MCM8_HUMAN
ID MCM8_HUMAN Reviewed; 840 AA.
AC Q9UJA3; B2RBG7; D3DW08; E7EQU7; Q495R4; Q495R6; Q495R7; Q86US4; Q969I5;
DT 17-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 2.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=DNA helicase MCM8;
DE EC=3.6.4.12 {ECO:0000305|PubMed:26215093};
DE AltName: Full=Minichromosome maintenance 8;
GN Name=MCM8; Synonyms=C20orf154;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), POSSIBLE FUNCTION, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Liver;
RX PubMed=12527764; DOI=10.1093/nar/gkg136;
RA Gozuacik D., Chami M., Lagorce D., Faivre J., Murakami Y., Poch O.,
RA Biermann E., Knippers R., Brechot C., Paterlini-Brechot P.;
RT "Identification and functional characterization of a new member of the
RT human Mcm protein family: hMcm8.";
RL Nucleic Acids Res. 31:570-579(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING (ISOFORM 3),
RP AND TISSUE SPECIFICITY.
RC TISSUE=Cervix carcinoma, and Choriocarcinoma;
RX PubMed=12771218; DOI=10.1093/nar/gkg395;
RA Johnson E.M., Kinoshita Y., Daniel D.C.;
RT "A new member of the MCM protein family encoded by the human MCM8 gene,
RT located contrapodal to GCD10 at chromosome band 20p12.3-13.";
RL Nucleic Acids Res. 31:2915-2925(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Neuron, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 4).
RC TISSUE=Muscle, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, INTERACTION WITH CDC6 AND ORC2, AND SUBCELLULAR LOCATION.
RX PubMed=15684404; DOI=10.1128/mcb.25.4.1560-1568.2005;
RA Volkening M., Hoffmann I.;
RT "Involvement of human MCM8 in prereplication complex assembly by recruiting
RT hcdc6 to chromatin.";
RL Mol. Cell. Biol. 25:1560-1568(2005).
RN [8]
RP INDUCTION BY E2F1.
RX PubMed=16325355; DOI=10.1016/j.gene.2005.10.002;
RA Hayashi R., Goto Y., Haga A., Kobayashi D., Ikeda R., Yoshida K.;
RT "Comparative genomics on MCM8 orthologous genes reveals the transcriptional
RT regulation by transcription factor E2F.";
RL Gene 367:126-134(2006).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=18072282; DOI=10.1002/jemt.20553;
RA Kinoshita Y., Johnson E.M., Gordon R.E., Negri-Bell H., Evans M.T.,
RA Coolbaugh J., Rosario-Peralta Y., Samet J., Slusser E., Birkenbach M.P.,
RA Daniel D.C.;
RT "Colocalization of MCM8 and MCM7 with proteins involved in distinct aspects
RT of DNA replication.";
RL Microsc. Res. Tech. 71:288-297(2008).
RN [10]
RP FUNCTION, IDENTIFICATION IN THE MCM8-MCM9 COMPLEX, INTERACTION WITH RAD51,
RP AND SUBCELLULAR LOCATION.
RX PubMed=23401855; DOI=10.1128/mcb.01503-12;
RA Park J., Long D.T., Lee K.Y., Abbas T., Shibata E., Negishi M., Luo Y.,
RA Schimenti J.C., Gambus A., Walter J.C., Dutta A.;
RT "The MCM8-MCM9 complex promotes RAD51 recruitment at DNA damage sites to
RT facilitate homologous recombination.";
RL Mol. Cell. Biol. 33:1632-1644(2013).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-630, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [12]
RP FUNCTION, IDENTIFICATION IN THE MCM8-MCM9 COMPLEX, INTERACTION WITH THE MMR
RP COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=26300262; DOI=10.1016/j.molcel.2015.07.010;
RA Traver S., Coulombe P., Peiffer I., Hutchins J.R., Kitzmann M.,
RA Latreille D., Mechali M.;
RT "MCM9 Is Required for Mammalian DNA Mismatch Repair.";
RL Mol. Cell 59:831-839(2015).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH THE MRN COMPLEX, SUBCELLULAR
RP LOCATION, MUTAGENESIS OF PRO-456, AND CHARACTERIZATION OF VARIANT LYS-341.
RX PubMed=26215093; DOI=10.1038/ncomms8744;
RA Lee K.Y., Im J.S., Shibata E., Park J., Handa N., Kowalczykowski S.C.,
RA Dutta A.;
RT "MCM8-9 complex promotes resection of double-strand break ends by MRE11-
RT RAD50-NBS1 complex.";
RL Nat. Commun. 6:7744-7744(2015).
