MCM4_HUMAN
ID MCM4_HUMAN Reviewed; 863 AA.
AC P33991; Q8NEH1; Q99658;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 5.
DT 03-AUG-2022, entry version 219.
DE RecName: Full=DNA replication licensing factor MCM4;
DE EC=3.6.4.12 {ECO:0000250|UniProtKB:P49717};
DE AltName: Full=CDC21 homolog;
DE AltName: Full=P1-CDC21;
GN Name=MCM4 {ECO:0000312|HGNC:HGNC:6947}; Synonyms=CDC21;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT MET-650.
RX PubMed=7601140; DOI=10.1111/j.1432-1033.1995.tb20660.x;
RA Musahl C., Schulte D., Burkhart R., Knippers R.;
RT "A human homologue of the yeast replication protein Cdc21. Interactions
RT with other Mcm proteins.";
RL Eur. J. Biochem. 230:1096-1101(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLY-460.
RG NIEHS SNPs program;
RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-650.
RC TISSUE=Testis;
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-712.
RX PubMed=9465298; DOI=10.1006/geno.1997.5076;
RA Connelly M.A., Zhang H., Kieleczawa J., Anderson C.W.;
RT "The promoters for human DNA-PKcs (PRKDC) and MCM4: divergently transcribed
RT genes located at chromosome 8 band q11.";
RL Genomics 47:71-83(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-23.
RX PubMed=9284934; DOI=10.1159/000134594;
RA Ladenburger E.M., Fackelmayer F.O., Hameister H., Knippers R.;
RT "MCM4 and PRKDC, human genes encoding proteins MCM4 and DNA-PKcs, are close
RT neighbours located on chromosome 8q12-->q13.";
RL Cytogenet. Cell Genet. 77:268-270(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 440-863, AND VARIANT MET-650.
RC TISSUE=Cervix;
RX PubMed=8265339; DOI=10.1093/nar/21.23.5289-a;
RA Hu B., Burkhart R., Schulte D., Musahl C., Knippers R.;
RT "The P1 family: a new class of nuclear mammalian proteins related to the
RT yeast Mcm replication proteins.";
RL Nucleic Acids Res. 21:5289-5293(1993).
RN [7]
RP IDENTIFICATION IN THE MCM2-7 COMPLEX, AND FUNCTION.
RX PubMed=9305914; DOI=10.1074/jbc.272.39.24508;
RA Ishimi Y.;
RT "A DNA helicase activity is associated with an MCM4, -6, and -7 protein
RT complex.";
RL J. Biol. Chem. 272:24508-24513(1997).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-120, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [9]
RP IDENTIFICATION IN THE MCM2-7 COMPLEX, AND ATPASE ACTIVITY OF THE MCM2-7
RP COMPLEX.
RX PubMed=16899510; DOI=10.1091/mbc.e06-03-0241;
RA Tsuji T., Ficarro S.B., Jiang W.;
RT "Essential role of phosphorylation of MCM2 by Cdc7/Dbf4 in the initiation
RT of DNA replication in mammalian cells.";
RL Mol. Biol. Cell 17:4459-4472(2006).
RN [10]
RP HELICASE ACTIVITY OF THE MCM2-3 COMPLEX, INTERACTION WITH MCMBP,
RP IDENTIFICATION IN THE MCM2-7 COMPLEX, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=17296731; DOI=10.1128/mcb.02384-06;
RA Sakwe A.M., Nguyen T., Athanasopoulos V., Shire K., Frappier L.;
RT "Identification and characterization of a novel component of the human
RT minichromosome maintenance complex.";
RL Mol. Cell. Biol. 27:3044-3055(2007).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-120, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26; SER-31; SER-32 AND
RP SER-34, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-131, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-220 AND LYS-450, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-32; SER-120; SER-131; SER-142 AND SER-145, CLEAVAGE OF
RP INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-120 AND SER-131, CLEAVAGE OF INITIATOR METHIONINE [LARGE
RP SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [19]
RP INVOLVEMENT IN IMD54.
RX PubMed=22354170; DOI=10.1172/jci60224;
RA Hughes C.R., Guasti L., Meimaridou E., Chuang C.H., Schimenti J.C.,
RA King P.J., Costigan C., Clark A.J., Metherell L.A.;
RT "MCM4 mutation causes adrenal failure, short stature, and natural killer
RT cell deficiency in humans.";
RL J. Clin. Invest. 122:814-820(2012).
