IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
Q9BXM7 | P0CG48 | 1 | phosphorylation | up-regulates activity | 0.604 | Ubiquitin is phosphorylated by PINK1 to activate parkin|PINK1 phosphorylated ubiquitin at Ser65 both in vitro and in cells | SIGNOR-249691 |
P06401 | P24941 | 0 | phosphorylation | down-regulates | 0.441 | Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26s proteasome | SIGNOR-74708 |
P18031 | O60674 | 1 | dephosphorylation | down-regulates activity | 0.797 | Immunoblots with phospho-specific antibodies confirmed that PTP1B suppresses phosphorylation of the Jak2 activation site tyrosines (Y1007/Y1008) and Stat3 in a dose-dependent manner | SIGNOR-248405 |
P06239 | P43405 | 0 | phosphorylation | down-regulates activity | 0.592 | Our experiments indicate that the TCR-induced activation of Erk2 depends on the function of SH2 domain of Lck and is reduced by phosphorylation of wild type Lck at Tyr192 or by mutation of this site to a negatively charged amino acid. Such dependence on the SH2 domain has also been reported for the bulk of TCR-induced tyrosine phosphorylation and activation of the interleukin 2 gene (26). Thus, phosphorylation of Lck at Tyr192 may represent a negative feedback mechanism in the interplay between Src and Syk family PTKs in TCR signaling | SIGNOR-246562 |
O43521-1 | Q9H6Z9 | 0 | hydroxylation | up-regulates quantity by stabilization | 0.254 | EglN3 hydroxylase stabilizes BIM-EL linking VHL type 2C mutations to pheochromocytoma pathogenesis and chemotherapy resistance|EglN3 Hydroxylates BIM-EL at the Proline67/70 Residues | SIGNOR-262003 |
Q9UNA1 | P61586 | 1 | gtpase-activating protein | down-regulates activity | 0.629 | 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-260481 |
P34897 | P01106 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.291 | Myc regulates the de novo purine and pyrimidine synthetic genes in multiple biological systems. Intriguingly, MYC was found to directly activate the expression of SHMT1, and SHMT2, which are enzymes involved in single carbon metabolism and are essential for dNTP synthesis | SIGNOR-267380 |
O14965 | O15143 | 1 | phosphorylation | up-regulates activity | 0.46 | Aurora A phosphorylates Arpc1b on threonine 21, and expression of Arpc1b but not a nonphosphorylatable Arpc1b mutant in mammalian cells leads to Aurora A kinase activation and abnormal centrosome amplification in a Pak1-independent manner. | SIGNOR-279438 |
O75385 | Q14457 | 1 | phosphorylation | up-regulates activity | 0.771 | In the nucleation step of autophagy, The ULK1 complex phosphorylates and activates the Beclin-1-VPS34 complex. | SIGNOR-278503 |
Q9Y4K3 | P12931 | 0 | phosphorylation | up-regulates activity | 0.565 | To gain further insights into the molecular mechanisms, we employed mass spectrometry to identify the specific tyrosine residues of Traf6 that are phosphorylated by c-Src.By mutating these phosphorylation sites to phenylalanine, we disrupted Traf6-mediated polyubiquitination and subsequently observed the inactivation of AEP. This finding suggests that the phosphorylation of Traf6 by c-Src is crucial for AEP activation. | SIGNOR-277866 |
P12931 | P36544 | 1 | phosphorylation | down-regulates | 0.2 | Alpha7 neuronal nicotinic acetylcholine receptors are negatively regulated by tyrosine phosphorylation and src-family kinasesmutant alpha7 nachrs lacking cytoplasmic loop tyrosine residues because of alanine replacement of tyr-386 and tyr-442 were more active than wild-type receptorsexpression of active src reduced _7 nachr activity | SIGNOR-141311 |
P17252 | P15382 | 1 | phosphorylation | down-regulates activity | 0.307 | Inhibition of the current was not seen in channels in which Ser103 was replaced by Ala, although other properties of the current were unchanged. These results indicate that inhibition of the potassium current results from direct phosphorylation of the channel subunit protein at Ser103. | SIGNOR-248852 |
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 |
Q13464 | Q9Y613 | 1 | phosphorylation | up-regulates | 0.309 | Rock phosphorylates the c-terminal residues ser1131, ser1137, and thr1141 of formin homology domain protein 1 (fhod1). Phosphorylation of fhod1 at the three residues fully disrupts the autoinhibitory interaction, which culminates in formation of stress fibres. | SIGNOR-160548 |
