IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels float64 0 2 | mechanism stringclasses 40 values | effect stringclasses 10 values | score float64 0.1 0.99 ⌀ | sentence stringlengths 10 1.63k ⌀ | signor_id stringlengths 12 14 |
|---|---|---|---|---|---|---|---|
Q9UPX8 | P12814 | 1 | relocalization | up-regulates activity | 0.297 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264584 |
Q16611 | O95831 | 1 | relocalization | up-regulates | 0.297 | First, bax/bak-mediated momp leads to the release of a significant part of the cyt c, smac/diablo and htra2/omi proteins. in a third step, cyt c, smac/diablo and htra2/omi, which were released into the cytosol, trigger caspase activation. This is necessary to alter the physical association of aif and endog with the im to enable their relocation to the cytosol. | SIGNOR-192092 |
P78527 | P42575 | 1 | phosphorylation | up-regulates | 0.297 | Here we show that dna damage induced by gamma-radiation triggers the phosphorylation of nuclear caspase-2 at the s122 site within its prodomain, leading to its cleavage and activation. This phosphorylation is carried out by the nuclear serine/threonine protein kinase dna-pkcs | SIGNOR-183895 |
O95433 | P30793 | 1 | binding | up-regulates activity | 0.297 | The interaction of GCH1 with Aha1 may recruit GCH1 into the eNOS/Hsp90 complex so as to support local changes in nitric oxide production by endothelial cells. | SIGNOR-252213 |
P17612 | O00141 | 1 | phosphorylation | up-regulates activity | 0.297 | In this publication, we demonstrate that cAMP can activate Sgk and that this effect is mediated by PKA, which directly phosphorylates Thr369 in Sgk. | SIGNOR-275972 |
P31749 | Q96S44 | 1 | phosphorylation | up-regulates | 0.297 | Here we show that such an activation of prpk is mediated by another kinase, akt/pkb, which phosphorylates prpk at ser250. | SIGNOR-252503 |
Q3KR16 | P63000 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.297 | 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-260568 |
P08575 | Q05655 | 1 | dephosphorylation | down-regulates activity | 0.297 | Taken together, these data indicate that CD45 inhibits PMA dependent PKCdelta activation by impeding PMA dependent PKCdelta tyrosine phosphorylation.|reduction in CD45 expression caused the duration of peak PMA-induced MEK and extracellular signal-regulated kinase (ERK) 1/2 activity to increase from 5 min to 30 min while leading to a 4-fold increase in PMA-dependent PKCdelta activation. | SIGNOR-277028 |
Q15154 | O15182 | 1 | relocalization | up-regulates | 0.297 | Rna silencing of pcm-1 leads to reduced assembly of centrin, pericentrin, and ninein at the centrosome | SIGNOR-95016 |
Q99704 | P05107 | 1 | binding | down-regulates activity | 0.297 | 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-257680 |
P07384 | P49841 | 1 | cleavage | up-regulates activity | 0.297 | Thus, it has been shown that calpain cleaves the inhibitory domain of GSK3 generating two fragments of 40 and 30 kDa. This cleavage enhanced activity of the kinase | SIGNOR-251586 |
P24941 | P04183 | 1 | phosphorylation | down-regulates | 0.296 | Given that the dimeric form of tk1 is less active than the tetrameric, we propose that mitotic phosphorylation of serine-13 is of physiological importance, in that it may counteract atp-dependent activation of tk1 by affecting its quaternary structure, thus attenuating its enzymatic function at the g2/m phase. | SIGNOR-95578 |
P06493 | Q03060 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.296 | The MAPKs extracellular signal-regulated kinases 1 and 2 physically interact with ICER and mediated the phosphorylation of ICER on a critical serine residue (Ser-41). A mutant form of ICER in which Ser-41 was substituted by alanine had a half-life 4-5 h longer than its wild-type counterpart. This alteration in stability was due to the inability of the Ser-41-mutant ICER to be efficiently ubiquitinated and degraded via the ubiquitin-proteasome pathway. | SIGNOR-275979 |
Q15139 | P35670 | 1 | phosphorylation | up-regulates activity | 0.296 | ATP7B trafficking was markedly reduced by the Ser-478/481/1121/1453 to Ala mutation. We conclude that PKD plays a key role in copper-dependent serine phosphorylation, permitting high levels of ATP7B protein expression and trafficking. | SIGNOR-272295 |
