Details for: MCM2

Gene ID: 4171

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: MCM2

Ensembl ID: ENSG00000073111

Description: minichromosome maintenance complex component 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • granulocyte monocyte progenitor cell CL0000557
    CSI 6.72
    rCSI 5.82%
    PRS 97.91
  • early lymphoid progenitor CL0000936
    CSI 5.91
    rCSI 5.19%
    PRS 98.43
  • fallopian tube secretory epithelial cell CL4030006
    CSI 5.63
    rCSI 5.42%
    PRS 96.17
  • pro-B cell CL0000826
    CSI 4.89
    rCSI 4.05%
    PRS 97.78
  • neural crest cell CL0011012
    CSI 4.54
    rCSI 3.59%
    PRS 94.68
  • mesenchymal cell CL0008019
    CSI 3.73
    rCSI 9.48%
    PRS 95.62
  • neural progenitor cell CL0011020
    CSI 3.62
    rCSI 15.94%
    PRS 90.03
  • radial glial cell CL0000681
    CSI 3.54
    rCSI 4.91%
    PRS 96.6
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 3.45
    rCSI 3.99%
    PRS 92.97
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 3.33
    rCSI 3.01%
    PRS 96.87
  • plasmablast CL0000980
    CSI 3.16
    rCSI 2.49%
    PRS 97.25
  • stem cell CL0000034
    CSI 2.98
    rCSI 2.87%
    PRS 95.71
  • common myeloid progenitor CL0000049
    CSI 2.97
    rCSI 2.4%
    PRS 98.02
  • epithelial cell CL0000066
    CSI 2.97
    rCSI 4.56%
    PRS 89.22
  • glioblast CL0000030
    CSI 2.44
    rCSI 3.9%
    PRS 93.11
  • transit amplifying cell of colon CL0009011
    CSI 2.42
    rCSI 2.84%
    PRS 97.43
  • fraction A pre-pro B cell CL0002045
    CSI 2.33
    rCSI 2.67%
    PRS 98.55
  • large pre-B-II cell CL0000957
    CSI 2.31
    rCSI 6.61%
    PRS 96.24
  • oligodendrocyte precursor cell CL0002453
    CSI 2.26
    rCSI 4.97%
    PRS 86.11
  • placental villous trophoblast CL2000060
    CSI 2.11
    rCSI 3.26%
    PRS 95.96
  • promyelocyte CL0000836
    CSI 1.98
    rCSI 2.85%
    PRS 97.61
  • mesothelial cell CL0000077
    CSI 1.92
    rCSI 7.52%
    PRS 89.16
  • common dendritic progenitor CL0001029
    CSI 1.92
    rCSI 2.41%
    PRS 98.76
  • promonocyte CL0000559
    CSI 1.66
    rCSI 2.84%
    PRS 97.72
  • erythroid lineage cell CL0000764
    CSI 1.61
    rCSI 10.38%
    PRS 96.99
  • erythroblast CL0000765
    CSI 1.53
    rCSI 4.07%
    PRS 96.77
  • erythroid progenitor cell CL0000038
    CSI 1.51
    rCSI 8.68%
    PRS 97.82
  • basophil mast progenitor cell CL0002028
    CSI 1.5
    rCSI 8%
    PRS 99.02
  • primitive red blood cell CL0002355
    CSI 0.77
    rCSI 4.18%
    PRS 97.38

