IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels int64 0 2 | mechanism stringclasses 40 values | effect stringclasses 10 values | score float64 0.1 0.99 ⌀ | sentence stringlengths 10 1.63k ⌀ | signor_id stringlengths 12 14 |
|---|---|---|---|---|---|---|---|
Q49AN0 | Q9UKT7 | 2 | binding | down-regulates quantity by destabilization | 0.769 | We found that both Cry1 and Cry2 proteins are ubiquitinated and degraded via the SCF(Fbxl3) ubiquitin ligase complex. This regulation by SCF(Fbxl3) is a prerequisite for the efficient and timely reactivation of Clock-Bmal1 and the consequent expression of Per1 and Per2, two regulators of the circadian clock that display tumor suppressor activity. HEK293T cells were transfected with Cry2, Skp1, Cul1, and Roc1 in the absence or presence of either FLAG-tagged Fbxl3 or a FLAG-tagged Fbxl3(ΔF-box) mutant. Fbxl3, but not an inactive Fbxl3(ΔF-box) mutant (4), induced the ubiquitination of Cry2 (Fig. 2D), which supports the notion that the effect of Fbxl3 on Cry2 is direct. | SIGNOR-271648 |
Q9H4L7 | Q13263 | 2 | binding | up-regulates activity | 0.504 | SMARCAD1 interacts with HDAC1 and KAP1 and is required for their binding to heterochromatin | SIGNOR-239838 |
O43318 | O95819 | 2 | binding | up-regulates | 0.582 | The existence of an at least trimolecular complex consisting of nik, tak1, and ikk2, although the precise sequence of activation as well as the possible location of the kinases within the signalosome remains to be elucidated. | SIGNOR-77404 |
Q8WUP2 | Q86UX7 | 2 | binding | up-regulates activity | 0.488 | Kindlin binds migfilin tandem LIM domains and regulates migfilin focal adhesion localization and recruitment dynamics. Two integrin-binding proteins present in FAs, kindlin-1 and kindlin-2, are important for integrin activation, FA formation, and signaling. By binding filamin, migfilin provides a link between kindlin and the actin cytoskeleton. | SIGNOR-266104 |
P35221 | P46937 | 2 | binding | down-regulates | 0.353 | The trimeric complex of alfa-catenin, 14-3-3, and yap sequesters yap at ajs and prevents yap dephosphorylation/activation. | SIGNOR-201173 |
Q05397 | O14939 | 1 | phosphorylation | up-regulates activity | 0.32 | The kinase domain of FAK interacts with PLD2-PH and induces tyrosine phosphorylation and activation of PLD2. | SIGNOR-279480 |
Q9NQR1 | O60729 | 0 | dephosphorylation | down-regulates quantity by destabilization | 0.2 | The dephosphorylation of S29 during late mitosis by the Cdc14 phosphatases was required for APC(cdh1)-mediated ubiquitination of PR-Set7 and subsequent proteolysis. | SIGNOR-248339 |
P05129 | P04083 | 1 | phosphorylation | up-regulates | 0.2 | The authors identified several phosphorylated residues by a combination of peptide mapping and sequence analysis and showed that recombinant pp60c-src phosphorylates annexin a1 near its amino terminus, at tyrosine 21 (tyr21). Also polyoma virus middle t/pp60c-src complex, recombinant pp50v-abl, and the egf receptor/kinase phosphorylated the same tyrosine residue. It was also shown that serine 27 residue of anxa1 is the primary site phosphorylated by protein kinase c (pkc). In the same study, the threonine 41 residue has been identified as a pkc substrate as well. The adenosine cyclic 3_,5_-phosphate dependent protein kinase a (pka) phosphorylates anxa1 in its carboxyl-terminal core at the threonine 216 residue (thr216) [2].The phosphorylation of serine 27 is essential for annexin a1 membrane localization. | SIGNOR-202788 |
Q12857 | P54756 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8) | SIGNOR-268895 |
Q13480 | P12931 | 0 | phosphorylation | up-regulates | 0.704 | Using both mutagenesis and mass spectrometry approaches, y242, y259, y317, y373 and y627 of gab1 were identified to be phosphorylated by c-src a gab1 mutant with substitutions of the src phosphorylation sites failed to promote hgf-induced dna synthesis | SIGNOR-236314 |
Q9Y2X7 | Q9NZL9 | 2 | binding | up-regulates activity | 0.398 | We found both MAT2B variants interact with GIT1. MAT2B directly promoted binding of GIT1 and ERK2 to MEK1. MAT2B and GIT1 interact and are overexpressed in most human liver and colon cancer specimens. MAT2B and GIT1 require each other to activate MEK1/ERK and increase growth. | SIGNOR-261244 |
P63096 | P63000 | 2 | binding | up-regulates activity | 0.47 | These findings indicate that both G alpha(i) and G beta gamma stimulate Rac and Cdc42 pathways with lysophosphatidic acid-induced cell spreading on fibronectin | SIGNOR-256530 |
