IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P07196 | Q9C040 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.43 | Here, we show that TRIM RING finger protein TRIM2, highly expressed in the nervous system, is an UbcH5a-dependent ubiquitin ligase. We further demonstrate that TRIM2 binds to neurofilament light subunit (NF-L) and regulates NF-L ubiquitination. | SIGNOR-271776 |
P17612 | P30301 | 1 | phosphorylation | down-regulates activity | 0.312 | Phosphorylation at one of these sites (serine 243) could be increased by A kinase in vitro. phosphorylation of MIP reconstituted into single bilayers increased the voltage dependence and long-term closures of the channels observed. | SIGNOR-250018 |
P31751 | Q15365 | 1 | phosphorylation | down-regulates activity | 0.429 | We show that heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) binds a structural, 33-nucleotide TGF-beta-activated translation (BAT) element in the 3' untranslated region of disabled-2 (Dab2) and interleukin-like EMT inducer (ILEI) transcripts, and represses their translation.TGF-beta activation leads to phosphorylation at Ser 43 of hnRNP E1 by protein kinase Bbeta/Akt2, inducing its release from the BAT element and translational activation of Dab2 and ILEI messenger RNAs. | SIGNOR-262625 |
Q06187 | O60674 | 0 | phosphorylation | up-regulates activity | 0.447 | Jak2 and Lyn coimmunoprecipitated with Btk and phosphorylated Btk on tyrosine (XREF_FIG C). | SIGNOR-279196 |
Q15139 | Q15276 | 1 | phosphorylation | up-regulates activity | 0.382 | PKD phosphorylates Rabaptin-5 at Ser407, and this controls alphavbeta3 and alpha5beta1 integrin and EGFR recycling. | SIGNOR-278192 |
Q68D86 | Q9BV73 | 0 | relocalization | up-regulates activity | 0.2 | CCDC102B is recruited to the centrosome by C-Nap1 (also known as CEP250) and interacts with the centrosome linker components rootletin and LRRC45. CCDC102B decorates and facilitates the formation of rootletin filaments. Furthermore, CCDC102B is phosphorylated by Nek2A (an isoform encoded by NEK2) and is disassociated from the centrosome at the onset of mitosis. | SIGNOR-275625 |
O00168 | P17612 | 0 | phosphorylation | up-regulates activity | 0.45 | PKA-dependent, alpha 1-specific NKA activation may be mediated through phosphorylation of the accessory protein PLM, rather than direct alpha1 subunit phosphorylation. we propose that phosphorylation of the small accessory protein phospholemman (PLM) by PKA at serine 68 is responsible for the observed isoform-specific activation of NKA. | SIGNOR-263117 |
Q16539 | P19419 | 1 | phosphorylation | up-regulates | 0.526 | We demonstrate here that elk-1 is barely activated by a third subclass of map kinases (p38), most likely because the critical residues ser383 and ser389 are poorly phosphorylated by p38 map kinase. | SIGNOR-47630 |
Q9UKX5 | P14921 | 0 | null | up-regulates quantity by expression | 0.281 | We speculate that the "mesenchymal signature" of alpha11 integrin gene expression is controlled by the activity of Sp1/Sp3, fibroblast-specific combinations of Ets family members and yet unidentified enhancer-binding transcription factors. | SIGNOR-253352 |
Q86Y13 | Q96QV6 | 1 | monoubiquitination | up-regulates activity | 0.2 | 2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation. | SIGNOR-271761 |
Q5VWQ8 | Q9HCE7 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.262 | DAB2IP protein levels can be negatively regulated by the activity of the E3-ubiquitin ligases Fbw7, Skp2, and Smurf1 | SIGNOR-254776 |
P52566 | Q9NYL2 | 0 | phosphorylation | down-regulates activity | 0.2 | In the present study, we provide evidence that ZAK serves as a RhoGDIbeta kinase, and demonstrate the phosphorylation of RhoGDIbeta by ZAK in vitro, as well as the physical association between ZAK and RhoGDIbeta.|These two proteins could negatively regulate one another such that ZAK suppresses RhoGDIbeta functions through phosphorylation and RhoGDIbeta counteracts the effects of ZAK by physical interaction. | SIGNOR-279633 |
O43318 | O75688 | 0 | dephosphorylation | down-regulates activity | 0.551 | In vitro, PP2Cbeta-1 dephosphorylated and inactivated TAK1. | SIGNOR-277154 |
