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 |
|---|---|---|---|---|---|---|---|
Q07666 | Q9ULB1 | 1 | post transcriptional regulation | up-regulates activity | 0.332 | Activity-dependent alternative splicing of Nrxn1 requires the KH-domain RNA binding protein SAM68 which associates with RNA response elements in the Nrxn1 pre-mRNA. Our findings uncover SAM68 as a key regulator of dynamic control of Nrxn1 molecular diversity and activity-dependent alternative splicing in the central nervous system. | SIGNOR-269057 |
P07949 | Q16539 | 1 | phosphorylation | up-regulates | 0.332 | Dually phosphorylated on thr-180 and tyr-182 by the map2ks map2k3/mkk3, map2k4/mkk4 and map2k6/mkk6 in response to inflammatory citokines, environmental stress or growth factors, which activates the enzyme. | SIGNOR-40493 |
Q9HC98 | P40763 | 1 | phosphorylation | up-regulates activity | 0.332 | Our data also show that NEK6 interacts with STAT3, an oncogenic transcription factor, and phosphorylates STAT3 on Ser(727), which is important for transcriptional activation. These results demonstrate that NEK6 interacts with and phosphorylates STAT3, an event that could play an important role in oncogenesis. For the maximal activation of STAT3 signaling, phosphorylation of both Tyr705 and Ser727 is required. Phosphorylation of Tyr705 induces dimerization, nuclear translocation, and DNA binding of the STAT3 protein, whereas phosphorylation of Ser727 is important for transcriptional activation. | SIGNOR-273902 |
Q9Y463 | Q99801 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.332 | In addition, an in vitro kinase assay showed that DYRK1B phosphorylated NKX3.1 at serine 185, a residue critical for NKX3.1 steady-state turnover. | SIGNOR-279610 |
Q9UJ99 | P35222 | 1 | binding | up-regulates activity | 0.332 | At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin | SIGNOR-265860 |
P55795 | Q15554 | 1 | post transcriptional regulation | down-regulates quantity | 0.332 | During neuronal differentiation, use of an alternative splice site on the rat telomere repeat-binding factor 2 (TRF2) mRNA generates a short TRF2 protein isoform (TRF2-S) capable of derepressing neuronal genes. However, the RNA-binding proteins (RBPs) controlling this splicing event are unknown. Here, using affinity pull-down analysis, we identified heterogeneous nuclear ribonucleoproteins H1 and H2(HNRNPH) as RBPs specifically capable of interacting with the spliced RNA segment (exon 7) of Trf2 pre-mRNA. HNRNPH proteins prevent the production of the short isoform of Trf2 mRNA, as HNRNPH silencing selectively elevates TRF2-S levels. | SIGNOR-266806 |
O14965 | Q92974 | 1 | phosphorylation | down-regulates activity | 0.332 | The mitotic kinases Aurora A/B and Cdk1/Cyclin B phosphorylate GEF-H1, thereby inhibiting GEF-H1 catalytic activity. | SIGNOR-276061 |
Q13464 | Q9UPT6 | 1 | phosphorylation | up-regulates | 0.332 | Identification of rock1 as an upstream activator of the jip-3 to jnk signaling axis in response to uvb damage. phosphorylation of jip-3 by rock1 was crucial for the recruitment of jnk. Inhibition of the activity of rock1 in keratinocytes resulted in decreased activation of the jnk pathway and thus a reduction in apoptosis. | SIGNOR-134588 |
P0DP23 | P55040 | 1 | binding | up-regulates activity | 0.332 | Inhibition of voltage-gated calcium channels by Gem requires GTP and calmodulin binding, but not phosphorylation of serine 261 or 289. Calmodulin binding in the C-terminal extension of Gem is required for maximal inhibition of HVA Ca2+ channels by ectopically expressed Gem, as determined by measurement of electrical activity in primary neurons and by Ca2+-evoked secretion in PC12 cells. | SIGNOR-261726 |
Q00535 | F7VJQ1 | 1 | phosphorylation | up-regulates quantity | 0.332 | Cdk5 phosphorylated PrP induces the aggregation of non phosphorylated PrP.|Together, these results indicate that S43 is a major Cdk5 phosphorylation site in PrP. | SIGNOR-278920 |
O43541 | Q96FA3 | 1 | binding | up-regulates | 0.332 | Mad6-pellino-1 interaction abrogated signaling mediated by a complex of irak1. | SIGNOR-185128 |
P68400 | P52952 | 1 | phosphorylation | up-regulates activity | 0.332 | Mutational analysis and in vitro kinase assays suggested that this 40-kDa Csx/Nkx2.5 kinase is a catalytic subunit of casein kinase II (CKII) that phosphorylates the serine residue between the first and second helix of the homeodomain. This CKII site is phosphorylated in vivo. CKII-dependent phosphorylation of the homeodomain increased Csx/Nkx2. 5 DNA binding. Serine-to-alanine mutation at the CKII phosphorylation site reduced transcriptional activity when the carboxyl-terminal repressor domain was deleted. | SIGNOR-250924 |