Q7Z3C6 | O75385 | 0 | phosphorylation | up-regulates activity | 0.582 | 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-266369 |
P42574 | O14920 | 1 | cleavage | down-regulates | 0.364 | Ikappab kinase (ikk) beta was specifically proteolyzed by caspase-3-related caspases at aspartic acid residues 78, 242, 373, and 546 during tumor necrosis factor (tnf)-alpha-induced apoptosis. | SIGNOR-112792 |
O15194 | P06400 | 1 | dephosphorylation | up-regulates activity | 0.298 | ppRB (RB phosphorylated at Ser-807/811|Possible Mechanisms of HYA22 Action in Tumorigenesis: Dephosphorylation of RB by Transient Expression of HYA22 Isoforms. | SIGNOR-248304 |
P49840 | Q9NZ72 | 1 | phosphorylation | up-regulates activity | 0.252 | Altogether, these results indicate that CDK5 phosphorylates similarly serines 68 and 73, whereas ERK2 targets mostly serine 68 and GSK-3beta mostly serine 60.|This observation may support the hypothesis of a specific localization of stathmin 3 depending on its phosphorylation by GSK-3beta | SIGNOR-264883 |
Q9P289 | P46937 | 1 | phosphorylation | down-regulates activity | 0.2 | Further, and consistent with our aforementioned finding that MST4 inactivates YAP in response to serum starvation, this stress condition enhanced the YAP\u2013MST4 interaction ( xref ).|Here, we revealed that the MST4 kinase-mediated Thr83 phosphorylation of YAP represents such an additional mechanism of YAP inactivation. | SIGNOR-278994 |
O60729 | Q99618 | 1 | dephosphorylation | up-regulates | 0.281 | The phosphatase cdc14b translocates from the nucleolus to the nucleoplasm and induces the activation of the ubiquitin ligase apc/ccdh1 | SIGNOR-179664 |
Q9Y4H2 | P24394 | 0 | phosphorylation | up-regulates | 0.592 | Irs-1 and a homologous protein, irs-2 (also known as 4-phosphotyrosine substrate), are recruited to phosphorylated y497 of IL-4R After ligand binding, leading to phosphorylation and activation of irs-1 and irs-2. | SIGNOR-100771 |
Q6R327 | P23443 | 0 | phosphorylation | down-regulates | 0.715 | Phosphorylation of rictor on thr1135 did not affect mtorc2 assembly, kinase activity, or cellular localization. However, cells expressing a rictor t1135a mutant were found to have increased mtorc2-dependent phosphorylation of akt | SIGNOR-161995 |
Q13315 | Q969H0 | 1 | phosphorylation | up-regulates activity | 0.425 | In response to ionizing radiation, ATM phosphorylates FBXW7 at serine 26 to recruit it to DNA double-strand break (DSB) sites, whereas activated DNA-PKcs phosphorylates XRCC4 at serines 325/326, which promotes binding of XRCC4 to FBXW7 | SIGNOR-259942 |
Q6PIL6 | Q9NZV8 | 1 | relocalization | up-regulates activity | 0.773 | KChIP4 increased the current amplitude of Kv4.2, decelerated the inactivation, and accelerated the recovery from inactivation of Kv4.2. KChIP.is known to promote the translocation of Kv4.2 from the endoplasmic reticulum or Golgi to the cell surface | SIGNOR-269004 |
Q13976 | Q15637 | 1 | phosphorylation | down-regulates activity | 0.438 | PKG phosphorylates SF1 at Ser20, which inhibits the SF1-U2AF65 interaction leading to a block of pre-spliceosome assembly. Mutation of Ser20 to Ala or Thr also inhibits the interaction with U2AF65, indicating that Ser20 is essential for binding. | SIGNOR-249018 |
P23470 | P05556 | 1 | dephosphorylation | down-regulates activity | 0.265 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254706 |
P78352 | Q8N2Q7 | 0 | relocalization | up-regulates activity | 0.776 | Like NRXNs, NLGNs bind to intracellular PDZ-domain proteins, but in contrast to NRXNs, NLGNs bind to class I PDZ domains such as those contained in PSD95, a postsynaptic MAGUK protein65. PSD95 and its homologues are centrally involved in recruiting glutamate receptors at postsynaptic sites66. Similarly to CASK, PSD95 binds to intracellular adaptor proteins, and especially to GKAP (a protein that binds to the guanylate-kinase domain of PSD95), which, in turn, binds to SHANK proteins (Fig. 1b). A possible role of these interactions is to recruit postsynaptic adaptor proteins to the site of synaptic junctions. | SIGNOR-264191 |
