MCM7_HUMAN
ID MCM7_HUMAN Reviewed; 719 AA.
AC P33993; A4D2A1; A4D2A2; E9PGN9; Q15076; Q96D34; Q96GL1;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2002, sequence version 4.
DT 03-AUG-2022, entry version 226.
DE RecName: Full=DNA replication licensing factor MCM7;
DE EC=3.6.4.12 {ECO:0000269|PubMed:25661590};
DE AltName: Full=CDC47 homolog;
DE AltName: Full=P1.1-MCM3;
GN Name=MCM7 {ECO:0000312|HGNC:HGNC:6950}; Synonyms=CDC47, MCM2;
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] (ISOFORM 1), AND VARIANT SER-144.
RX PubMed=8626784; DOI=10.1074/jbc.271.8.4349;
RA Fujita M., Kiyono T., Hayashi Y., Ishibashi M.;
RT "hCDC47, a human member of the MCM family. Dissociation of the nucleus-
RT bound form during S phase.";
RL J. Biol. Chem. 271:4349-4354(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
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] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Lung;
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 PROTEIN SEQUENCE OF 2-12; 16-29; 33-39; 76-106; 134-147; 252-282; 472-481;
RP 500-514 AND 605-611, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT
RP ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Chronic myeloid leukemia cell;
RA Bienvenut W.V., von Kriegsheim A., Kolch W.;
RL Submitted (DEC-2008) to UniProtKB.
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 103-719.
RA Hu B.;
RL Submitted (FEB-1995) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 177-719.
RC TISSUE=Lung;
RX PubMed=7842741; DOI=10.1159/000133918;
RA Nakatsuru S., Sudo K., Nakamura Y.;
RT "Isolation and mapping of a human gene (MCM2) encoding a product homologous
RT to yeast proteins involved in DNA replication.";
RL Cytogenet. Cell Genet. 68:226-230(1995).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 261-557.
RC TISSUE=Cervix;
RX PubMed=8265339; DOI=10.1093/nar/21.23.5289-a;
RA Hu B., Burkhart R., Schulte D., Musahl C., Knippers R.;
RT "The P1 family: a new class of nuclear mammalian proteins related to the
RT yeast Mcm replication proteins.";
RL Nucleic Acids Res. 21:5289-5293(1993).
RN [11]
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 [12]
RP FUNCTION, AND INTERACTION WITH ATR; ATRIP AND RAD17.
RX PubMed=15538388; DOI=10.1038/sj.emboj.7600463;
RA Tsao C.-C., Geisen C., Abraham R.T.;
RT "Interaction between human MCM7 and Rad17 proteins is required for
RT replication checkpoint signaling.";
RL EMBO J. 23:4660-4669(2004).
RN [13]
RP INTERACTION WITH ATRIP, AND FUNCTION.
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 [14]
RP IDENTIFICATION IN THE MCM2-7 COMPLEX, AND ATPASE ACTIVITY OF THE MCM2-7
RP 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 [15]
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 [16]
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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-121 AND SER-500, AND
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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-121 AND SER-500, 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-500, AND IDENTIFICATION BY
RP 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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-121; SER-365 AND SER-500, AND
RP IDENTIFICATION BY MASS 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 [21]
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 [22]
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 [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=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 [24]
RP INTERACTION WITH ANKRD17.
RX PubMed=23711367; DOI=10.1016/j.febslet.2013.05.037;
RA Menning M., Kufer T.A.;
RT "A role for the Ankyrin repeat containing protein Ankrd17 in Nod1- and
RT Nod2-mediated inflammatory responses.";
RL FEBS Lett. 587:2137-2142(2013).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-121; SER-314; SER-500 AND
RP SER-678, AND IDENTIFICATION BY MASS 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 [26]
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 [27]
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 [28]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-15 AND LYS-28, AND IDENTIFICATION
RP BY MASS 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).
