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 |
|---|---|---|---|---|---|---|---|
Q8NE79 | Q15836 | 2 | binding | up-regulates activity | 0.42 | Taken together, these data demonstrate that Bves interacts with VAMP3 and facilitates receptor recycling both in vitro and during early development. | SIGNOR-237771 |
P04637 | Q92794 | 0 | acetylation | up-regulates | 0.67 | We show here that moz is an acetyltransferase of p53 at k120 and k382 and colocalizes with p53 in promyelocytic leukemia (pml) nuclear bodies following cellular stress. The moz-pml-p53 interaction enhances moz-mediated acetylation of p53, and this ternary complex enhances p53-dependent p21 expression | SIGNOR-201486 |
O14757 | Q13315 | 0 | phosphorylation | up-regulates | 0.845 | Atr (predominantly) or atm (to a lesser extent) phosphorylates chk1 at ser317/345, directly leading to activation. | SIGNOR-163106 |
Q08945 | P68400 | 0 | phosphorylation | down-regulates activity | 0.703 | CK2 phosphorylates SSRP1 and inhibits its DNA-binding activity. | we identified serines 510, 657, and 688 as phosphorylation targets of CK2 in vitro. Mutagenesis of the three serines revealed that serine 510 was more important for the regulation of SSRP1 DNA-binding activity. | SIGNOR-250961 |
P15248 | P31785 | 2 | binding | up-regulates | 0.58 | The common gamma-chain (gamma(c)) is an indispensable subunit of the functional receptor complexes for il-4, il-7, il-9, and il-15 as well as il-2. Here we show that the gamma(c) is also shared with the il-21r complex | SIGNOR-108867 |
Q9NRM7 | O14965 | 0 | phosphorylation | up-regulates | 0.38 | On the basis of these observations, we conclude that s83 of lats2 is a phosphorylation target of aurora-a and this phosphorylation plays a role of the centrosomal localization of lats2. | SIGNOR-124830 |
Q9UMX1 | Q8NEA6 | 2 | binding | down-regulates | 0.381 | These data indicate that the inhibition of glis3-mediated transactivation by sufu appears to rely on the interaction with glis3 through the ygh motif and is not related to an effect on the general transcriptional machinery | SIGNOR-173573 |
Q9UK17 | P07948 | 0 | phosphorylation | up-regulates activity | 0.2 | These results indicate that Y108 (for Src-family kinases) and Y136 (for EGFR kinase) are involved in the tyrosine phosphorylation of hKv4.3 channels. | SIGNOR-276395 |
P41235 | P27361 | 0 | phosphorylation | down-regulates activity | 0.494 | Activation of the ERK1/2 signalling pathway, inducing proliferation and survival, inhibits the expression of HNF4\u03b1.|Here we have demonstrated that ERK1 is able to phosphorylate HNF4\u03b1 at several serine and threonine residues. | SIGNOR-279070 |
P27986 | P22681 | 0 | ubiquitination | down-regulates | 0.694 | Cbl-b, a ring-type e3 ubiquitin protein ligase, is implicated in setting the threshold of t lymphocyte activation. The p85 regulatory subunit of phosphatidylinositol 3 kinase (pi3k) was identified as a substrate for cbl-b. We have shown that cbl-b negatively regulated p85 in a proteolysis-independent manner. | SIGNOR-110060 |
P12277 | Q96DX5 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.683 | We demonstrate that creatine kinase B (CKB) interacts with Asb-9 in a specific, SOCS box-independent manner. This interaction increases the polyubiquitylation of CKB and decreases total CKB levels within the cell. The targeting of CKB for degradation by Asb-9 was primarily SOCS box-dependent and suggests that Asb-9 acts as a specific ubiquitin ligase regulating levels of this evolutionarily conserved enzyme. | SIGNOR-271623 |
P13236 | P51681 | 2 | binding | up-regulates activity | 0.862 | The investigators showed that myoblasts constitutively express receptors for CCL2 (CCR2), CCL3 (CCR1 and CCR5), and CCL4 (CCR5), and that stimulation with either CCL2 or CCL4 was sufficient to promote myoblast proliferation. | SIGNOR-255116 |
