MCM6_DROME
ID MCM6_DROME Reviewed; 817 AA.
AC Q9V461; O96047; Q960E3;
DT 02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=DNA replication licensing factor Mcm6;
DE Short=DmMCM6;
DE EC=3.6.4.12 {ECO:0000250|UniProtKB:P97311};
GN Name=Mcm6 {ECO:0000312|EMBL:AAF46184.1, ECO:0000312|FlyBase:FBgn0025815};
GN ORFNames=CG4039;
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] {ECO:0000305, ECO:0000312|EMBL:BAA34732.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RC TISSUE=Oocyte {ECO:0000269|PubMed:9795205};
RX PubMed=9795205; DOI=10.1016/s0378-1119(98)00358-8;
RA Ohno K., Hirose F., Inoue Y.H., Takisawa H., Mimura S., Hashimoto Y.,
RA Kiyono T., Nishida Y., Matsukage A.;
RT "cDNA cloning and expression during development of Drosophila melanogaster
RT MCM3, MCM6 and MCM7.";
RL Gene 217:177-185(1998).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAD32858.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=10023044; DOI=10.1016/s0378-1119(98)00596-4;
RA Feger G.;
RT "Identification and complete cDNA sequence of the missing Drosophila MCMs:
RT DmMCM3, DmMCM6 and DmMCM7.";
RL Gene 227:149-155(1999).
RN [3] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, INTERACTION WITH MCM2; MCM4
RP AND MCM5, SUBCELLULAR LOCATION, AND MUTAGENESIS OF THR-157; GLY-388 AND
RP MET-676.
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 [4] {ECO:0000312|EMBL:AAF46184.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:10731132};
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 [5] {ECO:0000305, ECO:0000312|EMBL:AAF46184.1}
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 [6] {ECO:0000305, ECO:0000312|EMBL:AAK93526.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 231-817.
RC STRAIN=Berkeley {ECO:0000269|PubMed:12537569};
RC TISSUE=Embryo {ECO:0000269|PubMed:12537569};
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 [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 RECONSTITUTION OF THE MCM2-7 COMPLEX, FUNCTION OF THE MCM2-7 COMPLEX, AND
RP MUTAGENESIS OF LYS-394.
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. Required for mitotic cycles,
CC endocycles, and the special S phase associated with the amplification
CC of chorion genes; has a role in origin unwinding or fork elongation at
CC chorion loci. {ECO:0000269|PubMed:11854416,
CC ECO:0000269|PubMed:16798881, 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 Evidence={ECO:0000250|UniProtKB:P97311};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066;
CC Evidence={ECO:0000250|UniProtKB:P97311};
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). The heterodimers of Mcm4/Mcm6 and Mcm3/Mcm5
CC interact with Mcm2 and Mcm7. {ECO:0000269|PubMed:16798881,
CC ECO:0000305}.
CC -!- INTERACTION:
CC Q9V461; Q26454: dpa; NbExp=4; IntAct=EBI-869161, EBI-175772;
CC Q9V461; P49735: Mcm2; NbExp=12; IntAct=EBI-869161, EBI-138228;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11854416}.
CC Note=Associated with chromatin during cell cycles.
CC -!- TISSUE SPECIFICITY: In stage 12 embryos, strongly expressed in the CNS
CC and weakly in the gut. {ECO:0000269|PubMed:10023044}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC {ECO:0000269|PubMed:9795205}.
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:P97311}.
CC -!- SIMILARITY: Belongs to the MCM family. {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK93526.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB010108; BAA34732.1; -; mRNA.
DR EMBL; AF124744; AAD32858.1; -; mRNA.
DR EMBL; AE014298; AAF46184.1; -; Genomic_DNA.
DR EMBL; AY052102; AAK93526.1; ALT_INIT; mRNA.
DR RefSeq; NP_511065.1; NM_078510.3.
DR PDB; 6RAW; EM; 3.70 A; 6=1-817.
DR PDB; 6RAX; EM; 3.99 A; 6=1-817.
DR PDB; 6RAY; EM; 4.28 A; 6=1-817.
DR PDB; 6RAZ; EM; 4.46 A; 6=1-817.
DR PDBsum; 6RAW; -.
DR PDBsum; 6RAX; -.
DR PDBsum; 6RAY; -.
DR PDBsum; 6RAZ; -.
DR AlphaFoldDB; Q9V461; -.
DR SMR; Q9V461; -.
DR BioGRID; 58089; 15.
DR ComplexPortal; CPX-2942; MCM complex.
DR DIP; DIP-35347N; -.
DR IntAct; Q9V461; 8.
DR STRING; 7227.FBpp0070913; -.
DR PaxDb; Q9V461; -.
DR PRIDE; Q9V461; -.
DR EnsemblMetazoa; FBtr0070952; FBpp0070913; FBgn0025815.
DR GeneID; 31603; -.
DR KEGG; dme:Dmel_CG4039; -.
