MCM4 MCM DNA helicase complex subunit MCM4 [Saccharomyces cerevisiae S288C] - Gene

Summary

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Gene symbol: MCM4
Gene description: MCM DNA helicase complex subunit MCM4
Primary source: SGD:S000006223
Locus tag: YPR019W
See related: AllianceGenome:SGD:S000006223
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Saccharomyces cerevisiae S288C (strain: S288C)
Lineage: Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces
Also known as: CDC54; HCD21
Summary: Enables DNA replication origin binding activity and single-stranded DNA binding activity. Contributes to 3'-5' DNA helicase activity; four-way junction helicase activity; and single-stranded DNA helicase activity. Involved in DNA-dependent DNA replication; double-strand break repair via break-induced replication; and protein hexamerization. Located in cytoplasm and nuclear replication fork. Part of MCM complex; MCM core complex; and nuclear lumen. Used to study endometrial cancer. Human ortholog(s) of this gene implicated in immunodeficiency 54. Orthologous to human MCM4 (minichromosome maintenance complex component 4). [provided by Alliance of Genome Resources, Apr 2022]
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Genomic context

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See MCM4 in Genome Data Viewer

Location:: chromosome: XVI

Exon count:: 1

Sequence:: Chromosome: XVI; NC_001148.4 (596750..599551)

Chromosome XVI - NC_001148.4 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_001148.4

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The authors identified mutations in a conserved and essential Mcm4 motif that permit loading of two Mcm2-7 complexes but are defective for double-hexamer formation.
Title: A conserved Mcm4 motif is required for Mcm2-7 double-hexamer formation and origin DNA unwinding.
Sld3 binds specifically to DDK-phosphorylated peptides from two MCM subunits (Mcm4, 6) and then recruits Cdc45.
Title: Phosphopeptide binding by Sld3 links Dbf4-dependent kinase to MCM replicative helicase activation.
The Dbf4-dependent Cdc7 kinase (DDK), cyclin-dependent kinase (CDK), and Mec1 all target the structurally disordered N-terminal serine/threonine-rich domain of Mcm4, a subunit of the mini-chromosome maintenance replicative helicase complex.
Title: Domain within the helicase subunit Mcm4 integrates multiple kinase signals to control DNA replication initiation and fork progression.
constitutive overexpression of each individual MCM subunit was examined, and genotoxic sensitivity was found to be specific to Mcm2 or Mcm4 overexpression, further pointing to the importance of the DDK-MCM ring interaction.
Title: Dbf4 and Cdc7 proteins promote DNA replication through interactions with distinct Mcm2-7 protein subunits.
A defective MCM helicase causes genetic instability only in particular cell types.
Title: Ploidy dictates repair pathway choice under DNA replication stress.
The minimal functional unit of Mcm4/6/7 is a hexamer
Title: The effects of oligomerization on Saccharomyces cerevisiae Mcm4/6/7 function.
studies establish that the eukaryote-specific NSD of Mcm4 has evolved to integrate several protein kinase regulatory signals for progression through S phase
Title: The Dbf4-Cdc7 kinase promotes S phase by alleviating an inhibitory activity in Mcm4.
DNA runs through a central channel in the double hexamer, and, once loaded, Mcm2-7 can slide passively along double-stranded DNA.
Title: Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing.
using Saccharomyces cerevisiae containing a mcm4 helicase allele that was shown to cause cancer in mice.
Title: Aneuploidy and improved growth are coincident but not causal in a yeast cancer model.
The Mcm4/Mcm7 and Mcm4/Mcm6/Mcm7 assemblies can open to load onto circular DNA to initiate unwinding.
Title: Mcm subunits can assemble into two different active unwinding complexes.

