IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels int64 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 |
|---|---|---|---|---|---|---|---|
P51532 | P48730 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | We reveal that CK1δ phosphorylates Brg1 at Ser31/Ser35 residues to facilitate the binding of Brg1 to FBW7, leading to ubiquitination-mediated degradation. | SIGNOR-277407 |
Q96PM5 | O14579 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.471 | PIRH2 promotes the ubiquitylation of epsilon-COP in vitro and in vivo and consequently promotes the degradation of epsilon-COP. | SIGNOR-272630 |
Q92993 | Q01130 | 1 | acetylation | down-regulates | 0.466 | In this study, we provide the first evidence that the acetyltransferase tip60 acetylates srsf2 on its lysine 52 residue inside the rna recognition motif, and promotes its proteasomal degradation. | SIGNOR-170594 |
Q5T0W9 | Q8N752 | 2 | binding | up-regulates quantity | 0.2 | 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-273754 |
Q8IUC6 | Q9NWF9 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.355 | Triad3A promotes proteolytic degradation of adapter proteins. A, Triad3A promotes down-regulation of TIRAP, TRIF, and RIP1 proteins. | SIGNOR-271609 |
P12931 | Q99835 | 0 | phosphorylation | up-regulates | 0.436 | Instead, shh rapidly and locally stimulated phosphorylation of the src family kinase (sfk) members src and fyn in a smo-dependent fashion. | SIGNOR-178610 |
Q9C0C7 | Q96FJ2 | 2 | binding | down-regulates | 0.463 | The beclin 1 vps34 complex is tethered to the cytoskeleton through an interaction between the beclin 1 interacting protein ambra1 and dynein light chains 1/2 | SIGNOR-168289 |
P46531 | P25490 | 2 | binding | down-regulates activity | 0.623 | Taken together, these results indicate that transcription factor YY1 may modulate Notch signaling via association with the high molecular weight Notch complex [..] both YY1 and N1IC were present in a large complex of the nucleus to suppress the luciferase reporter activity transactivated by Notch signaling. | SIGNOR-251654 |
Q92837 | Q13144 | 2 | binding | up-regulates activity | 0.288 | In contrast to the GS‐1 peptide, glycogen synthase and the eIF2B peptide, the GSK3‐catalysed phosphorylation of Tau was completely inhibited by FRATtide|This prevents GSK3 from phosphorylating and inhibiting glycogen synthase [2, 3] and protein synthesis initiation factor eIF2B | SIGNOR-262835 |
Q05397 | P24844 | 1 | phosphorylation | up-regulates activity | 0.286 | It indicates that FAK positively regulates the phosphorylation of MLC2. | SIGNOR-280098 |
P04637 | Q96M02 | 0 | polyubiquitination | up-regulates quantity by stabilization | 0.459 | The E3 activity of FATS is required for promoting p53 stability and activation in response to DNA damage.FATS is an E2-independent ubiquitin ligase that stabilizes p53 and promotes its activation in response to DNA damage. Here, we show that FATS acts as a p53 activator by inhibiting Mdm2 binding to p53 and stimulating non-proteolytic polyubiquitination of p53. | SIGNOR-272142 |
Q13873 | Q9HAU4 | 0 | ubiquitination | down-regulates | 0.503 | Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degra-dation of smads and receptors for tgf-beta and bmps. | SIGNOR-193119 |
Q9BXW4 | Q9NT62 | 2 | binding | up-regulates activity | 0.782 | Lc3-i is activated by the same atg7 involved in atg12 conjugation, transferred to atg3, a second e2-like enzyme, and finally conjugated to pe | SIGNOR-191552 |
Q05655 | P31946 | 1 | phosphorylation | down-regulates | 0.493 | We provide a mechanism for these observations through the phosphorylation of 14-3-3 by ikk and pkc on serine residues ser132 and ser60, respectively, which interferes with its binding to ttp and hence the retention of ttp in the cytoplasm. | SIGNOR-138612 |
P41597 | P10147 | 2 | binding | up-regulates activity | 0.555 | The purpose of this study was to determine whether certain chemokines, which are highly expressed in injured skeletal muscle, are involved in the repair and functional recovery of the muscle after traumatic injury. In wild-type control mice, mRNA transcripts of macrophage inflammatory protein (MIP)-1, MIP-1, and monocyte chemoattractant protein (MCP)-1 as well as their major receptors, CCR5 and CCR2, increased after freeze injury and gradu- ally returned to control (uninjured) levels by 14 days. | SIGNOR-251723 |
