ID MCM5_HUMAN Reviewed; 734 AA. AC P33992; O60785; Q14578; Q9BTJ4; Q9BWL8; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 14-AUG-2001, sequence version 5. DT 02-SEP-2026, entry version 244. DE RecName: Full=DNA replication licensing factor MCM5 {ECO:0000303|Ref.3}; DE EC=3.6.4.12 {ECO:0000305|PubMed:32453425}; DE AltName: Full=CDC46 homolog {ECO:0000250|UniProtKB:P49718}; DE AltName: Full=P1-CDC46 {ECO:0000303|PubMed:8265339}; GN Name=MCM5; Synonyms=CDC46; 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]. RC TISSUE=Cervix carcinoma; RA Hu B.; RL Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases. RN [2] RP SEQUENCE REVISION. RA Goehring F., Jehnichen P., Hemmer W.H.; RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Mimura S., Nishimoto S., Kubota Y., Takisawa H., Nojima H.; RT "Homo sapiens DNA replication licensing factor (huMCM5)."; RL Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-136; SER-180 AND RP ILE-258. RG NIEHS SNPs program; RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lymph, and Placenta; 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 [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 352-590. 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 [9] RP IDENTIFICATION IN THE MCM2-7 COMPLEX, AND FUNCTION. 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 INTERACTION WITH MCMBP, IDENTIFICATION IN THE MCM2-7 COMPLEX, AND RP IDENTIFICATION BY MASS 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 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=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-392; LYS-396 AND LYS-696, 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 [13] 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 [14] 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=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [15] 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 [16] RP INTERACTION WITH ANKRD17. RX PubMed=23711367; DOI=10.1016/j.febslet.2013.05.037; RA Menning M., Kufer T.A.; RT "A role for the Ankyrin repeat containing protein Ankrd17 in Nod1- and RT Nod2-mediated inflammatory responses."; RL FEBS Lett. 587:2137-2142(2013). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315 AND SER-605, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=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 [18] RP INTERACTION WITH TONSL. RX PubMed=26527279; DOI=10.1016/j.molcel.2015.08.005; RA Campos E.I., Smits A.H., Kang Y.H., Landry S., Escobar T.M., Nayak S., RA Ueberheide B.M., Durocher D., Vermeulen M., Hurwitz J., Reinberg D.; RT "Analysis of the histone H3.1 interactome: a suitable chaperone for the RT right event."; RL Mol. Cell 60:697-709(2015). RN [19] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=35585232; DOI=10.1038/s41586-022-04759-1; RA Baris Y., Taylor M.R.G., Aria V., Yeeles J.T.P.; RT "Fast and efficient DNA replication with purified human proteins."; RL Nature 606:204-210(2022). RN [20] RP FUNCTION, UFMYLATION AT LYS-583, MUTAGENESIS OF LYS-583, AND SUBCELLULAR RP LOCATION. RX PubMed=40940420; DOI=10.1038/s44318-025-00562-6; RA Li Z., Wu X., Liu L., Rao S., Liao Y., Liu M., Peng B., Zhang Q., Xia Y., RA Zhai Y., Takeda S., Xu X.; RT "MCM5 UFMylation regulates replication origin firing and fork RT progression."; RL EMBO J. 0:0-0(2025). RN [21] {ECO:0007744|PDB:6XTX, ECO:0007744|PDB:6XTY} RP STRUCTURE BY ELECTRON MICROSCOPY (3.29 ANGSTROMS) IN COMPLEXES WITH ADP AND RP WDHD1 IN CMG COMPLEX, AND SUBUNIT. RX PubMed=32453425; DOI=10.1093/nar/gkaa429; RA Rzechorzek N.J., Hardwick S.W., Jatikusumo V.A., Chirgadze D.Y., RA Pellegrini L.; RT "CryoEM structures of human CMG-ATPgammaS-DNA and CMG-AND-1 complexes."; RL Nucleic Acids Res. 48:6980-6995(2020). RN [22] {ECO:0007744|PDB:7PLO} RP STRUCTURE BY ELECTRON MICROSCOPY (2.80 ANGSTROMS) IN REPLISOME, AND RP SUBUNIT. RX