IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P53667 | Q13153 | 0 | phosphorylation | up-regulates activity | 0.614 | Activation of lim-kinase by pak1 couplesp21-activated kinase (pak1) phosphorylates lim-kinase at threonine residue 508 within lim-kinase's activation loop | SIGNOR-72142 |
P04637 | P51812 | 0 | phosphorylation | up-regulates activity | 0.336 | Here we show that ribosomal S6 kinase 2 (RSK2) activates and phosphorylates p53 (Ser15) in vitro and in vivo and colocalizes with p53 in the nucleus. | SIGNOR-279567 |
P53350 | Q13158 | 1 | phosphorylation | down-regulates activity | 0.459 | Fas-associated death domain-containing protein (FADD) was first identified as an adapter molecule involved in formation of a death-inducing signaling complex upon Fas stimulation| Plk1 phosphorylates fadd at ser-194 in response to treatment with taxol Phosphorylation by polo-like kinase 1 induces the tumor-suppressing activity of FADD | SIGNOR-168204 |
Q8IW41 | P07101 | 1 | phosphorylation | up-regulates | 0.2 | Recombinant human tyrosine hydroxylase (hth1) was found to be phosphorylated by mitogen and stress-activated protein kinase 1 (msk1) at ser40 and by p38 regulated/activated kinase (prak) on ser19. Phosphorylation of both ser40 and ser19 induced a high-affinity binding of 14-3-3 proteins, but only the interaction of 14-3-3 with ser19 increased the hth1 activity. | SIGNOR-95479 |
Q9H1B7 | P01213 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.263 | EAP1 encoded a nuclear protein expressed in neurons involved in the inhibitory and facilitatory control of reproduction. EAP1 transactivated genes required for reproductive function, such as GNRH1, and repressed inhibitory genes, such as preproenkephalin. It contained a RING finger domain of the C3HC4 subclass required for this dual transcriptional activity.These results suggest that EAP1 is a transcriptional regulator that, acting within the neuroendocrine brain, contributes to controlling female reproductive function. | SIGNOR-267156 |
Q9NYL2 | P45985 | 1 | phosphorylation | up-regulates activity | 0.2 | We show here that members of the mixed-lineage kinase (MLK) family (including MLK1, MLK2, MLK3, and dual leucine zipper kinase [DLK]) are expressed in neuronal cells and are likely to act between Rac1/Cdc42 and MKK4 and -7 in death signaling. | SIGNOR-243348 |
P04818 | Q9HCK8 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.283 | In order to identify CHD8 target genes, we performed a transcriptomic analysis of CHD8-depleted cells, finding out that CHD8 controls the expression of cyclin E2 (CCNE2) and thymidylate synthetase (TYMS), two genes expressed in the G1/S transition of the cell cycle. CHD8 was also able to co-activate the CCNE2 promoter in transient transfection experiments. Chromatin immunoprecipitation experiments demonstrated that CHD8 binds directly to the 5' region of both CCNE2 and TYMS genes. | SIGNOR-268805 |
O95996 | P35222 | 1 | 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 |
O43318 | Q99558 | 1 | phosphorylation | up-regulates activity | 0.564 | The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway|Activated TAK1 phosphorylates NIK, which stimulates IKK-alpha activity. Our results indicate that TAK1 links TRAF6 to the NIK-IKK cascade in the IL-1 signalling pathway. | SIGNOR-262833 |
P23246 | Q9UM73 | 0 | phosphorylation | down-regulates | 0.2 | Furthermore, psf was shown to be a direct substrate of purified alk kinase domain in vitro, and psf tyr293 was identified as the site of phosphorylation. Psf phosphorylation also increased its binding to rna and decreased the psf-mediated suppression of gage6 expression. | SIGNOR-155298 |
Q8NFZ4 | P78352 | 1 | relocalization | up-regulates activity | 0.759 | 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-264193 |
Q13698 | P68400 | 0 | phosphorylation | up-regulates activity | 0.2 | To identify the regulatory sites of phosphorylation under physiologically relevant conditions, Ca(V)1.1 channels were purified from skeletal muscle and sites of phosphorylation on the α1 subunit were identified by mass spectrometry. Two phosphorylation sites were identified in the proximal C-terminal domain, serine 1575 (S1575) and threonine 1579 (T1579), which are conserved in cardiac Ca(V)1.2 channels (S1700 and T1704, respectively). In vitro phosphorylation revealed that Ca(V)1.1-S1575 is a substrate for both cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II, whereas Ca(V)1.1-T1579 is a substrate for casein kinase 2. | SIGNOR-263114 |
