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 |
|---|---|---|---|---|---|---|---|
P35813 | Q14653 | 1 | dephosphorylation | down-regulates activity | 0.247 | In contrast, coexpression of wild-type PPM1A, but not its D239N or R174G mutant, abolished IRF3 activation (XREF_FIG).|We found that PPM1A abolished the C-terminal phosphorylation of IRF3 (XREF_FIG), whereas depletion of PPM1A expression improved virus induced pIRF3 level (XREF_FIG and XREF_FIG). | SIGNOR-277152 |
Q9UKM9 | Q99873 | 1 | post transcriptional regulation | up-regulates quantity | 0.247 | RALY binds poly-U rich elements within several RNAs and regulates the expression as well as the stability of specific transcripts. Here we show that RALY binds PRMT1 mRNA and regulates its expression.|We demonstrate that RALY down-regulation decreases protein arginine N-methyltransferase 1 levels | SIGNOR-262273 |
Q15831 | Q13153 | 1 | phosphorylation | down-regulates | 0.247 | Lkb1 suppresses p21-activated kinase-1 (pak1) by phosphorylation of thr109 in the p21-binding domain. | SIGNOR-164814 |
O94901 | Q5MJ70 | 1 | binding | up-regulates activity | 0.247 | In this study, we found that SUN1 not only interacted with TERB1 but also interacted with MAJIN, and the interaction of SUN1 with MAJIN is stronger than TERB1. We also found that SUN1 interacted with SPDYA, an activator of CDK2. | Taken together, we speculate that speedy A is likely capable of interacting with both telomeres and the LINC complex and thus might function as the missing linkage between telomeres and the LINC complex during prophase I, stabilizing the telomere–NE connection | SIGNOR-263301 |
Q16539 | Q06330 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.247 | P38 MAPK phosphorylates RBP-Jk at Thr339 by physical binding, which subsequently induces the degradation and ubiquitylation of the RBP-Jk protein. | SIGNOR-276403 |
P27361 | Q02548 | 1 | phosphorylation | down-regulates activity | 0.247 | In this study, we demonstrated that PAX5 was phosphorylated by ERK1/2 in vitro and in vivo at serines 189 and 283. This phosphorylation attenuated the transcriptional repression of BLIMP1 by PAX5. | SIGNOR-269086 |
P50750 | Q15596 | 1 | phosphorylation | up-regulates activity | 0.246 | Interestingly, GRIP1 is phosphorylated at an N-terminal serine cluster by cyclin-dependent kinase-9 (CDK9), which is recruited into GC-induced GR:GRIP1:CDK9 hetero-complexes, producing distinct GRE-specific GRIP1 phospho-isoforms. Phosphorylation potentiates GRIP1 coactivator but, remarkably, not its corepressor properties. | SIGNOR-256098 |
Q9UKL3 | P19838 | 1 | binding | up-regulates | 0.246 | In addition, both cleavage products of c-flip turned out to be inducers of nf-kb activity by binding to the ikk complex. | SIGNOR-177104 |
P68400 | P03372 | 1 | phosphorylation | down-regulates | 0.246 | Additionally protein kinase ck2 was identified as a kinase that phosphorylated eralpha at s282 and s559 s282 and s559 represent the second and third sites of er_ regulation by ck2. Remarkably, mutation of s282 or s559 to alanine resulted in near opposite functional effects on er_ as compared to mutation of s167 to alanine. Er_ ligand independent transcriptional activity was markedly enhanced upon mutation of s282 and s559 to alanine | SIGNOR-162653 |
P45984 | P19793 | 1 | phosphorylation | down-regulates activity | 0.246 | Under stress conditions, hyperphosphorylated by activated jnk on ser-56, ser-70, thr-82 and ser-260. These findings indicate that inflammation-mediated cell signaling leads to rapid and profound reductions in nuclear rxralpha levels, via a multistep, jnk-dependent mechanism involving ser260, nuclear export, and proteasomal degradation. | SIGNOR-145301 |
P24941 | Q9H3D4 | 1 | phosphorylation | down-regulates | 0.246 | Atm kinase is a master switch for the delta np63 alpha phosphorylation/degradation in human head and neck squamous cell carcinoma cells upon dna damage. We previously found that the pro-apoptotic dna damaging agent, cisplatin, mediated the proteasome-dependent degradation of delta np63 alpha associated with its increased phosphorylated status. We found that delta np63 alpha is phosphorylated in the time-dependent fashion at the following positions: s385, t397 and s466, which were surrounded by recognition motifs for atm, cdk2 and p70s6k kinases, respectively | SIGNOR-180759 |
Q13310 | Q12986 | 1 | binding | up-regulates activity | 0.246 | We identifiednew protein partners of NFX1-123, including several cytoplasmic poly(A) binding proteins (PABPCs) thatinteracted with NFX1-123 through its N-terminal PAM2 motif. Central to our findings were our observations that PABPCs copurify with NFX1-123, that a PAM2 motif is present in NFX1, and this motif and the PABPCs are important in the enhancement of hTERT activity by NFX1-123. | SIGNOR-261051 |