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [MCM2](/details-gene/4171), or Minichromosome Maintenance Complex Component 2, is a protein-coding gene located on chromosome 3q21.3. It is a fundamental component of the MCM complex, which functions as the core DNA helicase essential for the initiation and elongation phases of eukaryotic DNA replication. The protein's primary role is to unwind the DNA double helix at replication origins, allowing for the synthesis of new DNA strands. Reflecting this core function in cell proliferation, [MCM2](/details-gene/4171) shows significant expression in a wide range of progenitor and stem cell populations, including hematopoietic progenitors like '[granulocyte monocyte progenitor cell](/details-cell/CL0000557)' and '[early lymphoid progenitor](/details-cell/CL0000936)', as well as mitotically active epithelial cells. Its essential role in the cell cycle is underscored by its clinical association (OMIM: [116945](https://omim.org/entry/116945)) and its function as a target of cell cycle checkpoint kinases. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [MCM2](/details-gene/4171) strongly indicates its role as a key regulator of cell proliferation and a marker for mitotically active cell populations. Its significance is highest in progenitor cells across multiple lineages, highlighting its universal requirement for genome duplication before cell division. The gene is most prominently expressed in hematopoietic progenitors, including '[granulocyte monocyte progenitor cell](/details-cell/CL0000557)', '[early lymphoid progenitor](/details-cell/CL0000936)', '[pro-B cell](/details-cell/CL0000826)', and '[megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050)'. This is consistent with the high turnover rate of the hematopoietic system. Similarly, high significance is observed in neural progenitors such as '[neural crest cell](/details-cell/CL0011012)', '[neural progenitor cell](/details-cell/CL0011020)', and '[radial glial cell](/details-cell/CL0000681)', which are critical for nervous system development. The high expression in '[fallopian tube secretory epithelial cell](/details-cell/CL4030006)' and other '[epithelial cell](/details-cell/CL0000066)' types further supports its role in tissues that undergo regular renewal. This broad expression pattern across diverse progenitor and stem cell types establishes [MCM2](/details-gene/4171) as a fundamental "workhorse" gene for cell division, rather than a lineage-specific marker. ## Pathways and Molecular Function The molecular functions of [MCM2](/details-gene/4171) are centrally tied to its role in the [MCM complex](/details-go/GO:0042555), which forms the catalytic core of the replicative helicase, the [CMG complex](/details-go/GO:0071162). Functionally, it exhibits [3'-5' dna helicase activity](/details-go/GO:0043138) that is dependent on [Atp hydrolysis activity](/details-go/GO:0016887). This activity is critical for the biological process of [Dna unwinding involved in dna replication](/details-go/GO:0006268) ([R-HSA-176974](https://reactome.org/content/detail/R-HSA-176974)), which is a prerequisite for DNA synthesis. Its involvement is crucial throughout the [Cell cycle](/details-go/R-HSA-1640170), particularly during the [G1/s transition](/details-go/R-HSA-69206) and the [S phase](/details-go/R-HSA-69242). [MCM2](/details-gene/4171) is loaded onto chromatin at replication origins during late M and G1 phases as part of the [Assembly of the pre-replicative complex](/details-go/R-HSA-68867). Its activation at the onset of S phase, a process that requires phosphorylation by kinases like Cdc7, triggers [Dna replication initiation](/details-go/GO:0006270) ([R-HSA-69002](https://reactome.org/content/detail/R-HSA-69002)) ([Link](https://pubmed.ncbi.nlm.nih.gov/16899510/)). Furthermore, [MCM2](/details-gene/4171) is a direct target of the ATM and ATR checkpoint kinases, linking its function to the cellular response to replication stress and DNA damage ([Link](https://pubmed.ncbi.nlm.nih.gov/15210935/)), as annotated in pathways such as [Activation of atr in response to replication stress](/details-go/R-HSA-176187) and [Cell cycle checkpoints](/details-go/R-HSA-69620). ## Research Directions Given its indispensable role in DNA replication, [MCM2](/details-gene/4171) is a well-established proliferation marker frequently overexpressed in various cancers. This positions it as a significant subject for both basic and translational research. ### Proposed Hypotheses: 1. Aberrant post-translational modifications of [MCM2](/details-gene/4171) that uncouple its activity from cell cycle regulation could be a mechanism for overcoming replication checkpoints in cancer cells, thereby promoting genomic instability and resistance to DNA-damaging chemotherapies. 2. Beyond its canonical role as a helicase, the loading of the MCM complex, including [MCM2](/details-gene/4171), onto chromatin during G1 phase may play a structural role in defining chromatin architecture and gene expression programs necessary for S-phase entry. ### Key Experimental Approach: To test the first hypothesis regarding the role of [MCM2](/details-gene/4171) modifications in checkpoint evasion, a compelling experiment would be to use mass spectrometry to create a comprehensive map of [MCM2](/details-gene/4171) phosphorylation sites in a panel of chemotherapy-sensitive versus chemotherapy-resistant cancer cell lines (e.g., ovarian or breast cancer). Key differential phosphorylation sites could then be functionally validated using CRISPR-Cas9 to introduce phosphomimetic (S/T to E/D) or phosphorylation-dead (S/T to A) mutations at these sites. The resulting cell lines would be assessed for their ability to progress through the cell cycle, repair DNA damage, and survive following treatment with agents that induce replication stress (e.g., PARP inhibitors or topoisomerase inhibitors). ### Therapeutic Potential: [MCM2](/details-gene/4171), as part of the essential replicative helicase, represents a prime therapeutic target for cancer. The strategy would be **inhibition**, as blocking its ATP-dependent helicase activity would selectively arrest the proliferation of rapidly dividing cancer cells. Its enzymatic nature makes it a druggable target for small molecule inhibitors. However, a major challenge is potential on-target toxicity in healthy proliferative tissues, such as bone marrow and the gastrointestinal epithelium. The development of next-generation inhibitors may require strategies that exploit cancer-specific dependencies or targeted delivery systems to improve the therapeutic window.

