MCM4_DROME
ID MCM4_DROME Reviewed; 866 AA.
AC Q26454; Q9V4M5;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2001, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=DNA replication licensing factor MCM4;
DE EC=3.6.4.12;
DE AltName: Full=Protein disc proliferation abnormal;
GN Name=dpa; ORFNames=CG1616;
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].
RX PubMed=7489728; DOI=10.1002/j.1460-2075.1995.tb00223.x;
RA Feger G., Vaessin H., Su T.T., Wolff E., Jan L.Y., Jan Y.N.;
RT "dpa, a member of the MCM family, is required for mitotic DNA replication
RT but not endoreplication in Drosophila.";
RL EMBO J. 14:5387-5398(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 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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-55, AND IDENTIFICATION BY
RP 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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-55; SER-81 AND THR-87, 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 [7]
RP RECONSTITUTION OF THE MCM2-7 COMPLEX, FUNCTION OF THE MCM2-7 COMPLEX, AND
RP MUTAGENESIS OF LYS-518.
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. Essential role in mitotic DNA
CC replication but not in endoreplication. {ECO:0000269|PubMed:16798881,
CC ECO:0000269|PubMed:20122406}.
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. The complex forms a toroidal
CC hexameric ring with the proposed subunit order Mcm2-Mcm6-Mcm4-Mcm7-
CC Mcm3-Mcm5 (Probable). {ECO:0000269|PubMed:16798881, ECO:0000305}.
CC -!- INTERACTION:
CC Q26454; Q9V461: Mcm6; NbExp=4; IntAct=EBI-175772, EBI-869161;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the MCM family. {ECO:0000305}.
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DR EMBL; S80255; AAB35644.1; -; mRNA.
DR EMBL; AE013599; AAF59242.1; -; Genomic_DNA.
DR PIR; S59872; S59872.
DR RefSeq; NP_001286160.1; NM_001299231.1.
DR RefSeq; NP_477185.1; NM_057837.5.
DR PDB; 6RAW; EM; 3.70 A; 4=1-866.
DR PDB; 6RAX; EM; 3.99 A; 4=1-866.
DR PDB; 6RAY; EM; 4.28 A; 4=1-866.
DR PDB; 6RAZ; EM; 4.46 A; 4=1-866.
DR PDBsum; 6RAW; -.
DR PDBsum; 6RAX; -.
DR PDBsum; 6RAY; -.
DR PDBsum; 6RAZ; -.
DR AlphaFoldDB; Q26454; -.
DR SMR; Q26454; -.
DR BioGRID; 61555; 17.
DR ComplexPortal; CPX-2942; MCM complex.
DR DIP; DIP-35346N; -.
DR IntAct; Q26454; 11.
DR STRING; 7227.FBpp0088055; -.
DR iPTMnet; Q26454; -.
DR PaxDb; Q26454; -.
DR PRIDE; Q26454; -.
DR EnsemblMetazoa; FBtr0088982; FBpp0088055; FBgn0015929.
DR EnsemblMetazoa; FBtr0345797; FBpp0311783; FBgn0015929.
DR GeneID; 35679; -.
DR KEGG; dme:Dmel_CG1616; -.
DR CTD; 103997; -.
DR FlyBase; FBgn0015929; dpa.
DR VEuPathDB; VectorBase:FBgn0015929; -.
DR eggNOG; KOG0478; Eukaryota.
DR GeneTree; ENSGT01050000244824; -.
DR HOGENOM; CLU_000995_7_1_1; -.
DR InParanoid; Q26454; -.
DR OMA; KNTIRIC; -.
DR OrthoDB; 266497at2759; -.
DR PhylomeDB; Q26454; -.
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; 35679; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 35679; -.
DR PRO; PR:Q26454; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0015929; Expressed in secondary oocyte and 45 other tissues.
DR ExpressionAtlas; Q26454; baseline and differential.
DR Genevisible; Q26454; 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:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003678; F:DNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0003697; F:single-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0006260; P:DNA replication; IMP:FlyBase.
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; 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:0007052; P:mitotic spindle organization; IMP:FlyBase.
DR GO; GO:0030174; P:regulation of DNA-templated DNA replication initiation; IC:ComplexPortal.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 2.40.50.140; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR031327; MCM.
DR InterPro; IPR008047; MCM_4.
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; IPR036388; WH-like_DNA-bd_sf.
DR PANTHER; PTHR11630; PTHR11630; 1.
DR PANTHER; PTHR11630:SF66; PTHR11630:SF66; 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; PR01660; MCMPROTEIN4.
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; ATP-binding; DNA replication; DNA-binding; Helicase;
KW Hydrolase; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..866
FT /note="DNA replication licensing factor MCM4"
FT /id="PRO_0000194104"
FT DOMAIN 460..669
FT /note="MCM"
FT REGION 1..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 81..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 124..145
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 644..647
FT /note="Arginine finger"
FT COMPBIAS 1..28
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 48..62
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 81..97
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 512..519
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 55
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17372656,
FT ECO:0000269|PubMed:18327897"
FT MOD_RES 81
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 87
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MUTAGEN 518
FT /note="K->A: Slihgtly reduces complex helicase activity."
FT /evidence="ECO:0000269|PubMed:20122406"
FT CONFLICT 435
FT /note="D -> E (in Ref. 1; AAB35644)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 866 AA; 96610 MW; CF6ED69D2ADDA04E CRC64;
MSSPARSPSV GGATPKQGAR TPTRGIASQD VETPMRMGPG RAVRPSDNIS LPPTSPGNIS
LPATSPARGL GANMSEIDLS SPLNYGTPSS MGSIRTPRSG IRGTPLRARP DIRTDKRIRQ
VAIGGGSGLE PIPEKGSETT DPVSESSQAP QLVVWGTNVV VSQCKSKFKS FIMRFIDPSA
EQDEISENID VNQPLYLQKL EEIHTLEEPY LNLNCAHLKT FDQDLYRQLI CYPQEVIPGF
DMAINEMFFE RYPAALLEHQ IQVRPFNADK TRNMRSLNPE DMDQLISISG MVIRSSNVIP
EMREAFFSCN ICSFSTTVEV DRGRINQPTL CTNCNTNHCF RLIHNRSEFT DKQLVKLQES
PDDMAAGQTP HNVLLYAHND LVDKVQPGDR VTVTGIYRAT PLKTGGLSSS VKSVYKTHVD
VVHFRKVDNK RLYEDEEGKD HIFPPERVEL LQLLAKKPDI YDRLARAIAP SIYENDDIKK
GILLQLFGGT KKKHATLGRQ NFRSEIHLLL CGDPGTSKSQ MLQYVFNLVP RSQYTSGRGS
SAVGLTAYVT KDPETRQLVL QTGALVLADN GVCCIDEFDK MNDSTRSVLH EVMEQQTLSI
AKAGIICQLN ARTSILAAAN PAESQWNKRK NIIDNVQLPH TLLSRFDLIF LVLDPQDEIF
DKRLASHLVS LYYVTRHEEE DTMFDMSVLR DYIAYAREHL SPTLSDEAQQ RLIQAYVDMR
KVGAGRGQIS AYPRQLESLI RLSEAHAKVR LSNQVELLDV EEAWRLHREA LKQSATDPLS
GKIDVGILTT GLSTAARKKR ADLVAAIKEN LKKKGKVLTV PYQKLFSDIK EGSQIMITRE
QFEDALKEVQ DEGAIVVMGK NTIRIC