P62136 | P27708 | 1 | dephosphorylation | down-regulates activity | 0.332 | Cyclic AMP-dependent protein kinase phosphorylates two serine residues on the protein termed sites 1 and 2| Site 1: Arg-Leu-Ser(P)-Ser-Phe-Val-Thr-Lys Site 2: Ile-His-Arg-Ala-Ser(P)-Asp-Pro-Gly-Leu-Pro-Ala-Glu-Glu-Pro-Lys | Both phosphorylation and activation can be reversed using purified preparations of the catalytic subunits of protein phosphatases 1- and -2A, and inactivation also correlates better with dephosphorylation of site 1 rather than site 2. | SIGNOR-263741 |
O95477 | Q96KG7 | 2 | binding | up-regulates activity | 0.332 | ABCA1 and MEGF10 interact during engulfment. MEGF10 function can be modulated by the ATP binding cassette transporter ABCA1, ortholog to CED-7. by the combined use of cellular and biochemical approaches we provide evidence that ABCA1 and MEGF10 interact at the molecular level. | SIGNOR-265164 |
Q14790 | P49810 | 1 | cleavage | up-regulates activity | 0.332 | In decreasing order of activity, caspase-8, -3, -1, -6 and -7 proteolysed PS2 at the recognition site D326SYD329. | SIGNOR-261752 |
P67775 | P37840 | 1 | dephosphorylation | down-regulates activity | 0.332 | α-Synuclein (α-Syn) is a key protein that accumulates as hyperphosphorylated aggregates in pathologic hallmark features of Parkinson's disease (PD) and other neurodegenerative disorders. Phosphorylation of this protein at serine 129 is believed to promote its aggregation and neurotoxicity, suggesting that this post-translational modification could be a therapeutic target. Here, we demonstrate that phosphoprotein phosphatase 2A (PP2A) dephosphorylates α-Syn at serine 129 | SIGNOR-248635 |
Q96KG7 | O95477 | 2 | binding | up-regulates activity | 0.332 | ABCA1 and MEGF10 interact during engulfment. MEGF10 function can be modulated by the ATP binding cassette transporter ABCA1, ortholog to CED-7. by the combined use of cellular and biochemical approaches we provide evidence that ABCA1 and MEGF10 interact at the molecular level. | SIGNOR-265165 |
Q12923 | P04626 | 1 | dephosphorylation | down-regulates activity | 0.332 | Since a previous report showed PTPN13 may dephosphorylate ErbB2 directly, we also examined levels of phospho-ErbB2 (tyr 1248), and we also observed a small effect in the presence of wild-type PTPN13 (XREF_FIG).|The fact that both ErbB2 and H-RasV12 were potentiated by PTPN13 loss and PTPN13 inhibited MAP kinase signaling downstream of multiple oncogenes (ErbB2, EGFR, H-RasV12), suggest that the phosphatase target that inhibits MAP kinase signaling may not only be limited to ErbB2 tyrosine 1248. | SIGNOR-277087 |
P49841 | O75925 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.332 | We discovered a ubiquitin E3 ligase, HECTD2, which ubiquitinated and mediated the degradation of PIAS1, thus increasing inflammation in an experimental pneumonia model. We found that GSK3β phosphorylation of PIAS1 provided a phosphodegron for HECTD2 targeting. | SIGNOR-276923 |
Q9Y261 | P80370 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.332 | Taken together, these data suggest that Foxa-2 is a direct transcriptional activator of the Pref-1 gene. | SIGNOR-254971 |
Q13976 | Q9NS28 | 1 | phosphorylation | up-regulates activity | 0.332 | Cyclic AMP- and cyclic GMP-dependent kinases (PKA, PKG) inhibit the interaction of RGS18 and 14-3-3 by phosphorylating S216. S216 phosphorylation might activate PP1 leading to dephosphorylation of both 14-3-3 binding sites, S49 and S218, and detachment of 14-3-3. Removal of 14-3-3 activates RGS18 to turn off Gq signaling thus contributing to platelet inhibition. | SIGNOR-273785 |
P05129 | Q99418 | 1 | phosphorylation | down-regulates activity | 0.332 | ARNO is phosphorylated in vivo by PKC on a single serine residue, S392, located within the carboxy-terminal polybasic domain. Mutation of S392 to alanine does not prevent ARNO-mediated actin rearrangements, suggesting that phosphorylation does not lead to ARNO activation [6]. Here, we report that phosphorylation negatively regulates ARNO exchange activity through a 'PH domain electrostatic switch'. | SIGNOR-249025 |
