Gene Report

Basic Information

Approved Symbol	MCM7
Approved Name	minichromosome maintenance complex component 7
Previous Symbol	MCM2
Previous Name	"minichromosome maintenance deficient (S. cerevisiae) 7", "MCM7 minichromosome maintenance deficient 7 (S. cerevisiae)"
Symbol Alias	CDC47
Location	7q21.3-q22.1
Position	chr7:99698918-99699115 (-)
External Links	Entrez Gene: 4176 Ensembl: ENSG00000166508 UCSC: uc003usw.1 HGNC ID: 6950
No. of Studies (Positive/Negative)	1(1/0)
Type	Literature-origin

Positive relationships between MCM7 and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
MCM7	Aston, 2005	patients and normal controls		Genes altered in major depressive disorder Genes altered in major depressive disorder

Positive relationships between MCM7 and other components at different levels (count: 0)

Positive relationship network of MCM7 in MK4MDD

Network loading ...

Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between MCM7 and MDD (count: 0)

Negative relationships between MCM7 and other components at different levels (count: 0)

MCM7 related SNPs in MK4MDD (count: 0)

MCM7 related proteins in MK4MDD (count: 0)

MCM7 related GO terms (count: 29)

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0005515	protein binding	molecular function	IPI[9705868\|10518787\|12364596\|15232106\|15538388\|15654075\|16289477\|16438930\|16899510\|17296731\|17310990\|17314511\|19150984\|22540012\|23397142\|23764002\|24299456\|25036637\|25416956\|26496610]
GO:0071364	cellular response to epidermal growth factor stimulus	biological process	IEA
GO:0042493	response to drug	biological process	IEA
GO:0004003	ATP-dependent DNA helicase activity	molecular function	IDA[9305914]
GO:0006270	DNA replication initiation	biological process	IEA
GO:0000278	mitotic cell cycle	biological process	TAS
GO:0008283	cell proliferation	biological process	IEA
GO:0042555	MCM complex	cellular component	IDA[17296731]; IMP[15538388]
GO:0000784	nuclear chromosome, telomeric region	cellular component	IDA[19135898]
GO:0032553	ribonucleotide binding	molecular function	IEA
GO:0032553	ribonucleotide binding	molecular function	IEA
GO:0000785	chromatin	cellular component	TAS[8798650]
GO:0003677	DNA binding	molecular function	TAS[15538388]
GO:0032553	ribonucleotide binding	molecular function	IEA
GO:0032553	ribonucleotide binding	molecular function	IEA
GO:0006271	DNA strand elongation involved in DNA replication	biological process	TAS
GO:0005654	nucleoplasm	cellular component	IDA; TAS
GO:0003697	single-stranded DNA binding	molecular function	IEA
GO:0016020	membrane	cellular component	IDA[19946888]
GO:0042325	regulation of phosphorylation	biological process	IMP[15538388]
GO:0005524	ATP binding	molecular function	IEA
GO:0005829	cytosol	cellular component	IEA
GO:0071466	cellular response to xenobiotic stimulus	biological process	IEA
GO:0006974	cellular response to DNA damage stimulus	biological process	IMP[15538388]
GO:0000082	G1/S transition of mitotic cell cycle	biological process	TAS
GO:0006268	DNA unwinding involved in DNA replication	biological process	IEA
GO:0032553	ribonucleotide binding	molecular function	IEA
GO:0006260	DNA replication	biological process	TAS
GO:0005737	cytoplasm	cellular component	IDA