P61586 | P15311 | 1 | phosphorylation | up-regulates activity | 0.76 | Rev-erbα interacted with OPHN-1, promoted RhoA activity and phosphorylation of ERM. etection of phosphorylated ezrin (Thr567)/radixin (Thr564)/moesin (Thr558)(p-ERM) in Rev-erbαfl/flCre− and Rev-erbαfl/flPF4Cre+ platelets using phospho-specific antibodies. | SIGNOR-268429 |
O14543 | O60674 | 2 | binding | down-regulates activity | 0.796 | The ability of SOCS3 to simultaneously bind to JAK and to the cytokine receptor explains the specificity of the suppression. SOCS3 binds JAK and gp130 receptor simultaneously, using two opposing surfaces: while the phosphotyrosine-binding groove on the SOCS3 SH2 domain is occupied by the gp130 receptor, a subdomain in the SH2 domain of SOCS3 is also required for inhibition of JAK, binding in a phospho-independent manner to a non-canonical surface of JAK2 (58, 59). The KIR of SOCS3 occludes the substrate-binding groove on JAK2. | SIGNOR-255329 |
Q96P20 | Q15139 | 0 | phosphorylation | up-regulates activity | 0.332 | PKD at the Golgi phosphorylates NLRP3 to release it from mitochondria-associated endoplasmic reticulum membranes, allowing for assembly of the mature inflammasome in the cytosol.|These data thus suggest that PKD activity at the Golgi is sufficient to activate the NLRP3 inflammasome. | SIGNOR-279428 |
Q15796 | Q9H6Z4 | 0 | relocalization | down-regulates activity | 0.436 | RanBP3 directly recognizes dephosphorylated Smad2/3, which results from the activity of nuclear Smad phosphatases, and mediates nuclear export of Smad2/3 in a Ran-dependent manner. | SIGNOR-217634 |
Q16623 | P68400 | 0 | phosphorylation | up-regulates | 0.366 | In this report, we show that syntaxin-1a is phosphorylated in vitro by cki on thr21. Casein kinase ii (ckii) has been shown previously to phosphorylate syntaxin-1a in vitro and we have identified ser14 as the ckii phosphorylation site. the phosphorylation of syntaxin-1a by ckii enhances its capacity to associate with synaptotagmin [21]. Therefore, phosphorylation of ser14 by ckii suggests an important role for this residue in regulating the interaction between syntaxin-1a and synaptotagmin | SIGNOR-114840 |
Q05084 | O43918 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.362 | Sequence variation in promoter of Ica1 gene, which encodes protein implicated in type 1 diabetes, causes transcription factor autoimmune regulator (AIRE) to increase its binding and down-regulate expression. | SIGNOR-268973 |
Q15121 | P17252 | 0 | phosphorylation | down-regulates | 0.384 | Pea-15 is phosphorylated on two ser residues, ser104 and ser116. Protein kinase c (pkc) phosphorylates ser104 / we report that phosphorylation of pea-15 blocks its interaction with erk1/2 in vitro and in vivo and that phosphorylation of both ser104 and ser116 is required for this effect. | SIGNOR-137841 |
O75581 | P45983 | 0 | phosphorylation | up-regulates | 0.382 | We show that several proline-directed mitogen-activated protein kinases (mapks), such as p38, erk1/2, and jnk1 are sufficient and required for the phosphorylation of ppps/tp motifs of lrp6. External stimuli, which control the activity of mapks, such as phorbol esters and fibroblast growth factor 2 (fgf2) control the choice of the lrp6-ppps/tp kinase and regulate the amplitude of lrp6 phosphorylation and wnt/beta-catenin-dependent transcription. | SIGNOR-169007 |
P68400 | P11473 | 1 | phosphorylation | up-regulates | 0.336 | Casein kinase ii (ckii) phosphorylates vdr both in vitro and in vivo at serine 208 within the hinge domain. This phosphorylation does not affect the ability of vdr to bind dna, but increases its ability to transactivate target promoters | SIGNOR-153711 |
P19086 | O60755 | 2 | binding | up-regulates activity | 0.25 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257114 |
P28289 | P06753 | 2 | binding | down-regulates activity | 0.731 | Tropomodulin is a 40.6-kDa protein that binds to one end of the rod-like tropomyosin and inhibits its cooperativity and binding to actin. [.] we demonstrate that it is the N-terminus of tropomyosin that interacts with tropomodulin. Among several tropomyosin isoforms tested, hTM5 encoded by the human gamma-tropomyosin gene has the highest affinity toward human erythrocyte tropomodulin. | SIGNOR-259111 |