P49841 | Q16665 | 1 | phosphorylation | down-regulates activity | 0.332 | Glycogen synthase kinase 3 \u03b2 (GSK3\u03b2) phosphorylates HIF-1\u03b1 at three serine residues (Ser-551, Ser-555, and Ser-589) located within its oxygen-dependent degradation domain (ODDD) [12] (Figure 5). Phosphorylation at these residues by GSK3\u03b2 enhances HIF-1\u03b1 degradation in a pVHL-independent manner, resulting in suppression of the HIF-1 activity [12,13].|Phosphorylation at these residues by GSK3beta enhances HIF-1alpha degradation in a pVHL independent manner, resulting in suppression of the HIF-1 activity , ]. | SIGNOR-278294 |
P17612 | Q12802 | 1 | phosphorylation | up-regulates | 0.332 | Using a combination of biochemical, enzymatic, and immunofluorescence techniques, we show that the anchoring protein contributes to pkd activation in two ways: it recruits an upstream kinase pkceta and coordinates pka phosphorylation events that release activated protein kinase d. Thus, akap-lbc synchronizes pka and pkc activities in a manner that leads to the activation of a third kinase. | SIGNOR-129345 |
P68400 | Q9BRS2 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.332 | Casein kinase 2 (CK2) phosphorylates RIOK1 at T410, which stabilizes RIOK1 by antagonizing K411 methylation and impeding the recruitment of FBXO6 to RIOK1. | SIGNOR-273630 |
Q9UNE7 | P06730 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.332 | This collaborative activity of cIAP1 and CHIP directs eIF4E toward degradation, controlling its levels and suppressing tumorigenesis.|We next sought to investigate whether eIF4E ubiquitination is enhanced by the collaborative activity of cIAP1 and CHIP, which we define as both the E3 ligase activity of cIAP1 alone and the E3 ligase activity of cIAP1 and CHIP together. | SIGNOR-278669 |
O00308 | Q9H074 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.332 | Here, we show that the E6AP carboxyl terminus (HECT)-type ubiquitin ligase WW domain-containing protein 2 (WWP2), a homolog of the HECT-type ubiquitin ligase WWP1, interacts with and targets Paip1 for ubiquitination and proteasomal degradation. | SIGNOR-272842 |
P42345 | P53396 | 1 | phosphorylation | up-regulates activity | 0.332 | Biochemical studies indicated that mTOR directly and specifically phosphorylated ACL on Ser 455 in vitro. | SIGNOR-278962 |
P43115 | P00533 | 1 | relocalization | up-regulates quantity | 0.332 | These results demonstrate that PGE2 -mediated EGFR nuclear translocation requires the EP3 receptor. | SIGNOR-278884 |
Q96PU4 | P24864 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.332 | 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-271886 |
Q13627 | P46527 | 1 | phosphorylation | up-regulates activity | 0.332 | DYRK1A phosphorylates p27 Kip1 at Ser10 in primary neurons and in vivo.|Thus, our results identify DYRK1A as the predominant kinase that phosphorylates and stabilizes p27Kip1 during neuronal differentiation. | SIGNOR-278250 |
P23771 | Q9UI32 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.332 | Thus, GATA3 contributes to the elevated expression of GLS2 in luminal-subtype breast cancers. | SIGNOR-268034 |
Q13131 | O15360 | 1 | phosphorylation | up-regulates activity | 0.332 | FANCA was phosphorylated by AMPK at S347 and phosphorylation increased with MMC treatment. MMC-induced FANCD2 monoubiquitination and nuclear foci formation were compromised in a U2OS cell line that stably overexpressed the S347A mutant form of FANCA compared to wild-type FANCA-overexpressing cells, indicating a requirement for FANCA phosphorylation at S347 for proper activation of the FA/BRCA pathway. | SIGNOR-277264 |
Q96AQ6 | P40424 | 1 | binding | down-regulates activity | 0.331 | This protein that we have termed hematopoietic PBX-interacting protein (HPIP) is mainly localized in the cytosol and in small amounts in the nucleus. The region of PBX that interacts with HPIP includes both the homeodomain and immediate N-terminal flanking sequences. Strikingly, electrophoretic mobility shift assays revealed that HPIP inhibits the ability of PBX-HOX heterodimers to bind to target sequences. | SIGNOR-273666 |
Q99523 | P02647 | 1 | binding | up-regulates quantity | 0.331 | Here, we identified the pro-neurotrophin receptor sortilin as major endocytic pathway for clearance of APOE/Aβ complexes in neurons. Sortilin binds APOE with high affinity. Lack of receptor expression in mice results in accumulation of APOE and of Aβ in the brain and in aggravated plaque burden. Sortilin interacts with all human APOE isoforms. | SIGNOR-273722 |
