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E2F3 E2F3 LRWD1 LRWD1 RB1 RB1 CDKN1B CDKN1B E2F2 E2F2 CDKN1A CDKN1A CCNE1 CCNE1 ORC3 ORC3 ORC2 ORC2 PRIM1 PRIM1 ORC6 ORC6 FZR1 FZR1 ORC4 ORC4 ORC5 ORC5 MCM4 MCM4 CDT1 CDT1 RPA1 RPA1 CDC25A CDC25A MCM5 MCM5 CCNB1 CCNB1 DBF4 DBF4 CDC45 CDC45 CDC7 CDC7 GMNN GMNN CLSPN CLSPN ATR ATR
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Network nodes represent proteins
splice isoforms or post-translational modifications are collapsed, i.e. each node represents all the proteins produced by a single, protein-coding gene locus.
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small nodes:
protein of unknown 3D structure
large protein node
large nodes:
some 3D structure is known or predicted
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colored nodes:
query proteins and first shell of interactors
non-colored protein node
white nodes:
second shell of interactors
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Edges represent protein-protein associations
associations are meant to be specific and meaningful, i.e. proteins jointly contribute to a shared function; this does not necessarily mean they are physically binding each other.
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from curated databases
experiment edge
experimentally determined
Predicted Interactions
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gene neighborhood
fusion edge
gene fusions
cooccurrence edge
gene co-occurrence
Others
textmining edge
textmining
coexpression edge
co-expression
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MCM5minichromosome maintenance complex component 5; 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 dif [...] (734 aa)
ORC6origin recognition complex, subunit 6; Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent, however specific DNA sequences that define origins of replication have not been identified so far. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication (252 aa)
CDKN1Bcyclin-dependent kinase inhibitor 1B (p27, Kip1); Important regulator of cell cycle progression. Involved in G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1- CDK4 complex activation. Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or stoichometry (198 aa)
GMNNgeminin, DNA replication inhibitor; Inhibits DNA replication by preventing the incorporation of MCM complex into pre-replication complex (pre-RC). It is degraded during the mitotic phase of the cell cycle. Its destruction at the metaphase-anaphase transition permits replication in the succeeding cell cycle (209 aa)
ORC2origin recognition complex, subunit 2; Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent, however specific DNA sequences that define origins of replication have not been identified so far. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication (577 aa)
CDC7cell division cycle 7 homolog (S. cerevisiae); Seems to phosphorylate critical substrates that regulate the G1/S phase transition and/or DNA replication. Can phosphorylates MCM2 and MCM3 (574 aa)
CDKN1Acyclin-dependent kinase inhibitor 1A (p21, Cip1); May be the important intermediate by which p53/TP53 mediates its role as an inhibitor of cellular proliferation in response to DNA damage. Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin- dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D- CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex (164 aa)
RPA1replication protein A1, 70kDa; Plays an essential role in several cellular processes in DNA metabolism including replication, recombination and DNA repair. Binds and subsequently stabilizes single-stranded DNA intermediates and thus prevents complementary DNA from reannealing (616 aa)
CCNB1cyclin B1; Essential for the control of the cell cycle at the G2/M (mitosis) transition (433 aa)
ORC3origin recognition complex, subunit 3 (712 aa)
MCM4minichromosome maintenance complex component 4; 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 dif [...] (863 aa)
CCNE1cyclin E1; Essential for the control of the cell cycle at the G1/S (start) transition (410 aa)
E2F3E2F transcription factor 3; Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5’-TTTC[CG]CGC- 3’ found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The DRTF1/E2F complex functions in the control of cell-cycle progression from G1 to S phase. E2F3 binds specifically to RB1 in a cell-cycle dependent manner (465 aa)
ORC4origin recognition complex, subunit 4; Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent, however specific DNA sequences that define origins of replication have not been identified so far. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication (436 aa)
DBF4DBF4 homolog (S. cerevisiae); Regulatory subunit for CDC7 which activates its kinase activity thereby playing a central role in DNA replication and cell proliferation. Required for progression of S phase. The complex CDC7-DBF4A selectively phosphorylates MCM2 subunit at ’Ser-40’ and ’Ser-53’ and then is involved in regulating the initiation of DNA replication during cell cycle (674 aa)
RB1retinoblastoma 1; Key regulator of entry into cell division that acts as a tumor suppressor. Promotes G0-G1 transition when phosphorylated by CDK3/cyclin-C. Acts as a transcription repressor of E2F1 target genes. The underphosphorylated, active form of RB1 interacts with E2F1 and represses its transcription activity, leading to cell cycle arrest. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV39H1, SUV [...] (928 aa)
LRWD1leucine-rich repeats and WD repeat domain containing 1; Associated component of the origin recognition complex (ORC) required to recruit and stabilize the ORC complex to chromatin. Probably required for the association of ORC on chromatin during G1 to establish pre-replication complex (preRC) and to heterochromatic sites in post-replicated cells. Binds a combination of DNA and histone methylation repressive marks on heterochromatin- binds histone H3 and H4 trimethylation marks H3K9me3, H3K27me3 and H4K20me3 in a cooperative manner with DNA methylation. It is unclear whether it recogniz [...] (647 aa)
ORC5origin recognition complex, subunit 5; Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent, however specific DNA sequences that define origins of replication have not been identified so far. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication (435 aa)
CDT1chromatin licensing and DNA replication factor 1; Cooperates with CDC6 to promote the loading of the mini- chromosome maintenance complex onto chromatin to form the pre- replication complex necessary to initiate DNA replication. Binds DNA in a sequence-, strand-, and conformation-independent manner. Potential oncogene (546 aa)
CDC25Acell division cycle 25 homolog A (S. pombe); Tyrosine protein phosphatase which functions as a dosage-dependent inducer of mitotic progression. Directly dephosphorylates CDK1 and stimulates its kinase activity. Also dephosphorylates CDK2 in complex with cyclin E, in vitro (524 aa)
CLSPNclaspin; Required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication or to DNA damage induced by both ionizing and UV irradiation. Adapter protein which binds to BRCA1 and the checkpoint kinase CHEK1 and facilitates the ATR- dependent phosphorylation of both proteins. Can also bind specifically to branched DNA structures and may associate with S- phase chromatin following formation of the pre-replication complex (pre-RC). This may indicate a role for this protein as a sensor which monitors the integrity of DNA replication forks (1339 aa)
ATRataxia telangiectasia and Rad3 related; Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates BRCA1, CHEK1, MCM2, RAD17, RPA2, SMC1 and p53/TP53, which collectively inhibit DNA replication and mitosis and promote DNA repair, recombination and apoptosis. Phosphorylates ’Ser-139’ of histone variant H2AX/H2AFX at sites of DNA damage, thereby regulating DNA damag [...] (2644 aa)
PRIM1primase, DNA, polypeptide 1 (49kDa); DNA primase is the polymerase that synthesizes small RNA primers for the Okazaki fragments made during discontinuous DNA replication (420 aa)
E2F2E2F transcription factor 2; Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5’-TTTC[CG]CGC- 3’ found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The DRTF1/E2F complex functions in the control of cell-cycle progression from g1 to s phase. E2F2 binds specifically to RB1 in a cell-cycle dependent manner (437 aa)
FZR1fizzy/cell division cycle 20 related 1 (Drosophila) (496 aa)
CDC45cell division cycle 45 homolog (S. cerevisiae); Required for initiation of chromosomal DNA replication (598 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, Homo, Homo sapiens, human, man
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