Q13535 | P23025 | 1 | phosphorylation | up-regulates activity | 0.492 | ATR mediated phosphorylation of XPA on S196 enhances cAMP-mediated optimization of NER, and is promoted by SIRT1-mediated deacetylation of XPA on K63, K67 and K215. | SIGNOR-258985 |
P59594 | P35354 | 1 | transcriptional regulation | up-regulates activity | 0.2 | Spike protein of SARS‐CoV activated COX‐2 expression in a protein concentration‐dependent manner | SIGNOR-262315 |
P01375 | P78536 | 0 | cleavage | up-regulates quantity | 0.704 | We have now purified and cloned a metalloproteinase that specifically cleaves precursor TNF-alpha. [...]This enzyme (called the tnf-alpha-converting enzyme, or tace) is a new member of the family of mammalian adamalysins (or adams), for which no physiological catalytic function has previously been identified. | SIGNOR-46754 |
Q13535 | O14757 | 1 | phosphorylation | up-regulates | 0.925 | Atr activation typically leads to chk1 phosphorylation and activation. In response to genotoxic stress, chk1 is phosphorylated on serines 317 (s317) and 345 (s345) by the ataxia-telangiectasia-related (atr) protein kinase. | SIGNOR-134716 |
P16220 | P59595 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | The transcription factors c-Fos, FosB, CREB-1, and ATF2 were all activated by the addition of SARS-CoV N protein to the sample well | SIGNOR-260729 |
Q5JU85 | P78352 | 1 | relocalization | up-regulates activity | 0.472 | Here, we characterized IQ-ArfGEF/BRAG1, a guanine nucleotide exchange factor (GEF) for Arf6, in the mouse brain. In vivo Arf pull down assay demonstrated that IQ-ArfGEF/BRAG1 activated Arf6 more potently than Arf1.IQ-ArfGEF/BRAG1 is a guanine nucleotide exchange factor for Arf6 that interacts with PSD-95 at postsynaptic density of excitatory synapses. Taken together, IQ-ArfGEF/BRAG1 forms a postsynaptic protein complex containing PSD-95 and NMDA receptors at excitatory synapses, where it may function as a GEF for Arf6. | SIGNOR-264907 |
Q9BZL4 | Q5VT25 | 0 | phosphorylation | down-regulates activity | 0.558 | Identification of the Phosphorylation Site of p85 on Threonine 560 by MRCKα-CAT | Wild-type p85 but not the mutant p85AA, when phosphorylated in vitro with MRCKα-CAT, showed significant reduction in the rate of MLC2 dephosphorylation. These results confirm a similar observation with MBS130 where phosphorylation of a conserved threonine 695 within a highly conserved motif was essential for the inhibition of phosphatase catalytic activity | SIGNOR-250724 |
P23470 | P49023 | 1 | dephosphorylation | up-regulates activity | 0.26 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254721 |
Q96GD4 | P01106 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.373 | AURKB directly phosphorylates MYC at serine 67, counteracting GSK3\u03b2-directed threonine 58 phosphorylation and subsequent FBXW7- mediated proteasomal degradation. | SIGNOR-279439 |
P61586 | Q96PE2 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.549 | 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-260542 |
Q9NP81 | P18848 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress. | SIGNOR-269425 |
Q96FW1 | P68400 | 0 | phosphorylation | up-regulates activity | 0.319 | Casein kinase 2 (CK2)-dependent phosphorylation of OTUB1 at Ser16 played a critical role in ODN- and cathepsin K siRNA-mediated p53 stabilization. |Furthermore, although OTUB1 dramatically induced p53 deubiquitination, its mutant (S16A) and deletion mutant did not have this effec | SIGNOR-276527 |
P28482 | Q13480 | 1 | phosphorylation | up-regulates activity | 0.602 | Our results demonstrate that ERK1/2 phosphorylate Gab1 at six serine/threonine residues (T312, S381, S454, T476, S581, S597) in consensus motifs for MAP kinase phosphorylation. |serine and threonine phosphorylation are capable of modulating the initial signal | SIGNOR-249395 |
Q9P286 | P17844 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | PAK5 promotes RNA helicase DDX5 sumoylation and miRNA-10b processing in a kinase-dependent manner in breast cancer|The increased expression levels of PAK5 and phospho-DDX5 threonine 69 are associated with metastasis and poor clinical outcomes of patients. PAK5 facilitates the phosphorylation-dependent sumoylation of DDX5 to stabilize DDX5. Both the phosphorylation and sumoylation of DDX5 enhance the formation of a DDX5/Drosha/DGCR8 complex, thus promoting microRNA-10b processing. | SIGNOR-275658 |
