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 |
|---|---|---|---|---|---|---|---|
Q15306 | O43353 | 2 | binding | down-regulates activity | 0.478 | These studies demonstrate that inhibition of RICK (RIPK2) polyubiquitination by IRF4 involves polyubiquitination of the kinase domain of RICK and this inhibition is facilitated by binding of IRF4 to the kinase and/or intermediate domains of RICK. | SIGNOR-280454 |
P00519 | O00213 | 1 | phosphorylation | up-regulates | 0.415 | The c-abl tyrosine kinase phosphorylates the fe65 adaptor protein to stimulate fe65/amyloid precursor protein nuclear signaling. Here, we show that active c-abl stimulates app/fe65-mediated gene transcription and that this effect is mediated by phosphorylation of fe65 on tyrosine 547 within its second ptb domain. | SIGNOR-123476 |
Q15418 | Q05195 | 1 | phosphorylation | down-regulates | 0.315 | In this study, we showed that mad1 is a substrate of p90 ribosomal kinase (rsk) and p70 s6 kinase (s6k). Both rsk and s6k phosphorylate serine 145 of mad1 upon serum or insulin stimulation. Ser-145 phosphorylation of mad1 accelerates the ubiquitination and degradation of mad1 through the 26s proteasome pathway | SIGNOR-178586 |
P12931 | Q15746 | 1 | phosphorylation | up-regulates | 0.417 | Ec mlck-1 is phosphorylated by p60(src) on tyr(464) and tyr(471), resulting in a 2- to 3-fold increase in ec mlck-1 enzymatic activity. | SIGNOR-85009 |
P04637 | Q92793 | 0 | acetylation | up-regulates activity | 0.912 | C-terminal acetylation of p53 by p300/CBP and PCAF promotes an open conformation of p53 by preventing the occlusion of the DNA binding domain by the C-terminal tail. This enhances p53 transcriptional activity, leading to growth arrest and/or apoptosis | SIGNOR-261495 |
Q9UQF2 | Q13387 | 2 | binding | up-regulates | 0.656 | Deletion analysis demonstrated that the cooh-terminal regions of jip1 and jip2 were sufficient for the formation of hetero-oligomeric complexes | SIGNOR-70863 |
P00519 | P43405 | 1 | phosphorylation | up-regulates activity | 0.253 | Abl kinases modulate Syk kinase activation.|Expression of constitutively active Abl (AblPP) increased Syk Y346 phosphorylation, whereas the phosphorylation was unaffected in cells expressing kinase inactive form of Abl (AblKR) (XREF_FIG). | SIGNOR-279665 |
P17655 | P27361 | 0 | phosphorylation | up-regulates | 0.565 | Epidermal growth factor activates m-calpain (calpain ii), at least in part, by extracellular signal-regulated kinase-mediated phosphorylation.We now show that erk directly phosphorylates and activates m-calpain both in vitro and in vivo. We identified serine 50 as required for epidermal growth factor (egf)-induced calpain activation in vitro and in vivo. | SIGNOR-123083 |
Q99836 | P58753 | 2 | binding | up-regulates activity | 0.635 | Here we describe a protein, Mal (MyD88-adapter-like), which joins MyD88 as a cytoplasmic TlR-domain-containing protein in the human genome. Mal activates NF-_B, Jun amino-terminal kinase and extracellular signal-regulated kinase-1 and -2. | SIGNOR-252063 |
P84022 | Q13485 | 2 | binding | up-regulates activity | 0.712 | TGF-² treatment initiates a kinase cascade that results in the phosphorylation of Smad3, followed by its heteromerization with Smad4 and subsequent translocation into the nucleus. | SIGNOR-235168 |
P17676 | Q8N2I9 | 2 | binding | down-regulates quantity by destabilization | 0.28 | The COP1-interacting protein STK40 (Durzynska et al., 2017), which was detected in c/EBPβ complexes from BMDMs (Figure 1B), also appeared to contribute to the suppression of c/EBPβ in microglia. Specifically, deletion of the STK40 pseudokinase increased the amount of c/EBPβ protein without increasing the amount of Cebpb mRNA | SIGNOR-261925 |
P35372 | P09471 | 2 | binding | up-regulates activity | 0.64 | 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-256990 |