O75592 | P62826 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.296 | MYCBP2 Is a Nuclear GEF for Ran in DRG Neurons—Next, we studied whether or not MYCBP2 modulates the interaction between Ran/RanGAP1. MYCBP2 contains an N-terminal RCC1-like domain (Fig. 8C) (13), and RCC1 is a known GEF for Ran, indicating a potential functional interaction between MYCBP2 and Ran. | SIGNOR-261204 |
P04150 | Q16649 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.296 | GR directly regulates transcription of circadian clock components in mouse and human primary MSCs. Per2, E4bp4, Per1, and Timeless rapidly respond to glucocorticoid stimulation. Primary glucocorticoid receptor (GR) target genes are those at which GR occupies a nearby genomic glucocorticoid response element (GRE) and regulates target gene transcription | SIGNOR-268051 |
P31749 | P53004 | 1 | phosphorylation | up-regulates activity | 0.296 | Site-directed mutagenesis, mass spectrometry, and kinetic analyses identified S(230) in hBVR (225)RNRYLSF sequence as the Akt1 target. | SIGNOR-275517 |
P78527 | Q9Y6K9 | 1 | phosphorylation | down-regulates activity | 0.296 | Here, we show that DNA-dependent protein kinase (DNA-PK), an enzyme involved in DNA double-strand break (DSB) repair, triggers the phosphorylation of NEMO by genotoxic stress, thereby enabling shuttling of NEMO through the nucleus with subsequent NF-κB activation. We identified serine 43 of NEMO as a DNA-PK phosphorylation site and point mutation of this serine to alanine led to a complete block of NF-κB activation by ionizing radiation (IR). | SIGNOR-277508 |
P28335 | P09471 | 1 | binding | up-regulates activity | 0.296 | 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-257013 |
Q05655 | P98082 | 1 | phosphorylation | down-regulates | 0.296 | Mutational analysis revealed that a dab2 ser(24) phosphorylation mutant (s24a) abrogated the inhibitory function of dab2. | SIGNOR-127198 |
P68400 | P18846 | 1 | phosphorylation | up-regulates | 0.296 | Camk ii phosphorylates only ser63 (corresponding to ser133 of creb), which is essential for the activation, and not ser72 (corresponding to ser142 of creb), which is a negative regulation site | SIGNOR-42565 |
P17612 | O96004 | 1 | phosphorylation | down-regulates activity | 0.296 | In vitro and in vivo phosphorylation studies show that both PKA and PKC can phosphorylate HAND1 and -2. T107; S109 within helix I and S98 within the basic domain, are the phosphorylated residues. We determined that modification of HAND1 at residues 107 and 109 affects dimerization affinities with E-proteins, thus changing the bHLH dimer equilibrium within the cell. These modifications also affect HAND1 function. | SIGNOR-249991 |
P08047 | P01137 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.296 | MAPKs have cis-acting regulatory elements in the mouse-TGF promoter region, which respond to various transcription factors, including specificity protein-1 and activating protein 1. Thus, it is possible that apoptotic cell-induced TGF-β mRNA expression is mediated through activation of these transcription factors via MAPK signaling. Xiao et al. reported that all of the MAPK members, including p38/ERK/JNK, are required for apoptotic Jurkat cells up-regulation of TGF-β production | SIGNOR-251740 |
Q9UQE7 | Q9BW11 | 1 | binding | down-regulates activity | 0.296 | We identified a novel ZIP-containing protein, Mmip1 (Mad member interacting protein 1) that strongly dimerizes with all four Mad members, but not with c-myc. Mmip1 can inhibit DNA binding by Max-Mad heterodimers and, in vivo, can reverse the suppressive eects of Mad proteins on c-myc functions. | SIGNOR-241281 |
Q92569 | P04637 | 1 | binding | up-regulates activity | 0.296 | N this study, we aimed to explore the interaction of p55PIK with p53 and the role of p55PIK in regulating p53-dependent apoptosis in cancer cells. We found that p55PIK directly binds to the DBD domain of p53 via N24 domain. Moreover, the upregulation of p55PIK expression increases transcriptional levels of p53-dependent apoptosis-related genes including GADD45α, S100A9, MDM2 and AIP1. Furthermore, synthetic N24 translocated to nucleus can significantly inhibit cancer cell growth. | SIGNOR-261492 |
