IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels float64 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 |
|---|---|---|---|---|---|---|---|
P38646 | P53602 | 1 | binding | down-regulates activity | 0.342 | Mortalin binds to mevalonate pyrophosphate decarboxyl ase in mammalian cell. Mot-2 inactivates MPD resulting in decreased amounts of the steady state Ras protein. | SIGNOR-265890 |
Q9UN86 | P25963 | 1 | relocalization | down-regulates activity | 0.342 | IkappaBalpha interacts with G3BP2 both in vivo and in vitrothrough the IkappaBalpha CRS. Overexpression of G3BP2 directly promotes retention of IkappaBalpha in the cytoplasm. | SIGNOR-260985 |
Q9UM11 | P04183 | 1 | binding | down-regulates quantity by destabilization | 0.342 | We show that hTK1 is degraded via a ubiquitin-proteasome pathway in mammalian cells and that anaphase-promoting complex/cyclosome (APC/C) activator Cdh1 is not only a necessary but also a rate-limiting factor for mitotic degradation of hTK1. By in vitro ubiquitinylation assays, we demonstrated that hTK1 is targeted for degradation by the APC/C-Cdh1 ubiquitin ligase dependent on this KEN box motif. | SIGNOR-272945 |
Q13523 | Q9Y2Y9 | 1 | phosphorylation | down-regulates | 0.342 | Using yeast two-hybrid screening of a human thymus cdna library, prp4, a serine/threonine protein kinase, was identified as a klf13-binding protein...coexpression of prp4 and klf13 increases nuclear localization of klf13 and ccl5 transcription. | SIGNOR-154951 |
Q9HD26 | P08588 | 1 | relocalization | down-regulates | 0.342 | Overexpression of cal reduces surface expression of beta1ar. Interaction with cal promotes retention of beta1ar within the cell | SIGNOR-128791 |
Q6X9E4 | Q8N6P7 | 1 | binding | down-regulates quantity by destabilization | 0.342 | FBXW12 causes depletion of endogenous and plasmid-derived IL-22R in lung epithelia, binds the E3 ligase constituent Skp-1, and facilitates ubiquitination of IL-22R in vitro. | SIGNOR-272426 |
P11387 | O00327 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.342 | We examined the mechanism of topoisomerase I (Top1) to understand the role of the unique chromatin structure in Bmal1 gene regulation. Promoter assays showed that the Top1-binding site is required for transcriptional suppression and that it functions cooperatively with the distal RORE, supporting that Bmal1 transcription is upregulated by Top1 inhibition. | SIGNOR-277354 |
P27361 | P33076 | 1 | phosphorylation | up-regulates | 0.341 | We found that in these cells, lipopolysaccharide stimulates the expression of mhc ii genes via the activation of erk1/2, which is mediated by toll-like receptor 4. Erk1/2 then phosphorylates the serine at position 357, which is located in a degron of ciita isoform 1 that leads to its monoubiquitylation. | SIGNOR-150545 |
Q9UK99 | Q09472 | 1 | binding | down-regulates quantity by destabilization | 0.341 | O clarify the role of PML in transcription regulation, we purified the PML complex and identified Fbxo3 (Fbx3), Skp1, and Cullin1 as novel components of this complex. Fbx3 formed SCF(Fbx3) ubiquitin ligase and promoted the degradation of HIPK2 and p300 by the ubiquitin-proteasome pathway. | SIGNOR-271742 |
Q9HCS4 | Q9H9S0 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.341 | These experiments showed that Tcf3 is associated with chromatin in the Nanog promoter regions and that the DNA-binding activity of Tcf3 was required for repression. | SIGNOR-266081 |
P68400 | Q13541 | 1 | phosphorylation | down-regulates | 0.341 | Phosphorylation at s112 directly affects binding of 4e-bp1 to eif4e without influencing phosphorylation of other sites. | SIGNOR-98280 |
P06493 | Q01196 | 1 | phosphorylation | up-regulates | 0.341 | Phosphorylation of runx1 on ser-303 by cdks leads its ubiquitin-mediated degradation during g2/m (19). We developed additional evidence that cdks phosphorylate ser-303 and found that ser-48 and ser-424 are also substrates of cdk1/cyclin b and cdk6/cyclin d3. Moreover, we demonstrated that phosphorylation of ser-48, ser-303, and ser-424 strengthens the ability of runx1 to activate transcription and to stimulate proliferation of the ba/f3 hematopoietic cell line (20). | SIGNOR-169322 |
P49841 | O15516 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.341 | We have identified a conserved cluster of serines that include, Ser431, which is a prerequisite phosphorylation site for the generation of BMAL dependent phospho-primed CLOCK and for the potential GSK-3 phosphorylation at Ser427. | SIGNOR-276270 |