Q01860 | P49137 | 0 | phosphorylation | up-regulates activity | 0.2 | MK2 mediated OCT4 transcriptional activation is a novel mechanism for activating the MYC oncogene in progressive disease neuroblastoma that provides a therapeutic target.|OCT4 phosphorylation at the S111 residue by MK2 was upstream of MYC transcriptional activation. | SIGNOR-279542 |
Q99986 | Q96GD4 | 1 | phosphorylation | up-regulates activity | 0.429 | In the VRK1 overexpression of experiment, VRK1 caused a significant stabilization of AURKB, with no change in level after 24h, which is consistent with protection of AURKB against its known degradation by ubiquitylation .|The phosphorylation of AURKB by VRK1 and VRK1 by AURKB was tested using a kinase-dead form as substrate. | SIGNOR-280160 |
P14778 | P01583 | 2 | binding | up-regulates activity | 0.767 | Interleukin-1 receptor (il-1r) is a cytokine receptor which binds interleukin 1. | SIGNOR-35077 |
O43829 | Q96RE7 | 2 | binding | up-regulates activity | 0.288 | NAC1 potentiated ZF5 mediated repression in Gal4-DBD fusion transient assays. GST pulldown assays further confirmed proteinprotein interactions between these proteins and NAC1. | SIGNOR-226443 |
P53350 | P33981 | 1 | phosphorylation | up-regulates activity | 0.381 | Here, we demonstrate that Plk1 promotes checkpoint signaling at kinetochores through the phosphorylation of at least two Mps1 substrates, including KNL-1 and Mps1 itself. As a result, Plk1 activity enhances Mps1 catalytic activity as well as the recruitment of the SAC components Mad1:C-Mad2 and Bub3:BubR1 to kinetochores. Plk1 Targets Mps1 Autophosphorylation Sites In Vitro | SIGNOR-276199 |
Q06187 | P00519 | 0 | phosphorylation | down-regulates activity | 0.336 | In this report we describe for the first time that ABL1 and Btk physically interact and that ABL1 can phosphorylate tyrosine 223 in the SH3 domain of Btk. | This is presumably due to the negative regulatory effectof Btk SH3 domain phosphorylation caused by ABL1,which would result in a decreased catalytic activity ofBtk resulting in impaired autophosphorylation. | SIGNOR-260801 |
Q16695 | Q9NRC8 | 0 | deacetylation | up-regulates activity | 0.2 | Besides confirming the previously reported histone H3K18 deacylation activity, our results revealed that SIRT7 has an astonishingly high activity to catalyze deacylation of H3K36 and is also catalytically active to deacylate H3K37. | SIGNOR-275876 |
P31749 | P98177 | 1 | phosphorylation | down-regulates | 0.763 | Foxo4 transcription factor, also referred to afx, contains three putative phosphorylation motif sites for protein kinase b (pkb), thr32, ser197, and ser262, and it is proposed that phosphorylated foxo4 stays in the cytosol and is imported to the nucleus through dephosphorylation to induce target gene expression | SIGNOR-252486 |
Q96EP0 | P51843 | 1 | monoubiquitination | up-regulates quantity by stabilization | 0.437 | RNF31 promotes monoubiquitination of DAX-1 in an RBR domain-dependent manner. In conclusion, our results suggest that the major DAX-1 modification observed in different experimental settings is likely to be monoubiquitination at one or more lysine residues (multiubiquitination) possibly located within the LBD of DAX-1. RNF31 stabilizes endogenous DAX-1. | SIGNOR-271786 |
Q8NEM2 | Q96GD4 | 0 | phosphorylation | up-regulates activity | 0.372 | AurB phosphorylates Ser634 of SHCBP1 during mitosis. We generated a phosphorylation site mutant, S634A-SHCBP1, which was prematurely recruited to the central spindle during anaphase and inhibited furrowing. | SIGNOR-273552 |
Q9UIG0 | Q16539 | 0 | phosphorylation | up-regulates | 0.2 | Moreover, this region (wac domain) was also phosphorylated by recombinant proteins of p38_? And jnk2_? But not by akt1 | SIGNOR-188160 |
O14746 | Q9NX24 | 2 | binding | up-regulates activity | 0.656 | A complex of four proteins (GAR1, NHP2, NOP10, and the putative pseudouridine synthase dyskerin) associates with snoRNAs to form small nucleolar ribonucleoprotein particles (snoRNPs), and the binding of this complex to the H/ACA domain of TERC may have a role in the biogenesis of the telomerase RNP | SIGNOR-263330 |
P49841 | P24864 | 1 | phosphorylation | down-regulates | 0.445 | Our experiments suggest that gsk3 is the kinase primarily responsible for phosphorylation of cyclin e on t380 | SIGNOR-118563 |