MCM7 related KEGG pathways (count: 2)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa03030	dna replication	DNA replication	A complex network of interacting proteins and enzymes is req...... A complex network of interacting proteins and enzymes is required for DNA replication. Generally, DNA replication follows a multistep enzymatic pathway. At the DNA replication fork, a DNA helicase (DnaB or MCM complex) precedes the DNA synthetic machinery and unwinds the duplex parental DNA in cooperation with the SSB or RPA. On the leading strand, replication occurs continuously in a 5 to 3 direction, whereas on the lagging strand, DNA replication occurs discontinuously by synthesis and joining of short Okazaki fragments. In prokaryotes, the leading strand replication apparatus consists of a DNA polymerase (pol III core), a sliding clamp (beta), and a clamp loader (gamma delta complex). The DNA primase (DnaG) is needed to form RNA primers. Normally, during replication of the lagging-strand DNA template, an RNA primer is removed either by an RNase H or by the 5 to 3 exonuclease activity of DNA pol I, and the DNA ligase joins the Okazaki fragments. In eukaryotes, three DNA polymerases (alpha, delta, and epsilon) have been identified. DNA primase forms a permanent complex with DNA polymerase alpha. PCNA and RFC function as a clamp and a clamp loader. FEN 1 and RNase H1 remove the RNA from the Okazaki fragments and DNA ligase I joins the DNA. More...
hsa04110	cell cycle	Cell cycle	Mitotic cell cycle progression is accomplished through a rep...... Mitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cyclin-dependent kinases (CDKs) are key regulatory enzymes, each consisting of a catalytic CDK subunit and an activating cyclin subunit. CDKs regulate the cell's progression through the phases of the cell cycle by modulating the activity of key substrates. Downstream targets of CDKs include transcription factor E2F and its regulator Rb. Precise activation and inactivation of CDKs at specific points in the cell cycle are required for orderly cell division. Cyclin-CDK inhibitors (CKIs), such as p16Ink4a, p15Ink4b, p27Kip1, and p21Cip1, are involved in the negative regulation of CDK activities, thus providing a pathway through which the cell cycle is negatively regulated. Eukaryotic cells respond to DNA damage by activating signaling pathways that promote cell cycle arrest and DNA repair. In response to DNA damage, the checkpoint kinase ATM phosphorylates and activates Chk2, which in turn directly phosphorylates and activates p53 tumor suppressor protein. p53 and its transcriptional targets play an important role in both G1 and G2 checkpoints. ATR-Chk1-mediated protein degradation of Cdc25A protein phosphatase is also a mechanism conferring intra-S-phase checkpoint activation. More...

MCM7 related BioCarta pathways (count: 1)

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
MCM_PATHWAY	mcm pathway	CDK Regulation of DNA Replication	Initiation of DNA replication in eukaryotes is a highly cons...... Initiation of DNA replication in eukaryotes is a highly conserved, multi-step process (replication licensing) designed to restrict initiation events to once per replication origin per S phase. Its control has been uncovered by the discovery of the cyclin dependent kinases (CDKs) as master regulators of the cell cycle and the initiator proteins of DNA replication, such as the Origin Recognition Complex (ORC), Cdc6/18, Cdt1 and the mini-chromosome maintenance complex (Mcm). The proteins and the sequence of events involved in this process are conserved throughout the eukaryotic kingdom. First, the ORC comprised of six proteins binds to replication origins in the chromosomal DNA. At the end of mitosis, ORC, Cdc6/18 and Cdt1 assist the binding of Mcm proteins 27 to chromatin, and chromatin becomes licensed for replication. The activated Mcm complex functions as a replicating helicase and moves along with the replication fork to bring the origins to the unlicensed state. The cycling of CDK activity in the cell cycle regulates the two states of replication origins, the licensed state in G1-phase and the unlicensed state for the rest of the cell cycle. The restriction on licensing is relieved when CDK falls off at the completion of mitosis to allow a new round of replication. More...

MCM7 related Reactome pathways (count: 14)

