MCM4B_XENLA
ID MCM4B_XENLA Reviewed; 863 AA.
AC P30664; Q6GQ77; Q91679;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 27-JUN-2006, sequence version 3.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=DNA replication licensing factor mcm4-B;
DE EC=3.6.4.12 {ECO:0000250|UniProtKB:P49717};
DE AltName: Full=CDC21 homolog-B;
DE AltName: Full=Minichromosome maintenance protein 4-B;
DE Short=xMCM4-B;
DE AltName: Full=P1-CDC21-B;
GN Name=mcm4-b;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RC TISSUE=Oocyte;
RX PubMed=8605878; DOI=10.1002/j.1460-2075.1996.tb00446.x;
RA Coue M., Kearsey S.E., Mechali M.;
RT "Chromotin binding, nuclear localization and phosphorylation of Xenopus
RT cdc21 are cell-cycle dependent and associated with the control of
RT initiation of DNA replication.";
RL EMBO J. 15:1085-1097(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION IN A COMPLEX WITH MMCM3 AND
RP MCM5, AND PHOSPHORYLATION.
RC TISSUE=Embryo;
RX PubMed=8901561; DOI=10.1073/pnas.93.22.12223;
RA Hendrickson M., Madine M., Dalton S., Gautier J.;
RT "Phosphorylation of MCM4 by cdc2 protein kinase inhibits the activity of
RT the minichromosome maintenance complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:12223-12228(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 513-588.
RX PubMed=1454522; DOI=10.1093/nar/20.21.5571;
RA Coxon A., Maundrell K., Kearsey S.E.;
RT "Fission yeast cdc21+ belongs to a family of proteins involved in an early
RT step of chromosome replication.";
RL Nucleic Acids Res. 20:5571-5577(1992).
RN [5]
RP IDENTIFICATION IN A COMPLEX WITH ZMCM6, AND DEVELOPMENTAL STAGE.
RC TISSUE=Embryo;
RX PubMed=9512418; DOI=10.1016/s0960-9822(98)70136-8;
RA Sible J.C., Erikson E., Hendrickson M., Maller J.L., Gautier J.;
RT "Developmental regulation of MCM replication factors in Xenopus laevis.";
RL Curr. Biol. 8:347-350(1998).
RN [6]
RP IDENTIFICATION IN MCM COMPLEXES.
RX PubMed=9851868; DOI=10.1006/excr.1998.4271;
RA Coue M., Amariglio F., Maiorano D., Bocquet S., Mechali M.;
RT "Evidence for different MCM subcomplexes with differential binding to
RT chromatin in Xenopus.";
RL Exp. Cell Res. 245:282-289(1998).
RN [7]
RP PHOSPHORYLATION.
RX PubMed=10779356; DOI=10.1128/mcb.20.10.3667-3676.2000;
RA Pereverzeva I., Whitmire E., Khan B., Coue M.;
RT "Distinct phosphoisoforms of the Xenopus Mcm4 protein regulate the function
RT of the Mcm complex.";
RL Mol. Cell. Biol. 20:3667-3676(2000).
RN [8]
RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH MCM2; MMCM3; MCM5; MMCM6 AND
RP MCM7.
RX PubMed=16369567; DOI=10.1038/sj.emboj.7600892;
RA Ying C.Y., Gautier J.;
RT "The ATPase activity of MCM2-7 is dispensable for pre-RC assembly but is
RT required for DNA unwinding.";
RL EMBO J. 24:4334-4344(2005).
RN [9]
RP PHOSPHORYLATION.
RX PubMed=16204181; DOI=10.1101/gad.1339805;
RA Takahashi T.S., Walter J.C.;
RT "Cdc7-Drf1 is a developmentally regulated protein kinase required for the
RT initiation of vertebrate DNA replication.";
RL Genes Dev. 19:2295-2300(2005).
RN [10]
RP IDENTIFICATION IN THE CMG HELICASE COMPLEX.