Q9NRM7 | P61981 | 1 | phosphorylation | up-regulates | 0.331 | Phosphorylation of 14-3-3_ on s59 by lats2. Ser(58) phosphorylation and lys(49) acetylation of 14-3-3_ occur in a coordinated time-dependent manner to regulate 14-3-3_ homodimerization. 14-3-3_ ser(58) phosphorylation is required for star interactions under control conditions, | SIGNOR-205247 |
Q9H0K1 | Q15078 | 1 | phosphorylation | down-regulates | 0.331 | Sik2 phosphorylates p35 at ser 91, to trigger its ubiquitylation by pja2 and promote insulin secretion. _-cell knockout of sik2 leads to accumulation of p35 and impaired secretion | SIGNOR-204648 |
P15173 | P38936 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.331 | P21 is regulated by MyoD and myogenin in normal muscle cells and the inactivation of these factors in RMS cells contributes to the silencing of p21 in RMS cells | SIGNOR-251575 |
O00141 | P10636 | 1 | phosphorylation | down-regulates | 0.331 | Second, sgk1 indirectly depolymerized mts through the phosphorylation of tau at ser214 | SIGNOR-161288 |
Q9Y314 | P19235 | 1 | ubiquitination | up-regulates activity | 0.331 | Erythropoietin receptors associate with a ubiquitin ligase, p33RUL, and require its activity for erythropoietin-induced proliferation. This receptor-associated ubiquitin ligase, RUL, co-precipitated with EpoR from mammalian cells and mediated ubiquitination of EpoR. RUL mediates EpoR ubiquitination in COS7 cells and is inducibly ubiquitinated after Epo treatment. This observation is consistent with the lack of effects on EpoR stability by RUL-mediated ubiquitination in COS7 cells (Fig. 4). | SIGNOR-271477 |
O00257 | O60315 | 1 | sumoylation | down-regulates quantity by destabilization | 0.331 | Pc2 can act directly as an E3 ligase for SIP1 sumoylation.SIP1 sumoylation having a negative effect on its repression of E-cadherin transcription. | SIGNOR-268955 |
Q9BV68 | P38936 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.331 | E3 ubiquitin ligase RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation.We showed that RNF126 interacts with p21 and RNF126 overexpression increased p21 protein ubiquitination in an E3 ligase activity-dependent manner. | SIGNOR-272033 |
Q96J02 | Q8NEA6 | 1 | ubiquitination | down-regulates quantity | 0.331 | Itch promotes proteolytic degradation of Glis3.|Since Itch interacts with and ubiquitinates Glis3, it was of interest to determine which regions were necessary for Itch directed degradation of Glis3. | SIGNOR-278653 |
P61077 | Q8NEG5 | 1 | binding | up-regulates activity | 0.331 | MEX can act as an E3, Ub (ubiquitin) ligase, through the E2, Ub-conjugating enzymes UbcH5a, UbcH5c or UbcH6. A region of MEX that contains the RING fingers and the ZZ zinc finger was required for interaction with UbcH5a and MEX self-association, whereas the SWIM domain was critical for MEX ubiquitination. The expression of MEX promoted apoptosis that was induced through Fas, DR (death receptor) 3 and DR4 signalling, but not that mediated by the BH3 (Bcl-2 homology 3)-only protein BimEL or the chemotherapeutic drug adriamycin. | SIGNOR-271557 |
O15111 | P42224 | 1 | phosphorylation | up-regulates activity | 0.331 | In addition, IKK\u03b1 also phosphorylated STAT1 in a type I IFN-independent manner [Fig 8, a dashed line (B)]. | SIGNOR-279732 |
Q00005 | O15530 | 1 | binding | down-regulates activity | 0.331 | Here, we show that PPP2R2B, encoding the B55² regulatory subunit of the PP2A complex, is epigenetically inactivated by DNA hypermethylation in colorectal cancer. B55²-associated PP2A interacts with PDK1 and modulates its activity toward Myc phosphorylation. | SIGNOR-243511 |
Q9UNE7 | P56545 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.331 | Our data showed that CHIP depletion resulted in up-regulation of the steady-state level of CtBP2 ( Fig. 1 B) and that CHIP ubiquitinated CtBP2 for proteasomal degradation ( Fig. 3 A). | SIGNOR-278722 |
Q86U44 | P00533 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.331 | Here we find that METTL3 promotes translation of certain mRNAs including epidermal growth factor receptor (EGFR) and the Hippo pathway effector TAZ in human cancer cells. | SIGNOR-265954 |
P49841 | Q96G01 | 1 | phosphorylation | up-regulates activity | 0.331 | Therefore, at least Ser585 and Thr597 in BICD1 are important phosphorylation sites for BICD1 to exert its functions, and GSK-3β-dependent phosphorylation is required for the interaction of BICD1 with dynein. | SIGNOR-262744 |