Q13464 | P45983 | 1 | phosphorylation | up-regulates activity | 0.296 | Instead, we found that rock activates jnk, which then phosphorylates c-jun and atf2 when bound to the c-jun promoter. | SIGNOR-123717 |
O15111 | P49815 | 1 | phosphorylation | down-regulates | 0.296 | Insulin activation of mtor requires akt in a manner that involves ikkalpha, preferentially to ikkbeta, and tsc2 phosphorylation | SIGNOR-178664 |
P24941 | Q03112 | 1 | phosphorylation | up-regulates activity | 0.296 | The motif harbouring S436 is a target of CDK2 and CDK3 kinases, which interacted with EVI1-WT. The methyltransferase DNMT3A bound preferentially to EVI1-WT compared with EVI1-S436A, and a hypomethylated cell population associated by EVI1-WT expression in murine haematopoietic progenitors is not maintained with EVI1-S436A. | SIGNOR-273426 |
Q15818 | P42261 | 1 | binding | up-regulates activity | 0.296 | We found that NP1 colocalizes and physically associates with the fast excitatory GluR1 AMPA receptors and that hypoxia induces a time-dependent increase in the NP1-GluR1 interactions. Thus hypoxia recruits NP1 protein to GluR1 subunits concurrent with the hypoxic excitotoxic cascade.|Rather we propose that through interactions with GluR1 clusters, NP1 modulates the function of AMPA receptors in a manner whereby increased NP1-GluR1 interactions sensitize neurons to hypoxia-induced excitotoxic death. | SIGNOR-261430 |
P11802 | P23760 | 1 | phosphorylation | up-regulates activity | 0.296 | In summary, our study showed that Cdk4 phosphorylates and activates PAX3-FOXO1, thereby promoting its oncogenic function.|These findings suggest that Cdk4 phosphorylates the Ser 430 residue of PAX3-FOXO1 in vitro . | SIGNOR-278512 |
P31749 | Q06187 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.296 | The activated serine/threonine kinase Akt/protein kinase B (PKB) phosphorylated Btk on two sites prior to 14-3-3ζ binding. The interaction sites were mapped to phosphoserine pS51 in the pleckstrin homology domain and phosphothreonine pT495 in the kinase domain. | SIGNOR-276466 |
Q9UQM7 | Q96PM5 | 1 | phosphorylation | down-regulates | 0.296 | Phosphorylation of pirh2 by calmodulin-dependent kinase ii impairs its ability to ubiquitinate p53 | SIGNOR-156064 |
P29275 | P09471 | 1 | binding | up-regulates activity | 0.296 | 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-257240 |
Q9UQE7 | Q05195 | 1 | binding | down-regulates activity | 0.296 | We identified a novel ZIP-containing protein, Mmip1 (Mad member interacting protein 1) that strongly dimerizes with all four Mad members, but not with c-myc. Mmip1 can inhibit DNA binding by Max-Mad heterodimers and, in vivo, can reverse the suppressive eects of Mad proteins on c-myc functions. | SIGNOR-241278 |
O75365 | P60484 | 1 | dephosphorylation | down-regulates quantity by destabilization | 0.296 | As expected, PRL3 clearly reduced PTEN phosphorylation at the tyrosine residue and PTEN protein in PRL3 overexpressing LO2 and HepG2 cell lines, with no significant changes in PRL3 (C104S) mutant cells.|PRL3 down-regulates PTEN expression, a negative regulator of the Akt pathway.11 Phosphorylation of PTEN at Tyr336 is required for maintenance of PTEN protein stability and prevention of PTEN degradation.17 We therefore speculated that PRL3 might dephosphorylate PTEN at tyrosine sites and consequently reduce the PTEN protein level. | SIGNOR-277010 |
Q9UM73 | P50750 | 1 | phosphorylation | up-regulates activity | 0.296 | We report that anaplastic lymphoma kinase (ALK) directly phosphorylates CDK9 at tyrosine-19 to promote homologous recombination (HR) repair and PARP inhibitor resistance. Phospho-CDK9-Tyr19 increases its kinase activity and nuclear localization to stabilize positive transcriptional elongation factor b and activate polymerase II-dependent transcription of HR-repair genes. | SIGNOR-277607 |
Q9UQE7 | Q14582 | 1 | binding | down-regulates activity | 0.296 | We identified a novel ZIP-containing protein, Mmip1 (Mad member interacting protein 1) that strongly dimerizes with all four Mad members, but not with c-myc. Mmip1 can inhibit DNA binding by Max-Mad heterodimers and, in vivo, can reverse the suppressive eects of Mad proteins on c-myc functions. | SIGNOR-241284 |