P37173 | Q9HAU4 | 0 | ubiquitination | down-regulates activity | 0.595 | Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degradation of smads and receptors for tgf-beta and bmps. | SIGNOR-195681 |
Q04760 | P07947 | 0 | phosphorylation | up-regulates activity | 0.2 | We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D). | SIGNOR-276185 |
P15692 | Q16665 | 0 | transcriptional regulation | up-regulates quantity | 0.773 | Transcription of the human erythropoietin (EPO) gene is activated in Hep3B cells exposed to hypoxia. Hypoxia-inducible factor 1 (HIF-1) is a nuclear factor whose DNA binding activity is induced by hypoxia in Hep3B cells, and HIF-1 binds at a site in the EPO gene enhancer that is required for hypoxic activation of transcription. | SIGNOR-256592 |
P04637 | Q05655 | 0 | phosphorylation | up-regulates | 0.677 | Here, we show that the pro-apoptotic kinase, protein kinase c delta (pkcdelta), is involved in phosphorylation of p53 on ser(46). pkcdelta potentiates p53-dependent apoptosis by ser(46) phosphorylation in response to genotoxic stress. | SIGNOR-143382 |
P31749 | Q96KG9 | 1 | phosphorylation | up-regulates activity | 0.255 | In previous work, we demonstrated that TEIF (transcriptional element-interacting factor) distributes in the centrosomes and regulates centrosome status under both physiologic and pathologic conditions.|A consensus motif for Akt phosphorylation (RHRVLT) proved to be involved in centrosomal TEIF localization, and the 469-threonine of this motif may be phosphorylated by Akt both in vitro and in vivo. Elimination of this phosphorylated site on TEIF caused reduced centrosome distribution and centrosome splitting or amplification. | SIGNOR-265496 |
Q6ZMZ3 | Q9H3D4 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Here we show that in the developing skin, epidermal progenitor cells of mice lacking p63 transcription factor display alterations in the nuclear shape accompanied by a marked decrease in expression of several nuclear envelope-associated components (Lamin B1, Lamin A/C, Sun1, Nesprin-3, Plectin) compared with controls. Furthermore, chromatin immunoprecipitation-quantitative PCR assay showed enrichment of p63 on Sun1, Syne3, and Plec promoters, suggesting them as p63 targets. | SIGNOR-263280 |
Q14289 | P29350 | 0 | dephosphorylation | down-regulates | 0.359 | Raftk binds constitutively to the protein tyrosine phosphatase shptp1.SHPTP1 Plays a negative role in pyk2/raftk signaling by dephosphorylating raftk on tyr-402, thereby inhibiting the interaction of the sh2 domain of c-src with raftk | SIGNOR-71414 |
Q96EB6 | Q15831 | 0 | phosphorylation | up-regulates activity | 0.573 | Resveratrol promotes the binding between LKB1 and Sirt1, which we first reported, and this binding leads to LKB1-mediated phosphorylation of Sirt1 at three different serine residues in the C terminus of Sirt1. Mechanistically, LKB1-mediated phosphorylation increases intramolecular interactions in Sirt1, such as the binding of the C terminus to the deacetylase core domain, thereby eliminating DBC1 (Deleted in Breast Cancer 1, Sirt1 endogenous inhibitor) inhibition and promoting Sirt1-substrate interaction. | SIGNOR-277323 |
P41002 | O43303 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.539 | Using a mode of substrate binding distinct from other F-box protein-substrate pairs, CP110 and Cyclin F physically associate on the centrioles during the G2 phase of the cell cycle, and CP110 is ubiquitylated by the SCF(Cyclin F) ubiquitin ligase complex, leading to its degradation. | SIGNOR-266364 |
Q9Y6E7 | P15336 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Our data suggest that mTORC1 promotes the binding of the E3 ligase, βTrCP, to CREB2 (Figure 4D), promoting CREB2 degradation by the proteasome (Figure 4E). Here, we show that mTORC1 promotes glutamine anaplerosis by activating glutamate dehydrogenase (GDH). This regulation requires transcriptional repression of SIRT4, the mitochondrial-localized sirtuin that inhibits GDH. Mechanistically, mTORC1 represses SIRT4 by promoting the proteasome-mediated destabilization of cAMP-responsive element binding 2 (CREB2). | SIGNOR-267831 |
P08670 | Q13464 | 0 | phosphorylation | down-regulates activity | 0.367 | We found that vimentin, the most widely expressed intermediate filament protein, served as an excellent substrate for Rho-associated kinase (Rho-kinase) and that vimentin phosphorylated by Rho-kinase lost its ability to form filaments in vitro. Two amino-terminal sites on vimentin, Ser38 and Ser71, were identified as the major phosphorylation sites for Rho-kinase, and Ser71 was the most favored and unique phosphorylation site for Rho-kinase in vitro. | SIGNOR-248998 |