P10636 | P60484 | 0 | dephosphorylation | up-regulates activity | 0.382 | Reduced phosphorylation of PTEN can dramatically increase tau phosphorylation and impair the ability of tau to bind to microtubules . | SIGNOR-277079 |
P60484 | P37231 | 0 | null | down-regulates activity | 0.456 | The PAX8-PPARγ rearrangement leads to strong induction of the PPARγ protein and the consequent abrogation of the normal PPARγ function. PPARγ overexpression abolishes the PTEN-inhibitory effect on immunoactive AKT, which in turn induces the PI3K signaling pathway. | SIGNOR-251997 |
Q06124 | Q8WU20 | 0 | phosphorylation | up-regulates | 0.78 | In addition to the direct interactions with grb2, tyrosine-phosphorylated frs2 forms a complex with the sh2 domain-containing protein tyrosine phosphatase shp2. This interaction results in tyrosine phosphorylation of shp2 and complex formation between shp2 and grb2. the catalytic activity of shp2 is essential for a sustained map kinase response and for potentiation of fgf-induced neurite outgrowth in pc12 cells | SIGNOR-58196 |
P17612 | P25098 | 1 | phosphorylation | up-regulates activity | 0.2 | PKA directly phosphorylates GRK2 on serine 685. This modification increases G subunit binding to GRK2 and thus enhances the ability of the kinase to translocate to the membrane and phosphorylate the receptor. | SIGNOR-250334 |
Q8IXJ6 | P18669 | 1 | deacetylation | up-regulates activity | 0.279 | Here we report that PGAM is acetylated at lysine 100 (K100), an active site residue that is invariably conserved from bacteria, to yeast, plant, and mammals. K100 acetylation is detected in fly, mouse, and human cells and in multiple tissues and decreases PGAM2 activity. The cytosolic protein deacetylase sirtuin 2 (SIRT2) deacetylates and activates PGAM2. | SIGNOR-266517 |
P17612 | Q07343 | 1 | phosphorylation | up-regulates activity | 0.605 | PKA-mediated phosphorylation of Ser-56 in UCR1 of PDE4B4 leads to activation of this long isoform | SIGNOR-250024 |
P12931 | P04049 | 1 | phosphorylation | up-regulates | 0.605 | We also show that phosphorylation of raf-1 on serine 338 by pak1 and tyrosines 340 and 341 by src relieves autoinhibition and that this occurs through a specific decrease in the binding of the raf-1 regulatory domain to its catalytic domain. | SIGNOR-97639 |
Q8NEB9 | O75385 | 0 | phosphorylation | up-regulates activity | 0.713 | In the nucleation step of autophagy, The ULK1 complex phosphorylates and activates the Beclin-1-VPS34 complex. | SIGNOR-279670 |
Q9UQM7 | P09917 | 1 | phosphorylation | up-regulates activity | 0.2 | Phosphorylation of serine 271 on 5-lipoxygenase and its role in nuclear export|We report here that 5-LO is constitutively phosphorylated on Ser-271 in transfected NIH 3T3 cells. This residue is nested in a classical nuclear export sequence, and phosphorylated Ser-271 5-LO was exclusively found in the nucleus by immunofluorescence and by fractionation techniques|Nuclear export of 5-LO can also be induced by KN-93, an inhibitor of Ca2+/calmodulin-dependent kinase II, and the effects of SB 203,580 plus KN-93 are additive. Finally, HeLa cells, which lack nuclear 5-LO, also lack constitutive phosphorylation of Ser-271. Taken together, these results indicate that the phosphorylation of Ser-271 serves to inhibit the nuclear export of 5-LO. | SIGNOR-264408 |
P27361 | O43524 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.595 | Phosphorylation of foxo3a by erk1/2 at residues ser 294, ser 344 and ser 425 increases foxo3amdm2 interaction and enhances foxo3a degradation via an mdm2-dependent ubiquitin-proteasome pathway | SIGNOR-184569 |
P06213 | Q13480 | 1 | phosphorylation | up-regulates activity | 0.502 | HGab-1 was phosphorylated by IR at eight tyrosine residues (Y242, Y285, Y373, Y447, Y472, Y619, Y657, and Y689). t Gab-1 is the major binding partner of PI-3 kinase in 3T3L1 cells when stimulated with insulin | SIGNOR-251310 |
P33981 | Q53HL2 | 1 | phosphorylation | up-regulates | 0.461 | First, we confirmed that wild-type borealin is phosphorylated at the previously described sites t88, t94, t169, and t230 when present in complex with survivin borealin might be a substrate for mps1. In the case of wild-type borealin, the fast exchange between the monomeric and dimeric forms may allow mps1 to phosphorylate the monomer. In turn, mps1 may regulate borealin function by unfolding the c-terminal domain and/or shifting the population to the monomeric form. | SIGNOR-186151 |