P61244 | P01106 | 2 | binding | up-regulates | 0.743 | In vivo transactivation assays suggest that myc-max and mad-max complexes have opposing functions in transcription and that max plays a central role in this network of transcription factors | SIGNOR-39137 |
Q53QZ3 | P63000 | 1 | gtpase-activating protein | down-regulates activity | 0.581 | 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-260470 |
Q9UI12 | Q92544 | 2 | binding | up-regulates activity | 0.271 | Here, we demonstrate that TM9SF4 represents a novel V-ATPase-associated protein involved in V-ATPase activation. We have observed in HCT116 and SW480 colon cancer cell lines that TM9SF4 interacts with the ATP6V1H subunit of the V-ATPase V1 sector. Suppression of TM9SF4 with small interfering RNAs strongly reduces assembly of V-ATPase V0/V1 sectors, thus reversing tumor pH gradient with a decrease of cytosolic pH, alkalization of intracellular vesicles and a reduction of extracellular acidity. | SIGNOR-266885 |
P18433 | P18433 | 2 | dephosphorylation | down-regulates activity | 0.2 | Transient overexpression of c-Src together with RPTP alpha in human embryonic kidney 293 cells increased phosphorylation of Tyr789, suggesting that c-Src may phosphorylate RPTP alpha in vivo. RPTP alpha had autodephosphorylation activity in vitro. When expressed in 293 cells the level of Tyr789 phosphorylation was higher in a non-functional mutant of RPTP alpha than in wild type RPTP alpha, indicating that RPTP alpha may have autodephosphorylation activity in vivo as well.|We show that RPTP alpha, but not a mutant of RPTP alpha with a Tyr-->Phe mutation at position 789, bound to GRB2 in vitro. | SIGNOR-248439 |
Q9Y4K3 | Q9UDY8 | 1 | ubiquitination | up-regulates | 0.755 | Traf6 associates with malt1 in response to t-cell activation and can function as an e3 ligase for malt1 in vitro and in vivo, mediating lysine 63-linked ubiquitination of malt1. Multiple lysine residues in the c-terminus of malt1 serve as acceptor sites for the assembly of polyubiquitin chains. (articolo-abstract) | SIGNOR-158554 |
Q14204 | P43034 | 2 | binding | up-regulates activity | 0.886 | We demonstrate that LIS1 directly interacts with the cytoplasmic dynein heavy chain (CDHC) and NUDEL. LIS1 specifically binds the P1 loop domain of CDHC, while NUDEL binds the C-terminal region as well as a distinct binding site in the P1 loop domain. LIS1 and NUDEL regulate CDHC localization and motor function. Reduction of LIS1 leads to mislocalization of NUDEL, CDHC, β-tubulin, and the Golgi complex | SIGNOR-252158 |
Q5VU43 | Q14896 | 2 | binding | up-regulates | 0.31 | This study ascribes a novel function to mmgl isoform 4: it meets all criteria for classification as an akap, and we show that is involved in the phosphorylation of cmybpc as well as ctni, hence mmgl is an important regulator of cardiac contractility. | SIGNOR-173766 |
Q08117 | O95475 | 2 | binding | down-regulates activity | 0.2 | Biochemical and mutational analysis shows that the Six domain of both SIX3 and SIX6 strongly interact with the QD domain of TLE1 and AES. AES abrogates SIX3- and SIX6-induced phenotypes | SIGNOR-234589 |
Q9UKG1 | Q86V24 | 2 | binding | up-regulates | 0.741 | Appl1 interacts with adiponectin receptors in mammalian cells and the interaction is stimulated by adiponectin. | SIGNOR-146215 |
Q96M91 | Q96NG3 | 2 | binding | up-regulates activity | 0.2 | CFAP53 likely facilitates the transport of TTC25 and the dyneins into cilia. CFAP53 at the centriolar satellites may form a complex with TTC25 and ODAs, including DNAH5 and DNAH11, and regulate their trafficking into the cilium (Fig 10B). | SIGNOR-265543 |
P42574 | Q06609 | 1 | cleavage | down-regulates quantity by destabilization | 0.466 | The RAD51 protein has been shown to be a substrate for caspase-3|he activated caspase-3 fragments (19 kDa and 17 kDa) and caspase-3 cleaved RAD51 fragment (∼23 kDa) was detected by Western analysis (Figure 3E). Activation of caspase-3 and the signature proteolytic degradation product of RAD51 only occurred in parental 32Dcl3 cells after treatment with cisplatin | SIGNOR-271709 |