P28482 | P37231 | 1 | relocalization | down-regulates | 0.457 | The genomic activity of ppargamma is modulated, in addition to ligand binding, by phosphorylation of a serine residue by mapks, such as extracellular signal-regulated protein kinases-1/2 (erk-1/2), or by nucleocytoplasmic compartmentalization through the erk activators mapk kinases-1/2 (mek-1/2). These mapks phosphorylate (in humans) ser 84 in the ppargamma1 and ser 114 in ppargamma2 isoform | SIGNOR-179400 |
P49815 | P54646 | 0 | phosphorylation | up-regulates | 0.577 | We have observed that ampk directly phosphorylates tsc2, and the ampk-dependent phosphorylation of tsc2 is critical for the coordination between cell growth and cellular energy levels. | SIGNOR-149388 |
P08253 | Q13753 | 1 | cleavage | up-regulates activity | 0.471 | Induction of Cell Migration by Matrix Metalloprotease-2 Cleavage of Laminin-5|MMP2 cleaved the Ln-5 gamma2 subunit at residue 587, exposing a putative cryptic promigratory site on Ln-5 that triggers cell motility. This altered form of Ln-5 is found in tumors and in tissues undergoing remodeling, but not in quiescent tissues. Cleavage of Ln-5 by MMP2 and the resulting activation of the Ln-5 cryptic site may provide new targets for modulation of tumor cell invasion and tissue remodeling. | SIGNOR-253240 |
Q13153 | Q9UQ88 | 0 | phosphorylation | up-regulates activity | 0.384 | CDK11p58 phosphorylation of PAK1 Ser174 promotes DLC2 binding and roles on cell cycle progression|We show that PAK1 is a substrate of CDK11p58 and can be strongly activated upon phosphorylation. | SIGNOR-273026 |
O14733 | Q9NYL2 | 0 | phosphorylation | up-regulates activity | 0.2 | We show here that members of the mixed-lineage kinase (MLK) family (including MLK1, MLK2, MLK3, and dual leucine zipper kinase [DLK]) are expressed in neuronal cells and are likely to act between Rac1/Cdc42 and MKK4 and -7 in death signaling. | SIGNOR-243345 |
P48729 | Q13315 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Mechanistically, CK1α phosphorylates the serine residue S1270 and modulates the protein abundance of ataxia telangiectasia mutated (ATM), a primary initiator of DNA double-strand break (DSB)-response signaling, which is compromised in ENZA-resistant cells and patients. Inhibition of CK1α stabilizes ATM, resulting in the restoration of DSB signaling, and thus increases ENZA-induced cell death and growth arrest. | SIGNOR-277918 |
P63167 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.2 | CDK5 activates the tumor suppressor DLC1 by phosphorylating and diminishing the binding of an autoinhibitory region of DLC1 to its Rho-GAP domain and allows it to localize to focal adhesions.|Here, we report that CDK5 coordinately activates multiple DLC1 functions, elucidate the mechanism underlying this activation, and identify a role for DLC1 inactivation in the pro oncogenic activity CDK5. | SIGNOR-279154 |
Q9UBN7 | O43791 | 0 | ubiquitination | down-regulates quantity | 0.2 | Cullin3 SPOP ubiquitin E3 ligase promotes the poly-ubiquitination and degradation of HDAC6 | SIGNOR-268862 |
Q9UQL6 | Q16566 | 0 | phosphorylation | down-regulates | 0.51 | Recently, camkiv, a calcium-calmodulindependent protein kinase, was also shown to activate mef2s by dissociating class ii histone deacetylases (e.g., Hdac5) from mef2s, thus relieving the transcriptional repressive effect of hdacs. | SIGNOR-236571 |
Q9UPU5 | Q09472 | 1 | deubiquitination | up-regulates quantity by stabilization | 0.271 | In this study, several cancer-related proteins (Bax, p300, E2F4 and securin) have been proven to be substrates of ubiquitin-specific peptidase 24 (USP24), and relevance has been shown between USP24 and its substrates in samples from clinical lung cancer patients. |Knockdown of USP24 decreases Bax and p300 levels | SIGNOR-275607 |
Q99459 | P06493 | 0 | phosphorylation | up-regulates activity | 0.624 | Cdc5-dependent Net1 phosphorylation and Cdc14 release from the nucleolus require prior Cdc5 activation by Cdk1 and active separase to promote Cdc14 activation.|Cdk1 initially phosphorylates Cdc5, mostly at T242 and T238 (T242 phosphorylation is especially relevant based on our results), and phosphorylation activates its kinase activity, which is essential for anaphase progression. | SIGNOR-279597 |
P16401 | P49841 | 0 | phosphorylation | up-regulates | 0.2 | We found that threonine 10 of h1.5 can be phosphorylated by glycogen synthase kinase-3 in vitro. We have generated an antiserum specific for human h1.5 phosphorylated at threonine 10. Immunofluorescence labeling of hela cells with this antiserum revealed that the phosphorylation at this site appears in prometaphase and disappears in telophase, and that this hyperphosphorylated form of h1.5 is mainly chromatin-bound in metaphase when chromatin condensation is maximal. | SIGNOR-183325 |