ID	Name	Description
Gene mapped Reactome pathways
REACT_734	dna replication_pre_initiation	Although, DNA replication occurs in the S phase of the cell ...... Although, DNA replication occurs in the S phase of the cell cycle, the formation of the DNA replication pre-initiation complex begins during late G1/M transition. More...
REACT_1095	activation of_the_pre_replicative_complex	In S. cerevisiae, two ORC subunits, Orc1 and Orc5, both bind...... In S. cerevisiae, two ORC subunits, Orc1 and Orc5, both bind ATP, and Orc1 in addition has ATPase activity. Both ATP binding and ATP hydrolysis appear to be essential functions in vivo. ATP binding by Orc1 is unaffected by the association of ORC with origin DNA (ARS) sequences, but ATP hydrolysis is ARS-dependent, being suppressed by associated double-stranded DNA and stimulated by associated single-stranded DNA. These data are consistent with the hypothesis that ORC functions as an ATPase switch, hydrolyzing bound ATP and changing state as DNA unwinds at the origin immediately before replication. It is attractive to speculate that ORC likewise functions as a switch as human pre-replicative complexes are activated, but human Orc proteins are not well enough characterized to allow the model to be critically tested. mRNAs encoding human orthologs of all six Orc proteins have been cloned, and ATP-binding amino acid sequence motifs have been identified in Orc1, Orc4, and Orc5. Interactions among proteins expressed from the cloned genes have been characterized, but the ATP-binding and hydrolyzing properties of these proteins and complexes of them have not been determined. More...
REACT_899	s phase	DNA synthesis occurs in the S phase, or the synthesis phase,...... DNA synthesis occurs in the S phase, or the synthesis phase, of the cell cycle. The cell duplicates its hereditary material, and two copies of the chromosome are formed. As DNA replication continues, the E type cyclins shared by the G1 and S phases, are destroyed and the levels of the mitotic cyclins rise. More...
REACT_1783	g1 s_transition	Cyclin E - Cdk2 complexes control the transition from G1 int...... Cyclin E - Cdk2 complexes control the transition from G1 into S-phase. In this case, the binding of p21Cip1/Waf1 or p27kip1 is inhibitory. Important substrates for Cyclin E - Cdk2 complexes include proteins involved in the initiation of DNA replication. The two Cyclin E proteins are subjected to ubiquitin-dependent proteolysis, under the control of an E3 ubiquitin ligase known as the SCF. Cyclin A - Cdk2 complexes, which are also regulated by p21Cip1/Waf1 and p27kip1, are likely to be important for continued DNA synthesis, and progression into G2. An additional level of control of Cdk2 is reversible phosphorylation of Threonine-14 (T14) and Tyrosine-15 (Y15), catalyzed by the Wee1 and Myt1 kinases, and dephosphorylated by the three Cdc25 phosphatases, Cdc25A, B and C. More...
REACT_2014	synthesis of_dna	The actual synthesis of DNA occurs in the S phase of the cel...... The actual synthesis of DNA occurs in the S phase of the cell cycle. This includes the initiation of DNA replication, when the first nucleotide of the new strand is laid down during the synthesis of the primer. The DNA replication preinitiation events begin in late M or early G1 phase. More...
REACT_152	cell cycle_mitotic	The replication of the genome and the subsequent segregation...... The replication of the genome and the subsequent segregation of chromosomes into daughter cells are controlled by a series of events collectively known as the cell cycle. DNA replication is carried out during a discrete temporal period known as the S (synthesis)-phase, and chromosome segregation occurs during a massive reorganization to cellular architecture at mitosis. Two gap-phases separate these major cell cycle events: G1 between mitosis and S-phase, and G2 between S-phase and mitosis. In the development of the human body, cells can exit the cell cycle for a period and enter a quiescent state known as G0, or terminally differentiate into cells that will not divide again, but undergo morphological development to carry out the wide variety of specialized functions of individual tissues. A family of protein serine/threonine kinases known as the cyclin-dependent kinases (CDKs) controls progression through the cell cycle. As the name suggests, the activity of the catalytic subunit is dependent on binding to a cyclin partner. The human genome encodes several cyclins and several CDKs, with their names largely derived from the order in which they were identified. The oscillation of cyclin abundance is one important mechanism by which these enzymes phosphorylate key substrates to promote events at the relevant time and place. Additional regulatory proteins and post-translational modifications ensure that CDK activity is precisely regulated, frequently confined to a narrow window of activity. More...
REACT_21300	mitotic m_m_g1_phases
REACT_932	dna strand_elongation	Accurate and efficient genome duplication requires coordinat...... Accurate and efficient genome duplication requires coordinated processes to replicate two template strands at eucaryotic replication forks. Knowledge of the fundamental reactions involved in replication fork progression is derived largely from biochemical studies of the replication of simian virus and from yeast genetic studies. Since duplex DNA forms an anti-parallel structure, and DNA polymerases are unidirectional, one of the new strands is synthesized continuously in the direction of fork movement. This strand is designated as the leading strand. The other strand grows in the direction away from fork movement, and is called the lagging strand. Several specific interactions among the various proteins involved in DNA replication underlie the mechanism of DNA synthesis, on both the leading and lagging strands, at a DNA replication fork. These interactions allow the replication enzymes to cooperate in the replication process. More...
