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 |
|---|---|---|---|---|---|---|---|
Q13237 | P29350 | 1 | phosphorylation | up-regulates activity | 0.2 | PKGII directly phosphorylated and stimulated SHP-1 activity | SIGNOR-276288 |
O75385 | P09467 | 1 | phosphorylation | down-regulates activity | 0.2 | Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown). | SIGNOR-274031 |
P17252 | P35611 | 1 | phosphorylation | up-regulates | 0.2 | These data demonstrate that adducin is a significant in vivo substrate for pkc or other pma-activated kinases in a variety of cells, and that phosphorylation of adducin occurs in dendritic spines that are believed to respond to external signals by changes in morphology and reorganization of cytoskeletal structures. Ser-726 and ser-713 in the c-terminal marcks-related domains of alpha- and beta-adducin, respectively, were identified as the major phosphorylation sites common for pka and pkc. | SIGNOR-43744 |
P49841 | P17947 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | We demonstrate that GSK3β phosphorylates PU.1 at Ser41 and Ser140 leading to its recognition and subsequent ubiquitin-mediated degradation by E3 ubiquitin ligase FBW7. | SIGNOR-277541 |
Q9HCE7 | Q9P2Y5 | 1 | ubiquitination | down-regulates activity | 0.2 | Here we report that UVRAG is ubiquitinated by SMURF1 at lysine residues 517 and 559, which decreases the association of UVRAG with RUBCN and promotes autophagosome maturation. However, the deubiquitinase ZRANB1 specifically cleaves SMURF1-induced K29 and K33-linked polyubiquitin chains from UVRAG, thereby increasing the binding of UVRAG to RUBCN and inhibiting autophagy flux. | SIGNOR-273652 |
Q8N431 | P01111 | 1 | binding | up-regulates | 0.2 | Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras. | SIGNOR-161511 |
Q96RI0 | P09471 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257245 |
Q76L83 | P37231 | 1 | binding | up-regulates activity | 0.2 | ASXL2, which does not bind HP1, promotes differentiation by binding to PPARγ and increasing the level of methylated H3K4, leading to the elevation of PPARγ activity. Our genome-wide analysis confirmed the physiological roles of ASXL1 and ASXL2 in adipogenesis at the molecular level, supporting the hypothesis that ASXL1 is an authentic corepressor of PPARγ, whereas ASXL2 is a PPARγ coactivator, and that together ASXL1 and ASXL2 fine-tune adipogenesis via differential regulation of PPARγ. | SIGNOR-260063 |
P67775 | P19484 | 1 | dephosphorylation | up-regulates activity | 0.2 | MS analysis revealed that PP2A dephosphorylates TFEB at several residues, including Ser-109, Ser-114, Ser-122, and Ser-211, thus facilitating TFEB activation. | SIGNOR-277881 |
P04626 | P04626 | 2 | phosphorylation | up-regulates | 0.2 | Stimulation of these molecules, however, failed to induce efficient cell migration in the absence of neu/erbb2 phosphorylation at tyr 1201 or tyr 1227 | SIGNOR-124860 |
Q8IYT8 | P06733 | 1 | phosphorylation | down-regulates activity | 0.2 | Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown). | SIGNOR-274037 |
Q9Y463 | Q9UKV0 | 1 | phosphorylation | down-regulates | 0.2 | Mirk activated mef2 not through direct phosphorylation of mef2 but by phosphorylation of its inhibitors, the class ii histone deacetylases (hdacs). Mef2 is sequestered by class ii hdacs such as hdac5 and mef2-interacting transcriptional repressor (mitr). Mirk antagonized the inhibition of mef2c by mitr, whereas kinase-inactive mirk was ineffective. Mirk phosphorylates class ii hdacs at a conserved site within the nuclear localization region, reducing their nuclear accumulation in a dose-dependent and kinase-dependent manner | SIGNOR-235813 |
Q13362 | P18846 | 1 | dephosphorylation | up-regulates | 0.2 | We propose that constitutive hyperphosphorylation by ck1/ck2 maintains atf1 in an inactive state that promotes transcriptional repression. Pp2a/b56c antagonizes phosphorylation of atm sites in both creb and atf5 | SIGNOR-167564 |