P80188 | O94916 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.329 | As expected, the depletion of NFAT5 decreased the S100A4 and LCN2 mRNA levels (Figure 3a). In addition, chromatin immunoprecipitation (ChIP) assay using NFAT5 antibody indicated that NFAT5 was bound to the S100A4 and LCN2 promoters (Figure 3b, Supplementary Figure S3), as expected (Chen et al., 2009). | SIGNOR-274114 |
Q06418 | Q8NB16 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | TAM kinases phosphorylate MLKL to promote necroptosis. MLKL is then recruited to the plasma membrane, where TAM kinases phosphorylate MLKL at Tyr376 (Figure 5G, step 5), promoting its oligomerization and formation of membrane-rupturing pores that result in necrotic cell death (Figure 5G, step 6). | SIGNOR-274120 |
P19086 | P08912 | 2 | binding | up-regulates activity | 0.253 | 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-257125 |
P49841 | P48436 | 1 | phosphorylation | down-regulates activity | 0.444 | (E) The SOX9 K2 domain is phosphorylated by GSK3\u03b2 at T236.|Based on our findings that inhibition of GSK3\u03b2 prevents DNA damage-induced SOX9 degradation, and that FBW7 targets SOX9 for degradation after DNA damage, we reasoned that phosphorylation of SOX9 by GSK3\u03b2 is required for FBW7-mediated SOX9 degradation. | SIGNOR-279725 |
Q9NPB9 | O15444 | 2 | binding | up-regulates activity | 0.664 | In the present study, however, we demonstrate for the first time the concentration-dependent recruitment of β-arrestins to the atypical chemokine receptor CCX-CKR upon stimulation with CCL19, CCL21, or CCL25 using three different methodologies in various transfected cell lines. | SIGNOR-268418 |
P21802 | Q06124 | 0 | dephosphorylation | down-regulates activity | 0.622 | In forming this heterotetrameric complex Grb2 inhibits both the dephosphorylation of FGFR2 by Shp2 and the phosphorylation of Shp2 by FGFR2 (XREF_FIG, respectively).|Knockdown of Grb2 elevates Shp2 phosphorylation (XREF_FIG), strongly suggesting that the inability of Shp2 to interact directly with the receptor in the presence of Grb2 prevents FGFR2 kinase activity toward Shp2. | SIGNOR-277030 |
P38398 | Q03468 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.441 | BRCA1 polyubiquitinates CSB and this polyubiquitination and subsequent degradation of CSB occur following UV irradiation, even in the absence of Cockayne syndrome A (CSA) protein. | SIGNOR-272754 |
P63104 | P11309 | 0 | phosphorylation | up-regulates activity | 0.31 | PIM1 phosphorylates the AR and 14-3-3 ζ and coordinates their interaction. PIM1 phosphorylation of the AR and 14-3-3 ζ enhances their interaction and shifts their occupancy on chromatin, resulting in 14-3-3 ζ co-regulation of AR, likely by recruiting other AR co-regulators such as hnRNPK and TRIM28. | SIGNOR-277574 |
P08134 | P52306 | 2 | binding | up-regulates | 0.298 | Smggds is a guanine nucleotide exchange factor that specifically activates rhoa and rhoc | SIGNOR-171399 |
Q9ULZ2 | P42680 | 2 | binding | up-regulates activity | 0.392 | In 293 cells expressing recombinant BRDG1 and various PTKs, Tec and Pyk2, but not Btk, Bmx, Lyn, Syk, or c-Abl, induced marked phosphorylation of BRDG1 on tyrosine residues. BRDG1 was also phosphorylated by Tec directly in vitro. Furthermore, BRDG1 was shown to participate in a positive feedback loop by increasing the activity of Tec. BRDG1 thus appears to function as a docking protein acting downstream of Tec in BCR signaling. BRDG1 may activate Tec by disrupting an intramolecular interaction. | SIGNOR-261819 |
P60953 | Q8NF50 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.767 | Recently, DOCK8 was identified as a guanine-nucleotide exchange factor (GEF) for Cdc42 activation and has been associated with human mental retardation. | SIGNOR-268412 |
Q96GD4 | P17661 | 1 | phosphorylation | down-regulates | 0.546 | We report here that aurora-b phosphorylates gfap and desmin in vitro, and this phosphorylation leads to a reduction in filament forming ability. In the present study, we found aurora-b phosphorylates desmin at ser-11, thr-16, and ser-59, in vitro. | SIGNOR-100107 |
