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 |
|---|---|---|---|---|---|---|---|
Q00535 | O43426 | 1 | phosphorylation | down-regulates activity | 0.505 | Cdk5 phosphorylation inhibited the inositol 5-phosphatase activity of synaptojanin 1, whereas dephosphorylation by calcineurin stimulated such activity.|The activity of synaptojanin 1 was also stimulated by its interaction with endophilin 1, its major binding partner at the synapse. Notably, Cdk5 phosphorylated serine 1144, which is adjacent to the endophilin binding site. | SIGNOR-279685 |
P50613 | Q13285 | 1 | phosphorylation | up-regulates | 0.366 | In conclusion, our results indicate that cdk7, as part of the cak complex and tfiih, phosphorylates sf1 at s203 followed by increased transcriptional activity of sf1 | SIGNOR-157952 |
Q00987 | P46934 | 0 | ubiquitination | up-regulates quantity by stabilization | 0.466 | NEDD4 promotes MDM2 ubiquitination in a dose- and time-dependent manner, whereas depletion of NEDD4 reduced the half-life of endogenous MDM2 [ xref ]. | SIGNOR-278769 |
P37288 | P63092 | 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 |
Q13352 | Q13153 | 0 | phosphorylation | up-regulates | 0.2 | Serine 28 phosphorylation of nrif3 confers its co-activator function for estrogen receptor-alpha transactivation. p21-activated protein kinase 1 (pak1) phosphorylates eralpha at ser305 and this modification is important in eralpha transactivation function. | SIGNOR-178795 |
P56524 | Q13557 | 0 | phosphorylation | up-regulates | 0.358 | These results demonstrate that camkiideltab preferentially targets hdac4, and this involves serine 210overexpression of camkiideltab in primary neonatal cardiomyocytes increases the activity of the mef2 transcription factor and completely rescues hdac4-mediated repression of mef2 | SIGNOR-151418 |
Q9BV47 | P11362 | 1 | dephosphorylation | down-regulates activity | 0.2 | NEAP and DUSP26 dephosphorylated TrkA and FGFR1 directly.|We found that NEAP, but not its phosphatase-defective mutant, suppressed nerve growth factor (NGF) receptor TrkA and fibroblast growth factor receptor 1 (FGFR1) activation in PC12 cells | SIGNOR-277104 |
O43541 | Q9C0C9 | 0 | ubiquitination | down-regulates | 0.464 | We showed that ube2o functions as an e2-e3 hybrid to monoubiquitinate smad6 at lysine 174 | SIGNOR-192255 |
P11362 | P05230 | 2 | binding | up-regulates activity | 0.914 | Together these data highlight the unique nature of the role of FGF-1 during the earliest stages of adipogenesis and establish a role for FGFR1 in human adipogenesis, identifying FGFR1 as a potential therapeutic target to reduce obesity. | SIGNOR-236936 |
Q96PZ7 | P01024 | 2 | binding | down-regulates quantity | 0.2 | CUB and sushi multiple domains 1 (CSMD1) is a relatively poorly studied large transmembrane protein of 390 kDa composed of 14 N-terminal CUB domains interspersed with complement control protein (CCP) domains followed by 15 consecutive CCP domains. The active domains of CSMD1 were then identified in CCP17-21, which were shown to interact with C4b and C3b and present these complement proteins for degradation by factor | SIGNOR-265148 |
P46734 | Q9Y6R4 | 0 | phosphorylation | up-regulates activity | 0.639 | These results, therefore, suggest that mtk1 directly phosphorylates and activates mkk3, mkk6 and sek1. | SIGNOR-50891 |
P60891 | P06493 | 0 | phosphorylation | up-regulates activity | 0.254 | CDK1 contributes to upregulation of PRPS1 activity by phosphorylating PRPS1 at S103|In conclusion, compared with upregulation of PRPS1 expression levels, increased PRPS1 activity, which is marked by S103 phosphorylation | SIGNOR-265728 |
Q14872 | Q9NRM7 | 0 | phosphorylation | down-regulates activity | 0.2 | The Hippo pathway kinases LATS1 and LATS2 attenuate cellular responses to heavy metals through phosphorylating MTF1|the Hippo pathway kinase LATS phosphorylates and inhibits MTF1|LATS phosphorylates MTF1 at S152 and disrupts its association with the promoters of heavy metal response genes, resulting in the loss of heavy metal response gene expression | SIGNOR-275475 |
Q9Y6K9 | O14920 | 2 | binding | up-regulates activity | 0.962 | The n-terminal domain of ikkgamma is required both for the binding of ikkalfa and ikkbeta and their assembly into a high-molecular-weight complex essential for activation | SIGNOR-91705 |