Q9H334 | P07333 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.296 | Overexpression of MFH/Foxp1 markedly attenuated phorbol ester-induced expression of c-fms, which encodes the M-CSF receptor and is obligatory for macrophage differentiation. | SIGNOR-269048 |
P60484 | Q13224 | 1 | dephosphorylation | down-regulates activity | 0.296 | GluN2B Y1472 site is dephosphorylated by PTEN . | SIGNOR-277165 |
Q86Y07 | Q9UKT8 | 1 | phosphorylation | down-regulates activity | 0.296 | Collectively, CK1 and VRK2, but not GRK2 kinase, appears to mediate FBXW2 phosphorylation at the beta-TrCP binding motif.|We followed this lead, and inactivated VRK2 and GRK2 by siRNA silencing, or CK1 and VRK2 by small molecule inhibitor IC-261, and found that GRK2 knockdown had no effect, whereas CK1 and VRK2 inhibition or VRK2 silencing largely blocked the degradation of exogenously expressed FBXW2 (XREF_FIG and XREF_SUPPLEMENTARY). | SIGNOR-280161 |
Q96GD4 | Q8WWK9 | 1 | phosphorylation | up-regulates | 0.296 | Here, we report that tmap is a novel substrate of the aurora b kinase. Ser627 of tmap was specifically phosphorylated by aurora b both in vitro and in vivo. Nearly all mutations at the phosphorylation motif had dramatic effects on the subcellular localization of tmap. | SIGNOR-165410 |
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 |
Q9UKV5 | Q99574 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.296 | In this study, we demonstrate that two ER-associated E3 ligases, Hrd1 and gp78, are involved in the ubiquitination and degradation of mutant neuroserpin. | SIGNOR-272756 |
P01375 | P48736 | 1 | binding | up-regulates | 0.296 | Tnf activates phosphatidylinositol-3-oh kinase (pi(3)k) | SIGNOR-70625 |
Q13464 | Q6WCQ1 | 1 | phosphorylation | down-regulates | 0.296 | Enhanced rho kinase activity induces endothelial barrier dysfunction by a contractile mechanism via inactivation of myosin phosphatase (mp).. | SIGNOR-157593 |
O60346 | Q13043 | 1 | dephosphorylation | up-regulates activity | 0.295 | PHLPPs dephosphorylate Mst1 on the T387 inhibitory site, which activate Mst1 and its downstream effectors p38 and JNK to induce apoptosis. | SIGNOR-248329 |
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 |
O43353 | P28482 | 1 | phosphorylation | up-regulates activity | 0.295 | RIP2 directly phosphorylates and activates ERK2 in vivo and in vitro. | SIGNOR-279106 |
Q96AX9 | Q13546 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.295 | These data suggest that after binding, MIB2 inhibits RIPK1 through a mechanism that is dependent on the E3 ligase activity of MIB2.|Whereas MIB2 readily ubiquitylated wild-type RIPK1, mutating K377 to R significantly reduced MIB2 mediated ubiquitylation of RIPK1 (XREF_SUPPLEMENTARY A). | SIGNOR-278633 |
P67775 | O95997 | 1 | dephosphorylation | up-regulates quantity by stabilization | 0.295 | CaMKII phosphorylates securin at PP2A substrate site(s).Securin is destabilized by phosphorylation and stabilized by PP2A-dependent dephosphorylation on separase | SIGNOR-276376 |
Q9BZL6 | Q9UQL6 | 1 | phosphorylation | up-regulates activity | 0.295 | Histone deacetylase (HDAC) 5 and 7, two members of the class II of classical HDAC [62], are in vivo substrates of PKD3 and PKD [63]. In response to a variety of signals, including phorbol esters, T cell receptor engagement, vascular endothelial growth factor and angiotensin stimulation, the activity of HDAC5 and 7 are regulated by a mechanism that involves PKD3 and PKD-mediated phosphorylation of the highly conserved Ser259 and Ser498 residues that are located in N-terminus of class II HDACs [63–67]. | SIGNOR-275929 |
P29350 | O43318 | 1 | dephosphorylation | down-regulates activity | 0.295 | Mechanistically, the association of EHEC Tir with SHP-1 facilitated the recruitment of SHP-1 to TAK1 and inhibited TAK1 phosphorylation, which then negatively regulated K63-linked polyubiquitination of TAK1 and downstream signal transduction.|SHP-1 inhibits TAK1 activity to down-regulate signal transduction and subsequent cytokine production.Innate immune responses are achieved by the activation of several pathogen-recognition receptors (PRPs), including TLRs, retinoic acid inducible gene I (RIG-I)-like receptors (RLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs). | SIGNOR-277128 |