REACT_1538	cell cycle_checkpoints	A hallmark of the human cell cycle in normal somatic cells i...... A hallmark of the human cell cycle in normal somatic cells is its precision. This remarkable fidelity is achieved by a number of signal transduction pathways, known as checkpoints, which monitor cell cycle progression ensuring an interdependency of S-phase and mitosis, the integrity of the genome and the fidelity of chromosome segregation. Checkpoints are layers of control that act to delay CDK activation when defects in the division program occur. As the CDKs functioning at different points in the cell cycle are regulated by different means, the various checkpoints differ in the biochemical mechanisms by which they elicit their effect. However, all checkpoints share a common hierarchy of a sensor, signal transducers, and effectors that interact with the CDKs. The stability of the genome in somatic cells contrasts to the almost universal genomic instability of tumor cells. There are a number of documented genetic lesions in checkpoint genes, or in cell cycle genes themselves, which result either directly in cancer or in a predisposition to certain cancer types. Indeed, restraint over cell cycle progression and failure to monitor genome integrity are likely prerequisites for the molecular evolution required for the development of a tumor. Perhaps most notable amongst these is the p53 tumor suppressor gene, which is mutated in >50% of human tumors. Thus, the importance of the checkpoint pathways to human biology is clear. More...
REACT_1725	m g1_transition	Finally, progression out of mitosis and division of the cell...... Finally, progression out of mitosis and division of the cell into two daughters (cytokinesis) requires the inactivation of Cyclin B - Cdc2 by ubiquitin-dependent proteolysis of Cyclin A and B, which is regulated by a large E3 ubiquitin ligase complex known as the Anaphase Promoting Complex (APC). The detailed annotation of the M/G1 transition will be completed in a later version of GK. More...
REACT_828	g2 m_checkpoints	G2/M checkpoints include the checks for damaged DNA, unrepli...... G2/M checkpoints include the checks for damaged DNA, unreplicated DNA, and checks that ensure that the genome is replicated once and only once per cell cycle. If cells pass these checkpoints, they follow normal transition to the M phase. However, if any of these checkpoints fail, mitotic entry is prevented by specific G2/M checkpoint events. The G2/M checkpoints can fail due to the presence of unreplicated DNA or damaged DNA. In such instances, the cyclin-dependent kinase, Cdc2(Cdk1), is maintained in its inactive, phosphorylated state, and mitotic entry is prevented. Events that ensure that origins of DNA replication fire once and only once per cell cycle are also an example of a G2/M checkpoint. In the event of high levels of DNA damage, the cells may also be directed to undergo apopotosis (not covered). More...
REACT_1156	orc1 removal_from_chromatin
REACT_6776	unwinding of_dna	DNA Replication is regulated accurately and precisely by var...... DNA Replication is regulated accurately and precisely by various protein complexes. Many members of the MCM protein family are assembled into the pre-Replication Complexes (pre-RC) at the end of M phase of the cell cycle. DNA helicase activity of some of the MCM family proteins are important for the unwinding of DNA and initiation of replication processes. This section contains four events which have been proved in different eukaryotic experimental systems to involve various proteins for this essential step during DNA Replication. More...
REACT_6769	activation of_atr_in_response_to_replication_stress	Genotoxic stress caused by DNA damage or stalled replication...... Genotoxic stress caused by DNA damage or stalled replication forks can lead to genomic instability. To guard against such instability, genotoxically-stressed cells activate checkpoint factors that halt or slow cell cycle progression. Among the pathways affected are DNA replication by reduction of replication origin firing, and mitosis by inhibiting activation of cyclin-dependent kinases (Cdks). A key factor involved in the response to stalled replication forks is the ATM- and rad3-related (ATR) kinase, a member of the phosphoinositide-3-kinase-related kinase (PIKK) family. Rather than responding to particular lesions in DNA, ATR and its binding partner ATRIP (ATR-interacting protein) sense replication fork stalling indirectly by associating with persistent ssDNA bound by RPA. These structures would be formed, for example, by dissociation of the replicative helicase from the leading or lagging strand DNA polymerase when the polymerase encounters a DNA lesion that blocks DNA synthesis. Along with phosphorylating the downstream transducer kinase Chk1 and the tumor suppressor p53, activated ATR modifies numerous factors that regulate cell cycle progression or the repair of DNA damage. The persistent ssDNA also stimulates recruitment of the RFC-like Rad17Rfc2-5 alternative clamp-loading complex, which subsequently loads the Rad9-Hus1-Rad1 complex onto the DNA. The latter '9-1-1' complex serves to facilitate Chk1 binding to the stalled replication fork, where Chk1 is phosphorylated by ATR and thereby activated. Upon activation, Chk1 can phosphorylate additional substrates including the Cdc25 family of phosphatases (Cdc25A, Cdc25B, and Cdc25C). These enzymes catalyze the removal of inhibitory phosphate residues from cyclin-dependent kinases (Cdks), allowing their activation. In particular, Cdc25A primarily functions at the G1/S transition to dephosphorylate Cdk2 at Thr 14 and Tyr 15, thus positively regulating the Cdk2-cyclin E complex for S-phase entry. Cdc25A also has mitotic functions. Phosphorylation of Cdc25A at Ser125 by Chk1 leads to Cdc25A ubiquitination and degradation, thus inhibiting DNA replication origin firing. In contrast, Cdc25B and Cdc25C regulate the onset of mitosis through dephosphorylation and activation of Cdk1-cyclin B complexes. In response to replication stress, Chk1 phosphorylates Cdc25B and Cdc25C leading to Cdc25B/C complex formation with 14-3-3 proteins. As these complexes are sequestered in the cytoplasm, they are unable to activate the nuclear Cdk1-cyclin B complex for mitotic entry. These events are outlined in the figure. Persistent single-stranded DNA associated with RPA binds claspin (A) and ATR:ATRIP (B), leading to claspin phosphorylation (C). In parallel, the same single-stranded DNA:RPA complex binds RAD17:RFC (D), enabling the loading of RAD9:HUS1:RAD1 (9-1-1) complex onto the DNA (E). The resulting complex of proteins can then repeatedly bind (F) and phosphorylate (G) CHK1, activating multiple copies of CHK1. More...