O43683 | Q13315 | 0 | phosphorylation | up-regulates | 0.461 | We also demonstrate that mitotically activated atm phosphorylates bub1, a critical kinetochore protein, on ser314. Atm-mediated bub1 ser314 phosphorylation is required for bub1 activity and is essential for the activation of the spindle checkpoint | SIGNOR-177276 |
Q14332 | Q68DV7 | 0 | relocalization | up-regulates | 0.308 | Frizzled receptors are regu__lated by cycles of ubiquitylation and deubiquitylation61 (see above), and znrf3 and rnf43 act as frizzled ubiquitin ligases, removing frizzled and possibly lrp6 from the plasma membrane | SIGNOR-199585 |
Q16665 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.259 | In conclusion, we obtained compelling evidence that CDK5 directly stabilizes the transcription factor hypoxia inducible factor-1\u03b1 by phosphorylation, and thus promotes the formation of blood vessels.|Mass spectrometry and site directed mutagenesis revealed a stabilizing phosphorylation of HIF-1\u03b1 at Ser687 by CDK5. | SIGNOR-279020 |
P01116 | Q5VWQ8 | 0 | gtpase-activating protein | down-regulates activity | 0.518 | The GAP domain of DAB2IP is homologous to other Ras-GAPs, such as GAP120 and neurofibromin (NF1), and can stimulate the GTPase activity of RAS proteins both in vitro and in cancer cell lines. DAB2IP is able to stimulate in vitro and in vivo the GTPase activity of RAS proteins (H-Ras, K-Ras, and N-Ras) facilitating GTP hydrolysis to GDP. | SIGNOR-254746 |
P12931 | P48048 | 1 | phosphorylation | down-regulates | 0.312 | Inhibition of c-src with herbimycin a significantly decreased the tyrosine phosphorylation level of romk1... tyrosine dephosphorylation enhances the exocytosis of romk1 | SIGNOR-97803 |
P35222 | O95996 | 0 | relocalization | down-regulates quantity by destabilization | 0.79 | The tumour-suppressing activity of apc largely involves facilitating the proteasome-mediated degradation of b-cateninit is possible that once exported from the nucleus, apc directs b-catenin along the cytoskeletal network to sites of degradation. | SIGNOR-81545 |
P10147 | P41597 | 2 | binding | up-regulates activity | 0.555 | The purpose of this study was to determine whether certain chemokines, which are highly expressed in injured skeletal muscle, are involved in the repair and functional recovery of the muscle after traumatic injury. In wild-type control mice, mRNA transcripts of macrophage inflammatory protein (MIP)-1, MIP-1, and monocyte chemoattractant protein (MCP)-1 as well as their major receptors, CCR5 and CCR2, increased after freeze injury and gradu- ally returned to control (uninjured) levels by 14 days. | SIGNOR-251723 |
P85298 | Q9UHA4 | 2 | binding | up-regulates activity | 0.252 | Furthermore, we identify that BPGAP1 (a BCH domain-containing, Cdc42GAP-like Rho GTPase-activating protein) promotes MEK partner 1 (MP1)-induced ERK activation on late endosome through scaffolding MP1/MEK1 complex. This regulatory function requires phosphorylation of BPGAP1 by JNK at its C terminal tail (Ser424) to unlock its autoinhibitory conformation. | SIGNOR-275551 |
Q12972 | P19784 | 0 | phosphorylation | up-regulates activity | 0.473 | Phosphorylation of NIPP-1 in a heterodimeric complex with the catalytic subunit of protein phosphatase-1 resulted in an activation of the holoenzyme without a release of NIPP-1. Sequencing and phosphoamino acid analysis of tryptic phosphopeptides enabled us to identify Ser178 and Ser199 as the phosphorylation sites of protein kinase A, whereas Thr161 and Ser204 were phosphorylated by protein kinase CK2. | SIGNOR-251023 |
P62879 | Q99835 | 2 | binding | up-regulates | 0.2 | Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling. | SIGNOR-199177 |
P12931 | O14976 | 1 | phosphorylation | up-regulates activity | 0.274 | GAK is phosphorylated by c-Src and translocated from the centrosome to chromatin at the end of telophase. Cyclin G-associated kinase (GAK) harbors a consensus phosphorylation motif (Y412) for c-Src; however, its physiological significance remains elusive. Here, we show that GAK is phosphorylated by c-Src not only at Y412 but also at Y1149. | SIGNOR-263197 |
