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 |
|---|---|---|---|---|---|---|---|
P35222 | P06241 | 0 | phosphorylation | down-regulates activity | 0.851 | Interaction of beta-catenin with alpha-catenin is regulated by the phosphorylation of beta-catenin Tyr-142. This residue can be phosphorylated in vitro by Fer or Fyn tyrosine kinases. Transfection of these kinases to epithelial cells disrupted the association between both catenins. | SIGNOR-251162 |
P38398 | Q86YC2 | 0 | binding | up-regulates activity | 0.851 | The BRCA1-PALB2 interaction is required for homologous recombination repair.Here, we report that PALB2, the partner and localizer of BRCA2, binds directly to BRCA1, and serves as the molecular scaffold in the formation of the BRCA1-PALB2-BRCA2 complex. | SIGNOR-244487 |
P30307 | O14757 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.85 | The signal for ubiquitination after uv and ir exposure is created by phosphorylation of cdc25a mediated by chk1 and chk2, respectively. Chk1 is a major kinase phosphorylating cdc25a (ser76/124) and cdc25c (ser216). | SIGNOR-163158 |
Q9H8S9 | Q13188 | 0 | phosphorylation | up-regulates | 0.85 | Mob1, which forms a complex with lats1/2, is also phosphorylated by mst1/2, resulting in an enhanced lats1/2 mob1 interaction. | SIGNOR-175809 |
Q8IUC6 | O00206 | 0 | binding | up-regulates activity | 0.85 | To initiate the innate immune response, Toll-like receptors (TLRs) associate with cytoplasmic adaptor proteins through TIR (Toll/interleukin-1 receptor) domain interactions. The four principal signaling adaptor proteins include MyD88, MAL, TRIF and TRAM, and the fifth protein SARM, involved in negative regulation of TLR pathways, is usually considered a part of the TIR domain-containing adaptor protein group | SIGNOR-252067 |
P46527 | P31749 | 0 | phosphorylation | down-regulates | 0.85 | Because Thr198-phosphorylated p27Kip1 was localized only in the cytoplasm, Akt might promote 14-3-3 binding to p27Kip1 by phosphorylation at Thr198, allowing its cytoplasmic localization and degradation. | SIGNOR-88294 |
P62993 | P04626 | 0 | relocalization | up-regulates | 0.85 | All erbb ligands and receptors couple to activation of the ras-mapk pathway, either directly through sh2 domain-mediated recruitment of grb-2 or indirectly through ptb domain-mediated binding of the shc adaptor | SIGNOR-121968 |
Q99594 | P46937 | 0 | binding | up-regulates | 0.85 | When dephosphorylated, yap/taz enter nuclei and induce gene transcription by interacting with transcription factors tead14. | SIGNOR-201471 |
O75385 | P42345 | 0 | phosphorylation | down-regulates activity | 0.849 | mTORC1, which is often referred to as the gatekeeper to autophagy, is a key regulator of the Ulk1-Atg13-FIP200 kinase complex.11,14,25 Under nutrient-rich conditions, active mTORC1 associates with and inactivates the Ulk1-Atg13-FIP200 complex by phosphorylating Ulk1 and Atg13. | SIGNOR-183903 |
O00141 | P42345 | 0 | phosphorylation | up-regulates | 0.849 | Mtor phosphorylated sgk1, but not sgk1-s422a, in vitro. Sgk1 phosphorylated p27 in vitro. These data implicate sgk1 as an mtorc1 (mtor-raptor) substrate. mtor may promote g1 progression in part through sgk1 activation | SIGNOR-179113 |
Q9UPX8 | Q9P1A6 | 0 | relocalization | up-regulates activity | 0.849 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264590 |
Q8IU57 | Q8IZI9 | 0 | binding | up-regulates | 0.849 | Il-28 and il-29 interacted with a heterodimeric class ii cytokine receptor that consisted of il-10 receptor beta (il-10rbeta) and an orphan class ii receptor chain, designated il-28ralpha. | SIGNOR-96243 |
Q16288 | P20783 | 0 | binding | up-regulates | 0.849 | Trkc, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3. | SIGNOR-20699 |
Q9Y6K9 | Q96EP0 | 0 | polyubiquitination | up-regulates activity | 0.849 | Involvement of Gln271 and Asp275 of NEMO in LUBAC-mediated linear polyubiquitination.vHOIP NZF1 also recognizes NEMO, and this recognition is involved in linear polyubiquitination of NEMO. Linear chains conjugated to NEMO are recognized by NEMO in trans on another IKK complex, thereby inducing multimerization of the IKK complex and trans autophosphorylation of IKK2. | SIGNOR-272052 |
