MCM4
Function
Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:16899510, PubMed:25661590, PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232, PubMed:9305914). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:16899510, PubMed:25661590, PubMed:32453425, PubMed:9305914).
Involvement in disease
Immunodeficiency 54
IMD54
An autosomal recessive disorder characterized by severe intra- and extrauterine growth retardation, microcephaly, decreased numbers of natural killer cells, and recurrent viral infections, most often affecting the respiratory tract and leading to respiratory failure. Affected individuals also have adrenal insufficiency requiring corticosteroid replacement therapy and may have an increased susceptibility to cancer.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Sumoylated; SUMO2 modified in response to stress caused by inhibition of proteasome activity (in vitro).
Sequence Similarities
Belongs to the MCM family.
Cellular localization
- Nucleus
- Chromosome
- Associated with chromatin before the formation of nuclei and detaches from it as DNA replication progresses.
Alternative names
CDC21, MCM4, DNA replication licensing factor MCM4, CDC21 homolog, P1-CDC21