GleghornLab/Signor_processed · Datasets at Hugging Face

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
Q13043	Q9H8S9	1	phosphorylation	up-regulates	0.9	Mob1, when phosphorylated by MST1/2, binds to the autoinhibitory motif in Lats1/2, which in turn leads to the phosphorylation of the Lats activation loop (Lats1 S909 and Lats2 S872) and thereby an increase of their kinase activity	SIGNOR-201306
P35222	Q9NQB0	1	binding	up-regulates activity	0.9	Hypophosphorylation of β-catenin and translocation into the nucleus leads to binding with members of the lymphoid-enhancer-binding factor/T-cell-specific transcription factor (LEF/TCF) family and activation of WNT target genesAs a member of LEF/TCF family, transcription factor 7 like 2 (Tcf7l2, formerly called Tcf4) is an important transcription factor triggering the downstream responsive genes of WNT signaling	SIGNOR-85757
Q9NW38	Q9BXW9	1	ubiquitination	up-regulates activity	0.9	Thus, eight of the nine components of the FA core complex are FA proteins (FANC‐A, B, C, E, F, G, L, and M). Furthermore, two of the newly discovered FA proteins have enzymatic activities: FANCL is a ubiquitin ligase essential for FANCD2 monoubiquitination in vivo	SIGNOR-263250
P52657	P20226	1	binding	up-regulates activity	0.9	The general transcription factor IIA (TFIIA) binds to the TATA binding protein (TBP) and mediates transcriptional activation by distinct classes of activators. \|Our results show that different activators utilize the general factor TFIIA in unique ways and that TFIIA contributes transcription activation functions in addition to the facilitation of TBP-DNA binding.	SIGNOR-262591
P51531	Q8TAQ2	1	binding	up-regulates	0.9	The remodeling activity of brg1 and hbrm is stimulated by baf170/baf155 and is further stimulated when ini1 is added.	SIGNOR-65435
O14798	P50591	1	binding	down-regulates	0.899	Albeit on binding the ligand, dcr1 and dcr2 do not transduce the apoptogenic signal,	SIGNOR-163611
P01135	P00533	1	binding	up-regulates activity	0.899	Our data indicate that a subset of cell lines is dependent on TGF-_-mediated activation of the EGFR for cell proliferation and strongly suggest that pancreatic tumors expressing high levels of TGF-_ and phosphorylated (activated) EGFR are EGFR-dependent in vitro and in vivo.	SIGNOR-93199
P30990	O95665	1	binding	down-regulates	0.898	Neurotensin binding to recombinant neurotensin nt2 receptor expressed in cho cells does not elicit a biological response as determined by second messenger measurements.	SIGNOR-62519
Q13625	P04637	1	binding	up-regulates	0.898	53bp2 interacts with the tumour suppressor p53 and enhances p53-mediated activation of transcription, possibly by facilitating the dephosphorylation of one or more sites on p53	SIGNOR-114762
P09038	P21802	1	binding	up-regulates	0.898	we determined the crystal structures of these two FGFR2 mutants in complex with fibroblast growth factor 2 (FGF2).These structures demonstrate that both mutations introduce additional interactions between FGFR2 and FGF2, thereby augmenting FGFR2-FGF2 affinity.	SIGNOR-86121
Q16576	O14929	1	binding	up-regulates activity	0.898	AMPK increased HAT1 activity through phosphorylation of HAT1-Ser190 and RBBP7-Ser314\| interaction between RBBP7 and HAT1 is required for acetyltransferase activity	SIGNOR-264786
Q96QV1	Q15465	1	binding	down-regulates activity	0.897	Hip encodes a membrane glycoprotein that binds to all three mammalian hedgehog proteins with an affinity comparable to that of ptc-1. our findings support a model in which hip attenuates hedgehog signalling as a result of binding to hedgehog proteins: a negative regulatory feedback loop established in this way could thus modulate the responses to any hedgehog signal.	SIGNOR-65078
Q06124	P35568	1	dephosphorylation	down-regulates	0.897	The specific activity of four candidate protein-tyrosine phosphatases (protein-tyrosine phosphatase 1b (ptp1b), sh2 domain-containing ptpase-2 (shp-2), leukocyte common antigen-related (lar), and leukocyte antigen-related phosphatase) (lrp) toward irs-1 dephosphorylation was studied using recombinant proteins in vitro. Ptp1b exhibited the highest specific activity these results provide new insight into novel molecular interactions involving ptp1b and grb2 that may influence the steady-state capacity of irs-1 to function as a phosphotyrosine scaffold and possibly affect the balance of postreceptor insulin signaling.	SIGNOR-74856
P18510	P14778	1	binding	down-regulates activity	0.897	Homozygous truncating mutations result in lack of secreted interleukin-1–receptor antagonist protein, which inhibits the proinflammatory cytokines interleukin-1α and interleukin-1β	SIGNOR-262302
P54619	P54646	1	binding	up-regulates	0.897	Gamma non-catalytic subunit mediates binding to amp, adp and atp, leading to activate or inhibit ampk: amp-binding results in allosteric activation of alpha catalytic subunit (prkaa1 or prkaa2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits.	SIGNOR-139173
P01008	P00740	1	cleavage	down-regulates activity	0.897	Antithrombin (AT), a member of the serine protease inhibitor (SERPIN) superfamily, is a major circulating inhibitor of blood coagulation proteases such as factor (F) IIa (known as thrombin), FXa and, to a lesser extent, FIXa, FXIa and FXIIa. SERPINC1, which encodes AT in humans, is located on chromosome 1q25.1	SIGNOR-264140
P35225	P24394	1	binding	up-regulates activity	0.896	IL-4 and IL-13 have overlapping but distinct effects on MFs, dependent on a common IL-4R, with profound changes in the expression of a range of cellular proteins and functions broadly implicated in the regulation of inflammation and repair.	SIGNOR-249528
P26927	Q04912	1	binding	up-regulates	0.896	P185ron is a tyrosine kinase activated by msp	SIGNOR-31107
O14788	Q9Y6Q6	1	binding	up-regulates activity	0.896	RANKL, a member of the tumour necrosis factor superfamily, is most abundantly expressed as a cell-surface protein by bone-marrow stromal cells. It interacts with its receptor RANK (which is encoded by Tnfrsf11a) on macrophages and mature osteoclasts.	SIGNOR-253042
O15111	P25963	1	phosphorylation	down-regulates quantity by destabilization	0.896	We described the purification of a 900 kda protein kinase complex, the ikb kinase (ikk), that phosphorylates ikbalfa and ikbbeta at the sites that mediate their ubiquitination and degradation	SIGNOR-52875
P52803	P54756	1	binding	up-regulates	0.896	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-52476
P13861	P22694	1	binding	down-regulates activity	0.896	Inactive PKA exists as a holoenzyme, comprised of two regulatory (R) subunits and two catalytic subunits . In the presence of cAMP, the holoenzyme becomes active by binding two cAMP molecules cooperatively to each R subunit, resulting in a conformational change in the R subunits, thus releasing the two C subunits to phosphorylate downstream targets	SIGNOR-258757
Q12933	Q13546	1	ubiquitination	up-regulates activity	0.895	Following binding to tradd, traf2 was thought to mediate non-degradative lys-63-linked polyubiquitination of rip1 via its ring e3 ligase domain. Rip1 is known to directly interact with traf2.	SIGNOR-59689
Q13490	Q9NR28	2	ubiquitination	down-regulates quantity by destabilization	0.895	Here we show that cIAP1 and cIAP2 are E3 ubiquitin-protein isopeptide ligases (ubiquitin ligases) for Smac. cIAPs stimulate Smac ubiquitination both in vivo and in vitro, leading to Smac degradation. cIAP1 and cIAP2 associate with overlapping but distinct subsets of E2 (ubiquitin carrier protein) ubiquitin-conjugating enzymes. The substrate-dependent E3 activity of cIAPs is mediated by their RING domains and is dependent on the specific interactions between cIAPs and Smac.	SIGNOR-271392