Q13158 | O14763 | 0 | binding | up-regulates | 0.849 | Fadd binds to ligated trailr1 or trail-r2 | SIGNOR-98565 |
Q15052 | Q9Y2X7 | 0 | binding | up-regulates activity | 0.849 | Screening for potential mediators of this effect resulted in the identification of the Rac1-specific GTPase-activating protein ARHGAP17 and the guanine nucleotide exchange factor ARHGEF6 as new PKA and PKG substrates in platelets. We mapped the PKA/PKG phosphorylation sites to serine 702 on ARHGAP17 using Phos-tag gels and to serine 684 on ARHGEF6. |we show that ARHGEF6 is constitutively linked to GIT1, a GAP of Arf family small G proteins, and that ARHGEF6 phosphorylation enables binding of the 14-3-3 adaptor protein to the ARHGEF6/GIT1 complex. | SIGNOR-272165 |
Q08999 | P24941 | 0 | phosphorylation | down-regulates | 0.849 | When expressed in u2os cells, the phosphorylation-deficient mutant p130(delta)(cdk4), in which the cdk4 specific sites were mutated to alanine residues, imposed a more sustained g1 arrest than a constitutively active prb(delta)(cdk), known to repress all cellular e2f activity | SIGNOR-87492 |
O75096 | O00468 | 0 | binding | up-regulates activity | 0.849 | AGRN is released by the nerve and binds to LRP4, which then binds to MuSK. This interaction leads to MuSK autophosphorylation and activation of its kinase function, leading to anterograde signalling by subsequent phosphorylation of DOK7 (not shown), which binds MuSK as a dimer. | SIGNOR-273849 |
P20042 | Q9NR50 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.848 | EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity. | SIGNOR-269131 |
P25963 | Q9Y6K9 | 0 | phosphorylation | down-regulates activity | 0.848 | IκB components are phosphorylated on two amino-terminal serine residues by the IκB kinase (IKK) complex, composed of two catalytic proteins, IKKα and IKKβ, and the regulatory subunit IKKγ (NEMO, IKBKG). This modification targets IκB for degradation by the proteasome, allowing the release and nuclear translocation of NF-κB. | SIGNOR-280462 |
P51617 | Q99836 | 0 | binding | up-regulates activity | 0.848 | Interleukin-1 (il-1) stimulates the association of the il-1 receptor-associated protein kinase (irak) with the heterodimer of il-iri and il-iracp via the adapter protein myd88. Myd88 binds to both irak (il-1 receptor-associated kinase) and the heterocomplex (the signaling complex) of the two receptor chains and thereby mediates the association of irak with the receptor. | SIGNOR-67143 |
Q01196 | Q13951 | 0 | binding | up-regulates quantity by stabilization | 0.848 | The RUNX genes encode the α subunit of the transcription factor PEBP2/CBF. The β subunit consists of the non-RUNX protein PEBP2β. We found that RUNX1/AML1, which is essential for hematopoiesis, is continuously subjected to proteolytic degradation mediated by the ubiquitin–proteasome pathway. When PEBP2β is present, however, the ubiquitylation of RUNX1 is abrogated and this causes a dramatic inhibition of RUNX1 proteolysis. | SIGNOR-255742 |
O60231 | Q92917 | 0 | binding | up-regulates quantity | 0.848 | In this report, we showed that GPKOW interacted directly with the DHX16/hPRP2 and with RNA. Immuno-depletion of GPKOW from HeLa nuclear extracts resulted in an inactive spliceosome that still bound DHX16. | SIGNOR-266312 |
O14777 | Q96GD4 | 0 | phosphorylation | down-regulates | 0.848 | To determine whether the combinatorial regulation of the kmn network by aurora b observed in vitro is critical to controlling kinetochore-microtubule attachments in vivo, we next investigated the effect of the phosphomimetic (to aspartate) and nonphosphorylatable (to alanine) mutants of dsn1, knl1, and ndc80 in vertebrate cells. We predicted that both types of mutations in critical phosphorylation sites would affect chromosome segregation, since preventing the inactivation of inappropriately attached kinetochores by aurora b (in the nonphosphorylatable mutant) or constitutively inactivating this attachment (in the phosphomimetic mutant). | SIGNOR-165558 |