P78556 | P51684 | 2 | binding | up-regulates activity | 0.2 | Liver and activation-regulated chemokine (LARC), also designated macrophage inflammatory protein-3alpha (MIP-3alpha), Exodus, or CCL20, is a C-C chemokine that attracts immature dendritic cells and memory T lymphocytes, both expressing CCR6. LARC/MIP-3α is exerting its activity through binding to CCR6 (11, 12, 18, 19, 20), which is not shared by any other known chemokine. CCR6 is found to be expressed on immature dendritic cells and memory T lymphocytes as well as on B lymphocytes, in various lymphoid organs, and in pancreas | SIGNOR-278040 |
O14713 | O96013 | 0 | phosphorylation | down-regulates activity | 0.2 | We further demonstrate that p21 activated kinase 4 (PAK4) can phosphorylate ICAP1 at Ser 10 both in vitro and in cultured cells, and that active PAK4 inhibits ICAP1 nuclear accumulation in a Ser-10-dependent manner.|We further demonstrate that p21-activated kinase 4 (PAK4) can phosphorylate ICAP1 at Ser-10 both in vitro and in cultured cells, and that active PAK4 inhibits ICAP1 nuclear accumulation in a Ser-10-dependent manner. | SIGNOR-280056 |
Q04206 | P08581 | 1 | transcriptional regulation | up-regulates quantity | 0.25 | Together, these results indicate that the Met gene is a direct target of NFkappaB and that Met participates in NFkappaB-mediated cell survival. | SIGNOR-241929 |
P22681 | P00519 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.614 | We found that while c-cbl e3 ligase induced ubiquitin-dependent degradation of mature and phosphorylated bcr-abl proteins | SIGNOR-167194 |
P10415 | P62714 | 0 | dephosphorylation | up-regulates activity | 0.385 | The phosphorylation of Bcl-2 resulted in a reduction in anti-apoptotic function, implying that dephosphorylation promoted the anti-apoptotic activity of Bcl-2 protein in human tumor cell lines. Thus, the present findings suggest that ERK and PP2A are physiological regulators of Bcl-2 phosphorylation, and these enzymes exert an influence on the anti-apoptotic function of Bcl-2.phosphorylation of Bcl2 at Ser70 is proposed to be a dynamic process regulated by the sequential action of an agonist-activated Bcl2 kinase and PP2A. | SIGNOR-248589 |
O43791 | Q49A26 | 2 | binding | down-regulates quantity by destabilization | 0.274 | Here, we analyzed changes in the ubiquitin landscape induced by prostate cancer-associated mutations of SPOP, an E3 ubiquitin ligase substrate-binding protein. SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. Of these, DEK and TRIM24 emerged as effector substrates consistently up-regulated by SPOP mutants. Up-regulation of DEK, TRIM24 and NCOA3 is a feature of prostate cancer SPOP mutations. | SIGNOR-272824 |
P07948 | P18433 | 0 | dephosphorylation | down-regulates activity | 0.3 | We found that PTPα and SHP-1 both dephosphorylate Lyn exclusively at Tyr-397|Lyn expressed in CHO cells has a substantially higher specific activity than Lyn in RBL cells because of high levels of phosphorylation at its active site Tyr-397 (Fig. 1). Enhanced Lyn kinase activity in the CHO cells leads to spontaneous phosphorylation of multiple cellular proteins, including FcϵRI | SIGNOR-248436 |
P38936 | Q99683 | 0 | phosphorylation | up-regulates | 0.589 | P21cip1 is phosphorylated in vitro by both ask1 and jnk1 at s98. /phosphorylation of p21cip1 at s98, which in vivo appears to be regulated by ask1, may therefore mediate negative feedback in the ask1 signaling pathway. | SIGNOR-153440 |
P38435 | P08709 | 1 | carboxylation | up-regulates activity | 0.688 | Thus, vitamin K acts as a cofactor for GGCX via the vitamin K cycle and exerts physiological effects through its regulation of VKDPs [29]. More than 20 VKDPs have been found. Osteocalcin promotes bone formation, and blood coagulation factors II, VII, IX, and X activate blood coagulation. Matrix Gla protein suppresses cardiovascular calcification, and brain-expressed Gas 6 promotes neural differentiation [29]. GGCX is an enzyme that converts glutamic acid (Glu) residues to Gla residues, so that the Gla-containing proteins can exert various physiological actions such as blood coagulation and bone formation. | SIGNOR-265919 |