RN [14]
RP INVOLVEMENT IN POF10, VARIANT POF10 ARG-149, AND CHARACTERIZATION OF
RP VARIANT POF10 ARG-149.
RX PubMed=25437880; DOI=10.1172/jci78473;
RA AlAsiri S., Basit S., Wood-Trageser M.A., Yatsenko S.A., Jeffries E.P.,
RA Surti U., Ketterer D.M., Afzal S., Ramzan K., Faiyaz-Ul Haque M., Jiang H.,
RA Trakselis M.A., Rajkovic A.;
RT "Exome sequencing reveals MCM8 mutation underlies ovarian failure and
RT chromosomal instability.";
RL J. Clin. Invest. 125:258-262(2015).
RN [15]
RP INTERACTION WITH HROB.
RX PubMed=31467087; DOI=10.1101/gad.329508.119;
RA Hustedt N., Saito Y., Zimmermann M., Alvarez-Quilon A., Setiaputra D.,
RA Adam S., McEwan A., Yuan J.Y., Olivieri M., Zhao Y., Kanemaki M.T.,
RA Jurisicova A., Durocher D.;
RT "Control of homologous recombination by the HROB-MCM8-MCM9 pathway.";
RL Genes Dev. 33:1397-1415(2019).
CC -!- FUNCTION: Component of the MCM8-MCM9 complex, a complex involved in the
CC repair of double-stranded DNA breaks (DBSs) and DNA interstrand cross-
CC links (ICLs) by homologous recombination (HR) (PubMed:23401855).
CC Required for DNA resection by the MRE11-RAD50-NBN/NBS1 (MRN) complex by
CC recruiting the MRN complex to the repair site and by promoting the
CC complex nuclease activity (PubMed:26215093). Probably by regulating the
CC localization of the MNR complex, indirectly regulates the recruitment
CC of downstream effector RAD51 to DNA damage sites including DBSs and
CC ICLs (PubMed:23401855). The MCM8-MCM9 complex is dispensable for DNA
CC replication and S phase progression (PubMed:23401855). However, may
CC play a non-essential for DNA replication: may be involved in the
CC activation of the prereplicative complex (pre-RC) during G(1) phase by
CC recruiting CDC6 to the origin recognition complex (ORC)
CC (PubMed:15684404). Probably by regulating HR, plays a key role during
CC gametogenesis (By similarity). Stabilizes MCM9 protein
CC (PubMed:23401855, PubMed:26215093). {ECO:0000250|UniProtKB:Q9CWV1,
CC ECO:0000269|PubMed:15684404, ECO:0000269|PubMed:23401855,
CC ECO:0000269|PubMed:26215093}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12;
CC Evidence={ECO:0000305|PubMed:26215093};
CC -!- SUBUNIT: Component of the MCM8-MCM9 complex, which forms a hexamer
CC composed of MCM8 and MCM9 (PubMed:23401855, PubMed:26300262). Interacts
CC with the DNA mismatch repair (MMR) complex composed at least of MSH2,
CC MSH3, MSH6, PMS1 and MLH1 (PubMed:26300262). Interacts with RAD51; the
CC interaction recruits RAD51 to DNA damage sites (PubMed:23401855).
CC Interacts with the MRN complex composed of MRE11, RAD50 and NBN/NBS1
CC (PubMed:26215093). Interacts with CDC6 and ORC2 (PubMed:15684404).
CC Interacts with HROB; the interaction recruits the MCM8-MCM9 complex to
CC DNA damage sites (PubMed:31467087). {ECO:0000269|PubMed:15684404,
CC ECO:0000269|PubMed:23401855, ECO:0000269|PubMed:26215093,
CC ECO:0000269|PubMed:26300262, ECO:0000269|PubMed:31467087}.