P23458 | Q9Y5X2 | 1 | phosphorylation | up-regulates activity | 0.341 | IFNγ induced JAK1-mediated phosphorylation of SNX8 at Tyr95 and Tyr126, which promoted the recruitment of IKKβ to the JAK1 complex. | SIGNOR-273647 |
P53779 | Q9NR28 | 1 | phosphorylation | down-regulates | 0.341 | Here we demonstrate that jnk3 can phosphorylate smac. Phosphorylation of smac by jnk3 attenuates its interaction with xiap. These results suggest that jnk3 activity can attenuate the progression of apoptosis through a novel mechanism of action, the down-regulation of interaction between smac and xiap. | SIGNOR-157280 |
Q13131 | Q9UQL6 | 1 | phosphorylation | down-regulates | 0.341 | Another recently described set of transcriptional regulators targeted by ampk and its related family members across a range of eukaryotes are the class iia family of histone deacetylases (hdacs) | SIGNOR-176479 |
P06493 | Q8TAP9 | 1 | phosphorylation | up-regulates | 0.341 | Ttdn1 is phosphorylated by cdk1 in vitro and in vivo. Ttdn1 is phosphorylated at multiple residues, including ser93 and ser104. Mutation of thr120 of ttdn1 abolishes its interaction with plk1, suggesting phosphorylation of thr120 in the consensus plk1-binding motif is required for its interaction with plk1 | SIGNOR-153308 |
Q9Y574 | Q02363 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.341 | Using JAR placental cells, we determined that ASB4 ubiquitinates and represses ID2 expression in a proteasome-dependent fashion. | SIGNOR-272053 |
P00533 | P12004 | 1 | phosphorylation | up-regulates | 0.341 | Here, we show that the chromatin-bound pcna protein is phosphorylated on tyr 211, which is required for maintaining its function on chromatin and is dependent on the tyrosine kinase activity of egf receptor (egfr) in the nucleus. Phosphorylation on tyr 211 by egfr stabilizes chromatin-bound pcna protein and associated functions. | SIGNOR-150852 |
P50281 | Q13443 | 1 | cleavage | down-regulates quantity by destabilization | 0.341 | Here we show that MT1-MMP forms a complex with FGFR2 and ADAM9 in osteoblasts and proteolytically inactivates ADAM9|Western blotting using antibodies against ectodomain of ADAM9 detected a fragment (around 26 kDa) of ADAM9 in the conditioned culture medium from cells cotransfected with wild-type MT1-MMP, but not in that with catalytic activity-dead MT1-MMP (Figure 6A, top). | SIGNOR-260301 |
Q5T6F2 | P07355 | 1 | ubiquitination | down-regulates quantity | 0.341 | UBAP2 formed a complex with Annexin A2 and promoted the degradation of Annexin A2 protein by ubiquitination | SIGNOR-261314 |
P61011 | Q01130 | 1 | binding | up-regulates activity | 0.341 | We have now demonstrated that p54 interacts not only with SC35 and ASF/SF2 but also with U2AF. Pairwise interactions between p54 and other RS domain-containing spliceosomal proteins in comparison with SC35 and ASF/SF2 as detected by the yeast two-hybrid interaction assay. . It is conceivable that p54 can mediate 59 and 39 splice site interaction by interacting directly with U2AF65 associated with the 39 splice site and at the same time interact with other SR proteins, such as ASF/SF2 and SC35, which in turn interact with U1-70K. In this scenario, p54 is different from SC35 or ASF/SF2 in that it cannot directly interact with the 59 component (U1-70K) but can interact with the protein associated with the 39 splice site (U2AF65). | SIGNOR-261160 |
P46777 | O15350 | 1 | binding | up-regulates | 0.341 | We report that rpl5 and rpl11 can also enhance the transcriptional activity of a p53 homolog tap73 | SIGNOR-205517 |
Q9H000 | Q04206 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.341 | MKRN2 promotes p65 ubiquitination and degradation through RING finger domain. | SIGNOR-278591 |
P17612 | P19544 | 1 | phosphorylation | down-regulates | 0.341 | Pka phosphorylated wt1 at ser-365 and ser-393 in vitro, as well as at additional sites, and this phosphorylation abolished the dna-binding activity of wt1 in vitro. Using wt1 mutants in which ser-365 and ser-393 were mutated to ala individually and in combination, we showed that phosphorylation of these sites was critical for inhibition of dna binding in vivo. | SIGNOR-53172 |
Q13362 | P23443 | 1 | binding | down-regulates | 0.341 | The human homolog of pp2a-b', ppp2r5c, also counteracts s6k1 phosphorylation, indicating a conserved mechanism in mammals | SIGNOR-165224 |