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. Required for S-phase
CC checkpoint activation upon UV-induced damage.
CC {ECO:0000269|PubMed:15210935, ECO:0000269|PubMed:15538388,
CC ECO:0000269|PubMed:25661590, 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: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). Interacts
CC with the ATR-ATRIP complex and with RAD17 (PubMed:15210935,
CC PubMed:15538388). Interacts with TIPIN (PubMed:17116885). Interacts
CC with MCMBP (PubMed:17296731). Interacts with ANKRD17 (PubMed:23711367).
CC Component of the replisome complex composed of at least DONSON, MCM2,
CC MCM7, PCNA and TICRR (PubMed:28191891). Component of the CMG helicase
CC complex, composed of the MCM2-7 complex, the GINS complex and CDC45 (By
CC similarity). {ECO:0000250|UniProtKB:Q91876,
CC ECO:0000269|PubMed:15210935, ECO:0000269|PubMed:15538388,
CC ECO:0000269|PubMed:16899510, ECO:0000269|PubMed:17116885,
CC ECO:0000269|PubMed:17296731, ECO:0000269|PubMed:23711367,
CC ECO:0000269|PubMed:28191891, ECO:0000269|PubMed:9305914}.
CC -!- INTERACTION:
CC P33993; Q96MA6: AK8; NbExp=4; IntAct=EBI-355924, EBI-8466265;
CC P33993; Q68D86: CCDC102B; NbExp=3; IntAct=EBI-355924, EBI-10171570;
CC P33993; P46527: CDKN1B; NbExp=2; IntAct=EBI-355924, EBI-519280;
CC P33993; P49918: CDKN1C; NbExp=2; IntAct=EBI-355924, EBI-519256;
CC P33993; Q08379: GOLGA2; NbExp=3; IntAct=EBI-355924, EBI-618309;
CC P33993; Q9UL03: INTS6; NbExp=10; IntAct=EBI-355924, EBI-1381827;
CC P33993; Q9BVG8: KIFC3; NbExp=3; IntAct=EBI-355924, EBI-2125614;
CC P33993; P07948: LYN; NbExp=4; IntAct=EBI-355924, EBI-79452;
CC P33993; P07948-1: LYN; NbExp=5; IntAct=EBI-355924, EBI-6895930;
CC P33993; Q9NS73-5: MBIP; NbExp=3; IntAct=EBI-355924, EBI-10182361;
CC P33993; P49736: MCM2; NbExp=21; IntAct=EBI-355924, EBI-374819;
CC P33993; P33991: MCM4; NbExp=14; IntAct=EBI-355924, EBI-374938;
CC P33993; P33992: MCM5; NbExp=8; IntAct=EBI-355924, EBI-359410;
CC P33993; Q14566: MCM6; NbExp=6; IntAct=EBI-355924, EBI-374900;
CC P33993; Q9BTE3: MCMBP; NbExp=21; IntAct=EBI-355924, EBI-749378;
CC P33993; Q9BTE3-2: MCMBP; NbExp=6; IntAct=EBI-355924, EBI-9384556;
CC P33993; Q8TD10: MIPOL1; NbExp=3; IntAct=EBI-355924, EBI-2548751;
CC P33993; P01106: MYC; NbExp=6; IntAct=EBI-355924, EBI-447544;
CC P33993; Q15742: NAB2; NbExp=3; IntAct=EBI-355924, EBI-8641936;
CC P33993; P53350: PLK1; NbExp=4; IntAct=EBI-355924, EBI-476768;
CC P33993; Q8ND90: PNMA1; NbExp=3; IntAct=EBI-355924, EBI-302345;
CC P33993; Q14683: SMC1A; NbExp=8; IntAct=EBI-355924, EBI-80690;
CC P33993; Q02086: SP2; NbExp=3; IntAct=EBI-355924, EBI-8651703;
CC P33993; Q08945: SSRP1; NbExp=2; IntAct=EBI-355924, EBI-353771;
CC P33993; P14373: TRIM27; NbExp=3; IntAct=EBI-355924, EBI-719493;
CC P33993; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-355924, EBI-2130429;