P30405 | P31751 | 0 | phosphorylation | up-regulates activity | 0.2 | In turn, mitochondrial Akt2 phosphorylates Ser31 in cyclophilin D (CypD), a regulator of organelle functions. Akt2-phosphorylated CypD supports mitochondrial bioenergetics and opposes tumor cell death, conferring resistance to PI3K therapy. | SIGNOR-276875 |
P19086 | 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-257102 |
Q9UNE7 | Q99933 | 2 | binding | up-regulates activity | 0.54 | BAG-1 stimulates CHIP-induced degradation of the glucocorticoid hormone receptor (GR). A model for the cooperation of CHIP and BAG-1 in coupling Hsc/Hsp70 to the ubiquitin/proteasome system. CHIP associates with Hsc/Hsp70 via its TPR chaperone adaptor (TPR) and, at the same time, recruits E2 ubiquitin-conjugating enzymes of the Ubc4/5 family to the chaperone complex. BAG-1 binds to Hsp70 via its BAG domain (BAG) and utilizes its ubiquitin-like domain (ubl) for proteasomal association | SIGNOR-272587 |
P46663 | P08754 | 2 | binding | up-regulates activity | 0.435 | 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-257149 |
Q13571 | Q96J02 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.411 | Here, we found that the level of LAPTM5 protein is regulated negatively by the degradation through ubiquitination by ITCH, an E3 ubiquitin ligase. ITCH directly binds to the PPxY motif of LAPTM5 via its WW domains and promotes ubiquitination through a HECT-type ligase domain. | SIGNOR-272721 |
P78362 | Q99538 | 1 | phosphorylation | up-regulates activity | 0.2 | Here we report that serine-arginine protein kinase 2 (SRPK2) phosphorylates delta-secretase and enhances its enzymatic activity. SRPK2 phosphorylates serine 226 on delta-secretase and accelerates its autocatalytic cleavage, leading to its cytoplasmic translocation and escalated enzymatic activities. | SIGNOR-273569 |
O75385 | Q16543 | 1 | phosphorylation | down-regulates activity | 0.2 | Serine/Threonine Kinase Unc-51-like Kinase-1 (Ulk1) Phosphorylates the Co-chaperone Cell Division Cycle Protein 37 (Cdc37) and Thereby Disrupts the Stability of Cdc37 Client Proteins.|Ulk1-mediated phosphorylation of Ser-339 in Cdc37 compromised the recruitment of client kinases to a complex comprising Cdc37 and heat shock protein 90 (Hsp90) but only modestly affected Cdc37 binding to Hsp90. | SIGNOR-280158 |
P41231 | 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-257233 |
P31391 | P63096 | 2 | binding | up-regulates activity | 0.504 | 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-256680 |
P25105 | P09471 | 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-257262 |
P20339 | P51149 | 2 | binding | down-regulates activity | 0.699 | The absence of active Rab7 prolongs ALS2presence and Rab5 activation on macropinosomes, indicating that activeRab7 is necessary for Rab5 inactivation through ALS2 dissociation and playskey roles in the Rab switch on macropinosomes. Taken together, active Rab7is necessary for Rab5 down-regulation through ALS2dissociation, thereby acting as a central component inthe Rab5-to-Rab7 switch in macropinocytosis | SIGNOR-277780 |
Q14678 | Q9UQB8 | 2 | binding | down-regulates activity | 0.342 | In this study, we report that Kank disrupts the function of active Rac1 through IRSp53. The binding between IRSp53 and Kank inhibits the association of active Rac1 with IRSp53 rather than the association of active cdc42 with IRSp53. Kank inhibits the formation of lamellipodia and membrane ruffles induced by active Rac1 in NIH3T3 cells. Kank interacts with IRSp53 through their coiled-coil domains. Kank affected the interaction between IRSp53 and Rac1 and partially affected that between IRSp53 and cdc42 (Fig. 3). | SIGNOR-265553 |
P38405 | O60266 | 2 | binding | up-regulates activity | 0.641 | Subsequently, the Gaolf subunit activates the integral membrane protein adenylyl cyclase type III (AC3), leading to the conversion of adenosine triphosphate (ATP) into cyclic adenosine monophosphate (cAMP) | SIGNOR-278072 |