P05771 | P41180 | 1 | phosphorylation | down-regulates activity | 0.319 | Expression of a mutant CaR in which the major PKC phosphorylation site is altered by substitution of alanine for threonine (T888A) eliminated oscillatory behavior, producing [Ca(2+)](i) responses almost identical to those produced by the wild type CaR exposed to PKC inhibitors. These results support a model in which phosphorylation of the CaR at the inhibitory threonine 888 by PKC provides the negative feedback needed to cause [Ca(2+)](i) oscillations mediated by this receptor. | SIGNOR-249176 |
Q13936 | P43146 | 0 | 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-268291 |
Q8TCU6 | P63000 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.719 | 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-260569 |
P35226 | P31749 | 0 | phosphorylation | up-regulates activity | 0.437 | The polycomb group silencing protein Bmi1 can be phosphorylated by AKT, which enhances its oncogenic potential in PCa. Overexpression of Bmi1 can act in combination with PTEN haploinsufficiency to induce invasive carcinogenic formation in the prostate | SIGNOR-252559 |
P49336 | P42224 | 1 | phosphorylation | up-regulates activity | 0.392 | We previously demonstrated that Mediator kinase inhibitor cortistatin A (CA) reduced proliferation of JAK2-mutant AML in vitro and in vivo and also suppressed CDK8-dependent phosphorylation of STAT1 at serine 727. Here we report that phosphorylation of STAT1 S727 promotes the proliferation of AML cells with JAK-STAT pathway activation. | SIGNOR-273179 |
O75582 | P18846 | 1 | phosphorylation | up-regulates activity | 0.69 | Using embryonic fibroblasts derived from these mice we were able to demonstrate an important role for these enzymes in the activation of CREB and the closely related transcription factor ATF1. | Our results clearly demonstrate that MSK1 and MSK2 are the major, if not the only, protein kinases that mediate the phosphorylation of CREB at Ser133 and of ATF1 at Ser63 in fibroblasts | SIGNOR-249144 |
P48729 | Q13009 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.309 | Phosphorylation of Ser329, Ser334, and Thr340 in Tiam1 is required for its interaction with βTrCP1. The proteolysis of Tiam1 is prevented by βTrCP silencing, inhibition of CK1 and MEK, or mutation of the Tiam1 degron site. | SIGNOR-276673 |
Q9C0C7 | Q7Z6Z7 | 1 | relocalization | up-regulates activity | 0.2 | AMBRA1 regulates mitophagy at two critical steps. Upon mitophagy stimulation, AMBRA1 mediates the HUWE1 E3 ubiquitin ligase translocation from cytosol to mitochondria (light blue). AMBRA1 acts as a cofactor for HUWE1 E3 ubiquitin ligase activity, favouring its binding to its substrate MFN2 (and maybe other OMM substrates) and targeting it to the proteasome | SIGNOR-272962 |
Q8N1W1 | Q14344 | 2 | 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 |
O14733 | P21333 | 2 | binding | up-regulates activity | 0.259 | We used Filamin-A-deficient cells to show that Filamin A enhances MKK7 activation and is important for synergistic stress-induced JNK activation in vivo. Thus Filamin A is a novel member of the group of scaffold proteins whose function is to link two MAPKKs together and promote JNK activation. The present study provides evidence that Filamin A is one of the ‘binder’ molecules presumed to directly and closely connect MKK4 and MKK7 so that they can mediate this tyrosine/threonine phosphorylation. We showed that Filamin A (as well as Filamin B and C) associate with MKK7 and MKK4, but not with JNK1 itself | SIGNOR-260628 |
P78317 | P24941 | 0 | phosphorylation | up-regulates activity | 0.2 | Here we reported that CDK2 could phosphorylate RNF4 on T26 and T112 and enhance RNF4 E3 ligase activity, which is important for MDC1 degradation and proper HR repair during S phase. | SIGNOR-276900 |
O43312 | Q9UMX1 | 2 | binding | up-regulates | 0.438 | We found that in vitro translated gli1 and sufu bind to gst-mim, but not gst-mim?N399 Or gst columns (fig. 4f). Indicative of the importance of the mim/gli complex interactions, the mim?N399 Mutant that fails to interact with gli and sufu showed a markedly reduced capacity to potentiate gli-dependent transcription (fig. 4g). Although these results indicate that a mim/gli/sufu complex is important for mim-mediated transcriptional potentiation | SIGNOR-130545 |