Q96S52	O43292	1	binding	up-regulates activity	0.895	To determine roles for PIG-S and PIG-T, we disrupted these genes in mouse F9 cells by homologous recombination. PIG-S and PIG-T knockout cells were defective in transfer of GPI to proteins, particularly in formation of the carbonyl intermediates. We also demonstrate that PIG-S and PIG-T form a protein complex with GAA1 and GPI8, and that PIG-T maintains the complex by stabilizing the expression of GAA1 and GPI8.	SIGNOR-261361
Q9NR28	Q13490	2	binding	down-regulates quantity	0.895	Smac promotes caspase-9 activation by binding to inhibitor of apoptosis proteins, IAPs, and removing their inhibitory activity. Smac is normally a mitochondrial protein but is released into the cytosol when cells undergo apoptosis.	SIGNOR-80206
Q99933	P11142	1	binding	up-regulates activity	0.895	Heat shock cognate protein 70 (Hsc70) regulates protein homeostasis through its reversible interactions with client proteins. Hsc70 has two major domains: a nucleotide-binding domain (NBD), that hydrolyzes ATP, and a substrate-binding domain (SBD), where clients are bound. Members of the BAG family of co-chaperones, including Bag1 and Bag3, are known to accelerate release of both ADP and client from Hsc70.	SIGNOR-254115
P50613	P19447	1	phosphorylation	down-regulates quantity by destabilization	0.895	These results led us to propose a model that spironolactone may trigger the phosphorylation of XPB at Ser90 by CDK7, which promotes the recognition and polyubiquitination of XPB by SCFFBXL18 for proteasomal degradation.	SIGNOR-277433
P31323	P22694	1	binding	down-regulates activity	0.894	Inactive PKA exists as a holoenzyme, comprised of two regulatory (R) subunits and two catalytic subunits . In the presence of cAMP, the holoenzyme becomes active by binding two cAMP molecules cooperatively to each R subunit, resulting in a conformational change in the R subunits, thus releasing the two C subunits to phosphorylate downstream targets	SIGNOR-258758
P67775	P31749	1	dephosphorylation	down-regulates activity	0.893	Protein phosphatase 2A negatively regulates insulin's metabolic signaling pathway by inhibiting Akt (protein kinase B) activity in 3T3-L1 adipocytes	SIGNOR-252614
O15520	P21802	1	binding	up-regulates	0.893	Rfgf-10 bound the kgfr with high affinity comparable to that of kgf	SIGNOR-57380
Q9NRY4	P61586	1	gtpase-activating protein	down-regulates activity	0.893	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-260492
Q9Y4K3	O43318	1	ubiquitination	up-regulates activity	0.893	Intriguingly, TGF-beta-induced TRAF6-mediated Lys 63-linked polyubiquitylation of TAK1 Lys 34 correlates with TAK1 activation. Our data show that TGF-beta specifically activates TAK1 through interaction of TbetaRI with TRAF6, whereas activation of Smad2 is not dependent on TRAF6.	SIGNOR-236071
Q9GZX6	Q8N6P7	1	binding	up-regulates	0.893	In addition, il-22 mediates inflammation and binds class ii cytokine receptor heterodimers il-22 ra1/crf2-4.	SIGNOR-86340
Q07889	P01112	1	guanine nucleotide exchange factor	up-regulates activity	0.892	The enhancement of H-Ras GTP levels induced by oncogenic K-Ras was abrogated when the expression of endogenous Sos was suppressed, implicating Sos as an essential intermediate in the cross talk between oncogenic K-Ras and WT H-Ras.	SIGNOR-59472
Q12933	Q13489	2	binding	up-regulates	0.892	A traf2 trimer interacts with one ciap2 both in the crystal and in solution through its death domain and amino-terminal region, tradd recruits rip1 (receptor-interacting protein), traf2, and through its interaction with traf2, c-iap1 and c-iap2 (13). Traf2 recruit ciap1 and ciap2. A traf2 trimer interacts with one ciap2 both in the crystal and in solution.	SIGNOR-182124
O14944	P00533	1	binding	up-regulates	0.892	Chemical cross-linking experiments showed that [125i]epiregulin directly bound to each of egfr and erbb-4 but not to erbb-2 and erbb-3. remarkably, three members of the epidermal growth factor (egf) family (ereg, areg, and epgn) showed increased expression that was associated with elevated epidermal activation of the egf receptor (egfr) and stat3, a downstream effector of egfr signaling.	SIGNOR-54351
Q13489	Q12933	2	ubiquitination	down-regulates quantity by destabilization	0.892	Traf3-binding receptors stabilize nik by activating ciap-dependent degradation of traf2 and traf3.	SIGNOR-182131
P00749	Q03405	1	binding	up-regulates	0.891	The urokinase plasminogen activator binds to its cellular receptor with high affinity and initiates signaling cascades that are implicated in pathological processes including tumor growth, metastasis, and inflammation.	SIGNOR-144306
P25963	Q04206	1	binding	up-regulates activity	0.891	Nf-kappa b is an inducible transcription factor comprised of a 50-kd (p50) and a 65-kd (p65) subunit. Induction of nf-kappa b activity, which is a critical event in many signal transduction pathways, involves release from a cytoplasmic inhibitory protein, i kappa b, followed by translocation of the active transcription factor complex into the nucleus. we demonstrate by in vitro and in vivo methods that the recently cloned i kappa b/mad-3 interacts with both the p50 and p65 subunits of nf-kappa b.	SIGNOR-17691
P12644	P36894	1	binding	up-regulates	0.891	BMP interacts with specific receptors on the cell surface, BMP receptor types 1 and 2 (BMPr1 and BMPr2).	SIGNOR-253548
P30153	P62714	1	binding	up-regulates	0.891	Pr65/a acts as a scaffold protein for binding pp2ac and regulatory b subunits in a heterotrimeric holoenzyme	SIGNOR-138886
Q9BQI3	P05198	1	phosphorylation	down-regulates activity	0.89	HRI is an intracellular heme sensor that coordinates heme and globin synthesis in erythropoiesis by inhibiting protein synthesis of globins and heme biosynthetic enzymes during heme deficiency. HRI is a heme-regulated kinase that phosphorylates the α-subunit of eIF2 in heme deficiency, impairing another round of translational initiation and thereby inhibiting translation.	SIGNOR-251817
P01308	P08069	1	binding	up-regulates	0.89	Because of the sequence homology and tertiary structure similarities between proinsulin (pi) and insulin-like growth factor-i (igf-i), it is possible that pi interacts with the igf-i receptor with higher affinity than insulin.	SIGNOR-22083
O75381	O00628	1	binding	up-regulates activity	0.89	The peroxisomal docking complex is a key component of the import machinery for matrix proteins. The core protein of this complex, Pex14, is thought to represent the initial docking site for the import receptors Pex5 and Pex7.	SIGNOR-253028
Q9UMX1	P10071	1	binding	up-regulates quantity by stabilization	0.889	We show that loss of suppressor of fused (Sufu; an inhibitory effector for Gli proteins) results in destabilization of Gli2 and Gli3 full-length activators but not of their C-terminally processed repressors, whereas overexpression of Sufu stabilizes them.	SIGNOR-268868
Q8WUP2	P21333	1	binding	up-regulates activity	0.888	Kindlin binds migfilin tandem LIM domains and regulates migfilin focal adhesion localization and recruitment dynamics. Two integrin-binding proteins present in FAs, kindlin-1 and kindlin-2, are important for integrin activation, FA formation, and signaling. By binding filamin, migfilin provides a link between kindlin and the actin cytoskeleton.	SIGNOR-266105
P08700	P26951	1	binding	up-regulates	0.888	The results demonstrate that both the association and dissociation rates for the binding of il-3 to the il-3ralpha are altered by truncation and by amino acid substitution at individual sites. Intracellular signaling studies using k116w and e43n demonstrate that differences in the il-3alpha binding characteristics are reflected in magnitude and kinetics of stat5 phosphorylation.	SIGNOR-111404