Q86V86 | O95644 | 1 | phosphorylation | up-regulates activity | 0.246 | In addition to PIM1, also PIM2 and PIM3 were able to phosphorylate WT, but not MM NFATC1 in vitro (Fig. (Fig.22c). | SIGNOR-276773 |
P18848 | Q9UGM6 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.246 | QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress. | SIGNOR-269430 |
Q05513 | P52565 | 1 | phosphorylation | up-regulates activity | 0.246 | Hence, it may be reasonable to deduce that N-formyl-methionyl-leucyl-phenylalanine binds its receptors to activate protein kinase C\u03b6 to generate superoxide, which in turn stimulates the motility in an autocrine manner via the protein kinase C\u03b6-RhoGDI-1-RhoGTPase pathway.|In these cells, protein kinase C zeta was activated to phosphorylate RhoGDI-1, which liberated RhoGTPases, leading to their activation. | SIGNOR-280089 |
Q5SQI0 | Q9BQE3 | 1 | acetylation | up-regulates quantity by stabilization | 0.246 | Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules | SIGNOR-272247 |
O43865 | P51003 | 1 | binding | down-regulates activity | 0.246 | Inositol 1,4,5-triphosphate receptor-binding protein released with inositol 1,4,5-triphosphate (IRBIT) associates with components of the mRNA 3' processing machinery in a phosphorylation-dependent manner and inhibits polyadenylation|In addition to CPSF, IRBIT interacted in vitro with poly(A) polymerase (PAP), which is the enzyme recruited by CPSF to elongate the poly(A) tail, and inhibited PAP activity in a phosphorylation-dependent manner. | SIGNOR-268329 |
Q05655 | Q14247 | 1 | phosphorylation | up-regulates activity | 0.246 | Together these findings demonstrate that phosphorylation of cortactin on S405 and S418 residues is required for its interaction with WAVE2 in MCP1-induced cytoskeleton remodeling, facilitating HASMC migration. In addition, the MCP1-induced cortactin phosp | SIGNOR-260890 |
P24941 | Q14106 | 1 | phosphorylation | up-regulates activity | 0.246 | Taken together, these observations strongly support the notion that several different CDK-cyclin complexes are involved in the phosphorylation of Tob2 at S254.A more detailed regulatory context of Tob2 phosphorylation at S254 is provided by our findings from mass-spec and in vitro kinase analyses that suggest connections to PP2B and PP2C phosphatases and CDK-cyclin complexes, particularly CDK1, CDK2, and CDK4 (Table 1; Supplemental Table S2).One possibility is that the phosphorylation of S254 helps stabilize the interaction of Tob2 with the Ccr4–Not complex, which could contribute to Tob2's ability to recruit the entire Ccr4–Not complex and thus further enhances deadenylation. | SIGNOR-273601 |
Q7Z6J0 | O14964 | 1 | ubiquitination | down-regulates quantity | 0.246 | Importantly, ubiquitination of Hrs mediated by POSH caused the reduction of Hrs level via the ubiquitin-proteasome pathway. | SIGNOR-278575 |
Q12857 | P15172 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.246 | NFIA binds to and activates the brown-fat-specific enhancers even before differentiation and later facilitates the binding of PPARgamma|NFIA has at least three functions on the transcriptional regulation of brown fat [2]. First, NFIA activates adipogenesis per se, through activating the transcription of Pparg, which encodes PPARgamma. Second, NFIA also activates the brown-fat-specific gene expression (such as Ucp1 and Ppargc1a) independent of the degree of adipocyte differentiation, through facilitating the binding of PPARgamma to the brown-fat-specific enhancers. Third, NFIA represses myogenesis through suppression of myogenic transcription factors such as Myod1 as well as Myog, | SIGNOR-263982 |
P68400 | P27986 | 1 | phosphorylation | up-regulates activity | 0.246 | Protein kinase CK2 phosphorylates p85α on Ser608 when p85α is free but not when it is complexed with p110α. | SIGNOR-276005 |
Q16236 | P24557 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.246 | Ecotopic expression of NF-E2 related factors showed that Nrf2, but not Nrf1, Nrf3, or Bach1, activated TXAS promoter in a dose-dependent manner. | SIGNOR-253907 |
O00712 | Q9Y6N7 | 1 | transcriptional regulation | up-regulates quantity | 0.246 | 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-268900 |
P62136 | P30281 | 1 | dephosphorylation | up-regulates | 0.246 | These results support the hypothesis that pp1 constitutively keeps cyclin d3 in a stable, dephosphorylated state | SIGNOR-142884 |
