MCM3_HUMAN
ID MCM3_HUMAN Reviewed; 808 AA.
AC P25205; B4DWW4; Q92660; Q9BTR3; Q9NUE7;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 14-AUG-2001, sequence version 3.
DT 03-AUG-2022, entry version 239.
DE RecName: Full=DNA replication licensing factor MCM3;
DE EC=3.6.4.12;
DE AltName: Full=DNA polymerase alpha holoenzyme-associated protein P1;
DE AltName: Full=P1-MCM3;
DE AltName: Full=RLF subunit beta;
DE AltName: Full=p102;
GN Name=MCM3;
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).
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 [2]
RP SEQUENCE REVISION.
RA Goehring F., Jehnichen P., Hemmer W.H.;
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Cervix;
RX PubMed=7758114; DOI=10.1016/0092-8674(95)90081-0;
RA Kubota Y., Mimura S., Nishimoto S., Takisawa H., Nojima H.;
RT "Identification of the yeast MCM3-related protein as a component of Xenopus
RT DNA replication licensing factor.";
RL Cell 81:601-609(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-280; LEU-287; LEU-590;
RP TRP-774 AND LYS-777.
RG NIEHS SNPs program;
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph, and Pancreas;
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 [9]
RP PROTEIN SEQUENCE OF 2-13; 47-55; 337-351 AND 749-756, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Osteosarcoma;
RA Bienvenut W.V., Glen H., Brunton V.G., Frame M.C.;
RL Submitted (JUL-2007) to UniProtKB.
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 563-808 (ISOFORM 1).
RX PubMed=1549468; DOI=10.1093/nar/20.5.1069;
RA Thoemmes P., Fett R., Schray B., Burkhart R., Barnes M., Kennedy C.,
RA Brown N.C., Knippers R.;
RT "Properties of the nuclear P1 protein, a mammalian homologue of the yeast
RT Mcm3 replication protein.";
RL Nucleic Acids Res. 20:1069-1074(1992).
RN [11]
RP INTERACTION WITH MCM3AP.
RX PubMed=9712829; DOI=10.1074/jbc.273.35.22177;
RA Takei Y., Tsujimoto G.;
RT "Identification of a novel MCM3-associated protein that facilitates MCM3
RT nuclear localization.";
RL J. Biol. Chem. 273:22177-22180(1998).
RN [12]
RP INTERACTION WITH MCM3AP, AND ACETYLATION.
RX PubMed=11258703; DOI=10.1093/embo-reports/kve026;
RA Takei Y., Swietlik M., Tanoue A., Tsujimoto G., Kouzarides T., Laskey R.;
RT "MCM3AP, a novel acetyltransferase that acetylates replication protein
RT MCM3.";
RL EMBO Rep. 2:119-123(2001).
RN [13]
RP INTERACTION WITH MCM3AP, AND ACETYLATION.
RX PubMed=12226073; DOI=10.1074/jbc.c200442200;
RA Takei Y., Assenberg M., Tsujimoto G., Laskey R.;
RT "The MCM3 acetylase MCM3AP inhibits initiation, but not elongation, of DNA
RT replication via interaction with MCM3.";
RL J. Biol. Chem. 277:43121-43125(2002).
RN [14]
RP PHOSPHORYLATION AT SER-535, AND MUTAGENESIS OF SER-535.
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-722, AND IDENTIFICATION BY
RP 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 [16]
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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-672 AND THR-674, 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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-722, AND IDENTIFICATION BY
RP 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 [19]
RP IDENTIFICATION IN THE MCM2-7 COMPLEX, INTERACTION WITH MCMBP, AND
RP IDENTIFICATION BY MASS 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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-722, AND IDENTIFICATION BY
RP 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 [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-160; SER-668; SER-672;
RP THR-674; SER-681; SER-711; THR-713 AND THR-722, AND IDENTIFICATION BY MASS
RP 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 [22]
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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-722, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-672; THR-674; TYR-708;
RP SER-711; THR-713; THR-722 AND THR-725, AND IDENTIFICATION BY MASS
RP 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-668; SER-672; SER-711 AND
RP THR-722, AND 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 [26]
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 [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-160; SER-672; THR-674 AND
RP SER-711, AND IDENTIFICATION BY MASS 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 [28]
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 [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 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 [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275; SER-611; SER-672;
RP THR-674 AND THR-722, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
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 DNA
CC replication and cell proliferation. {ECO:0000250|UniProtKB:P49739}.
