MCM4_CAEEL
ID MCM4_CAEEL Reviewed; 823 AA.
AC Q95XQ8;
DT 18-JAN-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=DNA replication licensing factor mcm-4 {ECO:0000305};
DE EC=3.6.4.12 {ECO:0000250|UniProtKB:Q9NXL9};
GN Name=mcm-4 {ECO:0000312|WormBase:Y39G10AR.14a};
GN Synonyms=let-358 {ECO:0000312|WormBase:Y39G10AR.14a},
GN lin-6 {ECO:0000303|PubMed:21146520};
GN ORFNames=Y39G10AR.14 {ECO:0000312|WormBase:Y39G10AR.14a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=21146520; DOI=10.1016/j.ydbio.2010.12.009;
RA Korzelius J., The I., Ruijtenberg S., Portegijs V., Xu H., Horvitz H.R.,
RA van den Heuvel S.;
RT "C. elegans MCM-4 is a general DNA replication and checkpoint component
RT with an epidermis-specific requirement for growth and viability.";
RL Dev. Biol. 350:358-369(2011).
RN [3]
RP INTERACTION WITH NMAD-1.
RX PubMed=31283754; DOI=10.1371/journal.pgen.1008252;
RA Wang S.Y., Mao H., Shibuya H., Uzawa S., O'Brown Z.K., Wesenberg S.,
RA Shin N., Saito T.T., Gao J., Meyer B.J., Colaiacovo M.P., Greer E.L.;
RT "The demethylase NMAD-1 regulates DNA replication and repair in the
RT Caenorhabditis elegans germline.";
RL PLoS Genet. 15:E1008252-E1008252(2019).
CC -!- FUNCTION: Acts as component of the mcm2-7 complex (mcm complex) which
CC is the putative replicative helicase essential for 'once per cell
CC cycle' DNA replication initiation and elongation in eukaryotic cells.
CC The active ATPase sites in the mcm2-7 ring are formed through the
CC interaction surfaces of two neighboring subunits such that a critical
CC structure of a conserved arginine finger motif is provided in trans
CC relative to the ATP-binding site of the Walker A box of the adjacent
CC subunit. The six ATPase active sites, however, are likely to contribute
CC differentially to the complex helicase activity (By similarity).
CC Required for DNA replication as well as for the subsequent DNA
CC replication checkpoint controlling entry into M phase in embryos and in
CC postembryonic somatic blast cells (PubMed:21146520). Required for
CC normal growth and viability, specifically via tissue-specific
CC expression in the hypodermis (PubMed:21146520).
CC {ECO:0000250|UniProtKB:P33991, ECO:0000269|PubMed:21146520}.
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:P49717};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066;
CC Evidence={ECO:0000250|UniProtKB:P49717};
CC -!- SUBUNIT: Component of the mcm2-7 complex (By similarity). The complex
CC forms a toroidal hexameric ring with the proposed subunit order mcm2-
CC mcm6-mcm4-mcm7-mcm3-mcm5 (By similarity). Interacts with nmad-1
CC (PubMed:31283754). {ECO:0000250|UniProtKB:P33991,
CC ECO:0000269|PubMed:31283754}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21146520}. Chromosome
CC {ECO:0000269|PubMed:21146520}. Note=Colocalizes with chromatin in late
CC anaphase but not in prophase or metaphase.
CC {ECO:0000269|PubMed:21146520}.
CC -!- TISSUE SPECIFICITY: Expressed in dividing cells with some protein being
CC retained in quiescent cells (at protein level).
CC {ECO:0000269|PubMed:21146520}.
CC -!- DEVELOPMENTAL STAGE: Expressed during all stages of development (at
CC protein level). {ECO:0000269|PubMed:21146520}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes embryonic arrest
CC due to continued mitotic DNA segregation despite lack of DNA
CC replication. Suppresses the S-phase checkpoint induced by rnr-1
CC inhibition or by hydroxyurea exposure. {ECO:0000269|PubMed:21146520}.
CC -!- MISCELLANEOUS: Early fractionation of eukaryotic MCM proteins yielded a
CC variety of dimeric, trimeric and tetrameric complexes with unclear
CC biological significance. Specifically a MCM467 subcomplex is shown to
CC have in vitro helicase activity which is inhibited by the MCM2 subunit.
CC The MCM2-7 hexamer is the proposed physiological active complex.
CC {ECO:0000250|UniProtKB:P49717}.
CC -!- SIMILARITY: Belongs to the MCM family. {ECO:0000255,
CC ECO:0000255|RuleBase:RU004070}.
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DR EMBL; BX284601; CCD69913.1; -; Genomic_DNA.
DR RefSeq; NP_490962.1; NM_058561.5.
DR AlphaFoldDB; Q95XQ8; -.
DR SMR; Q95XQ8; -.
DR ComplexPortal; CPX-4482; MCM complex.
DR IntAct; Q95XQ8; 1.
DR STRING; 6239.Y39G10AR.14.1; -.
DR EPD; Q95XQ8; -.
DR PaxDb; Q95XQ8; -.
DR PeptideAtlas; Q95XQ8; -.
DR EnsemblMetazoa; Y39G10AR.14a.1; Y39G10AR.14a.1; WBGene00003156.
DR GeneID; 171793; -.
DR KEGG; cel:CELE_Y39G10AR.14; -.
DR UCSC; Y39G10AR.14.1; c. elegans.
DR CTD; 171793; -.
DR WormBase; Y39G10AR.14a; CE21767; WBGene00003156; mcm-4.