Genular Protein ID: 3396235385

Symbol: MCM2_HUMAN

Name: Minichromosome maintenance protein 2 homolog

UniProtKB Accession Codes:

P49736 Q14577 Q15023 Q8N2V1 Q969W7 Q96AE1 Q9BRM7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CORUM 1 CPTAC 1 CTD 1 ChEBI 7 ChEMBL 1 ChiTaRS 1 ComplexPortal 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DisProt 1 EC 1 ELM 1 EMBL 12 EMDB 6 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 27 Gene3D 4 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 IDEAL 1 InParanoid 1 IntAct 1 InterPro 9 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 18 PDBsum 18 PIR 1 PRINTS 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 5 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 6 RefSeq 1 Rhea 2 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8175912

Title: A human nuclear protein with sequence homology to a family of early S phase proteins is required for entry into S phase and for cell division.

PubMed ID: 8175912

DOI: 10.1242/jcs.107.1.253

PubMed ID: 7584026

Title: Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1.

PubMed ID: 7584026

DOI: 10.1093/dnares/1.1.27

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 8258304

Title: The human gene for nuclear protein BM28 (CDCL1), a new member of the early S-phase family of proteins, maps to chromosome band 3q21.

PubMed ID: 8258304

DOI: 10.1159/000133647

PubMed ID: 9305914

Title: A DNA helicase activity is associated with an MCM4, -6, and -7 protein complex.

PubMed ID: 9305914

DOI: 10.1074/jbc.272.39.24508

PubMed ID: 11095689

Title: The human homolog of Saccharomyces cerevisiae Mcm10 interacts with replication factors and dissociates from nuclease-resistant nuclear structures in G(2) phase.

PubMed ID: 11095689

DOI: 10.1093/nar/28.23.4769

PubMed ID: 15210935

Title: Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases.

PubMed ID: 15210935

DOI: 10.1073/pnas.0403410101

PubMed ID: 17081983

Title: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.

PubMed ID: 17081983

DOI: 10.1016/j.cell.2006.09.026

PubMed ID: 16899510

Title: Essential role of phosphorylation of MCM2 by Cdc7/Dbf4 in the initiation of DNA replication in mammalian cells.

PubMed ID: 16899510

DOI: 10.1091/mbc.e06-03-0241

PubMed ID: 16387653

Title: ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation.

PubMed ID: 16387653

DOI: 10.1016/j.molcel.2005.12.007

PubMed ID: 16964243

Title: A probability-based approach for high-throughput protein phosphorylation analysis and site localization.

PubMed ID: 16964243

DOI: 10.1038/nbt1240

PubMed ID: 17487921

Title: Toward a global characterization of the phosphoproteome in prostate cancer cells: identification of phosphoproteins in the LNCaP cell line.

PubMed ID: 17487921

DOI: 10.1002/elps.200600782

PubMed ID: 17062569

Title: Cdc7 is an active kinase in human cancer cells undergoing replication stress.

PubMed ID: 17062569

DOI: 10.1074/jbc.m604457200

PubMed ID: 17296731

Title: Identification and characterization of a novel component of the human minichromosome maintenance complex.

PubMed ID: 17296731

DOI: 10.1128/mcb.02384-06

PubMed ID: 17525332

Title: ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.

PubMed ID: 17525332

DOI: 10.1126/science.1140321

PubMed ID: 18220336

Title: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.

PubMed ID: 18220336

DOI: 10.1021/pr0705441

PubMed ID: 19367720

Title: Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment.

PubMed ID: 19367720

DOI: 10.1021/pr800500r

PubMed ID: 18691976

Title: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.

