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TTBK2 TTBK2 VRK2 VRK2 CDS1 CDS1 TTBK1 TTBK1 RBX1 RBX1 CHEK2 CHEK2 CUL1 CUL1 SP1 SP1 ATM ATM SKP1 SKP1 VRK3 VRK3 PER3 PER3 PER1 PER1 PER2 PER2 TIMELESS TIMELESS VRK1 VRK1 CRY1 CRY1 CRY2 CRY2 CSNK1D CSNK1D CSNK1A1 CSNK1A1 CSNK1E CSNK1E CSNK1A1L CSNK1A1L CLOCK CLOCK NPAS2 NPAS2 ARNTL ARNTL ARNTL2 ARNTL2
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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 protein node
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
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
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from curated databases
experiment edge
experimentally determined
Predicted Interactions
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gene neighborhood
fusion edge
gene fusions
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gene co-occurrence
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textmining
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co-expression
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CRY1cryptochrome 1 (photolyase-like); Blue light-dependent regulator of the circadian feedback loop. Inhibits CLOCK|NPAS2-ARNTL E box-mediated transcription. Acts, in conjunction with CRY2, in maintaining period length and circadian rhythmicity. Has no photolyase activity. Capable of translocating circadian clock core proteins such as PER proteins to the nucleus. May inhibit CLOCK|NPAS2-ARNTL transcriptional activity through stabilizing the unphosphorylated form of ARNTL (586 aa)
RBX1ring-box 1, E3 ubiquitin protein ligase; E3 ubiquitin ligase component of multiple cullin-RING- based E3 ubiquitin-protein ligase 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. The functional specificity of the E3 ubiquitin-protein ligase complexes depends on the variable substrate recognition components. As a component of the CSA complex promotes the ubiquitination of ERCC6 resulting in pr [...] (108 aa)
VRK1vaccinia related kinase 1; Serine/threonine kinase involved in Golgi disassembly during the cell cycle- following phosphorylation by PLK3 during mitosis, required to induce Golgi fragmentation. Acts by mediating phosphorylation of downstream target protein. Phosphorylates ’Thr- 18’ of p53/TP53 and may thereby prevent the interaction between p53/TP53 and MDM2. Phosphorylates casein and histone H3. Phosphorylates BANF1- disrupts its ability to bind DNA, reduces its binding to LEM domain-containing proteins and causes its relocalization from the nucleus to the cytoplasm (396 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)
PER2period homolog 2 (Drosophila); Component of the circadian clock mechanism which is essential for generating circadian rhythms. Negative element in the circadian transcriptional loop. Influences clock function by interacting with other circadian regulatory proteins and transporting them to the nucleus. Negatively regulates CLOCK|NPAS2-BMAL1|BMAL2-induced transactivation (By similarity) (1255 aa)
TTBK1tau tubulin kinase 1; Serine/threonine kinase which is able to phosphorylate TAU on serine, threonine and tyrosine residues. Induces aggregation of TAU (1321 aa)
ARNTL2aryl hydrocarbon receptor nuclear translocator-like 2 (636 aa)
TTBK2tau tubulin kinase 2; Serine/threonine kinase that acts as a key regulator of ciliogenesis- controls the initiation of ciliogenesis by binding to the distal end of the basal body and promoting the removal of CCP110, which caps the mother centriole, leading to the recruitment of IFT proteins, which build the ciliary axoneme. Has some substrate preference for proteins that are already phosphorylated on a Tyr residue at the +2 position relative to the phosphorylation site. Able to phosphorylate tau on serines in vitro (1244 aa)
ATMataxia telangiectasia mutated; Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates ’Ser-139’ of histone variant H2AX/H2AFX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism. Also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and [...] (3056 aa)
CDS1CDP-diacylglycerol synthase (phosphatidate cytidylyltransferase) 1; Provides CDP-diacylglycerol an important precursor for the synthesis of phosphatidylinositol (PtdIns), phosphatidylglycerol, and cardiolipin. Overexpression may amplify cellular signaling responses from cytokines. May also play an important role in the signal transduction mechanism of retina and neural cells (461 aa)