Q8IV63 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.356 | Vaccinia-related kinase 3 (VRK3), a member of the VRK family, is widely expressed in human tissues and increases VHR phosphatase activity through a direct binding|Here we report that oxidative stress-induced cyclin-dependent kinase 5 (CDK5) activation stimulates neuroprotective signaling via phosphorylation of vaccinia-related kinase 3 (VRK3) at Ser 108. The binding of vaccinia H1-related (VHR) phosphatase to phosphorylated VRK3 increased its affinity for phospho-ERK and subsequently downregulated ERK activation| | SIGNOR-275544 |
Q9NQR1 | Q9UNH5 | 0 | dephosphorylation | down-regulates quantity by destabilization | 0.2 | The dephosphorylation of S29 during late mitosis by the Cdc14 phosphatases was required for APC(cdh1)-mediated ubiquitination of PR-Set7 and subsequent proteolysis. | SIGNOR-248835 |
P55017 | Q96J92 | 0 | phosphorylation | up-regulates activity | 0.579 | Threonine 48 was identified as the WNK4 phosphorylation site at mouse NCC|. Thus, WNK4 stimulates NCC in three ways: (1) direct phosphorylation and in turn increasing NCC protein abundance; (2) facilitating the phosphorylation of NCC by SPAK/OSR1 indirectly, and (3) phosphorylating and activating SPAK/OSR1.|Evidences from early studies using Xenopus oocytes and mammalian cells indicate that WNK4 inhibits NCC and PHAII-causing mutations relieve the inhibition | SIGNOR-264631 |
P42224 | P12931 | 0 | phosphorylation | up-regulates activity | 0.559 | The tyr701 phosphorylation of signal transducer and activator of transcription 1 (stat1) induced by interferon-gamma (ifn-gamma) and 12-o-tetradecanoylphorbol 13-acetate (tpa) was inhibited by the protein kinase c (pkc) inhibitor staurosporine, the tyrosine kinase inhibitor herbimycin, or the src kinase inhibitor pp2. An association between c-src and stat1 was increased by ifn-gamma and tpa, indicating the direct phosphorylation of stat1 by pkc-dependent c-src activation. | SIGNOR-235696 |
Q00535 | O94916 | 1 | phosphorylation | up-regulates | 0.2 | High nacl-induced activation of cdk5 increases phosphorylation of the osmoprotective transcription factor tonebp/orebp at threonine 135, which contributes to its rapid nuclear localization. n hek293 cells, mass spectrometry shows phosphorylation of tonebp/orebp-s120, -s134, -t135, and -s155. | SIGNOR-170886 |
P01106 | Q8N1E6 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.349 | In this study, we demonstrate that the deubiquitinase USP13 stabilizes c-Myc by antagonizing FBXL14-mediated ubiquitination to maintain GSC self-renewal and tumorigenic potential. USP13 was preferentially expressed in GSCs, and its depletion potently inhibited GSC proliferation and tumor growth by promoting c-Myc ubiquitination and degradation. | SIGNOR-274125 |
O60674 | O60885 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.324 | JAK2 induces tyrosine phosphorylation of BRD4 at Y97/Y98, resulting in BRD4 stabilization. | SIGNOR-277312 |
P54253 | Q00987 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.334 | NICD and MDM2 ubiquitinate and degrade ATXN1.|These results suggest that NICD and MDM2 synergistically reduce ATXN1 expression at the posttranscriptional level. | SIGNOR-278823 |
Q96HS1 | P48163 | 1 | dephosphorylation | up-regulates activity | 0.2 | PGAM5-mediated dephosphorylation of malic enzyme 1 (ME1) at S336 allows increased ACAT1-mediated K337 acetylation, leading to ME1 dimerization and activation, both of which are reversed by NEK1 kinase-mediated S336 phosphorylation. SIRT6 deacetylase antagonizes ACAT1 function in a manner that involves mutually exclusive ME1 S336 phosphorylation and K337 acetylation. | SIGNOR-275569 |
P49715 | Q06945 | 1 | transcriptional regulation | down-regulates | 0.382 | In summary, our data demonstrate that C/EBPα negatively regulates Sox4 transcription via direct DNA-binding. | SIGNOR-255675 |
