ID   MCM2_XENLA              Reviewed;         886 AA.
AC   P55861; O42588; Q7ZX05;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   13-JUN-2006, sequence version 2.
DT   27-MAR-2024, entry version 138.
DE   RecName: Full=DNA replication licensing factor mcm2;
DE            EC=3.6.4.12 {ECO:0000250|UniProtKB:P49736};
DE   AltName: Full=BM28-homolog;
DE   AltName: Full=Minichromosome maintenance protein 2;
DE            Short=xMCM2;
DE   AltName: Full=p112;
GN   Name=mcm2;
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], AND IDENTIFICATION IN A COMPLEX WITH MCM5.
RC   TISSUE=Oocyte;
RX   PubMed=8917078; DOI=10.1016/0378-1119(96)00122-9;
RA   Miyake S., Saito I., Kobayashi H., Yamashita S.;
RT   "Identification of two Xenopus laevis genes, xMCM2 and xCDC46, with
RT   sequence homology to MCM genes involved in DNA replication.";
RL   Gene 175:71-75(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, IDENTIFICATION IN A COMPLEX WITH
RP   MMCM3; MCM4; MCM5; MMCM6 AND MCM7, AND SUBCELLULAR LOCATION.
RC   TISSUE=Oocyte;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Embryo;
RG   NIH - Xenopus Gene Collection (XGC) project;
RL   Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4]
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   [5]
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   [6]
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   [7]
RP   FUNCTION OF THE MCM2-7 COMPLEX, AND IDENTIFICATION IN A COMPLEX WITH MMCM3;
RP   MCM4; MCM5; MMCM6 AND 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   [8]
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   [9]
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   [10]
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 a component of the MCM2-7 complex (MCM complex) which
CC       is the replicative helicase essential for 'once per cell cycle' DNA
CC       replication initiation and elongation in eukaryotic cells. Core
CC       component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that
CC       unwinds template DNA during replication, and around which the replisome
CC       is built. The active ATPase sites in the MCM2-7 ring are formed through
CC       the interaction surfaces of two neighboring subunits such that a
CC       critical structure of a conserved arginine finger motif is provided in
CC       trans relative to the ATP-binding site of the Walker A box of the
CC       adjacent subunit. The six ATPase active sites, however, are likely to
CC       contribute differentially to the complex helicase activity. Required
CC       for the entry in S phase and for cell division.
CC       {ECO:0000269|PubMed:16369567, ECO:0000269|PubMed:9214646,
CC       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:P49736};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066;
CC         Evidence={ECO:0000250|UniProtKB:P49736};
CC   -!- SUBUNIT: Component of the mcm2-7 complex (RLF-M) (PubMed:16369567,
CC       PubMed:8917078, PubMed:9214646, PubMed:9214647, PubMed:9851868). The
CC       complex forms a toroidal hexameric ring with the proposed subunit order
CC       mcm2-mcm6-mcm4-mcm7-mcm3-mcm5 (PubMed:16369567, PubMed:8917078,
CC       PubMed:9214646, PubMed:9214647, PubMed:9851868). Component of the
CC       replisome complex (By similarity). Component of the CMG helicase
CC       complex, composed of the mcm2-7 complex, the GINS complex and cdc45
CC       (PubMed:30979826, PubMed:30842657). {ECO:0000250|UniProtKB:P49736,
CC       ECO:0000269|PubMed:16369567, ECO:0000269|PubMed:30842657,
CC       ECO:0000269|PubMed:30979826, ECO:0000269|PubMed:8917078,
CC       ECO:0000269|PubMed:9214646, ECO:0000269|PubMed:9214647,
CC       ECO:0000269|PubMed:9851868}.
CC   -!- INTERACTION:
CC       P55861; P49739: mmcm3; NbExp=9; IntAct=EBI-876864, EBI-491720;
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: May be in a phosphorylated state in the mitotic mcm complex.
CC       Phosphorylated in the interphase mcm complex. Phosphorylated by the
CC       cdc7-dbf4 and cdc7-dbf4b complexes. {ECO:0000269|PubMed:10779356,
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:P49736}.
CC   -!- SIMILARITY: Belongs to the MCM family. {ECO:0000305}.
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DR   EMBL; D63919; BAA09948.1; -; mRNA.
DR   EMBL; U44047; AAC60223.1; -; mRNA.
DR   EMBL; BC046274; AAH46274.1; -; mRNA.
DR   PIR; JC5085; JC5085.
DR   RefSeq; NP_001080759.1; NM_001087290.2.
DR   PDB; 8Q6O; EM; 3.14 A; 2/A=1-886.
DR   PDB; 8Q6P; EM; 3.53 A; 2=1-886.
DR   PDBsum; 8Q6O; -.
DR   PDBsum; 8Q6P; -.
DR   AlphaFoldDB; P55861; -.
DR   EMDB; EMD-18191; -.
DR   EMDB; EMD-18192; -.
DR   EMDB; EMD-18195; -.
DR   SMR; P55861; -.
DR   BioGRID; 98693; 13.
DR   ComplexPortal; CPX-2943; MCM complex.
DR   IntAct; P55861; 7.
DR   MINT; P55861; -.
DR   iPTMnet; P55861; -.
DR   MaxQB; P55861; -.
DR   DNASU; 380451; -.
DR   GeneID; 380451; -.
DR   KEGG; xla:380451; -.
DR   AGR; Xenbase:XB-GENE-999979; -.
