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 27-MAR-2024, entry version 248. DE RecName: Full=DNA replication licensing factor MCM3 {ECO:0000305}; DE EC=3.6.4.12 {ECO:0000269|PubMed:32453425}; 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 {ECO:0000312|HGNC:HGNC:6945}; 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). RN [33] 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 [34] {ECO:0007744|PDB:6XTX, ECO:0007744|PDB:6XTY} RP STRUCTURE BY ELECTRON MICROSCOPY (3.29 ANGSTROMS) IN COMPLEXES WITH ADP; RP ATP ANALOG AND WDHD1 IN CMG COMPLEX, SUBUNIT, 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 [35] {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 [36] {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). 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 (Probable). {ECO:0000269|PubMed:32453425, CC ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, CC ECO:0000269|PubMed:35585232, ECO:0000305|PubMed:35585232}. 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: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, PubMed:34700328, PubMed:34694004, PubMed:32453425). CC Component of the CMG helicase complex, a hexameric ring of related CC MCM2-7 subunits stabilized by CDC45 and the tetrameric GINS complex CC (PubMed:34700328, PubMed:34694004, PubMed:32453425). Associated with CC the replication-specific DNA polymerase alpha (By similarity). CC Interacts with MCMBP (PubMed:17296731). Interacts with ANKRD17 CC (PubMed:23711367). Interacts with MCM3AP isoform MCM3AP; this CC interaction leads to MCM3 acetylation (PubMed:9712829, PubMed:11258703, CC PubMed:12226073). {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:32453425, ECO:0000269|PubMed:34694004, CC ECO:0000269|PubMed:34700328, 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:0000305|PubMed:35585232}. 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:0000305|PubMed:35585232}. 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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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; CCDS4940.3; -. [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 PDB; 7W1Y; EM; 2.59 A; 3/B=1-808. DR PDB; 7W68; EM; 4.40 A; B=1-808. DR PDB; 8B9D; EM; 3.40 A; 3=1-808. DR PDBsum; 6XTX; -. DR PDBsum; 6XTY; -. DR PDBsum; 7PFO; -. DR PDBsum; 7PLO; -. DR PDBsum; 7W1Y; -. DR PDBsum; 7W68; -. DR PDBsum; 8B9D; -. DR AlphaFoldDB; P25205; -. DR EMDB; EMD-10619; -. DR EMDB; EMD-10621; -. DR EMDB; EMD-13375; -. DR EMDB; EMD-13494; -. DR EMDB; EMD-32326; -. DR SMR; P25205; -. DR BioGRID; 110340; 344. DR ComplexPortal; CPX-2940; MCM complex. DR CORUM; P25205; -. DR DIP; DIP-31726N; -. DR IntAct; P25205; 116. DR MINT; P25205; -. DR STRING; 9606.ENSP00000480987; -. DR ChEMBL; CHEMBL4630813; -. DR GlyCosmos; P25205; 2 sites, 1 glycan. 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; 9606-ENSP00000480987; -. DR PeptideAtlas; P25205; -. DR ProteomicsDB; 54265; -. [P25205-1] DR Pumba; P25205; -. DR Antibodypedia; 1433; 581 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 AGR; HGNC:6945; -. 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; 5476523at2759; -. 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; 750 hits in 1153 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 204 other cell types or tissues. DR ExpressionAtlas; P25205; baseline and differential. 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:InterPro. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0004386; F:helicase activity; IEA:UniProtKB-KW. 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; NAS:ComplexPortal. DR CDD; cd17754; MCM3; 1. DR Gene3D; 2.20.28.10; -; 1. DR Gene3D; 3.30.1640.10; mini-chromosome maintenance (MCM) complex, chain A, domain 1; 1. DR Gene3D; 2.40.50.140; Nucleic acid-binding proteins; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR 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; DNA REPLICATION LICENSING FACTOR MCM FAMILY MEMBER; 1. DR PANTHER; PTHR11630:SF46; DNA REPLICATION LICENSING FACTOR MCM3; 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; 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. DR Genevisible; P25205; HS. 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 353 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /ligand_note="ligand shared with MCM5" FT /evidence="ECO:0000305|PubMed:32453425, FT ECO:0007744|PDB:6XTX" FT BINDING 393 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /ligand_note="ligand shared with MCM5" FT /evidence="ECO:0000305|PubMed:32453425, FT ECO:0007744|PDB:6XTX" FT BINDING 394 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /ligand_note="ligand shared with MCM5" FT /evidence="ECO:0000305|PubMed:32453425, FT ECO:0007744|PDB:6XTX" FT BINDING 395 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /ligand_note="ligand shared with MCM5" FT /evidence="ECO:0000305|PubMed:32453425, FT ECO:0007744|PDB:6XTX" FT BINDING 397 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /ligand_note="ligand shared with MCM5" FT /evidence="ECO:0000305|PubMed:32453425, FT ECO:0007744|PDB:6XTX" FT BINDING 523 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="ligand shared with MCM7" FT /evidence="ECO:0000305|PubMed:32453425, FT ECO:0007744|PDB:6XTX" FT BINDING 664 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="ligand shared with MCM7" FT /evidence="ECO:0000305|PubMed:32453425, FT ECO:0007744|PDB:6XTX" 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 //