P41212 | P28482 | 0 | phosphorylation | down-regulates | 0.317 | Tel became phosphorylated by erk on two serine residues, ser213 and ser257, in the internal domain between the hlh and ets domains. Tel lost its abilities to repress transcription through the phosphorylation. | SIGNOR-260086 |
Q09472 | Q9H0K1 | 0 | phosphorylation | down-regulates activity | 0.278 | Indeed, overexpression of SIK2 increased p300 phosphorylation at Ser89, while knockdown of SIK2 decreased it (Fig. 4B). | SIGNOR-278368 |
P17252 | P05204 | 1 | phosphorylation | down-regulates | 0.29 | Protein kinases that phosphorylate hmg-14 17 at the major sites have been implicated from previous in vitro studies. Protein kinase c and a similar calcium phospholipid-dependent kinase have been reported to phosphorylate both proteins in vitro, where the phosphorylation of hmg-17 occurs predominantly at ser24 and to a lesser degree at ser28. Phosphorylation of hmg-14 at ser6 by camp- or cgmp-dependent kinases has also been reported. Thus, other kinases may contribute to phosphorylation at ser6 in response to oa. Ser88 and ser98 on hmg-14 are also phosphorylated by casein kinase ii in vitro. we conclude that the correlation we observe reflects a causal relationship, in which phosphorylation somehow facilitates the redistribution of hmg-14 and -17 toward non-nuclear pools. | SIGNOR-76320 |
P42574 | Q13813 | 1 | cleavage | down-regulates | 0.675 | Caspase-3 is required for alpha-fodrin cleavage but dispensable for cleavage of other death substrates in apoptosis. | SIGNOR-57891 |
O43524 | Q96KS0 | 0 | hydroxylation | down-regulates activity | 0.287 | Prolyl hydroxylation by EglN2 destabilizes FOXO3a by blocking its interaction with the USP9x deubiquitinase.|Here we report that EglN2 can hydroxylate FOXO3a on two specific prolyl residues in vitro and in vivo. Hydroxylation of these sites prevents the binding of USP9x deubiquitinase, thereby promoting the proteasomal degradation of FOXO3a. | SIGNOR-261998 |
P60763 | O75398 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Affymetrix gene profiling studies revealed Rac3 as a potential target gene and quantitative RT-PCR analysis confirmed that Rac3 was upregulated by Deaf-1 in immortalized mouse mammary epithelial cells. | SIGNOR-269059 |
P19474 | Q9C035 | 1 | monoubiquitination | up-regulates quantity | 0.344 | Here, we show that TRIM5alpha functions as a RING-finger-type E3 ubiquitin ligase both in vitro and in vivo and ubiquitinates itself in cooperation with the E2 ubiquitin-conjugating enzyme UbcH5B. Thus, the ubiquitination of TRIM5alpha is catalyzed by itself and Ro52. Unexpectedly, although TRIM5alpha is ubiquitinated, our results have revealed that the proteasome inhibitors MG115 and MG132 do not stabilize it in HeLa cells, suggesting that the ubiquitination of TRIM5alpha does not lead to proteasomal degradation. Importantly, TRIM5alpha is clearly conjugated by a single ubiquitin molecule (monoubiquitination). Our monoubiquitin-fusion assay suggests that monoubiquitination is a signal for TRIM5alpha to translocate from cytoplasmic bodies to the cytoplasm. | SIGNOR-271672 |
Q9Y4P8 | Q8TEV9 | 0 | transcriptional regulation | up-regulates quantity | 0.271 | Global mRNA expression analysis revealed that SMCR8 regulates transcription of several other autophagy genes including WIPI2 | SIGNOR-252028 |
P38936 | P31749 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.84 | Pim-1, PKC, and Akt1 kinases phosphorylate Thr-145 and Ser-146 sites on p21 protein. Phosphorylation at Thr-145 promotes cytoplasmic translocation and stability of p21. Ser-146 phosphorylation mediated by Akt1 enhances p21 stabilization and promotes cell survival. | SIGNOR-157790 |
Q9HCK8 | Q92886 | 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-268919 |
P09467 | Q13263 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.31 | In this study, we demonstrated that the tripartite motif-containing protein 28 (TRIM28) binds directly to and promotes FBP1 for ubiquitination and degradation. MAGE-A3 and MAGE-C2, which are known to be overexpressed in HCC, can enhance TRIM28-dependent degradation of FBP1 by forming ubiquitin ligase complexes with TRIM28. | SIGNOR-267591 |