P19105 | P53355 | 0 | phosphorylation | up-regulates activity | 0.275 | DAPK Phosphorylates Myosin II RLC in Vitro and in Vivo. Together these results show that similar to the conventional MLCKs, Ser-19 is the primary RLC residue phosphorylated by DAPK and that phosphorylation of Thr-18 is also possible. | SIGNOR-262842 |
P27695 | P68400 | 0 | phosphorylation | up-regulates activity | 0.485 | Here we demonstrate that APE/Ref-1 is phosphorylated by casein kinase II (CKII). This was shown for both the recombinant APE/Ref-1 protein (Km=0.55 mM) and for APE/Ref-1 expressed in COS cells. Phosphorylation of APE/Ref-1 did not alter the repair activity of the enzyme, whereas it stimulated its redox capability towards AP-1, thus promoting DNA binding activity of AP-1. | SIGNOR-250825 |
P17252 | O60869 | 1 | phosphorylation | down-regulates activity | 0.301 | EDF-1 was phosphorylated in vitro by PKC in the presence of Ca2+ and phospholipids | This results shows that introduction of a single negative charge by phosphorylation at Thr-91 inhibited CaM-EDF-1 interactions. | SIGNOR-249041 |
Q9BXM7 | O60260 | 1 | phosphorylation | up-regulates | 0.2 | We show that human pink1 is specifically activated by mitochondrial membrane potential (??m) depolarization, enabling it to phosphorylate parkin at ser(65). We further show that phosphorylation of parkin at ser(65) leads to marked activation of its e3 ligase activity that is prevented by mutation of ser(65) or inactivation of pink1. | SIGNOR-197976 |
P48730 | P17302 | 1 | phosphorylation | up-regulates activity | 0.6 | We have examined the role of casein kinase 1 (CK1) in connexin-43 (Cx43) gap junction assembly. Cellular co-immunoprecipitation experiments and in vitro CK1 phosphorylation reactions indicate that CK1 interacted with and phosphorylated Cx43, initially on serine(s) 325, 328, or 330.| To examine CK1 function, normal rat kidney cells were treated with CKI-7, and Cx43 content was analyzed by Triton X-100 extraction, cell-surface biotinylation, and immunofluorescence. Western blot analysis indicated a slight increase in total Cx43, whereas gap junctional (Triton-insoluble) Cx43 decreased, and non-junctional plasma membrane Cx43 increased (as detected by cell surface biotinylation). | SIGNOR-249331 |
P24394 | Q9Y4H2 | 1 | phosphorylation | up-regulates | 0.592 | Irs-1 and a homologous protein, irs-2 (also known as 4-phosphotyrosine substrate), are recruited to phosphorylated y497 of IL-4R After ligand binding, leading to phosphorylation and activation of irs-1 and irs-2. | SIGNOR-100771 |
P28482 | P04049 | 1 | phosphorylation | down-regulates activity | 0.632 | Here, we identify six residues of Raf-1 (S29, S43, S289, S296, S301, and S642) that become hyperphosphorylated in a manner coincident with Raf-1 inactivation. | Five of the identified sites are proline-directed targets of activated ERK, and phosphorylation of all six sites requires MEK signaling, indicating a negative feedback mechanism. Hyperphosphorylation of these six sites inhibits the Ras/Raf-1 interaction and desensitizes Raf-1 to additional stimuli.|FLAG-Raf-1 phosphorylated by activated ERK2 | SIGNOR-249441 |
Q12913 | P17948 | 1 | dephosphorylation | down-regulates | 0.362 | Vegf acts by binding to two high affinity receptor tyrosine kinases: vegf receptor (vegfr)* 1 also called flt-1, and vegfr-2, also called flk-1/kdr a dominant-negative mutant of high cell densityenhanced ptp 1 (dep-1)//cd148 as well as reduction of its expression by rna interference partially restore vegfr-2 phosphorylation and map kinase activation. | SIGNOR-101272 |
P33176 | Q9UBS5 | 1 | relocalization | up-regulates activity | 0.255 | GABABR1 co-immunoprecipitated with Marlin-1 and kinesin-I, providing evidence for the existence of a complex between these proteins. Kinesin-I modulates GABAB receptor transport. | SIGNOR-260990 |
O43791 | P52945 | 1 | ubiquitination | down-regulates quantity | 0.326 | Pdx1 C terminus-interacting factor-1 (Pcif1, also known as SPOP) is a nuclear protein that inhibits Pdx1 transactivation. Here, we show that Pcif1 targets Pdx1 for ubiquitination and proteasomal degradation. | SIGNOR-268859 |