RN [20]
RP INVOLVEMENT IN IMD54.
RX PubMed=22354167; DOI=10.1172/jci61014;
RA Gineau L., Cognet C., Kara N., Lach F.P., Dunne J., Veturi U., Picard C.,
RA Trouillet C., Eidenschenk C., Aoufouchi S., Alcais A., Smith O.,
RA Geissmann F., Feighery C., Abel L., Smogorzewska A., Stillman B.,
RA Vivier E., Casanova J.L., Jouanguy E.;
RT "Partial MCM4 deficiency in patients with growth retardation, adrenal
RT insufficiency, and natural killer cell deficiency.";
RL J. Clin. Invest. 122:821-832(2012).
RN [21]
RP INVOLVEMENT IN IMD54.
RX PubMed=22499342; DOI=10.1136/jmedgenet-2012-100803;
RA Casey J.P., Nobbs M., McGettigan P., Lynch S., Ennis S.;
RT "Recessive mutations in MCM4/PRKDC cause a novel syndrome involving a
RT primary immunodeficiency and a disorder of DNA repair.";
RL J. Med. Genet. 49:242-245(2012).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26; SER-32; THR-102; SER-105;
RP THR-110; SER-120 AND SER-131, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [24]
RP FUNCTION, MUTAGENESIS OF GLY-364, AND CATALYTIC ACTIVITY.
RX PubMed=25661590; DOI=10.1093/jb/mvv015;
RA Ishimi Y., Irie D.;
RT "G364R mutation of MCM4 detected in human skin cancer cells affects DNA
RT helicase activity of MCM4/6/7 complex.";
RL J. Biochem. 157:561-569(2015).
RN [25]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-439 AND LYS-798, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
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:16899510, ECO:0000269|PubMed:25661590,
CC ECO:0000269|PubMed:9305914}.
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:25661590};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066;
CC Evidence={ECO:0000269|PubMed:25661590};
CC -!- SUBUNIT: Component of the MCM2-7 complex (PubMed:16899510,
CC PubMed:9305914). The complex forms a toroidal hexameric ring with the
CC proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5 (PubMed:16899510,
CC PubMed:9305914). Interacts with MCMBP (PubMed:17296731). Component of
CC the CMG helicase complex, composed of the MCM2-7 complex, the GINS
CC complex and CDC45 (By similarity). {ECO:0000250|UniProtKB:P30664,
CC ECO:0000269|PubMed:16899510, ECO:0000269|PubMed:17296731,
CC ECO:0000269|PubMed:9305914}.
CC -!- INTERACTION:
CC P33991; P33993: MCM7; NbExp=14; IntAct=EBI-374938, EBI-355924;
CC P33991; Q9BTE3: MCMBP; NbExp=14; IntAct=EBI-374938, EBI-749378;
CC P33991; Q08945: SSRP1; NbExp=6; IntAct=EBI-374938, EBI-353771;
CC P33991; Q9Y5B9: SUPT16H; NbExp=3; IntAct=EBI-374938, EBI-1046849;
CC P33991; Q9Q2G4: ORF; Xeno; NbExp=3; IntAct=EBI-374938, EBI-6248094;
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:0000250|UniProtKB:P49717}.
CC -!- DISEASE: Immunodeficiency 54 (IMD54) [MIM:609981]: An autosomal
CC recessive disorder characterized by severe intra- and extrauterine
CC growth retardation, microcephaly, decreased numbers of natural killer
CC cells, and recurrent viral infections, most often affecting the
CC respiratory tract and leading to respiratory failure. Affected
CC individuals also have adrenal insufficiency requiring corticosteroid
CC replacement therapy and may have an increased susceptibility to cancer.
CC {ECO:0000269|PubMed:22354167, ECO:0000269|PubMed:22354170,
CC ECO:0000269|PubMed:22499342}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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:P49717}.
CC -!- SIMILARITY: Belongs to the MCM family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/mcm4/";
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DR EMBL; X74794; CAA52801.1; -; mRNA.
DR EMBL; AY588245; AAS83108.1; -; Genomic_DNA.
DR EMBL; BC031061; AAH31061.1; -; mRNA.