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 -!- SUBUNIT: Component of the MCM2-7 complex (PubMed:16899510,
CC PubMed:17296731). The complex forms a toroidal hexameric ring with the
CC proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5 (PubMed:16899510,
CC PubMed:17296731). Associated with the replication-specific DNA
CC polymerase alpha (By similarity). Interacts with MCMBP
CC (PubMed:17296731). Interacts with ANKRD17 (PubMed:23711367). Interacts
CC with MCM3AP isoform MCM3AP; this interaction leads to MCM3 acetylation
CC (PubMed:9712829, PubMed:11258703, PubMed:12226073). Component of the
CC CMG helicase complex, composed of the MCM2-7 complex, the GINS complex
CC and CDC45 (By similarity). {ECO:0000250|UniProtKB:P25206,
CC ECO:0000250|UniProtKB:P49739, ECO:0000269|PubMed:11258703,
CC ECO:0000269|PubMed:12226073, ECO:0000269|PubMed:16899510,
CC ECO:0000269|PubMed:17296731, ECO:0000269|PubMed:23711367,
CC ECO:0000269|PubMed:9712829}.
CC -!- INTERACTION:
CC P25205; P62805: H4C9; NbExp=2; IntAct=EBI-355153, EBI-302023;
CC P25205; P49736: MCM2; NbExp=8; IntAct=EBI-355153, EBI-374819;
CC P25205; P33992: MCM5; NbExp=5; IntAct=EBI-355153, EBI-359410;
CC P25205; Q14566: MCM6; NbExp=4; IntAct=EBI-355153, EBI-374900;
CC P25205; Q9BTE3: MCMBP; NbExp=11; IntAct=EBI-355153, EBI-749378;
CC P25205; Q13416: ORC2; NbExp=2; IntAct=EBI-355153, EBI-374957;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P49739}.
CC Chromosome {ECO:0000250|UniProtKB:P49739}. Note=Associated with
CC chromatin before the formation of nuclei and detaches from it as DNA
CC replication progresses. {ECO:0000250|UniProtKB:P49739}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P25205-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P25205-2; Sequence=VSP_057050;
CC -!- PTM: Acetylated by MCM3AP. {ECO:0000269|PubMed:11258703,
CC ECO:0000269|PubMed:12226073}.
CC -!- PTM: O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner.
CC {ECO:0000269|PubMed:22967762}.
CC -!- MISCELLANEOUS: Early fractionation of eukaryotic MCM proteins yielded a
CC variety of dimeric, trimeric and tetrameric complexes with unclear
CC biological significance. The MCM2-7 hexamer is the proposed
CC physiological active complex.
CC -!- SIMILARITY: Belongs to the MCM family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/mcm3/";
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DR EMBL; X62153; CAA44078.2; -; mRNA.
DR EMBL; D38073; BAA07267.1; -; mRNA.
DR EMBL; AK301704; BAG63176.1; -; mRNA.
DR EMBL; AY621074; AAT27321.1; -; Genomic_DNA.
DR EMBL; AL034343; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX04367.1; -; Genomic_DNA.
DR EMBL; BC001626; AAH01626.1; -; mRNA.
DR EMBL; BC003509; AAH03509.2; -; mRNA.
DR CCDS; CCDS4940.2; -. [P25205-1]
DR PIR; S62594; S62594.
DR RefSeq; NP_001257401.1; NM_001270472.1.
DR RefSeq; NP_002379.3; NM_002388.4. [P25205-1]
DR PDB; 6XTX; EM; 3.29 A; 3=1-808.
DR PDB; 6XTY; EM; 6.77 A; 3=1-808.
DR PDB; 7PFO; EM; 3.20 A; 3=1-808.
DR PDB; 7PLO; EM; 2.80 A; 3=1-808.
DR PDBsum; 6XTX; -.
DR PDBsum; 6XTY; -.
DR PDBsum; 7PFO; -.