P31749 | Q9H9Q4 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.358 | Akt1 phosphorylates XLF at T181 Here, we report that Akt phosphorylates XLF at Thr181 to trigger its dissociation from the DNA ligase IV/XRCC4 complex, and promotes its interaction with 14-3-3β leading to XLF cytoplasmic retention, where cytosolic XLF is subsequently degraded by SCF(β-TRCP) in a CKI-dependent manner. | SIGNOR-276881 |
Q9P107 | P60953 | 1 | gtpase-activating protein | down-regulates activity | 0.512 | 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-260507 |
P84022 | Q9Y297 | 0 | ubiquitination | down-regulates | 0.389 | An e3 ubiquitin ligase complex roc1-scffbw1a consisting of roc1, skp1, cullin1, and fbw1a (also termed trcp1) induces ubiquitination of smad3. | SIGNOR-108237 |
P60484 | Q9Y2H9 | 0 | phosphorylation | down-regulates | 0.515 | Mast1 was found to associate to pten. | SIGNOR-138003 |
Q9UPW6 | O75925 | 0 | sumoylation | down-regulates activity | 0.583 | We found that SATB2 differs from the closely related thymocyte-specific protein SATB1 by modifications of two lysines with the small ubiquitive related modifier (SUMO), which are augmented specifically by the SUMO E3 ligase PIAS1. | SIGNOR-269112 |
Q9UQC2 | P06241 | 0 | phosphorylation | up-regulates activity | 0.605 | Our studies show that Gab2 is activated by Fyn kinase upon the engagement of ligand to TNFR1, IL-1R, or TLR4.|TNF\u03b1, IL-1\u03b2, and LPS induce Fyn kinase-mediated phosphorylation of Gab2. | SIGNOR-279984 |
Q14680 | Q12778 | 1 | phosphorylation | down-regulates quantity | 0.257 | Direct phosphorylation of FOXO1 and FOXO3 by MELK.|Our findings revealed that siRNA mediated MELK knockdown increased protein levels of FOXO1 and FOXO3, which might increase p21 transcriptional level in a p53 independent manner. | SIGNOR-279543 |
P08069 | P42345 | 0 | phosphorylation | up-regulates activity | 0.494 | Both recombinant mTOR and immunoprecipitated mTORC2 phosphorylate IGF-IR and InsR on Tyr1131/1136 and Tyr1146/1151, respectively.|Here we show that mTOR possesses unexpected tyrosine kinase activity and activates IGF-IR/InsR. | SIGNOR-280044 |
P27361 | P47712 | 1 | phosphorylation | up-regulates | 0.658 | Activated map kinase phosphorylates cpla2 at ser-505, causing increased enzymatic activity of cpla2, which is only realized upon translocation of cpla2 to the membrane. | SIGNOR-38434 |
Q13237 | P00533 | 1 | phosphorylation | down-regulates activity | 0.2 | Recombinant PKG II inhibited the epidermal growth factor (EGF)-induced activation of the EGF receptor via phosphorylating the T406 of the extracellular domain and blocked EGF-triggered proliferation of various cancer cells. | SIGNOR-277589 |
P11055 | O43508 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | TWEAK induces ubiquitination of MyHCf and expression of atrogin-1 and MuRF1 in myotubes. our data show that TWEAK rapidly increases the conjugation of ubiquitin to MyHCf (Fig. 3A) and ubiquitination preceded the degradation of MyHCf (Fig. 2C and Fig. 3A). | SIGNOR-272628 |
Q02539 | Q15369 | 0 | phosphorylation | up-regulates | 0.2 | Our results also show the potential function of p-tefb phosphorylation of h1, namely, to increase h1 dissociation from actively transcribed dna. P-tefb preferentially phosphorylates the ser-183 phosphorylation site of histone h1.1 | SIGNOR-166120 |
Q9NR48 | P68431 | 1 | trimethylation | up-regulates activity | 0.2 | We show that human ASH1L specifically methylates histone H3 Lys-36. Our data implicate that there may be a regulatory mechanism of ASH1L histone methyltransferases | SIGNOR-269055 |
Q13043 | O60346 | 0 | 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 |
Q9Y5T5 | P53350 | 0 | phosphorylation | up-regulates activity | 0.344 | Plk1 phosphorylates and activates Usp16. In vitro phosphorylation of Usp16 with single (S330A, S386A, or S486A) or collective 3A (S330A/S386A/S486A) mutation showed that Plk1 phosphorylated Usp16 at all three sites (Fig. S2 D). | SIGNOR-274015 |
P20823 | Q13315 | 0 | phosphorylation | up-regulates | 0.256 | Serine 249 phosphorylation by atm protein kinase regulates hepatocyte nuclear factor-1_ transactivation | SIGNOR-205087 |
Q00535 | P09874 | 1 | phosphorylation | down-regulates activity | 0.258 | These results would suggest that the phosphorylation of PARP-1 via Cdk5's kinase activity is necessary for its persistence at damage sites.Based on these results and the recruitment data, we hypothesize that the phosphorylation of the PARP-1 protein by Cdk5 on one or more of the serines 782, 785, and 786 results in an attenuation of its ribosylating activity facilitating its persistence at the sites of DNA damage. | SIGNOR-276359 |
