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
P09619	P19174	1	phosphorylation	up-regulates	0.859	Tyrosine phosphorylation has been shown to increase the enzymatic activity of plc-? / we show that the human pdgf ?- And ?-Receptors differ quantitatively in their abilities to associate with and phosphorylate plc-? And to stimulate inositol phosphate production.	SIGNOR-28179
P06493	P30307	2	phosphorylation	up-regulates	0.858	Phosphorylation at thr-48, thr-67, ser-122, thr-130, ser-168 and ser-214 occurs at g2 and g2-m transition and is catalyzed by cdk1. Ser-168 phosphorylation levels are lower than those at the other 5 cdk1 sites. Phosphorylation by cdk1 leads to increased activity.	SIGNOR-64960
P06493	P30291	2	phosphorylation	down-regulates	0.858	We have found also that the major M-phase kinases polo-like kinase 1 (Plk1) and Cdc2 are responsible for the phosphorylation of S53 and S123, respectively, and that in each case phosphorylation generates an unconventional phospho-degron (signal for degradation) that can be recognized by beta-TrCP	SIGNOR-123824
Q13535	O75943	1	phosphorylation	up-regulates activity	0.858	Here we demonstrate that atr but not atm phosphorylates the human rad17 (hrad17) checkpoint protein on ser(635) and ser(645) in vitro.The rfc-related checkpoint protein rad17, a phosphorylation substrate of atr, is critical for atr-mediated checkpoint signaling and cell survival.	SIGNOR-111248
P30307	P06493	2	dephosphorylation	up-regulates	0.858	Cdk1/cdc2 activation involves tyr15/thr14 dephosphorylation by cdc25c	SIGNOR-186621
Q14563	O75051	1	binding	up-regulates	0.858	Plexins form stable complexes with neuropilin-1 or -2.	SIGNOR-75168
P30291	P06493	2	phosphorylation	down-regulates	0.858	The wee1 kinase phosphorylates and inhibits cyclin-dependent kinase 1 (cdk1), thereby delaying entry into mitosis until appropriate conditions have been met	SIGNOR-139491
P05112	P31785	1	binding	up-regulates	0.858	The common gamma-chain (gamma(c)) is an indispensable subunit of the functional receptor complexes for il-4, il-7, il-9, and il-15 as well as il-2. Here we show that the gamma(c) is also shared with the il-21r complex	SIGNOR-108861
Q13616	Q9UBF6	1	binding	up-regulates activity	0.857	SAG was found to be the second family member of Rbx (RING box protein) or ROC (Regulator of cullins) or Hrt that is a component of SCF E3 ubiquitin ligase. Indeed, like ROC1/Rbx1/Hrt1, SAG binds to Cul1 and SAG-Cul1 complex has ubiquitin ligase activity to promote poly-ubiquitination of E2/Cdc34.	SIGNOR-271444
O14976	Q00610	1	phosphorylation	up-regulates activity	0.857	Clathrin heavy chain (CHC) was phosphorylated at T606 by its association partner cyclin G-associated kinase (GAK). This phosphorylation was required for proper cell proliferation and tumor growth of cells implanted into nude mice.	SIGNOR-275448
P01042	P30411	1	binding	up-regulates activity	0.857	BK binds receptor B2 (B2R) and triggers inflammation, edema, and symptoms of anaphylaxis.	SIGNOR-263554
O43557	Q92956	1	binding	up-regulates	0.857	A member of the tumor necrosis factor (tnf) superfamily, human tnfsf14 (htnfsf14)/hvem-l (herpes virus entry mediator ligand) was isolated as a cellular ligand for hvem/tr2 and human lymphotoxin beta receptor (ltbetar). Tnfsf14 induces apoptosis and suppresses tumor formation	SIGNOR-79328
P04141	P15509	1	binding	up-regulates	0.857	We have determined the nmr structure of a ligand-binding domain of the granulocyte colony-stimulating factor (g-csf) receptor comparisons between the spectra of the 15n-labelled domain with and without g-csf indicate that the major ligand-recognition site is on the fg loop just upstream of the wsxws sequence.	SIGNOR-72458
P01303	P25929	1	binding	up-regulates	0.857	Analogs of npy and pyy have been synthesized that contain a proline residue in position 34 of the molecule, i.e., [leu31, pro34]npy (fuhlendorff et al., 1990) or [pro34]pyy (grandt et al., 1994b), and are much more potent at y1 than y2receptors.	SIGNOR-56522
O14757	P30304	1	phosphorylation	down-regulates	0.857	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-163134
O14490	Q9Y566	1	relocalization	up-regulates activity	0.857	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-264586
Q9UM47	Q06330	1	binding	up-regulates	0.857	Both notch 1 and notch 3 ics displace the co-repressor smrt from the dna-binding protein rbp-j kappa on the hes promoter. The latter observation suggests that both notch 3 ic and notch 1 ic can access rbp-j kappa in vivo, and that the difference in activation capacity instead stems from structural differences in the two ics when positioned on rbp-j kappa.	SIGNOR-86128