P04049 | Q13118 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | RAF1 phosphorylates the Thr93 site of KLF10 in vivo. Since the phosphorylation of Thr93 enables KLF10 and PIN1 to bind, it seems likely that RAF-1 will have an effect on KLF10 stability that is similar to that of PIN1.PIN1 facilitates KLF10 protein degradation. ( | SIGNOR-276502 |
Q9BYV8 | Q16665 | 1 | binding | up-regulates activity | 0.2 | We performed these assays in HEK 293T cells and observed CEP41 binds HIF1α under both normoxic and hypoxic conditions. Of note, we found hypoxia induces more expression of HIF1α and increases its binding to CEP41 (Fig 8B and C). Hence, these results suggest CEP41 modulates the activation of HIF1α via a physical interaction | SIGNOR-269662 |
Q9UKB1 | Q13485 | 1 | ubiquitination | up-regulates | 0.2 | We have identified scf(beta-trcp1), a ubiquitin (e3) ligase, as a critical determinant for the protein degradation of smad4 protein. | SIGNOR-123060 |
Q06330 | P52657 | 1 | binding | up-regulates | 0.2 | Rbp interacts with two transcriptional coactivators: dtafii110, a subunit of tfiid, and tfiia to repress transcription. The domain of dtafii110 targeted by rbp is the same domain that interacts with tfiia | SIGNOR-57832 |
Q9Y5H5 | P05556 | 1 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. | SIGNOR-265662 |
P49593 | O14757 | 1 | dephosphorylation | down-regulates activity | 0.2 | As a result, inactivation of Chk1 by POPX2 leads to impaired G1S checkpoint activation and cells are able to proceed from G1 to S phase despite DNA damage.|We also determined that POPX2 can dephosphorylate Chk1Ser317 and -Ser345 and is a potential regulator of Chk1 function in the cell. | SIGNOR-276988 |
P05091 | O15379 | 1 | binding | up-regulates activity | 0.2 | Consistent with previous data, HDAC3 only bound to the ATP6V0E2 promoter in the presence of ALDH2.|Taken together, our data demonstrate that in the macrophages of LDLR-KO or ALDH2 rs671 mutant, AMPK phosphorylates ALDH2 at T356, which enables its nuclear translocation. Once in the nucleus, ALDH2 binds to HDAC3 and suppresses the transcription and protein expression of ATP6V0E2. | SIGNOR-271867 |
Q6A1A2 | P31749 | 1 | phosphorylation | up-regulates | 0.2 | Akt to the plasma membrane where it is phosphorylated and activated by phosphoinositide-dependent kinase (pdk) 1 and pdk2. | SIGNOR-252628 |
P00519 | Q13188 | 2 | phosphorylation | up-regulates | 0.2 | We demonstrate that c-abl kinase phosphorylates mst2 at an evolutionarily conserved site, y81, within the kinase domain. We further show that the phosphorylation of mst2 by c-abl leads to the disruption of the interaction with raf-1 proteins and the enhancement of homodimerization of mst2 proteins. It thereby enhances the mst2 activation and induces neuronal cell death. | SIGNOR-197538 |
P33981 | P33981 | 2 | phosphorylation | down-regulates | 0.2 | We have identified 16 sites of mps1 autophosphorylation in vitro, several of which are required for catalytic activity / mutation of thr675 to alanine increased mps1 catalytic domain activity, and this was reduced to wt levels by mutation to aspartate | SIGNOR-179904 |
Q14493 | Q8IUE6 | 1 | 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-265406 |
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 |
P59595 | P35354 | 1 | transcriptional regulation | up-regulates activity | 0.2 | SARS-CoV N protein activates COX-2 promoter and induces COX-2 protein expression | SIGNOR-262314 |
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 |
P45984 | Q9UIG0 | 1 | phosphorylation | up-regulates | 0.2 | Wstf, a specific component of two chromatin remodeling complexes (swi/snf-type winac and iswi-type wich), was phosphorylated by the stimulation of mapk cascades in vitro and in vivo. Ser-158 residue in the wac (wstf/acf1/cbpq46) domain, located close to the n terminus of wstf, was identified as a major phosphorylation target | SIGNOR-188168 |