P29372 | Q9NRP7 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Here, we show that MID1 catalyzes the ubiquitination and proteasomal cleavage of the GLI3 regulator Fu. | SIGNOR-272466 |
P32119 | P00519 | 0 | phosphorylation | down-regulates activity | 0.284 | Inactivation of peroxiredoxin I by phosphorylation allows localized H(2)O(2) accumulation for cell signaling. To determine whether Prxs are phosphorylated, we subjected recombinant human PrxI and II to an in vitro kinase assay with two nonreceptor PTKs, Lck and Abl, in the presence of [γ-32P]ATP. Both PTKs phosphorylated PrxI and PrxII. Phosphorylation of the wild-type protein was detected, whereas that of the Y194F mutant was not (Figure 1B), indicating that Tyr194 is the only site of tyrosine phosphorylation. | SIGNOR-276280 |
P53350 | Q9Y266 | 1 | phosphorylation | up-regulates activity | 0.73 | Here, we characterize the interaction between plk1 and nudc, show that plk1 phosphorylates nudc at conserved s274 and s326 residues in vitro, and present evidence that nudc is also a substrate for plk1 in vivo. Downregulation of nudc by rna interference results in multiple mitotic defects, including multinucleation and cells arrested at the midbody stage, which are rescued by ectopic expression of wild-type nudc, but not by nudc with mutations in the plk1 phosphorylation sites. | SIGNOR-103403 |
P24723 | P49840 | 1 | phosphorylation | down-regulates | 0.321 | Furthermore, several pkc isotypes phosphorylate gsk-3 in vitro and in vivo. in the presence of atp, several isoforms (?, ___, _, ?, And of pkc phosphorylated both gsk-3? At ser 21 and gsk-3_ at ser 9 | SIGNOR-115730 |
Q6PGN9 | P06493 | 0 | phosphorylation | down-regulates activity | 0.236 | MT-polymerizing activity was decreased from samples with DDA3 phosphorylated by Cdk1 ( xref , lanes 4 vs 6) and Aurora A ( xref , lanes 14 vs 16).|Taken together, the mitotic Cdk1 and Aurora A kinases inhibit MT polymerization activities and MT bundling activities of DDA3. | SIGNOR-279601 |
Q9NYQ6 | P53350 | 0 | phosphorylation | down-regulates activity | 0.2 | In contrast to the non autonomous polarity defects caused by transgenic expression of Celsr1 LLtoAA, Plk1 inhibition did not cause a significant alteration in Celsr1 interphase polarity (XREF_FIG).|Plk1 phosphorylates the Celsr1 cytoplasmic domain in\nvitro . | SIGNOR-279094 |
P27361 | O95997 | 1 | phosphorylation | up-regulates | 0.304 | Pttg is phosphorylated in vitro on ser(162) by map kinase and this phosphorylation site plays an essential role in pttg transactivation function. | SIGNOR-79519 |
P09874 | Q00535 | 0 | phosphorylation | down-regulates activity | 0.258 | These results would suggest that the phosphorylation of PARP-1 via Cdk5's kinase activity is necessary for its persistence at damage sites.Based on these results and the recruitment data, we hypothesize that the phosphorylation of the PARP-1 protein by Cdk5 on one or more of the serines 782, 785, and 786 results in an attenuation of its ribosylating activity facilitating its persistence at the sites of DNA damage. | SIGNOR-276359 |
Q8IZL8 | P11802 | 0 | phosphorylation | up-regulates | 0.351 | Using site-directed mutagenesis and in vitro kinase assays, we identified ser(477) and ser(991) of pelp1 as cdk phosphorylation sites. we identified pelp1 as a novel substrate of cdks and found that cdk phosphorylation is important for the proper function of pelp1 in modulating hormone-driven cell cycle progression and also for optimal e2f transactivation function. | SIGNOR-167770 |
Q96CF2 | Q96GD4 | 0 | phosphorylation | up-regulates | 0.469 | Moreover, we find that the cpc's catalytic subunit, aurora b kinase, phosphorylates one of the three human snf7 paralogues-chmp4c-in its c-terminal tail, a region known to regulate its ability to form polymers and associate with membranes. Phosphorylation at these sites appears essential for chmp4c function because their mutation leads to cytokinesis defects. The introduction of the s214a and s215a mutations together with s210a almost completely abolished aurora b phosphorylation | SIGNOR-197967 |
P78348 | Q9NRD5 | 0 | relocalization | up-regulates activity | 0.537 | we found that the PDZ domain-containing protein PICK1 (protein interacting with C kinase) interacts specifically with the C-termini of BNC1 and ASIC. Our studies showing association of recombinant PICK1 with ASIC and BNC1, and the presence of both PICK1 and ASIC in the synaptosomal fraction | SIGNOR-223417 |