P53779	P05412	1	phosphorylation	up-regulates	0.887	With epidermal growth factor treatment, overexpression of erk8 in jb6 cl41 cells caused an increased phosphorylation of c-jun at ser(63) and ser(73), resulting in increased activator protein-1 transactivation.	SIGNOR-164800
P00734	P25116	1	cleavage	up-regulates	0.887	The par1 receptor subtype is activated when the n terminus is proteolytically cleaved by the serine protease thrombin, resulting in an irreversible activation of the receptor. Thrombin activates platelets by binding and cleaving protease-activated receptors 1 and 4 (par1 and par4).	SIGNOR-199007
P01160	P16066	1	binding	up-regulates	0.887	Natriuretic peptide receptor-a (npra) is the biological receptor of the peptide hormones atrial natriuretic peptide (anp) and brain natriuretic peptide (bnp)	SIGNOR-137600
Q99418	P62330	1	guanine nucleotide exchange factor	up-regulates activity	0.887	Effects of ARNO upon Axonogenesis Are Mediated by Downstream Activation of ARF6. ARNO/ARF6 signaling pathways that could modulate actin reorganization in the axonal growth cone. ARNO stimulates GTP exchange on ARF6, thereby increasing the amount of active ARF6.	SIGNOR-264910
P10644	P17612	1	binding	down-regulates activity	0.886	Inactive PKA exists as a holoenzyme, comprised of two regulatory (R) subunits and two catalytic subunits . In the presence of cAMP, the holoenzyme becomes active by binding two cAMP molecules cooperatively to each R subunit, resulting in a conformational change in the R subunits, thus releasing the two C subunits to phosphorylate downstream targets	SIGNOR-258751
P43034	Q14204	1	binding	up-regulates activity	0.886	We demonstrate that LIS1 directly interacts with the cytoplasmic dynein heavy chain (CDHC) and NUDEL. LIS1 specifically binds the P1 loop domain of CDHC, while NUDEL binds the C-terminal region as well as a distinct binding site in the P1 loop domain. LIS1 and NUDEL regulate CDHC localization and motor function. Reduction of LIS1 leads to mislocalization of NUDEL, CDHC, β-tubulin, and the Golgi complex	SIGNOR-252158
O14920	Q04206	1	phosphorylation	up-regulates activity	0.886	Rela is phosphorylated at ser536 by ikkbeta, ikkalfa, ikkepsilon, nf-kb activating kinase (nak, also known as tank-binding kinase-1 tbk1) and rsk1 (also known as p90 ribosomal protein s6 kinase (p90s6k). We now present evidence that suggests that the upstream kinase ikkbeta plays an important role in tax-induced p53 inhibition through phosphorylation of p65/rela at ser-536. Ikkbeta plays an important role in tax-induced p53 inhibition through phosphorylation of p65/rela at ser-536.	SIGNOR-138903
P01579	P15260	1	binding	up-regulates	0.886	Ifn-g Binds to the ifn-g Receptor binding subunit (ifn-gR1;receptor chain 1), a species-specific cell surface transmembrane receptor chain (41, 42). A second transmembrane protein (ifn-gR2) (4345) is required for signal transduction	SIGNOR-95626
P00533	P22681	2	relocalization	up-regulates	0.886	Likewise, cbl is recruited to erbb1 either directly (tyr1045), or indirectly, trough grb2	SIGNOR-147826
P22681	P00533	2	ubiquitination	down-regulates quantity by destabilization	0.886	Ligand binding to EGFR also leads to rapid internalization and proteosomal/lysosomal degradation of the receptors. This process results in a dramatic downregulation of both total and cell surface receptors. EGF-induced degradation of EGFR is thought to be initiated by phosphorylation of tyrosine 1045 of the receptor followed by binding of Cbl adaptor proteins and ubiquitination of the receptor. Internalized EGFR is transported to early endosomes where receptor-ligand complexes are sorted for either degradation or recycling to the cell surface.	SIGNOR-65642
P12757	Q13485	1	binding	down-regulates activity	0.886	Thus, SnoN can interact with Smad4 and Smad2 and inhibit their abilities to activate transcription.	SIGNOR-71633
Q9H4B6	Q13043	2	binding	up-regulates quantity by stabilization	0.886	Association of mammalian sterile twenty kinases, Mst1 and Mst2, with hSalvador via C-terminal coiled-coil domains, leads to its stabilization and phosphorylation.	SIGNOR-261958
Q6W2J9	P41182	1	binding	up-regulates activity	0.886	In this study we have shown that BCoR interacts with BCL-6 and potentiates transcriptional repression by BCL-6 with striking specificity.	SIGNOR-252235
Q13043	Q9H4B6	2	null	up-regulates	0.886	In vitro phosphorylation experiments indicate that the phosphorylation of Sav by Mst is direct. The stabilizing effect of Mst was much greater on N-terminally truncated hSav mutants, as long as they retained the ability to bind Mst. Mst mutants that lacked the C-terminal coiled-coil domain and were unable to bind to hSav, also failed to stabilize or phosphorylate hSav	SIGNOR-217833
P60953	Q13177	1	binding	up-regulates activity	0.885	A new brain serine/threonine protein kinase may be a target for the p21ras-related proteins Cdc42 and Rac1. The kinase sequence is related to that of the yeast protein STE20, implicated in pheromone-response pathways.	SIGNOR-248253
P49771	P36888	1	binding	up-regulates	0.885	Flt3 ligand (fl) is an early-acting potent co-stimulatory cytokine that regulates proliferation and differentiation of a number of blood cell lineages. Its receptor flt3/flk2 belongs to class iii receptor tyrosine kinases that also include the receptors for colony-stimulating factor 1	SIGNOR-65564
P46937	Q15562	1	binding	up-regulates	0.884	When dephosphorylated, yap/taz enter nuclei and induce gene transcription by interacting with transcription factors tead14.	SIGNOR-201468
P24941	P06400	1	phosphorylation	down-regulates	0.884	We demonstrate that phosphorylation by either cdk2-cyclin a, which phosphorylates t821, or cdk4-cyclin d1, which phosphorylates threonine 826, can disable prb for subsequent binding of an lxcxe protein.	SIGNOR-47895
P45984	P05412	1	binding	up-regulates	0.884	C-jun is targeted for ubiquitination by its association with inactive c-jun nh2-terminal kinase (jnk).Phosphorylation By activated jnk protects c-jun from ubiquitination.	SIGNOR-53791
P55072	Q9BUN8	1	binding	up-regulates activity	0.884	VIMP mediates p97 binding to hDerlin-1. these data suggest that Derlin-1 and VIMP form a membrane protein complex that serves as a receptor for p97.	SIGNOR-261372
P52799	P54753	1	binding	up-regulates	0.883	Lerk-5 is a ligand for both elk and hek and induces receptor phosphorylation	SIGNOR-52583
O75061	P11142	1	relocalization	up-regulates activity	0.883	Hsc70, recruited by the J-domain protein auxilin, mediates clathrin uncoating and release of a free vesicle, primed to fuse with a target membrane.	SIGNOR-260719
P05113	Q01344	1	binding	up-regulates	0.883	Single chain and wt il5 also had similar binding affinity for soluble il5 receptor alpha chain, the specificity subunit of the il5 receptor, as measured kinetically with an optical biosensor.	SIGNOR-40039
O15105	Q9HCE7	2	relocalization	up-regulates activity	0.882	One of the major mechanisms underlying the inhibitory effect of Smad7 on TGF-_ signaling operates through accelerating T_RI turnover by recruiting ubiquitin E3 ligases such as Smurf1 and Smurf2	SIGNOR-175269
Q9HCE7	O15105	2	ubiquitination	down-regulates activity	0.882	Smad ubiquitin regulatory factor 1 (Smurf1), a HECT type E3 ubiquitin ligase, interacts with inhibitory Smad7 and induces translocation of Smad7 to the cytoplasm	SIGNOR-97064
P00734	P12259	1	null	up-regulates activity	0.882	Thrombin also activates the cofactors FVIII (to FVIIIa) and FV (to FVa) and activates platelets such that they provide a procoagulant membrane surface to which these proteins then bind	SIGNOR-263530
P78406	P52948	1	binding	up-regulates activity	0.882	Nup98 is a major interacting partner of Rae1 and known to beinvolved in mRNA export.	SIGNOR-260868