PubMed=34700328; DOI=10.1038/s41586-021-04145-3; RA Jenkyn-Bedford M., Jones M.L., Baris Y., Labib K.P.M., Cannone G., RA Yeeles J.T.P., Deegan T.D.; RT "A conserved mechanism for regulating replisome disassembly in RT eukaryotes."; RL Nature 600:743-747(2021). RN [23] {ECO:0007744|PDB:7PFO} RP STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) IN REPLISOME, AND RP SUBUNIT. RX PubMed=34694004; DOI=10.15252/embj.2021108819; RA Jones M.L., Baris Y., Taylor M.R.G., Yeeles J.T.P.; RT "Structure of a human replisome shows the organisation and interactions of RT a DNA replication machine."; RL EMBO J. 40:e108819-e108819(2021). RN [24] RP INVOLVEMENT IN MGORS8, VARIANT MGORS8 ILE-466, AND SUBCELLULAR LOCATION. RX PubMed=28198391; DOI=10.1038/ejhg.2017.5; RA Vetro A., Savasta S., Russo Raucci A., Cerqua C., Sartori G., RA Limongelli I., Forlino A., Maruelli S., Perucca P., Vergani D., Mazzini G., RA Mattevi A., Stivala L.A., Salviati L., Zuffardi O.; RT "MCM5: a new actor in the link between DNA replication and Meier-Gorlin RT syndrome."; RL Eur. J. Hum. Genet. 25:646-650(2017). 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 CC (PubMed:40940420). Core component of CDC45-MCM-GINS (CMG) helicase, the CC molecular machine that unwinds template DNA during replication, and CC around which the replisome is built (PubMed:16899510, PubMed:32453425, CC PubMed:34694004, PubMed:34700328, PubMed:35585232). The active ATPase CC sites in the MCM2-7 ring are formed through the interaction surfaces of CC two neighboring subunits such that a critical structure of a conserved CC arginine finger motif is provided in trans relative to the ATP-binding CC site of the Walker A box of the adjacent subunit. The six ATPase active CC sites, however, are likely to contribute differentially to the complex CC helicase activity (PubMed:32453425). {ECO:0000269|PubMed:16899510, CC ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, CC ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, CC ECO:0000269|PubMed:40940420}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + phosphate + H(+); 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:0000305|PubMed:32453425}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066; CC Evidence={ECO:0000305|PubMed:32453425}; CC -!- SUBUNIT: Component of the MCM2-7 complex (PubMed:16899510, CC PubMed:17296731). The complex forms a toroidal hexameric ring with the CC proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5 (PubMed:16899510, CC PubMed:17296731, PubMed:32453425). Component of the CMG helicase CC complex, a hexameric ring of related MCM2-7 subunits stabilized by CC CDC45 and the tetrameric GINS complex (PubMed:32453425, CC PubMed:34694004, PubMed:34700328). Interacts with ANKRD17 CC (PubMed:23711367). Interacts with MCMBP (PubMed:17296731). Interacts CC with TONSL; the interaction is direct (PubMed:26527279). CC {ECO:0000269|PubMed:16899510, ECO:0000269|PubMed:17296731, CC ECO:0000269|PubMed:23711367, ECO:0000269|PubMed:26527279, CC ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, CC ECO:0000269|PubMed:34700328}. CC -!- INTERACTION: CC P33992; P62805: H4C9; NbExp=2; IntAct=EBI-359410, EBI-302023; CC P33992; Q9Y468: L3MBTL1; NbExp=2; IntAct=EBI-359410, EBI-1265089; CC P33992; P49736: MCM2; NbExp=5; IntAct=EBI-359410, EBI-374819; CC P33992; P25205: MCM3; NbExp=8; IntAct=EBI-359410, EBI-355153; CC P33992; P33993: MCM7; NbExp=12; IntAct=EBI-359410, EBI-355924; CC P33992; Q9BTE3: MCMBP; NbExp=16; IntAct=EBI-359410, EBI-749378; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305|PubMed:35585232}. Chromosome CC {ECO:0000269|PubMed:40940420, ECO:0000305|PubMed:35585232}. CC Note=Associated with chromatin before the formation of nuclei and CC detaches from it as DNA replication progresses. CC {ECO:0000305|PubMed:35585232}. CC -!