Q9Y243 | P15056 | 1 | phosphorylation | down-regulates | 0.289 | We show that phosphorylation of b-raf by akt occurs at multiple residues within its aminoterminal regulatory domain, at both the conserved and unique phosphorylation sites. Akt phosphorylated b-raf on s364 and s428 to inactivate its kinase activity. | SIGNOR-78693 |
Q9NRM7 | P17612 | 0 | phosphorylation | up-regulates | 0.2 | Here, we show that cyclic amp (camp)-dependent protein kinase (pka) phosphorylates lats and thereby enhances its activity sufficiently to phosphorylate yap on ser381. | SIGNOR-236994 |
O95999 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.468 | Upon DNA damage, ATM phosphorylates the residue T91 of BCL10, promoting binding of BCL10 to RNF8 and simultaneously presenting UBC13 to RNF8.|When cells were pre-treated with different PIKK inhibitors, the ATM specific inhibitor KU55933 efficiently reduced etoposide induced focus formation of BCL10, whereas pretreatment of cells with NU6027, an ATR specific inhibitor, or NU7026, a DNA-PKcs-specific inhibitor, did not compromise etoposide induced focus formation of BCL10 (XREF_FIG). | SIGNOR-278392 |
P05771 | P19429 | 1 | phosphorylation | down-regulates | 0.2 | Pkc-betaii sensitizes cardiac myofilaments to ca2+ by phosphorylating troponin i on threonine-144. | SIGNOR-149957 |
Q06124 | P00519 | 0 | phosphorylation | up-regulates activity | 0.374 | Direct phosphorylation of SHP-2 by Abl kinases (Y580) promotes sustained activation of SHP-2 signaling and proliferation, and c-Abl/Abl-Related Gene-dependent activation of tyrosine kinase X further potentiates SHP-2 signaling by phosphorylating SHP-2 on Y63.|Endogenous Abl kinases phosphorylate SHP-2 on Y580 and induce sustained ERK phosphorylation in response to PDGF. | SIGNOR-278217 |
P45983 | P63104 | 1 | phosphorylation | down-regulates | 0.371 | Jnk phosphorylated 14-3-3 at ser-184 and 14-3-3 at ser-186 both in vitro and in vivo, and such phosphorylation reduced the affinity of 14-3-3 proteins for bax | SIGNOR-124020 |
P04637 | Q8IUQ4 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.372 | P53 directly induces the expression of Siah-1 and in turn formation of a unique SCF-like complex (SCF(TBL1)) comprised of Siah-1, Siah-1-interacting protein (SIP), Skp1, transducin β-like 1 (TBL1), and APC | SIGNOR-271953 |
Q15910 | P52333 | 0 | phosphorylation | up-regulates activity | 0.428 | These results demonstrate that phosphorylation of EZH2 by JAK3 on the Y244 increases the interaction with Polymerase II and decreases the association with PRC2 components promoting the expression of non-canonical genes.|To explore the mechanism of JAK3 mediated EZH2 activation, the authors performed co-immunoprecipitation assays, which revealed interaction of EZH2 with JAK3 and polymerase II. | SIGNOR-278518 |
P46531 | Q92630 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.288 | We demonstrate that DYRK2 phosphorylates Notch1-IC in response to chemotherapeutic agents and facilitates its proteasomal degradation by FBXW7 ubiquitin ligase through a Thr-2512 phosphorylation-dependent mechanism. | SIGNOR-279035 |
P45984 | O14733 | 0 | phosphorylation | up-regulates | 0.637 | Here we report that mkk4 shows a striking preference for the tyrosine residue (tyr-185), and mkk7 a striking preference for the threonine residue (thr-183) in three sapk1/jnk1 isoforms tested (jnk1 alpha 1, jnk2 alpha 2 and jnk3 alpha 1). These results indicate that hgk, a novel activator of the jnk pathway, may function through tak1, and that the hgk --> tak1 --> mkk4, mkk7 --> jnk kinase cascade may mediate the TNF-alphalpha signaling pathway. | SIGNOR-83744 |
Q9NZJ5 | Q08209 | 1 | phosphorylation | down-regulates activity | 0.2 | CN becomes phosphorylated by PERK, decreasing its activity.|Finally, evidence is presented that PERK phosphorylates CN-A at low resting levels of Ca 2+. | SIGNOR-278933 |
