MCM6_MOUSE
ID MCM6_MOUSE Reviewed; 821 AA.
AC P97311; Q80YQ7;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=DNA replication licensing factor MCM6;
DE EC=3.6.4.12 {ECO:0000269|PubMed:10567526};
DE AltName: Full=Mis5 homolog;
GN Name=Mcm6; Synonyms=Mcmd6, Mis5;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=9077461; DOI=10.1046/j.1365-2443.1996.840284.x;
RA Kimura H., Ohtomo T., Yamaguchi M., Ishii A., Sugimoto K.;
RT "Mouse MCM proteins: complex formation and transportation to the nucleus.";
RL Genes Cells 1:977-993(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [3]
RP FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION IN THE MCM2-7 COMPLEX,
RP MUTAGENESIS OF 402-LYS-SER-403 AND 460-ASP-GLU-461, AND ATP-BINDING.
RX PubMed=10567526; DOI=10.1128/mcb.19.12.8003;
RA You Z., Komamura Y., Ishimi Y.;
RT "Biochemical analysis of the intrinsic Mcm4-Mcm6-mcm7 DNA helicase
RT activity.";
RL Mol. Cell. Biol. 19:8003-8015(1999).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-791, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-271; SER-689; SER-704 AND
RP SER-762, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-643, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
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.
CC {ECO:0000269|PubMed:10567526}.
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:10567526};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066;
CC Evidence={ECO:0000269|PubMed:10567526};
CC -!- SUBUNIT: Component of the MCM2-7 complex (PubMed:10567526). The complex
CC forms a toroidal hexameric ring with the proposed subunit order MCM2-
CC MCM6-MCM4-MCM7-MCM3-MCM5. May interact with MCM10. Interacts with
CC TIPIN. Interacts with CDT1. Interacts with MCMBP. Interacts with DDI2
CC (By similarity). Component of the CMG helicase complex, composed of the
CC MCM2-7 complex, the GINS complex and CDC45 (By similarity).
CC {ECO:0000250|UniProtKB:Q14566, ECO:0000250|UniProtKB:Q5FWY4,
CC ECO:0000269|PubMed:10567526}.
CC -!- INTERACTION:
CC P97311; Q8R4E9: Cdt1; NbExp=2; IntAct=EBI-457132, EBI-457043;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q14566}.
CC Chromosome {ECO:0000250|UniProtKB:Q14566}. Note=Binds to chromatin
CC during G1 and detach from it during S phase.
CC {ECO:0000250|UniProtKB:Q14566}.
CC -!- PTM: O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner.
CC {ECO:0000250|UniProtKB:Q14566}.
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:0000269|PubMed:10567526}.
CC -!- SIMILARITY: Belongs to the MCM family. {ECO:0000305}.
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DR EMBL; D86726; BAA13159.1; -; mRNA.
DR EMBL; BC050886; AAH50886.2; -; mRNA.
DR EMBL; BC057584; AAH57584.1; -; mRNA.
DR CCDS; CCDS15252.1; -.
DR RefSeq; NP_032593.1; NM_008567.2.
DR AlphaFoldDB; P97311; -.
DR SMR; P97311; -.
DR BioGRID; 201349; 22.
DR ComplexPortal; CPX-2941; MCM complex.
DR CORUM; P97311; -.
DR IntAct; P97311; 8.
DR STRING; 10090.ENSMUSP00000027601; -.
DR iPTMnet; P97311; -.
DR PhosphoSitePlus; P97311; -.
DR SwissPalm; P97311; -.
DR EPD; P97311; -.
DR jPOST; P97311; -.
DR PaxDb; P97311; -.
DR PeptideAtlas; P97311; -.
DR PRIDE; P97311; -.
DR ProteomicsDB; 295840; -.
DR Antibodypedia; 1416; 366 antibodies from 35 providers.
DR DNASU; 17219; -.
DR Ensembl; ENSMUST00000027601; ENSMUSP00000027601; ENSMUSG00000026355.
DR GeneID; 17219; -.
DR KEGG; mmu:17219; -.
DR UCSC; uc007cln.1; mouse.
DR CTD; 4175; -.
DR MGI; MGI:1298227; Mcm6.
DR VEuPathDB; HostDB:ENSMUSG00000026355; -.
DR eggNOG; KOG0480; Eukaryota.
DR GeneTree; ENSGT01050000244824; -.
DR InParanoid; P97311; -.
DR OMA; KYYIAQI; -.
DR OrthoDB; 266497at2759; -.
DR PhylomeDB; P97311; -.
DR TreeFam; TF105646; -.