Q9UIJ5 | P24588 | 1 | palmitoylation | up-regulates activity | 0.331 | Here, we report that the recycling endosome-resident palmitoyl acyltransferase DHHC2 interacts with and palmitoylates AKAP79/150 to regulate these plasticity signaling mechanisms | SIGNOR-261289 |
Q13555 | Q15746 | 1 | phosphorylation | down-regulates activity | 0.331 | Phosphorylation of MLC kinase by CaM protein kinase II increased the dissociation constant of MLC kinase for calmodulin about 10 times without changing the Vmax. The location of the phosphorylation sites was identified by isolating and sequencing the tryptic phosphopeptides of MLC kinase. The preferred site was identified as serine 512 and the second site as serine 525. These sites are the same as the sites phosphorylated by cAMP-dependent protein kinase. | SIGNOR-250700 |
Q8TEU7 | P01111 | 1 | guanine nucleotide exchange factor | up-regulates | 0.331 | Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras. | SIGNOR-183799 |
P49840 | P05412 | 1 | phosphorylation | down-regulates | 0.331 | Phosphorylation of recombinant human c-jun proteins in vitro by gsk-3 decreases their dna-binding activity. | SIGNOR-21780 |
Q9UGI0 | Q15672 | 1 | deubiquitination | down-regulates activity | 0.331 | Trabid inhibits Twist1 activity by cleaving RNF8-mediated Twist1 K63-linked ubiquitination | SIGNOR-273502 |
P84022 | P55317 | 1 | binding | down-regulates activity | 0.331 | TGF-beta represses transcription of pulmonary surfactant protein-B gene in lung epithelial cells. Repression is mediated by SMAD3 through interactions with NKX2.1 and FOXA1, two key transcription factors that are positive regulators of SpB transcription. In this study, we found that SMAD3 interacts through its MAD domains, MH1 and MH2 with NKX2.1 and FOXA1 proteins. The sites of interaction on NKX2.1 are located within the NH2 and COOH domains, known to be involved in transactivation function. | SIGNOR-254168 |
P28482 | Q9UPT5 | 1 | phosphorylation | up-regulates | 0.331 | Erk1/2 phosphorylation enhances the binding of exo70 to other exocyst components and promotes the assembly of the exocyst complex in response to epidermal growth factor (egf) signaling. | SIGNOR-197543 |
P53350 | Q13188 | 1 | phosphorylation | down-regulates activity | 0.331 | We conclude that TRIM69A promotes multi-site phosphorylation of MST2.We demonstrate that TRIM69 stimulates formation of an MST2-PLK1 complex and promotes phosphorylation of MST2 at S15, a known PLK1 site. PLK1-mediated MST2 phosphorylation at S15 is necessary for subsequent phosphorylation of NEK2A to dissociate c-NAP1 from daughter centrioles (7). Thus, we provide a new molecular mechanism by which TRIM69 promotes MST2- and PLK1-mediated centrosome disjunction. | SIGNOR-277904 |
P17252 | Q01844 | 1 | phosphorylation | down-regulates activity | 0.331 | Here we report thatews, a nuclearrna-bindingprooncoprotein, contains an iq domain, is phosphorylated byproteinkinase c, and interacts with calmodulin. Interestingly, pkc phosphorylation of ews inhibits its binding to rna homopolymers, and conversely,rna binding to ews interferes with pkc phosphorylation./ these data indicate that ews contains an iq domain with ser266 acting as the primary site for pkc phosphorylation. | SIGNOR-52850 |
Q96K19 | Q14571 | 1 | polyubiquitination | down-regulates activity | 0.331 | In summary, here we present evidence that RNF170 is an E3 ligase that mediates IP3 receptor ubiquitination and processing by the UPP and that it is recruited to activated IP3 receptors by the erlin1/2 complex to which it is constitutively bound. | SIGNOR-271914 |
Q14012 | P29475 | 1 | phosphorylation | down-regulates activity | 0.331 | It was found that purified recombinant nNOS was phosphorylated by CaM-K Ialpha, CaM-K IIalpha, and CaM-K IV at Ser847 in vitro. Replacement of Ser847 with Ala (S847A) prevented phosphorylation by CaM kinases. Phosphorylated recombinant wild-type nNOS at Ser847 (approximately 0.5 mol of phosphate incorporation into nNOS) exhibited a 30% decrease of Vmax with little change of both the Km for L-arginine and Kact for CaM relative to unphosphorylated enzyme. The activity of mutant S847D was decreased to a level 50-60% as much as the wild-type enzyme. The decreased NOS enzyme activity of phosphorylated nNOS at Ser847 and mutant S847D was partially due to suppression of CaM binding, but not to impairment of dimer formation which is thought to be essential for enzyme activation. | SIGNOR-250614 |
