSELFRMNK FSHDLKRKMI LQQF //