P67870 | Q01105-2 | 1 | phosphorylation | down-regulates | 0.246 | Ckii-mediated phosphorylation at ser9 hinders nuclear import of set | SIGNOR-200806 |
Q5T4S7 | Q9NQA5 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.246 | Cytomix induced interaction between TRPV5 and UBR4 (Ubiquitin recoginition 4), an E3 ubiquitin ligase; knockdown of UBR4 with small interfering RNAs prevented cytomix-induced degradation of TRPV5. UBR4/p600 ubiquitin ligase is responsible for TRPV5 ubiquitination and proteasomal degradation in response to cytomix | SIGNOR-272117 |
Q969R5 | Q8IYW5 | 1 | binding | down-regulates quantity | 0.246 | L3MBTL2 links RNF8 and RNF168 in the DNA double strand break response. The protein kinase ATM phosphorylates L3MBTL2, which recruits it to the DNA lesion by promoting the interaction between MDC1 and L3MBTL2. L3MBTL2 is subsequently ubiquitinated by RNF8, which acts as a docking site for RNF168, thereby recruiting the ubiquitin ligase to the damage site. RNF168, in turn, ubiquitinates H2A-type histones to amplify the DNA damage response and recruit downstream DNA repair proteins for proper DSB signaling. | SIGNOR-266788 |
P07948 | Q8N6F7 | 1 | phosphorylation | up-regulates activity | 0.245 | Herein, we demonstrate phosphorylation of HGAL by Syk and Lyn kinases at tyrosines Y80, Y86, Y106Y107, Y128, and Y148. Y148 (in black) was already phosphorylated before the addition of kinases. We demonstrate that Grb2 facilitates HGAL and Syk binding following BCR stimulation but does not affect the HGAL-mediated increase in Syk kinase activity. Previous studies showed that Grb2 inhibits BCR signaling by decreasing the activation of Syk by Lyn.11 Thus, while HGAL and Grb2 oppositely affect Syk kinase activity, this is not due to direct Grb2 effects on HGAL-mediated Syk kinase activation. | SIGNOR-273560 |
P53779 | P30307 | 1 | phosphorylation | down-regulates | 0.245 | Here we show that jnk directly phosphorylates cdc25c at serine 168 during g(2) phase of the cell cycle. Cdc25c phosphorylation by jnk negatively regulates its phosphatase activity and thereby cdk1 activation, enabling a timely control of mitosis onset. | SIGNOR-164085 |
P17252 | P11831 | 1 | phosphorylation | up-regulates | 0.245 | Myotonic dystrophy protein kinase (DMPK), a muscle- and neuron-restricted kinase, enhanced SRF-mediated promoter activity of the skeletal and cardiac alpha-actin genes in C2C12 myoblasts as well as in nonmyogenic cells. | Threonine 159 in the MADS box alphaI coil was a specific phosphorylation target in vitro as well as in vivo of both DMPK and protein kinase C-alpha. | SIGNOR-188181 |
P17676 | P35318 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.245 | These findings suggest that NF-IL6 and AP-2 sites in the promoter region are the functional elements in the transcriptional regulation of human AM gene in vascular endothelial cells. | SIGNOR-254047 |
P12931 | Q9BXK1 | 1 | phosphorylation | up-regulates activity | 0.245 | We further confirmed that the Tyr-10 residue of KLF16 is phosphorylated in uterine cells (Fig. 7c). Additional experiments using both pharmacological and dominant negative inhibitors of Src further supported a role for this tyrosine kinase in modulating the activity of KLF16 (Fig. 7, d and f). | SIGNOR-276398 |
Q92793 | Q9NR30 | 1 | acetylation | down-regulates activity | 0.245 | Significantly, the activity of DDX21 is regulated by acetylation. Acetylation by CBP inhibits DDX21 activity, while deacetylation by SIRT7 augments helicase activity and overcomes R-loop-mediated stalling of RNA polymerases.|acetylation of K18, K137, and K600 impairs the helicase activity of DDX21. | SIGNOR-275904 |
P48730 | Q96T88 | 1 | phosphorylation | up-regulates | 0.245 | We further show that uhrf1 physically interacts with _-trcp1 in a manner dependent on phosphorylation of serine 108 (s108(uhrf1)) within the dsg degron. Furthermore, we demonstrate that s108(uhrf1) phosphorylation is catalyzed by casein kinase 1 delta (ck1_) and is important for the recognition of uhrf1 by scf(_-trcp). | SIGNOR-200349 |
O43896 | Q9H0N0 | 1 | relocalization | up-regulates quantity | 0.245 | Here, we identify Bicaudal-D-related protein 1 (BICDR-1) as an effector of the small GTPase Rab6 and key component of the molecular machinery that controls secretory vesicle transport in developing neurons. BICDR-1 interacts with kinesin motor Kif1C, the dynein/dynactin retrograde motor complex, regulates the pericentrosomal localization of Rab6-positive secretory vesicles and is required for neural development in zebrafish. In young neurons, BICDR-1 accumulates Rab6 secretory vesicles around the centrosome, restricts anterograde secretory transport and inhibits neuritogenesis. Later during development, BICDR-1 expression is strongly reduced, which permits anterograde secretory transport required for neurite outgrowth. These results indicate an important role for BICDR-1 as temporal regulator of secretory trafficking during the early phase of neuronal differentiation. | SIGNOR-266879 |
