ID MCM2_DROME Reviewed; 887 AA. AC P49735; Q9VHU2; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 04-NOV-2026, entry version 203. DE RecName: Full=DNA replication licensing factor Mcm2; DE EC=3.6.4.12 {ECO:0000250|UniProtKB:P49736}; DE AltName: Full=Minichromosome maintenance 2 protein; DE Short=DmMCM2; GN Name=Mcm2; ORFNames=CG7538; OS Drosophila melanogaster (Fruit fly). OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Altocrustacea; Allotriocarida; OC Hexapoda; Insecta; Pterygota; Neoptera; Eumetabola; Endopterygota; OC Aparaglossata; Panorpida; Diptera; Brachycera; Muscomorpha; Ephydroidea; OC Drosophilidae; Drosophila; Sophophora. OX NCBI_TaxID=7227; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION. RC TISSUE=Eye-antennal disk; RX PubMed=7622035; DOI=10.1101/gad.9.14.1709; RA Treisman J.E., Follette P.J., O'Farrell P.H., Rubin G.M.; RT "Cell proliferation and DNA replication defects in a Drosophila MCM2 RT mutant."; RL Genes Dev. 9:1709-1715(1995). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley; RX PubMed=10731132; DOI=10.1126/science.287.5461.2185; RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C., RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., RA Venter J.C.; RT "The genome sequence of Drosophila melanogaster."; RL Science 287:2185-2195(2000). RN [3] RP GENOME REANNOTATION. RC STRAIN=Berkeley; RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083; RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A., RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.; RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic RT review."; RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Berkeley; TISSUE=Embryo; RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080; RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., RA Celniker S.E.; RT "A Drosophila full-length cDNA resource."; RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002). RN [5] RP INTERACTION WITH MCM6. RX PubMed=11854416; DOI=10.1091/mbc.01-08-0400; RA Schwed G., May N., Pechersky Y., Calvi B.R.; RT "Drosophila minichromosome maintenance 6 is required for chorion gene RT amplification and genomic replication."; RL Mol. Biol. Cell 13:607-620(2002). RN [6] RP INTERACTION WITH MCM10. RX PubMed=12808023; DOI=10.1091/mbc.e02-11-0706; RA Christensen T.W., Tye B.K.; RT "Drosophila MCM10 interacts with members of the prereplication complex and RT is required for proper chromosome condensation."; RL Mol. Biol. Cell 14:2206-2215(2003). RN [7] RP IDENTIFICATION IN THE MCM2-7 COMPLEX, AND FUNCTION OF THE MCM2-7 COMPLEX. RX PubMed=16798881; DOI=10.1073/pnas.0602400103; RA Moyer S.E., Lewis P.W., Botchan M.R.; RT "Isolation of the Cdc45/Mcm2-7/GINS (CMG) complex, a candidate for the RT eukaryotic DNA replication fork helicase."; RL Proc. Natl. Acad. Sci. U.S.A. 103:10236-10241(2006). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-26; SER-27 AND SER-124, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=17372656; DOI=10.1039/b617545g; RA Bodenmiller B., Mueller L.N., Pedrioli P.G.A., Pflieger D., Juenger M.A., RA Eng J.K., Aebersold R., Tao W.A.; RT "An integrated chemical, mass spectrometric and computational strategy for RT (quantitative) phosphoproteomics: application to Drosophila melanogaster RT Kc167 cells."; RL Mol. Biosyst. 