O60934	Q13315	2	binding	up-regulates	0.856	Nbs1 can also immobilize atm at the site of the dsb via direct binding of atm to a c-terminal atm interaction motif on nbs1 . the mre11/rad50/nbs1 (mrn) complex maintains genomic stability by bridging dna ends and initiating dna damage signaling through activation of the atm	SIGNOR-134508
Q96KS0	Q16665	1	hydroxylation	down-regulates quantity by destabilization	0.856	There are three EglN family members in humans and mice (EglN1, EglN2, and EglN3). Their enzymatic activity requires oxygen, ascorbic acid, iron, and α-ketoglutarate (α-KG). Under hypoxic conditions, EglNs lose their activity and fail to hydroxylate HIFα, which leads to HIFα stabilization	SIGNOR-261999
Q13315	O60934	2	phosphorylation	up-regulates	0.856	In this report, we showed that atm phosphorylates a p95 peptide (ser-343) and a mre11 peptide (ser-264) in vitro, suggesting that atm may regulate the function of p95?Mre11? Rad50 repair complex in response to dna damage.	SIGNOR-73432
O96017	P30307	1	phosphorylation	down-regulates activity	0.856	Activated chk2 in turn phosphorylates cdc25c at serine-216 contributing to the g2/m checkpoints. Cds1 phosphorylates and inactivates cdc25 in vitro\|CDC25C is phosphorylated on Ser 216 throughout interphase, but not in mitosis. This creates a binding site for 14‐3‐3 proteins \| It has been suggested that 14‐3‐3 protein binding is responsible for retaining Cdc25C in the cytoplasm during interphase, thereby contributing to the prevention of premature initiation of mitotic events	SIGNOR-102779
P31321	P17612	1	binding	down-regulates activity	0.856	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-258753
Q9NP77	P24928	1	dephosphorylation	up-regulates activity	0.855	Phosphorylation of serine-2 (S2) and serine-5 (S5) of the C-terminal domain (CTD) of RNA polymerase II (RNAP II) is a dynamic process that regulates the transcription cycle and coordinates recruitment of RNA processing factors. The Fcp1 CTD phosphatase catalyzes dephosphorylation of S2-P.\| Depletion of Ssu72 impairs transcription in vitro	SIGNOR-248815
P30304	P14635	1	dephosphorylation	up-regulates activity	0.855	Cdc25A dephosphorylates and activates CyclinE\u2013Cdk2, CyclinA\u2013Cdk2 and CyclinB\u2013Cdk1, whereas Cdc25B and Cdc25C primarily target CyclinB\u2013Cdk1 [4,5] .	SIGNOR-277137
Q00534	P46527	1	phosphorylation	up-regulates	0.855	Phosphorylation on ser-10 is the major site of phosphorylation in resting cells, takes place at the g(0)-g1 phase and leads to protein stability.p27(kip1) was phosphorylated by v-cyclin-cdk6 predominantly on ser10, which enhances its cytoplasmic localization.	SIGNOR-140401
P27361	Q16828	2	phosphorylation	down-regulates	0.855	Phosphorylation of serines 159 and 197 by erk1/2 enhances proteasomal degradation of mkp-3	SIGNOR-132975
Q9H492	Q9NT62	1	binding	up-regulates	0.855	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-191543
P31948	P08238	1	binding	down-regulates activity	0.855	Hsp90 chaperone cycle is tightly regulated by another group of proteins referred to as ‘co-chaperones'. Their stability does not depend on Hsp90 function but they interact with distinct Hsp90 conformational states, providing directionality to the Hsp90 cycle4. Furthermore, certain co-chaperones, such as HOP and Cdc37p50 inhibit the Hsp90 chaperone cycle, assisting in delivery of distinct sets of client proteins (steroid hormone receptors and kinases, respectively) to the Hsp90 chaperone machine.	SIGNOR-261412
Q16828	P27361	2	dephosphorylation	down-regulates	0.855	P-erk1/2 proteins were efficiently dephosphorylated in vitro by protein phosphatases 1 and 2a (pp1/2a) and mapk phosphatase 3 (mkp3).	SIGNOR-103149
P52333	P42229	1	phosphorylation	up-regulates	0.854	For these assays, coexpression of wt jak3 with stat5a was found to result in tyrosine phosphorylation of stat5a (lane 2) mediated by jak3, since stat5a coexpressed with the kinase-inactive k855a mutant form of jak3 was not tyrosine phosphorylated.	SIGNOR-182817
P01111	P15056	1	binding	up-regulates activity	0.854	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-175219
P61088	Q13404	1	binding	up-regulates activity	0.854	Ubc13, the partner of rnf8 and rnf168, usually cooperates with an e2-like protein, uev1 (also known as ube2v1) or mms2 (also known as ube2v2), for the synthesis of lys63-linked polyubiquitin chains.	SIGNOR-166177