P06493 | P35251 | 1 | phosphorylation | down-regulates activity | 0.245 | Phosphorylation of the PCNA binding domain of the large subunit of replication factor C on Thr506 by cyclin-dependent kinases regulates binding to PCNA|Replication factor C (RF-C) complex binds to DNA primers and loads PCNA onto DNA, thereby increasing the processivity of DNA polymerases. |Phosphorylation of either RF-Cp145 as a part of the RF-C complex or RF-Cp145 domain B by cdk-cyclin kinases inhibits their ability to bind PCNA. | SIGNOR-265504 |
Q13261 | P29597 | 1 | null | up-regulates | 0.245 | Since Jak-STAT pathway primarily activated in IL-15-me- diated cell proliferation, we tested whether it is also participates in IL-15-mediated proliferation of FAPs. Interestingly, we found the expression of phospho-Jak3 and phospho-Tyk2, as well as their downstream, phospho- STAT3 and phospho-STAT5, was significantly upregulated | SIGNOR-256253 |
Q13618 | Q99426 | 1 | ubiquitination | down-regulates quantity | 0.245 | Gigaxonin is the substrate-specific adaptor for a new Cul3-E3-ubiquitin ligase family that promotes the proteasome dependent degradation of its partners MAP1B, MAP8 and tubulin cofactor B. | SIGNOR-268945 |
Q96KB5 | Q13547 | 1 | phosphorylation | up-regulates activity | 0.245 | TOPK overexpression promotes HDAC1 and HDAC2 phosphorylation and Histone 3 and Histone 4 acetylation in BV2 cells.|The results of in vitro studies further confirmed the effect of TOPK on HDAC activity by showing that TOPK overexpression significantly up-regulated p-HDAC1 and p-HDAC2, resulting in an increase in the acetylation of histones H3 and H4 in BV2 cells. | SIGNOR-279086 |
Q5SQI0 | Q9NY65 | 1 | acetylation | up-regulates quantity by stabilization | 0.244 | Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules | SIGNOR-272250 |
P10276 | P78396 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.244 | RARα is involved in the regulation of cyclin A1. Further studies using ligands selective for various retinoic acid receptors suggested that cyclin A1 expression is negatively regulated by activated RARα. | SIGNOR-249636 |
O43379 | P24941 | 1 | relocalization | up-regulates activity | 0.244 | Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome. | SIGNOR-271726 |
Q92915 | Q9NY46 | 1 | binding | down-regulates activity | 0.244 | Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels. | SIGNOR-253445 |
Q13237 | P32929 | 1 | phosphorylation | down-regulates activity | 0.244 | CO stimulated protein kinase G (PKG)-dependent phosphorylation of Ser(377) of CSE, inhibiting the production of H2S. | SIGNOR-275800 |
O15344 | Q9P0W2 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.244 | The E3 ubiquitin ligase MID1/TRIM18 promotes atypical ubiquitination of the BRCA2-associated factor 35, BRAF35. MID1 is implicated in BRAF35 ubiquitination promoting atypical poly-ubiquitination via K6-, K27- and K29-linkages. We found that MID1 depletion alters BRAF35 localization in these structures and increases BRAF35 stability affecting its cytoplasmic abundance | SIGNOR-272317 |
Q9NPG1 | Q14344 | 1 | binding | up-regulates | 0.244 | Gpcrs signal through four relatively small families of galfa proteins (galfas, galfai/o, galfaq, and galfa12/13), and if fzd receptors are classic gpcrs, they should signal through one of these four galfa families. | SIGNOR-122892 |
Q6ZUJ8 | P48736 | 1 | binding | up-regulates | 0.244 | This accumulation of tyrosine-phosphorylated bcap at the membrane with its associated pi3k would then allow for the catalysis of ptd ins p2 to ptd ins p3 and downstream pi3k-dependent signals. Therefore, bcap is an essential activator of the pi3k pathway downstream of tlr signaling, providing a brake to limit potentially pathogenic excessive tlr responses. | SIGNOR-191670 |
Q13188 | P51955 | 1 | phosphorylation | up-regulates | 0.244 | Our data suggest that mst2 phosphorylates nek2a thereby recruiting nek2a to centrosomes and promoting phosphorylation and displacement of centrosomal linker proteins | SIGNOR-169539 |
Q96GD4 | P42575 | 1 | phosphorylation | up-regulates activity | 0.244 | Furthermore, in vitro phosphorylation using GST-Casp2 363-423 WT or S384A confirmed that S384 of caspase-2 is phosphorylated by AURKB. | SIGNOR-279496 |