O60934 | Q13535 | 0 | phosphorylation | up-regulates | 0.785 | We demonstrate that mrn and atr/atr-interacting protein (trip) interact with each other, and the forkhead-associated/breast cancer c-terminal domains (fha/brct) of nbs1 play a significant role in mediating this interaction. Mutations in the fha/brct domains do not prevent atr activation but specifically impair atr-mediated nbs1 phosphorylation at ser-343, which results in a defect in the s-phase checkpoint. | SIGNOR-155214 |
P42345 | Q9UHD2 | 0 | phosphorylation | up-regulates activity | 0.42 | They later demonstrated that TANK-binding kinase 1 (TBK1) interacts with and phosphorylates mTOR on Ser 2159, to promote catalytic activity of mTOR [216]. | SIGNOR-278237 |
O15391 | P01100 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.392 | YY2 activated the p53 promoter. However, in contrast to YY1, which represses the activity of c-Fos, YY2 increased the activity of the c-Fos promoter. | SIGNOR-266212 |
P12830 | Q13363 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.6 | Carboxyl-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor with oncogenic potential. We found CtBP1 was recruited to the promoter regions of Brca1 and E-cadherin genes in breast cancer cells. | SIGNOR-259197 |
O14640 | Q76N89 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.641 | We have also found that NEDL1 targets Dishevelled-1 (Dvl1) for ubiquitination-mediated degradation and that mutant (but not wild-type) SOD1 affects the function of Dvl1. | SIGNOR-271499 |
Q05655 | P29474 | 1 | phosphorylation | down-regulates activity | 0.568 | The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites | SIGNOR-251631 |
P61586 | Q9P227 | 0 | gtpase-activating protein | down-regulates activity | 0.548 | 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-260479 |
Q15418 | P25963 | 1 | phosphorylation | up-regulates activity | 0.386 | Mitogen activated ribosomal S6 kinase (p90 rsk1) phosphorylates IkappaBalpha at S32, binds IkappaBalpha in vivo, and overexpression of dominant negative p90 rsk1 inhibits degradation of IkappaBalpha in response to TPA. | SIGNOR-279311 |
Q86Y13 | Q96KK5 | 1 | monoubiquitination | up-regulates activity | 0.2 | 2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation. | SIGNOR-271760 |
Q9NVW2 | P08047 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Thus, RLIM is a novel target of p53, and p53 exerts its inhibitory effect on RLIM expression by interfering with Sp1-mediated transcriptional activation on RLIM.|Although p53 does not directly bind to the RLIM promoter, it physically interacts with and prevents the binding of Sp1 to the RLIM promoter. | SIGNOR-268980 |
P49841 | P24385 | 1 | phosphorylation | down-regulates | 0.783 | Phosphorylation of cyclin d1 on a single threonine residue near the carboxyl terminus (thr-286) positively regulates proteasomal degradation of d1. Now, we demonstrate that glycogen synthase kinase-3beta (gsk-3beta) phosphorylates cyclin d1 specifically on thr-286, thereby triggering rapid cyclin d1 turnover now, we demonstrate that glycogen synthase kinase-3beta (gsk-3beta) phosphorylates cyclin d1 specifically on thr-286, thereby triggering rapid cyclin d1 turnover. | SIGNOR-144818 |
Q7KZI7 | P10636 | 1 | phosphorylation | down-regulates activity | 0.707 | We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs. | SIGNOR-275436 |
Q14643 | P35398 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.242 | RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice. | SIGNOR-266847 |
Q99986 | P38432 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.361 | The active murine VRK1, but not its kinase-dead mutant (K179E), also phosphorylates coilin in Ser184 ( xref ). | SIGNOR-279772 |
Q00535 | P16949 | 1 | phosphorylation | down-regulates | 0.376 | Involved in the regulation of the microtubule (mt) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. The kinases involved in phosphorylating stmn ser-16 and ser-63 include camp-dependent protein kinase (pka) and pak1, whereas stmn ser-25 and ser-38 have been shown to be targets for proline-directed serine/threonine kinases such as cyclin-dependent kinases, erk1/2, and members of the p38 mapk subfamily. | SIGNOR-166682 |
Q92466 | P00519 | 0 | phosphorylation | down-regulates | 0.458 | C-abl might act as a negative regulator of uv-ddb by phosphorylating ddb2 | SIGNOR-90446 |