CC -!- INTERACTION:
CC Q9UJA3; Q9NXL9: MCM9; NbExp=3; IntAct=EBI-8756095, EBI-2804985;
CC Q9UJA3; Q9BTE3: MCMBP; NbExp=3; IntAct=EBI-8756095, EBI-749378;
CC Q9UJA3-4; Q96JP0: FEM1C; NbExp=3; IntAct=EBI-13052514, EBI-2515330;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12527764,
CC ECO:0000269|PubMed:18072282, ECO:0000269|PubMed:23401855,
CC ECO:0000269|PubMed:26215093, ECO:0000269|PubMed:26300262}. Chromosome
CC {ECO:0000269|PubMed:15684404, ECO:0000269|PubMed:23401855,
CC ECO:0000269|PubMed:26215093}. Note=Localizes to nuclear foci
CC (PubMed:26215093). Localizes to double-stranded DNA breaks
CC (PubMed:23401855). Binds chromatin throughout the cell cycle
CC (PubMed:15684404). {ECO:0000269|PubMed:15684404,
CC ECO:0000269|PubMed:23401855, ECO:0000269|PubMed:26215093}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9UJA3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UJA3-2; Sequence=VSP_015785;
CC Name=3;
CC IsoId=Q9UJA3-3; Sequence=VSP_041308;
CC Name=4;
CC IsoId=Q9UJA3-4; Sequence=VSP_044179;
CC -!- TISSUE SPECIFICITY: Highest levels in placenta, lung and pancreas. Low
CC levels in skeletal muscle and kidney. Expressed in various tumors with
CC highest levels in colon and lung cancers.
CC {ECO:0000269|PubMed:12771218}.
CC -!- INDUCTION: By E2F1. {ECO:0000269|PubMed:16325355}.
CC -!- DISEASE: Premature ovarian failure 10 (POF10) [MIM:612885]: An ovarian
CC disorder defined as the cessation of ovarian function under the age of
CC 40 years. It is characterized by oligomenorrhea or amenorrhea, in the
CC presence of elevated levels of serum gonadotropins and low estradiol.
CC {ECO:0000269|PubMed:25437880}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 3]: No experimental confirmation available.
CC According to PubMed:12771218, this isoform could be derived from an
CC aberrant mRNA form found in placental choriocarcinoma.
CC -!- SIMILARITY: Belongs to the MCM family. {ECO:0000305}.
CC -!- CAUTION: Was initially thought to play a role in DNA replication
CC (PubMed:15684404). However, it was later shown that it is mainly
CC involved in homologous recombination repair (PubMed:23401855).
CC {ECO:0000305|PubMed:15684404, ECO:0000305|PubMed:23401855}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB55260.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ439063; CAD27750.1; -; mRNA.
DR EMBL; AY158211; AAO21222.1; -; mRNA.
DR EMBL; AK027644; BAB55260.1; ALT_INIT; mRNA.
DR EMBL; AK314654; BAG37214.1; -; mRNA.
DR EMBL; AL035461; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471133; EAX10403.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10404.1; -; Genomic_DNA.
DR EMBL; BC008830; AAH08830.2; -; mRNA.
DR EMBL; BC080656; AAH80656.1; -; mRNA.
DR EMBL; BC101054; AAI01055.1; -; mRNA.
DR EMBL; BC101055; AAI01056.1; -; mRNA.
DR EMBL; BC101056; AAI01057.1; -; mRNA.
DR EMBL; BC101057; AAI01058.1; -; mRNA.
DR CCDS; CCDS13094.1; -. [Q9UJA3-1]
DR CCDS; CCDS13095.1; -. [Q9UJA3-3]
DR CCDS; CCDS63226.1; -. [Q9UJA3-2]
DR CCDS; CCDS63227.1; -. [Q9UJA3-4]
DR RefSeq; NP_001268449.1; NM_001281520.1. [Q9UJA3-1]
DR RefSeq; NP_001268450.1; NM_001281521.1. [Q9UJA3-4]
DR RefSeq; NP_001268451.1; NM_001281522.1. [Q9UJA3-2]
DR RefSeq; NP_115874.3; NM_032485.5. [Q9UJA3-1]
DR RefSeq; NP_877954.1; NM_182802.2. [Q9UJA3-3]
DR RefSeq; XP_016883594.1; XM_017028105.1. [Q9UJA3-4]
DR PDB; 6L0O; X-ray; 1.21 A; A=770-840.
DR PDB; 7DP3; X-ray; 2.55 A; A/B=61-376.
DR PDBsum; 6L0O; -.
DR PDBsum; 7DP3; -.
DR AlphaFoldDB; Q9UJA3; -.
DR SMR; Q9UJA3; -.
DR BioGRID; 124109; 56.
DR ComplexPortal; CPX-7113; MCM8-MCM9 DNA helicase complex.
DR CORUM; Q9UJA3; -.
DR IntAct; Q9UJA3; 26.
DR MINT; Q9UJA3; -.