P01137	P37173	1	binding	up-regulates activity	0.853	A cdna encoding the tgf-beta type ii receptor protein has been isolated by an expression cloning strategy. The cloned cdna, when transfected into cos cells, leads to overexpression of an approximately 80 kd protein that specifically binds radioiodinated tgf-beta 1. Excess tgf-beta 1 competes for binding of radioiodinated tgf-beta 1 in a dose-dependent manner and is more effective than tgf-beta 2.	SIGNOR-236080
P62942	P36897	1	binding	down-regulates activity	0.853	Blocking fkbp12/type i receptor interaction with fk506 nonfunctional derivatives enhances the ligand activity, indicating that fkbp12 binding is inhibitory to the signaling pathways of the tgf beta family ligands	SIGNOR-236142
O14920	P19838	1	phosphorylation	down-regulates quantity by destabilization	0.853	Ikkbeta phosphorylates p105 resulting in its degradation, which releases tpl2 resulting in activation of the pro-proliferative map kinase- pathway.	SIGNOR-70473
P35225	P78552	1	binding	up-regulates	0.853	It is now known that this alternate receptor is a heterodimer, the type ii il-4 receptor or the il-13 receptor, which is comprised of IL-4R And IL-13R1.	SIGNOR-100750
P40933	P31785	1	binding	up-regulates	0.853	The common gamma-chain (gamma(c)) is an indispensable subunit of the functional receptor complexes for il-4, il-7, il-9, and il-15 as well as il-2. Here we show that the gamma(c) is also shared with the il-21r complex.	SIGNOR-108815
P01019	P30556	1	binding	up-regulates activity	0.852	AT(1) receptor (AngII type-1 receptor), a G-protein-coupled receptor, mediates most of the physiological and pathophysiological actions of AngII, and this receptor is predominantly expressed in cardiovascular cells, such as VSMCs (vascular smooth muscle cells)	SIGNOR-252293
P61586	Q16512	1	binding	up-regulates activity	0.852	PKNs bind to human pyrin and phosphorylate S208 and S242. Pyrin forms an inflammasome when mutant or in response to bacterial modification of the GTPase RhoA. We found that RhoA activated the serine-threonine kinases PKN1 and PKN2 that bind and phosphorylate pyrin. Phosphorylated pyrin bound to 14-3-3 proteins, regulatory proteins that in turn blocked the pyrin inflammasome.	SIGNOR-275465
P46020	P15735	1	binding	down-regulates activity	0.852	Phk is among the most complex of the protein kinases so far elucidated. It has one catalytic (gamma) subunit and three different regulatory (alpha, beta, and delta) subunits, a molecular mass of 1.3 X 106 daltons, and each holoenzyme molecule is presumed to contain four molecules of each subunit. The three regulatory subunits inhibit the phosphotransferase activity of the gamma subunit.	SIGNOR-267407
Q13253	P18075	1	binding	down-regulates activity	0.852	We report the crystal structure of the antagonist Noggin bound to BMP-7, which shows that Noggin inhibits BMP signalling by blocking the molecular interfaces of the binding epitopes for both type I and type II receptors.	SIGNOR-256484
Q13535	P54132	1	phosphorylation	up-regulates activity	0.852	It is noteworthy that an active BLM seems to be unnecessary to the activation of BRCA1, either after gamma-rays or HU, even though BRCA1 and BLM helicase are activated by ATR in response to stalled replication, and despite the fact that they colocalize after replication arrest.\|These results show that BLM phosphorylation by ATR after replication fork arrest is not important for its relocalization.	SIGNOR-278978
Q13043	Q7L9L4	1	phosphorylation	up-regulates	0.851	Mob1, which forms a complex with lats1/2, is also phosphorylated by mst1/2, resulting in an enhanced lats1/2mob1 interaction.	SIGNOR-175841
Q9UQK1	P13807	1	binding	up-regulates	0.851	In the liver, PTG and PPP1R3B(GL)are expressed at roughly equivalent levels [55], and they jointly promote hepatic glycogen mobilization and storage. PTG overexpression significantly increased glycogen content, mainly due to its ability to promote the redistribution of PP1 and glycogen synthase to glycogen granules, significantly increasing GS activity and glycogen synthesis (Figure 2)	SIGNOR-271733
Q02410	O14936	1	binding	up-regulates activity	0.851	Interaction with Munc18 increases Mint1 binding to CASK.	SIGNOR-264041
P22223	P35222	1	binding	up-regulates activity	0.851	At its C-terminus, cadherin interacts with Î²-catenin, which dynamically associates with Î±-catenin, a direct binding partner of filamentous actin	SIGNOR-265865
P27986	P42338	1	binding	up-regulates activity	0.851	Signal transduction pathways triggered by Tie2 have been extensively examined. Tyr-1101of Tie2 directly associates in a phosphotyrosine (pTyr)-dependent manner with the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase, which in turn activate PI 3-kinase, leading to cell motility and survival	SIGNOR-242640