Q96JK9	Q9UM47	1	binding	up-regulates	0.881	We report here the cloning and characterization of two new genes, maml2 and maml3, that also function as transcriptional coactivators for notch receptors.	SIGNOR-94100
O00566	Q9NV31	1	binding	up-regulates activity	0.881	Mpp10 represents a platform for the interaction of multiple factors within the 90S pre-ribosome. In eukaryotes, ribosome assembly is a highly complex process that involves more than 200 assembly factors that ensure the folding, modification and processing of the different rRNA species as well as the timely association of ribosomal proteins. One of these factors, Mpp10 associates with Imp3 and Imp4 to form a complex that is essential for the normal production of the 18S rRNA.	SIGNOR-261173
P17612	P31323	2	phosphorylation	up-regulates activity	0.881	Serine 114 phosphorylation is required for both nuclear localization and down-regulation of il-2 production by riibeta.	SIGNOR-125545
P31323	P17612	2	binding	down-regulates activity	0.881	Inactive PKA exists as a holoenzyme, comprised of two regulatory (R) subunits and two catalytic subunits . In the presence of cAMP, the holoenzyme becomes active by binding two cAMP molecules cooperatively to each R subunit, resulting in a conformational change in the R subunits, thus releasing the two C subunits to phosphorylate downstream targets	SIGNOR-258754
P38936	P06493	1	binding	down-regulates	0.881	P21 and p27 are key inhibitors of both cdk1 and cdk2.	SIGNOR-128442
P31321	P22694	1	binding	down-regulates activity	0.881	Inactive PKA exists as a holoenzyme, comprised of two regulatory (R) subunits and two catalytic subunits . In the presence of cAMP, the holoenzyme becomes active by binding two cAMP molecules cooperatively to each R subunit, resulting in a conformational change in the R subunits, thus releasing the two C subunits to phosphorylate downstream targets	SIGNOR-258756
Q6ZNE5	Q8NEB9	1	binding	up-regulates activity	0.881	Characterization of the new proteins revealed that atg14l enhances vps34 lipid kinase activity and upregulates autophagy,	SIGNOR-235448
P05305	P25101	1	binding	up-regulates	0.881	Endothelin-1 (et-1) and angiotensin ii (angii), two potent vasoactive peptides involved in the regulation of cardiovascular homeostasis, also induce mitogenic and pro-angiogenic responses in vitro and in vivo. Both peptides are produced by cleavage of inactive precursors by metalloproteases (endothelin-converting enzyme and angiotensin-converting enzyme, respectively) and activate two subtypes of membrane receptors (eta-r and etb-r for et-1, at1r and at2r for angii) that all belong to the superfamily of g-protein coupled receptors.	SIGNOR-145759
P62993	Q07890	1	binding	up-regulates	0.88	Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85.	SIGNOR-175180
Q9H4P4	P40818	2	ubiquitination	down-regulates quantity by destabilization	0.88	RNF41 redistributes and ubiquitylates USP8, and reduces USP8 levels.	SIGNOR-259106
P42773	Q00534	1	binding	down-regulates	0.88	The first group, including p16ink4a, p15ink4b,p18ink4cand p19ink4d, is specific for the g1 cdks,cdk4and cdk6, inhibiting the kinase activity of cyclin d/cdk4-cdk6 complexes on prb.	SIGNOR-44601
P53350	Q2NKX8	1	relocalization	up-regulates	0.88	Human pich was identified as an interaction partner and substrate of plk1. Our data indicate that plk1 prevents the association of pich with chromosome arms and restricts its localization to the kt/centromere region	SIGNOR-152136
P00519	Q8IZP0	2	phosphorylation	up-regulates	0.88	Abi-1 is an adaptor protein for abelson kinase (c-abl). Here, we identified a new phosphorylation site (y398) in the sh3 domain of abi1, and disruption of y398, combined with the previously identified phosphorylation site y213, significantly weakens the binding of abi-1 to c-abl. Phosphorylation of abi-1 is dependent on c-abl kinase	SIGNOR-172017
Q8IZP0	P00519	2	binding	up-regulates	0.88	Our results are in agreement with previous report showing that abi-1, the putative mouse homologue of e3b1, is a abl binding protein	SIGNOR-45994
P40818	Q9H4P4	2	deubiquitination	up-regulates quantity by stabilization	0.88	Ubiquitin-specific protease 8 (USP8), an RNF41-interacting deubiquitylating enzyme (DUB) stabilizes RNF41 and is involved in trafficking of various transmembrane proteins.	SIGNOR-259105
P42772	P11802	1	binding	down-regulates	0.879	We present evidence that the different subcellular location of p15 and p27 ensures the prior access of p15 to cdk4. In the cell, p15 is localized mostly in the cytoplasm, whereas p27 is nuclear. p15 prevails over p27 or a p27 construct consisting of the cdk inhibitory domain tagged with a nuclear localization signal. However, when p15 and p27 are forced to reside in the same subcellular location, either the cytoplasm or the nucleus, p15 no longer prevents p27 from binding to cdk4. These properties allow p15 and p27 to coordinately inhibit cdk4 and cdk2.	SIGNOR-46758
P00533	P40763	1	phosphorylation	up-regulates activity	0.879	The transcription factors stat1, stat3, and stat5 are directly phosphorylated by erbb-1, subsequent to which they dimerize through phosphotyrosine-sh2 domain interactions and translocate to the nucleus to activate gene trascription critical for proliferation.	SIGNOR-121965
Q08379	Q9BQQ3	1	binding	up-regulates quantity by stabilization	0.879	Previous studies have implicated the GM130–GRASP65 complex in diverse Golgi functions. Therefore, GM130–GRASP65 interactions are required for Golgi ribbon formation.\|A surprising clue came from the observation that GM130 was required for stability of GRASP65.	SIGNOR-260601
Q9UQF2	P45983	2	binding	down-regulates	0.879	The jip proteins function by aggregating components of a map kinase module (including mlk, mkk7, and jnk) and facilitate signal transmission by the protein kinase cascade. Overexpression of jip1 deactivates the jnk pathway selectively by cytoplasmic retention of jnk and thereby inhibits gene expression mediated by jnk, which occurs in the nucleus	SIGNOR-124727
Q14790	P55957	1	cleavage	up-regulates activity	0.879	Caspase-8 cleaves bid at aspartic acid residue 60 (asp60) cleavage of bid by casp8 releases its potent proapoptotic activity	SIGNOR-59655
P45983	Q9UQF2	2	phosphorylation	up-regulates activity	0.879	After mapping JNK-dependent JIP1 phosphorylation sites and testing their functional significance, it was observed that phosphorylation by JNK of JIP1 on Thr-103 and not other phosphorylated JIP1 residues is necessary for the regulation of DLK association with JIP1, DLK activation, and subsequent module activation. The data presented corroborates our previous observations using endogenous proteins, demonstrates that JNK binding to JIP1 is necessary for module activation, and shows that activation of JIP1-JNK module dynamics requires phosphorylation of JIP1 on Thr-103 by JNK. and Thr-205 are phosphorylated directly by JNK after JNK binds to JIP1.	SIGNOR-250128
Q04206	Q92793	2	binding	up-regulates	0.879	Both p53 and rela(p65) interact with the transcriptional coactivator proteins p300 and creb-binding protein (cbp), and we demonstrate that these results are consistent with competition for a limiting pool of p300/cbp complexes in vivo.	SIGNOR-66953
P99999	P55211	1	binding	up-regulates activity	0.879	Caspase-9 and apaf-1 bind to each other via their respective nh2-terminal ced-3 homologous domains in the presence of cytochrome c and datp, an event that leads to caspase-9 activation.	SIGNOR-53585
Q92793	Q04206	2	acetylation	up-regulates	0.879	Rela is also acetylated at several sites by p300 and cbp	SIGNOR-143396
P01112	P15056	1	binding	up-regulates activity	0.878	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-147327