Q00535 | P21860 | 1 | phosphorylation | up-regulates activity | 0.341 | We demonstrated that Cdk5 phosphorylated Ser-1176 in the neuregulin receptor ErbB2 and phosphorylated Thr-871 and Ser-1120 in the ErbB3 receptor. We identified the Ser-1120 sequence RSRSPR in ErbB3 as a novel phosphorylation consensus sequence of Cdk5. Finally, we found that Cdk5 activity is involved in neuregulin-induced Akt activity and neuregulin-mediated neuronal survival. | SIGNOR-250663 |
Q9ULJ8 | Q92974 | 1 | binding | up-regulates activity | 0.341 | The Rho Family GEF Lfc Interacts with Neurabin and Spinophilin. Neurabin and spinophilin are homologous protein phosphatase 1 and actin binding proteins that regulate dendritic spine function. The results obtained in the present study suggest a mechanism by which neurabin or spinophilin contributes to the organization of the F-actin cytoskeleton in dendritic spines, and in turn to the regulation of spine morphology, via the activity-dependent recruitment of the Rho-specific GEF Lfc | SIGNOR-269177 |
Q00535 | Q05682 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.341 | Together, these data demonstrate that phosphorylation of caldesmon on Ser527 by Cdk5 serves to down regulate its stability. | SIGNOR-280215 |
P05129 | P06127 | 1 | phosphorylation | up-regulates | 0.341 | Cd5 is a good pkc substrate. Phosphorylation of cd5 is necessary for cd5-mediated lipid second messenger generation. | SIGNOR-85183 |
Q7KZI7 | Q6WKZ4 | 1 | phosphorylation | up-regulates quantity | 0.341 | We have now found that MARK2 phosphorylates Rab11-FIP1B/C at serine 234 in a consensus site similar to that previously identified in Rab11-FIP2. | SIGNOR-273676 |
O60346 | P05771 | 1 | dephosphorylation | down-regulates quantity | 0.341 | Here we show that the two PHLPP isoforms, PHLPP1 and PHLPP2, also dephosphorylate the hydrophobic motif on PKC betaII, an event that shunts PKC to the detergent-insoluble fraction, effectively terminating its life cycle | SIGNOR-237047 |
P00519 | P37231 | 1 | phosphorylation | up-regulates quantity | 0.341 | We show that the tyrosine kinase Abelson murine leukemia viral oncogene (cAbl) is an adipogenic key regulator. c-Abl promotes adipogenesis by phosphorylation and subsequent stabilization of PPARγ. | SIGNOR-262297 |
P23470 | P00519 | 1 | dephosphorylation | down-regulates activity | 0.341 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254691 |
Q15759 | P10636 | 1 | phosphorylation | down-regulates activity | 0.341 | Phosphorylation of tau by SAPK3 and SAPK4 resulted in a marked reduction in its ability to promote microtubule assembly.|Tau phosphorylated by SAPK2b and SAPK2a also reacted with AT8, whereas AT8 failed to recognise tau phosphorylated by SAPK1gamma. | SIGNOR-279637 |
P08069 | O15530 | 1 | phosphorylation | up-regulates | 0.341 | Previous studies indicate that optimal activation of PDK1 requires phosphorylation of Tyr373/376 (11, 12, 14, 17), and growth factor receptor activation leads to PDK1 recruitment to the plasma membrane, followed by sequential phosphorylation of Tyr9 and then Tyr373/376 | SIGNOR-166710 |
P14780 | P10915 | 1 | cleavage | down-regulates quantity by destabilization | 0.341 | Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix. | SIGNOR-256328 |
Q07021 | P02746 | 1 | binding | down-regulates activity | 0.341 | Previous studies have shown that gC1qR inhibits aggregated IgG-mediated complement activation by binding to the gC1q site on C1q, thereby preventing IgG from binding to the gh’s (28), suggesting that the binding sites for gC1qR and IgG on C1q may be identical or at least overlapping. | SIGNOR-263403 |
Q9UFD9 | Q86UR5 | 1 | binding | down-regulates activity | 0.341 | SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins. | SIGNOR-264360 |
Q14344 | Q8N1W1 | 1 | binding | up-regulates activity | 0.341 | Taken together, the results suggest that active G13 and Gq form a complex with Rgnef and that G13 and Gq are upstream activators of Rgnef. | SIGNOR-278064 |
Q14164 | P03372 | 1 | phosphorylation | up-regulates | 0.341 | Here, we show that ikkepsilon interacts with and phosphorylates estrogen receptor alpha (eralpha) on serine 167 in vitro and in vivo. As a result, ikkepsilon induces eralpha transactivation activity and enhances eralpha binding to dna. | SIGNOR-161834 |