P43657 | Q03113 | 2 | binding | up-regulates activity | 0.359 | 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-257286 |
P09874 | Q70YC5 | 2 | binding | up-regulates activity | 0.2 | We identified ZNF365 as a necessary component of the HR repair pathway. ZNF365 interacts with PARP1 and tethers MRE11 to the nucleolytic resection sites for replication fork recovery | SIGNOR-272477 |
O15085 | Q03113 | 2 | binding | up-regulates activity | 0.631 | This RGS-like (RGL) domain provides a structural motif by which heterotrimeric G protein alpha subunits of the Galpha(12) family can bind and regulate the activity of RhoGEFs. Hence, these newly discovered RGL domain-containing RhoGEFs provide a direct link from Galpha(12) and Galpha(13) to Rho | SIGNOR-256516 |
P42226 | Q7KZF4 | 2 | binding | up-regulates activity | 0.479 | STAT6 interacted with p100 in vitro and in vivo. Here, we show that the TAD of STAT6 is interacting with p100. p100 was found to enhance the STAT6-mediated transcription [.]. | SIGNOR-259134 |
P43034 | Q9NRI5 | 2 | binding | up-regulates activity | 0.476 | Disrupted-In-Schizophrenia 1 (DISC1) is a candidate gene for susceptibility to schizophrenia. DISC1 is reported to interact with NudE-like (NUDEL), which forms a complex with lissencephaly-1 (LIS1) and 14-3-3ε. 14-3-3ε is involved in the proper localization of NUDEL and LIS1 in axons. the association with NUDEL and LIS1 supports the notion that DISC1 contributes to the neuronal development and morphology | SIGNOR-252163 |
Q8IWU2 | P62136 | 1 | phosphorylation | down-regulates activity | 0.57 | Kpi-2 kinase domain phosphorylated protein phosphatase-1 (pp1c) at thr(320), which attenuated pp1c activity. | SIGNOR-94631 |
P21796 | Q07817 | 2 | binding | down-regulates activity | 0.566 | The anti-apoptotic protein Bcl-x(L) closes VDAC by binding to it directly | SIGNOR-249614 |
P11274 | P37231 | 1 | phosphorylation | down-regulates activity | 0.2 | Overexpression of Bcr WT inhibited PPARgamma transcriptional activity (XREF_FIG).|Point-mutation and in vitro kinase analysis showed that PPAR\u03b3 was phosphorylated by Bcr at serine 82. | SIGNOR-279441 |
P45983 | P55957 | 1 | phosphorylation | up-regulates activity | 0.594 | (b) Phosphorylation of Bid at Thr59 by JNK1 and JNK2 (in vitro kinase assay). | SIGNOR-279076 |
P01019-PRO_0000032457 | P00797 | 0 | cleavage | up-regulates quantity | 0.2 | Renin is an aspartic protease that enzymatically cleaves its substrate angiotensinogen, which is produced by the liver, to form an inactive peptide: angiotensin (Ang)I or Ang (1–10). | SIGNOR-260225 |
P24863 | Q92585 | 0 | relocalization | up-regulates | 0.447 | Cycc:cdk8 and cyct1:cdk9/p-tefb are recruited with notch and associated coactivators (mam, skip) to the hes1 promoter in signaling cells. | SIGNOR-130709 |
Q63HK5 | O00213 | 0 | relocalization | up-regulates activity | 0.366 | We carried out yeast two-hybrid studies with a PTB domain of FE65, focusing on those genes that might be involved in nuclear signaling, and identified and validated Teashirt proteins as FE65 interacting proteins in neurons. Using reporter systems, we observed that FE65 could simultaneously recruit SET, a component of the inhibitor of acetyl transferase, and Teashirt, which in turn recruited histone deacetylases, to produce a powerful gene-silencing complex. | SIGNOR-264813 |
Q99814 | P11309 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.2 | PIM1 kinase directly phosphorylates HIF-1α at threonine 455, a previously uncharacterized site within its oxygen-dependent degradation domain. This phosphorylation event disrupts the ability of prolyl hydroxylases to bind and hydroxylate HIF-1α, interrupting its canonical degradation pathway and promoting constitutive transcription of HIF-1 target genes. Moreover, phosphorylation of the analogous site in HIF-2α (S435) stabilizes the protein through the same mechanism, indicating post-translational modification within the oxygen-dependent degradation domain as a mechanism of regulating the HIF-α subunits. | SIGNOR-277310 |