P61812 | Q03167 | 2 | binding | up-regulates | 0.518 | Betaglycan binds tgf-b isoforms with high affinity and increases the functional interaction between tgf-b and its type ii and type i signalling receptors. | SIGNOR-76473 |
Q969H0 | P49768 | 2 | binding | down-regulates quantity by destabilization | 0.493 | SEL-10 interacts with presenilin 1, facilitates its ubiquitination, and alters A-beta peptide production SEL-10 protein is a homologue of yeast Cdc4, a member of the SCF (Skp1-Cdc53/CUL1-F-box protein) E2-E3 ubiquitin ligase family. In this study, we show that human SEL-10 interacts with PS1 and enhances PS1 ubiquitination, thus altering cellular levels of unprocessed PS1 and its N- and C-terminal fragments. These observations suggest that SEL-10 mediated ubiquitination of PS1-CTF and PS1-NTF leads to their degradation. | SIGNOR-272600 |
P17252 | P24844 | 1 | phosphorylation | down-regulates | 0.278 | Rlc can also be phosphorylated at ser1/ser2/thr9 by protein kinase c (pkc). Biophysical studies show that phosphorylation at these sites leads to an increase in the km of myosin light chain kinase (mlck) for rlc, thereby indirectly inhibiting myosin ii activity | SIGNOR-192792 |
P06400 | Q16539 | 0 | phosphorylation | down-regulates | 0.539 | P38 bypasses the cell cycle-associated hierarchical phosphorylation and directly phosphorylates rb on ser567, which is not phosphorylated during the normal cell cycle. Phosphorylation by p38, but not cdks, triggers an interaction between rb and the human homolog of murine double minute 2 (hdm2), leading to degradation of rb, release of e2f1 and cell death. | SIGNOR-168178 |
Q9UJU6 | P43403 | 0 | phosphorylation | up-regulates | 0.64 | We found an interaction between the tyrosine kinase zap-70 and hip-55, which was induced by tcr stimulation. Zap-70 phosphorylated hip-55 at tyr-334 and tyr-344, which were shown to be the tyrosine phosphorylation sites of hip-55 in stimulated t cells.Our results demonstrate for the first time that hip-55 is an important adaptor protein for the jnk kinase cascade in tcr signaling. | SIGNOR-118695 |
P22607 | O43318 | 1 | phosphorylation | up-regulates activity | 0.293 | Indeed, we found that TAK1 was tyrosine phosphorylated in HEK293 cells transiently expressing constitutively active FGFR3 (K650E), but not the kinase-dead receptor (K508M), indicating that activated FGFR3 can either directly or indirectly tyrosine phosphorylate TAK1 (XREF_FIG). | SIGNOR-279176 |
O95837 | P32239 | 2 | binding | up-regulates activity | 0.453 | 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-257363 |
Q04771 | Q96JC1 | 2 | binding | up-regulates activity | 0.2 | TLP interacts with TGF-β and activin receptors in vivo. Endogenous TLP associates with both active and kinase-deficient TGF-beta and activin type II receptors, but interacts with the common-mediator Smad4 only in the presence of TGF-beta/activin signaling. | SIGNOR-261376 |
P06493 | P02545 | 1 | phosphorylation | up-regulates | 0.536 | Phosphorylation by mitotic cdc2 kinase at ser-22, ser-390, and ser-392 residues on lamin a/c, or by protein kinase c (pkc) during apoptosis, leads to the depolymerization of lamin (disassembly of the nuclear lamina), which may lead to their release from the inm | SIGNOR-181314 |
P68400 | Q9Y237 | 1 | phosphorylation | down-regulates activity | 0.326 | As proved by MALDI-TOF mass spectrometry and MS/MS fragmentation, hPar14 is phosphorylated at Ser19 in vitro and in vivo. In human HeLa cells the protein is most likely modified by casein kinase 2 (CK2). |In contrast to wild-type hPar14, the in vitro DNA-binding affinity of the Glu19 mutant is strongly reduced, suggesting that only the dephosphorylated protein is the active DNA-binding form of hPar14 in the nucleus. | SIGNOR-265753 |