P63000 | P31749 | 0 | phosphorylation | down-regulates activity | 0.725 | Akt protein kinase inhibits Rac1-GTP binding through phosphorylation at serine 71 of Rac1 | SIGNOR-252576 |
Q9UJZ1 | P19174 | 2 | binding | up-regulates activity | 0.2 | In these studies, we also found that SLP-2 interacted with Lck, ZAP70, LAT, and PLC-gamma1 during the 30-min period following stimulation in vitro|The SLP-2-associated pool of these molecules became phosphorylated/activated in a sequential manner, a profile compatible with their temporal involvement in early TCR signalling. | SIGNOR-260378 |
O60674 | Q92783 | 1 | phosphorylation | up-regulates | 0.617 | Stam is associated with jak3 and jak2 tyrosine kinases via its itam region and phosphorylated by jak3 and jak2 upon stimulation with il-2. | SIGNOR-47834 |
P38398 | P11387 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.463 | Here, we show that the Ku70/Ku80 heterodimer binds with topoI, and that the DNA-dependent protein kinase (DNA-PKcs) phosphorylates topoI on serine 10 (topoI-pS10), which is subsequently ubiquitinated by BRCA1. Taken together, we conclude that BRCA1 is the E3 ligase for topoI, and the rate of topoI proteasomal degradation determines CPT response. | SIGNOR-277353 |
P53350 | Q76N32 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.44 | We show that the intercentrosomal linker protein Cep68 is degraded in prometaphase through the SCF(βTrCP) (Skp1-Cul1-F-box protein) ubiquitin ligase complex. Cep68 degradation is initiated by PLK1 phosphorylation of Cep68 on Ser 332, allowing recognition by βTrCP. | SIGNOR-275621 |
P02679 | P04004 | 2 | binding | down-regulates activity | 0.422 | Fibrinogen y-chain carboxyterminal (GQQHHLGGAKQAGDV) peptides inhibit fibrinogen, fibronectin (Fn), vitronectin, and von Willebrand factor (vWF) binding to the platelet glycoprotein Ilb-Illa complex (GP lIbII1a). | SIGNOR-251969 |
Q13554 | Q13131 | 1 | phosphorylation | up-regulates | 0.2 | These data indicate that the camkks function in intact cells as ampkks, predicting wider roles for these kinases in regulating ampk activity in vivo. | SIGNOR-138360 |
Q9NQS5 | P08754 | 2 | binding | up-regulates activity | 0.277 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256847 |
O43474 | P15941 | 2 | binding | up-regulates activity | 0.281 | Previous work has shown that the Kruppel-like factor 4 (KLF4) transcription factor represses p53 transcription by binding to the PE21 element. Our results show that MUC1-C binds constitutively to KLF4, occupies PE21 with KLF4, and enhances the KLF4 occupancy of PE21. | SIGNOR-270543 |
P37840 | O60260 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Parkin is a protein of 465 amino acids, and its structure includes a ubiquitin homologous domain in its N terminus and two RING finger domains in its C terminus. Molecular studies have determined that parkin is an E3 ubiquitin ligase function, implicating parkin in the ubiquitin-proteasome system, and raising the possibility that mutations in the gene lead to loss or diminished function. Three substrates for the ubiquitin-ligase function of parkin have been identified to date.1. A 22kDa glycosolated form of alpha-synuclei|2. Parkin-associated endothelin receptor-like receptor (Pael-R). | SIGNOR-249705 |
Q9UEW8 | Q13621 | 1 | phosphorylation | up-regulates activity | 0.577 | We establish that the SPAK and OSR1 kinases activated by WNK interact with an RFQV motif on NKCC2 and directly phosphorylate Thr95, Thr100, Thr105 and, possibly, Ser91.Using these phosphorylation-specific antibodies we establish that hypotonic low-chloride stimulation induces marked phosphorylation of overexpressed NKCC2 in HEK-293 cells at Ser91, Thr100, Thr105 and Ser130 (Fig. 3A). | SIGNOR-276308 |
Q15797 | O95257 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation | SIGNOR-268937 |
P13984 | P35269 | 2 | binding | up-regulates activity | 0.962 | Direct Interaction Between the Subunit RAP30 of Transcription Factor IIF (TFIIF) and RNA Polymerase Subunit 5, Which Contributes to the Association Between TFIIF and RNA Polymerase II. we showed that RPB5 binds RAP30 but not RAP74 and associates to TFIIF through the binding to RAP30. | SIGNOR-261180 |
Q14814 | Q13469 | 2 | binding | up-regulates | 0.583 | Upon dephosphorylation by calcineurin, nfatc2, also referred to as nfatp/nfat1, translocates to the nucleus where it directly associates with mef2a and -d. Nfatc2 stimulates mef2-dependent transcription by facilitating recruitment of the p300 coactivator to mef2-response elements. | SIGNOR-117589 |