P35222 | Q9Y2T1 | 0 | binding | down-regulates | 0.848 | It has been found that a multiprotein complex assembled by the cytoplasmic component conductin induces degradation of cytoplasmic beta-catenin. The complex includes apc, the serine/threonine kinase gsk3 beta, and beta-catenin, which bind to conductin at distinct domains. | SIGNOR-79947 |
P60953 | Q15811 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.848 | Significantly, here we identify the long isoform of ITSN-1, which has Cdc42 GEF activity| We propose that GCC88 recruits ITSN-1-L to the TGN, which in turn activates Cdc42 at the trans-face of the Golgi (Figure 9A). | SIGNOR-260612 |
P29460 | P29459 | 0 | binding | up-regulates | 0.848 | However, a proper conformation required for high affinity binding is achieved only when p40 is associated with a p35 subunit or another p40 subunit. When p40 is associated with a p35 subunit, the heterodimer acts as an agonist mediating biologic activity. However, when p40 associates with another p40, the homodimer behaves as an antagonist in vitro | SIGNOR-27619 |
P01112 | P20936 | 0 | binding | down-regulates | 0.848 | The Ras protein sits at the center of a many-tiered cascade of molecular interactions. Most of the proteins along this cascade are activated by phosphorylation, but Ras uses a bound guanine nucleotide to toggle between its on and off states. Ras hydrolyzes GTP to GDP fairly quickly, turning itself off, and a collection of GTPase-activating proteins (GAPs) speed up the processthe complex between human h-ras bound to guanosine diphosphate and the guanosine triphosphatase (gtpase)-activating domain of the human gtpase-activating protein p120gap (gap-334) in the presence of aluminum fluoride was solved. | SIGNOR-68990 |
Q08334 | Q8IZI9 | 0 | binding | up-regulates | 0.848 | Il-28 and il-29 interacted with a heterodimeric class ii cytokine receptor that consisted of il-10 receptor beta (il-10rbeta) and an orphan class ii receptor chain, designated il-28ralpha. | SIGNOR-96246 |
Q04206 | O15111 | 0 | phosphorylation | up-regulates activity | 0.847 | Chromatographic fractionation of cell extracts allowed the identification of two distinct enzymatic activities phosphorylating ser-536. Peak 1 represents an unknown kinase, whereas peak 2 contained ikkalpha, ikkbeta, ikkepsilon, and tbk1. collectively, our results provide evidence for at least five kinases that converge on ser-536 of p65 and a novel function for this phosphorylation site in the recruitment of components of the basal transcriptional machinery to the interleukin-8 promoter. | SIGNOR-129931 |
P0CG48 | P45974 | 0 | cleavage | up-regulates quantity | 0.847 | Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors. | SIGNOR-270822 |
P04049 | P01116 | 0 | binding | up-regulates | 0.847 | Among other effectors, active ras binds and activates the raf kinase, iniziating a kinase cascade involving serine phosporylation of mek1/2 (mapkk) and tyrosine and threonine phosphorylation of erk1/2. the raf family of proteins (raf-1, a-raf, and b-raf) is serine/threonine kinases that bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases.. Association of ras with the mapk kinase kinase, raf, initiates the raf mek erk map kinase cascade. | SIGNOR-78911 |
O95166 | Q9NT62 | 0 | binding | up-regulates activity | 0.847 | Three human atg8 (hatg8) homologs, lc3, gabarap, and gate-16, have been characterized as modifiers in reactions mediated by hatg7 (an e1-like enzyme) and hatg3 (an e2-like enzyme) | SIGNOR-141868 |
P55199 | Q96JC9 | 0 | binding | up-regulates | 0.847 | Positive regulation of ell elongation activity depends on stable binding of eaf1 to the ell n terminus | SIGNOR-138516 |
P08476 | P19883 | 0 | binding | down-regulates activity | 0.846 | Blocking activin action by pre-treatment with its binding protein, follistatin, modifies the inflammatory cytokine cascade, and reduces the severity of the subsequent inflammatory response and mortality | SIGNOR-235134 |