MCM7 related interactors from protein-protein interaction data in HPRD (count: 37)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
MCM7	CCNH	No	in vivo	11056214
MCM7	ORC3L	No	yeast 2-hybrid	12614612
MCM7	MCM2	No	in vitro;in vivo	10748114 , 10567526 , 8798650 , 12207017 , 15232106
MCM7	RBL1	No	in vitro	9566894
MCM7	RB1	No	in vitro;in vivo;yeast 2-hybrid	9566894
MCM7	SMC1A	No	in vitro;in vivo	16438930
MCM7	RBM8A	Yes	yeast 2-hybrid	16189514
MCM7	MBIP	No	yeast 2-hybrid	16189514
MCM7	FHL2	No	in vitro;yeast 2-hybrid	10649446
MCM7	ORC6L	No	in vitro	15232106
MCM7	HIST3H3	No	in vitro	8798650
MCM7	MCM6	No	in vitro;in vivo;yeast 2-hybrid	12694531 , 12614612 , 16438930
MCM7	UBE3A	No	in vitro;in vivo	9852095
MCM7	MCM3	No	in vitro;in vivo;yeast 2-hybrid	12614612 , 10464337 , 8631321 , 7601140
MCM7	CDC6	No	in vivo	10464337 , 12614612
MCM7	CDK7	No	in vivo	11056214
MCM7	CRLS1	No	in vivo	12771218
MCM7	MCM5	No	in vitro	15232106
MCM7	CDC7	No	yeast 2-hybrid	12614612
MCM7	ORC1L	No	yeast 2-hybrid	12614612
MCM7	PLK1	No	in vitro;in vivo	15654075
MCM7	RPA1	No	yeast 2-hybrid	12614612
MCM7	ORC2L	No	in vitro;yeast 2-hybrid	12614612
MCM7	ORC4L	No	in vitro	15232106
MCM7	MCM4	No	in vitro;in vivo;yeast 2-hybrid	10748114 , 8798650 , 12207017 , 8631321 , 7601140 , 10567526 , 15232106 , 12614612
MCM7	RAD17	No	in vivo;yeast 2-hybrid	15538388
MCM7	DBF4	No	yeast 2-hybrid	12614612
MCM7	RBL2	No	in vitro	9566894
MCM7	CDC45L	No	in vitro	10518787 , 12614612
MCM7	CDKN1B	No	in vitro;in vivo;yeast 2-hybrid	16289477
MCM7	MCM10	No	in vitro	15232106
MCM7	MCM8	No	in vivo	12771218
MCM7	MCM7	Yes	yeast 2-hybrid	12614612
MCM7	NFKBIA	No	in vivo	14743216
MCM7	MNAT1	No	in vitro;yeast 2-hybrid	11056214
MCM7	ORC5L	No	yeast 2-hybrid	12614612
MCM7	TREX1	No	in vitro;in vivo	15210935

Gene Report

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped BioCarta pathways

Gene mapped Reactome pathways