Q13043

Q9H8S9

1

phosphorylation

up-regulates

0.9

Mob1, when phosphorylated by MST1/2, binds to the autoinhibitory motif in Lats1/2, which in turn leads to the phosphorylation of the Lats activation loop (Lats1 S909 and Lats2 S872) and thereby an increase of their kinase activity

SIGNOR-201306

P35222

Q9NQB0

1

binding

up-regulates activity

0.9

Hypophosphorylation of β-catenin and translocation into the nucleus leads to binding with members of the lymphoid-enhancer-binding factor/T-cell-specific transcription factor (LEF/TCF) family and activation of WNT target genesAs a member of LEF/TCF family, transcription factor 7 like 2 (Tcf7l2, formerly called Tcf4) is an important transcription factor triggering the downstream responsive genes of WNT signaling

SIGNOR-85757

Q9NW38

Q9BXW9

1

ubiquitination

up-regulates activity

0.9

Thus, eight of the nine components of the FA core complex are FA proteins (FANC‐A, B, C, E, F, G, L, and M). Furthermore, two of the newly discovered FA proteins have enzymatic activities: FANCL is a ubiquitin ligase essential for FANCD2 monoubiquitination in vivo

SIGNOR-263250

P52657

P20226

1

binding

up-regulates activity

0.9

The general transcription factor IIA (TFIIA) binds to the TATA binding protein (TBP) and mediates transcriptional activation by distinct classes of activators. |Our results show that different activators utilize the general factor TFIIA in unique ways and that TFIIA contributes transcription activation functions in addition to the facilitation of TBP-DNA binding.

SIGNOR-262591

P51531

Q8TAQ2

1

binding

up-regulates

0.9

The remodeling activity of brg1 and hbrm is stimulated by baf170/baf155 and is further stimulated when ini1 is added.

SIGNOR-65435

O14798

P50591

1

binding

down-regulates

0.899

Albeit on binding the ligand, dcr1 and dcr2 do not transduce the apoptogenic signal,

SIGNOR-163611

P01135

P00533

1

binding

up-regulates activity

0.899

Our data indicate that a subset of cell lines is dependent on TGF-_-mediated activation of the EGFR for cell proliferation and strongly suggest that pancreatic tumors expressing high levels of TGF-_ and phosphorylated (activated) EGFR are EGFR-dependent in vitro and in vivo.

SIGNOR-93199

P30990

O95665

1

binding

down-regulates

0.898

Neurotensin binding to recombinant neurotensin nt2 receptor expressed in cho cells does not elicit a biological response as determined by second messenger measurements.

SIGNOR-62519

Q13625

P04637

1

binding

up-regulates

0.898

53bp2 interacts with the tumour suppressor p53 and enhances p53-mediated activation of transcription, possibly by facilitating the dephosphorylation of one or more sites on p53

SIGNOR-114762

P09038

P21802

1

binding

up-regulates

0.898

we determined the crystal structures of these two FGFR2 mutants in complex with fibroblast growth factor 2 (FGF2).These structures demonstrate that both mutations introduce additional interactions between FGFR2 and FGF2, thereby augmenting FGFR2-FGF2 affinity.

SIGNOR-86121

Q16576

O14929

1

binding

up-regulates activity

0.898

AMPK increased HAT1 activity through phosphorylation of HAT1-Ser190 and RBBP7-Ser314| interaction between RBBP7 and HAT1 is required for acetyltransferase activity

SIGNOR-264786

Q96QV1

Q15465

1

binding

down-regulates activity

0.897

Hip encodes a membrane glycoprotein that binds to all three mammalian hedgehog proteins with an affinity comparable to that of ptc-1. our findings support a model in which hip attenuates hedgehog signalling as a result of binding to hedgehog proteins: a negative regulatory feedback loop established in this way could thus modulate the responses to any hedgehog signal.

SIGNOR-65078

Q06124

P35568

1

dephosphorylation

down-regulates

0.897

The specific activity of four candidate protein-tyrosine phosphatases (protein-tyrosine phosphatase 1b (ptp1b), sh2 domain-containing ptpase-2 (shp-2), leukocyte common antigen-related (lar), and leukocyte antigen-related phosphatase) (lrp) toward irs-1 dephosphorylation was studied using recombinant proteins in vitro. Ptp1b exhibited the highest specific activity these results provide new insight into novel molecular interactions involving ptp1b and grb2 that may influence the steady-state capacity of irs-1 to function as a phosphotyrosine scaffold and possibly affect the balance of postreceptor insulin signaling.

SIGNOR-74856

P18510

P14778

1

binding

down-regulates activity

0.897

Homozygous truncating mutations result in lack of secreted interleukin-1–receptor antagonist protein, which inhibits the proinflammatory cytokines interleukin-1α and interleukin-1β

SIGNOR-262302

P54619

P54646

1

binding

up-regulates

0.897

Gamma non-catalytic subunit mediates binding to amp, adp and atp, leading to activate or inhibit ampk: amp-binding results in allosteric activation of alpha catalytic subunit (prkaa1 or prkaa2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits.

SIGNOR-139173

P01008

P00740

1

cleavage

down-regulates activity

0.897

Antithrombin (AT), a member of the serine protease inhibitor (SERPIN) superfamily, is a major circulating inhibitor of blood coagulation proteases such as factor (F) IIa (known as thrombin), FXa and, to a lesser extent, FIXa, FXIa and FXIIa. SERPINC1, which encodes AT in humans, is located on chromosome 1q25.1

SIGNOR-264140

P35225

P24394

1

binding

up-regulates activity

0.896

IL-4 and IL-13 have overlapping but distinct effects on MFs, dependent on a common IL-4R, with profound changes in the expression of a range of cellular proteins and functions broadly implicated in the regulation of inflammation and repair.

SIGNOR-249528

P26927

Q04912

1

binding

up-regulates

0.896

P185ron is a tyrosine kinase activated by msp

SIGNOR-31107

O14788

Q9Y6Q6

1

binding

up-regulates activity

0.896

RANKL, a member of the tumour necrosis factor superfamily, is most abundantly expressed as a cell-surface protein by bone-marrow stromal cells. It interacts with its receptor RANK (which is encoded by Tnfrsf11a) on macrophages and mature osteoclasts.

SIGNOR-253042

O15111

P25963

1

phosphorylation

down-regulates quantity by destabilization

0.896

We described the purification of a 900 kda protein kinase complex, the ikb kinase (ikk), that phosphorylates ikbalfa and ikbbeta at the sites that mediate their ubiquitination and degradation

SIGNOR-52875

P52803

P54756

1

binding

up-regulates

0.896

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-52476

P13861

P22694

1

binding

down-regulates activity

0.896

Inactive PKA exists as a holoenzyme, comprised of two regulatory (R) subunits and two catalytic subunits . In the presence of cAMP, the holoenzyme becomes active by binding two cAMP molecules cooperatively to each R subunit, resulting in a conformational change in the R subunits, thus releasing the two C subunits to phosphorylate downstream targets

SIGNOR-258757

Q12933

Q13546

1

ubiquitination

up-regulates activity

0.895

Following binding to tradd, traf2 was thought to mediate non-degradative lys-63-linked polyubiquitination of rip1 via its ring e3 ligase domain. Rip1 is known to directly interact with traf2.

SIGNOR-59689

Q13490

Q9NR28

2

ubiquitination

down-regulates quantity by destabilization

0.895

Here we show that cIAP1 and cIAP2 are E3 ubiquitin-protein isopeptide ligases (ubiquitin ligases) for Smac. cIAPs stimulate Smac ubiquitination both in vivo and in vitro, leading to Smac degradation. cIAP1 and cIAP2 associate with overlapping but distinct subsets of E2 (ubiquitin carrier protein) ubiquitin-conjugating enzymes. The substrate-dependent E3 activity of cIAPs is mediated by their RING domains and is dependent on the specific interactions between cIAPs and Smac.