3:275-286(2007). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-89 AND SER-92, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Embryo; RX PubMed=18327897; DOI=10.1021/pr700696a; RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.; RT "Phosphoproteome analysis of Drosophila melanogaster embryos."; RL J. Proteome Res. 7:1675-1682(2008). RN [10] RP RECONSTITUTION OF THE MCM2-7 COMPLEX, FUNCTION OF THE MCM2-7 COMPLEX, AND RP MUTAGENESIS OF LYS-514. RX PubMed=20122406; DOI=10.1016/j.molcel.2009.12.030; RA Ilves I., Petojevic T., Pesavento J.J., Botchan M.R.; RT "Activation of the MCM2-7 helicase by association with Cdc45 and GINS RT proteins."; RL Mol. Cell 37:247-258(2010). RN [11] RP PHOSPHORYLATION. RX PubMed=25451925; DOI=10.1074/jbc.m114.597948; RA Stephenson R., Hosler M.R., Gavande N.S., Ghosh A.K., Weake V.M.; RT "Characterization of a Drosophila ortholog of the Cdc7 kinase: a role for RT Cdc7 in endoreplication independent of Chiffon."; RL J. Biol. Chem. 290:1332-1347(2015). CC -!- FUNCTION: Acts as a component of the MCM2-7 complex (MCM complex) which CC is the replicative helicase essential for 'once per cell cycle' DNA CC replication initiation and elongation in eukaryotic cells. Core CC component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that CC unwinds template DNA during replication, and around which the replisome CC is built. The active ATPase sites in the MCM2-7 ring are formed through CC the interaction surfaces of two neighboring subunits such that a CC critical structure of a conserved arginine finger motif is provided in CC 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. Required CC for the entry in S phase and for cell division. CC {ECO:0000269|PubMed:16798881, ECO:0000269|PubMed:20122406, CC ECO:0000269|PubMed:7622035}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + phosphate + H(+); Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12; CC Evidence={ECO:0000250|UniProtKB:P49736}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066; CC Evidence={ECO:0000250|UniProtKB:P49736}; CC -!- SUBUNIT: Component of the Mcm2-7 complex. The complex forms a toroidal CC hexameric ring with the proposed subunit order Mcm2-Mcm6-Mcm4-Mcm7- CC Mcm3-Mcm5 (Probable). Interacts with Mcm10. CC {ECO:0000269|PubMed:11854416, ECO:0000269|PubMed:12808023, CC ECO:0000269|PubMed:16798881, ECO:0000305}. CC -!- INTERACTION: CC P49735; Q9VIE6: Mcm10; NbExp=2; IntAct=EBI-138228, EBI-91264; CC P49735; Q9VGW6: Mcm5; NbExp=9; IntAct=EBI-138228, EBI-83298; CC P49735; Q9V461: Mcm6; NbExp=13; IntAct=EBI-138228, EBI-869161; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P25205}. CC Chromosome {ECO:0000250|UniProtKB:P25205}. Note=Associated with CC chromatin before the formation of nuclei and detaches from it as DNA CC replication progresses. {ECO:0000250|UniProtKB:P25205}. CC -!- PTM: Phosphorylated by the catalytic component of the Dbf4-dependent CC kinase (DDK) complex Cdc7. {ECO:0000269|PubMed:25451925}. 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:P49736}. CC -!