P18848 | Q5JTZ9 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.244 | QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress. | SIGNOR-269415 |
Q9BYW2 | P68363 | 1 | methylation | up-regulates activity | 0.244 | The histone methyltransferase SET-domain-containing 2 (SETD2), which is responsible for H3 lysine 36 trimethylation (H3K36me3) of histones, also methylates α-tubulin at lysine 40, the same lysine that is marked by acetylation on microtubules. Methylation of microtubules occurs during mitosis and cytokinesis and can be ablated by SETD2 deletion, which causes mitotic spindle and cytokinesis defects, micronuclei, and polyploidy | SIGNOR-269090 |
Q9NPG1 | Q03113 | 1 | binding | up-regulates | 0.244 | Gpcrs signal through four relatively small families of galfa proteins (galfas, galfai/o, galfaq, and galfa12/13), and if fzd receptors are classic gpcrs, they should signal through one of these four galfa families. | SIGNOR-122889 |
Q8IUQ4 | P67809 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.244 | Here, we identified that SIAH1 which was downregulated in chemoresistant EOC samples and cell lines functioned as novel E3 ligases to trigger degradation of YBX-1 at cytoplasm by RING finger domain.|SIAH1 ubiquitinated YBX-1 at its K304 through the RING domain. | SIGNOR-278780 |
O14965 | Q9Y657 | 1 | phosphorylation | up-regulates activity | 0.243 | The Ser84 and Ser99 amino acids within SPINDLIN1 were further identified as the key functional sites in WNT/TCF-4 signaling activation. Mutation of these two sites of SPINDLIN1 abolished its effects on promoting WNT/TCF-4 signaling and cancer cell proliferation. We further found that Aurora-A could interact with and phosphorylate SPINDLIN1 at its key functional sites, Ser84 and Ser99, suggesting that phosphorylation of SPINDLIN1 is involved in its oncogenic function. | SIGNOR-273550 |
P23470 | Q05397 | 1 | dephosphorylation | up-regulates activity | 0.243 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254719 |
Q00526 | P46531 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.243 | Mapping of cyclin C-dependent phosphosites on ICN1, using mass spectrometry revealed that several of them are located within the PEST-domain of Notch1, which controls ICN1 degradation38,39 (Fig. 5g and Supplementary Table 1). Three of them (T2512, S2514 and S2517) are localized within the consensus motif, “Cdc4 phosphodegron”, which is shared by most substrates of Fbw7 (Cdc4) ubiquitin ligase38. Two of these residues (S2514 and S2517) were previously shown by Fryer et al.20 to be phosphorylated by cyclin C-CDK8 in vitro, and all three were shown to play a role in controlling ICN1 stability via Fbw740. We verified that cyclin C-CDK8, C-CDK19 and C-CDK3 phosphorylate ICN1 on these three residues | SIGNOR-273167 |
P01106 | P20839 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.243 | Here, we report that the majority of genes in human purine and pyrimidine biosynthesis pathway were induced and directly bound by c-Myc in the P493-6 human Burkitt's lymphoma model cell line. The mRNA levels of IMPDH1 and IMPDH2, the rate-limiting enzyme in purine de novo synthesis, increased with MYC induction both in vitro and in vivo. | SIGNOR-267378 |
Q9P2J9 | Q15797 | 1 | dephosphorylation | down-regulates | 0.243 | We show that the mammalian pdps are important in dephosphorylation of bmp-activated smad1 but not tgf-beta-activated smad2 or smad3. Thus, pdps specifically inactivate smads in the bmp/dpp pathway. [...] These observations suggest that pdp1 and pdp2 are important for dephosphorylation of smad1. | SIGNOR-144909 |
P19525 | Q9UQ80 | 1 | phosphorylation | up-regulates activity | 0.243 | Ebp1 itself is phosphorylated by the PKR protein kinase, suggesting that the effects of Ebp1 overexpression evidenced in vivo on eIF2alpha phosphorylation could be achieved by competition between Ebp1 and eIF2alpha for PKR kinase activity. | SIGNOR-279170 |
Q9P0J1 | Q15797 | 1 | dephosphorylation | down-regulates | 0.243 | We show that the mammalian pdps are important in dephosphorylation of bmp-activated smad1 but not tgf-beta-activated smad2 or smad3. Thus, pdps specifically inactivate smads in the bmp/dpp pathway. [...] These observations suggest that pdp1 and pdp2 are important for dephosphorylation of smad1. | SIGNOR-144876 |
Q5TCY1 | Q16555 | 1 | phosphorylation | up-regulates activity | 0.243 | TTBK1 induces complex formation of pCRMP2 with pTau.|These data suggest that TTBK1-induced T514 CRMP2 phosphorylation is dependent on both S522 phosphorylation by Cdk5 and T555 phosphorylation by RhoK. | SIGNOR-279313 |