P27361 | Q99814 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.26 | The activation of ERK1/2 upon hypoxia promoted HIF-2alpha phosphorylation, enhancing its interaction with USP33.Here, we identified USP33 as essential deubiquitinase that stabilizes HIF-2alpha protein in an ERK1/2-dependent manner to promote hypoxia response in cancer cells. | SIGNOR-277584 |
P06241 | Q9NZA1 | 1 | phosphorylation | up-regulates activity | 0.296 | In this paper, we demonstrate that p64 becomes tyrosine phosphorylated when co-expressed with p59(fyn) in HeLa cells. | SIGNOR-274006 |
P21796 | P00441 | 2 | binding | down-regulates activity | 0.425 | Misfolded Mutant SOD1 Directly Inhibits VDAC1 Conductance in a Mouse Model of Inherited ALS|With conformation-specific antibodies, we now demonstrate that misfolded mutant SOD1 binds directly to the voltage-dependent anion channel (VDAC1), an integral membrane protein imbedded in the outer mitochondrial membrane. | SIGNOR-262798 |
O15553 | Q16512 | 0 | phosphorylation | down-regulates activity | 0.384 | PKNs bind to human pyrin and phosphorylate S208 and S242. Pyrin forms an inflammasome when mutant or in response to bacterial modification of the GTPase RhoA. We found that RhoA activated the serine-threonine kinases PKN1 and PKN2 that bind and phosphorylate pyrin. Phosphorylated pyrin bound to 14-3-3 proteins, regulatory proteins that in turn blocked the pyrin inflammasome. | SIGNOR-275461 |
Q9C026 | Q9C026 | 2 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Collectively, these results indicated that TRIM9 is an E3 ligase for its self-ubiquitination and that the ubiquitination of TRIM9 likely serves as a signal for proteasomal degradation. As shown in Fig. 1A, TRIM9 was ubiquitinated by itself when incubated with UbcH5b. In contrast, ubiquitination was observed when incubated with other E2 enzymes. These results suggest that TRIM9 cooperates with UbcH5b for its self-ubiquitination. N | SIGNOR-271419 |
Q9UM11 | P11309 | 0 | phosphorylation | down-regulates activity | 0.317 | Pim-1 phosphorylates Cdh1 and impairs binding of this protein to another APC/C complex member, CDC27. These modifications inhibit Skp2 from degradation.Pim-1 Impairs Cdh1 and CDC27 Interaction and Phosphorylates Cdh1. | SIGNOR-259820 |
Q9BZS1 | Q9NZQ7 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.468 | FOXP3 expression additionally increased programmed death ligand 1 (PD-L1) expression, which, when inhibited with CCL5, decreased the tumor burden and Treg infiltration in orthotopic murine, Pan-02 PDAC tumors | SIGNOR-277728 |
O95185 | P43146 | 2 | binding | down-regulates activity | 0.669 | In the presence of netrin-1, UNC5 co-immuno-precipitates with DCC, suggesting the formation of a ternary complex of netrin-1 with ecto-domains of DCC and UNC5. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists. | SIGNOR-268165 |
Q13153 | P36871 | 1 | phosphorylation | up-regulates | 0.343 | The signaling kinase p21-activated kinase 1 (pak1) binds to, phosphorylates and enhances the enzymatic activity of phosphoglucomutase 1 (pgm), | SIGNOR-127135 |
P02818 | P07711 | 0 | cleavage | down-regulates quantity by destabilization | 0.2 | This study has been undertaken to compare the degradation of BGP by the cysteine proteinases cathepsins L, B, H, S, and the aspartic proteinase cathepsin D. Cathepsins B, L, H, and S readily cleave BGP at the G7-A8 bond; cathepsin L also cleaves at R43-R44; cathepsin B also cleaves at R44-F45; and cathepsin D cleaves only at A41-Y42. | SIGNOR-256322 |
P68371 | Q14980 | 2 | binding | up-regulates | 0.405 | Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules. | SIGNOR-117078 |
Q9H270 | P15311 | 2 | binding | up-regulates activity | 0.35 | The interaction between the full-length Vps11 and ezrin was confirmed by immunoprecipitation and GST-pull down. ERM proteins and the HOPS complex are required for the transition from early to late endosomes | SIGNOR-261311 |
O14641 | O75581 | 2 | binding | up-regulates activity | 0.69 | Dvl is required for lrp6 phosphorylation, which is essential for subsequent steps of signal transduction. | SIGNOR-66362 |