O15055 | P04150 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.5 | GR directly regulates transcription of circadian clock components in mouse and human primary MSCs. Per2, E4bp4, Per1, and Timeless rapidly respond to glucocorticoid stimulation. Primary glucocorticoid receptor (GR) target genes are those at which GR occupies a nearby genomic glucocorticoid response element (GRE) and regulates target gene transcription | SIGNOR-268049 |
Q9Y666 | Q9BYP7 | 0 | phosphorylation | down-regulates activity | 0.451 | We have shown that with-no-lysine kinase 3 (WNK3) possesses several properties that suggest it could be the Cl−/volume-sensitive regulatory kinase that, in association with protein phosphatases, reciprocally modifies the phosphorylation/dephosphorylation states of the SLC12 proteins and thus their activities|WNK3 activates NKCC1/2 and NCC and inhibits the KCCs | SIGNOR-264630 |
P28482 | Q7LDG7 | 1 | phosphorylation | down-regulates activity | 0.396 | ERK2 phosphorylates RasGRP2 at Ser394 located in the linker region implicated in its autoinhibition. | SIGNOR-279537 |
Q14457 | Q14694 | 2 | deubiquitination | up-regulates quantity by stabilization | 0.509 | Interestingly, Beclin1 also controls the protein stabilities of USP10 and USP13 by regulating their deubiquitinating activities. | SIGNOR-260298 |
P19634 | P28482 | 0 | phosphorylation | up-regulates | 0.669 | We have demonstrated that the map kinases extracellular signal-regulated kinases 1 and 2 (erk1/2) are implicated in growth factor activation of nhe1. / our results suggest that amino acids ser770 and ser771 mediate erk-dependent activation of the na+/h+ exchanger in vivo. | SIGNOR-151925 |
Q96SN8 | Q96R06 | 0 | relocalization | up-regulates activity | 0.465 | By bringing CDK5RAP2 to the centrosome, the centriolar satellite proteins CEP72 and SPAG5 are required for the centrosomal localization of the other three MCPH proteins despite not interacting with them biochemically. | SIGNOR-271719 |
Q13485 | Q9UNE7 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.396 | We demonstrate that the coexpression of Smad1 and Smad4 with the CHIP protein results in the degradation of the Smad proteins through a ubiquitin-mediated process. | SIGNOR-272947 |
Q13283 | Q9UN86 | 2 | binding | up-regulates activity | 0.459 | Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is a component of SGs that initiates the assembly of SGs by forming a multimer. In this study, we examined the role of G3BP2, a close relative of G3BP1, in SG formation. Although single knockdown of either G3BP1 or G3BP2 in 293T cells partially reduced the number of SG-positive cells induced by arsenite, the knockdowns of both genes significantly reduced the number. G3BP2 formed a homo-multimer and a hetero-multimer with G3BP1. Moreover, like G3BP1, the overexpression of G3BP2 induced SGs even without stress stimuli. | SIGNOR-260862 |
Q13950 | Q09472 | 0 | acetylation | up-regulates quantity | 0.453 | Bmp-induced non-smad erk signaling pathway cooperatively regulates osteoblast differentiation, in part, through increasing the stability and transcriptional activity of runx2 or increasing runx2 acetylation by p300. | SIGNOR-195579 |
Q13976 | Q8N8S7 | 1 | phosphorylation | down-regulates activity | 0.302 | Vertebrate Ena/VASP proteins are phosphorylated by PKA, as well as PKG, and the phosphorylation is required for full function in a number of cellular contexts. PKG may preferentially phosphorylate sites of Ena/VASP proteins that reduce or inactivate these proteins. Inactivated Ena/VASP proteins dissociate from actin filaments, allowing capping proteins to bind and block monomer addition to plus ends, resulting in filament retraction. | SIGNOR-268288 |
Q53G59 | Q9C0E8 | 2 | binding | up-regulates activity | 0.2 | Lunapark Is Ubiquitylated by the CRL3KLHL12 Ubiquitin Ligase Complex. Taken together, these results demonstrate that Lunapark is ubiquitylated by the CRL3KLHL12 ubiquitin ligase, and the CRL3KLHL12-dependent ubiquitylation of Lunapark does not lead to its proteasomal degradation. Inhibition of Lunapark Ubiquitylation Affects Lysosomal Recruitment of mTORC1 | SIGNOR-272197 |
O60260 | Q9H4P4 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Here we further demonstrated that overexpression of Nrdp1 significantly reduced the endogenous Parkin level in an Nrdp1 dosage-dependent and proteasome-dependent manner. More importantly, Nrdp1 ubiquitinated Parkin and catalyzed the poly-ubiquitin chains on Parkin in vitro as well as in cells, indicating Parkin is an Nrdp1 substrate. | SIGNOR-272639 |