A8K4G0 | P06241 | 0 | phosphorylation | up-regulates activity | 0.308 | As CD300b phosphorylation was occurring only in the presence of both c-Fyn and DAP-12, we addressed whether tyrosine phosphorylation was required for association of CD300b and DAP-12. For this purpose, we generated a set of HA-tagged CD300b mutants affecting the transmembrane lysine (K158L), the cytoplasmic tyrosine (Y188F) or both residues.|As expected, the CD300b double mutant could neither recruit DAP-12 nor become phosphorylated in the presence of c-Fyn kinase (Fig. 5⇑C). Association between CD300b and DAP-12 was maintained in absence of the c-Fyn kinase, indicating that phosphorylation of the adaptor was not essential for the formation of the complex (data not shown) | SIGNOR-264771 |
Q02078 | P23409 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.589 | Myogenin and MEF2 function synergistically to activate the MRF4 promoter during myogenesis. | SIGNOR-238709 |
P14416 | P62166 | 2 | binding | down-regulates activity | 0.68 | Here we show that the neuronal calcium sensor-1 (NCS-1) can mediate desensitization of D2 dopamine receptors. Analysis of D2 receptors expressed in human embryonic kidney 293 cells indicates that NCS-1 attenuates agonist-induced receptor internalization via a mechanism that involves a reduction in D2 receptor phosphorylation. Coimmunoprecipitation experiments from striatal neurons reveal that NCS-1 is found in association with both the D2 receptor and G-protein-coupled receptor kinase 2, a regulator of D2 receptor desensitization. | SIGNOR-263964 |
Q96NM4 | Q9UL17 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.294 | We subsequently found that TOX2 was independent of ETS-1 but could directly upregulate the transcription of TBX21 (encoding T-BET). | SIGNOR-266097 |
P49841 | P12931 | 1 | phosphorylation | up-regulates activity | 0.383 | P -Ser9 GSK-3\u03b2 phosphorylates Ser43, Ser51, and Ser493 residues of src, regulating src activity. | SIGNOR-278444 |
P48539 | P35398 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | 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-266848 |
P51812 | P68431 | 1 | phosphorylation | down-regulates activity | 0.2 | Phosphorylation at ser-11 (h3s10ph) by rps6ka4 and rps6ka5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or uv irradiation and result in the activation of genes, such as c-fos and c-jun. | SIGNOR-119229 |
P49841 | P49715 | 1 | phosphorylation | up-regulates activity | 0.379 | Glycogen synthase kinase 3 (GSK3) phosphorylates T222 and T226, causing a conformational change in C/EBPα. GSK3-mediated phosphorylation does not, in itself, dramatically alter the activity of C/EBPα in our assays. phosphorylation of C/EBPalpha and other substrates by GSK3 may be required for adipogenesis, since treatment of differentiating preadipocytes with lithium inhibits their conversion to adipocytes. | SIGNOR-251231 |
Q9HC98 | P52948 | 1 | phosphorylation | down-regulates activity | 0.315 | To elucidate which of the identified sites can be targeted by CDK1/cyclin B1 and Nek6 in vitro (Figure S1D), we performed phosphorylation reactions using recombinant kinases and unlabeled ATP followed by phosphopeptide mapping (Table S1). MS analysis confirmed phosphorylation of S591 and S822 by Nek6 as well as phosphorylation of T529, T536, S595, S606, and T653 by CDK1. Phosphomimetic Mutants of Nup98 Show Defects in NPC Localization | SIGNOR-273893 |
Q5VWQ8 | O75460 | 2 | binding | up-regulates activity | 0.382 | DAB2IP binds IRE1α, and was shown to be required for activation of this signaling cascade in endothelial cells. IRE1α can trigger pro-apoptotic JNK signaling through recruitment of the TRAF2–ASK1 complex. DAB2IP facilitates IRE1α activation, and participates in a signaling complex required to induce TRAF2-dependent ASK1 activation and JNK phosphorylation. | SIGNOR-254749 |
P02675 | P45452 | 0 | cleavage | down-regulates quantity by destabilization | 0.2 | Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system.|MMP-13 27YVATRDN g-chain| 20ADSGEGD a-chain| 124RNSVDXLNXN b-chain| 442LRTGKEKV a-chain | SIGNOR-263615 |
Q99523 | O75914 | 0 | phosphorylation | down-regulates activity | 0.2 | PAKs specifically phosphorylate Ser15 of the sortilin-cd and alter its trafficking. It can be concluded that PAK1-3 may indeed instigate the phosphorylation of sortilin and that they target a single serine residue (Ser15) located in the kinase domain-binding site of the sortilin-cd. Full-length sortilins with the serine at position 793 (residue 15 in the cytoplasmic domain) (for the sequence, see Fig. 2). Phosphorylation (Ser15) downregulates the sortilin–AP-1 interaction. | SIGNOR-273719 |
