Full Link:
  • Version:
  • 10.0 (archived version)
STRINGSTRING
TK1 TK1 E2F6 E2F6 RBBP8 RBBP8 RBPJ RBPJ RRM2 RRM2 SKP2 SKP2 E2F3 E2F3 RB1 RB1 CDKN1A CDKN1A BRCA1 BRCA1 APAF1 APAF1 E2F1 E2F1 TFDP2 TFDP2 SMAD2 SMAD2 RBL1 RBL1 E2F2 E2F2 CDC6 CDC6 SKP1 SKP1 CDKN1B CDKN1B RANBP1 RANBP1 E2F4 E2F4 TRIM28 TRIM28 SIRT1 SIRT1 DYRK1A DYRK1A PRB1 PRB1
Nodes:
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.
Node Size
small protein node
small nodes:
protein of unknown 3D structure
large protein node
large nodes:
some 3D structure is known or predicted
Node Color
colored protein node
colored nodes:
query proteins and first shell of interactors
non-colored protein node
white nodes:
second shell of interactors
Edges:
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.
Known Interactions
database edge
from curated databases
experiment edge
experimentally determined
Predicted Interactions
neighborhood edge
gene neighborhood
fusion edge
gene fusions
cooccurrence edge
gene co-occurrence
Others
textmining edge
textmining
coexpression edge
co-expression
homology edge
protein homology
Your Input:
CDC6cell division cycle 6 homolog (S. cerevisiae); Involved in the initiation of DNA replication. Also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated (560 aa)
SIRT1sirtuin 1; NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell cycle, response to DNA damage, metobolism, apoptosis and autophagy. Can modulate chromatin function through deacetylation of histones and can promote alterations in the methylation of histones and DNA, leading to transcriptional repression. Deacetylates a broad range of transcription factors and coregulators, thereby regulating target gene expression positively and negatively. Se [...] (747 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)
SKP1S-phase kinase-associated protein 1; Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC [...] (163 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)
TRIM28tripartite motif containing 28; Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at ’Lys-9’ (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 ’Lys-9 and ’Lys-14’ acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitm [...] (835 aa)
SMAD2SMAD family member 2; Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD2/SMAD4 complex, activates transcription. May act as a tumor suppressor in colorectal carcinoma. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator (467 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)
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)
SKP2S-phase kinase-associated protein 2, E3 ubiquitin protein ligase; Substrate recognition component of a SCF (SKP1-CUL1-F- box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription. Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. Degradation of CDKN1B/p27kip also requires CKS1. Recognizes target proteins ORC1, CDT1, RBL2, MLL, CDK9, RAG2, FOXO1, UBP43, and probably MYC, TOB1 and [...] (424 aa)
TK1thymidine kinase 1, soluble (234 aa)
RBBP8retinoblastoma binding protein 8; Endonuclease that cooperates with the MRE11-RAD50-NBN (MRN) complex in processing meiotic and mitotic double-strand breaks (DSBs) by ensuring both resection and intrachromosomal association of the broken ends. Functions downstream of the MRN complex and ATM, promotes ATR activation and its recruitment to DSBs in the S/G2 phase facilitating the generation of ssDNA. Component of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage. Promotes microhomology-mediated alternative end joining (A-NHEJ) d [...] (897 aa)
RANBP1RAN binding protein 1; Inhibits GTP exchange on Ran. Forms a Ran-GTP-RANBP1 trimeric complex. Increase GTP hydrolysis induced by the Ran GTPase activating protein RANGAP1. May act in an intracellular signaling pathway which may control the progression through the cell cycle by regulating the transport of protein and nucleic acids across the nuclear membrane (201 aa)
RBPJrecombination signal binding protein for immunoglobulin kappa J region; Transcriptional regulator that plays a central role in Notch signaling, a signaling pathway involved in cell-cell communication that regulates a broad spectrum of cell-fate determinations. Acts as a transcriptional repressor when it is not associated with Notch proteins. When associated with some NICD product of Notch proteins (Notch intracellular domain), it acts as a transcriptional activator that activates transcription of Notch target genes. Probably represses or activates transcription via the recruitment of c [...] (500 aa)
E2F1E2F transcription factor 1; 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. E2F1 binds preferentially RB1 in a cell-cycle dependent manner. It can mediate both cell proliferation and TP53/p53-dependent apoptosis (437 aa)
RRM2ribonucleotide reductase M2; Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. Inhibits Wnt signaling (449 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)
RBL1retinoblastoma-like 1 (p107); Key regulator of entry into cell division. 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 SUV420H1 and SUV420H2, leading to epigenetic transcriptional repression. Controls histone H4 ’Lys-20’ trimethylation. Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters. Potent inhibitor of E2F-mediated trans-activation. Forms a complex with [...] (1068 aa)
E2F4E2F transcription factor 4, p107/p130-binding; 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. E2F4 binds with high affinity to RBL1 and RBL2. In some instances can also bind RB1 (413 aa)
E2F6E2F transcription factor 6; Inhibitor of E2F-dependent transcription. Binds DNA cooperatively with DP proteins through the E2 recognition site, 5’-TTTC[CG]CGC-3’. Has a preference for the 5’-TTTCCCGC-3’ E2F recognition site. E2F6 lacks the transcriptional activation and pocket protein binding domains. Appears to regulate a subset of E2F-dependent genes whose products are required for entry into the cell cycle but not for normal cell cycle progression. May silence expression via the recruitment of a chromatin remodeling complex containing histone H3-K9 methyltransferase activity. Overex [...] (281 aa)
DYRK1Adual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A; May play a role in a signaling pathway regulating nuclear functions of cell proliferation. Phosphorylates serine, threonine and tyrosine residues in its sequence and in exogenous substrates such as CRY2, FOXO1 and SIRT1 (763 aa)
BRCA1breast cancer 1, early onset; E3 ubiquitin-protein ligase that specifically mediates the formation of ’Lys-6’-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Reg [...] (1884 aa)
TFDP2transcription factor Dp-2 (E2F dimerization partner 2) (446 aa)
PRB1proline-rich protein BstNI subfamily 1 (198 aa)
APAF1apoptotic peptidase activating factor 1 (1248 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, Homo, Homo sapiens, human, man
Server load: medium (56%)