P45985 | P05412 | 1 | phosphorylation | up-regulates activity | 0.537 | SEK1 phosphorylates and activates both p38 and c-Jun NH(2)-terminal kinase (JNK), whereas MKK3 and MKK6 selectively phosphorylate and activate p38. | SIGNOR-279063 |
P67809 | Q15418 | 0 | phosphorylation | up-regulates | 0.543 | We therefore conclude that rsk1/rsk2 are novel activators of yb-1, able to phosphorylate the serine 102 residue. | SIGNOR-182497 |
O60934 | P15927 | 2 | binding | up-regulates | 0.548 | The response to replication stress requires the recruitment of rpa and the mre11-rad50-nbs1 (mrn) complex. We observe a direct interaction between rpa with both nbs1 and mre11. By utilizing rpa bound to ssdna, we demonstrate that substituting rpa with phosphorylated rpa or a phosphomimetic weakens the interaction with the mrn complex. | SIGNOR-186651 |
O95140 | Q9NX47 | 0 | ubiquitination | up-regulates activity | 0.2 | Taken together, these results suggested that MITOL regulates endoplasmic reticulum tethering to mitochondria by activating Mfn2 via K192 ubiquitination.|Therefore, MITOL specifically ubiquitinates mitochondrial Mfn2. | SIGNOR-278553 |
P15036 | P09486 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.305 | Ets2 is expressed at high levels during the differentiation and matrix mineralization phases of MC3T3-E1 culture. In addition, several extracellular matrix (ECM) associated gene products are targets of Ets2. Some of these matrix associated genes include: bone sialoprotein, osteonectin, osteocalcin and osteopontin | SIGNOR-259874 |
Q14469 | Q06330 | 2 | binding | down-regulates | 0.6 | Here we show that hrt2 and hes1 interact with rbp-jkappa to negatively regulate notch-dependent activation of hrt and hes expression. | SIGNOR-146684 |
P49841 | Q9BYG3 | 1 | phosphorylation | up-regulates activity | 0.2 | The forkhead-associated (FHA) domain of human Ki67 interacts with the human nucleolar protein hNIFK, recognizing a 44-residue fragment, hNIFK226-269, phosphorylated at Thr234. Here we show that high-affinity binding requires sequential phosphorylation by two kinases, CDK1 and GSK3, yielding pThr238, pThr234 and pSer230. phosphorylation of Thr234 by GSK3 proceeds only after Thr238 is already phosphorylated by CDK1. | SIGNOR-262698 |
Q9Y371 | P22681 | 2 | binding | up-regulates | 0.399 | Cbl rapidly recruits cin85 (cbl-interacting protein of 85k;ref. 6) and endophilins (regulatory components of clathrin-coated vesicles) to form a complex with activated egf receptors, thus controlling receptor internalization. | SIGNOR-115826 |
P01116 | Q9NS23 | 2 | binding | up-regulates activity | 0.648 | Mutant K-Ras promotes MST2 activation in two ways (i.e., by direct disruption of the inhibitory Raf-1-MST2 complex (Matallanas et al., 2008) and by forming an activating (i.e., by direct disruption of the inhibitory Raf-1-MST2 complex K-Ras-RASSF1AMST2 complex, as reported here | SIGNOR-249585 |
O43663 | O95239 | 2 | binding | up-regulates activity | 0.568 | These results suggest that KIF4 and its binding partner PRC1 play essential roles in the organization of central spindles and midzone formation. KIF4 deficiency leads to mislocalization of PRC1, MKLP1, CENP-E and chromosomal passenger proteins | SIGNOR-265988 |
O15264 | P16949 | 1 | phosphorylation | down-regulates | 0.414 | Serine 25 of oncoprotein 18 is a major cytosolic target for the mitogen-activated protein kinase. | SIGNOR-36362 |
Q02156 | Q99259 | 1 | phosphorylation | down-regulates activity | 0.321 | We have identified one specific phosphorylation site, threonine 91 (T91), in hGAD67 that can be phosphorylated by PKA using MALDI-TOF. Site-directed mutation of T91 to alanine abolished PKA-mediated phosphorylation and inhibition of GAD activity. | SIGNOR-249264 |
Q13322 | P36888 | 2 | binding | up-regulates activity | 0.364 | These results suggest that Grb10 binds to both normal and oncogenic FLT3 and induces PI3K–Akt and STAT5 signaling pathways resulting in an enhanced proliferation, survival and colony formation of hematopoietic cells. | SIGNOR-255947 |