P13569 | Q13976 | 0 | phosphorylation | up-regulates | 0.506 | Direct amino acid sequencing and peptide mapping of cf-2 revealed that serines 660, 700, 737, and 813 as well as serine 768, serine 795, or both were phosphorylated by pka and pkgcftr possesses a large cluster of strict dibasic consensus sites for phosphorylation by protein kinase a (pka) in the r-domain and an obligatory dependence on phosphorylation is a hallmark of cftr cl(-) channel function | SIGNOR-18249 |
Q9Y2K2 | Q53ET0 | 1 | phosphorylation | down-regulates activity | 0.635 | We found that QSK and SIK phosphorylated TORC2 at Ser171 as well as at least two additional residues, namely Ser70 and Ser348|QIK also phosphorylates the CREB co-activator TORC2, in unstimulated cells, to sequester it in the cell cytoplasm, thereby inhibiting CREB-dependent gene-expression | SIGNOR-249170 |
Q16633 | P09086 | 2 | binding | up-regulates | 0.562 | We have shown previously that both octamer binding transcription factors, namely the ubiquitous oct-1 and the b cell-specific oct-2a protein, can be enhanced in transcriptional activity by their association with the b cell-specific coactivator protein bob1, also calledobf-1or oca-b. | SIGNOR-42278 |
Q13131 | O75385 | 2 | phosphorylation | up-regulates activity | 0.572 | Ampk and ulk1 interact and that the latter is phosphorylated by ampk. This phosphorylation leads to the direct activation of ulk1 by ampk bypassing mtor-inhibition. | SIGNOR-173038 |
P07996 | P01138 | 2 | binding | up-regulates | 0.278 | We have identified a mechanism for the activation of latent tgf-beta that involves binding of the secreted and extracellular matrix protein, thrombospondin-1 (tsp-1), to the latent precursor. | SIGNOR-75624 |
P46934-4 | P12931 | 0 | phosphorylation | up-regulates activity | 0.417 | Activation of c-Src by epidermal growth factor (EGF) also promoted tyrosine phosphorylation and enhanced the activity of NEDD4. | SIGNOR-276860 |
O94992 | Q00987 | 0 | ubiquitination | up-regulates activity | 0.465 | Here we report that human double minute-2 protein (HDM2), a p53-specific E3 ubiquitin ligase, specifically ubiquitinates HEXIM1 through the lysine residues located within the basic region of HEXIM1.|However, the HDM2-induced HEXIM1 ubiquitination does not lead to proteasome-mediated protein degradation. | SIGNOR-278701 |
P05771 | Q5T7P8 | 1 | phosphorylation | up-regulates activity | 0.2 | We found by site-directed mutagenesis that Thr418 and/or Thr419 in the polybasic region (KKKTTIK) of the C2B domain--a key region for the function of synaptotagmins--are the PKC target that regulates its inhibitory effect on acrosomal exocytosis. Similarly, we showed that Thr284 in the polybasic region of C2A (KCKLQTR) is the target for PKC-mediated phosphorylation in this domain. | SIGNOR-273565 |
P01303 | P25929 | 2 | binding | up-regulates | 0.857 | Analogs of npy and pyy have been synthesized that contain a proline residue in position 34 of the molecule, i.e., [leu31, pro34]npy (fuhlendorff et al., 1990) or [pro34]pyy (grandt et al., 1994b), and are much more potent at y1 than y2receptors. | SIGNOR-56522 |
Q9Y4G8 | Q04759 | 0 | phosphorylation | up-regulates | 0.2 | After t-cell activation, the direct phosphorylation of rapgef2 at ser960 by pkc- theta regulates rap1 activation as well as lfa-1 adhesiveness to icam-1. Pkc- theta and its effector rapgef2 are critical factors in tcr signaling to rap1 | SIGNOR-181186 |
P11717 | Q7Z6M1 | 0 | relocalization | up-regulates activity | 0.385 | P40 is a very potent transport factor in that the pure, recombinant protein can stimulate, significantly, an in vitro transport assay that measures transport of mannose 6-phosphate receptors from endosomes to the trans-Golgi network. The functional importance of p40 is confirmed by the finding that anti-p40 antibodies inhibit in vitro transport. Finally, p40 shows synergy with Rab9 in terms of its ability to stimulate mannose 6-phosphate receptor transport. These data are consistent with a model in which p40 and Rab9 act together to drive the process of transport vesicle docking. | SIGNOR-253090 |