P17252 | Q15172 | 1 | phosphorylation | down-regulates activity | 0.341 | In this study, we identified a novel phosphorylation site at Ser(41) of B56α. This phosphoamino acid residue was efficiently phosphorylated in vitro by PKCα. | SIGNOR-276603 |
P49841 | P03372 | 1 | phosphorylation | up-regulates | 0.34 | The gsk-3 inhibitor lithium chloride was used to determine the role of gsk-3 in phosphorylation of ser-102, -104, and -106 and ser-118 in vivo and to explore the role of these serines in the regulation of eralpha function. Treatment of cells with lithium chloride resulted in dephosphorylation of ser-104 and -106 and ser-118, which suggests these serine residues as targets for gsk-3 in vivo. Our results further suggest that eralpha phosphorylation by gsk-3 stabilizes eralpha under resting conditions and modulates eralpha transcriptional activity upon ligand binding. Estradiol and phorbol ester cause phosphorylation of serine 118 in the human estrogen receptor. Potentiation of human estrogen receptor alpha transcriptional activation through phosphorylation of serines 104 and 106 by the cyclin a-cdk2 complex. | SIGNOR-139316 |
O43781 | Q96B36 | 1 | phosphorylation | down-regulates | 0.34 | When dyrk3 is active, it allows stress granule dissolution, releasing mtorc1 for signaling and promoting its activity by directly phosphorylating the mtorc1 inhibitor pras40 | SIGNOR-201002 |
P68400 | P35579 | 1 | phosphorylation | up-regulates | 0.34 | In egf-stimulated cells, the myosin-iia heavy chain is phosphorylated on the casein kinase 2 site (s1943) | SIGNOR-155987 |
P42684 | P04040 | 1 | phosphorylation | up-regulates activity | 0.34 | C-abl and arg phosphorylated catalase at tyr231 and tyr386 in vitrocatalase is a major effector in the defense of aerobic cells against oxidative stress. Recent studies have shown that catalase activity is stimulated by the c-abl and arg tyrosine kinases | SIGNOR-101306 |
Q7Z6Z7 | O43474 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.34 | K48 linked KLF4 ubiquitination by E3 ligase Mule controls T-cell proliferation and cell cycle progression.|Instead, we identified the transcription factor KLF4 as a novel Mule substrate that is ubiquitinated by this E3 ligase and thus undergoes proteasomal degradation in T cells.|Here we report that Lys-48-linked ubiquitination of the transcription factor KLF4 mediated by the E3 ligase Mule promotes T-cell entry into S phase. | SIGNOR-278749 |
P45984 | P50616 | 1 | phosphorylation | down-regulates | 0.34 | Biochemical analyses have then shown that erk mapk (erk2) and jnk/sapk (jnk2) bind to and phosphorylate tob in vitro. | SIGNOR-91067 |
P68400 | P10242 | 1 | phosphorylation | down-regulates activity | 0.34 | For c-Myb mutational analysis of the CKII phosphorylation sites showed altered steady state DNA binding. Replacing Ser-11/12 by alanine residues resulted in increased DNA binding compared to wt c-Myb or Myb Asp-11/12 as demonstrated by up to 10-fold differences in the dissociation constants. | SIGNOR-250918 |
P06493 | Q8NFH8 | 1 | phosphorylation | down-regulates activity | 0.34 | Phosphorylation of POB1 and Epsin by p34cdc2 kinase. Their phosphorylation sites (Ser411 of POB1 and Ser357 of Epsin) were determined. Phosphorylated Epsin and EpsinS357D formed a complex with α-adaptin less efficiently than wild type Epsin. | SIGNOR-262724 |
P27361 | Q9UJY1 | 1 | phosphorylation | up-regulates activity | 0.34 | Hsp22 is phosphorylated by protein kinase c (at residues ser(14) and thr(63)) and by p44 mitogen-activated protein kinase (at residues ser(27) and thr(87)). Concerning the possible function of hsp22, no definitive conclusions can be drawn with the available data, although its function might be to bind to and modulate the activity of hsp27.Some Studies claimed that phosphorylation is required for the translocation | SIGNOR-107680 |
Q76N32 | O95613 | 1 | relocalization | up-regulates activity | 0.34 | We also found that Cep68 forms a complex with Cep215 (also known as Cdk5Rap2) and PCNT (also known as pericentrin), two PCM (pericentriolar material) proteins involved in centriole engagement. |Cep68 stabilization increases the amount of PCNT at metaphase centrosomes, but does not affect its removal at the end of mitosis | SIGNOR-275623 |
Q9NZI8 | P60709 | 1 | post transcriptional regulation | up-regulates quantity | 0.34 | We found that ZBP1 is necessary for netrin-1 stimulated local translation of β-actin mRNA in axonal growth cones. ZBP1 binds to β-actin mRNA in the soma and transports it to the growth cone on microtubules. | SIGNOR-268160 |
