UniProt functional annotation for Q9NXL9



	UniProt functional annotation for Q9NXL9

UniProt code: Q9NXL9.

Organism: Homo sapiens (Human).

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

Function: Component of the MCM8-MCM9 complex, a complex involved in the repair of double-stranded DNA breaks (DBSs) and DNA interstrand cross- links (ICLs) by homologous recombination (HR) (PubMed:23401855). Required for DNA resection by the MRE11-RAD50-NBN/NBS1 (MRN) complex by recruiting the MRN complex to the repair site and by promoting the complex nuclease activity (PubMed:26215093). Probably by regulating the localization of the MRN complex, indirectly regulates the recruitment of downstream effector RAD51 to DNA damage sites including DBSs and ICLs (PubMed:23401855). Acts as a helicase in DNA mismatch repair (MMR) following DNA replication errors to unwind the mismatch containing DNA strand (PubMed:26300262). In addition, recruits MLH1, a component of the MMR complex, to chromatin (PubMed:26300262). The MCM8-MCM9 complex is dispensable for DNA replication and S phase progression (PubMed:23401855). Probably by regulating HR, plays a key role during gametogenesis (By similarity). {ECO:0000250|UniProtKB:Q2KHI9, ECO:0000269|PubMed:23401855, ECO:0000269|PubMed:26215093, ECO:0000269|PubMed:26300262}.

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; Evidence={ECO:0000269|PubMed:26300262};

Subunit: Component of the MCM8-MCM9 complex, which forms a hexamer composed of MCM8 and MCM9 (PubMed:23401855, PubMed:26300262, PubMed:26215093). Interacts with the DNA mismatch repair (MMR) complex composed at least of MSH2, MSH3, MSH6, PMS1 and MLH1 (PubMed:26300262). Interacts with MLH1; the interaction recruits MLH1 to chromatin (PubMed:26300262). Interacts with MSH2; the interaction recruits MCM9 to chromatin (PubMed:26300262). Interacts with MSH6 (PubMed:26300262). Interacts with the MRN complex composed of MRE11, RAD50 and NBN/NBS1; the interaction recruits the MRN complex to DNA damage sites (PubMed:26215093). Interacts with RAD51; the interaction recruits RAD51 to DNA damage sites (PubMed:23401855). {ECO:0000269|PubMed:23401855, ECO:0000269|PubMed:26215093, ECO:0000269|PubMed:26300262}.

Subcellular location: Nucleus {ECO:0000269|PubMed:23401855, ECO:0000269|PubMed:26300262}. Chromosome {ECO:0000269|PubMed:23401855, ECO:0000269|PubMed:26300262}. Note=Colocalizes to nuclear foci with RPA1 following DNA damage (PubMed:23401855). Localizes to double- stranded DNA breaks (PubMed:23401855). Recruited to chromatin by MSH2 (PubMed:26300262). {ECO:0000269|PubMed:23401855, ECO:0000269|PubMed:26300262}.

Developmental stage: The expression of isoform L and isoform M is cell cycle regulated: induced in S-phase, decreases through G2/M, and becomes constant through G1. {ECO:0000269|PubMed:23403237}.

Disease: Ovarian dysgenesis 4 (ODG4) [MIM:616185]: A form of ovarian dysgenesis, a disorder characterized by lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism as a result of streak gonads. ODG4 is an autosomal recessive condition. {ECO:0000269|PubMed:25480036}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: [Isoform L]: Most abundant isoform.

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

Sequence caution: Sequence=BAA90991.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAG61142.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={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:		Component of the MCM8-MCM9 complex, a complex involved in the repair of double-stranded DNA breaks (DBSs) and DNA interstrand cross- links (ICLs) by homologous recombination (HR) (PubMed:23401855). Required for DNA resection by the MRE11-RAD50-NBN/NBS1 (MRN) complex by recruiting the MRN complex to the repair site and by promoting the complex nuclease activity (PubMed:26215093). Probably by regulating the localization of the MRN complex, indirectly regulates the recruitment of downstream effector RAD51 to DNA damage sites including DBSs and ICLs (PubMed:23401855). Acts as a helicase in DNA mismatch repair (MMR) following DNA replication errors to unwind the mismatch containing DNA strand (PubMed:26300262). In addition, recruits MLH1, a component of the MMR complex, to chromatin (PubMed:26300262). The MCM8-MCM9 complex is dispensable for DNA replication and S phase progression (PubMed:23401855). Probably by regulating HR, plays a key role during gametogenesis (By similarity). {ECO:0000250\|UniProtKB:Q2KHI9, ECO:0000269\|PubMed:23401855, ECO:0000269\|PubMed:26215093, ECO:0000269\|PubMed:26300262}.


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; Evidence={ECO:0000269\|PubMed:26300262};
Subunit:		Component of the MCM8-MCM9 complex, which forms a hexamer composed of MCM8 and MCM9 (PubMed:23401855, PubMed:26300262, PubMed:26215093). Interacts with the DNA mismatch repair (MMR) complex composed at least of MSH2, MSH3, MSH6, PMS1 and MLH1 (PubMed:26300262). Interacts with MLH1; the interaction recruits MLH1 to chromatin (PubMed:26300262). Interacts with MSH2; the interaction recruits MCM9 to chromatin (PubMed:26300262). Interacts with MSH6 (PubMed:26300262). Interacts with the MRN complex composed of MRE11, RAD50 and NBN/NBS1; the interaction recruits the MRN complex to DNA damage sites (PubMed:26215093). Interacts with RAD51; the interaction recruits RAD51 to DNA damage sites (PubMed:23401855). {ECO:0000269\|PubMed:23401855, ECO:0000269\|PubMed:26215093, ECO:0000269\|PubMed:26300262}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:23401855, ECO:0000269\|PubMed:26300262}. Chromosome {ECO:0000269\|PubMed:23401855, ECO:0000269\|PubMed:26300262}. Note=Colocalizes to nuclear foci with RPA1 following DNA damage (PubMed:23401855). Localizes to double- stranded DNA breaks (PubMed:23401855). Recruited to chromatin by MSH2 (PubMed:26300262). {ECO:0000269\|PubMed:23401855, ECO:0000269\|PubMed:26300262}.
Developmental stage:		The expression of isoform L and isoform M is cell cycle regulated: induced in S-phase, decreases through G2/M, and becomes constant through G1. {ECO:0000269\|PubMed:23403237}.
Disease:		Ovarian dysgenesis 4 (ODG4) [MIM:616185]: A form of ovarian dysgenesis, a disorder characterized by lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism as a result of streak gonads. ODG4 is an autosomal recessive condition. {ECO:0000269\|PubMed:25480036}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		[Isoform L]: Most abundant isoform.
Similarity:		Belongs to the MCM family. {ECO:0000305}.
Sequence caution:		Sequence=BAA90991.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAG61142.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};