MCM8_MOUSE
ID MCM8_MOUSE Reviewed; 833 AA.
AC Q9CWV1; A2AVM8; A2AVM9; Q3UZG5; Q80US2; Q80VI0;
DT 17-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2005, sequence version 3.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=DNA helicase MCM8;
DE EC=3.6.4.12 {ECO:0000250|UniProtKB:Q9UJA3};
DE AltName: Full=Minichromosome maintenance 8;
GN Name=Mcm8;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Embryonic stem cell;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Fetal brain;
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 [5]
RP FUNCTION, IDENTIFICATION IN THE MCM8-MCM9 COMPLEX, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=22771120; DOI=10.1016/j.molcel.2012.05.048;
RA Lutzmann M., Grey C., Traver S., Ganier O., Maya-Mendoza A.,
RA Ranisavljevic N., Bernex F., Nishiyama A., Montel N., Gavois E.,
RA Forichon L., de Massy B., Mechali M.;
RT "MCM8- and MCM9-deficient mice reveal gametogenesis defects and genome
RT instability due to impaired homologous recombination.";
RL Mol. Cell 47:523-534(2012).
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). Required for DNA
CC resection by the MRE11-RAD50-NBN/NBS1 (MRN) complex by recruiting the
CC MRN complex to the repair site and by promoting the complex nuclease
CC activity. Probably by regulating the localization of the MNR complex,
CC indirectly regulates the recruitment of downstream effector RAD51 to
CC DNA damage sites including DBSs and ICLs. The MCM8-MCM9 complex is
CC dispensable for DNA replication and S phase progression. 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) (By
CC similarity). Probably by regulating HR, plays a key role during
CC gametogenesis (PubMed:22771120). Stabilizes MCM9 protein (By
CC similarity). {ECO:0000250|UniProtKB:Q9UJA3,
CC ECO:0000269|PubMed:22771120}.
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:0000250|UniProtKB:Q9UJA3};
CC -!- SUBUNIT: Component of the MCM8-MCM9 complex, which forms a hexamer
CC composed of MCM8 and MCM9. Interacts with the DNA mismatch repair (MMR)
CC complex composed at least of MSH2, MSH3, MSH6, PMS1 and MLH1. Interacts
CC with RAD51; the interaction recruits RAD51 to DNA damage sites.
CC Interacts with the MRN complex composed of MRE11, RAD50 and NBN/NBS1.
CC Interacts with CDC6 and ORC2. Interacts with HROB; the interaction
CC recruits the MCM8-MCM9 complex to DNA damage sites (By similarity).
CC {ECO:0000250|UniProtKB:Q9UJA3}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9UJA3}.
CC Chromosome {ECO:0000250|UniProtKB:Q9UJA3}. Note=Localizes to nuclear
CC foci. Localizes to double-stranded DNA breaks. Binds chromatin
CC throughout the cell cycle. {ECO:0000250|UniProtKB:Q9UJA3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9CWV1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9CWV1-2; Sequence=VSP_015786;
CC -!- DISRUPTION PHENOTYPE: Mice are viable but are sterile due to defects in
CC double-strand break repair during gametogenesis. Testes are apoptotic
CC and contain spermatocytes that have persistent DNA damage and
CC unsynapsed chromosomes due to defective homologous recombinatio.
CC Ovaries are characterized by an early block of follicle development,
CC and they later develop tumors. {ECO:0000269|PubMed:22771120}.
CC -!- SIMILARITY: Belongs to the MCM family. {ECO:0000305}.
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DR EMBL; AK010365; BAB26885.1; -; mRNA.
DR EMBL; AK133858; BAE21892.1; -; mRNA.
DR EMBL; AL929562; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466519; EDL28362.1; -; Genomic_DNA.
DR EMBL; BC046780; AAH46780.1; -; mRNA.
DR EMBL; BC052070; AAH52070.1; -; mRNA.
DR CCDS; CCDS16778.1; -. [Q9CWV1-2]
DR CCDS; CCDS71152.1; -. [Q9CWV1-1]
DR RefSeq; NP_001277983.1; NM_001291054.1. [Q9CWV1-1]
DR RefSeq; NP_079952.2; NM_025676.4. [Q9CWV1-2]
DR AlphaFoldDB; Q9CWV1; -.
DR SMR; Q9CWV1; -.
DR BioGRID; 211611; 1.
DR STRING; 10090.ENSMUSP00000066842; -.
DR iPTMnet; Q9CWV1; -.
DR PhosphoSitePlus; Q9CWV1; -.
DR EPD; Q9CWV1; -.
DR MaxQB; Q9CWV1; -.
DR PaxDb; Q9CWV1; -.
DR PeptideAtlas; Q9CWV1; -.
DR PRIDE; Q9CWV1; -.
DR ProteomicsDB; 295711; -. [Q9CWV1-1]
DR ProteomicsDB; 295712; -. [Q9CWV1-2]
DR DNASU; 66634; -.
DR Ensembl; ENSMUST00000028831; ENSMUSP00000028831; ENSMUSG00000027353. [Q9CWV1-1]
DR Ensembl; ENSMUST00000066559; ENSMUSP00000066842; ENSMUSG00000027353. [Q9CWV1-2]
DR GeneID; 66634; -.