P25098 | P35372 | 1 | phosphorylation | down-regulates activity | 0.2 | These results suggest that two C-terminal amino acids, Ser(355) and Thr(357), are required for short-term homologous desensitization and agonist-induced phosphorylation of mu-opioid receptors expressed in HEK 293 cells | SIGNOR-249661 |
Q15672 | P17252 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Because most of these sites were predicted to be phosphorylated by protein kinase C (PKC), we overexpressed PKCα in several cell lines and found that it phosphorylates Twist1 on Ser-144. we observed that PKCα-mediated Twist1 phosphorylation at Ser-144 inhibits Twist1 ubiquitination and consequently stabilizes it. | SIGNOR-277429 |
Q9ULJ8 | Q92974 | 2 | 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 |
P62834 | P47736 | 2 | binding | down-regulates activity | 0.837 | Overexpression of Rap1GAP significantly inhibited Rap1 activation, ERK and Akt phosphorylation of HUVECs compared with pcDNA transfection controls | SIGNOR-278054 |
Q8NEZ5 | O95863 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | FBXO22 elicits its antimetastatic effects by targeting SNAIL, a master regulator of EMT and breast cancer metastasis, for ubiquitin-mediated proteasomal degradation in a glycogen synthase kinase 3β phosphorylation-dependent manner. | SIGNOR-273446 |
P05186 | P10451 | 1 | dephosphorylation | down-regulates activity | 0.442 | This result suggests that endogenous mouse TNAP dephosphorylates OPN in osteoblasts and that overexpressed human TNAP dephosphorylates OPN, compensating for the lack of endogenous TNAP in [Col1a1-Tnap +/\u2212 ;Alpl \u2212/\u2212 ] cells. | SIGNOR-277045 |
P43146 | O00555 | 1 | null | up-regulates activity | 0.2 | DCC activation by a netrin-1 gradient creates a high-level [Ca2+]i gradient by triggering LCC activity and by stimulating the cAMP–PKA pathway, which further activates LCC in the plasma membrane (PM) and Ca2+ channels in the ER. | SIGNOR-268293 |
Q2M1Z3 | P61586 | 1 | gtpase-activating protein | down-regulates activity | 0.529 | 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-260488 |
Q13952 | P78317 | 2 | binding | up-regulates activity | 0.2 | Coactivator RNF4 is involved in the GCH gene expression. Through serial deletion and mutagenesis studies of the GCH promoter, we defined the RNF4-responsive element on GCH proximal promoter as a CCAAT box. RNF4 did not possess specific DNA binding activity toward this CCAAT box, which suggests that RNF4 may be a coactivator of the CCAAT boxbinding protein nuclear factor Y (NF-Y). RNF4 is a coactivator for nuclear factor Y on GTP cyclohydrolase I proximal promoter. | SIGNOR-252231 |
Q92830 | P0DPK5 | 1 | acetylation | down-regulates activity | 0.2 | The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14. | SIGNOR-269598 |
P63096 | Q9H3N8 | 2 | binding | up-regulates activity | 0.516 | 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-256672 |
P35354 | P11831 | 0 | null | up-regulates | 0.252 | Srf within myofibers modulates Il6 and Cox2/Il4 expressions and, therefore, exerts a paracrine control of satellite cell proliferation and fusion, respectively, which in turn support skeletal muscle hypertrophy. | SIGNOR-255965 |
Q9BTA9 | P06493 | 0 | phosphorylation | up-regulates activity | 0.2 | Cyclin-dependent kinase 1 (Cdk1) phosphorylates WAC, priming its direct interaction with the polo-box domain of Plk1. Knockdown of WAC compromises Plk1 activity and delays mitotic entry. | SIGNOR-265035 |
Q96KS0 | O43791 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.347 | Tumor suppressor SPOP ubiquitinates and degrades EglN2 to compromise growth of prostate cancer cells | SIGNOR-261996 |