P24941 | Q12800 | 1 | phosphorylation | down-regulates | 0.2 | In vitro, lsf is phosphorylated by cyclin e/cyclin-dependent kinase 2 (cdk2), cyclin c/cdk2, and cyclin c/cdk3, predominantly on s309. Phosphorylation by cyclin c/cyclin-dependent kinase 2 following mitogenic stimulation of murine fibroblasts inhibits transcriptional activity of lsf during g1 progression | SIGNOR-184160 |
P12931 | P57737 | 1 | phosphorylation | up-regulates activity | 0.339 | We establish that Src activity is indispensable for the interaction of Crn7 with Golgi membranes. Crn7 binds Src in vivo and can be phosphorylated by recombinant Src in vitro. We demonstrate that tyrosine-758 is the major Src phosphorylation site. | SIGNOR-274005 |
P06493 | P15172 | 1 | 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 |
P17612 | Q8IWU9 | 1 | phosphorylation | up-regulates | 0.254 | We also demonstrate that phosphorylation of serine 19, a protein kinase a consensus site located in this n-terminal domain, results in increased tph2 stability and consequent increases in enzyme output in cell culture systems | SIGNOR-178018 |
Q13415 | P06493 | 0 | phosphorylation | up-regulates | 0.637 | Horc1p contains three (s/t)px(k/r) consensus sites for cdk phosphorylation (ser258, ser273, and thr375). These data combined strongly suggest that skp2 promotes horc1p turnover and that the n-terminal domain of horc1p, containing most of the phosphorylation sites and overlapping with one of the skp2-interacting domains, is a regulatory element for horc1p stability. | SIGNOR-116329 |
P33076 | Q92769 | 0 | deacetylation | down-regulates quantity by repression | 0.413 | We report that CIITA and histone deacetylase 2 (HDAC2) interact in smooth muscle cells and macrophages as assayed by co-immunoprecipitations. HDAC2 deacetylates CIITA whereas both the HDAC inhibitor trichostatin A (TSA) and over-expression of HDAC2 interfering RNA increase CIITA acetylation. HDAC2 down-regulates CIITA recruitment to target promoters as evidenced by chromatin immunoprecipitation assays, and suppresses MHC II activation and collagen repression mediated by CIITA in luciferase reporter assays. | SIGNOR-254231 |
Q96EP1 | Q93009 | 0 | deubiquitination | up-regulates quantity by stabilization | 0.432 | In this study, we identified USP7 (also known as HAUSP), which is a member of a family of proteins that cleave polyubiquitin chains and/or ubiquitin precursors, as an interacting protein with Chfr by immunoaffinity purification and mass spectrometry, and their interaction greatly increases the stability of Chfr. In fact, USP7 can remove ubiquitin moiety from the autoubiquitinated Chfr both in vivo and in vitro, which results in the accumulation of Chfr in the cell. USP7 mediates deubiquitination of Chfr. | SIGNOR-271462 |
P53350 | O43524 | 1 | phosphorylation | down-regulates activity | 0.491 | Furthermore, PLK1 can directly phosphorylate FOXO3 in an in vitro kinase assay.|PLK1 induces translocation of FOXO3 from the nucleus to the cytoplasm and suppresses FOXO3 activity, measured by the decrease in the pro-apoptotic Bim protein levels and in the cell cycle inhibitor protein p27. | SIGNOR-279095 |
Q14247 | Q13153 | 0 | phosphorylation | up-regulates | 0.707 | Strikingly, we find that pak1 phosphorylation of cortactin on serine residues 405 and 418 increases its association with n-wasp. Thus, pak1, by controlling the interaction between cortactin and n-wasp, could regulate the polymerization of actin during clathrin-independent endocytosis. | SIGNOR-169690 |
P00533 | Q96CW1 | 0 | relocalization | down-regulates | 0.524 | The removal of the epidermal growth factor receptor (egfr) from the cell surface by endocytosis is triggered by receptor activation, but many facets of egfr trafficking remain unresolvedthe ap-2 complex is involved in the internalization of activated egfr. | SIGNOR-185124 |
Q15831 | P57059 | 1 | phosphorylation | up-regulates | 0.584 | Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1we recently demonstrated that the lkb1 tumour suppressor kinase, in complex with the pseudokinase strad and the scaffolding protein mo25, phosphorylates and activates amp-activated protein kinase (ampk). A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold | SIGNOR-122784 |
