UniProt functional annotation for Q14566



	UniProt functional annotation for Q14566

UniProt code: Q14566.

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: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:17296731, PubMed:9305914). The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7- MCM3-MCM5 (PubMed:16899510, PubMed:17296731, PubMed:9305914). May interact with MCM10 (PubMed:11095689). Interacts with TIPIN (PubMed:17116885). Interacts with CDT1 (PubMed:20202939). Interacts with MCMBP (PubMed:17296731). Interacts with DDI2 (PubMed:29290612). Component of the CMG helicase complex, composed of the MCM2-7 complex, the GINS complex and CDC45 (By similarity). {ECO:0000250|UniProtKB:Q5FWY4, ECO:0000269|PubMed:11095689, ECO:0000269|PubMed:16899510, ECO:0000269|PubMed:17116885, ECO:0000269|PubMed:17296731, ECO:0000269|PubMed:20202939, ECO:0000269|PubMed:29290612, ECO:0000269|PubMed:9305914}.

Subcellular location: Nucleus {ECO:0000269|PubMed:16899510}. Chromosome {ECO:0000269|PubMed:16899510}. Note=Binds to chromatin during G1 and detach from it during S phase. {ECO:0000269|PubMed:16899510}.

Ptm: O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner. {ECO:0000269|PubMed:22967762}.

Polymorphism: Intronic variations in MCM6 upstream from the LCT gene are associated with adult-type hypolactasia [MIM:223100] leading to lactose intolerance, or with lactase persistance. Lactose intolerance is a normal physiological phenomenon caused by developmental down- regulation of lactase activity during childhood or early adulthood. A non-coding variation in MCM6 affects the transcriptional regulation of the LCT gene resulting in down-regulation of lactase activity. However, the majority of Northern Europeans and some African populations have the ability to maintain lactase activity and digest lactose throughout life (lactase persistence). {ECO:0000269|PubMed:17159977}.

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.

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: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:17296731, PubMed:9305914). The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7- MCM3-MCM5 (PubMed:16899510, PubMed:17296731, PubMed:9305914). May interact with MCM10 (PubMed:11095689). Interacts with TIPIN (PubMed:17116885). Interacts with CDT1 (PubMed:20202939). Interacts with MCMBP (PubMed:17296731). Interacts with DDI2 (PubMed:29290612). Component of the CMG helicase complex, composed of the MCM2-7 complex, the GINS complex and CDC45 (By similarity). {ECO:0000250\|UniProtKB:Q5FWY4, ECO:0000269\|PubMed:11095689, ECO:0000269\|PubMed:16899510, ECO:0000269\|PubMed:17116885, ECO:0000269\|PubMed:17296731, ECO:0000269\|PubMed:20202939, ECO:0000269\|PubMed:29290612, ECO:0000269\|PubMed:9305914}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:16899510}. Chromosome {ECO:0000269\|PubMed:16899510}. Note=Binds to chromatin during G1 and detach from it during S phase. {ECO:0000269\|PubMed:16899510}.
Ptm:		O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner. {ECO:0000269\|PubMed:22967762}.
Polymorphism:		Intronic variations in MCM6 upstream from the LCT gene are associated with adult-type hypolactasia [MIM:223100] leading to lactose intolerance, or with lactase persistance. Lactose intolerance is a normal physiological phenomenon caused by developmental down- regulation of lactase activity during childhood or early adulthood. A non-coding variation in MCM6 affects the transcriptional regulation of the LCT gene resulting in down-regulation of lactase activity. However, the majority of Northern Europeans and some African populations have the ability to maintain lactase activity and digest lactose throughout life (lactase persistence). {ECO:0000269\|PubMed:17159977}.
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.
Similarity:		Belongs to the MCM family. {ECO:0000305}.