Format

Send to:

Choose Destination
    • Showing Current items.

    MCM4 minichromosome maintenance complex component 4 [ Homo sapiens (human) ]

    Gene ID: 4173, updated on 17-Jun-2019

    Summary

    Official Symbol
    MCM4provided by HGNC
    Official Full Name
    minichromosome maintenance complex component 4provided by HGNC
    Primary source
    HGNC:HGNC:6947
    See related
    Ensembl:ENSG00000104738 MIM:602638
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    NKCD; CDC21; CDC54; IMD54; NKGCD; hCdc21; P1-CDC21
    Summary
    The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. The MCM complex consisting of this protein and MCM2, 6 and 7 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. The phosphorylation of this protein by CDC2 kinase reduces the DNA helicase activity and chromatin binding of the MCM complex. This gene is mapped to a region on the chromosome 8 head-to-head next to the PRKDC/DNA-PK, a DNA-activated protein kinase involved in the repair of DNA double-strand breaks. Alternatively spliced transcript variants encoding the same protein have been reported. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in testis (RPKM 21.3), bone marrow (RPKM 19.5) and 24 other tissues See more
    Orthologs

    Genomic context

    See MCM4 in Genome Data Viewer
    Location:
    8q11.21
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    109.20190607 current GRCh38.p13 (GCF_000001405.39) 8 NC_000008.11 (47960941..47978160)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (48872763..48890720)

    Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene protein kinase, DNA-activated, catalytic subunit Neighboring gene uncharacterized LOC105375818 Neighboring gene origin of replication upstream of MCM4 Neighboring gene uncharacterized TCONS_00068220 Neighboring gene RNA, U6 small nuclear 519, pseudogene Neighboring gene ubiquitin conjugating enzyme E2 V2

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Pol gag-pol HIV-1 Pol is identified to have a physical interaction with minichromosome maintenance complex component 4 (MCM4) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from BioSystems