- PTM: UFMylated at Lys-583; UFMylation occurs at the ongoing replication CC fork and promotes the CMG replicative DNA helicase complex formation. CC {ECO:0000269|PubMed:40940420}. CC -!- DISEASE: Meier-Gorlin syndrome 8 (MGORS8) [MIM:617564]: A form of CC Meier-Gorlin syndrome, a syndrome characterized by bilateral microtia, CC aplasia/hypoplasia of the patellae, and severe intrauterine and CC postnatal growth retardation with short stature and poor weight gain. CC Additional clinical findings include anomalies of cranial sutures, CC microcephaly, apparently low-set and simple ears, microstomia, full CC lips, highly arched or cleft palate, micrognathia, genitourinary tract CC anomalies, and various skeletal anomalies. While almost all cases have CC primordial dwarfism with substantial prenatal and postnatal growth CC retardation, not all cases have microcephaly, and microtia and CC absent/hypoplastic patella are absent in some. Despite the presence of CC microcephaly, intellect is usually normal. MGORS8 inheritance is CC autosomal recessive. {ECO:0000269|PubMed:28198391}. Note=The disease is CC caused by variants 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. The MCM2-7 hexamer is the proposed CC physiological active complex. CC -!- SIMILARITY: Belongs to the MCM family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/41321/MCM5"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X74795; CAA52802.2; -; mRNA. DR EMBL; D83986; BAA12176.1; -; mRNA. DR EMBL; CR456517; CAG30403.1; -; mRNA. DR EMBL; AY212028; AAO21127.1; -; Genomic_DNA. DR EMBL; Z82244; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000142; AAH00142.1; -; mRNA. DR EMBL; BC003656; AAH03656.1; -; mRNA. DR CCDS; CCDS13915.1; -. DR PIR; I38080; I38080. DR RefSeq; NP_006730.2; NM_006739.4. DR PDB; 6XTX; EM; 3.29 A; 5=1-734. DR PDB; 6XTY; EM; 6.77 A; 5=1-734. DR PDB; 7PFO; EM; 3.20 A; 5=1-734. DR PDB; 7PLO; EM; 2.80 A; 5=1-734. DR PDB; 7W1Y; EM; 2.59 A; 5/D=1-734. DR PDB; 7W68; EM; 4.40 A; D=1-734. DR PDB; 8B9D; EM; 3.40 A; 5=1-734. DR PDB; 8S09; EM; 3.10 A; 5/D=1-734. DR PDB; 8S0A; EM; 3.20 A; 5=1-734. DR PDB; 8S0B; EM; 3.60 A; 5=1-734. DR PDB; 8S0D; EM; 3.60 A; 5=1-734. DR PDB; 8S0E; EM; 3.80 A; 5=1-734. DR PDB; 8S0F; EM; 4.10 A; 5=1-734. DR PDB; 8W0E; EM; 3.40 A; 5=1-734. DR PDB; 8W0F; EM; 2.80 A; 5/D=1-734. DR PDB; 8W0G; EM; 3.80 A; 5/D=1-734. DR PDB; 8W0I; EM; 3.50 A; 5=1-734. DR PDB; 9C6G; EM; 4.26 A; 5/A=1-734. DR PDB; 9CAQ; EM; 3.20 A; 5/D=1-734. DR PDB; 9E2Z; EM; 2.60 A; 5=1-734. DR PDB; 9LXD; EM; 3.27 A; 5=1-734. DR PDB; 9LXE; EM; 3.96 A; 5/H=1-734. DR PDB; 9LXF; EM; 3.86 A; 5/H=1-734. DR AlphaFoldDB; P33992; -. DR EMDB; EMD-10619; -. DR EMDB; EMD-10621; -. DR EMDB; EMD-13375; -. DR EMDB; EMD-13494; -. DR EMDB; EMD-19618; -. DR EMDB; EMD-19619; -. DR EMDB; EMD-19620; -. DR EMDB; EMD-19622; -. DR EMDB; EMD-19623; -. DR EMDB; EMD-19624; -. DR EMDB; EMD-32258; -. DR EMDB; EMD-32326; -. DR EMDB; EMD-43707; -. DR EMDB; EMD-43708; -. DR EMDB; EMD-43709; -. DR EMDB; EMD-43710; -. DR EMDB; EMD-45246; -. DR EMDB; EMD-45400; -. DR EMDB; EMD-47473; -. DR EMDB; EMD-63474; -. DR EMDB; EMD-63475; -. DR EMDB; EMD-63476; -. DR SMR; P33992; -. DR BioGRID; 110342; 475. DR ComplexPortal; CPX-2940; MCM complex. DR CORUM; P33992; -. DR DIP; DIP-27578N; -. DR FunCoup; P33992; 2011. DR IntAct; P33992; 138. DR MINT; P33992; -. DR NDEx; IQUERY-CP-MCM5; 6 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000216122; -. DR BindingDB; P33992; -. DR ChEMBL; CHEMBL4630815; -. DR GlyGen; P33992; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P33992; -. DR MetOSite; P33992; -. DR PhosphoSitePlus; P33992; -. DR SwissPalm; P33992; -. DR BioMuta; MCM5; -. DR DMDM; 19858646; -. DR jPOST; P33992; -. DR MassIVE; P33992; -. DR PaxDb; 9606-ENSP00000216122; -. DR PeptideAtlas; P33992; -. DR ProteomicsDB; 54935; -. DR Pumba; P33992; -. DR Antibodypedia; 244; 937 antibodies from 41 providers. DR DNASU; 