O15169 | P36894 | 1 | ubiquitination | down-regulates | 0.331 | Other proteins, such as the serine/threonine kinase fused (fu), can function in concert with the e3 ligase smurf to regulate ubiquitination and proteolysis of the bmp receptor | SIGNOR-195552 |
Q13315 | P15374 | 1 | phosphorylation | up-regulates activity | 0.331 | Mechanistically, in response to DNA damage, the deubiquitinase UCHL3 is phosphorylated and activated by ATM. | SIGNOR-279794 |
Q02156 | P29474 | 1 | phosphorylation | down-regulates activity | 0.331 | The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites | SIGNOR-251632 |
P50281 | P00748 | 1 | cleavage | down-regulates quantity by destabilization | 0.331 | The data presented in this study show for the first time the degradation of Factor XII of the blood clotting system by matrix metalloproteinases. MMP-12, MMP-13, and MMP-14 cleave at Gly376Leu377|However, no activity of Factor XII can be observed after MMPinduced cleavage. | SIGNOR-263610 |
P49593 | Q9UQM7 | 1 | dephosphorylation | down-regulates | 0.331 | Ppm1f specifically dephosphorylates the phospho-thr-286 in autophosphorylated camkii substrate and thus deactivates the camkii in vitro. | SIGNOR-124309 |
P17612 | Q01082 | 1 | phosphorylation | down-regulates activity | 0.331 | Short C-terminal splice variant of betaII-spectrin (betaIISigma2) is a substrate for phosphorylation. protein kinase A phosphorylates Thr-2159. Mammalian alphaII- and betaII-spectrin subunits form dimers that associate head to head with high affinity to form tetramers In vitro, protein kinase A phosphorylation of an active fragment of betaIISigma2 greatly reduced its interaction with alphaII-spectrin at the tetramerization site. | SIGNOR-250054 |
P08581 | Q92990 | 1 | relocalization | down-regulates | 0.331 | Significantly, nonphosphorylated hgf receptor prevents fap68 from stimulating p70s6k. fap68 binding to met requires the last 30 amino acids of the c-terminal tail, which are unique to the hgf receptor. | SIGNOR-110726 |
Q8TCJ0 | O00165 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.331 | FBXO25 encodes an orphan F-box protein that determines the substrate specificity of the SCF (SKP1-CUL1-F-box)(FBXO25) ubiquitin ligase complex. An unbiased screen uncovered the prosurvival protein HCLS1-associated protein X-1 (HAX-1) as the bona fide substrate of FBXO25 that is targeted after apoptotic stresses. Protein kinase Cdelta (PRKCD) initiates this process by phosphorylating FBXO25 and HAX-1, thereby spatially directing nuclear FBXO25 to mitochondrial HAX-1. | SIGNOR-275563 |
P06493 | P78549 | 1 | phosphorylation | up-regulates activity | 0.33 | The main cell cycle kinase Cdk1 directly phosphorylates and activates the trehalase Nth1 to trigger the flux of storage carbohydrates into central carbon metabolism. | SIGNOR-278916 |
Q92835 | Q9Y4K3 | 1 | binding | down-regulates activity | 0.33 | Of note, SHIP1 was associated with TRAF6 in co-transfected HEK293T cells (Fig. 6A). Moreover, SHIP1 overexpression suppressed TRAF6 autoubiquitination in a dose-dependent manner | SIGNOR-261429 |
O14920 | Q92905 | 1 | phosphorylation | down-regulates activity | 0.33 | Overexpression of IKKalpha or IKKbeta leads to enhanced phosphorylation of CSN5, the catalytic subunit for CSN deneddylase activity. Mutational analyses have revealed that phosphorylation at serine 201 and threonine 205 of CSN5 impairs CSN-mediated deneddylation activity in vitro. | SIGNOR-275519 |
Q15583 | Q9H0M0 | 1 | binding | up-regulates | 0.33 | We demonstrate that tiul1 degrades not only the activated type i receptor in association with smad7 but also smad2 in association with tgif.the steady-state levels of tgif are not affected by tiul1, but the interaction of tiul1 with tgif allows this ubiquitin ligase to target smad2 for degradation. | SIGNOR-128854 |
P31946 | P78362 | 1 | binding | down-regulates | 0.33 | 14-3-3 interacts with akt-phosphorylated srpk2 and blocks its nuclear translocation. kt phosphorylates SRPK2 on Thr-492 and promotes its nuclear translocation leading to cyclin D1 up-regulation, cell cycle reentry, and neuronal apoptosis. In addition, SRPK2 phosphorylates SC35 and, thus, inactivates p53, resulting in cyclin D1 up-regulation. 14-3-3 binding to SRPK2, regulated by Akt phosphorylation, inhibits these events. | SIGNOR-186767 |
P78527 | P14859 | 1 | phosphorylation | down-regulates | 0.33 | Through a similar strategy, t226 and s232 were characterized as the dna-pk phosphorylation sites | SIGNOR-53258 |