P46379 | P35558 | 1 | acetylation | down-regulates quantity by destabilization | 0.34 | These results indicate that BAT3 and P300 can both exist in the PEPCK1 protein complex, suggesting the possibility that BAT3 could be an enhancer of PEPCK1 acetylation. | indicating a synergistic effect of BAT3 and P300 to promote PEPCK1 acetylation. | SIGNOR-267598 |
P68400 | P18858 | 1 | phosphorylation | up-regulates activity | 0.34 | Moreover, these data confirmed the occurrence of Ser66 phosphorylation, which was previously studied with a specific monoclonal antibody (23). | SIGNOR-103258 |
P68400 | Q9UD71 | 1 | phosphorylation | up-regulates activity | 0.34 | Study of [Plphosphate release during manual Edman degradation confirmed that the phosphorylated residues in rat DARPP-32 were Ser45 and Ser102. | Phosphorylation by casein kinase II did not affect the potency of DARPP-32 as an inhibitor of protein phosphatase-1, which depended only on phosphorylation of Thr34 by cAMP-dependent protein kinase. However, phosphorylation of DARPP-32 by casein kinase II facilitated phosphorylation of Thr34 by cAMP-dependent protein kinase | SIGNOR-250927 |
Q9UBK2 | P05019 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.34 | PGC-1 alpha specifically induces IGF1 and represses myostatin, and expression of PGC-1a 4 in vitro and in vivo induces robust skeletal muscle hypertrophy | SIGNOR-256152 |
P11309 | Q13309 | 1 | phosphorylation | up-regulates activity | 0.34 | We found that expression of Pim-1 increases the level of Skp2 through direct binding and phosphorylation of multiple sites on this protein. Along with known Skp2 phosphorylation sites including Ser(64) and Ser(72), we have identified Thr(417) as a unique Pim-1 phosphorylation target. Phosphorylation of Thr(417) controls the stability of Skp2 and its ability to degrade p27. | SIGNOR-259819 |
Q02156 | Q92934 | 1 | phosphorylation | down-regulates | 0.34 | Pkcs phosphorylate bad under in vitro conditions, and the association of phosphorylated bad with pkc-mu or pkc-epsilon, as shown by immunoprecipitation, indicated direct involvement of pkcs in bad phosphorylation. To confirm these results, cells overexpressing pegfp-n1, wt-bad, or bad with a single site mutated (ser112ala;ser136ala;ser155ala), two sites mutated (ser(112/136)ala;ser(112/155)ala;ser(136/155)ala), or the triple mutant were tested. Igf-i protected completely against rapamycin-induced apoptosis in cells overexpressing wt-bad and mutants having either one or two sites of phosphorylation mutated | SIGNOR-163908 |
P31749 | Q8TDN4 | 1 | phosphorylation | down-regulates activity | 0.34 | Here, we report that Cables1 levels are controlled by a phosphorylation and 14-3-3-dependent mechanism. Mutagenic analyses identified two residues, T44 and T150, that are specifically critical for 14-3-3 binding and that serve as substrates for phosphorylation by the cell survival kinase Akt, which by binding directly to Cables1 recruits 14-3-3 to the complex.Ectopic expression of activated Akt (AKT1) prevented Cables1-induced apoptosis. | SIGNOR-276756 |
P68400 | P27540 | 1 | phosphorylation | down-regulates | 0.34 | Here, we show that arnt and alt arnt proteins are differentially phosphorylated by protein kinase ckii in vitro. Phosphorylation had an inhibitory effect on dna-binding to an e-box probe by alt arnt, but not arnt, homodimers. This inhibitory phosphorylation occurs through ser77. | SIGNOR-140034 |
P03372 | P06850 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.34 | Evidence of direct estrogenic regulation of human corticotropin-releasing hormone gene expression. Potential implications for the sexual dimophism of the stress response and immune/inflammatory reaction.|Gel retardation and immunoprecipitation demonstrated specific association between the perfect half-palindromic EREs of hCRH gene and the DNA binding domain of hER in vitro. | SIGNOR-268721 |
Q13470 | P19174 | 1 | binding | up-regulates quantity | 0.34 | GST-protein precipitations from cell lysates confirmed that GST-PLC-gamma1(SH3) associated with endogenously expressed Tnk1. | SIGNOR-273864 |
