MCM4_MOUSE
ID MCM4_MOUSE Reviewed; 862 AA.
AC P49717; O89056;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=DNA replication licensing factor MCM4;
DE EC=3.6.4.12 {ECO:0000269|PubMed:10567526, ECO:0000269|PubMed:12207017};
DE AltName: Full=CDC21 homolog;
DE AltName: Full=P1-CDC21;
GN Name=Mcm4; Synonyms=Cdc21, Mcmd4;
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].
RX PubMed=7610039; DOI=10.1093/nar/23.12.2097;
RA Kimura H., Takizawa N., Nozaki N., Sugimoto K.;
RT "Molecular cloning of cDNA encoding mouse Cdc21 and CDC46 homologs and
RT characterization of the products: physical interaction between P1(MCM3) and
RT CDC46 proteins.";
RL Nucleic Acids Res. 23:2097-2104(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 503-602.
RC STRAIN=BALB/cJ; TISSUE=Spleen;
RX PubMed=9798653; DOI=10.1016/s0161-5890(98)00031-5;
RA Chu C.C., Paul W.E.;
RT "Expressed genes in interleukin-4 treated B cells identified by cDNA
RT representational difference analysis.";
RL Mol. Immunol. 35:487-502(1998).
RN [3]
RP FUNCTION, IDENTIFICATION IN THE MCM2-7 COMPLEX, AND MUTAGENESIS OF
RP 573-ASP-GLU-574.
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 FUNCTION, IDENTIFICATION IN THE MCM2-7 COMPLEX, MUTAGENESIS OF
RP 305-CYS--CYS-308 AND 327-CYS--CYS-330, AND CATALYTIC ACTIVITY.
RX PubMed=12207017; DOI=10.1074/jbc.m205769200;
RA You Z., Ishimi Y., Masai H., Hanaoka F.;
RT "Roles of Mcm7 and Mcm4 subunits in the DNA helicase activity of the mouse
RT Mcm4/6/7 complex.";
RL J. Biol. Chem. 277:42471-42479(2002).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-19 AND SER-130, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Kidney, Liver, Lung, Pancreas, Spleen, 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-857, 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).
RN [7]
RP SUMOYLATION.
RX PubMed=26524493; DOI=10.1038/nsmb.3114;
RA Eisenhardt N., Chaugule V.K., Koidl S., Droescher M., Dogan E., Rettich J.,
RA Sutinen P., Imanishi S.Y., Hofmann K., Palvimo J.J., Pichler A.;
RT "A new vertebrate SUMO enzyme family reveals insights into SUMO-chain
RT assembly.";
RL Nat. Struct. Mol. Biol. 22:959-967(2015).
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:12207017}.
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, ECO:0000269|PubMed:12207017};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066;
CC Evidence={ECO:0000269|PubMed:10567526, ECO:0000269|PubMed:12207017};
CC -!- SUBUNIT: Component of the MCM2-7 complex (PubMed:12207017). The complex
CC forms a toroidal hexameric ring with the proposed subunit order MCM2-
CC MCM6-MCM4-MCM7-MCM3-MCM5. Interacts with MCMBP (By similarity).
CC Component of the CMG helicase complex, composed of the MCM2-7 complex,
CC the GINS complex and CDC45 (By similarity).
CC {ECO:0000250|UniProtKB:P30664, ECO:0000250|UniProtKB:P33991,
CC ECO:0000269|PubMed:12207017}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P30664}.
CC Chromosome {ECO:0000250|UniProtKB:P30664}. Note=Associated with
CC chromatin before the formation of nuclei and detaches from it as DNA
CC replication progresses. {ECO:0000250|UniProtKB:P30664}.
CC -!- PTM: Sumoylated; SUMO2 modified in response to stress caused by
CC inhibition of proteasome activity (in vitro).
CC {ECO:0000269|PubMed:26524493}.
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; D26089; BAA05082.1; -; mRNA.
DR EMBL; U89402; AAC36509.1; -; mRNA.
DR CCDS; CCDS27977.1; -.
DR PIR; S56766; S56766.
DR RefSeq; NP_032591.3; NM_008565.3.
DR AlphaFoldDB; P49717; -.
DR SMR; P49717; -.
DR BioGRID; 201347; 21.
DR ComplexPortal; CPX-2941; MCM complex.
DR CORUM; P49717; -.
DR IntAct; P49717; 3.
DR MINT; P49717; -.
DR STRING; 10090.ENSMUSP00000023353; -.
DR iPTMnet; P49717; -.
DR PhosphoSitePlus; P49717; -.
DR SwissPalm; P49717; -.
DR EPD; P49717; -.
DR PaxDb; P49717; -.
DR PeptideAtlas; P49717; -.
DR PRIDE; P49717; -.
DR ProteomicsDB; 295709; -.
DR Antibodypedia; 1452; 465 antibodies from 36 providers.
DR DNASU; 17217; -.
DR Ensembl; ENSMUST00000023353; ENSMUSP00000023353; ENSMUSG00000022673.
DR GeneID; 17217; -.
DR KEGG; mmu:17217; -.
DR UCSC; uc007yhr.2; mouse.
DR CTD; 4173; -.
DR MGI; MGI:103199; Mcm4.
