MCM4

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]

Full Name

Minichromosome Maintenance Complex Component 4

Function

Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. 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.

Biological Process

DNA replication Source: UniProtKB
DNA strand elongation involved in DNA replication Source: GO_Central
DNA unwinding involved in DNA replication Source: ComplexPortal
Double-strand break repair via break-induced replication Source: GO_Central
Mitotic DNA replication initiation Source: GO_Central
Regulation of DNA-dependent DNA replication initiation Source: ComplexPortal

Cellular Location

Nucleus
Other locations
Chromosome
Note: Associated with chromatin before the formation of nuclei and detaches from it as DNA replication progresses.

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.

PTM

Sumoylated; SUMO2 modified in response to stress caused by inhibition of proteasome activity (in vitro).