P36897 | P01137 | 0 | binding | up-regulates activity | 0.846 | TGFbeta signals are transmitted via a cell surface receptor complex consisting of the TGFbeta type I receptor (TbetaRI) and TGFbeta type II receptor (TbetaRII). To initiate signal transduction, TGFbeta binds to TbetaRII, which in turn recruits TbetaRI, leading to the formation of a tetrameric receptor complex. | SIGNOR-249548 |
Q14676 | Q13315 | 0 | phosphorylation | up-regulates | 0.846 | We show that, in response to ionizing radiation, mdc1 is hyperphosphorylated in an atm-dependent manner, and rapidly relocalizes to nuclear foci that also contain the mre11 complex, phosphorylated histone h2ax and 53bp1. | SIGNOR-98798 |
P42336 | Q92569 | 0 | binding | up-regulates | 0.846 | The region between the src homology 2 (sh2) domains of p55pik bound to the nh2 terminus region of p110alpha | SIGNOR-53597 |
O60566 | Q02224 | 0 | binding | up-regulates activity | 0.846 | Without CENP-E, diminished levels of BubR1 are recruited to kinetochores and BubR1 kinase activity remains at basal levels. CENP-E binds to and directly stimulates the kinase activity of purified BubR1 in vitro. Thus, CENP-E is required for enhancing recruitment of its binding partner BubR1 to each unattached kinetochore and for stimulating BubR1 kinase activity, implicating it as an essential amplifier of a basal mitotic checkpoint signal. | SIGNOR-252043 |
P12004 | Q9NS91 | 0 | ubiquitination | up-regulates activity | 0.846 | Second, these findings suggest the following model (XREF_FIG) : upon replication fork stalling at cisplatin induced DNA lesions, the RAD18 and RAD6 complex ubiquitylates PCNA on Lys164.|The DNA damage-activated E3 ubiquitin ligase RAD18 promotes repair of interstrand DNA cross-links by ubiquitylating PCNA and recruiting FANCL to chromatin. | SIGNOR-278612 |
P03372 | Q15788 | 0 | binding | up-regulates | 0.845 | Steroid receptor co-activator (src1) is one of a number of transcriptional co-activators that are capable of potentiating the activity of nuclear receptors including the oestrogen receptor (er). | SIGNOR-54442 |
O14757 | Q13315 | 0 | phosphorylation | up-regulates | 0.845 | Atr (predominantly) or atm (to a lesser extent) phosphorylates chk1 at ser317/345, directly leading to activation. | SIGNOR-163106 |
Q9BXW9 | P38398 | 0 | ubiquitination | up-regulates activity | 0.845 | The major genetic evidence supporting ubiquitin ligase function for BRCA1 in vivo comes from studies on the FANCD2 protein. Whereas in wild‐type cells the FANCD2 protein co‐localizes with BRCA1 in nuclear foci and becomes monoubiquitylated in response to DNA damage, HCC1937 cells, which encode a mutated form of BRCA1, are largely defective for both monoubiquitylation of FANCD2 and foci formation | SIGNOR-263236 |
O95999 | Q9BXL7 | 0 | binding | up-regulates | 0.845 | Card11 cooperates with bcl10 in a card domain-dependent manner.;These results implicate card11 in factor- specific activation of nf-kappab | SIGNOR-93869 |
P37198 | P61970 | 0 | binding | up-regulates activity | 0.845 | Our data suggest that NTF2 interacts directly with NPC protein 1362 and exerts its effect at a relatively late step in the nuclear protein import pathway. We obtained a cDNA encoding NTF2 and showed that the recombinant protein restores transport activity to p62-pretreated cytosol. | SIGNOR-261255 |
Q13257 | P51955 | 0 | phosphorylation | down-regulates activity | 0.845 | We demonstrated that overexpression of Nek2 can enhance the ability of Mad2 to cause delays in cell division.|We have demonstrated that Nek2 can bind and phosphorylate Mad2 and Cdc20. | SIGNOR-278446 |
P36941 | P01374 | 0 | binding | up-regulates | 0.845 | These experiments point toward the lt-alpha 1/beta 2 complex as the predominant membrane form of lt on the lymphocyte surface, and this complex is the primary ligand for the lt-beta receptor. | SIGNOR-35708 |