P05771 | P19484 | 1 | phosphorylation | up-regulates activity | 0.33 | This occurs following PKCβ phosphorylation of TFEB on three serine residues located in its last 15 amino acids. This post-translational modification stabilizes and increases the activity of this transcription factor. | SIGNOR-255315 |
P39900 | P00748 | 1 | cleavage | down-regulates quantity by destabilization | 0.33 | The data presented in this study show for the first time the degradation of Factor XII of the blood clotting system by matrix metalloproteinases. MMP-12, MMP-13, and MMP-14 cleave at Gly376Leu377|However, no activity of Factor XII can be observed after MMPinduced cleavage. | SIGNOR-263611 |
P53355 | O95786 | 1 | phosphorylation | down-regulates activity | 0.33 | DAPK1 also phosphorylates the N-terminal serine at position 8 (S8) of RIG-I, which is also reported to undergo phosphorylation by PKC-\u03b1/\u03b2 to suppress TRIM25-mediated RIG-I ubiquitination, thereby negatively regulating RIG-I activity (84). | SIGNOR-279519 |
P49841 | Q15910 | 1 | phosphorylation | down-regulates activity | 0.33 | GSK3beta phosphorylates EZH2 at Ser363 and Thr367 in vitro, and activating GSK3beta upregulates Thr367 phosphorylationin vivo. | SIGNOR-278176 |
P11362 | P18669 | 1 | phosphorylation | up-regulates activity | 0.33 | Nevertheless, these data suggest that FGFR1 dependent tyrosine phosphorylation " further " enhances PGAM1 activation.|Phosphorylation of PGAM1 WT by FGFR1 resulted in a significant increase in the amount of bound 2,3-BPG analogue, whereas substitution of PGAM1 Y26 abolished enhanced binding of cofactor in the presence of rFGFR1 (XREF_FIG). | SIGNOR-279175 |
P00533 | Q13501 | 1 | phosphorylation | down-regulates activity | 0.33 | Here we found that EGFR-stimulated phosphorylation of SQSTM1 at tyrosine 433 induces dimerization of its UBA domain, which disturbs the sequestration function of SQSTM1 and causes autophagic flux blocking. | SIGNOR-277500 |
P07858 | P02818 | 1 | cleavage | down-regulates quantity by destabilization | 0.33 | This study has been undertaken to compare the degradation of BGP by the cysteine proteinases cathepsins L, B, H, S, and the aspartic proteinase cathepsin D. Cathepsins B, L, H, and S readily cleave BGP at the G7-A8 bond; cathepsin L also cleaves at R43-R44; cathepsin B also cleaves at R44-F45; and cathepsin D cleaves only at A41-Y42. | SIGNOR-256318 |
P07949 | Q8N4X5 | 1 | phosphorylation | up-regulates activity | 0.33 | RET/PTC induced robust tyrosine phosphorylation of XB130, which promoted its subsequent association with the p85alpha subunit of phosphatidylinositol 3-kinase (PI 3-kinase). We identified tyrosine 54 of XB130 as the major target of RET/PTC-mediated phosphorylation and a critical binding site for the SH2 domains of p85alpha. | SIGNOR-263192 |
P18031 | P11274 | 1 | dephosphorylation | down-regulates | 0.33 | These results illustrate selectivity in the effects of ptps in a cellular context and suggest that ptp1b may function as a specific, negative regulator of p210 bcr-abl signalling in vivo. | SIGNOR-56818 |
Q5S007 | P61006 | 1 | phosphorylation | up-regulates activity | 0.33 | In a screen for Rab8A kinases we identify TAK1 and MST3 kinases that can efficiently phosphorylate the Switch II residue Threonine72 (Thr72) in a similar manner as LRRK2 in vitro. |Overall our data suggests that the phosphorylation of Rab8A at Ser111 may influence Switch II-binding by regulators, thus disrupting interactions with its cognate GEF and moderately impairs its interaction with GAPs.|The antagonistic interplay between Ser111 phosphorylation and Thr72 phosphorylation is genetically concordant with how respective mutations in PINK1 and LRRK2 cause Parkinson’s disease | SIGNOR-260267 |
Q15418 | O14745 | 1 | phosphorylation | up-regulates activity | 0.33 | In summary, these results demonstrate that Ras-RSK1 signaling promotes nuclear localization of EBP50.|Specifically, RSK1 phosphorylates EBP50 at threonine 156 (T156) residue in a cell cycle dependent manner, which is important for nuclear translocation of EBP50 to facilitate cellular proliferation and transformation. | SIGNOR-278290 |
Q6ZRV2 | P49674 | 1 | binding | up-regulates quantity | 0.33 | We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates. | SIGNOR-273764 |