P23409 | P17661 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.242 | Desmin, the muscle specific intermediate filament (IF) protein, is expressed at low levels in myoblasts and at the onset of differentiation its expression increases several fold. In an effort to explore the mechanism involved in the tissue-specific and developmentally regulated expression of desmin, we have isolated the mouse desmin gene.Co-transfection of myoD, myogenin, MRF4 and Myf5, with the desmin-CAT construct into 10T-1/2 cells demonstrated that all these factors could transactivate desmin gene expression | SIGNOR-241497 |
P60510 | Q13085 | 1 | dephosphorylation | up-regulates activity | 0.242 | PP4 was also found to directly interact with pACC1‑Ser79 in human HepG2 cells. In conclusion, the present study showed that PP4 may be a novel regulator in hepatic lipogenesis through dephosphorylating ACC1 on serine 79, suggesting that PP4 may be a promising therapeutic target in lipid metabolism disorders. | SIGNOR-267724 |
Q13118 | Q15582 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.242 | Analyzing the mechanism of TGFBI up-regulation in clear cell carcinoma, we identified a novel VHL target, a Kruppel-like transcriptional factor 10 (KLF10). The TGFBI promoter, which we isolated and studied in Luc-reporter assay, was induced by KLF10 but not hypoxia. | SIGNOR-253212 |
O76064 | Q969R5 | 1 | ubiquitination | up-regulates activity | 0.242 | L3MBTL2 links RNF8 and RNF168 in the DNA double strand break response. The protein kinase ATM phosphorylates L3MBTL2, which recruits it to the DNA lesion by promoting the interaction between MDC1 and L3MBTL2. L3MBTL2 is subsequently ubiquitinated by RNF8, which acts as a docking site for RNF168, thereby recruiting the ubiquitin ligase to the damage site. RNF168, in turn, ubiquitinates H2A-type histones to amplify the DNA damage response and recruit downstream DNA repair proteins for proper DSB signaling. | SIGNOR-266787 |
Q8N4C6 | O60674 | 1 | binding | down-regulates | 0.242 | We showed that jak2 directly phosphorylates the n-terminus ofnineinwhile the c-terminus ofnineininhibits jak2 kinase activity in vitro. | SIGNOR-205581 |
Q5SQI0 | P0DPH8 | 1 | acetylation | up-regulates quantity by stabilization | 0.242 | Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules | SIGNOR-272246 |
Q13618 | Q66K74 | 1 | ubiquitination | down-regulates quantity | 0.242 | Gigaxonin is the substrate-specific adaptor for a new Cul3-E3-ubiquitin ligase family that promotes the proteasome dependent degradation of its partners MAP1B, MAP8 and tubulin cofactor B. | SIGNOR-268947 |
Q5SQI0 | P0DPH7 | 1 | acetylation | up-regulates quantity by stabilization | 0.242 | Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules | SIGNOR-272244 |
Q8TBB1 | O95477 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.242 | We used the Ligand of Numb protein X (LNX) family of E3s, a group of PDZ domain-containing RING-type E3 ubiquitin ligases, to demonstrate the feasibility of this strategy. Many potential substrates of LNX E3s were identified. Eight of the nine selected candidates were ubiquitinated in vitro, and two novel endogenous substrates, PDZ-binding kinase (PBK) and breakpoint cluster region protein (BCR), were confirmed in vivo. | SIGNOR-272902 |
P35398 | Q14643 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.242 | RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice. | SIGNOR-266847 |
Q06413 | Q9UI47 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.241 | GATA-4 and MEF2C are known to bind to the GATA box 2 in the major promoter of CTNNA3 and this element is essential in directly regulating expression of CTNNA3 in cardiac muscle cells. The co-transfection of GATA-4 with MEF2C leads to a synergistic activation of the CTNNA3 promoter | SIGNOR-265491 |
P60484 | Q8IZP0 | 1 | dephosphorylation | down-regulates quantity by destabilization | 0.241 | After dephosphorylation by PTEN, Abi1 is degraded by calpains.|We demonstrate that PTEN dephosphorylation of Abi1 at Y213 and S216 results in Abi1 degradation through the calpain pathway. | SIGNOR-276948 |
Q9UM11 | Q9UBZ9 | 1 | binding | down-regulates quantity by destabilization | 0.241 | Here, we show that human REV1 undergoes proteosomal degradation mediated by the E3 ubiquitin ligase known as anaphase-promoting complex (APC). REV1 associates with APC. Overexpression of APC coactivator CDH1 or CDC20 promotes polyubiquitination and proteosomal degradation of REV1. | SIGNOR-272893 |
Q9UQM7 | O00631 | 1 | phosphorylation | down-regulates activity | 0.241 | SLN is also phosphorylated by CaMKII at Thr 5, and a phosphorylation mimic (Thr5Glu mutation) abolishes the inhibitory function of ectopically expressed SLN in adult rat ventricular myocytes| Thr 5 interacts with SERCA Trp 932, and phosphorylation at this site would cause a steric clash that destabilizes binding | SIGNOR-264778 |