Q13547 | Q63HK5 | 0 | relocalization | up-regulates activity | 0.2 | We carried out yeast two-hybrid studies with a PTB domain of FE65, focusing on those genes that might be involved in nuclear signaling, and identified and validated Teashirt proteins as FE65 interacting proteins in neurons. Using reporter systems, we observed that FE65 could simultaneously recruit SET, a component of the inhibitor of acetyl transferase, and Teashirt, which in turn recruited histone deacetylases, to produce a powerful gene-silencing complex.Endogenous HDAC1 was co-immunoprecipitated with FE65 when both FE65 and Teashirt3 were co-transfected (lane 4), but not when Teashirt3 or FE65 was omitted (lane 5 and 6), confirming that the association of HDAC1 with FE65 is dependent on, and mediated, by Teashirt3. | SIGNOR-264814 |
Q00653 | P62877 | 0 | ubiquitination | up-regulates | 0.281 | Mechanism of processing of the nf-kappa b2 p100 precursor: identification of the specific polyubiquitin chain-anchoring lysine residue and analysis of the role of nedd8-modification on the scf(beta-trcp) ubiquitin ligase. | SIGNOR-120342 |
P29317 | P31749 | 0 | phosphorylation | up-regulates activity | 0.355 | As non-canonical EphA2 activation requires phosphorylation of EphA2 at serine 897 by pAkt (Fig.\u00a02b), we sought to determine the effect of PTEN-mediated Akt regulation on invasion. | SIGNOR-279787 |
Q13535 | Q01094 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.377 | These results thus suggest that this serine 31 residue is indeed an atm/atr phosphorylation site and in fact is the major site for atm/atr-mediated phosphorylation within e2f1. Thus, it is possible that the atm/atr-mediated phosphorylation inhibits the binding and function of skp2 and thus prevents the normal degradation of e2f1 | SIGNOR-109420 |
P51452 | P00533 | 1 | dephosphorylation | down-regulates activity | 0.357 | We found that EGF receptor (EGFR) was a direct substrate of VHR and that overexpression of VHR down-regulated EGFR phosphorylation, particularly at Tyr-992 residue. Expression of VHR inhibited the activation of phospholipase Cγ and protein kinase C, both downstream effectors of Tyr-992 phosphorylation of EGFR. | SIGNOR-248532 |
Q9HCK8 | P41225 | 1 | transcriptional regulation | down-regulates quantity | 0.2 | Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells | SIGNOR-268920 |
P06241 | P29353 | 1 | phosphorylation | up-regulates | 0.732 | Syk and zap-70 were able to phosphorylate the y239 and y240 sites, and less efficiently the y317 site. Of the two potential grb2 binding sites (y239 and y317), y239 appears to play a greater role in recruiting sos through grb2. | SIGNOR-59623 |
Q13794 | Q9NX47 | 0 | ubiquitination | down-regulates quantity | 0.2 | MARCH5 promotes ubiquitination of MCL1 and NOXA.|Of note, MARCH5 depletion led to the accumulation of MCL1 and NOXA in asynchronous as well as G2 cells, suggesting that MARCH5 controls NOXA/MCL1 levels throughout the cell cycle. | SIGNOR-278758 |
Q14393 | P38435 | 0 | carboxylation | up-regulates activity | 0.525 | Thus, vitamin K acts as a cofactor for GGCX via the vitamin K cycle and exerts physiological effects through its regulation of VKDPs [29]. More than 20 VKDPs have been found. Osteocalcin promotes bone formation, and blood coagulation factors II, VII, IX, and X activate blood coagulation. Matrix Gla protein suppresses cardiovascular calcification, and brain-expressed Gas 6 promotes neural differentiation [29]. GGCX is an enzyme that converts glutamic acid (Glu) residues to Gla residues, so that the Gla-containing proteins can exert various physiological actions such as blood coagulation and bone formation. | SIGNOR-265923 |
Q13115 | Q16539 | 1 | dephosphorylation | down-regulates | 0.665 | This result suggests that dusp4 represses gluconeogenesis through dephosphorylation of p38 | SIGNOR-147958 |
P78527 | P23508 | 1 | phosphorylation | up-regulates activity | 0.2 | MCC is phosphorylated at the ATM/ATR consensus sites Ser118 and Ser120. Finally, mutation of S118/120 to alanine did not affect MCC nuclear shuttling following UV but did impair MCC G2/M checkpoint activity. | SIGNOR-273530 |