Q9UHD2 | O15379 | 1 | phosphorylation | up-regulates activity | 0.2 | The feedback of activation of HDAC3 by TBK1 was able to further enhance IFN production and IFN-STAT activation.|We found that HDAC3 could be phosphorylated by TBK1. | SIGNOR-279662 |
Q13315 | P41236 | 1 | phosphorylation | down-regulates | 0.2 | Atm phosphorylates i-2 on serine 43, leading to the dissociation of the pp1-i-2 complex and the activation of pp1. | SIGNOR-160648 |
O43541 | P49116 | 1 | binding | down-regulates | 0.2 | Smad6 interacts with tak1 and tab1, and smad7 with tab1 | SIGNOR-112636 |
P06241 | P52209 | 1 | phosphorylation | up-regulates activity | 0.2 | 6PGD is phosphorylated at tyrosine (Y) 481 by Src family kinase Fyn. This phosphorylation enhances 6PGD activity by increasing its binding affinity to NADP+ and therefore activates the PPP for NADPH and ribose-5-phosphate, which consequently detoxifies intracellular reactive oxygen species (ROS) and accelerates DNA synthesis. | SIGNOR-265758 |
Q8TAS1 | P02686 | 1 | phosphorylation | down-regulates | 0.2 | Phosphorylation decreased the ability of mbp to polymerize actin and to bundle actin filaments but had no effect on the dissociation constant of the mbp-actin complex or on the ability of ca2+-calmodulin to dissociate the complex. The most significant effect of phosphorylation on the mbp-actin complex was a dramatic reduction in its ability to bind to negatively charged lipid bilayers. Mass spectrometry and peptide sequencing allowed us to identify serine 164 of mbp as the unique site phosphorylated by kis. Phosphorylation of synthetic peptides indicated the importance of the proline residue at position +1. | SIGNOR-143485 |
P49841 | Q05516 | 1 | phosphorylation | up-regulates activity | 0.2 | Taken together, we conclude that S184 and T282 of ZBTB16 may be phosphorylated by GSK3beta in cells under serum starvation condition. | SIGNOR-279618 |
P33176 | Q96N16 | 1 | relocalization | up-regulates activity | 0.2 | Marlin-1 is associated with kinesin-I and suggest that the movement of Marlin-1 is mediated by plus end microtubuledependent molecular motors | SIGNOR-260989 |
P33076 | P15173 | 1 | binding | down-regulates | 0.2 | During early stages of myogenesis, CIITA binds directly to myogenin (MYOG) and inactivates it, preventing MYOG-mediated induction of myogenic genes that are required for muscle differentiation and function | SIGNOR-255111 |
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 |
Q13315 | Q9NZM5 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | PICT-1 S233 and T289 were identified as the key phosphorylation sites in this pathway, as mutating both to alanine abolished UVB-induced increase of PICT-1 phosporylation. Inhibition of PIKKs or ATM (with wortmannin and KU55933, respectively) prevented the agglomeration and degradation of PICT-1, suggesting that ATM is a key regulator of PICT-1. | SIGNOR-273506 |
P12931 | Q96P31 | 1 | phosphorylation | up-regulates activity | 0.2 | Tyrosine phosphorylation of SPAP2a by c-Src and in vitro. Tyrosine-phosphorylated SPAP2 is specifically associated with SH2 domain-containing tyrosine kinases Syk and Zap70 and SH2 domain-containing tyrosine phosphatases SHP-1 and SHP-2. Site-specific mutagenesis studies revealed that tyrosyl residues 650 and 662 embedded in the ITIMs are responsible for the binding of Syk and Zap70 while tyrosyl residues 692 and 722 embedded in the ITIMs are involved in interactions with SHP-1 and SHP-2. | SIGNOR-274008 |
P49840 | O75444 | 1 | phosphorylation | up-regulates | 0.2 | We showed that c-maf and mafb, like mafa, are indeed phosphorylated by gsk-3/ 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. | SIGNOR-159358 |