PubMed ID: 18691976

DOI: 10.1016/j.molcel.2008.07.007

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 19608861

Title: Lysine acetylation targets protein complexes and co-regulates major cellular functions.

PubMed ID: 19608861

DOI: 10.1126/science.1175371

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 22223895

Title: Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features.

PubMed ID: 22223895

DOI: 10.1074/mcp.m111.015131

PubMed ID: 22814378

Title: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

PubMed ID: 22814378

DOI: 10.1073/pnas.1210303109

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 27401717

Title: Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells.

PubMed ID: 27401717

DOI: 10.1038/ncomms12135

PubMed ID: 28191891

Title: Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism.

PubMed ID: 28191891

DOI: 10.1038/ng.3790

PubMed ID: 28112733

Title: Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.

PubMed ID: 28112733

DOI: 10.1038/nsmb.3366

PubMed ID: 35585232

Title: Fast and efficient DNA replication with purified human proteins.

PubMed ID: 35585232

DOI: 10.1038/s41586-022-04759-1

PubMed ID: 32453425

Title: CryoEM structures of human CMG-ATPgammaS-DNA and CMG-AND-1 complexes.

PubMed ID: 32453425

DOI: 10.1093/nar/gkaa429

PubMed ID: 33857403

Title: DNAJC9 integrates heat shock molecular chaperones into the histone chaperone network.

PubMed ID: 33857403

DOI: 10.1016/j.molcel.2021.03.041

PubMed ID: 34694004

Title: Structure of a human replisome shows the organisation and interactions of a DNA replication machine.

PubMed ID: 34694004

DOI: 10.15252/embj.2021108819

PubMed ID: 34700328

Title: A conserved mechanism for regulating replisome disassembly in eukaryotes.

PubMed ID: 34700328

DOI: 10.1038/s41586-021-04145-3

PubMed ID: 26196677

Title: Whole exome sequencing identified MCM2 as a novel causative gene for autosomal dominant nonsyndromic deafness in a chinese family.

PubMed ID: 26196677

DOI: 10.1371/journal.pone.0133522

Sequence Information:

  • Length: 904
  • Mass: 101896
  • Checksum: 52C6DC61F128B404
  • Sequence:
    • MAESSESFTM ASSPAQRRRG NDPLTSSPGR SSRRTDALTS SPGRDLPPFE DESEGLLGTE 
GPLEEEEDGE ELIGDGMERD YRAIPELDAY EAEGLALDDE DVEELTASQR EAAERAMRQR 
DREAGRGLGR MRRGLLYDSD EEDEERPARK RRQVERATED GEEDEEMIES IENLEDLKGH 
SVREWVSMAG PRLEIHHRFK NFLRTHVDSH GHNVFKERIS DMCKENRESL VVNYEDLAAR 
EHVLAYFLPE APAELLQIFD EAALEVVLAM YPKYDRITNH IHVRISHLPL VEELRSLRQL 
HLNQLIRTSG VVTSCTGVLP QLSMVKYNCN KCNFVLGPFC QSQNQEVKPG SCPECQSAGP 
FEVNMEETIY QNYQRIRIQE SPGKVAAGRL PRSKDAILLA DLVDSCKPGD EIELTGIYHN 
NYDGSLNTAN GFPVFATVIL ANHVAKKDNK VAVGELTDED VKMITSLSKD QQIGEKIFAS 
IAPSIYGHED IKRGLALALF GGEPKNPGGK HKVRGDINVL LCGDPGTAKS QFLKYIEKVS 
SRAIFTTGQG ASAVGLTAYV QRHPVSREWT LEAGALVLAD RGVCLIDEFD KMNDQDRTSI 
HEAMEQQSIS ISKAGIVTSL QARCTVIAAA NPIGGRYDPS LTFSENVDLT EPIISRFDIL 
CVVRDTVDPV QDEMLARFVV GSHVRHHPSN KEEEGLANGS AAEPAMPNTY GVEPLPQEVL 
KKYIIYAKER VHPKLNQMDQ DKVAKMYSDL RKESMATGSI PITVRHIESM IRMAEAHARI 
HLRDYVIEDD VNMAIRVMLE SFIDTQKFSV MRSMRKTFAR YLSFRRDNNE LLLFILKQLV 
AEQVTYQRNR FGAQQDTIEV PEKDLVDKAR QINIHNLSAF YDSELFRMNK FSHDLKRKMI 
LQQF