    • Activation of ATR in response to replication stress, organism-specific biosystem (from REACTOME)
      Activation of ATR in response to replication stress, organism-specific biosystemGenotoxic stress caused by DNA damage or stalled replication forks can lead to genomic instability. To guard against such instability, genotoxically-stressed cells activate checkpoint factors that ha...
    • Activation of the pre-replicative complex, organism-specific biosystem (from REACTOME)
      Activation of the pre-replicative complex, organism-specific biosystemIn S. cerevisiae, two ORC subunits, Orc1 and Orc5, both bind ATP, and Orc1 in addition has ATPase activity. Both ATP binding and ATP hydrolysis appear to be essential functions in vivo. ATP binding b...
    • Assembly of the pre-replicative complex, organism-specific biosystem (from REACTOME)
      Assembly of the pre-replicative complex, organism-specific biosystemDNA replication pre-initiation in eukaryotic cells begins with the formation of the pre-replicative complex (pre-RC) during the late M phase and continues in the G1 phase of the mitotic cell cycle, a...
    • C-MYB transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
      C-MYB transcription factor network, organism-specific biosystem
      C-MYB transcription factor network
    • Cell Cycle, organism-specific biosystem (from WikiPathways)
      Cell Cycle, organism-specific biosystemThe cell cycle is the series of events that takes place in a cell leading to its division and duplication (replication). Regulation of the cell cycle involves processes crucial to the survival of a c...
    • Cell Cycle, organism-specific biosystem (from REACTOME)
      Cell Cycle, organism-specific biosystem
      Cell Cycle
    • Cell Cycle Checkpoints, organism-specific biosystem (from REACTOME)
      Cell Cycle Checkpoints, organism-specific biosystemA hallmark of the human cell cycle in normal somatic cells is its precision. This remarkable fidelity is achieved by a number of signal transduction pathways, known as checkpoints, which monitor cell...
    • Cell Cycle, Mitotic, organism-specific biosystem (from REACTOME)
      Cell Cycle, Mitotic, organism-specific biosystemThe replication of the genome and the subsequent segregation of chromosomes into daughter cells are controlled by a series of events collectively known as the cell cycle. DNA replication is carried o...
    • Cell cycle, organism-specific biosystem (from KEGG)
      Cell cycle, organism-specific biosystemMitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cycli...
    • Cell cycle, conserved biosystem (from KEGG)
      Cell cycle, conserved biosystemMitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cycli...
    • DNA Replication, organism-specific biosystem (from REACTOME)
      DNA Replication, organism-specific biosystemStudies in the past decade have suggested that the basic mechanism of DNA replication initiation is conserved in all kingdoms of life. Initiation in unicellular eukaryotes, in particular Saccharomyce...
    • DNA Replication, organism-specific biosystem (from WikiPathways)
      DNA Replication, organism-specific biosystemStudies in the past decade have suggested that the basic mechanism of DNA replication initiation is conserved in all kingdoms of life. Initiation in unicellular eukaryotes, in particular Saccharomyce...
    • DNA Replication Pre-Initiation, organism-specific biosystem (from REACTOME)
      DNA Replication Pre-Initiation, organism-specific biosystemAlthough, DNA replication occurs in the S phase of the cell cycle, the formation of the DNA replication pre-initiation complex begins during G1 phase.
    • DNA replication, organism-specific biosystem (from KEGG)
      DNA replication, organism-specific biosystemA complex network of interacting proteins and enzymes is required for DNA replication. Generally, DNA replication follows a multistep enzymatic pathway. At the DNA replication fork, a DNA helicase (D...
    • DNA replication, conserved biosystem (from KEGG)
      DNA replication, conserved biosystemA complex network of interacting proteins and enzymes is required for DNA replication. Generally, DNA replication follows a multistep enzymatic pathway. At the DNA replication fork, a DNA helicase (D...
    • DNA strand elongation, organism-specific biosystem (from REACTOME)
      DNA strand elongation, organism-specific biosystemAccurate and efficient genome duplication requires coordinated processes to replicate two template strands at eucaryotic replication forks. Knowledge of the fundamental reactions involved in replicat...
    • G1 to S cell cycle control, organism-specific biosystem (from WikiPathways)
      G1 to S cell cycle control, organism-specific biosystemIn the G1 phase there are two types of DNA damage responses, the p53-dependent and the p53-independent pathways. The p53-dependent responses inhibit CDKs through the up-regulation of genes encoding C...
    • G1/S Transition, organism-specific biosystem (from REACTOME)
      G1/S Transition, organism-specific biosystemCyclin E - Cdk2 complexes control the transition from G1 into S-phase. In this case, the binding of p21Cip1/Waf1 or p27kip1 is inhibitory. Important substrates for Cyclin E - Cdk2 complexes include p...
    • G2/M Checkpoints, organism-specific biosystem (from REACTOME)
      G2/M Checkpoints, organism-specific biosystemG2/M checkpoints include the checks for damaged DNA, unreplicated DNA, and checks that ensure that the genome is replicated once and only once per cell cycle. If cells pass these checkpoints, they f...
    • Gastric Cancer Network 1, organism-specific biosystem (from WikiPathways)
      Gastric Cancer Network 1, organism-specific biosystemNetwork generated by mapping candidate oncogenes and tumor suppressor genes identified by integrated analysis of expression array and aCGH data. Networks generated by Ingenuity Pathway Analysis.
    • M/G1 Transition, organism-specific biosystem (from REACTOME)
      M/G1 Transition, organism-specific biosystemFinally, progression out of mitosis and division of the cell into two daughters (cytokinesis) requires the inactivation of Cyclin B - Cdc2 by ubiquitin-dependent proteolysis of Cyclin A and B, which ...
    • MCM complex, organism-specific biosystem (from KEGG)
      MCM complex, organism-specific biosystemStructural complex; Genetic information processing; Replication system
    • MCM complex, conserved biosystem (from KEGG)
      MCM complex, conserved biosystemStructural complex; Genetic information processing; Replication system
    • Mitotic G1-G1/S phases, organism-specific biosystem (from REACTOME)
      Mitotic G1-G1/S phases, organism-specific biosystem
      Mitotic G1-G1/S phases
    • Orc1 removal from chromatin, organism-specific biosystem (from REACTOME)
      Orc1 removal from chromatin, organism-specific biosystem
      Orc1 removal from chromatin
    • Regulation of DNA replication, organism-specific biosystem (from REACTOME)
      Regulation of DNA replication, organism-specific biosystemDNA replication is regulated at various levels via ORC proteins. This pathway includes annotation of individual events that lead to the regulation of replication.
    • Removal of licensing factors from origins, organism-specific biosystem (from REACTOME)
      Removal of licensing factors from origins, organism-specific biosystemLicensing factors are removed from the origin by various means like biochemical modification (phosphorylation) or by physical association with other proteins. This pathway includes the annotations of...
    • Retinoblastoma (RB) in Cancer, organism-specific biosystem (from WikiPathways)
      Retinoblastoma (RB) in Cancer, organism-specific biosystemDescribes the role of retinoblastoma (RB) gene in cancer.
    • S Phase, organism-specific biosystem (from REACTOME)
      S Phase, organism-specific biosystemDNA synthesis occurs in the S phase, or the synthesis phase, of the cell cycle. The cell duplicates its hereditary material, and two copies of the chromosome are formed. As DNA replication continues,...
    • Switching of origins to a post-replicative state, organism-specific biosystem (from REACTOME)
      Switching of origins to a post-replicative state, organism-specific biosystem
      Switching of origins to a post-replicative state
    • Synthesis of DNA, organism-specific biosystem (from REACTOME)
      Synthesis of DNA, organism-specific biosystemThe actual synthesis of DNA occurs in the S phase of the cell cycle. This includes the initiation of DNA replication, when the first nucleotide of the new strand is laid down during the synthesis of ...
    • Unwinding of DNA, organism-specific biosystem (from REACTOME)
      Unwinding of DNA, organism-specific biosystemDNA Replication is regulated accurately and precisely by various protein complexes. Many members of the MCM protein family are assembled into the pre-Replication Complexes (pre-RC) at the end of M ph...