4174; -. DR Ensembl; ENST00000216122.9; ENSP00000216122.3; ENSG00000100297.17. DR Ensembl; ENST00000909968.1; ENSP00000580027.1; ENSG00000100297.17. DR Ensembl; ENST00000917551.1; ENSP00000587610.1; ENSG00000100297.17. DR GeneID; 4174; -. DR KEGG; hsa:4174; -. DR MANE-Select; ENST00000216122.9; ENSP00000216122.3; NM_006739.4; NP_006730.2. DR UCSC; uc003anu.5; human. DR AGR; HGNC:6948; -. DR ClinPGx; PA30695; -. DR CTD; 4174; -. DR DisGeNET; 4174; -. DR GeneCards; MCM5; -. DR HGNC; HGNC:6948; MCM5. DR HPA; ENSG00000100297; Tissue enhanced (bone). DR MalaCards; MCM5; -. DR MIM; 602696; gene. DR MIM; 617564; phenotype. DR OpenTargets; ENSG00000100297; -. DR VEuPathDB; HostDB:ENSG00000100297; -. DR eggNOG; KOG0481; Eukaryota. DR GeneTree; ENSGT01150000286966; -. DR InParanoid; P33992; -. DR OMA; ITYCKTR; -. DR OrthoDB; 10036721at2759; -. DR PAN-GO; P33992; 7 GO annotations based on evolutionary models. DR PhylomeDB; P33992; -. DR PathwayCommons; P33992; -. 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 Reactome; R-HSA-9825895; Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence. DR SignaLink; P33992; -. DR SIGNOR; P33992; -. DR Agora; ENSG00000100297; -. DR BioGRID-ORCS; 4174; 829 hits in 1173 CRISPR screens. DR CD-CODE; 8C2F96ED; Centrosome. DR CD-CODE; 91857CE7; Nucleolus. DR CD-CODE; DEE660B4; Stress granule. DR ChiTaRS; MCM5; human. DR GeneWiki; MCM5; -. DR GenomeRNAi; 4174; -. DR Pharos; P33992; Tbio. DR PRO; PR:P33992; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; P33992; protein. DR Bgee; ENSG00000100297; Expressed in ventricular zone and 165 other cell types or tissues. DR ExpressionAtlas; P33992; baseline and differential. DR GO; GO:0005694; C:chromosome; EXP:UniProtKB. 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; IDA:ComplexPortal. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA. DR GO; GO:0003678; F:DNA helicase activity; IEA:UniProtKB-EC. DR GO; GO:0003688; F:DNA replication origin binding; IEA:InterPro. DR GO; GO:0003697; F:single-stranded DNA binding; IBA:GO_Central. DR GO; GO:0006260; P:DNA replication; IDA:ComplexPortal. DR GO; GO:0006270; P:DNA replication initiation; IBA:GO_Central. DR GO; GO:0000727; P:double-strand break repair via break-induced replication; IBA:GO_Central. DR GO; GO:0030174; P:regulation of DNA-templated DNA replication initiation; NAS:ComplexPortal. DR CDD; cd17756; MCM5; 1. DR FunFam; 2.20.28.10:FF:000005; DNA helicase; 1. DR FunFam; 3.30.1640.10:FF:000006; DNA helicase; 1. DR FunFam; 3.40.50.300:FF:000241; DNA helicase; 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; IPR008048; MCM5. DR InterPro; IPR054125; MCM5_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; DNA REPLICATION LICENSING FACTOR MCM FAMILY MEMBER; 1. DR PANTHER; PTHR11630:SF42; DNA REPLICATION LICENSING FACTOR MCM5; 1. DR Pfam; PF00493; MCM; 1. DR Pfam; PF21933; MCM5_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; PR01661; MCMPROTEIN5. 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_CTD; 1. DR PDBsum; 6XTX; -. DR PDBsum; 6XTY; -. DR PDBsum; 7PFO; -. DR PDBsum; 7PLO; -. DR PDBsum; 7W1Y; -. DR PDBsum; 7W68; -. DR PDBsum; 8B9D; -. DR PDBsum; 8S09; -. DR PDBsum; 8S0A; -. DR PDBsum; 8S0B; -. DR PDBsum; 8S0D; -. DR PDBsum; 8S0E; -. DR PDBsum; 8S0F; -. DR PDBsum; 8W0E; -. DR PDBsum; 8W0F; -. DR PDBsum; 8W0G; -. DR PDBsum; 8W0I; -. DR PDBsum; 9C6G; -. DR PDBsum; 9CAQ; -. DR PDBsum; 9E2Z; -. DR PDBsum; 9LXD; -. DR PDBsum; 9LXE; -. DR PDBsum; 9LXF; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; ATP-binding; Cell cycle; Chromosome; KW Disease variant; DNA replication; DNA-binding; Dwarfism; Helicase; KW Hydrolase; Isopeptide bond; Nucleotide-binding; Nucleus; Phosphoprotein; KW Proteomics identification; Reference proteome; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT CHAIN 2..734 FT /note="DNA replication licensing factor MCM5" FT /id="PRO_0000194107" FT DOMAIN 314..654 FT /note="MCM C-terminal AAA(+) ATPase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01410" FT MOTIF 381..388 FT /note="Walker A" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01410" FT MOTIF 445..448 FT /note="Walker B" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01410" FT BINDING 371 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /ligand_note="ligand shared with MCM3" FT /evidence="ECO:0000305|PubMed:32453425, FT ECO:0007744|PDB:6XTX" FT SITE 513 FT /note="Arginine finger" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01410" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT MOD_RES 315 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 392 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 396 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 605 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 696 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT CROSSLNK 583 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in UFM1)" FT /evidence="ECO:0000269|PubMed:40940420" FT VARIANT 136 FT /note="S -> T (in dbSNP:rs2307334)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_014813" FT VARIANT 180 FT /note="T -> S (in dbSNP:rs2307340)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_014814" FT VARIANT 258 FT /note="V -> I (in dbSNP:rs2230933)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_014815" FT VARIANT 466 FT /note="T -> I (in MGORS8; dbSNP:rs1131692169)" FT /evidence="ECO:0000269|PubMed:28198391" FT /id="VAR_079198" FT MUTAGEN 583 FT /note="K->R: Destabilizes the helicase complex, delaying FT origin firing and slowing replication fork progression." FT /evidence="ECO:0000269|PubMed:40940420" FT CONFLICT 41 FT /note="Q -> R (in Ref. 7; AAH03656)" FT /evidence="ECO:0000305" FT CONFLICT 434 FT /note="M -> W (in Ref. 8)" FT /evidence="ECO:0000305" FT CONFLICT 527 FT /note="E -> V (in Ref. 3; BAA12176)" FT /evidence="ECO:0000305" FT CONFLICT 591 FT /note="S -> T (in Ref. 3; BAA12176)" FT /evidence="ECO:0000305" FT CONFLICT 593..603 FT /note="ARQHERDSDRR -> PVSTRGTVTA (in Ref. 3; BAA12176)" FT /evidence="ECO:0000305" FT HELIX 25..27 FT /evidence="ECO:0007829|PDB:8W0F" FT HELIX 28..41 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 43..46 FT /evidence="ECO:0007829|PDB:7W1Y" FT TURN 47..49 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 50..53 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 54..65 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 69..73 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 74..80 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 82..90 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 92..111 FT /evidence="ECO:0007829|PDB:7W1Y" FT TURN 116..119 FT /evidence="ECO:0007829|PDB:8W0I" FT HELIX 121..123 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 125..129 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 133..136 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 137..139 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 142..144 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 147..158 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 159..161 FT /evidence="ECO:0007829|PDB:7PLO" FT STRAND 162..168 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 170..172 FT /evidence="ECO:0007829|PDB:7W1Y" FT TURN 173..175 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 178..183 FT /evidence="ECO:0007829|PDB:9E2Z" FT STRAND 186..192 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 201..204 FT /evidence="ECO:0007829|PDB:9E2Z" FT HELIX 205..208 FT /evidence="ECO:0007829|PDB:9E2Z" FT STRAND 212..214 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 216..218 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 220..230 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 233..235 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 