Q15080 | P17252 | 0 | phosphorylation | up-regulates activity | 0.2 | In murine and guinea pig neutrophils, PKCδ is required for the phosphorylation of p40phox, a subunit of the NADPH oxidase complex (Li et al., 2016; Someya et al., 1999). In particular, it mediates phosphorylation of the threonine 154 (T154) residue of p40phox, a key regulatory step in the activation of the NADPH oxidase complex in peripheral neutrophils and B cells, in both mice and humans. In conclusion, the EBV-B cells of patients with PKCδ deficiency have impaired ROS production, associated with lower levels of phosphorylation of the cytosolic NADPH oxidase subunit p40phox by PKCδ. | SIGNOR-277628 |
Q13043 | Q9H4B6 | 2 | null | up-regulates | 0.886 | In vitro phosphorylation experiments indicate that the phosphorylation of Sav by Mst is direct. The stabilizing effect of Mst was much greater on N-terminally truncated hSav mutants, as long as they retained the ability to bind Mst. Mst mutants that lacked the C-terminal coiled-coil domain and were unable to bind to hSav, also failed to stabilize or phosphorylate hSav | SIGNOR-217833 |
P06702 | P49715 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.227 | Among several known transcription factor binding motifs, nuclear protein(s) of VD3-treated HL-60 cells and THP-1 cells bound to the CCAAT/enhancer binding protein (C/EBP)-binding motif that was located in the upstream region of the MRP14 gene (-81), as evidenced by the competitive gel mobility-shift assay.|Thus, it was concluded that C/EBP alpha and -beta were able to bind to the C/EBP motif, and that C/EBP alpha bound to the motif in THP-1 cells and C/EBP beta bound to that in the VD3-treated HL-60 cells. | SIGNOR-254041 |
Q9UK17 | P12931 | 0 | phosphorylation | up-regulates activity | 0.337 | These results indicate that Y108 (for Src-family kinases) and Y136 (for EGFR kinase) are involved in the tyrosine phosphorylation of hKv4.3 channels. | SIGNOR-276393 |
P16035 | P98164 | 2 | binding | up-regulates quantity | 0.2 | We show that megalin/LRP-2 acts as an endocytic receptor for proMMP-2:TIMP-2 complex. We found that RAP, an antagonist of the LDL receptor family18, competed with binding of proMMP-2:TIMP-2 complex onto rat BN16 epithelial cells. | SIGNOR-265254 |
Q05655 | P00519 | 0 | phosphorylation | up-regulates activity | 0.384 | Specifically, we have shown that nuclear targeting of PKCdelta is necessary and sufficient for epithelial cell apoptosis, and that nuclear translocation requires phosphorylation of PKCdelta at Y155 and Y64 by c-Abl and c-Src, respectively. | SIGNOR-279436 |
P42345 | Q9Y4K3 | 0 | ubiquitination | up-regulates activity | 0.438 | Together, these results demonstrate that mTOR polyubiquitination by TRAF6 modulates its activation in response to amino acids and point to a role for K63 ubiquitin modification as a sensor of nutrient status. | SIGNOR-278789 |
Q7L7L0 | Q14493 | 0 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265409 |
Q9HBM1 | Q9BRS2 | 2 | binding | up-regulates activity | 0.2 | This study demonstrates that SPC25 acts as a molecular scaffold, mediating SPC25/RIOK1/MYH9 complex formation and triggering the RIOK1‐mediated phosphorylation of MYH9 at Ser1943.Taken together, these results suggested that SPC25 increases MYH9 phosphorylation at Ser1943, enhancing the nuclear accumulation of MYH9 and consequently modulating the transcription of CTNNB1. | SIGNOR-278893 |
P19086 | P43115 | 2 | binding | up-regulates activity | 0.27 | 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-257111 |
P00441 | Q9NZJ5 | 2 | binding | up-regulates activity | 0.274 | SOD1mut-induced ER stress |we first examined whether SOD1mut induces ER stress in NSC34 motor neurons, as assessed by band-shift analyses of the ER transmembrane kinase receptors IRE1 and PERK. Adenovirus (Ad)-mediated expression of ALS-linked SOD1mut (SOD1G93A) was detectable within 48 h of infection (Supplemental Fig. S1A). SOD1mut (SOD1A4V, SOD1G85R, and SOD1G93A) but not wild-type SOD1 (SOD1wt) activated IRE1 and PERK | SIGNOR-262787 |
