MCM2_DROME
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 03-AUG-2022, entry version 186.
DE RecName: Full=DNA replication licensing factor Mcm2;
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; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; 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).
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:0000269|PubMed:16798881,
CC ECO:0000269|PubMed:20122406, ECO:0000269|PubMed:7622035}.
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=12; IntAct=EBI-138228, EBI-869161;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
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}.
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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 PDBsum; 6RAW; -.
DR PDBsum; 6RAX; -.
DR PDBsum; 6RAY; -.
DR PDBsum; 6RAZ; -.
DR AlphaFoldDB; P49735; -.
DR SMR; P49735; -.
DR BioGRID; 66154; 17.
DR ComplexPortal; CPX-2942; MCM complex.
DR DIP; DIP-22529N; -.
DR IntAct; P49735; 12.
DR STRING; 7227.FBpp0081317; -.
DR iPTMnet; P49735; -.
DR PaxDb; P49735; -.
DR PRIDE; P49735; -.
DR EnsemblMetazoa; FBtr0081827; FBpp0081317; FBgn0014861.
DR GeneID; 40973; -.
DR KEGG; dme:Dmel_CG7538; -.
DR CTD; 4171; -.
DR FlyBase; FBgn0014861; Mcm2.
DR VEuPathDB; VectorBase:FBgn0014861; -.
DR eggNOG; KOG0477; Eukaryota.
DR GeneTree; ENSGT01050000244824; -.
DR HOGENOM; CLU_000995_0_1_1; -.
DR InParanoid; P49735; -.
DR OMA; DCVKCGY; -.
DR OrthoDB; 266497at2759; -.
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 tissues.
DR Genevisible; P49735; DM.
DR GO; GO:0071162; C:CMG complex; IDA:FlyBase.
DR GO; GO:0042555; C:MCM complex; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003678; F:DNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003697; F:single-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0030261; P:chromosome condensation; IMP:FlyBase.
DR GO; GO:0006260; P:DNA replication; TAS:FlyBase.
DR GO; GO:0006268; P:DNA unwinding involved in DNA replication; IBA:GO_Central.
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:1905775; P:negative regulation of DNA helicase activity; IEA:InterPro.
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; IPR031327; MCM.
DR InterPro; IPR008045; MCM2.
DR InterPro; IPR018525; MCM_CS.
DR InterPro; IPR001208; MCM_dom.
DR InterPro; IPR041562; MCM_lid.
DR InterPro; IPR027925; MCM_N.
DR InterPro; IPR033762; MCM_OB.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR11630; PTHR11630; 1.
DR PANTHER; PTHR11630:SF44; PTHR11630:SF44; 1.
DR Pfam; PF00493; MCM; 1.
DR Pfam; PF12619; MCM2_N; 1.
DR Pfam; PF17855; MCM_lid; 1.
DR Pfam; PF14551; MCM_N; 1.
DR Pfam; PF17207; MCM_OB; 1.
DR PRINTS; PR01657; MCMFAMILY.
DR PRINTS; PR01658; MCMPROTEIN2.
DR SMART; SM00350; MCM; 1.
DR SUPFAM; SSF50249; 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; ATP-binding; Cell cycle; Cell division; DNA replication;
KW DNA-binding; Helicase; Hydrolase; Metal-binding; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..887
FT /note="DNA replication licensing factor Mcm2"
FT /id="PRO_0000194090"
FT DOMAIN 458..665
FT /note="MCM"
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 640..643
FT /note="Arginine finger"
FT COMPBIAS 33..61
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 62..78
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 91..148
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 508..515
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
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
