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TP53 TP53 MSH6 MSH6 DNMT1 DNMT1 MCM7 MCM7 CCDC6 CCDC6 E2F1 E2F1 CDK2 CDK2 CDC45 CDC45 H2AFZ H2AFZ RAF1 RAF1 WEE1 WEE1 SUV39H1 SUV39H1 CCNE1 CCNE1 CCNE2 CCNE2 POLE2 POLE2 CCNA2 CCNA2 CCNB2 CCNB2 RBBP4 RBBP4 PCNA PCNA RPA2 RPA2 RB1 RB1 TYMS TYMS POLE POLE DHFR DHFR POLA1 POLA1 RRM2 RRM2 CDKN1A CDKN1A MYC MYC SMC2 SMC2 RPA1 RPA1 SIN3A SIN3A MAPK13 MAPK13 CDK1 CDK1 NPAT NPAT MCM3 MCM3 RFC3 RFC3 DCK DCK RRM1 RRM1 RPA3 RPA3 RABIF RABIF SKP2 SKP2 FAF1 FAF1 HMGB2 HMGB2 SAP30 SAP30 PRKDC PRKDC CCND1 CCND1 CHEK1 CHEK1 E2F2 E2F2 SMC1A SMC1A CDKN1B CDKN1B CCNB1 CCNB1 E2F3 E2F3 HLTF HLTF CCND3 CCND3 SMC3 SMC3 BARD1 BARD1 TTK TTK ORC1 ORC1 MCM6 MCM6 PLK4 PLK4 MCM4 MCM4 FANCG FANCG TOP2A TOP2A SMARCA2 SMARCA2 ABL1 ABL1 RFC5 RFC5 RBBP7 RBBP7 KIF4A KIF4A PRMT2 PRMT2 TFDP1 TFDP1 CDK6 CDK6 CDC25B CDC25B CDC7 CDC7 PRIM1 PRIM1 HDAC1 HDAC1 TFDP2 TFDP2 MDM2 MDM2 CDC25A CDC25A
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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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query proteins and first shell of interactors
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second shell of interactors
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proteins of unknown 3D structure
filled nodes:
a 3D structure is known or predicted
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Known Interactions
from curated databases
experimentally determined
Predicted Interactions
gene neighborhood
gene fusions
gene co-occurrence
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textmining
co-expression
protein homology
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TP53Cellular tumor antigen p53; Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. Its pro-apoptotic activity is activated via its intera [...] (386 aa)
MSH6DNA mismatch repair protein; Component of the post-replicative DNA mismatch repair system (MMR). (1262 aa)
DNMT1DNA (cytosine-5)-methyltransferase 1; Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In a [...] (1644 aa)
MCM7DNA replication licensing factor MCM7; 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 differential [...] (719 aa)
CCDC6Coiled-coil domain containing 6. (477 aa)
E2F1E2F transcription factor 1. (437 aa)
CDK2Cyclin-dependent kinase 2; Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK [...] (298 aa)
CDC45Cell division cycle 45. (616 aa)
H2AFZHistone H2A.Z; Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post- translational modifications of histones, also called histone code, and nucleosome remodeling. May be involved in the formation of constitutive heterochromatin. May be required for c [...] (128 aa)
RAF1RAF proto-oncogene serine/threonine-protein kinase; Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal- regulated kin [...] (668 aa)
WEE1Wee1-like protein kinase. (646 aa)
SUV39H1Histone-lysine N-methyltransferase SUV39H1; Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3 using monomethylated H3 'Lys-9' as substrate. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin at pericentric and telomere regions. H3 'Lys-9' trimethylation is also required to direct DNA methylation at pericentric re [...] (412 aa)
CCNE1Cyclin E1; Belongs to the cyclin family. (411 aa)
CCNE2G1/S-specific cyclin-E2; Essential for the control of the cell cycle at the late G1 and early S phase; Belongs to the cyclin family. Cyclin E subfamily. (404 aa)
POLE2DNA polymerase epsilon subunit 2; Accessory component of the DNA polymerase epsilon complex (By similarity). Participates in DNA repair and in chromosomal DNA replication (By similarity). (527 aa)
CCNA2Cyclin-A2; Cyclin which controls both the G1/S and the G2/M transition phases of the cell cycle. Functions through the formation of specific serine/threonine kinase holoenzyme complexes with the cyclin-dependent protein kinases CDK1 and CDK2. The cyclin subunit confers the substrate specificity of these complexes and differentially interacts with and activates CDK1 and CDK2 throughout the cell cycle. (429 aa)
CCNB2G2/mitotic-specific cyclin-B2; Essential for the control of the cell cycle at the G2/M (mitosis) transition. (398 aa)