DR CTD; 4175; -.
DR FlyBase; FBgn0025815; Mcm6.
DR VEuPathDB; VectorBase:FBgn0025815; -.
DR eggNOG; KOG0480; Eukaryota.
DR GeneTree; ENSGT01050000244824; -.
DR HOGENOM; CLU_000995_3_2_1; -.
DR InParanoid; Q9V461; -.
DR OMA; KYYIAQI; -.
DR OrthoDB; 266497at2759; -.
DR PhylomeDB; Q9V461; -.
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; 31603; 1 hit in 1 CRISPR screen.
DR GenomeRNAi; 31603; -.
DR PRO; PR:Q9V461; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0025815; Expressed in cleaving embryo and 21 other tissues.
DR ExpressionAtlas; Q9V461; baseline and differential.
DR Genevisible; Q9V461; 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; IDA:UniProtKB.
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: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:0006260; P:DNA replication; IMP:UniProtKB.
DR GO; GO:0006270; P:DNA replication initiation; IEA:InterPro.
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:0007307; P:eggshell chorion gene amplification; IMP:FlyBase.
DR GO; GO:1902969; P:mitotic DNA replication; 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; IPR031327; MCM.
DR InterPro; IPR008049; MCM6.
DR InterPro; IPR041024; Mcm6_C.
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; PF18263; MCM6_C; 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; PR01662; MCMPROTEIN6.
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; Mitosis;
KW Nucleotide-binding; Nucleus; Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..817
FT /note="DNA replication licensing factor Mcm6"
FT /id="PRO_0000233315"
FT DOMAIN 338..544
FT /note="MCM"
FT /evidence="ECO:0000255"
FT ZN_FING 152..179
FT /note="C4-type"
FT /evidence="ECO:0000255"
FT MOTIF 520..523
FT /note="Arginine finger"
FT BINDING 388..395
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MUTAGEN 157
FT /note="T->M: In allele 4; homozygous lethal."
FT /evidence="ECO:0000269|PubMed:11854416"
FT MUTAGEN 388
FT /note="G->D: In allele 5; homozygous lethal."
FT /evidence="ECO:0000269|PubMed:11854416"
FT MUTAGEN 394
FT /note="K->A: Slihgtly reduces complex helicase activity."
FT /evidence="ECO:0000269|PubMed:20122406"
FT MUTAGEN 676
FT /note="M->K: In allele K1214; eggs exhibit thin shell and
FT flimsy dorsal appendages."
FT /evidence="ECO:0000269|PubMed:11854416"
FT CONFLICT 10..11
FT /note="QL -> HV (in Ref. 1; BAA34732)"
FT /evidence="ECO:0000305"
FT CONFLICT 550
FT /note="N -> K (in Ref. 1; BAA34732)"
FT /evidence="ECO:0000305"
FT CONFLICT 695
FT /note="A -> G (in Ref. 1 and 6)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 817 AA; 92353 MW; 0B7921FB3D888980 CRC64;
MDVADAQVGQ LRVKDEVGIR AQKLFQDFLE EFKEDGEIKY TRPAASLESP DRCTLEVSFE
DVEKYDQNLA TAIIEEYYHI YPFLCQSVSN YVKDRIGLKT QKDCYVAFTE VPTRHKVRDL
TTSKIGTLIR ISGQVVRTHP VHPELVSGVF MCLDCQTEIR NVEQQFKFTN PTICRNPVCS
NRKRFMLDVE KSLFLDFQKI RIQETQAELP RGCIPRAVEI ILRSELVETV QAGDRYDFTG
TLIVVPDVSV LAGVGTRAEN SSRHKPGEGM DGVTGLKALG MRELNYRMAF LACSVQATTA
RFGGTDLPMS EVTAEDMKKQ MTDAEWHKIY EMSKDRNLYQ NLISSLFPSI YGNDEVKRGI
LLQQFGGVAK TTTEKTSLRG DINVCIVGDP STAKSQFLKQ VSDFSPRAIY TSGKASSAAG
LTAAVVRDEE SFDFVIEAGA LMLADNGICC IDEFDKMDQR DQVAIHEAME QQTISIARAG
VRATLNARTS ILAAANPING RYDRSKSLQQ NIQLSAPIMS RFDLFFILVD ECNEVVDYAI
ARKIVDLHSN IEESVERAYT REEVLRYVTF ARQFKPVISQ EAGHMLVENY GHLRQRDTGT
SGRSTWRITV RQLESMIRLS EAMAKLECSN RVLERHVKEA FRLLNKSIIR VEQPDIHLDD
DEGLDMDDGI QHDIDMENNG AAANVDENNG MDTSASGAVQ KKKFTLSFED YKNLSTMLVL
HMRAEEARCE VEGNDTGIKR SNVVTWYLEQ VADQIESEDE LISRKNLIEK LIDRLIYHDQ
VIIPLKTSTL KPRIQVQKDF VEEDDPLLVV HPNYVVE