Submit: New GeneRIF Correction See all GeneRIFs (11)

Pathways from PubChem

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

Orthologs from OrthoDB

Gene Ontology Provided by SGD

Function	Evidence Code	Pubs
contributes_to 3'-5' DNA helicase activity	IDA Inferred from Direct Assay more info	PubMed
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP hydrolysis activity	IEA Inferred from Electronic Annotation more info
enables DNA binding	IEA Inferred from Electronic Annotation more info
enables DNA helicase activity	IEA Inferred from Electronic Annotation more info
enables DNA replication origin binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA replication origin binding	IEA Inferred from Electronic Annotation more info
contributes_to four-way junction helicase activity	IDA Inferred from Direct Assay more info	PubMed
enables helicase activity	IEA Inferred from Electronic Annotation more info
enables hydrolase activity	IEA Inferred from Electronic Annotation more info
enables single-stranded DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables single-stranded DNA binding	IMP Inferred from Mutant Phenotype more info	PubMed
contributes_to single-stranded DNA helicase activity	IBA Inferred from Biological aspect of Ancestor more info
contributes_to single-stranded DNA helicase activity	IDA Inferred from Direct Assay more info	PubMed
enables zinc ion binding	RCA inferred from Reviewed Computational Analysis more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA duplex unwinding	IEA Inferred from Electronic Annotation more info
involved_in DNA replication	IEA Inferred from Electronic Annotation more info
involved_in DNA replication initiation	IEA Inferred from Electronic Annotation more info
involved_in DNA replication initiation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in DNA strand elongation involved in DNA replication	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA strand elongation involved in DNA replication	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in DNA unwinding involved in DNA replication	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA unwinding involved in DNA replication	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA unwinding involved in DNA replication	IEA Inferred from Electronic Annotation more info
involved_in cell cycle	IEA Inferred from Electronic Annotation more info
involved_in double-strand break repair via break-induced replication	IBA Inferred from Biological aspect of Ancestor more info
involved_in double-strand break repair via break-induced replication	IEA Inferred from Electronic Annotation more info
involved_in double-strand break repair via break-induced replication	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitotic DNA replication initiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in nuclear DNA replication	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in pre-replicative complex assembly involved in nuclear cell cycle DNA replication	IDA Inferred from Direct Assay more info	PubMed
involved_in pre-replicative complex assembly involved in nuclear cell cycle DNA replication	IEA Inferred from Electronic Annotation more info
involved_in premeiotic DNA replication	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of CMG complex	IDA Inferred from Direct Assay more info	PubMed
part_of CMG complex	IEA Inferred from Electronic Annotation more info
part_of DNA replication preinitiation complex	IDA Inferred from Direct Assay more info	PubMed
part_of MCM complex	IBA Inferred from Biological aspect of Ancestor more info
part_of MCM complex	IDA Inferred from Direct Assay more info	PubMed
part_of MCM complex	IEA Inferred from Electronic Annotation more info
part_of MCM core complex	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
part_of nuclear pre-replicative complex	IDA Inferred from Direct Assay more info	PubMed
part_of nuclear pre-replicative complex	IEA Inferred from Electronic Annotation more info
located_in nuclear replication fork	IDA Inferred from Direct Assay more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IEA Inferred from Electronic Annotation more info
part_of replication fork protection complex	IDA Inferred from Direct Assay more info	PubMed
part_of replication fork protection complex	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: MCM DNA helicase complex subunit MCM4

NP_015344.1

EC 3.6.4.12

Essential helicase component of heterohexameric MCM2-7 complexes; MCM2-7 complexes bind pre-replication complexes on DNA and melt DNA prior to replication; forms an Mcm4p-6p-7p subcomplex; shows nuclear accumulation in G1; homolog of S. pombe Cdc21p

NCBI Reference Sequences (RefSeq)

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Genome Annotation

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

Reference assembly

Genomic

NC_001148.4 Reference assembly

Range

596750..599551

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001184116.1 → NP_015344.1 TPA: MCM DNA helicase complex subunit MCM4 [Saccharomyces cerevisiae S288C]

See identical proteins and their annotated locations for NP_015344.1

Status: REVIEWED

UniProtKB/Swiss-Prot

D6W429, P30665

UniProtKB/TrEMBL

A0A8H4BU27, A6ZWR2, B3LL80, C7GQB9, C8ZJ44, N1NW04

Conserved Domains (2) summary

smart00350
Location:310 → 834

MCM; minichromosome maintenance proteins

pfam14551
Location:194 → 306

MCM_N; MCM N-terminal domain