Q9NZQ7 | P46977 | 0 | glycosylation | up-regulates quantity by stabilization | 0.2 | Together, these results support a notion that the two STT3 isoforms regulate EMT-mediated PD-L1 induction through PD-L1 protein N-glycosylation and stabilization. | SIGNOR-274975 |
P05107 | O14713 | 2 | binding | down-regulates activity | 0.313 | Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation | SIGNOR-257649 |
P11279 | P19484 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.441 | Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants | SIGNOR-276555 |
P19237 | Q969Q1 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.36 | We used MuRF1 as the E3 as it functions with all these E2s to ubiquitinate one of its typical substrates, troponin I Although UbcH1 and UbcH13/Uev1a support ubiquitination of troponin I by MuRF1, these E2s do not support ubiquitination of S5a, unlike Class I E2s. | SIGNOR-272736 |
O14757 | P53350 | 1 | phosphorylation | down-regulates activity | 0.314 | Chk1 directly phosphorylates Plk1 to disturb its interaction with Sgo1. | SIGNOR-277914 |
P00533 | O95477 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.295 | We further provide in vitro evidence that epidermal growth factor receptor (EGFR)-mediated phosphorylation regulated ABCA1 ubiquitination |The EGFR selective inhibitor PD168393 blocked the EGFR-ABCA1 interaction and abolished ABCA1Ser2054 phosphorylation| | SIGNOR-264419 |
P24941 | P35813 | 0 | dephosphorylation | down-regulates activity | 0.292 | Moreover, purified recombinant PP2C alpha and PP2C beta 2 proteins efficiently dephosphorylated monomeric Cdk2/Cdk6 in vitro. | SIGNOR-277107 |
P13725 | Q99650 | 2 | binding | up-regulates | 0.793 | The oncostatin m receptor (osmr) is part of receptor complexes for oncostatin m and interleukin-31. | SIGNOR-141588 |
Q13422 | P36873 | 0 | dephosphorylation | up-regulates | 0.329 | Ikarosis dephosphorylated by protein phosphatase 1 (pp1) via interaction at a consensus pp1-binding motif/ hyperphosphorylation of ikaros promotes its degradation by the ubiquitin/proteasome pathway | SIGNOR-174865 |
P36897 | P68104 | 1 | phosphorylation | down-regulates | 0.343 | Phosphorylation of eEF1A1 at Ser300 by T_R-I results in inhibition of mRNA translation | SIGNOR-167943 |
P05305 | P23946 | 0 | cleavage | up-regulates activity | 0.472 | Chymase from human mast cells selectively cleaved big endothelins (ETs) at the Tyr31-Gly32 bond and produced novel trachea-constricting 31-amino acid-length endothelins, ETs(1-31), without any further degradation products. | SIGNOR-256356 |
P55040 | O75116 | 2 | binding | down-regulates activity | 0.29 | Two functions for Gem have been demonstrated, including inhibition of voltage-gated calcium channel activity and inhibition of Rho kinase-mediated cytoskeletal reorganization, such as stress fiber formation and neurite retraction. These functions for Gem have been ascribed to its interaction with the calcium channel Β subunit and Rho kinase Β, respectively. | SIGNOR-261711 |
Q15418 | Q8N122 | 1 | phosphorylation | up-regulates | 0.546 | Ser719, ser721, and ser722 are the predominant rsk-dependent phosphorylation sites in raptor raptor phosphorylation regulates mtorc1 activity | SIGNOR-180466 |
P17612 | P24390 | 1 | phosphorylation | up-regulates | 0.309 | We conclude that pka phosphorylation of serine 209 is required for the retrograde transport of the kdel receptor from the golgi complex to the er from which the retrieval of proteins bearing the kdel signal depends. | SIGNOR-118257 |
O43293 | P40763 | 1 | phosphorylation | up-regulates activity | 0.401 | ZIPK phosphorylated STAT3 on serine 727 (Ser727) and enhanced STAT3 transcriptional activity. | SIGNOR-279702 |
P40337 | Q96PY6 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.257 | Nek1 phosphorylates Von Hippel-Lindau tumor suppressor to promote its proteasomal degradation and ciliary destabilization. Mutation of pVHL at S-168 increases protein stability. | SIGNOR-276434 |