DR KEGG; mmu:66634; -.
DR UCSC; uc008mni.2; mouse. [Q9CWV1-2]
DR UCSC; uc008mnj.2; mouse. [Q9CWV1-1]
DR CTD; 84515; -.
DR MGI; MGI:1913884; Mcm8.
DR VEuPathDB; HostDB:ENSMUSG00000027353; -.
DR eggNOG; KOG0480; Eukaryota.
DR GeneTree; ENSGT01050000244972; -.
DR HOGENOM; CLU_000995_7_2_1; -.
DR InParanoid; Q9CWV1; -.
DR OMA; THTVDWQ; -.
DR OrthoDB; 266497at2759; -.
DR PhylomeDB; Q9CWV1; -.
DR TreeFam; TF323155; -.
DR Reactome; R-MMU-176187; Activation of ATR in response to replication stress.
DR Reactome; R-MMU-68689; CDC6 association with the ORC:origin complex.
DR Reactome; R-MMU-68949; Orc1 removal from chromatin.
DR Reactome; R-MMU-68962; Activation of the pre-replicative complex.
DR BioGRID-ORCS; 66634; 14 hits in 110 CRISPR screens.
DR ChiTaRS; Mcm8; mouse.
DR PRO; PR:Q9CWV1; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9CWV1; protein.
DR Bgee; ENSMUSG00000027353; Expressed in embryonic post-anal tail and 155 other tissues.
DR Genevisible; Q9CWV1; MM.
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:0005634; C:nucleus; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0003678; F:DNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0032406; F:MutLbeta complex binding; ISO:MGI.
DR GO; GO:0032407; F:MutSalpha complex binding; ISO:MGI.
DR GO; GO:0032408; F:MutSbeta complex binding; ISO:MGI.
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; IMP:UniProtKB.
DR GO; GO:0032508; P:DNA duplex unwinding; ISO:MGI.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:UniProtKB.
DR GO; GO:0007292; P:female gamete generation; IMP:UniProtKB.
DR GO; GO:0048232; P:male gamete generation; IMP:UniProtKB.
DR GO; GO:0071168; P:protein localization to chromatin; ISO:MGI.
DR GO; GO:0050821; P:protein stabilization; ISO:MGI.
DR GO; GO:0036298; P:recombinational interstrand cross-link repair; ISO:MGI.
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 Alternative splicing; ATP-binding; Cell cycle; Chromosome; DNA damage;
KW DNA repair; DNA replication; DNA-binding; Helicase; Hydrolase;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..833
FT /note="DNA helicase MCM8"
FT /id="PRO_0000194126"
FT DOMAIN 395..602
FT /note="MCM"
FT BINDING 447..454
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 623
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UJA3"
FT VAR_SEQ 50..77
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015786"
FT CONFLICT 379
FT /note="S -> Y (in Ref. 1; BAE21892)"
FT /evidence="ECO:0000305"
FT CONFLICT 550
FT /note="I -> V (in Ref. 4; AAH46780)"
FT /evidence="ECO:0000305"
FT CONFLICT 749
FT /note="F -> L (in Ref. 1; BAB26885)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 833 AA; 92371 MW; B45385BFB778B9E0 CRC64;
MSGAYRGRGF GRGRFQSWKR GRGGGNFSGR WRERENRVDL NEASGKHASA QASQPLLQQS
TLDQFIPYKG WKLYFSEVYS NNSPFIEKIQ AFEKFFTRHI DLYDKDEIER KGSILVDFKE
LTKADEITNL IPDIENALRD APEKTLACMG LAIHQVLTKD LERHAAELQA QEGLSNGGET
MVNVPHIYAR VYNYEPLTHL KNIRATCYGK YISIRGTVVR VSNIKPLCTN MAFQCAACGE
IQSFPLPDGK YTLPTKCPVP ACRGRSFAPL RSSPLTVTLD WQLIKIQELM SDAQREAGRI
PRTIECELVH DLVDSCVPGD TVTVTGIVKV SNSEEGSRNK NDKCMFLLYI EANSVSNSKG
PKAQTAEDGC KHGTLMEFSL KDLYAIREIQ AEENLLKLVV NSLCPVIFGH ELVKAGLTLA
LFGGSQKYAD DKNRIPIRGD PHVLIVGDPG LGKSQMLQAA CNVAPRGVYV CGNTTTSSGL
TVTLSKDSSS GDFALEAGAL VLGDQGICGI DEFDKMGNQH QALLEAMEQQ SISLAKAGVV
CSLPARTSII AAANPVGGHY NKARTVSENL KMGSALLSRF DLVFILLDTP NEQHDHLLSE
HVIAIRAGKQ KAVSSATVTR VLSQDSNTSV LEVVSEKPLS ERLKVAPGEQ TDPIPHQLLR
KYIGYARQYV HPRLSTDAAQ ALQDFYLELR KQSQRVGSSP ITTRQLESLI RLTEARARLE
LREEATREDA EDIIEIMKHS MLGTYSDEFG NLDFERSQHG SGMSNRSTAK RFISALNSIA
ERTYNNIFQY HQLRQIAKEL NIQVADFENF IGSLNDQGYL LKKGPKIYQL QTM