P24941 | Q86WB0 | 1 | phosphorylation | down-regulates | 0.2 | Moreover, we found cyclin b1/cdk1 to phosphorylate nipa at ser-395 in mitosis. Mutation of both ser-359 and ser-395 impaired effective inactivation of the scfnipa complex, resulting in reduced levels of mitotic cyclin b1 | SIGNOR-154051 |
P50876 | P09874 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | As RNF144A is a newly characterized E3 ubiquitin ligase , ], we next investigated whether RNF144A could promote PARP1 ubiquitination.|RNF144A promotes the proteasomal degradation of PARP1. | SIGNOR-278776 |
P23443 | P07814 | 1 | phosphorylation | up-regulates activity | 0.2 | Our studies reveal an unexpected adipogenic pathway resulting from mTORC1-S6K1 activation of EPRS ( xref ).|These results establish the requirement for mTORC1-activated S6K1 to phosphorylate EPRS at Ser 999 ( xref ). | SIGNOR-279483 |
P78527 | P16403 | 1 | phosphorylation | down-regulates activity | 0.2 | Similarly, DNA-PK-mediated phosphorylation of H1.2 at T146 enhances p53 transcriptional activity by impeding H1.2 binding to p53 and thereby attenuating its suppressive effects on p53 transactivation. | SIGNOR-273834 |
P25098 | P16671 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | We, therefore, propose a pathway by which inhibition of GRK2 in the failing heart prevents CD36 phosphorylation, ubiquitination, and, in turn, induces its proteasomal degradation.|Our data reveal direct phosphorylation of CD36 by GRK2. | SIGNOR-279524 |
Q13535 | Q02952 | 1 | phosphorylation | up-regulates activity | 0.2 | The expression of either ATR-KD or the addition of the ATR kinase inhibitor VE-821 to ATR-WT expressing cells caused AKAP12 to be retained within the cytoplasm.|With UV damage, ATR phosphorylates AKAP12 at S732 which stimulates nuclear translocation of an AKAP12\u2013ATR-pS435 complex that results in enhanced 5\u2032 strand incision of NER. | SIGNOR-278292 |
O94782 | Q8WYQ5 | 1 | deubiquitination | up-regulates quantity by stabilization | 0.2 | Specifically, radiation-induced ATM-dependent phosphorylation of DGCR8 at serine 677 facilitates USP51 to bind, deubiquitinate, and stabilize DGCR8, which leads to the recruitment of DGCR8 and DGCR8's binding partner RNF168 to MDC1 and RNF8 at DSBs. | SIGNOR-277308 |
P07949 | P07949 | 2 | phosphorylation | up-regulates | 0.2 | Mass spectrometric analysis revealed that ret tyr(900) was autophosphorylation site. Tyr900 can partially replace the function of tyr905 as a local switch for kinase activation | SIGNOR-148992 |
P68400 | Q9Y6K1 | 1 | phosphorylation | down-regulates activity | 0.2 | This modulation can be directly attributed to CK2-mediated phosphorylation of Dnmt3a. We also find that CK2-mediated phosphorylation is required for localization of Dnmt3a to heterochromatin. | SIGNOR-276650 |
P10721 | P10721 | 2 | phosphorylation | up-regulates | 0.2 | Identification of tyr-703 and tyr-936 as autophosphorylation sites in c-kit/scfr | SIGNOR-68643 |
P49840 | Q8NHW3 | 1 | phosphorylation | up-regulates activity | 0.2 | 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-159377 |
Q96LB1 | P50148 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257385 |
O14920 | Q96BF3 | 1 | phosphorylation | up-regulates activity | 0.2 | Manipulating the IκB kinase β activity coupled with in vivo and in vitro kinase assays demonstrated that IκB kinase β is a key serine/threonine kinase activated by autophagy stimuli and that it catalyzes phosphorylation of IGPR-1 at Ser220 The subsequent activation of IGPR-1, in turn, stimulates phosphorylation of AMP-activated protein kinase, which leads to phosphorylation of the major pro-autophagy proteins ULK1 and Beclin-1 (BECN1), increased LC3-II levels, and accumulation of LC3 punctum. | SIGNOR-273642 |