P13349 | P17661 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.241 | Desmin, the muscle specific intermediate filament (IF) protein, is expressed at low levels in myoblasts and at the onset of differentiation its expression increases several fold. In an effort to explore the mechanism involved in the tissue-specific and developmentally regulated expression of desmin, we have isolated the mouse desmin gene.Co-transfection of myoD, myogenin, MRF4 and Myf5, with the desmin-CAT construct into 10T-1/2 cells demonstrated that all these factors could transactivate desmin gene expression | SIGNOR-241494 |
P06493 | Q96QE3 | 1 | phosphorylation | down-regulates activity | 0.24 | To determine whether mitotic CDK phosphorylates ATAD5, a CDK1 inhibitor (RO3306) was applied to nocodazole-arrested cells (Figure S3F). CDK1 inhibition resulted in a loss of S653 phosphorylation (Figure S3F). These data meant that the S653 residue in the BET BD of ATAD5 is phosphorylated by mitotic CDK. This result suggested that the BRD4-ATAD5 interaction is inhibited during mitosis. | SIGNOR-266410 |
P15172 | P17661 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.24 | MyoD and HDAC2 repress myogenic late genes at early times of differentiation.A time course of Ckm, Des and Acta1 gene expression demonstrated that these genes were prematurely expressed when differentiation was driven by myogenin and Mef2D1b (Figure _(Figure6A).6A). Since MyoD is not expressed under these conditions, it cannot bind to these genes; ChIP assays demonstrated that HDAC2 also was not present on the Ckm, Des and Acta1 regulatory sequences under these conditions (Figure _(Figure6B).6B). Therefore the presence of MyoD and HDAC2 prior to gene expression functions to repress late gene expression at early times of differentiation. | SIGNOR-241762 |
O15297 | P06744 | 1 | dephosphorylation | down-regulates activity | 0.24 | The WIP1 mediated inhibition of NLK activity markedly decreased the phosphorylation of lymphoid enhancer binding factor 1 (LEF1), enhancing its interaction with beta-catenin.|Wip1 directly dephosphorylates NLK and increases Wnt activity during germ cell development. | SIGNOR-277155 |
P68400 | Q13283 | 1 | phosphorylation | down-regulates activity | 0.239 | We also show that casein kinase 2 phosphorylates G3BP1 at serine 149 in vitro and in cells. These data support a role for casein kinase 2 in regulation of protein synthesis by downregulating stress granule formation through G3BP1.CK2 regulates SG disassembly during stress recovery.G3BP1 is among the strongest SG nucleating proteins, and previous work indicated that G3BP1 phosphorylation at S149 restricts stress granule assembly by partly inhibiting G3BP1 oligomerization | SIGNOR-260748 |
Q9UJX6 | O14640 | 1 | binding | down-regulates | 0.239 | We now report that the anaphase-promoting complex (apc/c) recognizes a d-box motif of dvl and ubiquitylates dvl on a highly conserved lysine residue.We now report that expression of the apc/c subunit anapc2 activates the apc/c-dependent degradation of dvl by disrupting canonical wnt signaling. | SIGNOR-188393 |
Q96T37 | P18583 | 1 | binding | up-regulates | 0.239 | Here we report that the human nxf1-binding protein rbm15 binds specifically to human dbp5 and facilitates its direct contact with mrna in vivo. | SIGNOR-188264 |
Q9UQM7 | Q9UBS5 | 1 | phosphorylation | down-regulates | 0.237 | Nmda-dependent internalization of gabab receptors requires activation of ca2+/calmodulin-dependent protein kinase ii (camkii), which associates with gabab receptors in vivo and phosphorylates serine 867 (s867) in the intracellular c terminus of the gabab1 subunit. | SIGNOR-166846 |
O14757 | Q9HC98 | 1 | phosphorylation | down-regulates activity | 0.237 | Nek6 is also directly phosphorylated by the checkpoint kinases Chk1 and Chk2 in vitro . | SIGNOR-279403 |
P04070 | P08709 | 1 | cleavage | down-regulates activity | 0.237 | Activated protein C (APC), which cleaves and inactivates both FVIIIa and FVa, thereby shutting down both the tenase and prothrombinase complexes | SIGNOR-263527 |
O75688 | Q13627 | 1 | dephosphorylation | down-regulates activity | 0.236 | In conclusion, our study demonstrates that DYRK1A autophosphorylates Ser258, the dephosphorylation target of PPM1B, and PPM1B negatively regulates DYRK1A activity.|We found that PPM1B dephosphorylates DYRK1A at Ser258, contributing to the inhibition of DYRK1A activity. | SIGNOR-277108 |