P53611 | P20339 | 1 | lipidation | up-regulates activity | 0.491 | Prenylation (or geranylgeranylation) of Rab GTPases is catalysed by RGGT (Rab geranylgeranyl transferase) and requires REP (Rab escort protein). In the classical pathway, REP associates first with unprenylated Rab, which is then prenylated by RGGT. In the alternative pathway, REP associates first with RGGT; this complex then binds and prenylates Rab proteins. Rab GTPases need to be geranylgeranylated on either one or two cysteine residues in their Ctermini in order to localize to the correct intracellular membrane and be functional | SIGNOR-265573 |
Q15418 | P78371 | 1 | phosphorylation | up-regulates | 0.249 | Furthermore, both the s260a and s260d mutants showed a decreased folding capacity as compared to cells expressing the wild-type cct_ subunit ( fig.?_5e), suggesting that a cyclic phosphorylation of the s260 site by s6k1 is likely to be important for chaperonin function and that mutation of this site interferes with this process. | SIGNOR-172986 |
Q9UKV0 | Q96GD4 | 0 | phosphorylation | down-regulates | 0.262 | We define the precise site of aurb-mediated phosphorylation as a conserved serine within the nuclear localization signals of hdac4, hdac5, and hdac9 at ser265, ser278, and ser242, respectivelyduring mitosis, aurb-mediated phosphorylation may localize class iia hdacs to a phosphorylation gradient at the spindle midzone, permitting temporal and spatial regulatory mechanisms altering hdac protein interactions | SIGNOR-198654 |
P43657 | P63092 | 2 | binding | up-regulates activity | 0.323 | LPAR1 is reported to associate with Gia,G12/13a,orGqa; LPAR3 with Gia or Gqa; and LPAR6 withGia,G12/13a,orGsa. | SIGNOR-278873 |
Q9P286 | Q9BY11 | 1 | phosphorylation | up-regulates activity | 0.2 | We identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo. | SIGNOR-263025 |
P78536 | O14944 | 1 | cleavage | up-regulates activity | 0.565 | ADAM17 is involved in the release and activation of several growth factors and cytokine receptor ligands. Among the growth factors activated by ADAM17 are TGF-alpha, amphiregulin, epiregulin and HB-EGF | SIGNOR-259843 |
P08069 | Q13322 | 2 | binding | down-regulates | 0.739 | Grb10 negatively regulates growth factor signaling. It binds the insulinand insulin-like growth factor 1 (igf-1) receptors, and mice without grb10 are larger and exhibit enhanced insulin sensitivity | SIGNOR-174062 |
P13569 | Q9UNE7 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.471 | Here we show that CHIP functions with Hsc70 to sense the folded state of CFTR and targets aberrant forms for proteasomal degradation by promoting their ubiquitination. | SIGNOR-272584 |
Q9Y4X5 | Q13616 | 2 | binding | up-regulates activity | 0.356 | Here, we provide evidence that Ariadne RBR E3 ubiquitin ligases such as TRIAD1 and HHARI can bind and be activated by CRL complexes. Whereas TRIAD1 specifically associates with CUL5–RBX2, HHARI is more promiscuous towards cullin types and associates with RBX1-associated cullins 1, 2, 3, and 4A. Interestingly, both TRIAD1 and HHARI show a strong preference for binding the neddylated form of the cullin. Our data suggest a novel function of NEDD8 in directing specific CRLs to Ariadne RBR ligases, which in turn exert influence on the levels of their cognate neddylated cullin. | SIGNOR-268844 |
P02452 | P01137 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.485 | COL1A1 expression is regulated by upstream genes and the binding of regulatory elements at multiple binding sites upstream of its promoter. During cancer progression, CAFs reorganize and cross-link COL1A1, which accumulates and stiffens in the tumor stroma [12], [18]. This process may involve fibrogenic factors, especially transforming growth factor-beta (TGF-β1). Indeed, a TGF-β1 response sequence was identified 174 nucleotides upstream of the COL1A1 transcription start site, and was shown to up-regulate COL1A1 promoter activity | SIGNOR-277678 |
P06493 | O94916 | 1 | phosphorylation | up-regulates | 0.2 | High nacl-induced activation of cdk5 increases phosphorylation of the osmoprotective transcription factor tonebp/orebp at threonine 135, which contributes to its rapid nuclear localization. we performed in vitro kinase assays using the tonebp/orebp peptide containing t135 as substrate (figure 3b, right panel) and various recombinant kinases. The peptide is strongly phosphorylated by cdk5, less by cdk1. | SIGNOR-170882 |