RX PubMed=30979826; DOI=10.26508/lsa.201900390;
RA Priego Moreno S., Jones R.M., Poovathumkadavil D., Scaramuzza S.,
RA Gambus A.;
RT "Mitotic replisome disassembly depends on TRAIP ubiquitin ligase
RT activity.";
RL Life. Sci Alliance 2:0-0(2019).
RN [11]
RP IDENTIFICATION IN THE CMG HELICASE COMPLEX.
RX PubMed=30842657; DOI=10.1038/s41586-019-1002-0;
RA Wu R.A., Semlow D.R., Kamimae-Lanning A.N., Kochenova O.V., Chistol G.,
RA Hodskinson M.R., Amunugama R., Sparks J.L., Wang M., Deng L., Mimoso C.A.,
RA Low E., Patel K.J., Walter J.C.;
RT "TRAIP is a master regulator of DNA interstrand crosslink repair.";
RL Nature 567:267-272(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.
CC {ECO:0000269|PubMed:16369567}.
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 (RLF-M) (PubMed:16369567,
CC PubMed:8901561, PubMed:9851868). The complex forms a toroidal hexameric
CC ring with the proposed subunit order mcm2-mcm6-mcm4-mcm7-mcm3-mcm5
CC (PubMed:16369567, PubMed:8901561, PubMed:9851868). The heterodimer of
CC mmcm3/mcm5 interacts with mcm4, mmcm6, mcm7 and weakly with mcm2
CC (PubMed:16369567, PubMed:8901561, PubMed:9851868). Begins to associate
CC with zmcm6 at the neurula stage (PubMed:9512418). Component of the CMG
CC helicase complex, composed of the mcm2-7 complex, the GINS complex and
CC cdc45 (PubMed:30842657). {ECO:0000269|PubMed:16369567,
CC ECO:0000269|PubMed:30842657, ECO:0000269|PubMed:8901561,
CC ECO:0000269|PubMed:9512418, ECO:0000269|PubMed:9851868}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:8605878}. Chromosome
CC {ECO:0000269|PubMed:8605878}. Note=Associated with chromatin before the
CC formation of nuclei and detaches from it as DNA replication progresses.
CC {ECO:0000269|PubMed:30979826, ECO:0000269|PubMed:8605878}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout development.
CC {ECO:0000269|PubMed:9512418}.
CC -!- PTM: Hyperphosphorylated during mitosis in a mechanism requiring cdc2-
CC cyclin B and other kinases. Undergoes dephosphorylation after exiting
CC mitosis, existing in a partially phosphorylated state in the cytosolic
CC interphase mcm complex which associates with the pre-replication
CC complexes (pre-Rcs). Complete dephosphorylation inactivates the mcm
CC complex, preventing its binding to chromatin. Becomes actively
CC phosphorylated during S phase once the mcm complex is assembled on the
CC chromatin. This chromatin-associated phosphorylation occurs during the
CC activation of the pre-Rcs and is independent of cdks. Phosphorylated by
CC the cdc7-dbf4b complex. {ECO:0000269|PubMed:10779356,
CC ECO:0000269|PubMed:16204181, ECO:0000269|PubMed:8605878,
CC ECO:0000269|PubMed:8901561}.
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:0000305}.
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DR EMBL; U29178; AAB01680.1; -; mRNA.
DR EMBL; U46131; AAA91232.1; -; mRNA.
DR EMBL; BC072870; AAH72870.1; -; mRNA.
DR EMBL; Z15033; CAA78751.1; -; Genomic_DNA.
DR PIR; S64720; S64720.
DR RefSeq; NP_001081448.1; NM_001087979.1.
DR AlphaFoldDB; P30664; -.
DR SMR; P30664; -.
DR BioGRID; 99182; 1.
DR ComplexPortal; CPX-2943; MCM complex.
DR IntAct; P30664; 2.
DR GeneID; 397843; -.
DR KEGG; xla:397843; -.
DR CTD; 397843; -.
DR Xenbase; XB-GENE-1011486; mcm4.L.