P06493 | Q6PGN9 | 1 | 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 |
P61328 | Q9NY46 | 1 | binding | down-regulates activity | 0.235 | Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels. | SIGNOR-253444 |
Q9NXA8 | P34897 | 1 | post translational modification | down-regulates activity | 0.235 | Mitochondrial serine hydroxymethyl transferase (SHMT2) is a rate-limiting enzyme that catalyzes the catabolism of serine and drives the proliferation of osteosarcoma cells and colon cancer cells. SIRT5 directly mediates the desuccinylation of Lysine 280 on SHMT2. Therefore, SIRT5 is a candidate target to inhibit serine catabolism | SIGNOR-267644 |
Q02156 | P46459 | 1 | phosphorylation | up-regulates activity | 0.234 | PKCepsilon phosphorylation enhances the ATPase activity of NSF.|These results indicate that PKCepsilon phosphorylates NSF at both S460 and T461 in vitro. | SIGNOR-278300 |
P68400 | Q92688 | 1 | phosphorylation | up-regulates | 0.234 | Here, we are able to report that casein kinase 2 (ck2) phosphorylates april on residue threonine244 (thr(244)) and demonstrate that the ck2-specific inhibitor 4,5,6,7-tetrabromo-2-azabenzimidazole abolishes cd83 expression in activated jurkat t cells by interfering with the nucleocytoplasmic translocation of cd83 mrna | SIGNOR-183158 |
Q13976 | P10644 | 1 | phosphorylation | up-regulates activity | 0.234 | In this study, we further examined the potential of RIα phosphorylation to regulate physiologically relevant "desensitization" of PKAc activity. First, the serine 101 site of RIα was validated as a target of PKGIα phosphorylation both in vitro and in cells.These findings suggest that RIα phosphorylation may be a novel mechanism to circumvent the requirement of cAMP stimulus to activate type I PKA in cells. | SIGNOR-277383 |
Q02156 | P18507 | 1 | phosphorylation | down-regulates activity | 0.233 | Protein kinase C epsilon regulates gamma-aminobutyrate type A receptor sensitivity to ethanol and benzodiazepines through phosphorylation of gamma2 subunits. Our findings indicate that PKCepsilon phosphorylation of gamma2 regulates the response of GABA(A) receptors to specific allosteric modulators, and, in particular, PKCepsilon inhibition renders these receptors sensitive to low intoxicating concentrations of ethanol. | SIGNOR-263174 |
O96017 | Q9HC98 | 1 | phosphorylation | down-regulates activity | 0.229 | Nek6 is also directly phosphorylated by the checkpoint kinases Chk1 and Chk2 in vitro . | SIGNOR-279404 |
P49715 | P06702 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.227 | Among several known transcription factor binding motifs, nuclear protein(s) of VD3-treated HL-60 cells and THP-1 cells bound to the CCAAT/enhancer binding protein (C/EBP)-binding motif that was located in the upstream region of the MRP14 gene (-81), as evidenced by the competitive gel mobility-shift assay.|Thus, it was concluded that C/EBP alpha and -beta were able to bind to the C/EBP motif, and that C/EBP alpha bound to the motif in THP-1 cells and C/EBP beta bound to that in the VD3-treated HL-60 cells. | SIGNOR-254041 |
Q9UM11 | P23919 | 1 | binding | down-regulates quantity by destabilization | 0.226 | We demonstrate that TMPK is recognized and degraded by APC/C-Cdc20/Cdh1-mediated pathways from mitosis to the early G1 phase, whereas TK1 is targeted for degradation by APC/C-Cdh1 after mitotic exit. | SIGNOR-272652 |
P68400 | P78344 | 1 | phosphorylation | up-regulates activity | 0.226 | DAP5(S902) is phosphorylated by CK2α. Phosphorylation of DAP5(S902) by CK2α is required for eIF2β binding. | SIGNOR-266384 |
P11802 | Q06830 | 1 | phosphorylation | down-regulates | 0.226 | Peroxiredoxin (prx) i is a member of the peroxiredoxin family of peroxidases and contains a consensus site (thr(90)-pro-lys-lys) for phosphorylation by cyclin-dependent kinases (cdks). This protein has now been shown to be phosphorylated specifically on thr(90) by several cdks, including cdc2, in vitro. Phosphorylation of prx i on thr(90) reduced the peroxidase activity of this protein by 80%.Prx i was also phosphorylated, with an efficiency similar to that observed with cdc2, when incubated in vitro with cdk2, cdk4, or cdk6 that had been immunoprecipitated from hela cell lysates with specific antibodies (data not shown). | SIGNOR-87105 |
P17612 | Q07002 | 1 | phosphorylation | up-regulates activity | 0.225 | We previously revealed that PCTK3 is activated by two pathways: interaction with cytoplasmic cyclin A and phosphorylation at Ser-12 by protein kinase A (PKA)12. Activated PCTK3 phosphorylates retinoblastoma protein (Rb) in vitro. | SIGNOR-264560 |
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