DR EMBL; U63630; AAC52018.1; -; Genomic_DNA.
DR EMBL; U90415; AAB51723.3; -; Genomic_DNA.
DR CCDS; CCDS6143.1; -.
DR PIR; S65954; S65954.
DR RefSeq; NP_005905.2; NM_005914.3.
DR RefSeq; NP_877423.1; NM_182746.2.
DR PDB; 6XTX; EM; 3.29 A; 4=1-863.
DR PDB; 6XTY; EM; 6.77 A; 4=1-863.
DR PDB; 7PFO; EM; 3.20 A; 4=1-863.
DR PDB; 7PLO; EM; 2.80 A; 4=1-863.
DR PDBsum; 6XTX; -.
DR PDBsum; 6XTY; -.
DR PDBsum; 7PFO; -.
DR PDBsum; 7PLO; -.
DR AlphaFoldDB; P33991; -.
DR SMR; P33991; -.
DR BioGRID; 110341; 220.
DR ComplexPortal; CPX-2940; MCM complex.
DR CORUM; P33991; -.
DR DIP; DIP-31729N; -.
DR IntAct; P33991; 98.
DR MINT; P33991; -.
DR STRING; 9606.ENSP00000262105; -.
DR ChEMBL; CHEMBL4105745; -.
DR GlyGen; P33991; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P33991; -.
DR MetOSite; P33991; -.
DR PhosphoSitePlus; P33991; -.
DR SwissPalm; P33991; -.
DR BioMuta; MCM4; -.
DR DMDM; 68571766; -.
DR EPD; P33991; -.
DR jPOST; P33991; -.
DR MassIVE; P33991; -.
DR MaxQB; P33991; -.
DR PaxDb; P33991; -.
DR PeptideAtlas; P33991; -.
DR PRIDE; P33991; -.
DR ProteomicsDB; 54934; -.
DR TopDownProteomics; P33991; -.
DR Antibodypedia; 1452; 465 antibodies from 36 providers.
DR DNASU; 4173; -.
DR Ensembl; ENST00000262105.6; ENSP00000262105.2; ENSG00000104738.18.
DR Ensembl; ENST00000649973.1; ENSP00000496964.1; ENSG00000104738.18.
DR GeneID; 4173; -.
DR KEGG; hsa:4173; -.
DR MANE-Select; ENST00000649973.1; ENSP00000496964.1; NM_182746.3; NP_877423.1.
DR UCSC; uc003xqk.3; human.
DR CTD; 4173; -.
DR DisGeNET; 4173; -.
DR GeneCards; MCM4; -.
DR HGNC; HGNC:6947; MCM4.
DR HPA; ENSG00000104738; Tissue enhanced (bone).
DR MalaCards; MCM4; -.
DR MIM; 602638; gene.
DR MIM; 609981; phenotype.
DR neXtProt; NX_P33991; -.
DR OpenTargets; ENSG00000104738; -.
DR Orphanet; 75391; Primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency.
DR PharmGKB; PA30694; -.
DR VEuPathDB; HostDB:ENSG00000104738; -.
DR eggNOG; KOG0478; Eukaryota.
DR GeneTree; ENSGT01050000244824; -.
DR HOGENOM; CLU_000995_7_1_1; -.
DR InParanoid; P33991; -.
DR OrthoDB; 266497at2759; -.
DR PhylomeDB; P33991; -.
DR TreeFam; TF300463; -.
DR PathwayCommons; P33991; -.
DR Reactome; R-HSA-176187; Activation of ATR in response to replication stress.
DR Reactome; R-HSA-176974; Unwinding of DNA.
DR Reactome; R-HSA-68867; Assembly of the pre-replicative complex.
DR Reactome; R-HSA-68949; Orc1 removal from chromatin.
DR Reactome; R-HSA-68962; Activation of the pre-replicative complex.
DR Reactome; R-HSA-69052; Switching of origins to a post-replicative state.
DR SignaLink; P33991; -.
DR SIGNOR; P33991; -.
DR BioGRID-ORCS; 4173; 742 hits in 1089 CRISPR screens.
DR ChiTaRS; MCM4; human.
DR GeneWiki; MCM4; -.
DR GenomeRNAi; 4173; -.
DR Pharos; P33991; Tchem.