P29353 | P04629 | 0 | binding | up-regulates | 0.844 | Autophosphorylated trka binds directly to plc?, Abl, and shc. | SIGNOR-75408 |
Q12933 | P25942 | 0 | binding | up-regulates activity | 0.844 | Cd40, a tumor necrosis factor receptor (tnfr) family member, forms a complex containing adaptor molecules traf2 and traf3. | SIGNOR-179473 |
P42336 | P01111 | 0 | binding | up-regulates activity | 0.844 | Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85./it was also described that ras interacts with pi3k in a direct manner./lysine residue 227 is essential for the interaction of ras with pi3k | SIGNOR-175222 |
P60520 | Q9Y4P1 | 0 | cleavage | up-regulates activity | 0.844 | In mammals, at least three atg8 homologs, lc3, gabarap, and gate-16, have been identified (fig. 1a), all of which have structural ubiquitin folds (1416). In vivo and in vitro biochemical analyses have shown that human atg4b is an authentic cysteine protease essential for cleavage of the c terminus of each atg8 homolog to expose the c-terminal gly | SIGNOR-141932 |
P30304 | O96017 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.843 | We show that IR-induced destruction of Cdc25A requires both ATM and the Chk2-mediated phosphorylation of Cdc25A on serine 123. | SIGNOR-106808 |
P04637 | Q13315 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.843 | In response to ionizing radiation (ir), atm, the gene product mutated in ataxia telangiectasia, stabilizes and activates p53 through phosphorylation of ser15 and (indirectly) ser20. Here we show that phosphorylation of p53 on ser46, a residue important for p53 apoptotic activity, as well as on ser9, in response to ir also is dependent on the atm protein kinase. one pathway involves the phosphorylation of p53 and its negative regulator mdm2 by ataxia telangiectasia mutated (atm) and chk2 causing p53 activation and stabilization. | SIGNOR-115348 |
P17948 | P15692 | 0 | binding | up-regulates | 0.843 | Vegf exerts its action by binding to vegfr-1 and vegfr-2. | SIGNOR-121132 |
Q9GZM8 | P43034 | 0 | binding | up-regulates activity | 0.843 | We demonstrate that LIS1 directly interacts with the cytoplasmic dynein heavy chain (CDHC) and NUDEL. LIS1 is required for the proper distribution of NUDEL and cellular components regulated by CDHC function. Reduction of LIS1 leads to mislocalization of NUDEL, CDHC, β-tubulin, and the Golgi complex | SIGNOR-252157 |
Q06609 | O14757 | 0 | phosphorylation | up-regulates | 0.843 | We demonstrate that chk1 interacts with rad51, and that rad51 is phosphorylated on thr 309 in a chk1-dependent manner | SIGNOR-133375 |
P36941 | Q06643 | 0 | binding | up-regulates activity | 0.843 | These experiments point toward the lt-alpha 1/beta 2 complex as the predominant membrane form of lt on the lymphocyte surface, and this complex is the primary ligand for the lt-beta receptor. | SIGNOR-35759 |
Q9NVI1 | Q9NW38 | 0 | ubiquitination | up-regulates activity | 0.842 | Phosphorylation of FANCD2 and Fanconi anemia core components (broken pink circles) affects the efficiency of, but is not essential for, ID ubiquitination by the FA core complex, together with E1 and UBE2T. Analogously, ubiquitination of FANCD2 (solid orange ovals) is essential for DNA repair, activating the ID complex for chromatin binding | SIGNOR-263266 |
O15534 | P49674 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.842 | We show here that mPer proteins, negative limbs of the autoregulatory loop, are specific substrates for CKIepsilon and CKIdelta. The CKI phosphorylation of mPer1 and mPer3 proteins results in their rapid degradation, which is dependent on the ubiquitin-proteasome pathway. | SIGNOR-267997 |
O14727 | Q07817 | 0 | binding | down-regulates activity | 0.842 | These experiments demonstrate that bcl-xl associates with caspase-9 and apaf-1, and show that bcl-xl inhibits the maturation of caspase-9 mediated by apaf-1. | SIGNOR-56399 |