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Clone Names

    • MGC33310

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    contributes_to DNA helicase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    DNA replication origin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    single-stranded DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    Process Evidence Code Pubs
    DNA replication NAS
    Non-traceable Author Statement
    more info
    PubMed 
    DNA replication TAS
    Traceable Author Statement
    more info
     
    DNA strand elongation involved in DNA replication IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    DNA unwinding involved in DNA replication IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    G1/S transition of mitotic cell cycle TAS
    Traceable Author Statement
    more info
     
    double-strand break repair via break-induced replication IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    mitotic DNA replication initiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    pre-replicative complex assembly involved in nuclear cell cycle DNA replication IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    Component Evidence Code Pubs
    MCM complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    MCM complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    membrane HDA PubMed 
    nuclear chromosome, telomeric region HDA PubMed 
    nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    nucleoplasm TAS
    Traceable Author Statement
    more info
     
    nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    nucleus NAS
    Non-traceable Author Statement
    more info
    PubMed 

    General protein information

    Preferred Names
    DNA replication licensing factor MCM4
    Names
    homolog of S. pombe cell devision cycle 21
    minichromosome maintenance deficient 4
    NP_005905.2
    NP_877423.1

    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_032967.1 RefSeqGene

      Range
      5739..22958
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1239

    mRNA and Protein(s)

    1. NM_005914.4NP_005905.2  DNA replication licensing factor MCM4

      See identical proteins and their annotated locations for NP_005905.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents a longer transcript and differs in the 5' UTR, as compared to variant 2. Both variants encode the same protein.
      Source sequence(s)
      AC021236, AK296913, BC031061, BF793151, BQ689703
      Consensus CDS
      CCDS6143.1
      UniProtKB/Swiss-Prot
      P33991
      UniProtKB/TrEMBL
      B4DLA6
      Related
      ENSP00000262105.2, ENST00000262105.6
      Conserved Domains (3) summary
      smart00350
      Location:267770
      MCM; minichromosome maintenance proteins
      pfam14551
      Location:166287
      MCM_N; MCM N-terminal domain
      cl21455
      Location:505644
      P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
    2. NM_182746.3NP_877423.1  DNA replication licensing factor MCM4

      See identical proteins and their annotated locations for NP_877423.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks a segment in the 5' UTR, when compared to variant 1. Both variants encode the same protein.
      Source sequence(s)
      AC021236, AK022899, BC031061, BQ689703
      Consensus CDS
      CCDS6143.1
      UniProtKB/Swiss-Prot
      P33991
      UniProtKB/TrEMBL
      B3KMX0
      Related
      ENSP00000430194.1, ENST00000523944.5
      Conserved Domains (3) summary
      smart00350
      Location:267770
      MCM; minichromosome maintenance proteins
      pfam14551
      Location:166287
      MCM_N; MCM N-terminal domain
      cl21455
      Location:505644
      P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p13 Primary Assembly

    Genomic

    1. NC_000008.11 Reference GRCh38.p13 Primary Assembly

      Range
      47960941..47978160
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Support Center