P49137 | P30304 | 1 | phosphorylation | down-regulates | 0.364 | Mk2 was required for the degradation of cdc25a. Mk2 phosphorylates cdc25a in vitro. Phosphorylation of cdc25a in vivo has been shown to facilitate its ubiquitin-mediated proteolysis | SIGNOR-152996 |
P00519 | Q13547 | 1 | phosphorylation | up-regulates activity | 0.507 | Despite the fact that HDAC1 was phosphorylated by co-expression with c-Abl, stabilization of HDAC1 by c-Abl was not affected by mutations in its sites phosphorylated by c-Abl.|c-Abl induces stabilization of histone deacetylase 1 (HDAC1) in a kinase activity dependent manner. | SIGNOR-280169 |
P31749 | P49918 | 1 | phosphorylation | down-regulates | 0.447 | Cdk inhibitor p57 (kip2) is downregulated by akt during her2-mediated tumorigenicityakt phosphorylates p57 on ser 282 or thr310. Akt activity results in destabilization of p57 by accelerating turnover rate of p57 and enhancing p57 ubiquitination | SIGNOR-252535 |
Q96PU5 | O75385 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.361 | NEDD4L ubiquitylates ULK1 at lysine 925 and lysine 933.|Next, we found that down-regulation of the ULK1 protein by NEDD4L is blocked by proteasome inhibitors (MG132 and lactacystin), but not by lysosomal inhibitors (leupeptin and Clq; XREF_FIG and S2 C), indicating that NEDD4L triggers ULK1 degradation exclusively through the proteasome pathway. | SIGNOR-278523 |
Q71UI9 | 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-265410 |
P06400 | Q00526 | 0 | phosphorylation | down-regulates | 0.443 | The active form of prb is underphosphorylated. Cdk3/cyclin-c-mediated phosphorylation at ser-807 and ser-811 is required for g0-g1 transition. | SIGNOR-124212 |
P47736 | Q9Y297 | 0 | ubiquitination | down-regulates | 0.342 | Here, we demonstrated that rap1gap is ubiquitinated and degraded through proteasome pathway in mitosis. Proteolysis of rap1gap requires the plk1 kinase and _-trcp ubiquitin ligase complex. | SIGNOR-203548 |
Q05513 | O14920 | 1 | phosphorylation | up-regulates activity | 0.517 | Activation of IkappaB kinase beta by protein kinase C isoforms. | Interestingly, recombinant active zetaPKC and alphaPKC are able to stimulate in vitro the activity of IKKbeta but not that of IKKalpha. In addition, evidence is presented here that recombinant zetaPKC directly phosphorylates IKKbeta in vitro, involving Ser177 and Ser181. Collectively, these results demonstrate a critical role for the PKC isoforms in the NF-kappaB pathway at the level of IKKbeta activation and IkappaB degradation. | SIGNOR-249015 |
O75896 | P46934 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | NEDD4 Degrades TUSC2 to Promote Glioblastoma Progression.|NEDD4 E3 ubiquitin ligase polyubiquitinates TUSC2 at residue K71, and the TUSC2-K71R mutant is resistant to NEDD4-mediated proteasomal degradation. | SIGNOR-278638 |
Q92985 | P19474 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.677 | Furthermore, this Ro52 mediated degradation of IRF7 was inhibited in the presence of MG132, a proteasome inhibitor, indicating that IRF7 is targeted to the proteasome for degradation (XREF_FIG).|Ro52 ubiquitinates IRF7 in a dose dependent manner. | SIGNOR-278619 |
P31947 | P45983 | 0 | phosphorylation | down-regulates | 0.338 | Jnk phosphorylates 14-3-3zeta_ at ser-184 and 14-3-3sigma_ at ser-187. | SIGNOR-124016 |
P37840 | P00519 | 0 | phosphorylation | up-regulates quantity | 0.424 | C-Abl interacts with alpha-synuclein and phosphorylates alpha-synuclein at Y39 (XREF_FIG) . | SIGNOR-279582 |
P17612 | O60716 | 1 | phosphorylation | down-regulates | 0.2 | We showed that pkc_ phosphorylation of p120 at serine (s)879 in response to thrombin or lipopolysaccharide challenge reduced p120 binding affinity for ve-cadherin and mediated aj disassembly secondary to ve-cadherin internalization | SIGNOR-198288 |
P04049 | O15530 | 0 | phosphorylation | up-regulates activity | 0.311 | PDK1, but not PKCs, phosphorylate and activate Raf1 in MAPK pathway when platelets are stimulated with 2MeSADP. | SIGNOR-280063 |
O75385 | Q9UGI9 | 1 | phosphorylation | down-regulates | 0.406 | Ulk1/2 in turn phosphorylates all three subunits of ampk and thereby negatively regulates its activity phosphorylation of ampk by ulk1 represents a negative feedback circuit. | SIGNOR-173053 |