SIGNOR-271392

Q96S52

O43292

1

binding

up-regulates activity

0.895

To determine roles for PIG-S and PIG-T, we disrupted these genes in mouse F9 cells by homologous recombination. PIG-S and PIG-T knockout cells were defective in transfer of GPI to proteins, particularly in formation of the carbonyl intermediates. We also demonstrate that PIG-S and PIG-T form a protein complex with GAA1 and GPI8, and that PIG-T maintains the complex by stabilizing the expression of GAA1 and GPI8.

SIGNOR-261361

Q9NR28

Q13490

2

binding

down-regulates quantity

0.895

Smac promotes caspase-9 activation by binding to inhibitor of apoptosis proteins, IAPs, and removing their inhibitory activity. Smac is normally a mitochondrial protein but is released into the cytosol when cells undergo apoptosis.

SIGNOR-80206

Q99933

P11142

1

binding

up-regulates activity

0.895

Heat shock cognate protein 70 (Hsc70) regulates protein homeostasis through its reversible interactions with client proteins. Hsc70 has two major domains: a nucleotide-binding domain (NBD), that hydrolyzes ATP, and a substrate-binding domain (SBD), where clients are bound. Members of the BAG family of co-chaperones, including Bag1 and Bag3, are known to accelerate release of both ADP and client from Hsc70.

SIGNOR-254115

P50613

P19447

1

phosphorylation

down-regulates quantity by destabilization

0.895

These results led us to propose a model that spironolactone may trigger the phosphorylation of XPB at Ser90 by CDK7, which promotes the recognition and polyubiquitination of XPB by SCFFBXL18 for proteasomal degradation.

SIGNOR-277433

P31323

P22694

1

binding

down-regulates activity

0.894

Inactive PKA exists as a holoenzyme, comprised of two regulatory (R) subunits and two catalytic subunits . In the presence of cAMP, the holoenzyme becomes active by binding two cAMP molecules cooperatively to each R subunit, resulting in a conformational change in the R subunits, thus releasing the two C subunits to phosphorylate downstream targets

SIGNOR-258758

P67775

P31749

1

dephosphorylation

down-regulates activity

0.893

Protein phosphatase 2A negatively regulates insulin's metabolic signaling pathway by inhibiting Akt (protein kinase B) activity in 3T3-L1 adipocytes

SIGNOR-252614

O15520

P21802

1

binding

up-regulates

0.893

Rfgf-10 bound the kgfr with high affinity comparable to that of kgf

SIGNOR-57380

Q9NRY4

P61586

1

gtpase-activating protein

down-regulates activity

0.893

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-260492

Q9Y4K3

O43318

1

ubiquitination

up-regulates activity

0.893

Intriguingly, TGF-beta-induced TRAF6-mediated Lys 63-linked polyubiquitylation of TAK1 Lys 34 correlates with TAK1 activation. Our data show that TGF-beta specifically activates TAK1 through interaction of TbetaRI with TRAF6, whereas activation of Smad2 is not dependent on TRAF6.

SIGNOR-236071

Q9GZX6

Q8N6P7

1

binding

up-regulates

0.893

In addition, il-22 mediates inflammation and binds class ii cytokine receptor heterodimers il-22 ra1/crf2-4.

SIGNOR-86340

Q07889

P01112

1

guanine nucleotide exchange factor

up-regulates activity

0.892

The enhancement of H-Ras GTP levels induced by oncogenic K-Ras was abrogated when the expression of endogenous Sos was suppressed, implicating Sos as an essential intermediate in the cross talk between oncogenic K-Ras and WT H-Ras.

SIGNOR-59472

Q12933

Q13489

2

binding

up-regulates

0.892

A traf2 trimer interacts with one ciap2 both in the crystal and in solution through its death domain and amino-terminal region, tradd recruits rip1 (receptor-interacting protein), traf2, and through its interaction with traf2, c-iap1 and c-iap2 (13). Traf2 recruit ciap1 and ciap2. A traf2 trimer interacts with one ciap2 both in the crystal and in solution.

SIGNOR-182124

O14944

P00533

1

binding

up-regulates

0.892

Chemical cross-linking experiments showed that [125i]epiregulin directly bound to each of egfr and erbb-4 but not to erbb-2 and erbb-3. remarkably, three members of the epidermal growth factor (egf) family (ereg, areg, and epgn) showed increased expression that was associated with elevated epidermal activation of the egf receptor (egfr) and stat3, a downstream effector of egfr signaling.

SIGNOR-54351

Q13489

Q12933

2

ubiquitination

down-regulates quantity by destabilization

0.892

Traf3-binding receptors stabilize nik by activating ciap-dependent degradation of traf2 and traf3.

SIGNOR-182131

P00749

Q03405

1

binding

up-regulates

0.891

The urokinase plasminogen activator binds to its cellular receptor with high affinity and initiates signaling cascades that are implicated in pathological processes including tumor growth, metastasis, and inflammation.

SIGNOR-144306

P25963

Q04206

1

binding

up-regulates activity

0.891

Nf-kappa b is an inducible transcription factor comprised of a 50-kd (p50) and a 65-kd (p65) subunit. Induction of nf-kappa b activity, which is a critical event in many signal transduction pathways, involves release from a cytoplasmic inhibitory protein, i kappa b, followed by translocation of the active transcription factor complex into the nucleus. we demonstrate by in vitro and in vivo methods that the recently cloned i kappa b/mad-3 interacts with both the p50 and p65 subunits of nf-kappa b.

SIGNOR-17691

P12644

P36894

1

binding

up-regulates

0.891

BMP interacts with specific receptors on the cell surface, BMP receptor types 1 and 2 (BMPr1 and BMPr2).

SIGNOR-253548

P30153

P62714

1

binding

up-regulates

0.891

Pr65/a acts as a scaffold protein for binding pp2ac and regulatory b subunits in a heterotrimeric holoenzyme

SIGNOR-138886

Q9BQI3

P05198

1

phosphorylation

down-regulates activity

0.89

HRI is an intracellular heme sensor that coordinates heme and globin synthesis in erythropoiesis by inhibiting protein synthesis of globins and heme biosynthetic enzymes during heme deficiency. HRI is a heme-regulated kinase that phosphorylates the α-subunit of eIF2 in heme deficiency, impairing another round of translational initiation and thereby inhibiting translation.

SIGNOR-251817

P01308

P08069

1

binding

up-regulates

0.89

Because of the sequence homology and tertiary structure similarities between proinsulin (pi) and insulin-like growth factor-i (igf-i), it is possible that pi interacts with the igf-i receptor with higher affinity than insulin.

SIGNOR-22083

O75381

O00628

1

binding

up-regulates activity

0.89

The peroxisomal docking complex is a key component of the import machinery for matrix proteins. The core protein of this complex, Pex14, is thought to represent the initial docking site for the import receptors Pex5 and Pex7.

SIGNOR-253028

Q9UMX1

P10071

1

binding

up-regulates quantity by stabilization

0.889

We show that loss of suppressor of fused (Sufu; an inhibitory effector for Gli proteins) results in destabilization of Gli2 and Gli3 full-length activators but not of their C-terminally processed repressors, whereas overexpression of Sufu stabilizes them.

SIGNOR-268868

Q8WUP2

P21333

1

binding

up-regulates activity

0.888

Kindlin binds migfilin tandem LIM domains and regulates migfilin focal adhesion localization and recruitment dynamics. Two integrin-binding proteins present in FAs, kindlin-1 and kindlin-2, are important for integrin activation, FA formation, and signaling. By binding filamin, migfilin provides a link between kindlin and the actin cytoskeleton.

SIGNOR-266105

P08700

P26951

1

binding

up-regulates

0.888

The results demonstrate that both the association and dissociation rates for the binding of il-3 to the il-3ralpha are altered by truncation and by amino acid substitution at individual sites. Intracellular signaling studies using k116w and e43n demonstrate that differences in the il-3alpha binding characteristics are reflected in magnitude and kinetics of stat5 phosphorylation.

SIGNOR-111404

P53779

P05412

1

phosphorylation

up-regulates

0.887

With epidermal growth factor treatment, overexpression of erk8 in jb6 cl41 cells caused an increased phosphorylation of c-jun at ser(63) and ser(73), resulting in increased activator protein-1 transactivation.