P43405 | Q8N6F7 | 1 | phosphorylation | up-regulates activity | 0.356 | Herein, we demonstrate phosphorylation of HGAL by Syk and Lyn kinases at tyrosines Y80, Y86, Y106Y107, Y128, and Y148. Y148 (in black) was already phosphorylated before the addition of kinases. We demonstrate that Grb2 facilitates HGAL and Syk binding following BCR stimulation but does not affect the HGAL-mediated increase in Syk kinase activity. Previous studies showed that Grb2 inhibits BCR signaling by decreasing the activation of Syk by Lyn.11 Thus, while HGAL and Grb2 oppositely affect Syk kinase activity, this is not due to direct Grb2 effects on HGAL-mediated Syk kinase activation. | SIGNOR-273570 |
Q2M2I3 | P48730 | 2 | binding | up-regulates quantity | 0.2 | We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates. | SIGNOR-273767 |
Q14653 | P67775 | 0 | dephosphorylation | down-regulates activity | 0.314 | RACK1 Negatively Regulates the Type I IFN pathway. 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-260944 |
Q9BT92 | Q8N5Z5 | 2 | binding | down-regulates quantity by destabilization | 0.336 | We have identified KCTD17 as a substrate-adaptor for Cul3-RING E3 ligases (CRL3s) that polyubiquitylates trichoplein. Depletion of KCTD17 specifically arrests ciliogenesis at the initial step of axoneme extension through aberrant trichoplein-Aurora-A activity. Thus, CRL3-KCTD17 targets trichoplein to proteolysis to initiate the axoneme extension during ciliogenesis. | SIGNOR-272463 |
P14210 | P03951 | 0 | cleavage | up-regulates activity | 0.313 | the ability of plasma kallikrein and FXIa to activate pro-HGF in vitro raises the possibility that mediators of inflammation and blood coagulation may also regulate processes that involve the HGF/c-Met pathway, such as tissue repair and angiogenesis.Unlike other known activators, both FXIa and kallikrein processed pro-HGF by cleavage at two sites. Using N-terminal sequencing they were identified as the normal cleavage site Arg(494)-Val(495) and the novel site Arg(424)-His(425) located in the K4 domain of the alpha-chain. | SIGNOR-256515 |
P00533 | Q13480 | 1 | phosphorylation | up-regulates | 0.76 | Gab-1 is a multisubstrate docking protein downstream in the signaling pathways of different receptor tyrosine kinases, including the epidermal growth factor receptor (egfr)the entire protein was phosphorylated by regfr at eight tyrosine residues (y285, y373, y406, y447, y472, y619, y657, and y689). | SIGNOR-236400 |
O95837 | P21918 | 2 | binding | up-regulates activity | 0.264 | 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-257418 |
P08908 | Q5BJH7 | 0 | relocalization | up-regulates activity | 0.399 | Together, our results provide strong evidence that Yif1B is a member of the ER/Golgi trafficking machinery, which plays a key role in specific targeting of 5-HT(1A)R to the neuronal dendrites. This finding opens up new pathways for the study of 5-HT(1A)R regulation by partner proteins and for the development of novel antidepressant drugs.|We confirmed 5-HT(1A)R-Yif1B interaction by glutathione S-transferase pull-down experiments using rat brain extracts and transfected cell lines. | SIGNOR-268299 |
P54646 | P41235 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.367 | AMPK directly phosphorylates HNF4alpha and represses its transcriptional activity. AMPK-mediated phosphorylation of HNF4alpha on serine 304 had a 2-fold effect, reducing the ability of the transcription factor to form homodimers and bind DNA and increasing its degradation rate in vivo. Phosphorylation of HNF4α on Ser-304 reduces protein stability. | SIGNOR-250322 |
P54756 | Q12857 | 0 | transcriptional regulation | up-regulates quantity | 0.2 | For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8) | SIGNOR-268895 |
P17535 | P27361 | 0 | phosphorylation | up-regulates | 0.459 | Menin binds the jun family transcription factor jund and inhibits its transcriptional activity. The menin-jund interaction blocks jun n-terminal kinase (jnk)-mediated jund phosphorylation and suppresses jund-induced transcription. We found a role for phosphorylation of the ser100 residue of jund;jund phosphorylation were prevented by inhibitors of calcium, calmodulin, or erk1/2 kinase. | SIGNOR-196034 |
P49840 | P46531 | 1 | phosphorylation | down-regulates | 0.319 | Taken together, our results indicate that gsk-3alfa is a negative regulator of notch1/nicd. | SIGNOR-183969 |