O95155 | O95997 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | We further demonstrate that Ufd2 directly and efficiently ubiquitylates securin in vitro and is required for securin polyubiquitylation in vivo. This is the first description of a physiologic substrate for Ufd2, establishing this E4 enzyme as an important regulator of chromosome condensation and separation during mitosis in human cells. | SIGNOR-271523 |
Q16512 | P06493 | 0 | phosphorylation | up-regulates activity | 0.436 | CDK1 phosphorylates PKN1 at S533, S537, S562, and S916 in vitro and in cells during drug-induced mitotic arrest. Immunofluorescence staining further confirmed that PKN1 phosphorylation occurs during normal mitosis in a CDK1-dependent manner.Knockdown of PKN1 significantly inhibited anchorage-independent growth and migration without affecting proliferation in multiple cancer cell lines. | SIGNOR-276831 |
Q96FA3 | P51617 | 2 | ubiquitination | up-regulates quantity by expression | 0.767 | These results were consistent with the observations made in vitro, namely that pellino isoforms are activated by irak1-catalysed phosphorylation and that, once activated, can ubiquitinate irak1 in cells. | SIGNOR-159055 |
P40763 | P07332 | 0 | phosphorylation | up-regulates activity | 0.402 | Fes also induced Tyr 705 phosphorylation and DNA binding activity of STAT3, in agreement with the idea that Fes can regulate transcriptional activation through Fes dependent phosphorylation of transcription factors.On the basis of these findings, we propose that Fes activation of critical transcriptional regulators such as PU.1 is part of the mechanism by which this kinase induces macrophage differentiation of myeloid progenitors.|We conclude that Fes may regulate granulocytic differentiation at least in part through activation of C/EBP-alpha and STAT3.In 32D cells, Fes activated STAT3 and C/EBP-alpha, two important regulators of granulocytic differentiation [14,15]. | SIGNOR-278937 |
Q01094 | Q13490 | 0 | ubiquitination | up-regulates activity | 0.336 | The ability of cIAP1 to promote wt E2F1 transcriptional activity was retained by all E2F1 mutants, except the K161R/164R mutant for which cIAP1 was completely inactive and the K185R whose basal transactivation activity was weakly enhanced by cIAP1 (XREF_FIG).|Here, we demonstrated that the E3-ubiquitin ligase cellular inhibitor of apoptosis 1 (cIAP1) increases E2F1 K63-poly-ubiquitination on the lysine residue 161/164 cluster, which is associated with the transcriptional factor stability and activity. | SIGNOR-278688 |
P05556 | Q9P2E7 | 2 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. | SIGNOR-269034 |
Q9UER7 | Q13315 | 0 | phosphorylation | down-regulates | 0.499 | The main phosphorylation site of daxx is identified to be ser564, which is a direct target of atm. Phosphorylation of endogenous daxx at ser564 occurs rapidly during the dna damage response and precedes p53 activation. Blockage of this phosphorylation event prevents the separation of daxx from mdm2, stabilizes mdm2, and inhibits dna damage-induced p53 activation. | SIGNOR-200889 |
Q9Y243 | P24666 | 0 | dephosphorylation | down-regulates activity | 0.2 | Reduction in the levels of both LMW-PTP isoforms in vitro and in vivo increased tyrosine phosphorylation of IR and AktSer473 and increased IRS-1- and IRS-2-associated PI3-K activities in both liver and fat.|Activated PI3-K stimulates Akt (or protein kinase B) that in turn phosphorylates and inactivates glycogen synthase kinase-3 | SIGNOR-248457 |
P49841 | P11308 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Here, we demonstrate that DNA damage induces proteasomal degradation of wild-type ERG and TMPRSS2-ERG oncoprotein through ERG threonine-187 and tyrosine-190 phosphorylation mediated by GSK3β and WEE1, respectively. | SIGNOR-277528 |
P29353 | P29376 | 0 | phosphorylation | up-regulates | 0.424 | Recently, we demonstrated that ltk utilizes shc and irs-1 as two major substrates and while both equally activate the ras pathway, only irs-1 suppresses apoptosis of hematopoietic cells. | SIGNOR-49625 |