Q8NHW3 | P49841 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.257 | We also demonstrate that gsk-3 triggers mafa sequential phosphorylation on residues s61, t57, t53, and s49 /we demonstrated that phosphorylation by gsk-3 is conserved among the large maf proteins. It couples ubiquitination/degradation and transcriptional activation and modulates maf biological activity./ Taken together, these results suggest that, in contrast to what can be expected from ubiquitination/degradation, gsk-3-mediated mafa phosphorylation increases its transactivating ability, thereby controlling its biological activity. | SIGNOR-159462 |
P08047 | P49585 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Sp1 and Sp3 function as transcriptional activators of the Ctpct promoter | SIGNOR-266231 |
O15294 | P46937 | 1 | glycosylation | up-regulates activity | 0.283 | Mass spectrometry analysis showed that YAP was the effector protein modified by OGT. In details, YAP Ser109 O-GlcNAcylation promoted the malignant phenotypes in PTC cells by inducing YAP Ser127 dephosphorylation and activation. | SIGNOR-276942 |
P31749 | P36873 | 0 | dephosphorylation | down-regulates activity | 0.383 | Here, we identify PP1 as a serine/threonine phosphatase that associates with and dephosphorylates AKT in breast cancer cells|The heat shock protein 90 inhibitor geldanamycin and the ErbB inhibitor ZD1839 promote rapid PP1 phosphatase-dependent inactivation of AKT in ErbB2 overexpressing breast cancer cells | SIGNOR-252605 |
P52564 | P45984 | 1 | phosphorylation | up-regulates | 0.473 | A map kinase kinase kinase (mapkkk), termed ask1, was identified that activated two different subs of map kinase kinases (mapkk), sek1 (or mkk4) and mkk3/mapkk6 (or mkk6), which in turn activated stress-activated protein kinase (sapk, also known as jnk;c-jun amino-terminal kinase) | SIGNOR-45369 |
Q96GG9 | P46934 | 0 | monoubiquitination | up-regulates quantity | 0.368 | Here we revealed a previously unknown mechanism that regulates hDCNL1. In cultured mammalian cells ectopically expressed hDCNL1 was mono-ubiquitinated predominantly at K143, K149, and K171. Using a classical chromatographic purification strategy, we identified Nedd4-1 as an E3 ligase that can catalyze mono-ubiquitination of hDCNL1 in a reconstituted ubiquitination system.Taken together, these results suggest a mono-ubiquitination-mediated mechanism that governs nuclear-cytoplasmic trafficking of hDCNL1, | SIGNOR-272719 |
P68400 | P41002 | 1 | phosphorylation | down-regulates activity | 0.249 | We determined that casein kinase II (CK2) can phosphorylate Ser621 and thereby regulate the E3 ligase activity of the SCF(cyclin F) complex. | SIGNOR-266373 |
P27361 | P30304 | 0 | dephosphorylation | down-regulates | 0.395 | We found that cdc25a physically interacted with and de-phosphorylated phospho-erk both in vitro and in cell culture. | SIGNOR-133392 |
Q05084 | O43918 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.362 | Sequence variation in promoter of Ica1 gene, which encodes protein implicated in type 1 diabetes, causes transcription factor autoimmune regulator (AIRE) to increase its binding and down-regulate expression. | SIGNOR-268973 |
Q13501 | P06493 | 0 | phosphorylation | up-regulates | 0.343 | Here we show that cdk1 phosphorylates p62 in vitro and in vivo at t269 and s272, which is necessary for the maintenance of appropriate cyclin b1 levels and the levels of cdk1 activity necessary to allow cells to properly enter and exit mitosis. | SIGNOR-169012 |
P35590 | Q02763 | 0 | phosphorylation | up-regulates activity | 0.348 | Thus, Tie2 was able to induce Tie1 phosphorylation.|When cotransfected, Tie2 formed heteromeric complexes with Tie1, enhanced Tie1 activation, and induced phosphorylation of a kinase-inactive Tie1 in a ligand-dependent manner. | SIGNOR-279769 |
Q14674 | P06493 | 0 | phosphorylation | down-regulates | 0.572 | Both cdc2/cyclinb1 and mapk (erk2) efficiently phosphorylate separase at its major inhibitory site in vitro | SIGNOR-113126 |
Q13185 | P17612 | 0 | phosphorylation | up-regulates | 0.2 | We demonstrate that p-ser 83-hp1gamma has an exclusively euchromatic localization, interacts with ku70 (a regulatory protein involved in multiple nuclear procesess), has impaired silencing activity and serves as a marker for transcription elongation. | SIGNOR-145109 |
Q00535 | Q05193 | 1 | phosphorylation | up-regulates activity | 0.516 | Here, we show that cyclin-dependent kinase 5 (Cdk5) phosphorylates dynamin I on Ser 774 and Ser 778 in vitro, which are identical to its endogenous phosphorylation sites in vivo. Cdk5 antagonists and expression of dominant-negative Cdk5 block phosphorylation of dynamin I, but not of amphiphysin or AP180, in nerve terminals and inhibit SVE. | SIGNOR-250661 |