Q86T82 | Q9UM11 | 2 | binding | down-regulates activity | 0.336 | Here we show that USP37 binds the APC/C coactivator CDH1|Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry | SIGNOR-265054 |
P49768 | Q99590 | 0 | cleavage | up-regulates activity | 0.294 | Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis. | SIGNOR-261758 |
Q9UQB9 | O75410 | 1 | phosphorylation | up-regulates activity | 0.399 | Aurora-C interacts with and phosphorylates the transforming acidic coiled-coil 1 protein. The results demonstrated that TACC1 is phosphorylated by Aurora-C on a serine at position 228. although the patho-physiological meaning of TACC1 phosphorylation by Aurora-C in normal and in malignant somatic cells remains to be fully investigated, our observations suggest that Aurora-C has a role in the later stage of mitosis, when an interaction with TACC1 may be relevant for the correct progression of the cell cycle. | SIGNOR-262663 |
Q02750 | P00540 | 0 | phosphorylation | up-regulates activity | 0.485 | Our data indicate that Mos activated MEK1 in vitro as well as in vivo by phosphorylating Ser 222. | SIGNOR-260920 |
P01106 | Q9Y4L5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.448 | These results suggest that Rabring7 antagonizes function of c-Myc possibly through degradation of c-Myc.|Unexpectedly, we found that Rabring7 more strongly binds to c-Myc than to MM-1 (XREF_FIG) and that Rabring7 stimulates poly-ubiquitination of c-Myc in a T58 dependent manner (XREF_FIG). | SIGNOR-278662 |
P07948 | O75807 | 1 | phosphorylation | up-regulates | 0.334 | Gadd34 was tyrosine-phosphorylated in vivo in a lyn-dependent manner. | SIGNOR-109934 |
Q03113 | O00398 | 2 | binding | up-regulates activity | 0.2 | 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-257287 |
Q13469 | Q14814 | 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 |
P51168 | O95180 | 2 | binding | up-regulates activity | 0.2 | This study describes the functional interaction between Cav3.2 calcium channels and the Epithelial Sodium Channel (ENaC). β- and γ-ENaC subunits could be co-immunoprecipitated with Cav3.2 calcium channels from brain lysates, dorsal horn and lumbar dorsal root ganglia. Αβγ-ENaC channels enhanced Cav3.2 calcium channel trafficking to the plasma membrane in tsA-201 cells. This effect was reciprocal such that Cav3.2 channel expression also enhanced β-ENaC trafficking to the cell surface. these findings reveal ENaC as an interactor and potential regulator of Cav3.2 calcium channels expressed in neuronal tissues. | SIGNOR-269273 |
P63244 | P67775 | 2 | binding | up-regulates activity | 0.2 | RACK1 Mediates the Formation of the IRF3-RACK1-PP2A Complex and Promotes the Dephosphorylation of IRF3.Here we report that IRF3 is deactivated via dephosphorylation mediated by the serine and threonine phosphatase PP2A and its adaptor protein RACK1. The PP2A-RACK1 complex negatively regulated the IRF3 pathway after LPS or poly(I:C) stimulation or Sendai virus (SeV) infection. | SIGNOR-260945 |
Q9UPW0 | Q06413 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.317 | Foxj3 transcriptionally activates Mef2c and regulates adult skeletal muscle fiber type identity. | SIGNOR-261606 |
Q08828 | P38405 | 2 | binding | up-regulates activity | 0.539 | D1-class dopamine receptors (D1 and D5) activate the G s/olf family of G proteins to stimulate cAMP produc tion by AC and are found exclusively postsynaptically on dopamine-receptive cells, such as GABA-ergic medium spiny neurons (MSNs) in the striatum. | SIGNOR-264992 |
P0DMV8 | P04150 | 2 | binding | down-regulates | 0.633 | Interestingly, FKBP51 forms complexes in mitochondria with the glucocorticoid receptor and the Hsp90/Hsp70-based chaperone heterocomplex | SIGNOR-251668 |