P06241 | P22681 | 1 | phosphorylation | up-regulates activity | 0.812 | Fyn associates with cbl and phosphorylates tyrosine 731 in cbl, a binding site for phosphatidylinositol 3-kinasecbl represents a substrate for src-like kinases that are activated in response to the engagement of cell surface receptors, and that src-like kinases are responsible for the phosphorylation of a tyrosine residue in cbl that may regulate activation of phosphatidylinositol 3-kinase | SIGNOR-63968 |
P31749 | P63000 | 1 | phosphorylation | down-regulates activity | 0.725 | Akt protein kinase inhibits Rac1-GTP binding through phosphorylation at serine 71 of Rac1 | SIGNOR-252576 |
P48200 | Q9UNH5 | 0 | dephosphorylation | up-regulates activity | 0.348 | IRP2 Ser-157 is phosphorylated by Cdk1/cyclin B1 during G(2)/M and is dephosphorylated during mitotic exit by the phosphatase Cdc14A. Ser-157 phosphorylation during G(2)/M reduces IRP2 RNA-binding activity and increases ferritin synthesis, whereas Ser-157 dephosphorylation during mitotic exit restores IRP2 RNA-binding activity and represses ferritin synthesis. | SIGNOR-248829 |
P45983 | P31947 | 1 | phosphorylation | down-regulates | 0.338 | Jnk phosphorylates 14-3-3zeta_ at ser-184 and 14-3-3sigma_ at ser-187. | SIGNOR-124016 |
Q96G91 | P50148 | 2 | binding | up-regulates activity | 0.385 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257386 |
O14672 | Q14576 | 0 | post transcriptional regulation | up-regulates quantity | 0.2 | Neuronal ELAV (nELAV) proteins are RNA-binding proteins which play a physiological role in controlling gene expression in memory formation, and their alteration may contribute to cognitive impairment associated with neurodegenerative pathologies such as Alzheimer's disease (AD). The experiments show for the first time that ADAM10mRNA represents a nELAV target and that these RNA-binding proteins can play a role in the post-transcriptional regulation of ADAM10 expression. nELAV proteins specifically bind the ADAM10 mRNA and this binding is disrupted following Aβ exposure | SIGNOR-266864 |
Q92913 | Q9NY46 | 2 | binding | down-regulates activity | 0.2 | Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels. | SIGNOR-253443 |
Q05086 | O60936 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Incubation of transfected HEK293T cells with the proteasome inhibitor, MG132 blocked Ube3A mediated degradation of Arc suggesting that Ube3A degrades Arc via the ubiquitin proteasome system .|The ubiquitination of Arc by Ube3A was confirmed by mass spectrometry which revealed that Ube3A catalyzed the polyubiquitination of Arc on Lysine 268 and 269 ( xref ). | SIGNOR-278522 |
Q96S44 | Q96KB5 | 0 | phosphorylation | up-regulates activity | 0.418 | In this study, we provide evidence showing that TOPK promotes metastasis of colorectal carcinoma, which is mediated through its phosphorylation of PRPK at Ser250.|Therefore, we conclude that TOPK directly promotes metastasis of colorectal cancer by modulating PRPK. | SIGNOR-278236 |
O60260 | O43236 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Thus, Parkin degrades ARTS in a proteasome dependent manner.|Together, these results suggest that Parkin specifically ubiquitinates and degrades ARTS, and that this degradation may be linked to the pro-apoptotic function of ARTS. | SIGNOR-278642 |
P31749 | Q7L5N1 | 1 | phosphorylation | up-regulates | 0.282 | Mechanistic studies show that akt causes csn6 phosphorylation at ser 60, which, in turn, reduces ubiquitin-mediated protein degradation of csn6. | SIGNOR-252532 |
Q00987 | Q13535 | 0 | phosphorylation | down-regulates activity | 0.522 | We found that a major kinase responsible for s407 phosphorylation is atrs407 phosphorylation of mdm2 by atr reduces mdm2-dependent export of p53 from nuclei to cytoplasm. | SIGNOR-119546 |
P08631 | Q9UHD2 | 1 | phosphorylation | down-regulates activity | 0.2 | The Src family kinases (SFKs) Lck, Hck, and Fgr directly phosphorylate TBK1 at Tyr354/394, to prevent TBK1 dimerization and activation. | SIGNOR-276727 |
Q04206 | Q5JXC2 | 2 | binding | up-regulates activity | 0.2 | Here, we show that EGF stimulation induces PKCε-dependent phosphorylation of migration and invasion inhibitory protein (MIIP) at Ser303; this phosphorylation promotes the interaction between MIIP and RelA in the nucleus, by which MIIP prevents histone deacetylase 6 (HDAC6)-mediated RelA deacetylation, and thus enhances transcriptional activity of RelA and facilitates tumor metastasis. | SIGNOR-273829 |
P42261 | P17612 | 0 | phosphorylation | up-regulates activity | 0.494 | Phosphorylation of Ser-845 on GluR1 by PKA potentiates its response to glutamate. | SIGNOR-249987 |