DR PDBsum; 7PLO; -.
DR AlphaFoldDB; P25205; -.
DR SMR; P25205; -.
DR BioGRID; 110340; 249.
DR ComplexPortal; CPX-2940; MCM complex.
DR CORUM; P25205; -.
DR DIP; DIP-31726N; -.
DR IntAct; P25205; 114.
DR MINT; P25205; -.
DR STRING; 9606.ENSP00000480987; -.
DR ChEMBL; CHEMBL4630813; -.
DR GlyGen; P25205; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; P25205; -.
DR MetOSite; P25205; -.
DR PhosphoSitePlus; P25205; -.
DR SwissPalm; P25205; -.
DR BioMuta; MCM3; -.
DR DMDM; 19857543; -.
DR EPD; P25205; -.
DR jPOST; P25205; -.
DR MassIVE; P25205; -.
DR MaxQB; P25205; -.
DR PaxDb; P25205; -.
DR PeptideAtlas; P25205; -.
DR PRIDE; P25205; -.
DR ProteomicsDB; 54265; -. [P25205-1]
DR Antibodypedia; 1433; 520 antibodies from 40 providers.
DR DNASU; 4172; -.
DR Ensembl; ENST00000596288.7; ENSP00000472940.2; ENSG00000112118.20. [P25205-1]
DR Ensembl; ENST00000616552.4; ENSP00000480987.1; ENSG00000112118.20. [P25205-2]
DR GeneID; 4172; -.
DR KEGG; hsa:4172; -.
DR MANE-Select; ENST00000596288.7; ENSP00000472940.2; NM_002388.6; NP_002379.4.
DR UCSC; uc003pan.2; human. [P25205-1]
DR CTD; 4172; -.
DR DisGeNET; 4172; -.
DR GeneCards; MCM3; -.
DR HGNC; HGNC:6945; MCM3.
DR HPA; ENSG00000112118; Low tissue specificity.
DR MIM; 602693; gene.
DR neXtProt; NX_P25205; -.
DR OpenTargets; ENSG00000112118; -.
DR PharmGKB; PA30691; -.
DR VEuPathDB; HostDB:ENSG00000112118; -.
DR eggNOG; KOG0479; Eukaryota.
DR GeneTree; ENSGT01050000244824; -.
DR HOGENOM; CLU_000995_6_0_1; -.
DR InParanoid; P25205; -.
DR OrthoDB; 266497at2759; -.
DR PhylomeDB; P25205; -.
DR TreeFam; TF106459; -.
DR PathwayCommons; P25205; -.
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; P25205; -.
DR SIGNOR; P25205; -.
DR BioGRID-ORCS; 4172; 722 hits in 1067 CRISPR screens.
DR ChiTaRS; MCM3; human.
DR GeneWiki; MCM3; -.
DR GenomeRNAi; 4172; -.
DR Pharos; P25205; Tbio.
DR PRO; PR:P25205; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P25205; protein.
DR Bgee; ENSG00000112118; Expressed in ventricular zone and 202 other tissues.
DR ExpressionAtlas; P25205; baseline and differential.
DR Genevisible; P25205; HS.
DR GO; GO:0005658; C:alpha DNA polymerase:primase complex; TAS:ProtInc.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0000781; C:chromosome, telomeric region; HDA:BHF-UCL.
DR GO; GO:0071162; C:CMG complex; IPI:ComplexPortal.
DR GO; GO:0042555; C:MCM complex; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
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:0003678; F:DNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0003697; F:single-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0006270; P:DNA replication initiation; TAS:ProtInc.
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:1902975; P:mitotic DNA replication initiation; IBA:GO_Central.
DR GO; GO:0030174; P:regulation of DNA-templated DNA replication initiation; IC:ComplexPortal.
DR Gene3D; 2.40.50.140; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR031327; MCM.
DR InterPro; IPR008046; Mcm3.
DR InterPro; IPR018525; MCM_CS.
DR InterPro; IPR001208; MCM_dom.
DR InterPro; IPR041562; MCM_lid.
DR InterPro; IPR027925; MCM_N.
DR InterPro; IPR033762; MCM_OB.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR11630; PTHR11630; 1.