O00141 | Q9HBA0 | 1 | phosphorylation | up-regulates activity | 0.361 | Recently, we identified that TRPV4 is also one of SGK1 substrate proteins (Fig. . , and the phosphorylation on serine 824 by SGK1 regulates the binding affinity to actin or tubulin [31].|Therefore, we propose the hypothesis that the SGK1 phosphorylation may enhance TRPV4 channel density in the plasma membrane through the dissociation from STIM1, similar with the regulation mechanism of GLUT4 or AQP2 by insulin or vasopressin, respectively , ]. | SIGNOR-279386 |
P68366 | P43405 | 0 | phosphorylation | up-regulates activity | 0.33 | Syk, Activated by Cross-linking the B-cell Antigen Receptor, Localizes to the Cytosol Where It Interacts with and Phosphorylates alpha-Tubulin on Tyrosine | SIGNOR-246626 |
P16220 | Q13315 | 0 | phosphorylation | down-regulates | 0.522 | Individual ala substitutions at thr-100, ser-111, or ser-121 inhibited atm-catalyzed phosphate incorporationatm phosphorylated creb in vitro and in vivo in response to ionizing radiation (ir) and h(2)o(2) on a stress-inducible domain. Ir-induced phosphorylation of creb correlated with a decrease in creb transactivation potential and reduced interaction between creb and its transcriptional coactivator, creb-binding protein (cbp) | SIGNOR-124051 |
Q13049 | O96017 | 0 | phosphorylation | up-regulates activity | 0.2 | We show that CHK2 binds and phosphorylates TRIM32 at the S55 site, which then mediates K63-linked ubiquitination of ATG7 at the K45 site to initiate autophagy. | SIGNOR-277790 |
P06493 | Q14493 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.419 | Phosphorylation of threonine 61 by cyclin a/Cdk1 triggers degradation of stem-loop binding protein at the end of S phase | SIGNOR-265258 |
P05026 | P04150 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Together these data indicate that the 21-base pair sequence represents a true MRE/GRE and that optimal activation of the human Na/K-ATPase beta1 promoter is controlled by mineralocorticoid and glucocorticoid hormones. It appears that an interaction of MR with GR on the beta1 promoter effectively down-regulates transcription. | SIGNOR-254864 |
Q8TEA8 | P68400 | 0 | phosphorylation | up-regulates activity | 0.285 | Here we show that DUE-B is de-phosphorylated in M phase and phosphorylated in G1/S phase. Phosphorylated DUE-B forms homodimers, whereas de-phosphorylated DUE-B interacts with the Mcm2–7 complex and aminoacyl-tRNA synthetases. We find that CKII can prime DUE-B for Cdc7 phosphorylation. Confirming the importance of DUE-B phosphorylation in replication initiation, a C-terminal Ser/Thr to Ala mutant blocks Cdc45 and RPA loading on sperm chromatin and inhibits DNA replication. DUE-B C-terminal phosphorylation sites (serine 179, 181, 182, 194, 196, 197, 204, 205, and threonine 187) were mutated to unphosphorylatable alanine (DUE-B(S/T)-A) or phosphomimic aspartic acid (DUE-B(S/T)-D). | SIGNOR-273970 |
P06241 | Q14524 | 1 | phosphorylation | down-regulates | 0.293 | This study addresses the effects of the src family tyrosine kinase fyn on na(v)1.5 cardiac sodium channels. Sodium currents were acquired by whole cell recording on hek-293 cells transiently expressing na(v)1.5. Acute treatment of cells with insulin caused a depolarizing shift in steady-state inactivation, an effect eliminated by the src-specific tyrosine kinase inhibitor pp2 we provide evidence that this linker is a substrate for fyn in vitro, and that y1495 is a preferred phosphorylation site. | SIGNOR-135600 |
P11717 | O60664 | 0 | relocalization | up-regulates activity | 0.725 | TIP47 is present in cytosol and on endosomes and is required for MPR transport from endosomes to the trans-Golgi network in vitro and in vivo. TIP47 recognizes a phenylalanine/tryptophan signal in the tail of the cation-dependent MPR that is essential for its proper sorting within the endosomal pathway. These data suggest that TIP47 binds MPR cytoplasmic domains and facilitates their collection into transport vesicles destined for the Golgi. | SIGNOR-253092 |
Q86TM6 | Q99574 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | 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-272757 |