P61586 | P52735 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.75 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260582 |
P56704 | O75487 | 2 | binding | up-regulates | 0.35 | Gpc4 bound to wnt3a and wnt5a which activate the beta-catenin-dependent and -independent pathways, respectively, and colocalized with wnts on the cell surface. Expression of gpc4 enhanced the wnt3a-dependent beta-catenin pathway and the wnt5a-dependent beta-catenin-independent pathway, and knockdown of gpc4 suppressed both pathways | SIGNOR-195749 |
P46934 | Q12809 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.268 | We have previously shown that the E3 ubiquitin (Ub) ligase Nedd4-2 (neural precursor cell expressed developmentally down-regulated protein 4-2) targets the PY motif of hERG channels to initiate channel degradation. Although both immature and mature hERG channels contain the PY motif, Nedd4-2 selectively mediates the degradation of mature hERG channels. | SIGNOR-260998 |
O95835 | Q13043 | 0 | phosphorylation | up-regulates | 0.623 | We show that Mst2 and hWW45 interact with each other in human cells and that both Mst2 and Mst1 are able to phosphorylate Lats1 and Lats2, thereby stimulating Lats kinase activity. | SIGNOR-133551 |
O15169 | P48730 | 2 | binding | up-regulates | 0.556 | Complex of axin and casein kinase i (cki) induces beta-catenin phosphorylation at a single site: serine 45 (s45). | SIGNOR-87401 |
P20810 | Q8TDC3 | 0 | phosphorylation | up-regulates activity | 0.2 | Here, we show that an AZ cytomatrix protein CAST and an AZ-associated protein kinase SAD-B coordinately regulate STD by controlling reloading of the AZ with release-ready synaptic vesicles. SAD-B phosphorylates the N-terminal serine (S45) of CAST, and S45 phosphorylation increases with higher firing rate. | SIGNOR-263051 |
P98177 | O43638 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Fkhl18 suppressed the transcriptional activity of FoxO3a and FoxO4. | SIGNOR-261611 |
P53350 | Q06609 | 1 | phosphorylation | up-regulates activity | 0.508 | Mechanistically, TOPBP1 physically binds PLK1 and promotes PLK1 kinase-mediated phosphorylation of RAD51 at serine 14, a modification required for RAD51 recruitment to chromatin.|Mechanistically, TOPBP1 physically binds PLK1 and promotes PLK1 kinase\u2013mediated phosphorylation of RAD51 at serine 14, a modification required for RAD51 recruitment to chromatin. | SIGNOR-278187 |
Q12778 | Q13627 | 0 | phosphorylation | down-regulates | 0.506 | Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity. | SIGNOR-183670 |
P60953 | Q96N67 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.739 | As a GEF, Dock7 exchanges GDP for GTP on Cdc42 and Rac1, causing their activation, followed by activation of downstream effectors, including the dephosphorylation (activation) of cofilin, a key regulator of actin turnover. | SIGNOR-261886 |
P51608 | Q06413 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.346 | MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1. | SIGNOR-264680 |
Q9UHD2 | P0DTD1-PRO_0000449630 | 2 | binding | down-regulates activity | 0.2 | We use unbiased screening to identify SARS-CoV-2 proteins that antagonize type I interferon (IFN-I) response. We found three proteins that antagonize IFN-I production via distinct mechanisms: nonstructural protein 6 (nsp6) binds TANK binding kinase 1 (TBK1) to suppress interferon regulatory factor 3 (IRF3) phosphorylation, nsp13 binds and blocks TBK1 phosphorylation, and open reading frame 6 (ORF6) binds importin Karyopherin α 2 (KPNA2) to inhibit IRF3 nuclear translocation. the results indicate that (1) nsp6 binds to TBK1 without affecting TBK1 phosphorylation, but the nsp6/TBK1 interaction decreases IRF3 phosphorylation, which leads to reduced IFN-β production; and (2) nsp13 binds and inhibits TBK1 phosphorylation, resulting in decreased IRF3 activation and IFN-β production (Figure 2F). | SIGNOR-262512 |
P51617 | P40763 | 1 | phosphorylation | up-regulates | 0.55 | Irak1 can directly use stat3 as a substrate and cause stat3 serine 727 phosphorylation. | SIGNOR-129685 |
P18846 | O75582 | 0 | phosphorylation | up-regulates activity | 0.69 | Using embryonic fibroblasts derived from these mice we were able to demonstrate an important role for these enzymes in the activation of CREB and the closely related transcription factor ATF1. | Our results clearly demonstrate that MSK1 and MSK2 are the major, if not the only, protein kinases that mediate the phosphorylation of CREB at Ser133 and of ATF1 at Ser63 in fibroblasts | SIGNOR-249144 |