Q9Y4K3 | Q9GZQ8 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.295 | TRAF6 catalyzes K63-linked polyubiquitination of LC3B and promotes the formation of the LC3B-ATG7 and LC3B-CTNNB1 complexes. | SIGNOR-277439 |
P17706 | P10912 | 1 | dephosphorylation | down-regulates activity | 0.295 | PTPH1 only bound Tyr534, whereas PTP1B and TC-PTP bound multiple phosphopeptides. Earlier work suggests that Tyr332, Tyr487, Tyr534, Tyr566, and Tyr627 are all phosphorylated after GH stimulation (21). Apart from Tyr627, all of these also appear good PTP substrates | SIGNOR-248394 |
P18146 | Q15637 | 1 | binding | up-regulates activity | 0.295 | GNRH1 induces expression of early growth response 1 (EGR1), which interacts with steroidogenic factor 1 (SF1) and paired-like homeodomain transcription factor 1 (PITX1) to regulate Lhb promoter activity. | SIGNOR-254914 |
Q9UPW6 | P43354 | 1 | transcriptional regulation | down-regulates quantity | 0.295 | Satb2 represses the transcription of Nr4a2. The misexpression of Nr4a2 together with Ctip2 induces expression of SubC-specific genes in wild-type Rsp, and simultaneous knockdown of these two genes in Rsp Satb2-mutant cells prevents their fate transition to SubC identity. Thus, Satb2 serves as a determinant gene in the Rsp regionalization by repressing Nr4a2 and Ctip2 during cortical development | SIGNOR-268930 |
O43823 | P17612 | 1 | binding | up-regulates activity | 0.295 | To determine whether AKAP95 and p105 were present in a complex in mammalian cells, FLAG-tagged AKAP95 wascoexpressed with Myc-tagged p105 in human embryonic kidney (HEK) 293 cells. Immunoprecipitation of either protein pulled down a complex containing AKAP95, p105, and PKA-Ca (Fig. 6D).|The identification of a PKA phosphorylation site in the C-terminal region of p105 suggests that p105 is a candidate substrate for AKAP95-targeted PKA. | SIGNOR-260302 |
P49841 | P50219 | 1 | phosphorylation | down-regulates | 0.295 | Here we show that gsk-3_ inactivates the proapoptotic activity of hlxb9 by phosphorylating hlxb9 at ser-78/ser-80 (phlxb9). | SIGNOR-203657 |
O75534 | P01100 | 1 | post transcriptional regulation | down-regulates quantity | 0.295 | By testing different classes of mammalian poly(A) nucleases, we identified CCR4 as a poly(A) nuclease involved in the mCRD-mediated rapid deadenylation in viv | SIGNOR-261145 |
Q9HD43 | P10912 | 1 | dephosphorylation | down-regulates activity | 0.295 | Protein tyrosine phosphatases (PTPs) play key roles in switching off tyrosine phosphorylation cascades, such as initiated by cytokine receptors. We have used substrate-trapping mutants of a large set of PTPs to identify members of the PTP family that have substrate specificity for the phosphorylated human GH receptor (GHR) intracellular domain. Among 31 PTPs tested, T cell (TC)-PTP, PTP-beta, PTP1B, stomach cancer-associated PTP 1 (SAP-1), Pyst-2, Meg-2, and PTP-H1 showed specificity for phosphorylated GHR | SIGNOR-248802 |
Q9Y2M5 | Q8NEB9 | 1 | binding | down-regulates quantity by destabilization | 0.295 | Cul3-KLHL20 Ubiquitin Ligase Governs the Turnover of ULK1 and VPS34 Complexes to Control Autophagy Termination. KLHL20 promotes ubiquitination of phagophore-residing VPS34 and Beclin-1 | SIGNOR-272414 |
Q8IYA7 | P35711 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.295 | MKX is a meniscus-enriched transcription factor. In human meniscus cells, MKX regulates the expression of meniscus marker genes, OA-related genes, and other transcription factors, including Scleraxis (SCX), SRY Box 5 (SOX5), and Runt domain-related transcription factor 2 (RUNX2). | SIGNOR-267214 |
P23467 | P10912 | 1 | dephosphorylation | down-regulates | 0.295 | Inally, mrna tissue distribution of these ptps by rt-pcr analysis and coexpression of the wild-type ptps to test their ability to dephosphorylate ligand-activated ghr suggest ptp-h1 and ptp1b as potential candidates involved in ghr signaling. | SIGNOR-104580 |
Q15139 | Q92481 | 1 | phosphorylation | down-regulates activity | 0.295 | Mechanistically, we observed that PKD phosphorylates AP2\u03b2 at Ser-258 and Ser-277 and suppresses its nuclear accumulation.|Using ChIP analyses, here we found that PKD knockdown in HUVECs increases binding of AP2beta to the VEGFR-2 promoter. | SIGNOR-279267 |