P31749 | Q6PIY7 | 1 | phosphorylation | down-regulates activity | 0.2 | We found that Gld2 activity is regulated by site-specific phosphorylation in its disordered N-terminal domain. We identified two phosphorylation sites (S62, S110) where phosphomimetic substitutions increased Gld2 activity and one site (S116) that markedly reduced activity. Using mass spectrometry, we confirmed that HEK 293 cells readily phosphorylate the N-terminus of Gld2. We identified protein kinase A (PKA) and protein kinase B (Akt1) as the kinases that site-specifically phosphorylate Gld2 at S116, abolishing Gld2-mediated nucleotide addition. | SIGNOR-259405 |
P68400 | Q6ZMG9 | 1 | phosphorylation | up-regulates activity | 0.2 | Most of the phosphorylated residues conformed to a consensus motif for phosphorylation by casein kinase 2 (CK2), and treatment of cells with the CK2-specific inhibitor CX-4945 lowered the phosphorylation levels of CERS2, -4, -5, and -6. Phosphorylation of CERS2 was especially important for its catalytic activity, acting mainly by increasing itsVmaxvalue. | SIGNOR-273992 |
Q9BYT3 | O75969 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Differential phosphoproteomic analysis and in vitro kinase assay identified novel phosphorylation substrates of STK33, fibrous sheath components AKAP3 and AKAP4, whose expression levels decreased in testis after deletion of Stk33. | SIGNOR-272955 |
Q9UQM7 | P41134 | 1 | phosphorylation | up-regulates activity | 0.2 | Here we show that CaMKII can directly phosphorylate Beclin 1 at Ser90 to promote K63-linked ubiquitination of Beclin 1 and activation of autophagy. | SIGNOR-277367 |
O75151 | Q16695 | 1 | demethylation | down-regulates activity | 0.2 | PHF2, a jmjC demethylase, is enzymatically inactive by itself, but becomes an active H3K9Me2 demethylase through PKA-mediated phosphorylation. This modification leads to targeting of the PHF2–ARID5B complex to its target promoters, where it removes the repressive H3K9Me2 mark. | SIGNOR-264520 |
P06493 | Q16584 | 1 | phosphorylation | down-regulates activity | 0.2 | Using in vitro kinase assays and phosphomutants, we determined that CDK1 phosphorylates MLK3 on Ser548 and decreases MLK3 activity during mitosis, whereas CDK2 phosphorylates MLK3 on Ser770 and increases MLK3 activity during G1/S and G2 phases. | SIGNOR-277603 |
Q13153 | P15336 | 1 | phosphorylation | down-regulates activity | 0.2 | Overall, our results unequivocally confirmed that Pak1 physically interacts with ATF2 and phosphorylates ATF2 on the Ser62 residue, and this process secludes ATF2 in the cytoplasm. | SIGNOR-279377 |
P05771 | O75144 | 1 | phosphorylation | up-regulates activity | 0.2 | PKCα and PKCβ are required for phosphorylation of ICOSL and ICOSL-mediated cytokine induction | SIGNOR-273797 |
P31751 | O43464 | 1 | phosphorylation | down-regulates | 0.2 | Akt attenuation of the serine protease activity of htra2/omi through phosphorylation of serine 212 | SIGNOR-153327 |
Q8IYT8 | P08237 | 1 | phosphorylation | down-regulates activity | 0.2 | Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown). | SIGNOR-274044 |
Q92630 | P30304 | 2 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Here we describe a novel ubiquitin/proteasome-mediated pathway negatively regulating CDC25A stability, dependent on its phosphorylation by the serine/threonine kinase DYRK2. DYRK2 phosphorylates CDC25A on at least 7 residues, resulting in its degradation independent of the known CDC25A E3 ubiquitin ligases. | SIGNOR-276737 |
Q16620 | Q16620 | 2 | phosphorylation | up-regulates activity | 0.2 | TrkB autophosphorylation occurs on five cytoplasmic tyrosines: Y484, Y670, Y674, Y675, and Y785. Mutagenesis of Y484 inhibits the interaction between Shc and TrkB, and also block the E3DNF-inducible tyrosine phoslphorylation of Shc | SIGNOR-250204 |
