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Details on Person UniProt:Q9UJA3-2 MCM8

Class:IdReferenceIsoform:169499
_chainChangeLogchain:1-840 added on Fri February 6 2015
_displayNameUniProt:Q9UJA3-2 MCM8
_timestamp2026-02-20 21:51:01
chainchain:1-840
checksum6349339A92FEBF88
commentFUNCTION 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
descriptionrecommendedName: DNA helicase MCM8 ecNumber evidence="16 22"5.6.2.4 alternativeName: fullName evidence="19"DNA 3'-5' helicase MCM8 alternativeName: Minichromosome maintenance 8
geneNameMCM8
C20orf154
identifierQ9UJA3
isoformParent
isSequenceChangedFALSE
keyword3D-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
nameMCM8
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8997816] ENSEMBL:ENSG00000125885 MCM8 [Homo sapiens]
secondaryIdentifierMCM8_HUMAN
B2RBG7
D3DW08
E7EQU7
Q495R4
Q495R6
Q495R7
Q86US4
Q969I5
sequenceLength840
species[Species:48887] Homo sapiens
variantIdentifierQ9UJA3-2
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