P46459 | P60880 | 2 | binding | down-regulates activity | 0.722 | NSF is an important regulator of SNARE assembly/disassembly. NSF binds to SNAP-25, while in complex with other SNAREs, and hydrolyzes adenosine triphosphate to disassemble the SNARE complex down to monomers | SIGNOR-263974 |
P16298 | Q13469 | 1 | dephosphorylation | up-regulates | 0.614 | Calcineurin dephosphorylates members of the nuclear factor of activated T cells (NFAT)2 transcription factor family, allowing NFAT to translocate to the nucleus where it cooperates with other transcription factors to induce transcription of target genes. | SIGNOR-233438 |
P41970 | P45984 | 0 | phosphorylation | down-regulates activity | 0.323 | JNK binds to the J box in the middle of the protein, and binding is required for phosphorylation of the adjacent EXport motif. Both the binding and phosphorylation sites (the JEX element) are important for Net export. | SIGNOR-250138 |
O14965 | Q9NS23 | 1 | phosphorylation | down-regulates | 0.448 | Aurora-a appears to phosphorylate rassf1a at threonine202 and/or serine203 that reside within the known microtubule-binding domain of rassf1a. Substitutions of these residues with glutamic acid at both positions, mimicking constitutive phosphorylation of rassf1a, disrupt rassf1a interactions with microtubules and abolish its ability to induce m-phase cell cycle arrest. | SIGNOR-155815 |
Q92831 | P08151 | 1 | acetylation | down-regulates activity | 0.469 | NR3C1 impaired GLI1 function by dynamically modulating the recruitment of PCAF acetyltransferase | SIGNOR-269270 |
P53805 | O43318 | 0 | phosphorylation | up-regulates activity | 0.2 | Here we showed that TAK1 directly phosphorylated RCAN1 at two novel sites (serine 94 and -136), resulting in activation of calcineurin-NFAT signaling.|Indeed, low doses of RCAN1 facilitated calcineurin-nuclear factor of activated T cells signaling in the presence of TGF-\u03b2-activated kinase 1+TAB1 ( ), suggesting that TGF-\u03b2-activated kinase 1 augments calcineurin-nuclear factor of activated T cells signaling through RCAN1. | SIGNOR-279535 |
P17302 | P05771 | 0 | phosphorylation | down-regulates activity | 0.388 | Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication.|These data strongly suggest that PKC directly phosphorylates Cx43 on S368 in vivo, which results in a change in single channel behavior that contributes to a decrease in intercellular communication. | SIGNOR-249049 |
P04637 | O94953 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.281 | KDM4B/JMJD2B is a p53 target gene that modulates the amplitude of p53 response after DNA damage. p53 directly regulates JMJD2B gene expression by binding to a canonical p53-consensus motif in the JMJD2B promoter. | SIGNOR-263729 |
Q9BT56 | O43603 | 2 | binding | up-regulates activity | 0.339 | Coevolution of the spexin/galanin/kisspeptin family: Spexin activates galanin receptor type II and III. | SIGNOR-268574 |
Q03113 | O14842 | 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-257338 |
P24844 | O75116 | 0 | phosphorylation | up-regulates activity | 0.647 | Here we found that Rho-kinase stoichiometrically phosphorylated myosin light chain (MLC). Peptide mapping and phosphoamino acid analyses revealed that the primary phosphorylation site of MLC by Rho-kinase was Ser-19, which is the site phosphorylated by MLC kinase. Rho-kinase phosphorylated recombinant MLC, whereas it failed to phosphorylate recombinant MLC, which contained Ala substituted for both Thr-18 and Ser-19. We also found that the phosphorylation of MLC by Rho-kinase resulted in the facilitation of the actin activation of myosin ATPase. | SIGNOR-261709 |
P42229 | Q9BZS1 | 1 | null | up-regulates | 0.48 | We demonstrate that the signal transducer and activator of transcription 5 (STAT5)-signaling cytokines, IL-2, IL-15 and to a lesser extent IL-7, induce FOXP3 up-regulation in vitro in activated human Teff cell | SIGNOR-254301 |
O14818 | P51149 | 2 | binding | up-regulates activity | 0.343 | Rab7 Forms a Complex with the Proteasome -Subunit XAPC. In this study the proteasome alpha-subunit XAPC7 (also known as PSMA7, RC6-1, and HSPC in mammals) was identified to interact specifically with Rab7 and was recruited to multivesicular late endosomes through this interaction. | SIGNOR-261303 |