P06241	P35222	1	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
Q86YC2	P38398	1	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
O14757	P30307	1	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
Q13188	Q9H8S9	1	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
O00206	Q8IUC6	1	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
P31749	P46527	1	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
P04626	P62993	1	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
P46937	Q99594	1	binding	up-regulates	0.85	When dephosphorylated, yap/taz enter nuclei and induce gene transcription by interacting with transcription factors tead14.	SIGNOR-201471
P42345	O75385	1	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
P42345	O00141	1	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
Q9P1A6	Q9UPX8	1	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
Q8IZI9	Q8IU57	1	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
P20783	Q16288	1	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
Q96EP0	Q9Y6K9	1	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
O14763	Q13158	1	binding	up-regulates	0.849	Fadd binds to ligated trailr1 or trail-r2	SIGNOR-98565
Q9Y2X7	Q15052	1	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
P24941	Q08999	1	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
O00468	O75096	1	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
Q9NR50	P20042	1	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
Q9Y6K9	P25963	1	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
Q99836	P51617	1	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
Q92934	Q07817	2	binding	down-regulates activity	0.848	Bad binds more strongly to Bcl-x, than Bcl-2 in mammalian cells, and it reversed the death repressor activity of Bcl-x,, but not that of Bcl-2. When Bad dimerized with Bcl-x,, Bax was displaced and apoptosis was restored.	SIGNOR-249617
Q07817	Q92934	2	binding	up-regulates activity	0.848	Bad dimerizes with bcl-xl at the mitochondrial membrane where it exert its killing effects. Phosphorylation of bad promotes its binding to 14-3-3 protein, which may sequester bad from bcl-xl, thus promoting cell cells survival.	SIGNOR-81125
Q13951	Q01196	1	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
Q92917	O60231	1	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
Q96GD4	O14777	1	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
Q9Y2T1	P35222	1	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
Q15811	P60953	1	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
P29459	P29460	1	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
P20936	P01112	1	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
Q8IZI9	Q08334	1	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
O15111	Q04206	1	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
P45974	P0CG48	1	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
P01116	P04049	1	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
Q9NT62	O95166	1	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
Q96JC9	P55199	1	binding	up-regulates	0.847	Positive regulation of ell elongation activity depends on stable binding of eaf1 to the ell n terminus	SIGNOR-138516
P19883	P08476	1	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
P01137	P36897	1	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
Q13315	Q14676	1	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
Q92569	P42336	1	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
Q02224	O60566	1	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
Q9NS91	P12004	1	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
Q15788	P03372	1	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
Q13315	O14757	1	phosphorylation	up-regulates	0.845	Atr (predominantly) or atm (to a lesser extent) phosphorylates chk1 at ser317/345, directly leading to activation.	SIGNOR-163106
P38398	Q9BXW9	1	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
Q9BXL7	O95999	1	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
P61970	P37198	1	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
P51955	Q13257	1	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
P01374	P36941	1	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
P04629	P29353	1	binding	up-regulates	0.844	Autophosphorylated trka binds directly to plc?, Abl, and shc.	SIGNOR-75408
P25942	Q12933	1	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
P01111	P42336	1	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
Q9Y4P1	P60520	1	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