DR   CTD; 380451; -.
DR   Xenbase; XB-GENE-999979; mcm2.L.
DR   OMA; NGFPVFF; -.
DR   OrthoDB; 5476523at2759; -.
DR   Proteomes; UP000186698; Chromosome 4L.
DR   Bgee; 380451; Expressed in oocyte and 18 other cell types or 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:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0004386; F:helicase activity; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; 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:0006279; P:premeiotic DNA replication; IDA:ComplexPortal.
DR   GO; GO:0030174; P:regulation of DNA-templated DNA replication initiation; IDA:UniProtKB.
DR   CDD; cd17753; MCM2; 1.
DR   Gene3D; 2.20.28.10; -; 1.
DR   Gene3D; 3.30.1640.10; mini-chromosome maintenance (MCM) complex, chain A, domain 1; 1.
DR   Gene3D; 2.40.50.140; Nucleic acid-binding proteins; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR   InterPro; IPR031327; MCM.
DR   InterPro; IPR008045; MCM2.
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; DNA REPLICATION LICENSING FACTOR MCM FAMILY MEMBER; 1.
DR   PANTHER; PTHR11630:SF44; DNA REPLICATION LICENSING FACTOR MCM2; 1.
DR   Pfam; PF00493; MCM; 1.
DR   Pfam; PF12619; MCM2_N; 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; PR01658; MCMPROTEIN2.
DR   SMART; SM00350; MCM; 1.
DR   SUPFAM; SSF50249; Nucleic acid-binding proteins; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   PROSITE; PS00847; MCM_1; 1.
DR   PROSITE; PS50051; MCM_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Cell cycle; Chromosome; DNA replication;
KW   DNA-binding; Helicase; Hydrolase; Metal-binding; Nucleotide-binding;
KW   Nucleus; Reference proteome; Zinc; Zinc-finger.
FT   CHAIN           1..886
FT                   /note="DNA replication licensing factor mcm2"
FT                   /id="PRO_0000194089"
FT   DOMAIN          458..665
FT                   /note="MCM"
FT   ZN_FING         314..340
FT                   /note="C4-type"
FT                   /evidence="ECO:0000255"
FT   REGION          1..65
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          77..104
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          120..151
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           640..643
FT                   /note="Arginine finger"
FT   COMPBIAS        1..20
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        42..59
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        120..143
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         515
FT                   /ligand="ADP"
FT                   /ligand_id="ChEBI:CHEBI:456216"
FT                   /ligand_note="ligand shared with MCM6"
FT                   /evidence="ECO:0000250|UniProtKB:P49736"
FT   BINDING         516
FT                   /ligand="ADP"
FT                   /ligand_id="ChEBI:CHEBI:456216"
FT                   /ligand_note="ligand shared with MCM6"
FT                   /evidence="ECO:0000250|UniProtKB:P49736"
FT   CONFLICT        169
FT                   /note="E -> K (in Ref. 2; AAC60223)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        439
FT                   /note="G -> R (in Ref. 1; BAA09948)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        563
FT                   /note="L -> F (in Ref. 1; BAA09948)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        728
FT                   /note="M -> I (in Ref. 1; BAA09948)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   886 AA;  100262 MW;  524C7B3673E2B2DD CRC64;
     MADSSESFNI ATSPRAGSRR DALTSSPGRD LPPFEDESEG MFGDGVVPEE EEDGEELIGD
     AMERDYRPIS ELDRYEVEGL DDEEDVEDLT ASQREAAEQS MRMRDREMGR ELGRMRRGLL
     YDSDEEEEDR PARKRRMAER AAEGAPEEDE EMIESIENLE DMKGHTVREW VSMAATRLEI
     YHRFKNFLRT HVDEHGHNVF KEKISDMCKE NKESLPVNYE DLAAREHVLA YFLPEAPAEM
     LKIFDEAAKE VVLVMYPKYD RIAREIHVRI SHLPLVEELR SLRQLHLNQL IRTSGVVTCC
     TGVLPQLSMV KYNCNKCNFI LGPFFQSQNQ EVRPGSCPEC QSFGPFEINM EETVYQNYQR
     ITIQESPGKV AAGRLPRSKD AILLADLVDS CKPGDEIELT GIYHNNYDGS LNTANGFPVF
     ATVILANHIT KKDDKVAVGE LTDEDVKAIV ALSKDERIGE RIFASIAPSI YGHEDIKRGL
     ALALFGGEAK NPGGKHKVRG DINVLLCGDP GTAKSQFLKY VEKVASRAVF TTGQGASAVG
     LTAYVQRHPV TKEWTLEAGA LVLADRGVCL IDEFDKMNDQ DRTSIHEAME QQSISISKAG
     IVTSLQARCT VIAASNPIGG RYDPSLTFSE NVDLTEPIVS RFDILCVVRD TVDPVQDEML
     ARFVVSSHIK HHPSSKDIAN GDAAEFALPN TFGVEALPQE VLKKYIMYAK EKIRPKLNQM
     DQDKVAKMYS DLRKESMATG SIPITVRHIE SMIRMAEAHA RMHLRDYVVE DDVNMAIRVM
     LESFIDTQKF SVMRSMRKTF ARYLAFRRDN NELLLFVLKQ LIAEQVTYQR NRYGAQQDTI
     EVPEKDLVDK ARQINIHNLS AFYDSDLFKM NKFTHDVKKK LIIQQF
//