CC P33993; P0CG47: UBB; NbExp=2; IntAct=EBI-355924, EBI-413034;
CC P33993; Q9UMX0-2: UBQLN1; NbExp=3; IntAct=EBI-355924, EBI-10173939;
CC P33993; Q8N6Y0: USHBP1; NbExp=3; IntAct=EBI-355924, EBI-739895;
CC P33993; P03126: E6; Xeno; NbExp=2; IntAct=EBI-355924, EBI-1177242;
CC P33993; P06462: E6; Xeno; NbExp=2; IntAct=EBI-355924, EBI-7069993;
CC P33993; P06463: E6; Xeno; NbExp=2; IntAct=EBI-355924, EBI-1186926;
CC P33993-2; P22607: FGFR3; NbExp=3; IntAct=EBI-11741465, EBI-348399;
CC P33993-2; P06396: GSN; NbExp=3; IntAct=EBI-11741465, EBI-351506;
CC P33993-2; Q9Y649; NbExp=3; IntAct=EBI-11741465, EBI-25900580;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q91876}.
CC Chromosome {ECO:0000250|UniProtKB:Q91876}. Note=Associated with
CC chromatin before the formation of nuclei and detaches from it as DNA
CC replication progresses. {ECO:0000250|UniProtKB:Q91876}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P33993-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P33993-2; Sequence=VSP_003205;
CC Name=3;
CC IsoId=P33993-3; Sequence=VSP_044310;
CC -!- PTM: O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner.
CC {ECO:0000269|PubMed:22967762}.
CC -!- PTM: Ubiquitinated by traip when forks converge following formation of
CC DNA interstrand cross-links. Short ubiquitin chains on MCM7 promote
CC recruitment of DNA glycosylase NEIL3. If the interstrand cross-link
CC cannot be cleaved by NEIL3, the ubiquitin chains continue to grow on
CC MCM7, promoting the unloading of the CMG helicase complex by the
CC VCP/p97 ATPase. {ECO:0000250|UniProtKB:Q91876}.
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:Q61881}.
CC -!- SIMILARITY: Belongs to the MCM family. {ECO:0000305}.
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DR EMBL; D55716; BAA09534.1; -; mRNA.
DR EMBL; AK055379; BAG51508.1; -; mRNA.
DR EMBL; AC073842; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH236956; EAL23855.1; -; Genomic_DNA.
DR EMBL; CH236956; EAL23856.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76598.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76599.1; -; Genomic_DNA.
DR EMBL; BC009398; AAH09398.1; -; mRNA.
DR EMBL; BC013375; AAH13375.1; -; mRNA.
DR EMBL; X74796; CAA52803.1; -; mRNA.
DR EMBL; D28480; BAA05839.1; -; mRNA.
DR CCDS; CCDS5683.1; -. [P33993-1]
DR CCDS; CCDS5684.1; -. [P33993-3]
DR PIR; S70583; S70583.
DR RefSeq; NP_001265524.1; NM_001278595.1. [P33993-3]
DR RefSeq; NP_005907.3; NM_005916.4. [P33993-1]
DR RefSeq; NP_877577.1; NM_182776.2. [P33993-3]
DR PDB; 6XTX; EM; 3.29 A; 7=1-719.
DR PDB; 6XTY; EM; 6.77 A; 7=1-719.
DR PDB; 7PFO; EM; 3.20 A; 7=1-719.
DR PDB; 7PLO; EM; 2.80 A; 7=1-719.
DR PDBsum; 6XTX; -.
DR PDBsum; 6XTY; -.
DR PDBsum; 7PFO; -.
DR PDBsum; 7PLO; -.
DR AlphaFoldDB; P33993; -.
DR SMR; P33993; -.