Q8IVH8 | Q04759 | 1 | phosphorylation | up-regulates | 0.38 | We report that the kinase glk (map4k3) directly activated pkc-? During tcr signaling. | SIGNOR-176744 |
Q13451 | Q9H3Y6 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.267 | SRMS binds FKBP51 and phosphorylates tyrosine 54. Under nutrient-replete conditions, SRMS phosphorylates the PHLPP scaffold FK506-binding protein 51 (FKBP51), disrupts the FKBP51-PHLPP complex, and promotes FKBP51 degradation through the ubiquitin-proteasome pathway. | SIGNOR-277564 |
Q8NG31 | Q96GD4 | 0 | phosphorylation | down-regulates | 0.2 | To determine whether the combinatorial regulation of the kmn network by aurora b observed in vitro is critical to controlling kinetochore-microtubule attachments in vivo, we next investigated the effect of the phosphomimetic (to aspartate) and nonphosphorylatable (to alanine) mutants of dsn1, knl1, and ndc80 in vertebrate cells. We predicted that both types of mutations in critical phosphorylation sites would affect chromosome segregation, since preventing the inactivation of inappropriately attached kinetochores by aurora b (in the nonphosphorylatable mutant) or constitutively inactivating this attachment (in the phosphomimetic mutant). | SIGNOR-165502 |
O14713 | P05556 | 2 | binding | down-regulates activity | 0.732 | 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-257638 |
O95837 | Q5NUL3 | 2 | binding | up-regulates activity | 0.46 | 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-257420 |
P49841 | O15169 | 1 | phosphorylation | up-regulates activity | 0.92 | Axin residues T609 and S614 are physiological GSK3beta targets. Axin phosphorylation in the regulation of b-catenin stability. When active (left), GSK3b phosphorylates Axin as well as APC and b-catenin. The phosphorylated form of Axin binds strongly to b-catenin and promotes the phosphorylation of b-catenin by GSK3b, leading to strong interaction with b-TrCP | SIGNOR-251221 |
O43193 | P08754 | 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-256880 |
P23409 | P50461 | 2 | binding | up-regulates activity | 0.446 | we found that nuclear MLP functions through a physical interaction with the muscle basic helix-loop-helix (bHLH) transcription factors MyoD, MRF4, and myogenin. we propose that it serves as a cofactor for the myogenic bHLH proteins by increasing their interaction with specific DNA regulatory elements. | SIGNOR-241096 |
P42345 | Q13615 | 0 | null | down-regulates activity | 0.354 | The PtdIns3-phosphatase MTMR3 interacts with mTORC1 and suppresses its activity. | SIGNOR-245105 |
P19838 | Q9Y297 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.589 | Here we demonstrate that following IkappaB kinase (IkappaK)-mediated phosphorylation, the C-terminal domain of p105 (residues 918-934) serves as a recognition motif for the SCF(beta)(-TrCP) ubiquitin ligase.In vitro, SCF(beta)(-TrCP) specifically conjugates and promotes processing of phosphorylated p105. | SIGNOR-272570 |
P63000 | P15882 | 0 | gtpase-activating protein | down-regulates activity | 0.666 | 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-260499 |
Q05655 | O15530 | 0 | phosphorylation | up-regulates activity | 0.577 | PDK1 phosphorylated the activation loop sites of PKCzeta and PKCdelta in vitro and in a phosphoinositide 3-kinase (PI 3-kinase)-dependent manner in vivo in human embryonic kidney (293) cells. PKCδ was also phosphorylated in the activation loop site (T505) | SIGNOR-250269 |
P05556 | Q9Y5H7 | 2 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. | SIGNOR-265669 |
P63092 | P37288 | 2 | binding | up-regulates activity | 0.447 | 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 ‚â• -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 ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0. | SIGNOR-256805 |