SIGNOR-164800

P00734

P25116

1

cleavage

up-regulates

0.887

The par1 receptor subtype is activated when the n terminus is proteolytically cleaved by the serine protease thrombin, resulting in an irreversible activation of the receptor. Thrombin activates platelets by binding and cleaving protease-activated receptors 1 and 4 (par1 and par4).

SIGNOR-199007

P01160

P16066

1

binding

up-regulates

0.887

Natriuretic peptide receptor-a (npra) is the biological receptor of the peptide hormones atrial natriuretic peptide (anp) and brain natriuretic peptide (bnp)

SIGNOR-137600

Q99418

P62330

1

guanine nucleotide exchange factor

up-regulates activity

0.887

Effects of ARNO upon Axonogenesis Are Mediated by Downstream Activation of ARF6. ARNO/ARF6 signaling pathways that could modulate actin reorganization in the axonal growth cone. ARNO stimulates GTP exchange on ARF6, thereby increasing the amount of active ARF6.

SIGNOR-264910

P10644

P17612

1

binding

down-regulates activity

0.886

Inactive PKA exists as a holoenzyme, comprised of two regulatory (R) subunits and two catalytic subunits . In the presence of cAMP, the holoenzyme becomes active by binding two cAMP molecules cooperatively to each R subunit, resulting in a conformational change in the R subunits, thus releasing the two C subunits to phosphorylate downstream targets

SIGNOR-258751

P43034

Q14204

1

binding

up-regulates activity

0.886

We demonstrate that LIS1 directly interacts with the cytoplasmic dynein heavy chain (CDHC) and NUDEL. LIS1 specifically binds the P1 loop domain of CDHC, while NUDEL binds the C-terminal region as well as a distinct binding site in the P1 loop domain. LIS1 and NUDEL regulate CDHC localization and motor function. Reduction of LIS1 leads to mislocalization of NUDEL, CDHC, β-tubulin, and the Golgi complex

SIGNOR-252158

O14920

Q04206

1

phosphorylation

up-regulates activity

0.886

Rela is phosphorylated at ser536 by ikkbeta, ikkalfa, ikkepsilon, nf-kb activating kinase (nak, also known as tank-binding kinase-1 tbk1) and rsk1 (also known as p90 ribosomal protein s6 kinase (p90s6k). We now present evidence that suggests that the upstream kinase ikkbeta plays an important role in tax-induced p53 inhibition through phosphorylation of p65/rela at ser-536. Ikkbeta plays an important role in tax-induced p53 inhibition through phosphorylation of p65/rela at ser-536.

SIGNOR-138903

P01579

P15260

1

binding

up-regulates

0.886

Ifn-g Binds to the ifn-g Receptor binding subunit (ifn-gR1;receptor chain 1), a species-specific cell surface transmembrane receptor chain (41, 42). A second transmembrane protein (ifn-gR2) (4345) is required for signal transduction

SIGNOR-95626

P00533

P22681

2

relocalization

up-regulates

0.886

Likewise, cbl is recruited to erbb1 either directly (tyr1045), or indirectly, trough grb2

SIGNOR-147826

P22681

P00533

2

ubiquitination

down-regulates quantity by destabilization

0.886

Ligand binding to EGFR also leads to rapid internalization and proteosomal/lysosomal degradation of the receptors. This process results in a dramatic downregulation of both total and cell surface receptors. EGF-induced degradation of EGFR is thought to be initiated by phosphorylation of tyrosine 1045 of the receptor followed by binding of Cbl adaptor proteins and ubiquitination of the receptor. Internalized EGFR is transported to early endosomes where receptor-ligand complexes are sorted for either degradation or recycling to the cell surface.

SIGNOR-65642

P12757

Q13485

1

binding

down-regulates activity

0.886

Thus, SnoN can interact with Smad4 and Smad2 and inhibit their abilities to activate transcription.

SIGNOR-71633

Q9H4B6

Q13043

2

binding

up-regulates quantity by stabilization

0.886

Association of mammalian sterile twenty kinases, Mst1 and Mst2, with hSalvador via C-terminal coiled-coil domains, leads to its stabilization and phosphorylation.

SIGNOR-261958

Q6W2J9

P41182

1

binding

up-regulates activity

0.886

In this study we have shown that BCoR interacts with BCL-6 and potentiates transcriptional repression by BCL-6 with striking specificity.

SIGNOR-252235

Q13043

Q9H4B6

2

null

up-regulates

0.886

In vitro phosphorylation experiments indicate that the phosphorylation of Sav by Mst is direct. The stabilizing effect of Mst was much greater on N-terminally truncated hSav mutants, as long as they retained the ability to bind Mst. Mst mutants that lacked the C-terminal coiled-coil domain and were unable to bind to hSav, also failed to stabilize or phosphorylate hSav

SIGNOR-217833

P60953

Q13177

1

binding

up-regulates activity

0.885

A new brain serine/threonine protein kinase may be a target for the p21ras-related proteins Cdc42 and Rac1. The kinase sequence is related to that of the yeast protein STE20, implicated in pheromone-response pathways.

SIGNOR-248253

P49771

P36888

1

binding

up-regulates

0.885

Flt3 ligand (fl) is an early-acting potent co-stimulatory cytokine that regulates proliferation and differentiation of a number of blood cell lineages. Its receptor flt3/flk2 belongs to class iii receptor tyrosine kinases that also include the receptors for colony-stimulating factor 1

SIGNOR-65564

P46937

Q15562

1

binding

up-regulates

0.884

When dephosphorylated, yap/taz enter nuclei and induce gene transcription by interacting with transcription factors tead14.

SIGNOR-201468

P24941

P06400

1

phosphorylation

down-regulates

0.884

We demonstrate that phosphorylation by either cdk2-cyclin a, which phosphorylates t821, or cdk4-cyclin d1, which phosphorylates threonine 826, can disable prb for subsequent binding of an lxcxe protein.

SIGNOR-47895

P45984

P05412

1

binding

up-regulates

0.884

C-jun is targeted for ubiquitination by its association with inactive c-jun nh2-terminal kinase (jnk).Phosphorylation By activated jnk protects c-jun from ubiquitination.

SIGNOR-53791

P55072

Q9BUN8

1

binding

up-regulates activity

0.884

VIMP mediates p97 binding to hDerlin-1. these data suggest that Derlin-1 and VIMP form a membrane protein complex that serves as a receptor for p97.

SIGNOR-261372

P52799

P54753

1

binding

up-regulates

0.883

Lerk-5 is a ligand for both elk and hek and induces receptor phosphorylation

SIGNOR-52583

O75061

P11142

1

relocalization

up-regulates activity

0.883

Hsc70, recruited by the J-domain protein auxilin, mediates clathrin uncoating and release of a free vesicle, primed to fuse with a target membrane.

SIGNOR-260719

P05113

Q01344

1

binding

up-regulates

0.883

Single chain and wt il5 also had similar binding affinity for soluble il5 receptor alpha chain, the specificity subunit of the il5 receptor, as measured kinetically with an optical biosensor.

SIGNOR-40039

O15105

Q9HCE7

2

relocalization

up-regulates activity

0.882

One of the major mechanisms underlying the inhibitory effect of Smad7 on TGF-_ signaling operates through accelerating T_RI turnover by recruiting ubiquitin E3 ligases such as Smurf1 and Smurf2

SIGNOR-175269

Q9HCE7

O15105

2

ubiquitination

down-regulates activity

0.882

Smad ubiquitin regulatory factor 1 (Smurf1), a HECT type E3 ubiquitin ligase, interacts with inhibitory Smad7 and induces translocation of Smad7 to the cytoplasm

SIGNOR-97064

P00734

P12259

1

null

up-regulates activity

0.882

Thrombin also activates the cofactors FVIII (to FVIIIa) and FV (to FVa) and activates platelets such that they provide a procoagulant membrane surface to which these proteins then bind

SIGNOR-263530

P78406

P52948

1

binding

up-regulates activity

0.882

Nup98 is a major interacting partner of Rae1 and known to beinvolved in mRNA export.

