UniProt functional annotation for P33993



	UniProt functional annotation for P33993

UniProt code: P33993.

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. Required for S-phase checkpoint activation upon UV-induced damage. {ECO:0000269|PubMed:15210935, ECO:0000269|PubMed:15538388, 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:9305914, PubMed:16899510, PubMed:17296731). The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7- MCM3-MCM5 (PubMed:9305914, PubMed:16899510, PubMed:17296731). Interacts with the ATR-ATRIP complex and with RAD17 (PubMed:15210935, PubMed:15538388). Interacts with TIPIN (PubMed:17116885). Interacts with MCMBP (PubMed:17296731). Interacts with ANKRD17 (PubMed:23711367). Component of the replisome complex composed of at least DONSON, MCM2, MCM7, PCNA and TICRR (PubMed:28191891). Component of the CMG helicase complex, composed of the MCM2-7 complex, the GINS complex and CDC45 (By similarity). {ECO:0000250|UniProtKB:Q91876, ECO:0000269|PubMed:15210935, ECO:0000269|PubMed:15538388, ECO:0000269|PubMed:16899510, ECO:0000269|PubMed:17116885, ECO:0000269|PubMed:17296731, ECO:0000269|PubMed:23711367, ECO:0000269|PubMed:28191891, ECO:0000269|PubMed:9305914}.

Subcellular location: Nucleus {ECO:0000250|UniProtKB:Q91876}. Chromosome {ECO:0000250|UniProtKB:Q91876}. Note=Associated with chromatin before the formation of nuclei and detaches from it as DNA replication progresses. {ECO:0000250|UniProtKB:Q91876}.

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

Ptm: Ubiquitinated by traip when forks converge following formation of DNA interstrand cross-links. Short ubiquitin chains on MCM7 promote recruitment of DNA glycosylase NEIL3. If the interstrand cross-link cannot be cleaved by NEIL3, the ubiquitin chains continue to grow on MCM7, promoting the unloading of the CMG helicase complex by the VCP/p97 ATPase. {ECO:0000250|UniProtKB:Q91876}.

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. Required for S-phase checkpoint activation upon UV-induced damage. {ECO:0000269\|PubMed:15210935, ECO:0000269\|PubMed:15538388, 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:9305914, PubMed:16899510, PubMed:17296731). The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7- MCM3-MCM5 (PubMed:9305914, PubMed:16899510, PubMed:17296731). Interacts with the ATR-ATRIP complex and with RAD17 (PubMed:15210935, PubMed:15538388). Interacts with TIPIN (PubMed:17116885). Interacts with MCMBP (PubMed:17296731). Interacts with ANKRD17 (PubMed:23711367). Component of the replisome complex composed of at least DONSON, MCM2, MCM7, PCNA and TICRR (PubMed:28191891). Component of the CMG helicase complex, composed of the MCM2-7 complex, the GINS complex and CDC45 (By similarity). {ECO:0000250\|UniProtKB:Q91876, ECO:0000269\|PubMed:15210935, ECO:0000269\|PubMed:15538388, ECO:0000269\|PubMed:16899510, ECO:0000269\|PubMed:17116885, ECO:0000269\|PubMed:17296731, ECO:0000269\|PubMed:23711367, ECO:0000269\|PubMed:28191891, ECO:0000269\|PubMed:9305914}.
Subcellular location:		Nucleus {ECO:0000250\|UniProtKB:Q91876}. Chromosome {ECO:0000250\|UniProtKB:Q91876}. Note=Associated with chromatin before the formation of nuclei and detaches from it as DNA replication progresses. {ECO:0000250\|UniProtKB:Q91876}.
Ptm:		O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner. {ECO:0000269\|PubMed:22967762}.
Ptm:		Ubiquitinated by traip when forks converge following formation of DNA interstrand cross-links. Short ubiquitin chains on MCM7 promote recruitment of DNA glycosylase NEIL3. If the interstrand cross-link cannot be cleaved by NEIL3, the ubiquitin chains continue to grow on MCM7, promoting the unloading of the CMG helicase complex by the VCP/p97 ATPase. {ECO:0000250\|UniProtKB:Q91876}.
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}.