DR Reactome; R-MMU-176187; Activation of ATR in response to replication stress.
DR Reactome; R-MMU-68867; Assembly of the pre-replicative complex.
DR Reactome; R-MMU-68949; Orc1 removal from chromatin.
DR Reactome; R-MMU-68962; Activation of the pre-replicative complex.
DR Reactome; R-MMU-69052; Switching of origins to a post-replicative state.
DR BioGRID-ORCS; 17219; 28 hits in 74 CRISPR screens.
DR ChiTaRS; Mcm6; mouse.
DR PRO; PR:P97311; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; P97311; protein.
DR Bgee; ENSMUSG00000026355; Expressed in somite and 230 other tissues.
DR ExpressionAtlas; P97311; baseline and differential.
DR Genevisible; P97311; MM.
DR GO; GO:0071162; C:CMG complex; ISS:UniProtKB.
DR GO; GO:0042555; C:MCM complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
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; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0003697; F:single-stranded DNA binding; IPI:MGI.
DR GO; GO:0006270; P:DNA replication initiation; IEA:InterPro.
DR GO; GO:0006268; P:DNA unwinding involved in DNA replication; IPI:MGI.
DR GO; GO:0000727; P:double-strand break repair via break-induced replication; IBA:GO_Central.
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 Acetylation; ATP-binding; Cell cycle; Chromosome;
KW Direct protein sequencing; DNA replication; DNA-binding; Glycoprotein;
KW Helicase; Hydrolase; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..821
FT /note="DNA replication licensing factor MCM6"
FT /id="PRO_0000194114"
FT DOMAIN 346..553
FT /note="MCM"
FT REGION 676..708
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 528..531
FT /note="Arginine finger"
FT COMPBIAS 693..708
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 396..403
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q14566"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14566"
FT MOD_RES 219
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14566"
FT MOD_RES 271
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 278
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14566"
FT MOD_RES 643
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 689
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 704
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 762
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 791
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT MUTAGEN 402..403
FT /note="KS->AA: Decreased MCM complex DNA helicase activity.
FT Loss of ATP-binding. Decreased MCM complex ATPase activity.
FT No effect on MCM complex formation."
FT /evidence="ECO:0000269|PubMed:10567526"
FT MUTAGEN 460..461
FT /note="DE->AA: Loss of MCM complex DNA helicase activity.
FT Loss of ATP-binding. No effect on MCM complex formation. No
FT effect on MCM complex ATPase activity and ssDNA binding."
FT /evidence="ECO:0000269|PubMed:10567526"
SQ SEQUENCE 821 AA; 92867 MW; 79E753D2DA218CBF CRC64;
MDLAAAAEPG AGSQHPEVRD EVAEKCQKLF LDFLEEFQGS DGEIKYLQFA EELIRPERNT
LVVSFADLEQ FNQQLSTTIQ EEFYRVYPYL CRALKTFVKD RKEIPFAKDF YVAFQDLPTR
HKIRELTSSR IGLLTRISGQ VVRTHPVHPE LVSGTFLCLD CQTVIKDVEQ QFKYTQPNIC
RNPVCANRKR FLLDTNKSRF VDFQKVRIQE TQAELPRGSI PRSLEVILRA EAVESAQAGD
RCDFTGALIV VPDVSKLSTP GARAETNSRV SGADGYETEG IRGLRALGVR DLSYRLVFLA
CHVAPTNPRF GGKELRDEEQ TAESIKNQMT VKEWEKVFEM SQDKNLYHNL CTSLFPTIHG
NDEVKRGVLL MLFGGVPKTT GEGTSLRGDI NVCIVGDPST AKSQFLKHVD EFSPRAVYTS
GKASSAAGLT AAVVRDEESH EFVIEAGALM LADNGVCCID EFDKMDMRDQ VAIHEAMEQQ
TISITKAGVK ATLNARTSIL AAANPVSGHY DRSKSLKQNI NLSAPIMSRF DLFFILVDEC
NEVTDYAIAR RIVDLHSRIE ESIDRVYSLD DIRRYLLFAR QFKPKISKES EDFIVEQYKR
LRQRDGSGVT KSSWRITVRQ LESMIRLSES MARMHCCDEV QPKHVKEAFR LLNKSIIRVE
TPDVNLDQEE EIQMETDEGQ GGVNGHADSP APVNRFNGSS EDASQETVSK PSLRLGFAEY
CRISNLIVLH LRKMEEEEDE SALKRSELVN WYLKEIESEI DSEEELINKK TIIEKVVHRL
THYDHVLIEL TQAGLKGSSE GSESYEEDPY LVVNPNYLLE D
