MCM4A_XENLA
ID MCM4A_XENLA Reviewed; 858 AA.
AC Q5XK83; O42589;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=DNA replication licensing factor mcm4-A;
DE EC=3.6.4.12 {ECO:0000250|UniProtKB:P49717};
DE AltName: Full=CDC21 homolog-A;
DE AltName: Full=Minichromosome maintenance protein 4-A;
DE Short=xMCM4-A;
DE AltName: Full=P1-CDC21-A;
DE AltName: Full=p98;
GN Name=mcm4-a;
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] {ECO:0000305, ECO:0000312|EMBL:AAC60225.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, IDENTIFICATION IN A COMPLEX WITH
RP MCM2; MMCM3; MCM5; MMCM6 AND MCM7, AND SUBCELLULAR LOCATION.
RC TISSUE=Oocyte {ECO:0000269|PubMed:9214647};
RX PubMed=9214647; DOI=10.1093/emboj/16.11.3320;
RA Kubota Y., Mimura S., Nishimoto S., Masuda T., Nojima H., Takisawa H.;
RT "Licensing of DNA replication by a multi-protein complex of MCM/P1 proteins
RT in Xenopus eggs.";
RL EMBO J. 16:3320-3331(1997).
RN [2] {ECO:0000312|EMBL:AAH83031.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo {ECO:0000312|EMBL:AAH83031.1};
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305}
RP FUNCTION, IDENTIFICATION IN RLF-M COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=9214646; DOI=10.1093/emboj/16.11.3312;
RA Thommes P., Kubota Y., Takisawa H., Blow J.J.;
RT "The RLF-M component of the replication licensing system forms complexes
RT containing all six MCM/P1 polypeptides.";
RL EMBO J. 16:3312-3319(1997).
RN [4]
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 [5]
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 [6]
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:9214646, ECO:0000269|PubMed:9214647}.
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:9214646,
CC PubMed:9214647). The complex forms a toroidal hexameric ring with the
CC proposed subunit order mcm2-mcm6-mcm4-mcm7-mcm3-mcm5 (PubMed:9214646,
CC PubMed:9214647). The heterodimer of mmcm3/mcm5 interacts with mcm4,
CC mmcm6, mcm7 and weakly with mcm2 (PubMed:9214646, PubMed:9214647).
CC Component of the CMG helicase complex, composed of the mcm2-7 complex,
CC the GINS complex and cdc45 (PubMed:30979826, PubMed:30842657).
CC {ECO:0000269|PubMed:30842657, ECO:0000269|PubMed:30979826,
CC ECO:0000269|PubMed:9214646, ECO:0000269|PubMed:9214647}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9214646,
CC ECO:0000269|PubMed:9214647}. Chromosome {ECO:0000269|PubMed:9214646,
CC ECO:0000269|PubMed:9214647}. Note=Associated with chromatin before the
CC formation of nuclei and detaches from it as DNA replication progresses.
CC {ECO:0000269|PubMed:9214646, ECO:0000269|PubMed:9214647}.
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 (By similarity).
CC Phosphorylated by the cdc7-dbf4b complex. {ECO:0000250,
CC ECO:0000269|PubMed:16204181}.
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 -!- SEQUENCE CAUTION:
CC Sequence=AAC60225.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U44049; AAC60225.1; ALT_FRAME; mRNA.
DR EMBL; BC083031; AAH83031.1; -; mRNA.
DR PIR; T47223; T47223.
DR RefSeq; NP_001079069.1; NM_001085600.2.
DR AlphaFoldDB; Q5XK83; -.
DR SMR; Q5XK83; -.
DR BioGRID; 96822; 2.
DR IntAct; Q5XK83; 3.
DR MINT; Q5XK83; -.
DR GeneID; 373601; -.
DR KEGG; xla:373601; -.
DR CTD; 373601; -.
DR Xenbase; XB-GENE-6252896; mcm4.S.
DR Proteomes; UP000186698; Chromosome 6S.
DR Bgee; 373601; Expressed in testis 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; ISS: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..858
FT /note="DNA replication licensing factor mcm4-A"
FT /id="PRO_0000240594"
FT DOMAIN 453..662
FT /note="MCM"
FT /evidence="ECO:0000255"
FT ZN_FING 301..326
FT /note="C4-type"
FT /evidence="ECO:0000255"
FT REGION 1..125
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 637..640
FT /note="Arginine finger"
FT COMPBIAS 46..98
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 505..512
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT CONFLICT 354
FT /note="E -> G (in Ref. 1; AAC60225)"
FT /evidence="ECO:0000305"
FT CONFLICT 663
FT /note="A -> V (in Ref. 1; AAC60225)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 858 AA; 96635 MW; 11812FE311FE5CF9 CRC64;
MSSPTSTPSR RKSKRGRGSN PPTPRGEEVQ SPPSQKRRTE DSTSIGELLP MPTSPSGDIQ
SPLFSSPAPS RHSAHQSELD LSSPLTYGTP SSRVEGTPRS GIRGTPARQR ADLGSARKVK
QVDLHSDQPA AEELVTSEQS LGQKLVIWGT DVNVAICKEK FQRFVQRFID PLAKEEENVG
LDLNEPIYMQ RLEEINVVGE PFLNIDCDHL RSFDQDLYRQ LVCYPQEVIP TFDMAANEIF
FERYPDSILE HQIQVRPYNA LKTRNMRSLN PEDIDQLITI SGMVIRTSQI IPEMQESFFK
CQVCAFTTRV EIDRGRIAEP SVCKHCNTTH SMALIHNRSM FSDKQMIKLQ ESPEDMPAGQ
TPHTTILYAH NDLVDKVQPG DRVNVTGIYR AVPIRVNPRV RNVKSVYKTH IDVIHYRKTD
SKRLHGIDED TEQKMFTEER VAVLKELAAK PDIYERLAAA LAPSIYEHED IKKGILLQLF
GGTRKDFSHT GRGKFRAEVN ILLCGDPGTS KSQLLQYVYN LVPRGQYTSG KGSSAVGLTA
YVMKDPETRQ LVLQTGALVL SDNGICCIDE FDKMNESTRS VLHEVMEQQT LSIAKAGIIC
QLNARTSVLA AANPVESQWN PKKTTIENIQ LPHTLLSRFD LIFLMLDPQD ETYDRRLAHH
LVALYYQSEE QLKEEHLDMA VLKDYIAYAR TYVNPRLGEE ASQALIEAYV DMRKIGSGRG
MVSAYPRQLE SLIRLSEAHA KVRFSSKVET IDVEEAKRLH REALKQSATD PRTGIVDISI
LTTGMSATAR KRKEELAQVL KKLIQSKGKT PAFKYQQLFE DLRGQSDAAI TKDMFDEALH
ALADEDYLTV TGKTVRLL