P19174 | P00533 | 0 | phosphorylation | up-regulates | 0.841 | We have identified the sites phosphorylated in vitro by epidermal growth factor (egf) receptor kinase in bovine brain phospholipase c-gamma (plc-gamma). They are tyrosine residues 472, 771, 783, and 1254. we propose, therefore, that the phosphorylation of plc-gamma by egf receptor kinase alters its interaction with putative inhibitory proteins and leads to its activation. | SIGNOR-20984 |
Q9NPB6 | Q05513 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.841 | APKC associates and phosphorylates Par6 on S345. aPKC expression stabilizes Par6 protein levels. We show that the aPKC, PKCι, interacts with TGF-β receptors through Par6 and that these proteins localize to the leading edge of migrating cells. Furthermore, Par6 phosphorylation on serine 345 by TGF-β receptors is enhanced in the presence of aPKC. aPKC kinase activity, as well as an association with Par6, were found to be important for Par6 phosphorylation. | SIGNOR-276433 |
P05198 | Q13144 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.84 | EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity. | SIGNOR-269123 |
O60566 | P53350 | 0 | phosphorylation | up-regulates | 0.84 | We identify s676 as a plk1-specific phosphorylation site on bubr1. These findings describe the first in vivo verified phosphorylation site for human bubr1, identify plk1 as the kinase responsible for causing the characteristic mitotic bubr1 upshift, and attribute a kt-specific function to the hyperphosphorylated form of bubr1 in the stabilization of kt-mt interactions. | SIGNOR-157646 |
Q14789 | O60763 | 0 | binding | up-regulates activity | 0.84 | The “cis-golgin tether” is one of the most well-characterized golgin tether complexes. It is composed of the COPI vesicle-associated golgin giantin linked to Golgi membrane-associated GM130 via p115. GM130 is in turn linked to GRASP65 via a PDZ-like domain. GRASP65 is anchored to the Golgi membrane through N-terminal myristoylation as well as through binding to other Golgi proteins [10]. Together, these proteins appear to mediate vesicle tethering at the cis-Golgi membrane. | SIGNOR-261237 |
P58400 | Q8N2Q7 | 0 | binding | up-regulates activity | 0.84 | 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-264149 |
P25054 | Q9Y2T1 | 0 | binding | up-regulates | 0.84 | It has been found that a multiprotein complex assembled by the cytoplasmic component conductin induces degradation of cytoplasmic beta-catenin. The complex includes apc, the serine/threonine kinase gsk3 beta, and beta-catenin, which bind to conductin at distinct domains. | SIGNOR-79944 |
Q9ULB1 | Q8N2Q7 | 0 | binding | up-regulates activity | 0.84 | 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-264144 |
Q9ULB1 | Q9NZ94 | 0 | binding | up-regulates activity | 0.84 | 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-264142 |
P46937 | O95835 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.84 | We show that YAP is phosphorylated by Lats on Ser 381 in one of the HXRXXS motifs, and this phosphorylation provides the priming signal for CK1delta/epsilon to phosphorylate a phosphodegron in YAP. The phosphorylated phosphodegron recruits beta-TRCP, leading to YAP ubiquitination and degradation under conditions of elevated Hippo pathway activity, such as cell contact inhibition | SIGNOR-218034 |
P38936 | P31749 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.84 | Pim-1, PKC, and Akt1 kinases phosphorylate Thr-145 and Ser-146 sites on p21 protein. Phosphorylation at Thr-145 promotes cytoplasmic translocation and stability of p21. Ser-146 phosphorylation mediated by Akt1 enhances p21 stabilization and promotes cell survival. | SIGNOR-157790 |
P58400 | Q9NZ94 | 0 | binding | up-regulates activity | 0.84 | 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-264147 |
P04150 | Q15596 | 0 | binding | up-regulates activity | 0.839 | Here we report that GRIP1 loss in macrophages attenuates glucocorticoid induction of several anti-inflammatory targets, and that GC treatment of quiescent macrophages globally directs GRIP1 toward GR binding sites dominated by palindromic GC response elements (GRE), suggesting a non-redundant GRIP1 function as a GR coactivator. | SIGNOR-256095 |