P06241 | Q9UQC2 | 1 | phosphorylation | up-regulates activity | 0.605 | Our studies show that Gab2 is activated by Fyn kinase upon the engagement of ligand to TNFR1, IL-1R, or TLR4.|TNF\u03b1, IL-1\u03b2, and LPS induce Fyn kinase-mediated phosphorylation of Gab2. | SIGNOR-279984 |
Q05469 | Q13131 | 0 | phosphorylation | down-regulates | 0.41 | Phosphorylation of bovine hormone-sensitive lipase by the amp-activated protein kinase. | SIGNOR-58255 |
Q13769 | P17252 | 0 | phosphorylation | up-regulates | 0.327 | We conclude m-csf-mediated activation of pkcalpha can potentiate fmip action to initiate survival/differentiation signaling. | SIGNOR-126572 |
Q8N5S9 | Q8TDC3 | 1 | phosphorylation | up-regulates activity | 0.307 | In transfected COS-7 cells, kinase activity and Thr (189) phosphorylation of overexpressed SAD-B were significantly enhanced by coexpression of constitutively active CaMKKalpha (residues 1-434) in a manner similar to that observed with coexpression of LKB1, STRAD, and MO25.|Taken together, these results indicate that CaMKKalpha is capable of activating SAD-B through phosphorylation of Thr (189) both in vitro and in vivo and demonstrate for the first time that CaMKK may be an alternative activating kinase for SAD-B. | SIGNOR-280202 |
Q96EB6 | P06493 | 0 | phosphorylation | up-regulates | 0.528 | We identified cyclinb/cdk1 as a cell cycle-dependent kinase that forms a complex with and phosphorylates sirt1. Mutation of two residues phosphorylated by cyclin b/cdk1 (threonine 530 and serine 540) disturbs normal cell cycle progression and fails to rescue proliferation defects in sirt1-deficient cells | SIGNOR-182863 |
P30307 | O00444 | 0 | phosphorylation | up-regulates quantity | 0.461 | Conclusion: PLK4 contributes to the formation of PGCCs by regulating the expression of CDC25C and is associated with the expression and subcellular location of CDC25C, pCDC25C-ser216 and pCDC25C-ser198.|PLK4 could interact with CDC25C and promote CDC25C phosphorylation which was associated with the formation of PGCCs. | SIGNOR-280074 |
P20823 | Q9HAW9 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.281 | Using gel shift and functional assays, HNF1alpha was demonstrated to bind to and activate the UGT1A8, -1A9, and -1A10 promoters. In contrast, Cdx2 bound to and activated the UGT1A8 and -1A10 promoters but could not activate the UGT1A9 promoter. | SIGNOR-253972 |
Q5S007 | Q99683 | 1 | phosphorylation | up-regulates activity | 0.325 | LRRK2 phosphorylated ASK1 at Thr832 that is adjacent to Thr845, which serves as an autophosphorylation site. | SIGNOR-277251 |
Q9UNH5 | Q9NQR1 | 1 | 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-248835 |
P40424 | P12830 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.267 | We show that the Pbx1 and Meis2 homeodomain proteins interact with Klf4 and can be recruited to DNA elements comprising a Klf4 site or G C box, with adjacent Meis and Pbx sites. Meis2d and Pbx1a activate expression of p15(Ink4a) and E-cadherin, dependent on the Meis2d transcriptional activation domain. We suggest a model in which genes with Klf4 sites can be cooperatively activated by Meis2/Pbx1 and Klf4, dependent primarily on recruitment by Klf4. | SIGNOR-267241 |
Q13164 | Q05397 | 1 | phosphorylation | up-regulates activity | 0.291 | Remarkably, the reduction in ERK5 expression correlated with decreased p-FAK(Tyr397) staining, consistent with the requirement of ERK5 for mediating FAK activation in vivo (Fig. 6C).|We confirmed that JWG-045, a novel pharmacological inhibitor of ERK5 exhibiting significantly reduced affinity for BRD4 compared with XMD8-92 (25, 26), did not suppress FAK phosphorylation at Tyr397 in MDA-MB-231 cells (Supplementary Fig. S3B and C). | SIGNOR-279304 |
P62714 | P04637 | 1 | dephosphorylation | up-regulates quantity by stabilization | 0.437 | A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-induced dephosphorylation of p53 at Thr55| In this study, we reported that the specific B regulatory subunits of PP2A B56gamma1 and B56gamma3 mediate dephosphorylation of p53 at Thr55. Ablation of the B56gamma protein by RNAi, which abolishes the Thr55 dephosphorylation in response to DNA damage, reduces p53 stabilization, Bax expression and cell apoptosis | SIGNOR-248583 |