Q9Y2G1 | Q02750 | 0 | phosphorylation | down-regulates activity | 0.258 | Mek1 phosphorylation of Ndt80 therefore provides an elegant way for cells to know when it is safe to enter the first meiotic division.|These observations suggest that phosphorylation of the DBD by Mek1 prevents Ndt80 from binding to MSEs and explains how Mek1 phosphorylation can inhibit Ndt80 activity. | SIGNOR-279416 |
Q05209 | P06213 | 1 | dephosphorylation | down-regulates | 0.378 | Interestingly, all PTPs that were tested could completely dephosphorylate the receptor, given sufficient time, including a negative control (PTP-PEST) that failed to bind IRK as a trapping mutant. | SIGNOR-75894 |
P05771 | Q03721 | 1 | phosphorylation | down-regulates | 0.2 | We found that pkc specifically eliminates rapid inactivation of a cloned human a-type k+ channel (hkv3.4), converting this channel from a rapidly inactivating a type to a noninactivating delayed rectifier type. | SIGNOR-35626 |
P43405 | P00519 | 0 | phosphorylation | up-regulates activity | 0.253 | Abl kinases modulate Syk kinase activation.|Expression of constitutively active Abl (AblPP) increased Syk Y346 phosphorylation, whereas the phosphorylation was unaffected in cells expressing kinase inactive form of Abl (AblKR) (XREF_FIG). | SIGNOR-279665 |
P23769 | P20396 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.263 | The rat prepro-TRH gene is activated by GATA2. | SIGNOR-267259 |
P43405 | Q9UHP3 | 1 | phosphorylation | down-regulates quantity | 0.385 | Altogether, these data strengthen our results that SYK specifically phosphorylates USP25 and suggest that Y740 is the most probable phosphorylated tyrosine on USP25.We also assessed whether the SYK mediated phosphorylation of USP25 alters its protease activity.|Preliminary data indicate that proteasome inhibition by MG132 treatment did not modify the SYK dependent decrease of USP25 levels in contrary to accumulation of USP25 protein by MG132 treatment in the absence of SYK overexpression. | SIGNOR-278458 |
P62136 | Q13263 | 1 | dephosphorylation | up-regulates activity | 0.322 | PP1\u03b1 dephosphorylates KAP1 at Ser 824 . | SIGNOR-277075 |
P49023 | P23470 | 0 | dephosphorylation | up-regulates activity | 0.26 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254721 |
Q9Y4X5 | O60573 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.678 | Human homologue of Drosophila ariadne (HHARI) is a RING-IBR-RING domain protein identified through its ability to bind the human ubiquitin-conjugating enzyme, UbcH7. Thus, by promoting the ubiquitin-mediated degradation of 4EHP, HHARI may have a role in both protein degradation and protein translation. | SIGNOR-268848 |
O15534 | P48730 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.807 | Human casein kinase Idelta phosphorylation of human circadian clock proteins period 1 and 2. We have now extended our previous studies to show that human casein kinase Idelta (hCKIdelta), the closest homologue to hCKIepsilon, associates with and phosphorylates hPER1 and causes protein instability. Furthermore, we observed that both hCKIdelta and hCKIepsilon phosphorylated and caused protein instability of human period 2 protein (hPER2). | SIGNOR-268001 |
Q86T82 | Q01094 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | USP37 was induced by E2F transcription factors in G1|Ectopic E2F1 activated the wild-type promoter, but not the mutant promoter, 3-fold over basal levels in 293T cells (Figure 4F), confirming the functionality of the E2F binding sites in the USP37 promoter. | SIGNOR-265047 |
P43629 | P05771 | 0 | phosphorylation | down-regulates activity | 0.2 | Functional studies of the wild-type receptor and serine/threonine mutants indicated that phosphorylation of Ser(394) by protein kinase C slightly suppresses KIR3DL1 inhibitory function, and reduces receptor internalization and turnover.Both CKII and PKC phosphorylate KIR3DL1 in vitro. Ser364 can be phosphorylated after phosphorylation of Ser367 by CKII. | SIGNOR-276079 |
Q9NR50 | P41091 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.735 | 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-269136 |
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