P62993 | P21860 | 0 | binding | up-regulates | 0.839 | All erbb ligands and receptors couple to activation of the ras-mapk pathway, either directly through sh2 domain-mediated recruitment of grb-2 or indirectly through ptb domain-mediated binding of the shc adaptor. In this study, we identify grb2 as a specific binding partner to tyrosines y1199 and y1268 of erbb3. | SIGNOR-121971 |
Q13635 | Q14623 | 0 | binding | down-regulates activity | 0.838 | Biochemical analysis of ptch and ptch2 shows that they both bind to all hedgehog family members with similar affinity and that they can form a complex with smo.Current models suggest that binding of Shh to PTCH prevents the normal inhibition of the seven-transmembrane-protein Smoothened (SMO) by PTCH. | SIGNOR-61311 |
P54764 | Q15768 | 0 | binding | up-regulates | 0.838 | Receptors of the epha group preferentially interact with glycosylphosphatidylinositol (gpi)-linked ligands (of the ephrin-a subclass, which comprises five ligands), while receptors of the ephb group preferentially interact with transmembrane ligands (of the ephrin-b subclass, which comprises three ligands) (table 1). In either case, binding of a ligand results in eph receptor autophosphorylation on tyrosine residues and activation of the kinase activity of the eph receptor | SIGNOR-52621 |
P10398 | P01112 | 0 | binding | up-regulates | 0.838 | The raf family of proteins (raf-1, a-raf, and b-raf) is serine/threonine kinases that bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases. | SIGNOR-175183 |
P04626 | Q06124 | 0 | dephosphorylation | down-regulates | 0.838 | ...which in turn suggests the importance SHP2 dephosphorylation of pTyr992 in EGFR and pTyr1023 in HER2 to mediate signaling.|More specifically, we show that acidic residues N-terminal to the substrate pTyr in EGFR and HER2 mediate specific binding by the SHP2 active site, leading to blockade of RasGAP binding and optimal signaling by the two receptors. | SIGNOR-262957 |
P24844 | Q15746 | 0 | phosphorylation | up-regulates | 0.838 | More than a dozen kinases have been reported to phosphorylate the rlcs of nm ii (fig. 2), including myosin light chain kinase (mlck;also known as mylk), rho-associated, coiled coil-containing kinase (rock), citron kinase, leucine zipper interacting kinase (zipk;also known as dapk3) and myotonic dystrophy kinase-related cdc42-binding kinase (mrck;also known as cdc42bp)6,34,45,46. These kinases phosphorylate rlcs on ser19, thr18 or both, to relieve the inhibition imposed on the myosin molecule by unphosphorylated rlcs and the head_head interaction outlined above. | SIGNOR-188797 |
Q96MU8 | O94907 | 0 | binding | up-regulates | 0.838 | Dkk1 has been shown to inhibitwnt by binding to and antagonizing lrp5/6. Here we show that the transmembrane proteins kremen1 and kremen2 are high-affinity dkk1 receptors that functionally cooperate with dkk1 to blockwnt/betBeta-catenin. Kremen2 forms a ternary complex with dkk1 and lrp6, and induces rapid endocytosis and removal of thewntreceptor lrp6 from the plasma membrane. | SIGNOR-88838 |
Q13501 | Q9GZQ8 | 0 | binding | up-regulates | 0.837 | Sqstm1/p62 (named a170 in the mouse;hereafter p62) is the first proposed example of such proteins (bj_?_?Rk_?_?Y et al.,2005). It binds polyubiquitinated protein aggregates via its uba domain and interacts with lc3 on the autophagosome/ this interaction is necessary for autophagic degradation of p62-positive cytoplasmic inclusion bodies containing ubiquitinated proteins. We also demonstrate that alis are indistinguishable from p62 inclusion bodies and that p62 is required for their formation. | SIGNOR-184255 |
Q16611 | O43521 | 0 | binding | up-regulates | 0.837 | Bim, and puma bind with high affinity to all pro-survival proteins | SIGNOR-196932 |
Q12968 | P45983 | 0 | phosphorylation | down-regulates | 0.837 | Jnks directly phosphorylate nuclear factor of activated t-cell (nfat) transcription factors, thus antagonizing the effects of calcium-regulated signaling through the protein phosphatase calcineurin | SIGNOR-118220 |