RBBP4Histone-binding protein RBBP4; Core histone-binding subunit that may target chromatin assembly factors, chromatin remodeling factors and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA. Component of several complexes which regulate chromatin metabolism. These include the chromatin assembly factor 1 (CAF-1) complex, which is required for chromatin assembly following DNA replication and DNA repair; the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression; the nucleosome re [...] (425 aa)
PCNAProliferating cell nuclear antigen; Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'- phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA rep [...] (261 aa)
RPA2Replication protein A2, 32kDa. (270 aa)
RB1RB transcriptional corepressor 1. (928 aa)
TYMSThymidylate synthase; Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. (354 aa)
POLEDNA polymerase epsilon catalytic subunit; DNA polymerase II participates in chromosomal DNA replication; Belongs to the DNA polymerase type-B family. (2289 aa)
DHFRDihydrofolate reductase; Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFR2 (By similarity). (187 aa)
POLA1DNA polymerase. (1468 aa)
RRM2Ribonucleotide reductase regulatory subunit M2. (389 aa)
CDKN1ACyclin dependent kinase inhibitor 1A. (161 aa)
MYCMyc proto-oncogene protein; Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Activates the transcription of growth-related genes. Binds to the VEGFA promoter, promoting VEGFA production and subsequent sprouting angiogenesis. Regulator of somatic reprogramming, controls self-renewal of embryonic stem cells. Functions with TAF6L to activate target gene expression through RNA polymerase II pause release (By similarity). (439 aa)
SMC2Structural maintenance of chromosomes protein. (1191 aa)
RPA1Replication protein A subunit; As part of the heterotrimeric replication protein A complex (RPA/RP-A), binds and stabilizes single-stranded DNA intermediates, that form during DNA replication or upon DNA stress. It prevents their reannealing and in parallel, recruits and activates different proteins and complexes involved in DNA metabolism. Thereby, it plays an essential role both in DNA replication and the cellular response to DNA damage. (616 aa)
SIN3ASIN3 transcription regulator family member A. (1274 aa)
MAPK13Mitogen-activated protein kinase 13; Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK13 is one of the less studie [...] (366 aa)
CDK1Cyclin-dependent kinase 1; Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition, and regulates G1 progress and G1-S transition via association with multiple interphase cyclins. Required in higher cells for entry into S-phase and mitosis. Phosphorylates PARVA/actopaxin, APC, AMPH, APC, BARD1, Bcl-xL/BCL2L1, BRCA2, CALD1, CASP8, CDC7, CDC20, CDC25A, CDC25C, CC2D1A, CENPA, CSNK2 proteins/CKII, FZR1/CDH1, CDK7, CEBPB, CHAMP1, DMD/dystrophin, EEF1 proteins/EF-1, EZH2, KIF11/EG5, EGFR, FANCG, FOS, G [...] (297 aa)
NPATNuclear protein, coactivator of histone transcription. (1433 aa)
MCM3DNA replication licensing factor MCM3; 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 differential [...] (808 aa)
RFC3Replication factor C subunit 3; The elongation of primed DNA templates by DNA polymerase delta and epsilon requires the action of the accessory proteins proliferating cell nuclear antigen (PCNA) and activator 1. (356 aa)
DCKDeoxycytidine kinase; Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). (260 aa)
RRM1Ribonucleoside-diphosphate reductase; Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. (791 aa)
RPA3Replication protein A3, 14kDa. (121 aa)
RABIFRAB interacting factor. (123 aa)
SKP2SKP2 protein. (424 aa)
FAF1Fas (TNFRSF6) associated factor 1. (650 aa)
HMGB2High mobility group protein B2; Multifunctional protein with various roles in different cellular compartments. May act in a redox sensitive manner. In the nucleus is an abundant chromatin-associated non-histone protein involved in transcription, chromatin remodeling and V(D)J recombination and probably other processes (By similarity). Binds DNA with a preference to non-canonical DNA structures such as single-stranded DNA. Can bent DNA and enhance DNA flexibility by looping thus providing a mechanism to promote activities on various gene promoters by enhancing transcription factor bindi [...] (209 aa)
SAP30Sin3A associated protein 30. (220 aa)
PRKDCProtein kinase, DNA-activated, catalytic subunit; Belongs to the PI3/PI4-kinase family. (4124 aa)
CCND1G1/S-specific cyclin-D1; Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. A [...] (428 aa)
CHEK1Checkpoint kinase 1. (677 aa)