DR STRING; 9606.ENSP00000368164; -.
DR iPTMnet; Q9UJA3; -.
DR PhosphoSitePlus; Q9UJA3; -.
DR BioMuta; MCM8; -.
DR DMDM; 27805609; -.
DR EPD; Q9UJA3; -.
DR jPOST; Q9UJA3; -.
DR MassIVE; Q9UJA3; -.
DR MaxQB; Q9UJA3; -.
DR PaxDb; Q9UJA3; -.
DR PeptideAtlas; Q9UJA3; -.
DR PRIDE; Q9UJA3; -.
DR ProteomicsDB; 17650; -.
DR ProteomicsDB; 84610; -. [Q9UJA3-1]
DR ProteomicsDB; 84611; -. [Q9UJA3-2]
DR ProteomicsDB; 84612; -. [Q9UJA3-3]
DR Antibodypedia; 8265; 270 antibodies from 30 providers.
DR DNASU; 84515; -.
DR Ensembl; ENST00000265187.4; ENSP00000265187.4; ENSG00000125885.13. [Q9UJA3-3]
DR Ensembl; ENST00000378883.5; ENSP00000368161.1; ENSG00000125885.13. [Q9UJA3-2]
DR Ensembl; ENST00000378886.6; ENSP00000368164.2; ENSG00000125885.13. [Q9UJA3-4]
DR Ensembl; ENST00000378896.7; ENSP00000368174.3; ENSG00000125885.13. [Q9UJA3-1]
DR Ensembl; ENST00000610722.4; ENSP00000478141.1; ENSG00000125885.13. [Q9UJA3-1]
DR GeneID; 84515; -.
DR KEGG; hsa:84515; -.
DR MANE-Select; ENST00000610722.4; ENSP00000478141.1; NM_032485.6; NP_115874.3.
DR UCSC; uc002wmi.5; human. [Q9UJA3-1]
DR CTD; 84515; -.
DR DisGeNET; 84515; -.
DR GeneCards; MCM8; -.
DR HGNC; HGNC:16147; MCM8.
DR HPA; ENSG00000125885; Low tissue specificity.
DR MalaCards; MCM8; -.
DR MIM; 608187; gene.
DR MIM; 612885; phenotype.
DR neXtProt; NX_Q9UJA3; -.
DR OpenTargets; ENSG00000125885; -.
DR Orphanet; 619; NON RARE IN EUROPE: Primary ovarian failure.
DR PharmGKB; PA25696; -.
DR VEuPathDB; HostDB:ENSG00000125885; -.
DR eggNOG; KOG0480; Eukaryota.
DR GeneTree; ENSGT01050000244972; -.
DR HOGENOM; CLU_000995_7_2_1; -.
DR InParanoid; Q9UJA3; -.
DR OMA; THTVDWQ; -.
DR OrthoDB; 266497at2759; -.
DR PhylomeDB; Q9UJA3; -.
DR TreeFam; TF323155; -.
DR PathwayCommons; Q9UJA3; -.
DR Reactome; R-HSA-113507; E2F-enabled inhibition of pre-replication complex formation.
DR Reactome; R-HSA-176187; Activation of ATR in response to replication stress.
DR Reactome; R-HSA-176974; Unwinding of DNA.
DR Reactome; R-HSA-68689; CDC6 association with the ORC:origin complex.
DR Reactome; R-HSA-68949; Orc1 removal from chromatin.
DR Reactome; R-HSA-68962; Activation of the pre-replicative complex.
DR SignaLink; Q9UJA3; -.
DR BioGRID-ORCS; 84515; 22 hits in 1082 CRISPR screens.
DR ChiTaRS; MCM8; human.
DR GeneWiki; MCM8; -.
DR GenomeRNAi; 84515; -.
DR Pharos; Q9UJA3; Tbio.
DR PRO; PR:Q9UJA3; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9UJA3; protein.
DR Bgee; ENSG00000125885; Expressed in buccal mucosa cell and 171 other tissues.
DR Genevisible; Q9UJA3; HS.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0042555; C:MCM complex; IBA:GO_Central.
DR GO; GO:0097362; C:MCM8-MCM9 complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0003678; F:DNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0032406; F:MutLbeta complex binding; IDA:UniProtKB.
DR GO; GO:0032407; F:MutSalpha complex binding; IDA:UniProtKB.
DR GO; GO:0032408; F:MutSbeta complex binding; IDA:UniProtKB.