O95260 | P11021 | 1 | post transcriptional regulation | down-regulates quantity by destabilization | 0.295 | We showed that the molecular chaperone BiP (also known as GRP78) was short-lived under basal conditions and ER stress. The turnover of BiP was in part driven by its amino-terminal arginylation (Nt-arginylation) by the arginyltransferase ATE1, which generated an autophagic N-degron of the N-end rule pathway. | SIGNOR-261345 |
P23443 | Q92934 | 1 | phosphorylation | down-regulates activity | 0.295 | P70S6K, the downstream target of mTORC1, can phosphorylate and inactivate pro apoptotic BAD by producing a reaction that disrupts BAD 's binding to other pro apoptotic molecules thereby allowing cell survival.|p70S6K, the downstream target of mTORC1, can phosphorylate and inactivate pro-apoptotic BAD by producing a reaction that disrupts BAD\u2019s binding to other pro-apoptotic molecules thereby allowing cell survival. xref , xref On the other hand, in a recent study, Li et al showed that increased expression of anti-apoptotic BCL2 was induced in myeloid progenitor cells upon activation of p76S6K, thereby promoting cell survival. xref Further studies are needed to better understand the effect of rapamycin and its derivatives on apoptosis in various cancer cells. | SIGNOR-280016 |
P17612 | Q15208 | 1 | phosphorylation | down-regulates activity | 0.295 | GSK-3β phosphorylated STK38 on residues S6 and T7 in vitro, depending largely on a PKA-mediated priming phosphorylation of STK38 on residues S10 and S11, respectively. Our results indicate that that GSK-3β inhibits STK38's full activation, and suggest that STK38 activation is required to prevent cell death in response to oxidative stress. | SIGNOR-276390 |
Q16611 | O43464 | 1 | relocalization | up-regulates | 0.295 | Bax and/or bak-mediated release of pro-apoptotic mediators including smac/diablo and omi | SIGNOR-118908 |
O96013 | Q9BY11 | 1 | phosphorylation | up-regulates activity | 0.295 | We identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo. | SIGNOR-263023 |
Q96NM4 | Q9UL17 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.294 | We subsequently found that TOX2 was independent of ETS-1 but could directly upregulate the transcription of TBX21 (encoding T-BET). | SIGNOR-266097 |
Q9NUX5 | P27694 | 1 | binding | down-regulates activity | 0.294 | The current model for how telomeres repress ATR signaling proposes that POT1/TPP1 prevents the binding of RPA to the single-stranded telomeric DNA | SIGNOR-263325 |
Q99704 | P18084 | 1 | binding | down-regulates activity | 0.294 | 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-257691 |
Q86Y07 | Q9UHP3 | 1 | phosphorylation | down-regulates activity | 0.294 | Here, we report that USP25 is a novel TRiC interacting protein that is also phosphorylated by VRK2. USP25 catalyzed deubiquitination of the TRiC protein and stabilized the chaperonin, thereby reducing accumulation of misfolded polyglutamine protein aggregates. Notably, USP25 deubiquitinating activity was suppressed when VRK2 phosphorylated the Thr(680), Thr(727), and Ser(745) residues. | SIGNOR-273579 |
Q99590 | P49768 | 1 | 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 |
Q8TBB1 | P56750 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.294 | We used the Ligand of Numb protein X (LNX) family of E3s, a group of PDZ domain-containing RING-type E3 ubiquitin ligases, to demonstrate the feasibility of this strategy. Many potential substrates of LNX E3s were identified. Eight of the nine selected candidates were ubiquitinated in vitro, and two novel endogenous substrates, PDZ-binding kinase (PBK) and breakpoint cluster region protein (BCR), were confirmed in vivo. | SIGNOR-272900 |
P63092 | P27986 | 1 | binding | up-regulates | 0.294 | Notably, the fzd7 receptor complex was associated with g_?(s) and pi(3)k and these components were required for wnt7a to activate the akt/mtor growth pathway in myotubes. These data led us to hypothesize that g_?s Mediates the activation of pi3kinase following wnt7a binding to fzd7. | SIGNOR-191561 |
P49840 | O75030 | 1 | phosphorylation | up-regulates | 0.294 | Glycogen synthase kinase 3 (gsk3) was found to phosphorylate ser298 in vitro, thereby enhancing the binding of mitf to the tyrosinase promoter | SIGNOR-72878 |