Q16665 | O60341 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.265 | To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a. | SIGNOR-271573 |
P00533 | P10586 | 0 | dephosphorylation | down-regulates activity | 0.336 | Some 10 years ago, Hashimoto et al. (87) had shown that the LAR catalytic domain can dephosphorylate the EGFR receptor in vitro, and more recently, Kulas and colleagues (88) have demonstrated that the antisense mediated suppression of LAR can enhance the growth factor induced activation of EGFR in rat hepatoma cells.|These data indicate that LAR and RPTPsigma may have a significant role in GPCR induced EGFR signalling.Whereas in A431 cells LAR and RPTPsigma may act to suppress the EGFR in response to GPCR activation, it is possible that the converse may also be true in other cell types. | SIGNOR-277029 |
P15056 | Q96TA1 | 1 | phosphorylation | down-regulates activity | 0.2 | Overall, this indicates that BRAF-dependent phosphorylation of FAM129B controls its cellular localization and thus its ability to bind to KEAP1 to block NRF2 degradation. | SIGNOR-279595 |
P24941 | O75469 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.372 | PXR Phosphorylation at S350 by CDK2 Triggers PXR Degradation via the Ubiquitin-Proteasome Pathway. | SIGNOR-279397 |
P26038 | Q5S007 | 0 | phosphorylation | up-regulates activity | 0.551 | This led to the discovery that moesin, a protein which anchors the actin cytoskeleton to the plasma membrane, is efficiently phosphorylated by lrrk2, at thr558. Moesin phosphorylation could be essential to support the cytoskeletal changes accompanying this process. | SIGNOR-154498 |
Q9H2X6 | O15297 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.419 | HIPK2 phosphorylates WIP1 at Ser54 and Ser85, and phosphorylated WIP1 is subject to proteasomal degradation so that WIP1 is maintained at low levels. | SIGNOR-278230 |
O15379 | Q9H2X6 | 0 | phosphorylation | down-regulates activity | 0.2 | Mechanistically, HIPK2 bound and phosphorylated histone deacetylase 3 (HDAC3) at serine 374 to inhibit its enzymatic activity, thus reducing the deacetylation of p65 at lysine 218 to suppress NF-κB activation. | SIGNOR-277568 |
P20333 | Q9HAU4 | 0 | ubiquitination | up-regulates activity | 0.326 | However, co-transfection of Smurf2, but not Smurf2-C/A, drastically increased the potential of TNF-R2 to induce JNK phosphorylation.|In conclusion, these results indicate that Smurf2 is able to ubiquitinate TNF-R2, which is further enhanced by the TRAF2-mediated targeting of Smurf2 to TNF-R2. | SIGNOR-278716 |
P15498 | P63000 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.765 | 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-260581 |
Q15078 | P07384 | 0 | cleavage | up-regulates activity | 0.571 | Calpains also modulate the activity of CDK5. Physiologically, CDK 5 is activated by p35 and its cleaved product p25. The latter has a longer half life than p35 and therefore it is a more potent activator of CDK5. The cleavage of p35 to p25 is mediated by calpain | SIGNOR-251583 |
P06127 | P68400 | 0 | phosphorylation | up-regulates | 0.342 | In this study, we use jurkat t cell transfectants of cd5 cytoplasmic tail mutants to reveal phosphorylation sites relevant to signal transduction. Our results show that casein kinase ii (ckii) is responsible for the constitutive phosphorylation of cd5 molecules at a cluster of three serine residues located at the extreme c terminus (s458, s459, and s461) | SIGNOR-62311 |
Q9BXM7 | O00429 | 1 | phosphorylation | up-regulates activity | 0.6 | We here demonstrate that PINK1 directly phosphorylates Drp1 on S616. | SIGNOR-279548 |
P35222 | P10721 | 0 | phosphorylation | up-regulates activity | 0.392 | These results suggest that active KIT can directly phosphorylate tyrosine residues of beta-catenin. | SIGNOR-278361 |
P24723 | Q15139 | 1 | phosphorylation | up-regulates | 0.355 | These results provide direct evidence that pkd becomes activated in vivo as a consequence of pkc-mediated phosphorylation of serines 744 and 748. | SIGNOR-66734 |
Q9BYP7 | P55011 | 1 | phosphorylation | up-regulates activity | 0.525 | 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-264625 |
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