Q9HCE7 | P31749 | 0 | phosphorylation | up-regulates activity | 0.352 | Furthermore, phosphorylation of Smurf1 by Akt1 was carried out specifically on the T145 residue, as mutation of this site abolished recognition of Smurf1 by the Akt1 phosphorylation motif antibody (Figure 5D).|We also identified that Smurf1 itself is targeted for phosphorylation by Akt1 and Akt2, regulating its stability. | SIGNOR-279778 |
P06493 | P62820 | 1 | phosphorylation | down-regulates activity | 0.526 | We now present biochemical evidence for a mitosis-specific p34cdc2 phosphorylation of RablAp and Rab4p.We also show that the distribution of RablAp and Rab4p between cytosolic and membrane-bound forms is different in interphase and mitotic cells. | SIGNOR-261284 |
P00734 | Q07954 | 2 | binding | up-regulates | 0.282 | In vitro binding studies revealed that antithrombin iii (atiii)thrombin, heparin cofactor ii (hcii)thrombin, and ?1-antitrypsin (?1AT)trypsin bound to purified lrp | SIGNOR-41090 |
Q12888 | Q15759 | 0 | phosphorylation | down-regulates activity | 0.2 | Here we show that 53BP1 is phosphorylated during mitosis on two residues, T1609 and S1618, located in its well-conserved ubiquitination-dependent recruitment (UDR) motif.|Dephosphorylation enables the recruitment of 53BP1 to double-strand DNA breaks |phosphorylation of T1609 is likely to be mediated by p38 MAPK | SIGNOR-264447 |
P67809 | P51812 | 0 | phosphorylation | up-regulates | 0.538 | We therefore conclude that rsk1/rsk2 are novel activators of yb-1, able to phosphorylate the serine 102 residue. | SIGNOR-182165 |
P08912 | P50148 | 2 | binding | up-regulates activity | 0.452 | 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-257217 |
Q15910 | P52333 | 0 | phosphorylation | up-regulates activity | 0.428 | These results demonstrate that phosphorylation of EZH2 by JAK3 on the Y244 increases the interaction with Polymerase II and decreases the association with PRC2 components promoting the expression of non-canonical genes.|To explore the mechanism of JAK3 mediated EZH2 activation, the authors performed co-immunoprecipitation assays, which revealed interaction of EZH2 with JAK3 and polymerase II. | SIGNOR-278518 |
P04198 | P49841 | 0 | 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 |
P49841 | P01106 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.72 | Phosphorylation of Thr 58, likely mediated by GSK-3 but dependent on the prior phosphorylation of Ser 62, is associated with degradation of Myc. | SIGNOR-252080 |
O95271 | P53350 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.427 | Here, we report that Plk1 forms a complex with TNKS1 in vitro and in vivo, and phosphorylates TNKS1. Phosphorylation of TNKS1 by Plk1 appears to increase TNKS1 stability and telomeric poly(ADP-ribose) polymerase (PARP) activity. By contrast, targeted inhibition of Plk1 or mutation of phosphorylation sites decreased the stability and PARP activity of TNKS1, leading to distort mitotic spindle-pole assembly and telomeric ends. | SIGNOR-276245 |
Q9H0H3 | P53396 | 2 | binding | down-regulates quantity by destabilization | 0.344 | Here, we found that CUL3 interacts with ACLY through its adaptor protein, KLHL25 (Kelch-like family member 25), to ubiquitinate and degrade ACLY in cells. | SIGNOR-272333 |
Q9ULB1 | Q8N0W4 | 2 | binding | up-regulates activity | 0.77 | Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c) | SIGNOR-264145 |
Q15058 | O14578 | 2 | binding | up-regulates activity | 0.723 | We find that KIF14 targets to the central spindle via its interaction with PRC1 and has an essential function in cytokinesis. In KIF14-depleted cells, citron kinase but not other components of the central spindle and cleavage furrow fail to localize. Furthermore, the localization of KIF14 and citron kinase to the central spindle and midbody is codependent, and they form a complex depending on the activation state of citron kinase. | SIGNOR-266422 |
P08670 | Q13177 | 0 | phosphorylation | down-regulates activity | 0.307 | In vitro analyses revealed that vimentin served as an excellent substrate for PAK. This phosphorylated vimentin lost the potential to form 10 nm filaments. We identified Ser25, Ser38, Ser50, Ser65 and Ser72 in the amino-terminal head domain as the major phosphorylation sites on vimentin for PAK. | SIGNOR-250243 |
P51677 | P51671 | 2 | binding | up-regulates | 0.936 | Eotaxin (CCL11) is a specific ligand for CCR3 and serves as a potent chemoattractant for eosinophils | SIGNOR-254356 |