DR Pfam; PF00493; MCM; 1.
DR Pfam; PF17855; MCM_lid; 1.
DR Pfam; PF14551; MCM_N; 1.
DR Pfam; PF17207; MCM_OB; 1.
DR PRINTS; PR01657; MCMFAMILY.
DR PRINTS; PR01659; MCMPROTEIN3.
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; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.9, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT CHAIN 2..808
FT /note="DNA replication licensing factor MCM3"
FT /id="PRO_0000194093"
FT DOMAIN 295..502
FT /note="MCM"
FT REGION 662..739
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 477..480
FT /note="Arginine finger"
FT COMPBIAS 682..707
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 714..739
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 345..352
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.9, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT MOD_RES 160
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 275
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 293
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P25206"
FT MOD_RES 535
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000269|PubMed:15210935"
FT MOD_RES 547
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P25206"
FT MOD_RES 611
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 668
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 672
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 674
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 681
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 708
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 711
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 713
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 722
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:17487921, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 725
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 728
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P25206"
FT MOD_RES 734
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P25206"
FT VAR_SEQ 1
FT /note="M -> MLPRSPPLPRGNLWWREEFGSFRAGVESSWEPPRDFGGGSSLAAGM
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057050"
FT VARIANT 105
FT /note="S -> G (in dbSNP:rs2307332)"
FT /id="VAR_014810"
FT VARIANT 280
FT /note="D -> V (in dbSNP:rs2307329)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_014811"
FT VARIANT 287
FT /note="F -> L (in dbSNP:rs2307328)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_014812"
FT VARIANT 590
FT /note="I -> L (in dbSNP:rs17240063)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_020516"
FT VARIANT 774
FT /note="R -> W (in dbSNP:rs2230239)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_020517"
FT VARIANT 777
FT /note="E -> K (in dbSNP:rs2230240)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_020427"
FT MUTAGEN 535
FT /note="S->A: 50% reduction in phosphorylation by ATM or
FT ATR."
FT /evidence="ECO:0000269|PubMed:15210935"
FT CONFLICT 230..231
FT /note="KP -> NA (in Ref. 3; BAA07267)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 808 AA; 90981 MW; C967C068B7090558 CRC64;
MAGTVVLDDV ELREAQRDYL DFLDDEEDQG IYQSKVRELI SDNQYRLIVN VNDLRRKNEK
RANRLLNNAF EELVAFQRAL KDFVASIDAT YAKQYEEFYV GLEGSFGSKH VSPRTLTSCF
LSCVVCVEGI VTKCSLVRPK VVRSVHYCPA TKKTIERRYS DLTTLVAFPS SSVYPTKDEE
NNPLETEYGL SVYKDHQTIT IQEMPEKAPA GQLPRSVDVI LDDDLVDKAK PGDRVQVVGT
YRCLPGKKGG YTSGTFRTVL IACNVKQMSK DAQPSFSAED IAKIKKFSKT RSKDIFDQLA
KSLAPSIHGH DYVKKAILCL LLGGVERDLE NGSHIRGDIN ILLIGDPSVA KSQLLRYVLC
TAPRAIPTTG RGSSGVGLTA AVTTDQETGE RRLEAGAMVL ADRGVVCIDE FDKMSDMDRT
AIHEVMEQGR VTIAKAGIHA RLNARCSVLA AANPVYGRYD QYKTPMENIG LQDSLLSRFD
LLFIMLDQMD PEQDREISDH VLRMHRYRAP GEQDGDAMPL GSAVDILATD DPNFSQEDQQ
DTQIYEKHDN LLHGTKKKKE KMVSAAFMKK YIHVAKIIKP VLTQESATYI AEEYSRLRSQ
DSMSSDTART SPVTARTLET LIRLATAHAK ARMSKTVDLQ DAEEAVELVQ YAYFKKVLEK
EKKRKKRSED ESETEDEEEK SQEDQEQKRK RRKTRQPDAK DGDSYDPYDF SDTEEEMPQV
HTPKTADSQE TKESQKVELS ESRLKAFKVA LLDVFREAHA QSIGMNRLTE SINRDSEEPF
SSVEIQAALS KMQDDNQVMV SEGIIFLI