P16109 | Q14242 | 2 | binding | up-regulates | 0.927 | The major ligand for p-selectin on leukocytes is p-selectin glycoprotein ligand-1 (PSGL-1) | SIGNOR-47625 |
Q14451 | P10721 | 2 | binding | up-regulates activity | 0.584 | We furthermore demonstrate that the adapter protein Grb2 is a specific binding partner for both phosphorylated Tyr-703 and phosphorylated Tyr-936, whereas the adapter protein Grb7 binds selectively to phosphorylated Tyr-936. | SIGNOR-248291 |
P08069 | P35568 | 1 | phosphorylation | up-regulates | 0.868 | Binding of IGF1 to its receptor leads to activation of its intrinsic tyrosine kinase and autophosphorylation, thus generating docking sites for insulin receptor substrate (IRS), which is also phosphorylated by the IGF1 receptor. | SIGNOR-175665 |
P00742 | P01008 | 0 | cleavage | down-regulates activity | 0.877 | Antithrombin (AT), a member of the serine protease inhibitor (SERPIN) superfamily, is a major circulating inhibitor of blood coagulation proteases such as factor (F) IIa (known as thrombin), FXa and, to a lesser extent, FIXa, FXIa and FXIIa. SERPINC1, which encodes AT in humans, is located on chromosome 1q25.1 | SIGNOR-264138 |
P60484 | P49841 | 0 | phosphorylation | down-regulates activity | 0.424 | Gsk3beta Phosphorylates pten at thr-366 in intact cells phosphorylation of pten at thr-366 reduces the activity of pten in cells | SIGNOR-236641 |
P18754 | P06493 | 0 | phosphorylation | up-regulates activity | 0.504 | We show here that Cdc2 kinase phosphorylates the serines located in or near the nuclear localization signal (NLS) of hum an RCC1, the nucleotide exchange factor for Ran. This phosphorylation is necessary for RCC1 to generate RanGTP on mitotic chromosomes in mammalian cells, which in turn is required for spindle assembly and chromosome segregation. However, when both S2 and S11 were simultaneously mutated to As, the resulting 6His-RCC1S2,11A failed to be phosphorylated, whereas all of the other double mutants were phosphorylated (Fig. 1C). As expected, mutating all four sites to As (the 6His-RCC1S2,11,387A-T274A) also blocked phosphorylation (Fig. 1C). | SIGNOR-262704 |
P49593 | Q14012 | 1 | dephosphorylation | down-regulates activity | 0.461 | Calmodulin-dependent protein kinase phosphatase (CaMKP) dephosphorylates and concomitantly deactivates multifunctional Ca(2+)/calmodulin-dependent protein kinases , such as CaMKI, CaMKII, and CaMKIV. | SIGNOR-277111 |
Q5VWQ8 | P42336 | 2 | binding | down-regulates activity | 0.2 | DAB2IP inhibits the PI3K–AKT axis by directly interacting with both proteins, reducing phosphorylation and activation of AKT. The GAP activity of DAB2IP can further enforce inhibition of the PI3K–AKT axis by reducing Ras-dependent activation of PI3K p110α subunit. | SIGNOR-254750 |
Q92859 | O95631 | 2 | binding | up-regulates activity | 0.825 | Experiments have demonstrated that Neogenin also mediates Netrin-1 attractive functions. Both DCC and Neogenin are type I transmembrane receptors that belong to the immunoglobulin superfamily proteins. | SIGNOR-268169 |
O00192 | Q07157 | 2 | binding | up-regulates activity | 0.454 | We identified ARVCF as a binding partner of ZO-1 and ZO-2 and characterized the role of PDZ-domain proteins in plasma membrane and nuclear localization of ARVCF. E-cadherin, ZO-1, and ARVCF are recruited to sites of initial cell-cell contact. Binding of the ZO-1 PDZ domains per se does not facilitate membrane recruitment of ARVCF, indicating a requirement for the intact ZO-1 and possibly its association with membrane proteins and/or the cytoskeleton for this process. | SIGNOR-252121 |
Q13351 | Q01543 | 2 | binding | down-regulates activity | 0.371 | The present study also shows that EKLF itself inhibits FLI-1 activity. As suggested above for the inhibition of EKLF activity, the inhibition of FLI-1 activity most probably involves the indirect recruitment of EKLF to FLI-1 target promoters by protein-protein interaction. | SIGNOR-256046 |
P63096 | Q92847 | 2 | binding | up-regulates activity | 0.373 | 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-257054 |