DR OMA; KNTIRIC; -.
DR OrthoDB; 266497at2759; -.
DR Proteomes; UP000186698; Chromosome 6L.
DR Bgee; 397843; Expressed in ovary and 19 other tissues.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0071162; C:CMG complex; IDA:UniProtKB.
DR GO; GO:0042555; C:MCM complex; 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:CAFA.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
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:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006270; P:DNA replication initiation; IEA:InterPro.
DR GO; GO:0006268; P:DNA unwinding involved in DNA replication; IDA:UniProtKB.
DR GO; GO:0030174; P:regulation of DNA-templated DNA replication initiation; IDA:UniProtKB.
DR Gene3D; 2.40.50.140; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
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; 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..863
FT /note="DNA replication licensing factor mcm4-B"
FT /id="PRO_0000194103"
FT DOMAIN 458..667
FT /note="MCM"
FT ZN_FING 306..331
FT /note="C4-type"
FT /evidence="ECO:0000255"
FT REGION 1..130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 642..645
FT /note="Arginine finger"
FT COMPBIAS 46..103
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 510..517
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT CONFLICT 73
FT /note="A -> V (in Ref. 1; AAB01680)"
FT /evidence="ECO:0000305"
FT CONFLICT 524
FT /note="F -> Y (in Ref. 4; CAA78751)"
FT /evidence="ECO:0000305"
FT CONFLICT 539
FT /note="S -> G (in Ref. 4; CAA78751)"
FT /evidence="ECO:0000305"
FT CONFLICT 554
FT /note="R -> G (in Ref. 4; CAA78751)"
FT /evidence="ECO:0000305"
FT CONFLICT 740..741
FT /note="LS -> RA (in Ref. 1; AAB01680)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 863 AA; 97123 MW; CA05A827EE16803D CRC64;
MSSPTSTPSR RRNKRGRGSN PPTPHGEEVQ SPPSQRRRTE DSTSIGELLP MPTSPSGDVQ
SPSGQELLFS SPAPSRHSAH QSELDLSSPL TYGTPSSRVE GTPRSGIRGT PARQRPDLGS
ARKVKQVDLH SDQPAAEELV TSEQSLGQKL VIWGTDVNVA TCKEKFQRFV QRFIDPSAKE
EDNVGLDLNE PIYMQRLEEI NVVGDPFLNI DCDHLRNFDQ DLYRQLVCYP QEVIPTFDMA
ANEIFFERYP DSILEHQIQV RPYNALKTRN MRSLNPEDID QLITISGMVI RTSQIIPEMQ
EAFFKCQVCA FTTRVEIDRG RIAEPSVCKH CNTTHSMALI HNRSMFSDKQ MIKLQESPED
MPAGQTPHTT ILYGHNDLVD KVQPGDRVNV TGIYRAVPIR VNPRVRNVKS VYKTHIDVIH
YRKTDSKRLH GIDEDTEQKL FTEERVAMLK ELAAKPDIYE RLAAALAPSI YEHEDIKKGI
LLQLFGGTRK DFSHTGRGKF RAEVNILLCG DPGTSKSQLL QYVFNLVPRG QYTSGKGSSA
VGLTAYVMKD PETRQLVLQT GALVLSDNGI CCIDEFDKMN ESTRSVLHEV MEQQTLSIAK
AGIICQLNAR TSVLAAANPV ESQWNPKKTT IENIQLPHTL LSRFDLIFLM LDPQDEAYDR
RLAHHLVALY YQSEEQMKEE HLDMAVLKDY IAYARTYVNP RLSEEASQAL IEAYVSMRKI
GSGRGMVSAY PRQLESLIRL SEAHAKVRFS NKVETIDVEE AKRLHREALK QSATDPRTGI
VDISILTTGM SATARKRKEE LAQVLKKLIQ SKGKTPALKY QQLFEDLRGQ SDAAITKDMF
DEALHALADD DYLTVTGKTV RLL