DR GO; GO:0003697; F:single-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0032508; P:DNA duplex unwinding; IDA:ComplexPortal.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:UniProtKB.
DR GO; GO:0007292; P:female gamete generation; ISS:UniProtKB.
DR GO; GO:0048232; P:male gamete generation; ISS:UniProtKB.
DR GO; GO:0070716; P:mismatch repair involved in maintenance of fidelity involved in DNA-dependent DNA replication; IC:ComplexPortal.
DR GO; GO:0071168; P:protein localization to chromatin; IMP:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IMP:UniProtKB.
DR GO; GO:0036298; P:recombinational interstrand cross-link repair; IMP:UniProtKB.
DR Gene3D; 2.40.50.140; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR031327; MCM.
DR InterPro; IPR001208; MCM_dom.
DR InterPro; IPR041562; MCM_lid.
DR InterPro; IPR033762; MCM_OB.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR11630; PTHR11630; 1.
DR Pfam; PF00493; MCM; 1.
DR Pfam; PF17855; MCM_lid; 1.
DR Pfam; PF17207; MCM_OB; 1.
DR PRINTS; PR01657; MCMFAMILY.
DR SMART; SM00382; AAA; 1.
DR SMART; SM00350; MCM; 1.
DR SUPFAM; SSF50249; SSF50249; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50051; MCM_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell cycle; Chromosome;
KW Disease variant; DNA damage; DNA repair; DNA replication; DNA-binding;
KW Helicase; Hydrolase; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Premature ovarian failure; Reference proteome.
FT CHAIN 1..840
FT /note="DNA helicase MCM8"
FT /id="PRO_0000194125"
FT DOMAIN 402..609
FT /note="MCM"
FT REGION 16..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 26..44
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 454..461
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 630
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 342..357
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_041308"
FT VAR_SEQ 408..418
FT /note="NSLCPVIFGHE -> KWSLALSPRLEYSGAISAHCNLHLPSSNSSPTSACRV
FT AGTTGMRHQTQLLL (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_044179"
FT VAR_SEQ 419..465
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015785"
FT VARIANT 63
FT /note="Q -> K (in dbSNP:rs236110)"
FT /id="VAR_015145"
FT VARIANT 101
FT /note="K -> N (in dbSNP:rs6117014)"
FT /id="VAR_050281"
FT VARIANT 149
FT /note="P -> R (in POF10; inhibits protein recruitment to
FT sites of DNA damage; shows significant reduction in DNA-
FT binding affinity for single-strand DNA; dbSNP:rs606231343)"
FT /evidence="ECO:0000269|PubMed:25437880"
FT /id="VAR_073417"
FT VARIANT 183
FT /note="N -> S (in dbSNP:rs16991591)"
FT /id="VAR_050282"
FT VARIANT 341
FT /note="E -> K (decreases the formation of MRE11 and RPA1
FT foci in response to cisplatin-induced DNA damage;
FT dbSNP:rs16991615)"
FT /evidence="ECO:0000269|PubMed:26215093"
FT /id="VAR_050283"
FT VARIANT 365
FT /note="S -> N (in dbSNP:rs28403619)"
FT /id="VAR_050284"
FT VARIANT 785
FT /note="N -> S (in dbSNP:rs16991638)"
FT /id="VAR_050285"
FT MUTAGEN 456
FT /note="P->A: Decreases the formation of MRE11 and RPA1 foci
FT in response to cisplatin-induced DNA damage."