P06241 | O43294 | 1 | phosphorylation | up-regulates activity | 0.34 | Hic-5 is a CAKbeta-binding protein localized at focal adhesions. Here we show that overexpression of CAKbeta or Fyn, but not FAK, enhanced the tyrosine phosphorylation of coexpressed Hic-5 in COS-7 cells. The Y60F mutant of Hic-5 was not phosphorylated, and Hic-5 phosphorylated on tyrosine 60 was bound specifically to the SH2 domain of Csk. Specific phosphorylation of Hic-5 by CAKbeta and Fyn may activate a signaling pathway mediated by Hic-5. | SIGNOR-262875 |
P68400 | P08047 | 1 | phosphorylation | down-regulates activity | 0.34 | Casein kinase II-mediated phosphorylation of the C terminus of Sp1 decreases its DNA binding activity. | Mutation of a consensus CKII site at amino acid 579, within the second zinc finger, eliminates phosphorylation of this site and the CKII-mediated inhibition of Sp1 binding. | SIGNOR-250954 |
Q14432 | P16615 | 1 | binding | down-regulates activity | 0.34 | Regulation of sarcoplasmic reticulum Ca2+ ATPase 2 (SERCA2) activity by phosphodiesterase 3A (PDE3A) in human myocardium: phosphorylation-dependent interaction of PDE3A1 with SERCA2.|PDE3A co-localized with PLB, SERCA2, and an AKAP18 variant|our studies show that PDE3-selective inhibition (but not PDE4 inhibition) potentiates the phosphorylation of PLB by endogenous PKA and stimulation of SERCA2 activity and Ca2+ uptake in SR-enriched vesicles prepared from human myocardium. | SIGNOR-262051 |
P24752 | Q9P0J1 | 1 | acetylation | down-regulates activity | 0.34 | We previously reported that the mitochondrial fraction of FLT3 activates acetyl-CoA acetyltransferase ACAT1 in mitochondria via Y407 phosphorylation to acetylate and inhibit mitochondrial pyruvate dehydrogenase A (PDHA) and PDH phosphatase 1 (PDP1) | SIGNOR-267635 |
Q13315 | P48730 | 1 | phosphorylation | up-regulates activity | 0.34 | These results elucidated the specificity of this in vivo degradation assay, and further implicated that CKI\u03b4-dependent phosphorylation events is the major signaling route through which DNA damage-dependent activation of ATM might control timely turnover of Mdm2 during genotoxic stress. (A) ATM-mediated phosphorylation of CK1\u03b4 promotes CK1\u03b4 nuclear localization.|We further demonstrated that DNA damage-induced activation of ATM directly phosphorylated CKI\u03b4 at two well-conserved S/TQ sites, which promotes CKI\u03b4 nuclear localization to increase CKI\u03b4-mediated phosphorylation of Mdm2, thereby facilitating subsequent Mdm2 ubiquitination by SCF\u03b2-TRCP. | SIGNOR-279504 |
O15303 | P63092 | 1 | binding | up-regulates activity | 0.34 | MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits. | SIGNOR-264084 |
Q14814 | P12882 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.34 | Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation | SIGNOR-238751 |
P00519 | Q15139 | 1 | phosphorylation | up-regulates | 0.339 | By using a phospho-specific antibody, we show that abl directly phosphorylates pkd at tyr(463) in vitro, and in cells phosphorylation of this site is sufficient to mediate full activation of pkd | SIGNOR-99255 |
O14920 | Q07817 | 1 | phosphorylation | down-regulates quantity | 0.339 | We present evidence for a signaling network that involves phosphorylation and reduction of Bcl-xL by IKKbeta, and subsequent activation of caspases, which can cleave Htt.|We propose that IKKbeta reduces Bcl-xL levels by phosphorylation (XREF_FIG), a modification known to promote Bcl-xL degradation . | SIGNOR-279529 |
Q86TM6 | P05067 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.339 | Thus, HRD1 ubiquitinates and degrades denaturated APP as well as unfolded proteins, suggesting that HRD1 affects APP-A\u03b2 dynamics in the brains of AD patients. | SIGNOR-278616 |
O96013 | Q15796 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.339 | In addition, PAK4 phosphorylates Smad2 on Ser465, leading to the degradation of Smad2 through ubiquitin-proteasome-dependent pathway under hepatocyte growth factor (HGF) stimulation. | SIGNOR-279084 |
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 |
Q8WU20 | Q13588 | 1 | binding | up-regulates | 0.339 | Complex formation between grb2 and frs2_ is mediated by y196, y306, y349, and y392 of frs2_ (designated direct grb2-binding sites;ref. 1). In addition, frs2_ recruits grb2 indirectly by means of the protein tyrosine phosphatase shp2 by way of residues y436 and y471 (designated shp2-binding sites;ref. 2). | SIGNOR-87169 |
Q02086 | P10914 | 1 | binding | up-regulates activity | 0.339 | Sp2 could be also able to interact with IRF-1 and this interaction is also observed on DNA indicating that by this way Sp2 is able to modulate IRF-1 transcriptional activity. | SIGNOR-226478 |