P27361 | P49841 | 1 | phosphorylation | down-regulates activity | 0.294 | We demonstrate that insulin-mediated activation of ERK1/2 results in phosphorylation of GSK3β at S9 independently of Akt/mTORC1 activity in Tsc2 null mouse embryonic fibroblasts. In addition, we show that inhibition of ERK1/2 rescues GSK3β activity and restores protein synthesis in Tsc2 −/− MEFs to normal levels | SIGNOR-262523 |
P28482 | Q9H3M7 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.294 | ERK-dependent Txnip ubiquitination and proteasome degradation depended upon phosphorylation of a PXTP motif threonine (Thr349) located within the C-terminal α-arrestin domain and proximal to a previously characterized E3 ubiquitin ligase-binding site. | SIGNOR-277468 |
P54727 | P23760 | 1 | binding | down-regulates activity | 0.294 | Monoubiquitinated Pax3 was shuttled to the intrinsic proteasomal protein S5a by interacting specifically with the ubiquitin-binding protein Rad23B. | SIGNOR-237667 |
Q14469 | P15172 | 1 | transcriptional regulation | down-regulates activity | 0.294 | Notch signaling up-regulated HES1 mRNA expression within 1 h and subsequently reduced expression of MyoD mRNA | SIGNOR-243181 |
Q9UQB3 | P22223 | 1 | binding | up-regulates quantity by stabilization | 0.294 | To clarify the role of p120 in mammalian cells, we have knocked down p120 with siRNA in cells expressing epithelial (E-), placental (P-), neuronal (N-), and vascular endothelial (VE-) cadherins. We report that each of these cadherins, as well as α- and β-catenins, were rapidly degraded in the absence of p120, resulting in loss of cell–cell adhesion. The effect was clearly dose dependent, indicating that p120 expression levels may directly determine cadherin levels. Degradation of p120-uncoupled cadherin occurred after its arrival at the surface, indicating that p120 regulates cadherin turnover at the level of internalization or recycling. p120 homologues ARVCF and δ-catenin could substitute for p120, so at least one family member is likely required to maintain adhesion. Thus, cadherin complexes are rapidly turned over and degraded in mammalian cells in the absence of direct interaction with p120 or a p120 family member. | SIGNOR-252130 |
P01106 | P12268 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.294 | Analysis of in vivo C-MYC interactions with TS, IMPDH2 and PRPS2 genes confirmed that they are direct C-MYC targets. C-MYC depletion did not significantly affect levels of E2F1 protein reported to regulate expression of many S-phase specific genes, but resulted in the repression of several genes encoding enzymes rate-limiting for dNTP metabolism. These included thymidylate synthase (TS), inosine monophosphate dehydrogenase 2 (IMPDH2) and phosphoribosyl pyrophosphate synthetase 2 (PRPS2). C-MYC depletion also resulted in reduction in the amounts of deoxyribonucleoside triphosphates (dNTPs) and inhibition of proliferation. | SIGNOR-267375 |
P62136 | P15056 | 1 | dephosphorylation | up-regulates activity | 0.294 | To address whether PP1\u03b1 activates B-Raf through these inhibitory sites, we made use of B-Raf protein mutants in which an individual inhibitory site, as well as all four sites (4A), were mutated to alanine.|We confirmed that GST-B-Raf was phosphorylated by ERK2 in vitro xref , mainly on S151 and T753 (Fig.\u00a0 xref ), and found that PP1\u03b1 dephosphorylated B-Raf on both ERK phosphorylation sites (Fig.\u00a0 xref ). | SIGNOR-277160 |
P11309 | P53350 | 1 | phosphorylation | down-regulates activity | 0.294 | This data strongly indicates that Pim1 phosphorylates PLK1 at threonine 210, a site previously reported to be phosphorylated by aurora A kinase during mitosis. | SIGNOR-279749 |
Q92935 | Q15465 | 1 | binding | down-regulates | 0.294 | A study in mice suggests that ext1 proteins might negatively regulate shh signaling by synthesizing hspgs, which sequester the ligand | SIGNOR-132606 |
Q53ET0 | P04150 | 1 | binding | up-regulates activity | 0.294 | We show here that CRTC2 also functions as a coactivator for the glucocorticoid receptor (GR). | SIGNOR-256101 |
