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Details on Person UniProt:Q9UJA3-2 MCM8
| Class:Id | ReferenceIsoform:169499 |
|---|---|
| _chainChangeLog | chain:1-840 added on Fri February 6 2015 |
| _displayName | UniProt:Q9UJA3-2 MCM8 |
| _timestamp | 2026-02-20 21:51:01 |
| chain | chain:1-840 |
| checksum | 6349339A92FEBF88 |
| comment | FUNCTION Component of the MCM8-MCM9 complex, which is involved in the repair of double-stranded DNA breaks (DBSs) and DNA interstrand cross-links (ICLs) by homologous recombination (HR) (PubMed:23401855). The MCM8-MCM9 complex is a 3'-5' DNA helicase and single-stranded (ss)DNA-stimulated ATPase which binds ssDNA in the presence of nucleoside triphosphates (PubMed:37309874). 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). Indirectly regulates the recruitment of downstream effector RAD51 to DNA damage sites including DBSs and ICLs, probably by regulating the localization of the MNR complex (PubMed:23401855). The MCM8-MCM9 complex is dispensable for DNA replication and S phase progression (PubMed:23401855). May play a non-essential for DNA replication: may be involved in the activation of the prereplicative complex (pre-RC) during G(1) phase by recruiting CDC6 to the origin recognition complex (ORC) (PubMed:15684404). Facilitates somatic mitochondrial (mt)DNA recombination (PubMed:36355348). Plays a key role during gametogenesis, probably by regulating HR (By similarity). Stabilizes MCM9 protein (PubMed:23401855, PubMed:26215093).CATALYTIC ACTIVITY Couples ATP hydrolysis with the unwinding of duplex DNA by translocating in the 3'-5' direction.CATALYTIC ACTIVITY ATP + H2O = ADP + phosphate + H(+)COFACTOR Binds 1 Zn(2+) ion per subunit; may also bind Fe(3+) at the same site.ACTIVITY REGULATION The helicase reaction is stimulated by the C-terminal domain of HROB; binding of HROB changes the conformation of the complex.SUBUNIT Component of the MCM8-MCM9 complex, which forms a heterohexamer (PubMed:23401855, PubMed:26215093, PubMed:26300262, PubMed:34043945, PubMed:37309874) with a repeating heterodimer of trimers configuration (PubMed:34043945, PubMed:37309874). Interacts with the DNA mismatch repair (MMR) complex composed at least of MSH2, MSH3, MSH6, PMS1 and MLH1 (PubMed:26300262). Interacts with RAD51; the interaction recruits RAD51 to DNA damage sites (PubMed:23401855). Interacts with the MRN complex composed of MRE11, RAD50 and NBN/NBS1 (PubMed:26215093). Interacts with CDC6 and ORC2 (PubMed:15684404). Interacts with HROB; the interaction recruits the MCM8-MCM9 complex to DNA damage sites (PubMed:31467087) and stimulates the helicase activity (PubMed:37535404).INTERACTION Localizes to nuclear foci (PubMed:26215093). Localizes to double-stranded DNA breaks (PubMed:23401855). Binds chromatin throughout the cell cycle (PubMed:15684404). Colocalizes with mitochondrial DNA (PubMed:36355348).ALTERNATIVE PRODUCTS Highest levels in placenta, lung and pancreas. Low levels in skeletal muscle and kidney. Expressed in various tumors with highest levels in colon and lung cancers.INDUCTION By E2F1.DOMAIN The ADP-bound heterohexamer forms around a central hole large enough to bind double-stranded (ds)DNA (PubMed:34043945, PubMed:37309874). Has 2 tiers; the N-terminal tier (residues 1-365) and the C-terminal ATPase tier (residues 401-754) joined by a linker which is essential for function (PubMed:37535404, PubMed:37309874). The C-terminal tier rotates compared to the N-terminal tier, which is required for helicase activity (PubMed:37535404). ATP binds in the C-terminal AAA(+) ATPase domain at the boundary between the alternating subunits (PubMed:37309874).DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS No experimental confirmation available. According to PubMed:12771218, this isoform could be derived from an aberrant mRNA form found in placental choriocarcinoma.SIMILARITY Belongs to the MCM family.CAUTION Was initially thought to play a role in DNA replication (PubMed:15684404). However, it was later shown that it is mainly involved in homologous recombination repair (PubMed:23401855).SEQUENCE CAUTION Truncated N-terminus. |
| created | [InstanceEdit:169495] Gopinathrao, G, 2005-11-29 20:48:39 |
| description | recommendedName: DNA helicase MCM8 ecNumber evidence="16 22"5.6.2.4 alternativeName: fullName evidence="19"DNA 3'-5' helicase MCM8 alternativeName: Minichromosome maintenance 8 |
| geneName | MCM8 C20orf154 |
| identifier | Q9UJA3 |
| isoformParent | |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing ATP-binding Cell cycle Chromosome Cytoplasm Disease variant DNA damage DNA repair DNA replication DNA-binding Helicase Hydrolase Isomerase Mitochondrion Nucleotide-binding Nucleus Phosphoprotein Premature ovarian failure Proteomics identification Reference proteome Zinc |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | MCM8 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8997816] ENSEMBL:ENSG00000125885 MCM8 [Homo sapiens] |
| secondaryIdentifier | MCM8_HUMAN B2RBG7 D3DW08 E7EQU7 Q495R4 Q495R6 Q495R7 Q86US4 Q969I5 |
| sequenceLength | 840 |
| species | [Species:48887] Homo sapiens |
| variantIdentifier | Q9UJA3-2 |
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No pathways have been reviewed or authored by UniProt:Q9UJA3-2 MCM8 (169499)