DR eggNOG; KOG0478; Eukaryota.
DR GeneTree; ENSGT01050000244824; -.
DR HOGENOM; CLU_000995_7_2_1; -.
DR InParanoid; Q95XQ8; -.
DR OMA; KNTIRIC; -.
DR OrthoDB; 266497at2759; -.
DR PhylomeDB; Q95XQ8; -.
DR Reactome; R-CEL-68867; Assembly of the pre-replicative complex.
DR Reactome; R-CEL-68949; Orc1 removal from chromatin.
DR Reactome; R-CEL-68962; Activation of the pre-replicative complex.
DR Reactome; R-CEL-69052; Switching of origins to a post-replicative state.
DR PRO; PR:Q95XQ8; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00003156; Expressed in germ line (C elegans) and 4 other tissues.
DR ExpressionAtlas; Q95XQ8; baseline and differential.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0042555; C:MCM complex; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003678; F:DNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003697; F:single-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0006271; P:DNA strand elongation involved in DNA replication; IBA:GO_Central.
DR GO; GO:0006268; P:DNA unwinding involved in DNA replication; IBA:GO_Central.
DR GO; GO:0000727; P:double-strand break repair via break-induced replication; IBA:GO_Central.
DR GO; GO:0008406; P:gonad development; IMP:WormBase.
DR GO; GO:0040011; P:locomotion; IMP:WormBase.
DR GO; GO:1902975; P:mitotic DNA replication initiation; IBA:GO_Central.
DR GO; GO:0007399; P:nervous system development; IMP:WormBase.
DR GO; GO:0030174; P:regulation of DNA-templated DNA replication initiation; IC:ComplexPortal.
DR GO; GO:0000003; P:reproduction; IMP:WormBase.
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; IPR008047; MCM_4.
DR InterPro; IPR018525; MCM_CS.
DR InterPro; IPR001208; MCM_dom.
DR InterPro; IPR041562; MCM_lid.
DR InterPro; IPR027925; MCM_N.
DR InterPro; IPR033762; MCM_OB.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR11630; PTHR11630; 1.
DR PANTHER; PTHR11630:SF66; PTHR11630:SF66; 1.
DR Pfam; PF00493; MCM; 1.
DR Pfam; PF17855; MCM_lid; 1.
DR Pfam; PF14551; MCM_N; 1.
DR Pfam; PF17207; MCM_OB; 1.
DR PRINTS; PR01657; MCMFAMILY.
DR PRINTS; PR01660; MCMPROTEIN4.
DR SMART; SM00382; AAA; 1.
DR SMART; SM00350; MCM; 1.
DR SUPFAM; SSF50249; SSF50249; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00847; MCM_1; 1.
DR PROSITE; PS50051; MCM_2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell cycle; Chromosome; DNA replication; DNA-binding;
KW Helicase; Hydrolase; Metal-binding; Nucleotide-binding; Nucleus;
KW Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..823
FT /note="DNA replication licensing factor mcm-4"
FT /id="PRO_0000438802"
FT DOMAIN 405..729
FT /note="MCM"
FT /evidence="ECO:0000255"
FT ZN_FING 269..294
FT /note="C4-type"
FT /evidence="ECO:0000255"
FT REGION 1..77
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 601..604
FT /note="Arginine finger"
FT /evidence="ECO:0000305"
FT COMPBIAS 1..68
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 469..476
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
SQ SEQUENCE 823 AA; 91572 MW; DD577743F48F816F CRC64;
MPRSNDPAEP QSESADLFAE PSSQHSSMRS GSEQVAGNMS PRSTSSASAL QYGSEMGSVS
QMSSASTLRR GGPRGDLGIA AVDHRTVQIR GMEDEMAGDD GQPRLYVWGT RICVADVQRS
FRDFLTTFKI SQLAEDENMM TGHDEALHEI DVNHPYYMER LLECNDAEVT HINLNLKHLN
AFSEALYRKV IAYPADVIPY LDIVVNEVFA ERFNRTLAQS IELRPFNAQK TRNMRGLNPN
DVDQLITISG MVTRTSSLIP EMRSGYFQCA VCAFGIESEV DKGRIEEPVV CTNCSNTHCF
QLVHNRSVFL DKQVVKLQES PDDMPSGETP HTVSVYAHGS LVESVQPGDR ITVTGIFRAT
GMKVNPKQRA LASVYRTSID ALHFRKMDTS RLHQDNGETI TEERIQQIIE LSKRPDIMDA
LAQSIAPSIY EHDDVKRGLL CLLFGGTRKD DETTNKTKLR SEINILLCGD PGTSKSQMLQ
YVYRLLPRSQ YTSGKGSSAV GLTASVSRDA DTKQLVLQTG ALVLADNGVC CIDEFDKMNE
SARSVLHEVM EQQTLSIAKA GIICQLNARA SVLAAANPVD SKWNRNKTIV ENITLPHTLL
SRFDLIFLIV DAQDEMQDRR LGNHLVSLYF ENDGNQEKTE HVDMNLLRDY IAYAKANIHP
KLSEEASQFI IEKYLFMRKA GAQHGQITAY PRQLESLIRL SEAHAKIRLS QEVSVDDVEK
AFTLWREALK QSAVDPSTGR VDVAILASGM SASGRKAVEA MCEAVLKQLK TAKGFVTSKA
LFHTLKSADK TCQREVFDEA INELSKKESI ARSGDRIRFQ TEA