238..240 FT /evidence="ECO:0007829|PDB:8W0F" FT HELIX 241..243 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 244..249 FT /evidence="ECO:0007829|PDB:7W1Y" FT TURN 251..255 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 262..271 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 277..279 FT /evidence="ECO:0007829|PDB:8S09" FT STRAND 281..283 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 287..289 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 292..301 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 313..315 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 316..326 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 331..337 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 343..345 FT /evidence="ECO:0007829|PDB:9CAQ" FT HELIX 347..358 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 366..368 FT /evidence="ECO:0007829|PDB:9CAQ" FT STRAND 377..381 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 383..386 FT /evidence="ECO:0007829|PDB:9E2Z" FT HELIX 387..397 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 398..405 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 411..414 FT /evidence="ECO:0007829|PDB:9E2Z" FT STRAND 417..420 FT /evidence="ECO:0007829|PDB:7W1Y" FT TURN 422..424 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 427..430 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 433..436 FT /evidence="ECO:0007829|PDB:7W1Y" FT TURN 437..439 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 440..446 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 447..449 FT /evidence="ECO:0007829|PDB:9E2Z" FT HELIX 452..462 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 466..470 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 475..479 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 483..488 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 491..494 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 497..499 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 500..503 FT /evidence="ECO:0007829|PDB:9E2Z" FT HELIX 508..511 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 515..520 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 530..540 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 542..544 FT /evidence="ECO:0007829|PDB:9E2Z" FT STRAND 551..553 FT /evidence="ECO:0007829|PDB:7PLO" FT HELIX 556..569 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 576..600 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 610..626 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 630..632 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 634..651 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 653..674 FT /evidence="ECO:0007829|PDB:7W1Y" FT TURN 675..677 FT /evidence="ECO:0007829|PDB:7W1Y" FT STRAND 678..683 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 689..697 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 705..718 FT /evidence="ECO:0007829|PDB:7W1Y" FT HELIX 722..733 FT /evidence="ECO:0007829|PDB:7W1Y" SQ SEQUENCE 734 AA; 82286 MW; A80280E61749998D CRC64; MSGFDDPGIF YSDSFGGDAQ ADEGQARKSQ LQRRFKEFLR QYRVGTDRTG FTFKYRDELK RHYNLGEYWI EVEMEDLASF DEDLADYLYK QPAEHLQLLE EAAKEVADEV TRPRPSGEEV LQDIQVMLKS DASPSSIRSL KSDMMSHLVK IPGIIIAASA VRAKATRISI QCRSCRNTLT NIAMRPGLEG YALPRKCNTD QAGRPKCPLD PYFIMPDKCK CVDFQTLKLQ ELPDAVPHGE MPRHMQLYCD RYLCDKVVPG NRVTIMGIYS IKKFGLTTSR GRDRVGVGIR SSYIRVLGIQ VDTDGSGRSF AGAVSPQEEE EFRRLAALPN VYEVISKSIA PSIFGGTDMK KAIACLLFGG SRKRLPDGLT RRGDINLLML GDPGTAKSQL LKFVEKCSPI GVYTSGKGSS AAGLTASVMR DPSSRNFIME GGAMVLADGG VVCIDEFDKM REDDRVAIHE AMEQQTISIA KAGITTTLNS RCSVLAAANS VFGRWDETKG EDNIDFMPTI LSRFDMIFIV KDEHNEERDV MLAKHVITLH VSALTQTQAV EGEIDLAKLK KFIAYCRVKC GPRLSAEAAE KLKNRYIIMR SGARQHERDS DRRSSIPITV RQLEAIVRIA EALSKMKLQP FATEADVEEA LRLFQVSTLD AALSGTLSGV EGFTSQEDQE MLSRIEKQLK RRFAIGSQVS EHSIIKDFTK QKYPEHAIHK VLQLMLRRGE IQHRMQRKVL YRLK //