P37231 | P45983 | 0 | phosphorylation | down-regulates activity | 0.527 | The a/b domain of human ppargamma1 was phosphorylated in vivo, and this was abolished either by mutation of serine 84 to alanine (s84a) or coexpression of a phosphoprotein phosphatase. In vitro, this domain was phosphorylated by erk2 and jnk, and this was markedly reduced in the s84a mutant. Thus, phosphorylation of a mitogen-activated protein kinase site in the a/b region of ppargamma inhibits both ligand-independent and ligand-dependent transactivation functions. | SIGNOR-46518 |
P51684 | P14780 | 1 | null | up-regulates activity | 0.2 | We hypothesized that MIP-3alpha promotes pancreatic cancer invasion through the up-regulation of MMP-9, a Type 4 collagenase. | SIGNOR-278042 |
Q15257 | P31749 | 1 | dephosphorylation | down-regulates | 0.2 | Consistent with previous reports (2830), we found that expression of sv40st, suppression of either pp2a c or b resulted in elevated levels of akt phosphorylation (ser473) | SIGNOR-252607 |
P23458 | P17706 | 0 | dephosphorylation | down-regulates activity | 0.767 | Upon ligand binding, IL-2R , IL-6R or LeptinR , IFN-_R , IFN-_R and PRLR or growth hormone (GH) receptor associated JAKs become activated. These JAKs mediate phosphorylation of specific tyrosine residues and recruit STATs. Activated STATs are released from the receptor and translocate to the nucleus. PTP1B dephosphorylates JAK2, TYK2 and STAT5 . The 45-kDa form of TC-PTP was shown to dephosphorylate JAK1 and JAK3 as well as STAT1, STAT3 and STAT5. | SIGNOR-134620 |
P42702 | P27361 | 0 | phosphorylation | down-regulates | 0.299 | Thus, our results identify the human lifr as a substrate for mapk and suggest a mechanism of heterologous receptor regulation of lifr signaling occurring at ser-1044. | SIGNOR-32757 |
Q9Y572 | P09622 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we show that RIP3 activates the pyruvate dehydrogenase complex (PDC, also known as PDH), the rate-limiting enzyme linking glycolysis to aerobic respiration, by directly phosphorylating the PDC E3 subunit (PDC-E3) on T135. | SIGNOR-266372 |
P05771 | Q92686 | 1 | phosphorylation | up-regulates activity | 0.361 | Phosphorylation of RC3 by PKC alpha, beta, or gamma was stimulated by Ca2+, phospholipid, and diacylglycerol. A single site, Ser36, which is adjacent to the predicted calmodulin (CaM)-binding domain, was phosphorylated by these enzymes. Phosphorylation of RC3 by PKC or PKM, a protease-degraded PKC, was inhibited by CaM. The effect of CaM apparently targets at RC3, as phosphorylation of protamine sulfate by PKM was not inhibited by CaM. | SIGNOR-248914 |
P27361 | Q08499 | 1 | phosphorylation | down-regulates | 0.252 | These straddle the target residue, ser(579), for erk2 phosphorylation of pde4d3. Mutation of either or both of these docking sites prevented erk2 from being co-immunoprecipitated with pde4d3, ablated the ability of epidermal growth factor to inhibit pde4d3 through erk2 action in transfected cos cells, and attenuated the ability of erk2 to phosphorylate pde4d3 in vitro. | SIGNOR-77578 |
Q8IWA4 | Q9UKV5 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.309 | Gp78 induces ubiquitylation and proteasomal degradation of Mfn1 and Mfn2. | SIGNOR-272886 |
P12931 | P51636 | 1 | phosphorylation | down-regulates | 0.676 | Here, we show that cav-2 is phosphorylated at both tyrosines 19 and 27. We reconstituted this phosphorylation event by recombinantly coexpressing c-src and cav-2.Further functional analysis revealed that tyrosine phosphorylation of cav-2 has no effect on its targeting to lipid rafts, but clearly disrupts the hetero-oligomerization of cav-2 with cav-1. | SIGNOR-129961 |
Q07002 | P41181 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.26 | CDK18 controls AQP2 through phosphorylation at serine 261 and STUB1-mediated ubiquitination. |We had previously observed that a decrease in the phosphorylation of AQP2 at S261 is associated with a decrease in its poly-ubiquitination and an increase in its abundance | SIGNOR-264562 |
Q9P035 | P49327 | 1 | chemical activation | up-regulates activity | 0.2 | Very long-chain fatty acids are produced through a four-step cycle. However, the 3-hydroxyacyl-CoA dehydratase catalyzing the third step in mammals has remained unidentified. Mammals have four candidates, HACD1-4, based on sequence similarities to the recently identified yeast Phs1, although HACD3 and HACD4 share relatively weak similarity. We demonstrate that all four of these human proteins are indeed 3-hydroxyacyl-CoA dehydratases, | SIGNOR-267762 |
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