DR VEuPathDB; HostDB:ENSMUSG00000022673; -.
DR eggNOG; KOG0478; Eukaryota.
DR GeneTree; ENSGT01050000244824; -.
DR HOGENOM; CLU_000995_7_1_1; -.
DR InParanoid; P49717; -.
DR OMA; KNTIRIC; -.
DR OrthoDB; 266497at2759; -.
DR PhylomeDB; P49717; -.
DR TreeFam; TF300463; -.
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; 17217; 24 hits in 76 CRISPR screens.
DR ChiTaRS; Mcm4; mouse.
DR PRO; PR:P49717; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; P49717; protein.
DR Bgee; ENSMUSG00000022673; Expressed in indifferent gonad and 258 other tissues.
DR ExpressionAtlas; P49717; baseline and differential.
DR Genevisible; P49717; 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; 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; IDA:MGI.
DR GO; GO:0003697; F:single-stranded DNA binding; IPI:MGI.
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; IPI:MGI.
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: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; 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 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; 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; DNA replication;
KW DNA-binding; Helicase; Hydrolase; Isopeptide bond; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P33991"
FT CHAIN 2..862
FT /note="DNA replication licensing factor MCM4"
FT /id="PRO_0000194102"
FT DOMAIN 457..666
FT /note="MCM"
FT REGION 1..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 90..121
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 641..644
FT /note="Arginine finger"
FT COMPBIAS 1..28
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 29..43
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 57..71
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 509..516
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P33991"
FT MOD_RES 19
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P33991"
FT MOD_RES 31
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P33991"
FT MOD_RES 32
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P33991"
FT MOD_RES 101
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P33991"
FT MOD_RES 104
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P33991"
FT MOD_RES 109
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P33991"
FT MOD_RES 119
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P33991"
FT MOD_RES 130
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 141
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P33991"
FT MOD_RES 144
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P33991"
FT MOD_RES 219
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P33991"
FT MOD_RES 449
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P33991"
FT MOD_RES 857
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CROSSLNK 438
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P33991"
FT CROSSLNK 797
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P33991"
FT MUTAGEN 305..308
FT /note="CQVC->AQVA: Results in unstable hexamers. Increased
FT MCM complex DNA helicase activity."
FT /evidence="ECO:0000269|PubMed:12207017"
FT MUTAGEN 327..330
FT /note="CVHC->AVHA: Results in unstable hexamers. Increased
FT MCM complex DNA helicase activity."
FT /evidence="ECO:0000269|PubMed:12207017"
FT MUTAGEN 573..574
FT /note="DE->AA: Decreased MCM complex DNA helicase activity.
FT Reduced ssDNA binding. No effect on MCM complex formation.
FT No effect on MCM complex ATP binding and ATPase activity."
FT /evidence="ECO:0000269|PubMed:10567526"
FT CONFLICT 530
FT /note="Q -> R (in Ref. 2; AAC36509)"
FT /evidence="ECO:0000305"
FT CONFLICT 572
FT /note="I -> T (in Ref. 2; AAC36509)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 862 AA; 96736 MW; 516ACC1A3C6FB16E CRC64;
MSSPASTPSR RSSRRGRVTP TQSLRSEESR SSPNRRRRGE DSSTGELLPM PTSPGADLQS
PPAQNALFSS PPQMHSLAIP LDFDVSSPLT YGTPSSRVEG TPRSGVRGTP VRQRPDLGSA
RKGLQVDLQS DGAAAEDIVP SEQSLGQKLV IWGTDVNVAT CKENFQRFLQ CFTDPLAKEE
ENVGIDITQP LYMQQLGEIN ITGEPFLNVN CEHIKSFSKN LYRQLISYPQ EVIPTFDMAV
NEIFFDRYPD SILEHQIQVR PFNALKTKSM RNLNPEDIDQ LITISGMVIR TSQLIPEMQE
AFFQCQVCAH TTRVEIDRGR IAEPCSCVHC HTTHSMALIH NRSFFSDKQM IKLQESPEDM
PAGQTPHTIV LFAHNDLVDK VQPGDRVNVT GIYRAVPIRV NPRVSNVKSV YKTHIDVIHY
RKTDAKRLHG LDEEAEQKLF SEKRVKLLKE LSRKPDIYER LASALAPSIY EHEDIKKGIL
LQLFGGTRKD FSHTGRGKFR AEINILLCGD PGTSKSQLLQ YVYNLVPRGQ YTSGKGSSAV
GLTAYVMKDP ETRQLVLQTG ALVLSDNGIC CIDEFDKMNE STRSVLHEVM EQQTLSIAKA
GIICQLNART SVLAAANPIE SQWNPKKTTI ENIQLPHTLL SRFDLIFLML DPQDEAYDRR
LAHHLVSLYY QSEEQVEEEF LDMAVLKDYI AYAHSTIMPR LSEEASQALI EAYVNMRKIG
SSRGMVSAYP RQLESLIRLA EAHAKVRFSN KVEAIDVEEA KRLHREALKQ SATDPRTGIV
DISILTTGMS ATSRKRKEEL AEALRKLILS KGKTPALKYQ QLFEDIRGQS DTAITKDMFE
EALRALADDD FLTVTGKTVR LL
