ID:MCM4_HUMAN DESCRIPTION: RecName: Full=DNA replication licensing factor MCM4; EC=3.6.4.12; AltName: Full=CDC21 homolog; AltName: Full=P1-CDC21; FUNCTION: Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate. SUBUNIT: Component of the MCM2-7 complex. The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6- MCM4-MCM7-MCM3-MCM5 (By simililarity). Interacts with MCMBP. INTERACTION: P33993:MCM7; NbExp=6; IntAct=EBI-374938, EBI-355924; Q9Q2G4:ORF (xeno); NbExp=3; IntAct=EBI-374938, EBI-6248094; SUBCELLULAR LOCATION: Nucleus (By similarity). MISCELLANEOUS: Early fractionation of eukaryotic MCM proteins yielded a variety of dimeric, trimeric and tetrameric complexes with unclear biological significance. Specifically a MCM467 subcomplex is shown to have in vitro helicase activity which is inhibited by the MCM2 subunit. The MCM2-7 hexamer is the proposed physiological active complex. SIMILARITY: Belongs to the MCM family. SIMILARITY: Contains 1 MCM domain. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/mcm4/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P33991
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000082 G1/S transition of mitotic cell cycle GO:0006260 DNA replication GO:0006268 DNA unwinding involved in DNA replication GO:0006270 DNA replication initiation GO:0007049 cell cycle
BC038772 - Homo sapiens cDNA clone IMAGE:5270727, **** WARNING: chimeric clone ****. AK309812 - Homo sapiens cDNA, FLJ99853. AK296913 - Homo sapiens cDNA FLJ54365 complete cds, highly similar to DNA replication licensing factor MCM4. AK022899 - Homo sapiens cDNA FLJ12837 fis, clone NT2RP2003228, highly similar to DNA replication licensing factor MCM4. X74794 - H.sapiens P1-Cdc21 mRNA. BC031061 - Homo sapiens minichromosome maintenance complex component 4, mRNA (cDNA clone MGC:33310 IMAGE:5273457), complete cds. AB590735 - Synthetic construct DNA, clone: pFN21AE2132, Homo sapiens MCM4 gene for minichromosome maintenance complex component 4, without stop codon, in Flexi system. AM493756 - Homo sapiens partial mRNA for minichromosome maintenance protein 4 (MCM4 gene) isolated from bone marrow. JD536007 - Sequence 517031 from Patent EP1572962. DQ587614 - Homo sapiens piRNA piR-54726, complete sequence. JD396793 - Sequence 377817 from Patent EP1572962. JD189252 - Sequence 170276 from Patent EP1572962. JD481292 - Sequence 462316 from Patent EP1572962. JD209027 - Sequence 190051 from Patent EP1572962. JD431366 - Sequence 412390 from Patent EP1572962. JD257085 - Sequence 238109 from Patent EP1572962. JD204596 - Sequence 185620 from Patent EP1572962. JD428822 - Sequence 409846 from Patent EP1572962. JD502424 - Sequence 483448 from Patent EP1572962. JD036853 - Sequence 17877 from Patent EP1572962. JD041453 - Sequence 22477 from Patent EP1572962. JD041454 - Sequence 22478 from Patent EP1572962. JD321214 - Sequence 302238 from Patent EP1572962. JD388686 - Sequence 369710 from Patent EP1572962. JD388687 - Sequence 369711 from Patent EP1572962. JD517216 - Sequence 498240 from Patent EP1572962. JD105047 - Sequence 86071 from Patent EP1572962. JD531396 - Sequence 512420 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_mcmPathway - CDK Regulation of DNA Replication
Reactome (by CSHL, EBI, and GO)
Protein P33991 (Reactome details) participates in the following event(s):
R-HSA-68849 Mcm2-7 associates with the Cdt1:CDC6:ORC:origin complex, forming the pre-replicative complex (preRC) R-HSA-68954 Mcm2-7 is phosphorylated by DDK R-HSA-69019 Mcm4,6,7 trimer forms and associates with the replication fork R-HSA-176942 Multiple proteins are localized at replication fork R-HSA-68919 Mcm10 associates with the pre-replicative complex, stabilizing Mcm2-7 R-HSA-68944 Orc1 is phosphorylated by cyclin A/CDK2 R-HSA-169468 MCM2-7 mediated fork unwinding R-HSA-68940 Cdt1 is displaced from the pre-replicative complex. R-HSA-68918 CDK and DDK associate with the Mcm10:pre-replicative complex R-HSA-68917 Cdc45 associates with the pre-replicative complex at the origin R-HSA-68916 DNA Replication Factor A (RPA) associates with the pre-replicative complex at the origin R-HSA-176318 Loading of claspin onto DNA during replication origin firing R-HSA-176298 Activation of claspin R-HSA-68867 Assembly of the pre-replicative complex R-HSA-68962 Activation of the pre-replicative complex R-HSA-69052 Switching of origins to a post-replicative state R-HSA-176974 Unwinding of DNA R-HSA-68949 Orc1 removal from chromatin R-HSA-69002 DNA Replication Pre-Initiation R-HSA-69206 G1/S Transition R-HSA-69239 Synthesis of DNA R-HSA-69190 DNA strand elongation R-HSA-68874 M/G1 Transition R-HSA-453279 Mitotic G1-G1/S phases R-HSA-69242 S Phase R-HSA-69306 DNA Replication R-HSA-69278 Cell Cycle (Mitotic) R-HSA-176187 Activation of ATR in response to replication stress R-HSA-1640170 Cell Cycle R-HSA-69481 G2/M Checkpoints R-HSA-69620 Cell Cycle Checkpoints