UniProt functional annotation for P33991



	UniProt functional annotation for P33991

UniProt code: P33991.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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. {ECO:0000269|PubMed:16899510, ECO:0000269|PubMed:9305914}.

Catalytic activity: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12;

Subunit: Component of the MCM2-7 complex (PubMed:16899510, PubMed:9305914). The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5 (PubMed:16899510, PubMed:9305914). Interacts with MCMBP (PubMed:17296731). Component of the CMG helicase complex, composed of the MCM2-7 complex, the GINS complex and CDC45 (By similarity). {ECO:0000250|UniProtKB:P30664, ECO:0000269|PubMed:16899510, ECO:0000269|PubMed:17296731, ECO:0000269|PubMed:9305914}.

Subcellular location: Nucleus {ECO:0000250|UniProtKB:P30664}. Chromosome {ECO:0000250|UniProtKB:P30664}. Note=Associated with chromatin before the formation of nuclei and detaches from it as DNA replication progresses. {ECO:0000250|UniProtKB:P30664}.

Ptm: Sumoylated; SUMO2 modified in response to stress caused by inhibition of proteasome activity (in vitro). {ECO:0000250|UniProtKB:P49717}.

Disease: Immunodeficiency 54 (IMD54) [MIM:609981]: 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. {ECO:0000269|PubMed:22354167, ECO:0000269|PubMed:22354170, ECO:0000269|PubMed:22499342}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: Early fractionation of eukaryotic MCM proteins yielded a variety of dimeric, trimeric and tetrameric complexes with unclear biological significance. Specifically a MCM467 subcomplex is shown to have in vitro helicase activity which is inhibited by the MCM2 subunit. The MCM2-7 hexamer is the proposed physiological active complex. {ECO:0000305}.

Similarity: Belongs to the MCM family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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. {ECO:0000269\|PubMed:16899510, ECO:0000269\|PubMed:9305914}.


Catalytic activity:		Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12;
Subunit:		Component of the MCM2-7 complex (PubMed:16899510, PubMed:9305914). The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5 (PubMed:16899510, PubMed:9305914). Interacts with MCMBP (PubMed:17296731). Component of the CMG helicase complex, composed of the MCM2-7 complex, the GINS complex and CDC45 (By similarity). {ECO:0000250\|UniProtKB:P30664, ECO:0000269\|PubMed:16899510, ECO:0000269\|PubMed:17296731, ECO:0000269\|PubMed:9305914}.
Subcellular location:		Nucleus {ECO:0000250\|UniProtKB:P30664}. Chromosome {ECO:0000250\|UniProtKB:P30664}. Note=Associated with chromatin before the formation of nuclei and detaches from it as DNA replication progresses. {ECO:0000250\|UniProtKB:P30664}.
Ptm:		Sumoylated; SUMO2 modified in response to stress caused by inhibition of proteasome activity (in vitro). {ECO:0000250\|UniProtKB:P49717}.
Disease:		Immunodeficiency 54 (IMD54) [MIM:609981]: 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. {ECO:0000269\|PubMed:22354167, ECO:0000269\|PubMed:22354170, ECO:0000269\|PubMed:22499342}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		Early fractionation of eukaryotic MCM proteins yielded a variety of dimeric, trimeric and tetrameric complexes with unclear biological significance. Specifically a MCM467 subcomplex is shown to have in vitro helicase activity which is inhibited by the MCM2 subunit. The MCM2-7 hexamer is the proposed physiological active complex. {ECO:0000305}.
Similarity:		Belongs to the MCM family. {ECO:0000305}.