Q8TDY4 | Q15052 | 1 | binding | up-regulates activity | 0.294 | ArfGAP With Coiled-Coil, Ankyrin Repeat And PH Domains 4 (ACAP4) is an ADP-ribosylation factor 6 (ARF6) GTPase-activating protein essential for EGF-elicited cell migration. |The crystal structure of the catalytic core of ACAP4 in a complex with ARF6 reveals the structural determinants underlying ACAP4 selectivity and specificity as an ARF6 GTPase-activating protein | SIGNOR-272235 |
P61981 | P07196 | 1 | binding | down-regulates activity | 0.294 | These results suggest the important role of 14-3-3 in the dynamic regulation of NF-L assembly, and in the capacity to prevent the formation of NF-L aggregates. all seven isoforms specifically interacted with NF-L, but not NF-M or NF-H. specific interaction of 14-3-3 proteins with phosphorylated NF-L subunits also indicated the role of 14-3-3 and NF-L phosphorylation in the disassembly of neurofilaments. What is more, binding of 14-3-3 to phosphorylated NF-L subunits may prevent the dephosphorylation of these subunits by phosphatases, maintaining the hyperphosphorylation state of the subunits, which facilitates the disassembly of neurofilaments. | SIGNOR-252400 |
Q96PU4 | P24385 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.294 | We found that NIRF directly ubiquitinated cyclins D1 and E1, as evidenced by the appearance of the tail (Fig. 4B). In summary, the above findings suggest that NIRF tightly cooperates with the core cell cycle machinery and induces G1 arrest, which is accompanied by ubiquitination of cyclins D1 and E1. | SIGNOR-271885 |
P24941 | Q9ULW0 | 1 | phosphorylation | down-regulates activity | 0.294 | In this study, we characterize the phosphorylation of threonine 72 (Thr(72)) in human TPX2, a residue highly conserved across species. We find that Cdk1/2 phosphorylate TPX2 in vitro and in vivo. |Endogenous TPX2 phosphorylated at Thr(72) does not associate with the mitotic spindle. Furthermore, ectopic GFP-TPX2 T72A preferentially concentrates on the spindle | SIGNOR-265099 |
O43379 | O14733 | 1 | relocalization | up-regulates activity | 0.294 | In the WT brain, the WDR62 scaffold organizes a protein complex including MEKK3, MKK4/7, and JNK1 to control NPC development during corticogenesis | SIGNOR-271716 |
Q03112 | Q9Y6K1 | 1 | binding | up-regulates activity | 0.293 | The oncoprotein EVI1 and the DNA methyltransferase Dnmt3 co-operate in binding and de novo methylation of target DNA|Here we show that EVI1 physically interacts with DNA methyltransferases 3a and 3b (Dnmt3a/b), which are the only de novo DNA methyltransferases identified to date in mouse and man, and that it forms an enzymatically active protein complex that induces de novo DNA methylation in vitro. | SIGNOR-273432 |
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 |
P28335 | P63096 | 1 | binding | up-regulates activity | 0.293 | 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-256734 |
Q13131 | P04406 | 1 | phosphorylation | up-regulates activity | 0.293 | Under glucose starvation, but not amino acid starvation, cytoplasmic GAPDH is phosphorylated on Ser122 by activated AMPK. This causes GAPDH to redistribute into the nucleus. Inside the nucleus, GAPDH interacts directly with Sirt1, displacing Sirt1's repressor and causing Sirt1 to become activated. | SIGNOR-259857 |
P16157 | O14983 | 1 | binding | down-regulates activity | 0.293 | We recently reported that small ankyrin 1 (sAnk1) interacts with the sarco(endo)plasmic reticulum Ca2+-ATPase in skeletal muscle (SERCA1) to inhibit its activity. | SIGNOR-265927 |
Q969H4 | P54762 | 1 | binding | up-regulates activity | 0.293 | 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-275921 |
P31751 | P99999 | 1 | phosphorylation | down-regulates activity | 0.293 | Finally, we propose that pro-survival kinase Akt (protein kinase B) is a likely mediator of the S47 phosphorylation of Cytc in the brain. | SIGNOR-277236 |
P27361 | O60716 | 1 | phosphorylation | down-regulates activity | 0.293 | Upon TGFβ treatment, activated extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylates T900 of p120-catenin to promote its interaction with Smurf1 and subsequent monoubiquitination. TGFβ promotes monoubiquitination of p120-catenin through Smurf1 to induce junction dissociation. | SIGNOR-277506 |
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