SIGNOR-260868

Q96JK9

Q9UM47

1

binding

up-regulates

0.881

We report here the cloning and characterization of two new genes, maml2 and maml3, that also function as transcriptional coactivators for notch receptors.

SIGNOR-94100

O00566

Q9NV31

1

binding

up-regulates activity

0.881

Mpp10 represents a platform for the interaction of multiple factors within the 90S pre-ribosome. In eukaryotes, ribosome assembly is a highly complex process that involves more than 200 assembly factors that ensure the folding, modification and processing of the different rRNA species as well as the timely association of ribosomal proteins. One of these factors, Mpp10 associates with Imp3 and Imp4 to form a complex that is essential for the normal production of the 18S rRNA.

SIGNOR-261173

P17612

P31323

2

phosphorylation

up-regulates activity

0.881

Serine 114 phosphorylation is required for both nuclear localization and down-regulation of il-2 production by riibeta.

SIGNOR-125545

P31323

P17612

2

binding

down-regulates activity

0.881

Inactive PKA exists as a holoenzyme, comprised of two regulatory (R) subunits and two catalytic subunits . In the presence of cAMP, the holoenzyme becomes active by binding two cAMP molecules cooperatively to each R subunit, resulting in a conformational change in the R subunits, thus releasing the two C subunits to phosphorylate downstream targets

SIGNOR-258754

P38936

P06493

1

binding

down-regulates

0.881

P21 and p27 are key inhibitors of both cdk1 and cdk2.

SIGNOR-128442

P31321

P22694

1

binding

down-regulates activity

0.881

Inactive PKA exists as a holoenzyme, comprised of two regulatory (R) subunits and two catalytic subunits . In the presence of cAMP, the holoenzyme becomes active by binding two cAMP molecules cooperatively to each R subunit, resulting in a conformational change in the R subunits, thus releasing the two C subunits to phosphorylate downstream targets

SIGNOR-258756

Q6ZNE5

Q8NEB9

1

binding

up-regulates activity

0.881

Characterization of the new proteins revealed that atg14l enhances vps34 lipid kinase activity and upregulates autophagy,

SIGNOR-235448

P05305

P25101

1

binding

up-regulates

0.881

Endothelin-1 (et-1) and angiotensin ii (angii), two potent vasoactive peptides involved in the regulation of cardiovascular homeostasis, also induce mitogenic and pro-angiogenic responses in vitro and in vivo. Both peptides are produced by cleavage of inactive precursors by metalloproteases (endothelin-converting enzyme and angiotensin-converting enzyme, respectively) and activate two subtypes of membrane receptors (eta-r and etb-r for et-1, at1r and at2r for angii) that all belong to the superfamily of g-protein coupled receptors.

SIGNOR-145759

P62993

Q07890

1

binding

up-regulates

0.88

Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85.

SIGNOR-175180

Q9H4P4

P40818

2

ubiquitination

down-regulates quantity by destabilization

0.88

RNF41 redistributes and ubiquitylates USP8, and reduces USP8 levels.

SIGNOR-259106

P42773

Q00534

1

binding

down-regulates

0.88

The first group, including p16ink4a, p15ink4b,p18ink4cand p19ink4d, is specific for the g1 cdks,cdk4and cdk6, inhibiting the kinase activity of cyclin d/cdk4-cdk6 complexes on prb.

SIGNOR-44601

P53350

Q2NKX8

1

relocalization

up-regulates

0.88

Human pich was identified as an interaction partner and substrate of plk1. Our data indicate that plk1 prevents the association of pich with chromosome arms and restricts its localization to the kt/centromere region

SIGNOR-152136

P00519

Q8IZP0

2

phosphorylation

up-regulates

0.88

Abi-1 is an adaptor protein for abelson kinase (c-abl). Here, we identified a new phosphorylation site (y398) in the sh3 domain of abi1, and disruption of y398, combined with the previously identified phosphorylation site y213, significantly weakens the binding of abi-1 to c-abl. Phosphorylation of abi-1 is dependent on c-abl kinase

SIGNOR-172017

Q8IZP0

P00519

2

binding

up-regulates

0.88

Our results are in agreement with previous report showing that abi-1, the putative mouse homologue of e3b1, is a abl binding protein

SIGNOR-45994

P40818

Q9H4P4

2

deubiquitination

up-regulates quantity by stabilization

0.88

Ubiquitin-specific protease 8 (USP8), an RNF41-interacting deubiquitylating enzyme (DUB) stabilizes RNF41 and is involved in trafficking of various transmembrane proteins.

SIGNOR-259105

P42772

P11802

1

binding

down-regulates

0.879

We present evidence that the different subcellular location of p15 and p27 ensures the prior access of p15 to cdk4. In the cell, p15 is localized mostly in the cytoplasm, whereas p27 is nuclear. p15 prevails over p27 or a p27 construct consisting of the cdk inhibitory domain tagged with a nuclear localization signal. However, when p15 and p27 are forced to reside in the same subcellular location, either the cytoplasm or the nucleus, p15 no longer prevents p27 from binding to cdk4. These properties allow p15 and p27 to coordinately inhibit cdk4 and cdk2.

SIGNOR-46758

P00533

P40763

1

phosphorylation

up-regulates activity

0.879

The transcription factors stat1, stat3, and stat5 are directly phosphorylated by erbb-1, subsequent to which they dimerize through phosphotyrosine-sh2 domain interactions and translocate to the nucleus to activate gene trascription critical for proliferation.

SIGNOR-121965

Q08379

Q9BQQ3

1

binding

up-regulates quantity by stabilization

0.879

Previous studies have implicated the GM130–GRASP65 complex in diverse Golgi functions. Therefore, GM130–GRASP65 interactions are required for Golgi ribbon formation.|A surprising clue came from the observation that GM130 was required for stability of GRASP65.

SIGNOR-260601

Q9UQF2

P45983

2

binding

down-regulates

0.879

The jip proteins function by aggregating components of a map kinase module (including mlk, mkk7, and jnk) and facilitate signal transmission by the protein kinase cascade. Overexpression of jip1 deactivates the jnk pathway selectively by cytoplasmic retention of jnk and thereby inhibits gene expression mediated by jnk, which occurs in the nucleus

SIGNOR-124727

Q14790

P55957

1

cleavage

up-regulates activity

0.879

Caspase-8 cleaves bid at aspartic acid residue 60 (asp60) cleavage of bid by casp8 releases its potent proapoptotic activity

SIGNOR-59655

P45983

Q9UQF2

2

phosphorylation

up-regulates activity

0.879

After mapping JNK-dependent JIP1 phosphorylation sites and testing their functional significance, it was observed that phosphorylation by JNK of JIP1 on Thr-103 and not other phosphorylated JIP1 residues is necessary for the regulation of DLK association with JIP1, DLK activation, and subsequent module activation. The data presented corroborates our previous observations using endogenous proteins, demonstrates that JNK binding to JIP1 is necessary for module activation, and shows that activation of JIP1-JNK module dynamics requires phosphorylation of JIP1 on Thr-103 by JNK. and Thr-205 are phosphorylated directly by JNK after JNK binds to JIP1.

SIGNOR-250128

Q04206

Q92793

2

binding

up-regulates

0.879

Both p53 and rela(p65) interact with the transcriptional coactivator proteins p300 and creb-binding protein (cbp), and we demonstrate that these results are consistent with competition for a limiting pool of p300/cbp complexes in vivo.

SIGNOR-66953

P99999

P55211

1

binding

up-regulates activity

0.879

Caspase-9 and apaf-1 bind to each other via their respective nh2-terminal ced-3 homologous domains in the presence of cytochrome c and datp, an event that leads to caspase-9 activation.

SIGNOR-53585

Q92793

Q04206

2

acetylation

up-regulates

0.879

Rela is also acetylated at several sites by p300 and cbp

SIGNOR-143396

P01112

P15056

1

binding

up-regulates activity

0.878

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-147327