P19021 | P01178-PRO_0000020495 | 1 | cleavage | up-regulates activity | 0.2 | Nevertheless, overall the results of this study show that peptide sequence recognition is an important aspect of the interactions of the prohormone substrates prooxytocin (3d) and procalcitonin (7e) with PAM, which is mirrored in the potency of analogous peptidomimetic glycolate inhibitors of the enzyme. | SIGNOR-268551 |
Q15173 | P42574 | 1 | dephosphorylation | up-regulates | 0.2 | Dephosphorylation of caspase-3 at ser150 site by pp2a increased caspase-3 activity,which was essential to trigger apoptosis in neutrophils. | SIGNOR-131435 |
P51812 | Q99683 | 1 | phosphorylation | down-regulates activity | 0.2 | We provide evidence to show that RSK2 inhibits ASK1 by phosphorylating S83, T1109, and T1326 through a novel mechanism in which phospho-T1109/T1326 inhibits ATP binding to ASK1, while phospho-S83 attenuates ASK1 substrate MKK6 binding. | SIGNOR-276463 |
Q05086 | Q6IAA8 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Ube3a regulates mTORC1 signaling by targeting p18, a subunit of the Ragulator. Ube3a ubiquinates p18, resulting in its proteasomal degradation, and Ube3a deficiency in the hippocampus of AS mice induces increased lysosomal localization of p18 and other members of the Ragulator-Rag complex, and increased mTORC1 activity | SIGNOR-256145 |
Q8NEV1 | P00451 | 1 | phosphorylation | down-regulates activity | 0.2 | Our findings suggest that phosphorylation of factors Va and VIIIa by a platelet casein kinase II-like kinase may downregulate the activity of the two cofactors.| Recombinant human factor VIII also showed incorporation of radioactivity in the presence of purified casein kinase II at the acidic NH2-terminal portion of factor VIII light chain (residues 1648 through 1689). Based on all the considerations reported above Se1657 is the most likely candidate within this region capable of incorporation of radioactivity | SIGNOR-263649 |
Q14680 | Q14680 | 2 | phosphorylation | up-regulates | 0.2 | We have mapped no less than 16 autophosphorylation sites including serines, threonines, and a tyrosine residue and show that the phosphorylation of thr167 and ser171 is required for the activation of melk.We have not yet explored the role of autophosphorylation of nine residues in the c-terminal, autoinhibitory domain (fig. 4c). An enticing hypothesis is that these autophosphorylations decrease the inhibitory potency of this domain and thereby contribute to the activation of the kinase. | SIGNOR-141030 |
Q96P68 | P19086 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257310 |
Q14938 | P54756 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8) | SIGNOR-268909 |
Q86YJ5 | P01880 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets. | SIGNOR-271542 |
P17252 | Q07954 | 1 | phosphorylation | up-regulates | 0.2 | Serine and threonine phosphorylation of the low density lipoprotein receptor-related protein by protein kinase calpha regulates endocytosis and association with adaptor moleculesthese results indicate that elimination of serine and threonine phosphorylation sites in the lrp cytoplasmic domain reduces the extent of tyr63 phosphorylation and leads to impaired association with the adaptor protein shc. | SIGNOR-127215 |
Q96GD4 | P84243 | 1 | phosphorylation | up-regulates activity | 0.2 | Phosphorylation at ser-11 (h3s10ph) by aurkb is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. Phosphorylation at ser-11 (h3s10ph) by aurkb is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. | SIGNOR-118890 |
Q13554 | Q9NQC7 | 1 | phosphorylation | up-regulates | 0.2 | Purified camkii phosphorylates cyld on at least three residues (s-362, s-418, and s-772 on the human cyld protein q9nqc7-1) and promotes its deubiquitinase activity. | SIGNOR-91403 |
Q9HC98 | Q13200 | 1 | phosphorylation | up-regulates activity | 0.2 | Seven of these kinases (PIM1/2/3, MAP4K1/2, PKA, and NEK6) directly and robustly phosphorylated recombinant GST-Rpn1 at S361 in vitro (Fig. 3D and SI Appendix, Fig. S3 A and B). | SIGNOR-273894 |