- SIMILARITY: Belongs to the MCM family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L42762; AAB36617.1; -; mRNA. DR EMBL; AE014297; AAF54207.1; -; Genomic_DNA. DR EMBL; AY069702; AAL39847.1; -; mRNA. DR RefSeq; NP_477121.1; NM_057773.4. DR PDB; 6RAW; EM; 3.70 A; 2=1-887. DR PDB; 6RAX; EM; 3.99 A; 2=1-887. DR PDB; 6RAY; EM; 4.28 A; 2=1-887. DR PDB; 6RAZ; EM; 4.46 A; 2=1-887. DR AlphaFoldDB; P49735; -. DR EMDB; EMD-2772; -. DR EMDB; EMD-3318; -. DR EMDB; EMD-3319; -. DR EMDB; EMD-3320; -. DR EMDB; EMD-3321; -. DR EMDB; EMD-4785; -. DR EMDB; EMD-4786; -. DR EMDB; EMD-4787; -. DR EMDB; EMD-4788; -. DR SMR; P49735; -. DR BioGRID; 66154; 19. DR ComplexPortal; CPX-2942; MCM complex. DR DIP; DIP-22529N; -. DR FunCoup; P49735; 1397. DR IntAct; P49735; 55. DR STRING; 7227.FBpp0081317; -. DR iPTMnet; P49735; -. DR PaxDb; 7227-FBpp0081317; -. DR PeptideAtlas; P49735; -. DR EnsemblMetazoa; FBtr0081827; FBpp0081317; FBgn0014861. DR GeneID; 40973; -. DR KEGG; dme:Dmel_CG7538; -. DR AGR; FB:FBgn0014861; -. DR CTD; 4171; -. DR FlyBase; FBgn0014861; Mcm2. DR VEuPathDB; VectorBase:FBgn0014861; -. DR eggNOG; KOG0477; Eukaryota. DR HOGENOM; CLU_000995_0_1_1; -. DR InParanoid; P49735; -. DR OMA; AAANPIX; -. DR OrthoDB; 844at2759; -. DR PhylomeDB; P49735; -. DR Reactome; R-DME-176187; Activation of ATR in response to replication stress. DR Reactome; R-DME-68867; Assembly of the pre-replicative complex. DR Reactome; R-DME-68949; Orc1 removal from chromatin. DR Reactome; R-DME-68962; Activation of the pre-replicative complex. DR Reactome; R-DME-69052; Switching of origins to a post-replicative state. DR BioGRID-ORCS; 40973; 0 hits in 1 CRISPR screen. DR GenomeRNAi; 40973; -. DR PRO; PR:P49735; -. DR Proteomes; UP000000803; Chromosome 3R. DR Bgee; FBgn0014861; Expressed in secondary oocyte and 46 other cell types or tissues. DR GO; GO:0005694; C:chromosome; ISS:UniProtKB. DR GO; GO:0071162; C:CMG complex; IDA:FlyBase. DR GO; GO:0042555; C:MCM complex; IDA:FlyBase. DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0016887; F:ATP hydrolysis activity; ISS:UniProtKB. 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:0030261; P:chromosome condensation; IMP:FlyBase. DR GO; GO:0006260; P: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:0006279; P:premeiotic DNA replication; NAS:ComplexPortal. DR CDD; cd17753; MCM2; 1. DR FunFam; 2.20.28.10:FF:000002; DNA helicase; 1. DR FunFam; 3.30.1640.10:FF:000020; DNA helicase; 1. DR FunFam; 3.40.50.300:FF:000138; DNA helicase; 1. DR Gene3D; 2.20.28.10; -; 1. DR Gene3D; 3.30.1640.10; mini-chromosome maintenance (MCM) complex, chain A, domain 1; 1. DR Gene3D; 2.40.50.140; Nucleic acid-binding proteins; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR031327; MCM. DR InterPro; IPR008045; MCM2. DR InterPro; IPR061506; MCM2_N. DR InterPro; IPR018525; MCM_CS. DR InterPro; IPR001208; MCM_dom. DR InterPro; IPR041562; MCM_lid. DR InterPro; IPR027925; MCM_N. DR InterPro; IPR033762; MCM_OB. DR InterPro; IPR012340; NA-bd_OB-fold. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR059098; WHD_MCM2. DR PANTHER; PTHR11630; DNA REPLICATION LICENSING FACTOR MCM FAMILY MEMBER; 1. DR PANTHER; PTHR11630:SF44; DNA REPLICATION LICENSING FACTOR MCM2; 1. DR Pfam; PF00493; MCM; 1. DR Pfam; PF12619; MCM2_N; 1. DR Pfam; PF17855; MCM_lid; 1. DR Pfam; PF14551; MCM_N; 1. DR Pfam; PF17207; MCM_OB; 1. DR Pfam; PF23669; WHD_MCM2; 1. DR PRINTS; PR01657; MCMFAMILY. DR PRINTS; PR01658; MCMPROTEIN2. DR SMART; SM00350; MCM; 1. DR SUPFAM; SSF50249; Nucleic acid-binding proteins; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS00847; MCM_1; 1. DR PROSITE; PS50051; MCM_CTD; 1. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Cell cycle; Cell division; Chromosome; KW DNA replication; DNA-binding; Helicase; Hydrolase; Metal-binding; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Zinc; KW Zinc-finger. FT CHAIN 1..887 FT /note="DNA replication licensing factor Mcm2" FT /id="PRO_0000194090" FT DOMAIN 441..785 FT /note="MCM C-terminal AAA(+) ATPase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01410" FT ZN_FING 314..340 FT /note="C4-type" FT /evidence="ECO:0000255" FT REGION 1..150 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 508..515 FT /note="Walker A" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01410" FT MOTIF 572..575 FT /note="Walker B" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01410" FT COMPBIAS 1..11 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 33..42 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 50..60 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 66..78 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 97..119 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 515 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /ligand_note="ligand shared with MCM6" FT /evidence="ECO:0000250|UniProtKB:P49736" FT BINDING 516 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /ligand_note="ligand shared with MCM6" FT /evidence="ECO:0000250|UniProtKB:P49736" FT SITE 641 FT /note="Arginine finger" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01410" FT MOD_RES 26 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:17372656" FT MOD_RES 27 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:17372656" FT MOD_RES 89 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:18327897" FT MOD_RES 92 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:18327897" FT MOD_RES 124 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:17372656" FT MUTAGEN 514 FT /note="K->A: Reduces complex helicase activity." FT /evidence="ECO:0000269|PubMed:20122406" SQ SEQUENCE 887 AA; 100415 MW; 26A7092109F09CBE CRC64; MDNPSSPPPN TPSDAAERRD LRAAMTSPVG DFEPFENEDE ILGDQTVRDE AEEEDGEELF GDNMENDYRP MPELDHYDPA LLDDEDDFSE MSQGDRFAAE SEMRRRDRAA GIHRDDRDLG FGQSDDEDDV GPRAKRRAGE KAAVGEVEDT EMVESIENLE DTKGHSTKEW VSMLGPRTEI ANRFQSFLRT FVDERGAYTY RDRIRRMCEQ NMSSFVVSYT DLANKEHVLA YFLPEAPFQM LEIFDKVAKD MVLSIFPTYE RVTTEIHVRI SELPLIEELR TFRKLHLNQL VRTLGVVTAT TGVLPQLSVI KYDCVKCGYV LGPFVQSQNT EIKPGSCPEC QSTGPFSINM EQTLYRNYQK ITLQESPGRI PAGRIPRSKD VILLADLCDQ CKPGDELEVT GIYTNNYDGS LNTDQGFPVF ATVIIANHVV VKDSKQVVQS LTDEDIATIQ KLSKDPRIVE RVVASMAPSI YGHDYIKRAL ALALFGGESK NPGEKHKVRG DINLLICGDP GTAKSQFLKY TEKVAPRAVF TTGQGASAVG LTAYVRRNPV SREWTLEAGA LVLADQGVCL IDEFDKMNDQ DRTSIHEAME QQSISISKAG IVTSLQARCT VIAAANPIGG RYDPSMTFSE NVNLSEPILS RFDVLCVVKD EFDPMQDQQL AKFVVHSHMK HHPSEEEQPE LEEPQLKTVD EIPQDLLRQY IVYAKENIRP KLTNIDEDKI AKMYAQLRQE SFATGSLPIT VRHIESVIRM SEAHARMHLR ENVMEADVSM AIRMMLESFI EAQKFSVMKK MRSTFQKYLS FQKDHSELLF FILRQLTLDQ LAYIRCKDGP GATHVEIMER DLIERAKQLD IVNLKPFYES DLFRTNGFSY DPKRRIILQI VVDGNTA //