E2F2E2F transcription factor 2. (432 aa)
SMC1AStructural maintenance of chromosomes protein 1A; Involved in chromosome cohesion during cell cycle and in DNA repair. Involved in DNA repair via its interaction with BRCA1 and its related phosphorylation by ATM, and works as a downstream effector in the ATM/NBS1 branch of S-phase checkpoint (By similarity). Central component of cohesin complex. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and [...] (1233 aa)
CDKN1BCyclin dependent kinase inhibitor 1B. (198 aa)
CCNB1G2/mitotic-specific cyclin-B1; Essential for the control of the cell cycle at the G2/M (mitosis) transition; Belongs to the cyclin family. Cyclin AB subfamily. (427 aa)
E2F3E2F transcription factor 3. (463 aa)
HLTFHelicase like transcription factor. (1009 aa)
CCND3G1/S-specific cyclin-D3; Regulatory component of the cyclin D3-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. A [...] (292 aa)
SMC3Structural maintenance of chromosomes protein 3; Central component of cohesin, a complex required for chromosome cohesion during the cell cycle. The cohesin complex may form a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. Cohesion is coupled to DNA replication and is involved in DNA repair. The cohesin complex plays also an important role in spindle pole assembly during mitosis and in chromosomes movement; Belongs to the SMC family. SMC3 subfamily. (1217 aa)
BARD1BRCA1 associated RING domain 1. (773 aa)
TTKTTK protein kinase. (916 aa)
ORC1Origin recognition complex subunit 1; Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The specific DNA sequences that define origins of replication have not been identified yet. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication (By similarity); Belongs to the ORC1 family. (863 aa)
MCM6DNA replication licensing factor MCM6; 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 differential [...] (821 aa)
PLK4Serine/threonine-protein kinase PLK4; Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CENPJ/CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit [...] (893 aa)
MCM4DNA helicase; Belongs to the MCM family. (836 aa)
FANCGFA complementation group G. (570 aa)
TOP2ADNA topoisomerase 2; Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double- strand breaks. (1532 aa)
SMARCA2SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 2. (1554 aa)
ABL1Tyrosine-protein kinase. (1151 aa)
RFC5Replication factor C subunit 5. (516 aa)
RBBP7Histone-binding protein RBBP7; Core histone-binding subunit that may target chromatin remodeling factors, histone acetyltransferases and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA. Component of several complexes which regulate chromatin metabolism. These include the type B histone acetyltransferase (HAT) complex, which is required for chromatin assembly following DNA replication; the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression; the nucleosome remodeling and [...] (469 aa)
KIF4AKinesin motor domain-containing protein; Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. (1234 aa)
PRMT2Protein arginine methyltransferase 2; Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family. (480 aa)
TFDP1Transcription factor Dp-1; Can stimulate E2F-dependent transcription. Binds DNA cooperatively with E2F family members 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 E2F1:DP complex appears to mediate both cell proliferation and apoptosis. Blocks adipocyte differentiation by repressing CEBPA binding to its target gene promoters (By similarity). (410 aa)
CDK6Cyclin dependent kinase 6; Belongs to the protein kinase superfamily. (326 aa)
CDC25BCell division cycle 25B. (574 aa)
CDC7Cell division cycle 7 homolog (S. cerevisiae). (576 aa)
PRIM1DNA primase; Belongs to the eukaryotic-type primase small subunit family. (427 aa)
HDAC1Histone deacetylase 1; Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. Upon calcium st [...] (513 aa)
TFDP2Transcription factor. (450 aa)
MDM2E3 ubiquitin-protein ligase Mdm2; Belongs to the MDM2/MDM4 family. (492 aa)
CDC25AM-phase inducer phosphatase 1; 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 (By similarity). (525 aa)
Your Current Organism:
Bos taurus
NCBI taxonomy Id: 9913
Other names: B. taurus, Bos bovis, Bos primigenius taurus, Bovidae sp. Adi Nefas, bovine, cattle, cow, dairy cow, domestic cattle, domestic cow
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