Q00535 | P63167 | 1 | 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 |
Q9UBF6 | P25963 | 1 | ubiquitination | down-regulates activity | 0.2 | SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes. | SIGNOR-271451 |
Q9C0C7 | Q7Z6Z7 | 1 | relocalization | up-regulates activity | 0.2 | AMBRA1 regulates mitophagy at two critical steps. Upon mitophagy stimulation, AMBRA1 mediates the HUWE1 E3 ubiquitin ligase translocation from cytosol to mitochondria (light blue). AMBRA1 acts as a cofactor for HUWE1 E3 ubiquitin ligase activity, favouring its binding to its substrate MFN2 (and maybe other OMM substrates) and targeting it to the proteasome | SIGNOR-272962 |
Q12866 | Q12866 | 2 | phosphorylation | up-regulates | 0.2 | By using a vaccinia virus expression system to express a constitutively activated form of nyk, we identified the major sites of nyk autophosphorylation in tryptic peptide iy749sgdy753y754r. Tyr-749, tyr-753, and tyr-754 in this peptide lie in the activation loop of the kinase domain. | SIGNOR-42914 |
P48729 | O43524 | 1 | phosphorylation | down-regulates | 0.2 | Casein kinase (ck) 1 mediates the hierarchical phosphorylation of foxo3a at s318 and s321, which like foxo1 (rena et al., 2002 blue right-pointing triangle, 2004 blue right-pointing triangle), is probably to enhance its rate of nuclear export | SIGNOR-163676 |
P53350 | Q9H6R7 | 1 | phosphorylation | up-regulates activity | 0.2 | PLK1 Phosphorylates MMAP to Promote Its Interaction with KIF2A and MRE11. we performed in vitro kinase assays followed by mass spectrometry and found that two sites (S686 and S695) in this cluster were phosphorylated. Thus, all of these results are in agreement that this cluster is phosphorylated by PLK1. | SIGNOR-273730 |
P06493 | Q9BTA9 | 1 | phosphorylation | up-regulates activity | 0.2 | Cyclin-dependent kinase 1 (Cdk1) phosphorylates WAC, priming its direct interaction with the polo-box domain of Plk1. Knockdown of WAC compromises Plk1 activity and delays mitotic entry. | SIGNOR-265035 |
P17612 | O95180 | 1 | phosphorylation | down-regulates activity | 0.2 | Here, we identify protein kinase A (PKA) as a molecular switch that allows Gbeta(2)gammax dimers to effect voltage-independent inhibition of Ca(v)3.2 channels. Inhibition requires phosphorylation of Ser(1107), a critical serine residue on the II-III loop of the channel pore protein. S1107A prevents inhibition of unitary currents by recombinant Gbeta(2)gamma(2) dimers but does not disrupt dimer binding nor change its specificity. | SIGNOR-263110 |
Q9P2J3 | P17676 | 1 | binding | down-regulates quantity by destabilization | 0.2 | KLHL9 mediates poly-ubiquitylation of C/EBPβ and C/EBPδ isoforms. We confirmed KLHL9 deletions in an independent cohort and showed that this protein is necessary for Cul3-ligase mediated ubiquitylation and proteasomal degradation of established MES-GBM MRs, C/EBPβ and C/EBPδ. | SIGNOR-272458 |
Q13315 | Q9NRR5 | 1 | phosphorylation | up-regulates activity | 0.2 | These results suggest that UBQLN4 phosphorylation on S318 is functionally important for its role in the DSB response.>Particularly HRR is dependent on ATM activity (Dietlein et al., 2014). Here, we showed that UBQLN4 is an ATM substrate and that DSB sealing is markedly impaired in UBQLN4-depleted cells. HRR depends on a 5′-3′ DSB end resection, which is initiated by the MRE11 nuclease | SIGNOR-265076 |
O60260 | Q9Y2N7 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Here we show that IPAS is a key molecule involved in neuronal cell death in Parkinson's disease (PD). IPAS was ubiquitinated by Parkin for proteasomal degradation following carbonyl cyanide m-chlorophenyl hydrazone treatment. Phosphorylation of IPAS at Thr12 by PTEN-induced putative kinase 1 (PINK1) was required for ubiquitination to occur. | SIGNOR-263089 |