P04049 | O15530 | 0 | phosphorylation | up-regulates activity | 0.311 | PDK1, but not PKCs, phosphorylate and activate Raf1 in MAPK pathway when platelets are stimulated with 2MeSADP. | SIGNOR-280063 |
Q12959 | P11171 | 0 | relocalization | up-regulates activity | 0.472 | Together, our results demonstrate that in addition to the N-terminal targeting domain, the alternatively spliced I3 insertion plays a critical role in recruiting hDlg to the lateral membrane in epithelial cells via its interaction with protein 4.1R. | SIGNOR-266011 |
P51812 | P18848 | 1 | phosphorylation | up-regulates | 0.633 | Here, we show that rsk2 is required for osteoblast differentiation and function. We identify the transcription factor atf4 as a critical substrate of rsk2 that is required for the timely onset of osteoblast differentiation, for terminal differentiation of osteoblasts, and for osteoblast-specific gene expression | SIGNOR-124436 |
Q9Y4X5 | Q13618 | 2 | binding | up-regulates activity | 0.314 | Here, we provide evidence that Ariadne RBR E3 ubiquitin ligases such as TRIAD1 and HHARI can bind and be activated by CRL complexes. Whereas TRIAD1 specifically associates with CUL5–RBX2, HHARI is more promiscuous towards cullin types and associates with RBX1-associated cullins 1, 2, 3, and 4A. Interestingly, both TRIAD1 and HHARI show a strong preference for binding the neddylated form of the cullin. Our data suggest a novel function of NEDD8 in directing specific CRLs to Ariadne RBR ligases, which in turn exert influence on the levels of their cognate neddylated cullin. | SIGNOR-268846 |
P17535 | P45983 | 0 | phosphorylation | up-regulates | 0.796 | Menin binds the jun family transcription factor jund and inhibits its transcriptional activity. The menin-jund interaction blocks jun n-terminal kinase (jnk)-mediated jund phosphorylation and suppresses jund-induced transcription. We found a role for phosphorylation of the ser100 residue of jund;jund phosphorylation were prevented by inhibitors of calcium, calmodulin, or erk1/2 kinase. | SIGNOR-196038 |
P15172 | P06493 | 0 | phosphorylation | down-regulates | 0.364 | Myod is phosphorylated on ser5 and ser200 by cyclin b-cdc2, resulting in a decrease of its stability and down-regulation of both myod and p21. | SIGNOR-121601 |
P30622 | Q7Z460 | 2 | binding | up-regulates activity | 0.725 | CLIP-associating protein (CLASP) 1 and CLASP2 are mammalian microtubule (MT) plus-end binding proteins, which associate with CLIP-170 and CLIP-115.|We demonstrate that the middle part of CLASPs binds directly to EB1 and to MTs. | Both EB1- and cortex-binding domains of CLASP are required to promote MT stability. | SIGNOR-265091 |
P10242 | P19338 | 2 | binding | down-regulates activity | 0.401 | We identify nucleolin as one of the nuclear polypeptides that interact specifically with the A-Myb and c-Myb. We show that the interaction of nucleolin with Myb is functional because co-transfection of nucleolin down-regulates Myb transcriptional activity. | SIGNOR-221236 |
P08311 | P05546 | 1 | cleavage | down-regulates activity | 0.444 | Amino acid sequence analysis led to the conclusion that both neutrophil elastase and cathepsin G cleave HC at Ile66, which does not affect HC activity, and at Val439, near the reactive site Leu444, which inactivates HC. | SIGNOR-256509 |
O15105 | Q9H0M0 | 0 | relocalization | up-regulates activity | 0.731 | We found that WWP1 inhibited transcriptional activities induced by TGF-beta. Similar to Smurfs, WWP1 associated with Smad7 and induced its nuclear export, and enhanced binding of Smad7 to TGF-beta type I receptor to cause ubiquitination and degradation of the receptor. | SIGNOR-126578 |
P59768 | Q99835 | 2 | binding | up-regulates | 0.385 | Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling. | SIGNOR-199183 |
P67870 | Q9UBF6 | 1 | phosphorylation | up-regulates activity | 0.329 | In the present study, we show the evidence that CKBBP1 is phosphorylated on threonine residue at position 10 by CKII in vitro and in vivo. Most importantly, disruption of this phosphorylation in CKBBP1 results in accumulation of IκBα and p27Kip1 in HeLa cells and inhibits cell proliferation that appears to be linked to defects in G1/S transition. | SIGNOR-251081 |
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