P41091 | P49770 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.696 | EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity. | SIGNOR-269135 |
Q8TCQ1 | P06213 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH1 ubiquitinates INSR to decrease cell surface INSR levels, but unlike other INSR ubiquitin ligases, MARCH1 acts in the basal state rather than after insulin stimulation. | SIGNOR-278819 |
Q86YJ5 | Q8NHL6 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets. | SIGNOR-271534 |
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 |
P25490 | P07947 | 0 | phosphorylation | down-regulates activity | 0.2 | YY1 phosphorylation is mediated by Src family kinases. | SIGNOR-276941 |
Q9UQB3 | P12931 | 0 | phosphorylation | up-regulates activity | 0.329 | Furthermore, according to our data from immunoprecipitation to py20 antibody, c-Src can phosphorylate delta-catenin on Y1073, Y1176, Y1179 and Y1112, with the predominant sites being Y1073, Y1112 and Y1176.|Interestingly, we found that c-Src can increase the stability of delta-catenin in MEF cells. | SIGNOR-278327 |
P06850 | Q92731 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.386 | 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-268722 |
Q15389 | Q02763 | 2 | binding | up-regulates | 0.796 | Angiopoietin-1 (ang1) is an angiogenic factor that signals through the endothelial cell-specific tie2 receptor tyrosine kinase. | SIGNOR-49355 |
O15355 | P63162 | 1 | dephosphorylation | up-regulates quantity by stabilization | 0.2 | Dephosphorylation of survival motor neurons (SMN) by PPM1G and PP2Cgamma governs Cajal body localization and stability of the SMN complex.|This indicates that the catalytic activity of PPM1G promotes accumulation of the SMN complex in CBs and suggests that PPM1G is a major determinant of the SMN-complex localization in the nucleus. | SIGNOR-277021 |
Q96IV0 | P54727 | 2 | binding | up-regulates activity | 0.82 | The XPCB domain of Rad23 binds Png1, which in turn facilitates the substrate recognition of Rad23. Through interactions with Ub chains and the proteasome mediated by the UBA and UBL domains in Rad23, Rad23 facilitates substrate transfer to the proteasome. | SIGNOR-261061 |
P29323 | O43426 | 1 | phosphorylation | down-regulates | 0.57 | Ephb2 causes tyrosine phosphorylation in the proline-rich domain of synaptojanin 1, and inhibits both the interaction with endophilin and the 5'-phosphatase activity of synaptojanin 1 | SIGNOR-135274 |
P17612 | Q08499 | 1 | phosphorylation | up-regulates | 0.569 | Phosphorylation and activation of a camp-specific phosphodiesterase by the camp-dependent protein kinase. | SIGNOR-42515 |
P35368 | O95837 | 2 | binding | up-regulates activity | 0.435 | 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-257190 |
P53350 | P30305 | 1 | phosphorylation | up-regulates activity | 0.663 | These data indicated that PLK1 phosphorylates CDC25B and that pre-phosphorylation of CDC25B by CDK1/CyclinB enhances its substrate properties for PLK1 in vitro | SIGNOR-267560 |
P30153 | P67775 | 2 | binding | up-regulates | 0.959 | Pr65/a acts as a scaffold protein for binding pp2ac and regulatory b subunits in a heterotrimeric holoenzyme | SIGNOR-138883 |
P31749 | P20749 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.494 | Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3. Phosphorylation by Erk2 and IKK1/2 of Ser114 and Ser446 converts Bcl3 into a transcriptional coregulator by facilitating its recruitment to DNA. | SIGNOR-277358 |
Q92466 | Q01094 | 2 | binding | up-regulates | 0.367 | We show that ddb, a putative dna repair protein, associates with the activation domain of e2f1 / expression of ddb specifically stimulated e2f1-activated transcription | SIGNOR-54102 |
P49841 | Q14494 | 1 | phosphorylation | down-regulates | 0.4 | Glycogen synthase kinase 3 regulates expression of nuclear factor-erythroid-2 related transcription factor-1 (nrf1) and inhibits pro-survival function of nrf1 | SIGNOR-193450 |
