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   24-JAN-2024, entry version 182.
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 a component of the MCM2-7 complex (MCM complex) which
CC       is the replicative helicase essential for 'once per cell cycle' DNA
CC       replication initiation and elongation in eukaryotic cells. Core
CC       component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that
CC       unwinds template DNA during replication, and around which the replisome
CC       is built. The active ATPase sites in the MCM2-7 ring are formed through
CC       the interaction surfaces of two neighboring subunits such that a
CC       critical structure of a conserved arginine finger motif is provided in
CC       trans relative to the ATP-binding site of the Walker A box of the
CC       adjacent subunit. The six ATPase active sites, however, are likely to
CC       contribute 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. The complex forms a toroidal
CC       hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-
CC       MCM3-MCM5. Component of the CMG helicase complex, a hexameric ring of
CC       related MCM2-7 subunits stabilized by CDC45 and the tetrameric GINS
CC       complex (PubMed:12207017). Interacts with MCMBP (By similarity).
CC       {ECO:0000250|UniProtKB:P33991, 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; 22.
DR   ComplexPortal; CPX-2941; MCM complex.
DR   CORUM; P49717; -.
DR   IntAct; P49717; 3.
DR   MINT; P49717; -.
DR   STRING; 10090.ENSMUSP00000023353; -.
DR   GlyGen; P49717; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P49717; -.
DR   PhosphoSitePlus; P49717; -.
DR   SwissPalm; P49717; -.
DR   EPD; P49717; -.
DR   PaxDb; 10090-ENSMUSP00000023353; -.
DR   PeptideAtlas; P49717; -.
DR   ProteomicsDB; 295709; -.
DR   Pumba; P49717; -.
DR   Antibodypedia; 1452; 522 antibodies from 36 providers.
DR   DNASU; 17217; -.
DR   Ensembl; ENSMUST00000023353.4; ENSMUSP00000023353.4; ENSMUSG00000022673.6.
DR   GeneID; 17217; -.
DR   KEGG; mmu:17217; -.
DR   UCSC; uc007yhr.2; mouse.
DR   AGR; MGI:103199; -.
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; NRCSFAD; -.
DR   OrthoDB; 5476523at2759; -.
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 81 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 262 other cell types or tissues.
DR   ExpressionAtlas; P49717; baseline and differential.
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; ISO: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; IEA:Ensembl.
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:0006279; P:premeiotic DNA replication; NAS:ComplexPortal.
DR   CDD; cd17755; MCM4; 1.
DR   Gene3D; 2.20.28.10; -; 1.
DR   Gene3D; 3.30.1640.10; mini-chromosome maintenance (MCM) complex, chain A, domain 1; 1.
DR   Gene3D; 2.40.50.140; Nucleic acid-binding proteins; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 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; DNA REPLICATION LICENSING FACTOR MCM FAMILY MEMBER; 1.
DR   PANTHER; PTHR11630:SF66; DNA REPLICATION LICENSING FACTOR MCM4; 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; Nucleic acid-binding proteins; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   PROSITE; PS00847; MCM_1; 1.
DR   PROSITE; PS50051; MCM_2; 1.
DR   Genevisible; P49717; MM.
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         470
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_label="2"
FT                   /ligand_note="ligand shared with MCM7"
FT                   /evidence="ECO:0000250|UniProtKB:P33991"
FT   BINDING         496
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_label="1"
FT                   /ligand_note="ligand shared with MCM6"
FT                   /evidence="ECO:0000250|UniProtKB:P33991"
FT   BINDING         515
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_label="2"
FT                   /ligand_note="ligand shared with MCM7"
FT                   /evidence="ECO:0000250|UniProtKB:P33991"
FT   BINDING         516
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_label="2"
FT                   /ligand_note="ligand shared with MCM7"
FT                   /evidence="ECO:0000250|UniProtKB:P33991"
FT   BINDING         617
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_label="2"
FT                   /ligand_note="ligand shared with MCM7"
FT                   /evidence="ECO:0000250|UniProtKB:P33991"
FT   BINDING         642
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_label="1"
FT                   /ligand_note="ligand shared with MCM6"
FT                   /evidence="ECO:0000250|UniProtKB:P33991"
FT   BINDING         731
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_label="1"
FT                   /ligand_note="ligand shared with MCM6"
FT                   /evidence="ECO:0000250|UniProtKB:P33991"
FT   BINDING         734
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_label="1"
FT                   /ligand_note="ligand shared with MCM6"
FT                   /evidence="ECO:0000250|UniProtKB:P33991"
FT   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0000250|UniProtKB:P33991"
FT   MOD_RES         6
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P33991"
FT   MOD_RES         7
FT                   /note="Phosphothreonine"
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
//