Q99683 | Q5VWQ8 | 0 | binding | up-regulates activity | 0.837 | DAB2IP also mediates recruitment of PP2A to ASK1, binding both proteins through its C2 domain; this favors removal of the inhibitory S967 phosphorylation and further activation of ASK1 | SIGNOR-254748 |
O15350 | Q00987 | 0 | binding | down-regulates activity | 0.837 | Since HDM2, a key negative regulator of p53, also binds to and inhibits p73, we asked whether p73 could mediate Nutlin-3-induced apoptosis. | SIGNOR-255470 |
P49146 | P01303 | 0 | binding | up-regulates | 0.837 | 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-56568 |
P62834 | P47736 | 0 | binding | down-regulates activity | 0.837 | Overexpression of Rap1GAP significantly inhibited Rap1 activation, ERK and Akt phosphorylation of HUVECs compared with pcDNA transfection controls | SIGNOR-278054 |
P08138 | P01138 | 0 | binding | up-regulates | 0.836 | The low affinity neurotrophin receptor p75ntr can mediate cell survival as well as cell death of neural cells by ngf and other neurotrophins. | SIGNOR-76832 |
P61586 | Q86VW2 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.835 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260544 |
O96017 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.835 | Phosphorylation and activation of chk2 are ataxia telangiectasia-mutated (atm) dependent in response to ir | SIGNOR-81403 |
Q09472 | Q96EB6 | 0 | deacetylation | down-regulates | 0.835 | Sirt1 induces deacetylation and repression of p300 itself (81). Mutational analysis demonstrated that sirt1 repression of p300 involves both lysine 1020 and lysine 1024 | SIGNOR-182511 |
Q13478 | Q14116 | 0 | binding | up-regulates | 0.835 | Acpl was required for il-18 responsiveness in terms of nf?B Induction and jnk activation | SIGNOR-60991 |
O15169 | O75581 | 0 | relocalization | down-regulates activity | 0.835 | The phosphorylation of lrp6 generates a docking site for axin and recruits it to the plasma membrane, where axin is inactivated and/or targeted for degradation by an unknown mechanism. | SIGNOR-148668 |
P10398 | P01111 | 0 | binding | up-regulates | 0.835 | The raf family of proteins (raf-1, a-raf, and b-raf) is serine/threonine kinases that bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases. | SIGNOR-175216 |
Q9NT62 | Q9GZQ8 | 0 | binding | up-regulates | 0.835 | 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-191549 |
O60934 | Q14676 | 0 | binding | up-regulates | 0.834 | Mdc1 also undergoes phosphorylation by ck2 after dna damage to generate a phospho-motif on mdc1, which binds directly to nbs1. | SIGNOR-184141 |
Q9UBS0 | P42345 | 0 | phosphorylation | up-regulates | 0.834 | In response to insulin and nutrients, mtorc1, consisting of mtor, raptor (regulatory-associated protein of mtor), and mlst8, is activated and phosphorylates eukaryotic initiation factor 4e-binding protein (4ebp) and p70 s6 kinase to promote protein synthesis and cell size. | SIGNOR-154821 |
P60953 | O43307 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.834 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260534 |
P61956 | P78317 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.834 | Here we demonstrate that the RING-domain-containing ubiquitin E3 ligase, RNF4 (also known as SNURF), targets poly-SUMO-modified proteins for degradation mediated by ubiquitin. RNF4 depletion or proteasome inhibition led to accumulation of mixed, polyubiquitinated, poly-SUMO chains. PML protein accumulated in RNF4-depleted cells and was ubiquitinated by RNF4 in a SUMO-dependent fashion in vitro.RNF4 preferentially binds to and ubiquitinates SUMO-2 polymers over SUMO-2 monomers in vitro | SIGNOR-272640 |
O75791 | Q92918 | 0 | phosphorylation | down-regulates activity | 0.834 | Serine/threonine phosphorylation of the T cell adaptor proteins SLP76 and GADS by HPK1 induces their release from signaling microclusters and subsequent termination of the T cell response. | SIGNOR-279421 |
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