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

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; AllianceGenome:HGNC:6947
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: mouse all
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Genomic context

Location:: 8q11.21

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (47960941..47978160)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (48337189..48354408)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (48873501..48890720)

Chromosome 8 - NC_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Identification of MCM4 and PRKDC as new regulators of osteosarcoma cell dormancy based on 3D cell cultures.
Title: Identification of MCM4 and PRKDC as new regulators of osteosarcoma cell dormancy based on 3D cell cultures.
Minichromosome Maintenance 4 Is Associated with Cancer Stemness and Poor Survival of Patients with Gastric Cancer.
Title: Minichromosome Maintenance 4 Is Associated with Cancer Stemness and Poor Survival of Patients with Gastric Cancer.
Identification of MCM4 as a Prognostic Marker of Hepatocellular Carcinoma.
Title: Identification of MCM4 as a Prognostic Marker of Hepatocellular Carcinoma.
MCM4 in human hepatocellular carcinoma: a potent prognostic factor associated with cell proliferation.
Title: MCM4 in human hepatocellular carcinoma: a potent prognostic factor associated with cell proliferation.
MCM2, MCM4, and MCM6 labeling seems to outperform Ki67 as tools to assess cellular proliferation in breast cancer. The onset of sustained Ki67 expression occurs only in late G1 phase, while MCM can label all proliferative cells during the active phases of cell cycle
Title: MCM2, MCM4, and MCM6 in Breast Cancer: Clinical Utility in Diagnosis and Prognosis.
High MCM4 expression is associated with lung adenocarcinoma.
Title: Prognostic significance of minichromosome maintenance mRNA expression in human lung adenocarcinoma.
MCM4, MCM5, and MCM8 may have roles in lung adenocarcinoma prognosis with roles in regulating the cell cycle, DNA replication and other multiple biological processes and pathways
Title: Genome-wide investigation of the clinical significance and prospective molecular mechanism of minichromosome maintenance protein family genes in patients with Lung Adenocarcinoma.
siRNA of MCM4 inhibits proliferation and induces apoptosis of laryngeal squamous cell carcinoma (LSCC) cell line UMSCC 5. MCM4 mRNA is overexpressed in carcinoma tissues and correlates with male gender, smoking history and poor differentiation in Chinese LSCC patients.
Title: Minichromosome maintenance (MCM) protein 4 overexpression is a potential prognostic marker for laryngeal squamous cell carcinoma.
Data suggest that MCM4 phosphorylation by CDK2 plays role in DNA replication licensing system MCM4/MCM6/MCM7; this phosphorylation interferes with MCM complex function by lowering stability of MCM complex; MCM4 is highly phosphorylated in S phase. (MCM = minichromosome maintenance complex [hexamer of components 4/6/7]; CDK2 = cyclin-dependent kinase-2)
Title: Function of the amino-terminal region of human MCM4 in helicase activity.
MCM4 and MCM7 expression is significantly correlated with Ki-67, Bmi1, and cyclin E expression in esophageal adenocarcinoma, squamous cell carcinoma and precancerous lesions.
Title: MCM4 and MCM7, potential novel proliferation markers, significantly correlated with Ki-67, Bmi1, and cyclin E expression in esophageal adenocarcinoma, squamous cell carcinoma, and precancerous lesions.

Submit: New GeneRIF Correction See all GeneRIFs (34)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency MedGen: C1864947 OMIM: 609981 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

MCM4 (e-PCR), detects polymorphism
- UniSTS:504334

STS-N27515 (e-PCR)
- UniSTS:32529

PMC140533P1 (e-PCR)
- UniSTS:270934

PMC140533P2 (e-PCR)
- UniSTS:270935

PMC140533P3 (e-PCR)
- UniSTS:270936

L18426 (e-PCR)
- UniSTS:34648

PMC140533P4 (e-PCR)
- UniSTS:270937

PMC140533P5 (e-PCR)
- UniSTS:270938

PMC140533P6 (e-PCR)
- UniSTS:270939

D1S1423 (e-PCR)
- UniSTS:149619

G35510 (e-PCR)
- UniSTS:44150

SHGC-35380 (e-PCR)
- UniSTS:40572

RH102573 (e-PCR)
- UniSTS:96907

G32123 (e-PCR)
- UniSTS:52660

RH80868 (e-PCR)
- UniSTS:85179

RH78302 (e-PCR)
- UniSTS:52421

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP hydrolysis activity	IEA Inferred from Electronic Annotation more info
contributes_to DNA helicase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
contributes_to single-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed
contributes_to single-stranded DNA binding	ISS Inferred from Sequence or Structural Similarity more info
contributes_to single-stranded DNA helicase activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in DNA replication	NAS Non-traceable Author Statement more info	PubMed
involved_in DNA strand elongation involved in DNA replication	IBA Inferred from Biological aspect of Ancestor more info
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 double-strand break repair via break-induced replication	IBA Inferred from Biological aspect of Ancestor more info
involved_in mitotic DNA replication initiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of DNA-templated DNA replication initiation	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of CMG complex	IPI Inferred from Physical Interaction more info	PubMed
part_of CMG complex	ISS Inferred from Sequence or Structural Similarity more info
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	IPI Inferred from Physical Interaction more info	PubMed
located_in chromosome, telomeric region	HDA more info	PubMed
located_in membrane	HDA more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
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	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: DNA replication licensing factor MCM4

Names: homolog of S. pombe cell devision cycle 21; minichromosome maintenance deficient 4

NP_005905.2

EC 3.6.4.12

NP_877423.1

EC 3.6.4.12

NCBI Reference Sequences (RefSeq)

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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

NG_032967.1 RefSeqGene

Range

5739..22958

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1239

mRNA and Protein(s)

NM_005914.4 → NP_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, Q8NEH1, Q99658

UniProtKB/TrEMBL

B3KMX0

Related

ENSP00000262105.2, ENST00000262105.6

Conserved Domains (2) summary

smart00350
Location:267 → 770

MCM; minichromosome maintenance proteins

pfam14551
Location:163 → 263

MCM_N; MCM N-terminal domain
NM_182746.3 → NP_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, Q8NEH1, Q99658

UniProtKB/TrEMBL

B3KMX0

Related

ENSP00000496964.1, ENST00000649973.1

Conserved Domains (2) summary

smart00350
Location:267 → 770

MCM; minichromosome maintenance proteins

pfam14551
Location:163 → 263

MCM_N; MCM N-terminal domain