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CUL1 CUL1 RBX1 RBX1 MNAT1 MNAT1 PCNA PCNA CDKN1A CDKN1A CDKN1B CDKN1B CCNE2 CCNE2 TFDP1 TFDP1 SKP2 SKP2 CCNA2 CCNA2 CDKN1C CDKN1C CDK2 CDK2 CKS1B CKS1B CCND1 CCND1 CDK4 CDK4 CCNH CCNH CCND3 CCND3 CDK7 CDK7 CDKN2C CDKN2C CDK1 CDK1 CCND2 CCND2 CDK6 CDK6 CDK3 CDK3 CDKN2D CDKN2D CDKN2A CDKN2A CDKN2B CDKN2B
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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:
some 3D structure is known or predicted
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Known Interactions
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experimentally determined
Predicted Interactions
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RBX1E3 ubiquitin-protein ligase RBX1; E3 ubiquitin ligase component of multiple cullin-RING- based E3 ubiquitin-protein ligase (CRLs) complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins, including proteins involved in cell cycle progression, signal transduction, transcription and transcription- coupled nucleotide excision repair. CRLs complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins, ARIH1 mediating addition of the first ubiquitin on CRLs targets. The functional specificity of the E3 ubiquitin-protein li [...] (108 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 [...] (295 aa)
CDKN1BCyclin-dependent kinase inhibitor 1B; Important regulator of cell cycle progression. Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA. 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; Belongs to the CDI family (198 aa)
CDK7Cyclin-dependent kinase 7; Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription. Cyclin- dependent kinases (CDKs) are activated by the binding to a cyclin and mediate the progression through the cell cycle. Each different complex controls a specific transition between 2 subsequent phases in the cell cycle. Required for both activation and complex formation of CDK1/cyclin-B during G2-M transition, and for activation of CDK2/cyclins during G1-S transition (but not complex formation). CDK7 is the catalytic subunit of the CDK-activating [...] (346 aa)
CCNHCyclin-H; Regulates CDK7, the catalytic subunit of the CDK- activating kinase (CAK) enzymatic complex. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminal domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Involved in cell cycle control and in RNA transcription by RNA polymerase II. Its expression and activity are constant throughout [...] (323 aa)
CDK4Cyclin-dependent kinase 4; Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes 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. [...] (303 aa)
MNAT1CDK-activating kinase assembly factor MAT1; Stabilizes the cyclin H-CDK7 complex to form a functional CDK-activating kinase (CAK) enzymatic complex. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminal domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Involved in cell cycle control and in RNA transcription by RNA polymerase II; Nucleo [...] (309 aa)
CCND2G1/S-specific cyclin-D2; Regulatory component of the cyclin D2-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 [...] (289 aa)
CDKN2CCyclin-dependent kinase 4 inhibitor C; Interacts strongly with CDK6, weakly with CDK4. Inhibits cell growth and proliferation with a correlated dependence on endogenous retinoblastoma protein RB; Belongs to the CDKN2 cyclin-dependent kinase inhibitor family (168 aa)
CDK6Cyclin-dependent kinase 6; Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and regulates negatively cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cel [...] (326 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)
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 protein kinase holoenzyme complexes with the cyclin-dependent protein kinases CDK1 or CDK2. The cyclin subunit confers the substrate specificity of these complexes and differentially interacts with and activates CDK1 and CDK2 throughout the cell cycle; Cyclins (432 aa)
SKP2S-phase kinase-associated protein 2; 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, KMT2A/MLL1, CDK9, RAG2, FOXO1, UBP43, and probably MYC, TOB1 and TAL1. Degradation of T [...] (424 aa)
CDKN2BCyclin-dependent kinase 4 inhibitor B; Interacts strongly with CDK4 and CDK6. Potent inhibitor. Potential effector of TGF-beta induced cell cycle arrest; Belongs to the CDKN2 cyclin-dependent kinase inhibitor family (138 aa)
CKS1BCyclin-dependent kinases regulatory subunit 1; Binds to the catalytic subunit of the cyclin dependent kinases and is essential for their biological function (79 aa)
CUL1Cullin-1; Core component of multiple cullin-RING-based SCF (SKP1- CUL1-F-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. SCF complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins. In the SCF complex, serves as a rigid scaffold that organizes the SKP1-F-box protein and RBX1 subunits. May contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin- protein ligase activity of the [...] (776 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)
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; Belongs to the E2F/DP family (410 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 re [...] (261 aa)
CDKN2DCyclin-dependent kinase 4 inhibitor D; Interacts strongly with CDK4 and CDK6 and inhibits them; Belongs to the CDKN2 cyclin-dependent kinase inhibitor family (166 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, [...] (297 aa)
CDKN1ACyclin-dependent kinase inhibitor 1; May be involved in p53/TP53 mediated inhibition 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. Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 fo [...] (164 aa)
CDK3Cyclin-dependent kinase 3; Serine/threonine-protein kinase that plays a critical role in the control of the eukaryotic cell cycle; involved in G0- G1 and G1-S cell cycle transitions. Interacts with CCNC/cyclin-C during interphase. Phosphorylates histone H1, ATF1, RB1 and CABLES1. ATF1 phosphorylation triggers ATF1 transactivation and transcriptional activities, and promotes cell proliferation and transformation. CDK3/cyclin-C mediated RB1 phosphorylation is required for G0-G1 transition. Promotes G1-S transition probably by contributing to the activation of E2F1, E2F2 and E2F3 in a RB1 [...] (305 aa)
CDKN1CCyclin-dependent kinase inhibitor 1C; Potent tight-binding inhibitor of several G1 cyclin/CDK complexes (cyclin E-CDK2, cyclin D2-CDK4, and cyclin A-CDK2) and, to lesser extent, of the mitotic cyclin B-CDC2. Negative regulator of cell proliferation. May play a role in maintenance of the non- proliferative state throughout life; Belongs to the CDI family (316 aa)
CDKN2ACyclin-dependent kinase inhibitor 2A; Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6. This inhibits their ability to interact with cyclins D and to phosphorylate the retinoblastoma protein (167 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)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, Homo sapiens, human, man
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