DR BioGRID; 110344; 313.
DR ComplexPortal; CPX-2940; MCM complex.
DR CORUM; P33993; -.
DR DIP; DIP-27580N; -.
DR IntAct; P33993; 230.
DR MINT; P33993; -.
DR STRING; 9606.ENSP00000307288; -.
DR ChEMBL; CHEMBL4630816; -.
DR GlyGen; P33993; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P33993; -.
DR MetOSite; P33993; -.
DR PhosphoSitePlus; P33993; -.
DR SwissPalm; P33993; -.
DR BioMuta; MCM7; -.
DR DMDM; 20981696; -.
DR EPD; P33993; -.
DR jPOST; P33993; -.
DR MassIVE; P33993; -.
DR MaxQB; P33993; -.
DR PaxDb; P33993; -.
DR PeptideAtlas; P33993; -.
DR PRIDE; P33993; -.
DR ProteomicsDB; 54936; -. [P33993-1]
DR ProteomicsDB; 54937; -. [P33993-2]
DR ProteomicsDB; 641; -.
DR Antibodypedia; 1289; 1186 antibodies from 45 providers.
DR DNASU; 4176; -.
DR Ensembl; ENST00000303887.10; ENSP00000307288.5; ENSG00000166508.18. [P33993-1]
DR Ensembl; ENST00000343023.10; ENSP00000344006.6; ENSG00000166508.18. [P33993-2]
DR Ensembl; ENST00000354230.7; ENSP00000346171.3; ENSG00000166508.18. [P33993-3]
DR Ensembl; ENST00000621318.4; ENSP00000483795.1; ENSG00000166508.18. [P33993-3]
DR GeneID; 4176; -.
DR KEGG; hsa:4176; -.
DR MANE-Select; ENST00000303887.10; ENSP00000307288.5; NM_005916.5; NP_005907.3.
DR UCSC; uc003usv.3; human. [P33993-1]
DR CTD; 4176; -.
DR DisGeNET; 4176; -.
DR GeneCards; MCM7; -.
DR HGNC; HGNC:6950; MCM7.
DR HPA; ENSG00000166508; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 600592; gene.
DR neXtProt; NX_P33993; -.
DR OpenTargets; ENSG00000166508; -.
DR PharmGKB; PA30697; -.
DR VEuPathDB; HostDB:ENSG00000166508; -.
DR eggNOG; KOG0482; Eukaryota.
DR GeneTree; ENSGT01050000244824; -.
DR HOGENOM; CLU_000995_6_0_1; -.
DR InParanoid; P33993; -.
DR OMA; NAYTCDR; -.
DR PhylomeDB; P33993; -.
DR TreeFam; TF300400; -.
DR PathwayCommons; P33993; -.
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; P33993; -.
DR SIGNOR; P33993; -.
DR BioGRID-ORCS; 4176; 780 hits in 1088 CRISPR screens.
DR ChiTaRS; MCM7; human.
DR GeneWiki; MCM7; -.
DR GenomeRNAi; 4176; -.
DR Pharos; P33993; Tbio.
DR PRO; PR:P33993; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P33993; protein.
DR Bgee; ENSG00000166508; Expressed in ganglionic eminence and 97 other tissues.
DR ExpressionAtlas; P33993; baseline and differential.
DR Genevisible; P33993; HS.
DR GO; GO:0000785; C:chromatin; TAS:ProtInc.
DR GO; GO:0000781; C:chromosome, telomeric region; HDA:BHF-UCL.
DR GO; GO:0071162; C:CMG complex; IPI:ComplexPortal.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0042555; C:MCM complex; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
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:0003678; F:DNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0003697; F:single-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IEA:Ensembl.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0006260; P:DNA replication; TAS:ProtInc.
DR GO; GO:0006270; P:DNA replication initiation; IBA:GO_Central.
DR GO; GO:0006271; P:DNA strand elongation involved in DNA replication; IBA:GO_Central.