Q5S007 | P61026 | 1 | phosphorylation | down-regulates activity | 0.33 | To investigate whether the phosphorylation of Rab10 by LRRK2 is direct, we performed an in vitro kinase assay using recombinant components. Notably, we found that both wt and LRRK2-G2019S, but neither kinase inactive D1994A mutant nor small molecule-inhibited LRRK2, efficiently phosphorylated Rab10, proving a direct kinase-substrate relationship (Figure 2C). Furthermore, incubation of Rab10 with LRRK2 followed by tryptic digestion and MS analysis unambiguously identified T73 as the major phosphorylation site (Figure 2—figure supplement 1B)|In pathogenic conditions, in which LRRK2 is hyperactive, RabGTPases have strongly diminished affinities for GDIs. | SIGNOR-261277 |
P43405 | P68366 | 1 | 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 |
P01009 | P00748 | 1 | binding | down-regulates activity | 0.33 | C1INH is a serine protease inhibitor (serpin) that acts on both the complement pathway and the contact system and is the main inhibitor of the contact system by targeting both FXIIa and PK 9. Additionally, FXIIa can be inhibited by α1‐antitrypsin and plasminogen activator inhibitor‐1 (PAI‐1). | SIGNOR-263515 |
P03956 | Q99075 | 1 | cleavage | up-regulates activity | 0.33 | We have recently reported that HB-EGF is a substrate of MT1-MMP and that removal of the N-terminal fragment of HB-EGFby MT1-MMP converts the former into a hyperactive growthfactor that does not require heparin as a co-factor. | SIGNOR-278096 |
Q9H334 | Q9P283 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.33 | FoxP1 stimulates angiogenesis by repressing the inhibitory guidance protein semaphorin 5B in endothelial cells. | SIGNOR-269050 |
Q9BXM7 | O43318 | 1 | phosphorylation | up-regulates activity | 0.33 | PINK1 also enhances the association between TRAF6 and TAK1, phosphorylates TAK1, and stimulates polyubiquitination of TAK1. | SIGNOR-279644 |
P49841 | P04198 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.33 | Because GSK3\u03b2 phosphorylates Nmyc at T58, we assessed GSK3\u03b2 activation in Dex-treated MB cells. | SIGNOR-279722 |
Q9H0A0 | Q00987 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.33 | NAT10 acetylates p53 at K120 and stabilizes p53 by counteracting Mdm2 action. In addition, NAT10 promotes Mdm2 degradation with its intrinsic E3 ligase activity. | SIGNOR-272405 |
P24941 | Q13118 | 1 | phosphorylation | up-regulates quantity | 0.329 | In this study we have shown that CDK2 phosphorylates KLF10 at residue Ser 206 in vivo and in vitro .|In this study, we have shown that KLF10 protein has tightly controlled expression and that the expression level varies in a cell cycle dependent manner whereby CDK2 up-regulates activity the protein level of KLF10 through interference with the protein 's association with SIAH1. | SIGNOR-278394 |
Q9HCE7 | P08651 | 1 | ubiquitination | down-regulates quantity | 0.329 | In addition, Smurf1 knockdown also blocked the degradation of endogenous NFI-C in response to TGF-beta1 (XREF_FIG).|In particular, Smurf1 and Smurf2 markedly increased the polyubiquitination of NFI-C in the presence of TGF-beta1 (XREF_FIG and XREF_SUPPLEMENTARY). | SIGNOR-278753 |
P11802 | P15173 | 1 | binding | down-regulates | 0.329 | In contrast to cdk2, cyclin d/cdk4 blocks myod activity through an as yet unclear mechanism that may involve direct binding. Cyclin d/cdk4 can also block the activity of myogenin and all mef2 isoforms. | SIGNOR-176530 |
Q92769 | Q5VUA4 | 1 | binding | up-regulates activity | 0.329 | A central domain of TZF is required for repression of AR-mediated transactivation. The results revealed that HDAC2 was coimmunoprecipitated with TZF (Fig. 6A), These results indicate that AR, TZF and HDAC2 form a ternary complex during the repression of AR-mediated transactivation. | SIGNOR-261188 |
Q16512 | P10636 | 1 | phosphorylation | down-regulates | 0.329 | Phosphorylation of tau is regulated by pknthere is a pkn-specific phosphorylation site, ser-320, in mbdsthus pkn serves as a regulator of microtubules by specific phosphorylation of tau, which leads to disruption of tubulin assembly. | SIGNOR-84958 |
P17252 | P05023 | 1 | phosphorylation | down-regulates activity | 0.329 | Parathyroid hormone (PTH) inhibits Na+,K+-ATPase activity through protein kinase C- (PKC) and extracellular signal-regulated kinase- (ERK) dependent pathways and increases serine phosphorylation of the α1-subunit. These results suggest that PTH regulates Na(+),K(+)-ATPase by PKC and ERK-dependent alpha(1)-subunit phosphorylation and that the phosphorylation requires the expression of a serine at the 11 position of the Na(+),K(+)-ATPase alpha(1)-subunit. | SIGNOR-262941 |
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