CLOCKclock homolog (mouse); ARNTL/2-CLOCK heterodimers activate E-box element (5’- CACGTG-3’) transcription of a number of proteins of the circadian clock. Activates transcription of PER1 and PER2. This transcription is inhibited in a feedback loop by PER and CRY proteins. Has intrinsic histone acetyltransferase activity and this enzymatic function contributes to chromatin-remodeling events implicated in circadian control of gene expression (By similarity). Acetylates primarily histones H3 and H4 (By similarity). Acetylates also a non-histone substrate- ARNTL (By similarity). Plays a role i [...] (846 aa)
PER1period homolog 1 (Drosophila); Component of the circadian clock mechanism which is essential for generating circadian rhythms. Negative element in the circadian transcriptional loop. Influences clock function by interacting with other circadian regulatory proteins and transporting them to the nucleus. Negatively regulates CLOCK|NPAS2-BMAL1|BMAL2-induced transactivation. Can bind heme (By similarity) (1290 aa)
CSNK1Dcasein kinase 1, delta; Essential serine/threonine-protein kinase that regulates diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. It can phosphorylate a large number of proteins. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Phosphorylates connexin-43/GJA1, MAP1A, SNAPIN, MAPT/TAU, TOP2A, DCK, HIF1A, EIF6, p53/TP53, DVL2, DVL3, ESR1, AIB1/NCOA3, DNMT1, PKD2, YAP1, PER1 and PER2. Central component of the circadian clock. May act as a negative regulator [...] (415 aa)
VRK3vaccinia related kinase 3; Inactive kinase that suppresses ERK activity by promoting phosphatase activity of DUSP3 which specifically dephosphorylates and inactivates ERK in the nucleus (By similarity) (474 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. 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 complex is dependent on the neddylation of the cullin subunit and exchange of the substrate [...] (776 aa)
SP1Sp1 transcription factor; Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. Binds with high affinity to GC-rich motifs and regulates the expression of a large number of genes involved in a variety of processes such as cell growth, apoptosis, differentiation and immune responses. Highly regulated by post-translational modifications (phosphorylations, sumoylation, proteolytic cleavage, glycosylation and acetylation). Binds also the PDGFR- alpha G-box promoter. May have a role in modulating the cellular response to DNA d [...] (785 aa)
NPAS2neuronal PAS domain protein 2; BMAL1-NPAS2 heterodimers activate E-box element (5’- CACGTG-3’) transcription of a number of proteins of the circadian clock. This transcription is inhibited in a feedback loop by PER, and also by CRY proteins (By similarity) (824 aa)
VRK2vaccinia related kinase 2 (508 aa)
CSNK1Ecasein kinase 1, epsilon; Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates DVL1. Central component of the circadian clock. May act as a negative regulator of circadian rhythmicity by phosphorylating PER1 and PER2. Retains PER1 in the cytoplasm. Inhibits cytokine-induced granuloytic differentiation (416 aa)
PER3period homolog 3 (Drosophila) (1201 aa)
CSNK1A1Lcasein kinase 1, alpha 1-like; Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling (By similarity) (337 aa)
CHEK2checkpoint kinase 2 (586 aa)
ARNTLaryl hydrocarbon receptor nuclear translocator-like (625 aa)
CRY2cryptochrome 2 (photolyase-like); Blue light-dependent regulator of the circadian feedback loop. Inhibits CLOCK|NPAS2-ARNTL E box-mediated transcription. Acts, in conjunction with CRY2, in maintaining period length and circadian rhythmicity. Has no photolyase activity. Capable of translocating circadian clock core proteins such as PER proteins to the nucleus. May inhibit CLOCK|NPAS2-ARNTL transcriptional activity through stabilizing the unphosphorylated form of ARNTL (614 aa)
CSNK1A1casein kinase 1, alpha 1 (365 aa)
TIMELESStimeless homolog (Drosophila); Required for normal progression of S-phase. Involved in the circadian rhythm autoregulatory loop. Negatively regulates CLOCK-NPAS2/BMAL1-induced transactivation of PER1 possibly via translocation of PER1 into the nucleus. Promotes TIPIN nuclear localiZation. Involved in cell survival after DNA damage or replication stress. May be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by hydroxyurea or ultraviolet light. May also play an important role in epithelial cell morphogenesis and formation of branching tubules (1208 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, Homo, Homo sapiens, human, man
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