O60674 | Q92858 | 1 | phosphorylation | up-regulates quantity | 0.339 | We discovered tyrosine 78 of Atoh1 is phosphorylated by a Jak2-mediated pathway only in tumor-initiating cells and in human SHH-type medulloblastoma. Phosphorylation of tyrosine 78 stabilizes Atoh1, increases Atoh1’s transcriptional activity, and is independent of canonical Jak2 signaling. | SIGNOR-262201 |
P17252 | P06127 | 1 | phosphorylation | up-regulates | 0.339 | Cd5 is a good pkc substrate. Phosphorylation of cd5 is necessary for cd5-mediated lipid second messenger generation. | SIGNOR-85179 |
P27361 | P29590 | 1 | phosphorylation | up-regulates | 0.339 | Phosphorylation of pml by mitogen-activated protein kinases plays a key role in arsenic trioxide-mediated apoptosis. | SIGNOR-124317 |
P08253 | P10915 | 1 | cleavage | down-regulates quantity by destabilization | 0.339 | Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix. | SIGNOR-256333 |
P53779 | P61978 | 1 | phosphorylation | up-regulates activity | 0.339 | JNK Phosphorylation of HnRNP K Increases Its Transcriptional Activity. the primary site for JNK phosphorylation consists of serines 216 and 353 on the K protein. | SIGNOR-250083 |
P06493 | P78344 | 1 | phosphorylation | up-regulates activity | 0.339 | To test whether CDK1 phosphorylates T508, Flag-DAP5 was purified from dox-induced HEK293 cells and incubated with active recombinant JNK2 or CDK1 in the presence of ATP (Fig. 3G). DAP5(T508) was phosphorylated only upon incubation with CDK1 (Fig. 3G). | SIGNOR-266387 |
O75439 | Q9BXM7 | 1 | cleavage | down-regulates quantity by destabilization | 0.339 | Using an unbiased RNA-mediated interference (RNAi)-based screen, we identified four mitochondrial proteases, mitochondrial processing peptidase (MPP), presenilin-associated rhomboid-like protease (PARL), m-AAA and ClpXP, involved in PINK1 degradation. We find that PINK1 turnover is particularly sensitive to even modest reductions in MPP levels. Moreover, PINK1 cleavage by MPP is coupled to import such that reducing MPP activity induces PINK1 accumulation at the mitochondrial surface, leading to Parkin recruitment and mitophagy. | SIGNOR-261363 |
P49841 | Q9NX09 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.339 | It has been reported that GSK3beta phosphorylates REDD1 at residues Thr23 and Thr25, resulting in REDD1 recruitment to the Cullin 4a-beta-Trcp E3 ligase complex. | SIGNOR-279526 |
Q12834 | Q9UPP1 | 1 | binding | down-regulates quantity by destabilization | 0.339 | We showed that PHF8 interacts with the CDC20-containing APC (APC(cdc20)) primarily during mitosis. we demonstrate that mutations of the LXPKXLF motif abrogate polyubiquitylation of PHF8 by the APC. APC substrates are typically cell cycle regulators, and consistent with this, the loss of PHF8 leads to prolonged G2 phase and defective mitosis. | SIGNOR-272879 |
P53355 | Q16623 | 1 | phosphorylation | down-regulates activity | 0.339 | Syntaxin-1A phosphorylation by DAP kinase or its S188D mutant, which mimics a state of complete phosphorylation, significantly decreases syntaxin binding to Munc18-1, a syntaxin-binding protein that regulates SNARE complex formation and is required for synaptic vesicle docking. | SIGNOR-251083 |
P48730 | P27707 | 1 | phosphorylation | up-regulates activity | 0.339 | Site-directed mutagenesis demonstrated that only Ser-74 phosphorylation was involved in Deoxycytidine kinase activation by CKI delta, strengthening the key role of this residue in the control of Deoxycytidine kinase activity.|We showed that recombinant CKI delta phosphorylated several residues of bacterially overexpressed Deoxycytidine kinase: Ser-74, but also Ser-11, Ser-15, and Thr-72. | SIGNOR-280233 |
Q8NEZ5 | O75164 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.339 | SCF(FBXO22) regulates histone H3 lysine 9 and 36 methylation levels by targeting histone demethylase KDM4A for ubiquitin-mediated proteasomal degradation | SIGNOR-273442 |
P10586 | P56945 | 1 | dephosphorylation | down-regulates quantity by destabilization | 0.339 | LAR specifically dephosphorylates and destabilizes p130Cas and may play a role in regulating cell adhesion-mediated cell survival.|Transmembrane tyrosine phosphatase LAR induces apoptosis by dephosphorylating and destabilizing p130Cas. | SIGNOR-276998 |