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:0030174; P:regulation of DNA-templated DNA replication initiation; IC:ComplexPortal.
DR GO; GO:0042325; P:regulation of phosphorylation; IMP:UniProtKB.
DR CDD; cd17758; MCM7; 1.
DR Gene3D; 2.40.50.140; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR031327; MCM.
DR InterPro; IPR008050; MCM7.
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 PANTHER; PTHR11630:SF26; PTHR11630:SF26; 1.
DR Pfam; PF00493; MCM; 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; PR01663; MCMPROTEIN7.
DR SMART; SM00382; AAA; 1.
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; Alternative splicing; ATP-binding; Cell cycle;
KW Chromosome; Direct protein sequencing; DNA replication; DNA-binding;
KW Glycoprotein; Helicase; Hydrolase; Isopeptide bond; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.7, ECO:0007744|PubMed:22223895"
FT CHAIN 2..719
FT /note="DNA replication licensing factor MCM7"
FT /id="PRO_0000194119"
FT DOMAIN 332..538
FT /note="MCM"
FT REGION 521..564
FT /note="Interaction with RAD17"
FT /evidence="ECO:0000269|PubMed:15538388"
FT REGION 577..719
FT /note="Interaction with ATRIP"
FT MOTIF 513..516
FT /note="Arginine finger"
FT BINDING 381..388
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.7, ECO:0007744|PubMed:22223895"
FT MOD_RES 121
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 314
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 365
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 500
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 678
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 15
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 28
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..176
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044310"
FT VAR_SEQ 329..658
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_003205"
FT VARIANT 114
FT /note="R -> Q (in dbSNP:rs2307348)"
FT /id="VAR_029243"
FT VARIANT 144
FT /note="N -> S (in dbSNP:rs2070215)"
FT /evidence="ECO:0000269|PubMed:8626784"
FT /id="VAR_013297"
FT VARIANT 473
FT /note="G -> S (in dbSNP:rs2307347)"
FT /id="VAR_014817"
FT CONFLICT 103
FT /note="I -> L (in Ref. 6; CAA52803)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 719 AA; 81308 MW; 330A1DEFAEFBFB88 CRC64;
MALKDYALEK EKVKKFLQEF YQDDELGKKQ FKYGNQLVRL AHREQVALYV DLDDVAEDDP
ELVDSICENA RRYAKLFADA VQELLPQYKE REVVNKDVLD VYIEHRLMME QRSRDPGMVR
SPQNQYPAEL MRRFELYFQG PSSNKPRVIR EVRADSVGKL VTVRGIVTRV SEVKPKMVVA
TYTCDQCGAE TYQPIQSPTF MPLIMCPSQE CQTNRSGGRL YLQTRGSRFI KFQEMKMQEH
SDQVPVGNIP RSITVLVEGE NTRIAQPGDH VSVTGIFLPI LRTGFRQVVQ GLLSETYLEA
HRIVKMNKSE DDESGAGELT REELRQIAEE DFYEKLAASI APEIYGHEDV KKALLLLLVG
GVDQSPRGMK IRGNINICLM GDPGVAKSQL LSYIDRLAPR SQYTTGRGSS GVGLTAAVLR
DSVSGELTLE GGALVLADQG VCCIDEFDKM AEADRTAIHE VMEQQTISIA KAGILTTLNA
RCSILAAANP AYGRYNPRRS LEQNIQLPAA LLSRFDLLWL IQDRPDRDND LRLAQHITYV
HQHSRQPPSQ FEPLDMKLMR RYIAMCREKQ PMVPESLADY ITAAYVEMRR EAWASKDATY
TSARTLLAIL RLSTALARLR MVDVVEKEDV NEAIRLMEMS KDSLLGDKGQ TARTQRPADV
IFATVRELVS GGRSVRFSEA EQRCVSRGFT PAQFQAALDE YEELNVWQVN ASRTRITFV