Q96S44 | P31749 | 0 | phosphorylation | up-regulates | 0.297 | Here we show that such an activation of prpk is mediated by another kinase, akt/pkb, which phosphorylates prpk at ser250. | SIGNOR-252503 |
P49841 | Q5VWQ8 | 2 | binding | up-regulates activity | 0.311 | DAB2IP activates GSK-3β and antagonizes Wnt-mediated EMT. GSK-3β appears to directly associate with DAB2IP. Because DAB2IP is not a phosphatase, the mechanism of GSK-3β activation by DAB2IP is likely mediated by a separate phosphatase associated within this complex. PP2A is critical for DAB2IP-mediated GSK-3β activation and MET responses. | SIGNOR-254752 |
O60678 | P00352 | 2 | binding | down-regulates activity | 0.2 | We identified the specific residues in the catalytic domain of PRMT3 that facilitate interaction with the C-terminal region of ALDH1A1. PRMT3 inhibits the enzymatic activity of ALDH1A1 and negatively regulates the expression of retinoic acid responsive genes in a methyltransferase activity independent manner. | SIGNOR-276751 |
O96017 | O96017 | 2 | phosphorylation | up-regulates activity | 0.2 | Thus, activation of chk2 in irradiated cells may occur through oligomerization of chk2 via binding of the thr-68-phosphorylated region of one chk2 to the fha domain of another. Oligomerization of chk2 may therefore increase the efficiency of trans-autophosphorylation resulting in the release of active chk2 monomers that proceed to enforce checkpoint control in irradiated cells. | SIGNOR-116135 |
O00444 | P30307 | 1 | phosphorylation | up-regulates quantity | 0.461 | Conclusion: PLK4 contributes to the formation of PGCCs by regulating the expression of CDC25C and is associated with the expression and subcellular location of CDC25C, pCDC25C-ser216 and pCDC25C-ser198.|PLK4 could interact with CDC25C and promote CDC25C phosphorylation which was associated with the formation of PGCCs. | SIGNOR-280074 |
O15105 | P49910 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | ZNF165 drives the unrestrained activation of transforming growth factor β (TGFβ) signalling by directly inactivating the expression of negative feedback pathway regulators, SMURF2, SMAD7 and PMEPA1. | SIGNOR-266093 |
Q86Y13 | Q96KK5 | 1 | monoubiquitination | up-regulates activity | 0.2 | 2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation. | SIGNOR-271760 |
O15055 | P48730 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.869 | Human casein kinase Idelta phosphorylation of human circadian clock proteins period 1 and 2. We have now extended our previous studies to show that human casein kinase Idelta (hCKIdelta), the closest homologue to hCKIepsilon, associates with and phosphorylates hPER1 and causes protein instability. Furthermore, we observed that both hCKIdelta and hCKIepsilon phosphorylated and caused protein instability of human period 2 protein (hPER2). | SIGNOR-268000 |
P12931 | P33151 | 1 | phosphorylation | down-regulates activity | 0.567 | cadherins also act to prevent epithelial cell motilityCadherin-cytoskeletal interactions occur through a number of adaptor proteins that interact with the C-terminal portion of the cadherin cytoplasmic tail, including the _-, _-, and _-catenin (6, 10). Additionally, VE-cadherin stability at the plasma membrane may be regulated by the binding of p120-catenin to the juxtamembrane region of the cytoplasmic tailWe show here that tyrosine phosphorylation of the adherens junction protein VE-cadherin at two critical tyrosines, Tyr-658 and Tyr-731, via tyrosine kinase activation or phosphatase inactivation was sufficient to prevent the binding of p120- and beta-catenin, respectively, to the cytoplasmic tail of VE-cadherinVE-cadherin becomes phosphorylated on Tyr-658 and/or Tyr-731 in response to Src kinase activity. | SIGNOR-246462 |
Q5TCZ1 | P12931 | 0 | phosphorylation | up-regulates activity | 0.64 | First, we observed that the co-expression of both activated Src and wild-type Tks5 stimulated gelatin degradation beyond that of Tks5 overexpression alone ( ).|In melanoma cells Src dependent phosphorylation of Tks5 at tyrosine 557 is important for binding to Nck, for Nck recruitment to invadopodia, and for invadopodia associated matrix degradation activity . | SIGNOR-280134 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.