Q96DB2 | P25440 | 1 | binding | down-regulates activity | 0.339 | Ex vivo and cell-based assays revealed that HDAC11 catalytic activity suppresses the BAT transcriptional program, in both the basal state and in response to β-adrenergic receptor signaling, through a mechanism that is dependent on physical association with BRD2, a bromodomain and extraterminal (BET) acetyl-histone-binding protein. | SIGNOR-262058 |
P19525 | P35568 | 1 | phosphorylation | down-regulates activity | 0.339 | First, PKR induces phosphorylation of IRS1 at Ser312 and suppresses tyrosine phosphorylation of IRS1, mediated by the insulin receptor substrates kinases, JNK and I\u03baB kinase.|These results suggest that PKR induces the inhibitory phosphorylation of IRS1 at Ser312 in HepG2 cells, thereby suppressing the phosphorylation at Tyr941. | SIGNOR-278310 |
Q9BT56 | O43603 | 1 | binding | up-regulates activity | 0.339 | Coevolution of the spexin/galanin/kisspeptin family: Spexin activates galanin receptor type II and III. | SIGNOR-268574 |
P17252 | Q14315 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.338 | We identified the extended basophilic phosphosite motif RxRxxp[S/T]xxp[S/T] in various proteins including filamin-C (FLNc). Importantly, this extended motif, located in a unique insert in Ig-like domain 20 of FLNc, is doubly phosphorylated. The protein kinases responsible for this dual-site phosphorylation are Akt and PKCα. Proximity proteomics and interaction analysis identified filamin A-interacting protein 1 (FILIP1) as direct FLNc binding partner. FILIP1 binding induces filamin degradation, thereby negatively regulating its function. Here, dual-site phosphorylation of FLNc not only reduces FILIP1 binding, providing a mechanism to shield FLNc from FILIP1-mediated degradation, but also enables fast dynamics of FLNc necessary for its function as signaling adaptor in cross-striated muscle cells. In vitro kinase assays combined with LC-MS confirmed hFLNc-S2233 as a substrate of Akt, whereas PKCα preferentially targeted S2236. | SIGNOR-262617 |
P51965 | Q8NEG5 | 1 | binding | up-regulates activity | 0.338 | MEX can act as an E3, Ub (ubiquitin) ligase, through the E2, Ub-conjugating enzymes UbcH5a, UbcH5c or UbcH6. A region of MEX that contains the RING fingers and the ZZ zinc finger was required for interaction with UbcH5a and MEX self-association, whereas the SWIM domain was critical for MEX ubiquitination. The expression of MEX promoted apoptosis that was induced through Fas, DR (death receptor) 3 and DR4 signalling, but not that mediated by the BH3 (Bcl-2 homology 3)-only protein BimEL or the chemotherapeutic drug adriamycin. | SIGNOR-271555 |
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 |
Q13283 | O95786 | 1 | binding | down-regulates activity | 0.338 | G3BP1 binds RIG-I and that this interaction involves the C-terminal RGG domain of G3BP1, G3BP1 significantly enhances RIG-I-induced ifn-b mRNA synthesis. | SIGNOR-260980 |
Q9HC98 | O00141 | 1 | phosphorylation | up-regulates activity | 0.338 | The present study is the first report of a protein kinase (NEK6) capable of phosphorylating the hydrophobic motif of SGK1, although our data suggest that NEK6 may not mediate this reaction in cells. Nevertheless, the phosphorylation of the hydrophobic motif of SGK1in vitro, coupled with the phosphorylation of the T-loop with PDK1, may be a useful way of generating fully active wild type SGK1. Ser377 and Ser422of SGK1, and the CDK7 T-loop peptide, which are phosphorylated by NEK6. | SIGNOR-250297 |
P68400 | P17936 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.338 | The importance of Ser111 and Ser113 as targets for CK2 has also been shown in our laboratory, as mutation of either residue to alanine caused a major decrease in IGFBP-3 phosphorylation by this enzyme in vitro | These results indicate that IGFBP-3 interaction with acid-labile subunit and with the cell surface, both of which involve basic carboxyl-terminal residues, may be modulated by phosphorylation. Relative resistance to proteolysis and poor binding to cells suggest that CK2-phospho-IGFBP-3 may be a significant inhibitor of IGF activity in the extracellular environment. | SIGNOR-250903 |
Q9Y4A8 | P15559 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.338 | Deletion mutation analysis revealed that Nrf3 repression of NQO1 gene expression required heterodimerization and DNA binding domains but not transcriptional activation domain of Nrf3. | SIGNOR-268976 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.