P35637 | P08621 | 2 | binding | up-regulates activity | 0.469 | FUS functions in coupling transcription to splicing by mediating an interaction between RNAP II and U1 snRNP | SIGNOR-262823 |
P53674 | P43320 | 2 | binding | up-regulates activity | 0.2 | At high concentrations or in the lens, βB2-crystallin forms hetero-oligomers with other β-crystallins. These oligomeric β-crystallins further participate in the formation of a supramolecular assembly that is important in lens function-lens transparency. | SIGNOR-252153 |
O14641 | P57078 | 0 | phosphorylation | up-regulates activity | 0.44 | Co-transfection of a RIPK4-GFP fusion increased the percentage of cells containing DVL2 puncta to more than 75% ( and ), suggesting that RIPK4 facilitates DVL2 signalosome formation.|Phosphorylation of DVL2 at Ser 298 and Ser 480 by RIPK4 favored canonical Wnt signaling. | SIGNOR-279756 |
O00141 | P08047 | 1 | phosphorylation | up-regulates activity | 0.265 | In fact, SGK1 activates and phosphorylates SP1 on serine 59, a regulator of nucleocytoplasmic trafficking related genes .|In fact, SGK1 activates and phosphorylates SP1 on serine 59, a regulator of nucleocytoplasmic trafficking-related genes xref . | SIGNOR-279246 |
P53350 | P54274 | 1 | phosphorylation | up-regulates | 0.373 | Plk1 phosphorylation of trf1 is essential for its binding to telomeres | SIGNOR-179461 |
P56945 | P11362 | 0 | phosphorylation | up-regulates | 0.256 | Five tyrosine phosphorylation sites were identified in p130cas on tyr-128, tyr-249, tyr-306, tyr-327, and tyr-410. These tyrosine residues are all located in the substrate domain of p130cas that mediates binding to the sh2 domain of the adaptor molecule crk. Fgf-1-transduced fibroblasts demonstrated a > 10-fold increase in migration, an observation correlated with increased tyrosine phosphorylation of p125fak and p130cas. | SIGNOR-82760 |
Q9NPC1 | P63096 | 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-256674 |
Q9NYL2 | Q9NYL2 | 2 | phosphorylation | up-regulates | 0.2 | Ionizing radiation induces mrk autophosphorylation and activation. Within the mrk kinase loop between the dfg (subdomain vii) and ape (subdomain viii) residues, there are three conserved threonine/serine residues (thr161, thr162, and ser165) that are important for activation. | SIGNOR-128581 |
P27707 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.399 | Here we report that ATM phosphorylation of dCK on Serine 74 is essential to activate the G2/M checkpoint in response to DNA damage.|Together, these results indicate that the dCK-Cdk1 interaction is enhanced in response to DNA damage and that ATM mediated dCK Serine 74 phosphorylation is required for the interaction. | SIGNOR-278221 |
O00303 | P46531 | 1 | deubiquitination | up-regulates | 0.421 | The activated form of notch needs to be deubiquitinated before being processed by the gamma-secretase activity and entering the nucleus, where it fulfills its transcriptional function. The enzyme accounting for this deubiquitinase activity is eif3f, known so far as a translation initiation factor. | SIGNOR-170158 |
O43829 | O43829 | 2 | binding | up-regulates activity | 0.2 | ZF5, which we have cloned as a transcriptional repressor on the mouse c-myc promoter, has the POZ domain at the amino-terminus and the Kruppel-type zinc finger domain at the carboxy-terminus. We demonstrated that the POZ domain has a function mediating homomeric protein-protein interaction and this interaction requires the zinc finger domain. | SIGNOR-220534 |
P21359 | Q7Z699 | 2 | binding | up-regulates quantity | 0.636 | Sprouty-related, EVH1 domain-containing (SPRED) proteins negatively regulate RAS/mitogen-activated protein kinase (MAPK) signaling following growth factor stimulation. This inhibition of RAS is thought to occur primarily through SPRED1 binding and recruitment of neurofibromin, a RasGAP, to the plasma membrane. Here, we report the structure of neurofibromin (GTPase-activating protein [GAP]-related domain) complexed with SPRED1 (EVH1 domain) and KRAS. The structure provides insight into how the membrane targeting of neurofibromin by SPRED1 allows simultaneous interaction with activated KRAS. | SIGNOR-273660 |
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