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 27-MAR-2024, entry version 239.
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] {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 [38] {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 [39] {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 [40] {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 [41]
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 + 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: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:9305914,
CC PubMed:16899510, PubMed:17296731). The complex forms a toroidal
CC hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-
CC MCM3-MCM5 (PubMed:9305914, PubMed:16899510, PubMed:17296731,
CC PubMed:34700328, PubMed:34694004, PubMed:32453425). 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). 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). {ECO:0000250|UniProtKB:P55861,
CC ECO:0000250|UniProtKB:P97310, ECO:0000269|PubMed:11095689,
CC ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:16899510,
CC ECO:0000269|PubMed:17296731, ECO:0000269|PubMed:28191891,
CC ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:33857403,
CC ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328,
CC ECO:0000269|PubMed:9305914}.
CC -!- INTERACTION:
CC P49736; O43823: AKAP8; NbExp=7; IntAct=EBI-374819, EBI-1237481;
CC P49736; Q9Y294: ASF1A; NbExp=10; 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; P68431: H3C12; NbExp=6; IntAct=EBI-374819, EBI-79722;
CC P49736; P62805: H4C9; NbExp=9; IntAct=EBI-374819, EBI-302023;
CC P49736; Q9Y468: L3MBTL1; NbExp=2; IntAct=EBI-374819, EBI-1265089;
CC P49736; P25205: MCM3; NbExp=8; IntAct=EBI-374819, EBI-355153;
CC P49736; P33992: MCM5; NbExp=5; IntAct=EBI-374819, EBI-359410;
CC P49736; Q14566: MCM6; NbExp=16; IntAct=EBI-374819, EBI-374900;
CC P49736; P33993: MCM7; NbExp=21; IntAct=EBI-374819, EBI-355924;
CC P49736; Q9BTE3: MCMBP; NbExp=4; 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=3; 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 -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/mcm2/";
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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_004526.3.
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 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 AlphaFoldDB; P49736; -.
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; P49736; -.
DR BioGRID; 110339; 1078.
DR ComplexPortal; CPX-2940; MCM complex.
DR CORUM; P49736; -.
DR DIP; DIP-31732N; -.
DR ELM; P49736; -.
DR IntAct; P49736; 93.
DR MINT; P49736; -.
DR STRING; 9606.ENSP00000265056; -.
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 EPD; P49736; -.
DR jPOST; P49736; -.
DR MassIVE; P49736; -.
DR MaxQB; P49736; -.
DR PaxDb; 9606-ENSP00000265056; -.
DR PeptideAtlas; P49736; -.
DR ProteomicsDB; 56058; -.
DR Pumba; P49736; -.
DR Antibodypedia; 4369; 1304 antibodies from 43 providers.
DR DNASU; 4171; -.
DR Ensembl; ENST00000265056.12; ENSP00000265056.7; ENSG00000073111.14.
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 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 neXtProt; NX_P49736; -.
DR OpenTargets; ENSG00000073111; -.
DR Orphanet; 90635; Rare autosomal dominant non-syndromic sensorineural deafness type DFNA.
DR PharmGKB; PA164742061; -.
DR VEuPathDB; HostDB:ENSG00000073111; -.
DR eggNOG; KOG0477; Eukaryota.
DR GeneTree; ENSGT01050000244824; -.
DR HOGENOM; CLU_000995_0_1_1; -.
DR InParanoid; P49736; -.
DR OMA; TYERVTT; -.
DR OrthoDB; 5476523at2759; -.
DR PhylomeDB; P49736; -.
DR TreeFam; TF300772; -.
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 SignaLink; P49736; -.
DR SIGNOR; P49736; -.
DR BioGRID-ORCS; 4171; 835 hits in 1177 CRISPR screens.
DR ChiTaRS; MCM2; human.
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 Genevisible; P49736; HS.
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:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR GO; GO:0003688; F:DNA replication origin binding; IEA:Ensembl.
DR GO; GO:0019899; F:enzyme binding; IEA:Ensembl.
DR GO; GO:0004386; F:helicase activity; IEA:UniProtKB-KW.
DR GO; GO:0042393; F:histone binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003697; F:single-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IMP:UniProtKB.
DR GO; GO:0071353; P:cellular response to interleukin-4; IEA:Ensembl.
DR GO; GO:0090102; P:cochlea development; IMP:UniProtKB.
DR GO; GO:0006260; P:DNA replication; TAS:ProtInc.
DR GO; GO:0006270; P:DNA replication initiation; IMP:UniProtKB.
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:1902975; P:mitotic DNA replication initiation; IBA:GO_Central.
DR GO; GO:0006334; P:nucleosome assembly; IEA:Ensembl.
DR GO; GO:0030174; P:regulation of DNA-templated DNA replication initiation; NAS:ComplexPortal.
DR CDD; cd17753; MCM2; 1.
DR DisProt; DP01977; -.
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; 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: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 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_2; 1.
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; Reference proteome; Ubl conjugation; Zinc;
KW 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 473..679
FT /note="MCM"
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 655..658
FT /note="Arginine finger"
FT COMPBIAS 1..39
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 57..74
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 109..158
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 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 STRAND 70..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 107..124
FT /evidence="ECO:0007829|PDB:7CIZ"
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
//