FT /evidence="ECO:0000269|PubMed:26215093"
FT CONFLICT 590
FT /note="V -> A (in Ref. 6; AAI01056)"
FT /evidence="ECO:0000305"
FT CONFLICT 788
FT /note="E -> G (in Ref. 6; AAI01055)"
FT /evidence="ECO:0000305"
FT HELIX 78..80
FT /evidence="ECO:0007829|PDB:7DP3"
FT HELIX 92..105
FT /evidence="ECO:0007829|PDB:7DP3"
FT HELIX 107..109
FT /evidence="ECO:0007829|PDB:7DP3"
FT HELIX 112..118
FT /evidence="ECO:0007829|PDB:7DP3"
FT STRAND 120..124
FT /evidence="ECO:0007829|PDB:7DP3"
FT HELIX 125..128
FT /evidence="ECO:0007829|PDB:7DP3"
FT TURN 134..137
FT /evidence="ECO:0007829|PDB:7DP3"
FT HELIX 141..147
FT /evidence="ECO:0007829|PDB:7DP3"
FT HELIX 149..177
FT /evidence="ECO:0007829|PDB:7DP3"
FT STRAND 195..200
FT /evidence="ECO:0007829|PDB:7DP3"
FT STRAND 202..204
FT /evidence="ECO:0007829|PDB:7DP3"
FT HELIX 207..209
FT /evidence="ECO:0007829|PDB:7DP3"
FT HELIX 212..214
FT /evidence="ECO:0007829|PDB:7DP3"
FT STRAND 218..228
FT /evidence="ECO:0007829|PDB:7DP3"
FT STRAND 232..235
FT /evidence="ECO:0007829|PDB:7DP3"
FT STRAND 237..242
FT /evidence="ECO:0007829|PDB:7DP3"
FT TURN 243..245
FT /evidence="ECO:0007829|PDB:7DP3"
FT STRAND 248..252
FT /evidence="ECO:0007829|PDB:7DP3"
FT STRAND 265..268
FT /evidence="ECO:0007829|PDB:7DP3"
FT STRAND 274..277
FT /evidence="ECO:0007829|PDB:7DP3"
FT STRAND 285..295
FT /evidence="ECO:0007829|PDB:7DP3"
FT STRAND 299..302
FT /evidence="ECO:0007829|PDB:7DP3"
FT STRAND 310..316
FT /evidence="ECO:0007829|PDB:7DP3"
FT HELIX 317..319
FT /evidence="ECO:0007829|PDB:7DP3"
FT STRAND 328..337
FT /evidence="ECO:0007829|PDB:7DP3"
FT TURN 341..344
FT /evidence="ECO:0007829|PDB:7DP3"
FT STRAND 355..364
FT /evidence="ECO:0007829|PDB:7DP3"
FT HELIX 774..790
FT /evidence="ECO:0007829|PDB:6L0O"
FT STRAND 794..796
FT /evidence="ECO:0007829|PDB:6L0O"
FT HELIX 797..806
FT /evidence="ECO:0007829|PDB:6L0O"
FT HELIX 814..823
FT /evidence="ECO:0007829|PDB:6L0O"
FT STRAND 826..831
FT /evidence="ECO:0007829|PDB:6L0O"
FT STRAND 834..837
FT /evidence="ECO:0007829|PDB:6L0O"
SQ SEQUENCE 840 AA; 93697 MW; 6349339A92FEBF88 CRC64;
MNGEYRGRGF GRGRFQSWKR GRGGGNFSGK WREREHRPDL SKTTGKRTSE QTPQFLLSTK
TPQSMQSTLD RFIPYKGWKL YFSEVYSDSS PLIEKIQAFE KFFTRHIDLY DKDEIERKGS
ILVDFKELTE GGEVTNLIPD IATELRDAPE KTLACMGLAI HQVLTKDLER HAAELQAQEG
LSNDGETMVN VPHIHARVYN YEPLTQLKNV RANYYGKYIA LRGTVVRVSN IKPLCTKMAF
LCAACGEIQS FPLPDGKYSL PTKCPVPVCR GRSFTALRSS PLTVTMDWQS IKIQELMSDD
QREAGRIPRT IECELVHDLV DSCVPGDTVT ITGIVKVSNA EEGSRNKNDK CMFLLYIEAN
SISNSKGQKT KSSEDGCKHG MLMEFSLKDL YAIQEIQAEE NLFKLIVNSL CPVIFGHELV
KAGLALALFG GSQKYADDKN RIPIRGDPHI LVVGDPGLGK SQMLQAACNV APRGVYVCGN
TTTTSGLTVT LSKDSSSGDF ALEAGALVLG DQGICGIDEF DKMGNQHQAL LEAMEQQSIS
LAKAGVVCSL PARTSIIAAA NPVGGHYNKA KTVSENLKMG SALLSRFDLV FILLDTPNEH
HDHLLSEHVI AIRAGKQRTI SSATVARMNS QDSNTSVLEV VSEKPLSERL KVVPGETIDP
IPHQLLRKYI GYARQYVYPR LSTEAARVLQ DFYLELRKQS QRLNSSPITT RQLESLIRLT
EARARLELRE EATKEDAEDI VEIMKYSMLG TYSDEFGNLD FERSQHGSGM SNRSTAKRFI
SALNNVAERT YNNIFQFHQL RQIAKELNIQ VADFENFIGS LNDQGYLLKK GPKVYQLQTM