P31749 | P53602 | 1 | phosphorylation | up-regulates activity | 0.2 | Akt modulated the pathway by phosphorylating mevalonate diphosphate decarboxylase (MDD) at Ser96. These data suggest that Akt regulates Rac1 activity by directly phosphorylating MDD at Ser96, which augments Rac1 geranylgeranylation. | SIGNOR-265891 |
Q04206 | Q99966 | 1 | binding | up-regulates | 0.2 | The transcriptional coactivator cpb/p300 associates with nf-kappa b p65 through two sites, an n-terminal domain that interacts with the c-terminal region of unphosphorylated p65, and a second domain that only interacts with p65 phosphorylated on serine 276. | SIGNOR-59054 |
Q5VWC8 | 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-267763 |
P68400 | Q13133 | 1 | phosphorylation | down-regulates | 0.2 | Ck2? Also phosphorylated lxr? At s198 in vitro, suggesting that ck2 may be a bona fide s198 kinase. our results show that macrophage lxr? Phosphorylation at s198 affects the transcriptional activity of the receptor in a gene-specific manner (fig. ?(Fig.3a)3a) and restricts the repertoire of genes regulated by lxr? | SIGNOR-160640 |
Q14721 | Q9P0L0 | 1 | relocalization | up-regulates quantity | 0.2 | Confirmation that Kv2.1 and -2.2 bind VAPA and VAPB employed colocalization/redistribution, siRNA knockdown, and Förster resonance energy transfer (FRET)-based assays.|As Kv2.1 accumulates on the surface it begins to bind ER VAPs and form the large and stable membrane junctions. | SIGNOR-262122 |
P30530 | P07947 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we show that EphA2, YES1, and ANXA2 form a signal axis, in which YES1 activated by EphA2 phosphorylates ANXA2 at Tyr24 site, leading to ANXA2 activation and increased ANXA2 nuclear distribution in gastric cancer (GC) cells. | SIGNOR-277555 |
Q9Y5H9 | O60330 | 1 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites. | SIGNOR-265676 |
Q9UQM7 | P16070 | 1 | phosphorylation | up-regulates activity | 0.2 | In previous studies we have demonstrated that a key control point for this receptor is the phosphorylation of CD44 on a conserved cytoplasmic serine residue, Ser(325). This modification is not required for efficient ligand binding, but is an essential component of CD44-dependent cell migration on a hyaluronan substratum. We demonstrate here that cd44 is phosphorylated to high stoichiometry in resting cells and that ca(2+)/calmodulin-dependent protein kinase ii is a cd44 ser(325) kinase. | SIGNOR-109502 |
Q04741 | O14786 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | EMX1 activates the transcription of Nrp1 in vitro. | SIGNOR-261593 |
P78527 | P78527 | 2 | phosphorylation | up-regulates activity | 0.2 | We have identified seven in vitro autophosphorylation sites in DNA-PKcs. Six of these sites (Thr2609, Ser2612, Thr2620, Ser2624, Thr2638 and Thr2647) are clustered in a region of 38 amino acids in the central region of the protein. Five of these sites (Thr2609, Ser2612, Thr2638, Thr2647 and Ser3205) are conserved between six vertebrate species. Moreover, we show that DNA-PKcs is phosphorylated in vivo at Thr2609, Ser2612, Thr2638 and Thr2647 in okadaic acid-treated human cells. | Thus phosphorylation of DNA-PKcs at one or more of the autophosphorylation sites identified in this study is likely to be required for DNA-PKcs function. | SIGNOR-249157 |
Q9NRC8 | P62826 | 1 | deacetylation | down-regulates activity | 0.2 | N this study, we demonstrated that SIRT7 interacts with a small GTPase, Ras-related nuclear antigen (Ran), and deacetylates Ran at K37. |The nuclear export by CRM1 requires an interaction with the small GTPase Ras-related nuclear antigen (Ran), which cycles between GTP- and GDP-bound states. The binding of Ran GTP to CRM1 in the nucleus increases the affinity of CRM1 for cargo proteins [[18], [19], [20]]. Interestingly, Ran is a lysine-acetylated protein | SIGNOR-275849 |
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