Q9NPG1 | P04628 | 2 | binding | up-regulates activity | 0.628 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131571 |
P12931 | Q7Z3C6 | 1 | phosphorylation | up-regulates activity | 0.342 | Src phosphorylates mATG9 at Tyr8 to maintain its endocytic and constitutive trafficking in unstressed conditions. In response to starvation, phosphorylation of mATG9 at Tyr8 by Src and at Ser14 by ULK1 functionally cooperate to promote interactions between mATG9 and the AP1/2 complex, leading to redistribution of mATG9 from the plasma membrane and juxta-nuclear region to the peripheral pool for autophagy initiation. | SIGNOR-266367 |
Q7L576 | Q6T4R5 | 2 | binding | up-regulates activity | 0.2 | We show that the WHD of NHS interacts with the Abi family of proteins, HSPC300, Nap1 and Sra1, and is important for the localization of NHS to the leading edge. | SIGNOR-253575 |
P45985 | P54762 | 0 | relocalization | up-regulates activity | 0.2 | The phosphorylated CNK1 interacts with ephrinB1. The binding of ephrinB1 to CNK1 connects RhoA and p115RhoGEF with ephrinB1-associated MKK4, promoting JNK activation and cell migration. | SIGNOR-275922 |
Q12770 | O15503 | 2 | binding | down-regulates activity | 0.767 | Using coimmunoprecipitation and tandem mass spectrometry, we identify INSIG-1 as an ER protein that binds the sterol-sensing domain of SREBP cleavage-activating protein (SCAP) and facilitates retention of the SCAP/SREBP complex in the ER. | SIGNOR-267495 |
Q16695 | Q9H3R0 | 0 | demethylation | down-regulates activity | 0.2 | As one member of the Jumonji-C histone demethylase family, JMJD2C has the ability to demethylate tri- or di-methylated histone 3 and 2 in either K9 (lysine residue 9) or K36 (lysine residue 36) sites by an oxidative reaction, thereby affecting heterochromatin formation, genomic imprinting, X-chromosome inactivation, and transcriptional regulation of genes.JMJD2C has been proved to be a demethylase for H3K9 methylation, in the manner of catalyzing the demethylation of H3K9me3/me2 (the known repressive markers of gene regulation), a histone mark found in heterochromatin associated with euchromatic transcriptional silencing and heterochromatin formation | SIGNOR-263866 |
Q13164 | P43354 | 1 | phosphorylation | up-regulates activity | 0.2 | Activation of MEK, which in turns activates ERK5, does enhance the ERK5 induced nurr1 activity, while no increase is observed in the presence of a dn MEK5 or of the unphosphorylated ERK5 AEF, in which amino acids phosphorylated by MEK5 are mutated.|The A/B domain of nurr1 is highly phosphorylated in the presence of ERK5 and mutations of two amino acids in this same domain decrease significantly the ERK5 mediated nurr1 transcriptional response.|These data would suggest once again that the basal activity of ERK5 is responsible for the phosphorylation of nurr1.|As shown in XREF_FIG, nurr1 A/B domain was significantly phosphorylated by ERK5, while the GST protein alone was not a substrate for this kinase. | SIGNOR-279215 |
P03372 | Q9H3C7 | 2 | binding | down-regulates activity | 0.2 | We further demonstrate that GGNBP2 protein physically interacts with ERα, inhibits E2-induced activation of estrogen response element-driven reporter activity, and attenuates ER target gene expression in T47D cells. | SIGNOR-269076 |
P08603 | P02741 | 2 | binding | down-regulates activity | 0.551 | In this study, we provide mechanistic insight into how CRP contributes to the development of AMD. In particular, we show that monomeric CRP (mCRP) but not the pentameric form (pCRP) upregulates IL-8 and CCL2 levels in retinal pigment epithelial cells. Further, we show that complement factor H (FH) binds mCRP to dampen its proinflammatory activity. FH from AMD patients carrying the “risk” His402 polymorphism displays impaired binding to mCRP, and therefore proinflammatory effects of mCRP remain unrestrained. | SIGNOR-252145 |
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