P55010 | P67870 | 0 | phosphorylation | up-regulates activity | 0.379 | Mass spectrometric analysis of maximally in vitro phosphorylated eIF5 localized the major phosphorylation sites at Ser-387 and Ser-388 near the C-terminus of eIF5. These serine residues are embedded within a cluster of acidic amino acid residues and account for nearly 90% of the total in vitro eIF5 phosphorylation. A minor phosphorylation site at Ser-174 was also observed. | The results suggest that phosphorylation of eIF5 may have a role in stimulating the rate of eIF5-promoted GTP hydrolysis. | SIGNOR-251070 |
Q14974 | Q19QW5 | 0 | relocalization | down-regulates activity | 0.2 | ORF6 also retained KPNB1 at the ER/Golgi membrane in complex with KPNA2. Deletion of the N terminus of KPNA2, which binds KPNB1, no longer retained KPNB1 at the ER/Golgi membrane in the presence of ORF6 and did not antagonize STAT1 nuclear import in response to IFN-beta | SIGNOR-260275 |
P30411 | Q14344 | 2 | binding | up-regulates activity | 0.2 | 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-257399 |
Q15833 | O75558 | 2 | binding | up-regulates activity | 0.629 | Strikingly, addition of Munc18-2 substantially and selectively facilitates complete fusion mediated by lipid-anchored STX11 by promoting and stabilizing the assembly of SNARE complexes. | SIGNOR-261898 |
P01100 | P17612 | 0 | phosphorylation | up-regulates activity | 0.518 | Human c-Fos protein is phosphorylated in vitro by PKA. phosphorylation of Fos occurs at serine residue 362. Modification of the Fos protein by phosphorylation with PKA then allows it to act as a regulator of its own synthesis by downregulating fos gene expression at a transcriptional level | SIGNOR-250356 |
P30411 | P35626 | 0 | phosphorylation | down-regulates activity | 0.2 | Ligand-induced phosphorylation is found at Ser339 and Ser346/Ser348 that could be executed by several G protein-coupled receptor kinases. 32P labeling of peptide 3 containing pS346/pS348 was enhanced 1.5–3-fold as compared with mock-transfected cells in the order GRK6 < GRK5 < GRK2 < GRK4α < GRK3. several endogenous GRKs may phosphorylate the B2R and that the various GRKs, even without apparent effect on total GPCR phosphorylation levels, may induce distinct phosphorylation patterns with possible functional consequences for receptor desensitization and sequestration. | SIGNOR-251462 |
O14867 | P04406 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | BACH1 activates transcription of Hexokinase 2 and Gapdh and increases glucose uptake, glycolysis rates, and lactate secretion, thereby stimulating glycolysis-dependent metastasis of mouse and human lung cancer cells. | SIGNOR-259339 |
P30679 | P08912 | 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-257351 |
P09471 | P49286 | 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-256986 |
P13762 | Q5T0T0 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Two E3 ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to polyubiquitination. | SIGNOR-271407 |
Q16611 | O43521 | 2 | binding | up-regulates | 0.837 | Bim, and puma bind with high affinity to all pro-survival proteins | SIGNOR-196932 |
O75874 | O43524 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.248 | We identify FOXOs as transcriptional activators of IDH1. FOXOs promote IDH1 expression and thereby maintain the cytosolic levels of α-ketoglutarate and NADPH. | SIGNOR-260100 |
Q9NZQ7 | P40763 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.464 | STAT3 and HIF-1α cooperatively enhance PD-L1 expression in EML4-ALK-translocated pADC cells under hypoxia.The protein-DNA binding assay revealed that pSTAT3 was bound to the PD-L1 promoter region in H23 cells transfected with EML4-ALK. | SIGNOR-259188 |
Q16613 | P17612 | 0 | phosphorylation | up-regulates activity | 0.32 | AANAT1–207 was phosphorylated in vitro at both PKA sites, Thr-31 and Ser-205. regulation is achieved by binding to 14-3-3, which structurally modulates the substrate binding sites, leading to measurable effects on the affinity of AANAT for its substrates with an accompanying increase in activity at low substrate concentrations. | SIGNOR-250324 |
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