DR PRO; PR:P33991; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P33991; protein.
DR Bgee; ENSG00000104738; Expressed in ventricular zone and 200 other tissues.
DR ExpressionAtlas; P33991; baseline and differential.
DR Genevisible; P33991; HS.
DR GO; GO:0000781; C:chromosome, telomeric region; HDA:BHF-UCL.
DR GO; GO:0071162; C:CMG complex; IPI:ComplexPortal.
DR GO; GO:0042555; C:MCM complex; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
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; NAS:UniProtKB.
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; IDA:ComplexPortal.
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 3D-structure; Acetylation; ATP-binding; Cell cycle; Chromosome;
KW DNA replication; DNA-binding; Helicase; Hydrolase; Isopeptide bond;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:22814378"
FT CHAIN 2..863
FT /note="DNA replication licensing factor MCM4"
FT /id="PRO_0000194101"
FT DOMAIN 458..667
FT /note="MCM"
FT REGION 1..60
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 91..126
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 642..645
FT /note="Arginine finger"
FT COMPBIAS 44..60
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 510..517
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:22814378"
FT MOD_RES 19
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P49717"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 31
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 32
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 34
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 102
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 105
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 110
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 120
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 131
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 142
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 145
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 220
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 450
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 858
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P49717"
FT CROSSLNK 439
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 798
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 460
FT /note="E -> G (in dbSNP:rs17287663)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_020500"
FT VARIANT 650
FT /note="L -> M (in dbSNP:rs762679)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:7601140, ECO:0000269|PubMed:8265339"
FT /id="VAR_020501"
FT MUTAGEN 364
FT /note="G->R: Reduced MCM complex DNA helicase activity. No
FT effect on MCM complex formation. No effect on MCM complex
FT ssDNA binding and ATPase activity."
FT /evidence="ECO:0000269|PubMed:25661590"
FT CONFLICT 62
FT /note="P -> T (in Ref. 1; CAA52801)"
FT /evidence="ECO:0000305"
FT CONFLICT 206
FT /note="P -> Q (in Ref. 1; CAA52801)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 863 AA; 96558 MW; 96D9CA2A7D88D015 CRC64;
MSSPASTPSR RGSRRGRATP AQTPRSEDAR SSPSQRRRGE DSTSTGELQP MPTSPGVDLQ
SPAAQDVLFS SPPQMHSSAI PLDFDVSSPL TYGTPSSRVE GTPRSGVRGT PVRQRPDLGS
AQKGLQVDLQ SDGAAAEDIV ASEQSLGQKL VIWGTDVNVA ACKENFQRFL QRFIDPLAKE
EENVGIDITE PLYMQRLGEI NVIGEPFLNV NCEHIKSFDK NLYRQLISYP QEVIPTFDMA
VNEIFFDRYP DSILEHQIQV RPFNALKTKN MRNLNPEDID QLITISGMVI RTSQLIPEMQ
EAFFQCQVCA HTTRVEMDRG RIAEPSVCGR CHTTHSMALI HNRSLFSDKQ MIKLQESPED
MPAGQTPHTV ILFAHNDLVD KVQPGDRVNV TGIYRAVPIR VNPRVSNVKS VYKTHIDVIH
YRKTDAKRLH GLDEEAEQKL FSEKRVELLK ELSRKPDIYE RLASALAPSI YEHEDIKKGI
LLQLFGGTRK DFSHTGRGKF RAEINILLCG DPGTSKSQLL QYVYNLVPRG QYTSGKGSSA
VGLTAYVMKD PETRQLVLQT GALVLSDNGI CCIDEFDKMN ESTRSVLHEV MEQQTLSIAK
AGIICQLNAR TSVLAAANPI ESQWNPKKTT IENIQLPHTL LSRFDLIFLL LDPQDEAYDR
RLAHHLVALY YQSEEQAEEE LLDMAVLKDY IAYAHSTIMP RLSEEASQAL IEAYVDMRKI
GSSRGMVSAY PRQLESLIRL AEAHAKVRLS NKVEAIDVEE AKRLHREALK QSATDPRTGI
VDISILTTGM SATSRKRKEE LAEALKKLIL SKGKTPALKY QQLFEDIRGQ SDIAITKDMF
EEALRALADD DFLTVTGKTV RLL