P09619

P19174

1

phosphorylation

up-regulates

0.859

Tyrosine phosphorylation has been shown to increase the enzymatic activity of plc-? / we show that the human pdgf ?- And ?-Receptors differ quantitatively in their abilities to associate with and phosphorylate plc-? And to stimulate inositol phosphate production.

SIGNOR-28179

P06493

P30307

2

phosphorylation

up-regulates

0.858

Phosphorylation at thr-48, thr-67, ser-122, thr-130, ser-168 and ser-214 occurs at g2 and g2-m transition and is catalyzed by cdk1. Ser-168 phosphorylation levels are lower than those at the other 5 cdk1 sites. Phosphorylation by cdk1 leads to increased activity.

SIGNOR-64960

P06493

P30291

2

phosphorylation

down-regulates

0.858

We have found also that the major M-phase kinases polo-like kinase 1 (Plk1) and Cdc2 are responsible for the phosphorylation of S53 and S123, respectively, and that in each case phosphorylation generates an unconventional phospho-degron (signal for degradation) that can be recognized by beta-TrCP

SIGNOR-123824

Q13535

O75943

1

phosphorylation

up-regulates activity

0.858

Here we demonstrate that atr but not atm phosphorylates the human rad17 (hrad17) checkpoint protein on ser(635) and ser(645) in vitro.The rfc-related checkpoint protein rad17, a phosphorylation substrate of atr, is critical for atr-mediated checkpoint signaling and cell survival.

SIGNOR-111248

P30307

P06493

2

dephosphorylation

up-regulates

0.858

Cdk1/cdc2 activation involves tyr15/thr14 dephosphorylation by cdc25c

SIGNOR-186621

Q14563

O75051

1

binding

up-regulates

0.858

Plexins form stable complexes with neuropilin-1 or -2.

SIGNOR-75168

P30291

P06493

2

phosphorylation

down-regulates

0.858

The wee1 kinase phosphorylates and inhibits cyclin-dependent kinase 1 (cdk1), thereby delaying entry into mitosis until appropriate conditions have been met

SIGNOR-139491

P05112

P31785

1

binding

up-regulates

0.858

The common gamma-chain (gamma(c)) is an indispensable subunit of the functional receptor complexes for il-4, il-7, il-9, and il-15 as well as il-2. Here we show that the gamma(c) is also shared with the il-21r complex

SIGNOR-108861

Q13616

Q9UBF6

1

binding

up-regulates activity

0.857

SAG was found to be the second family member of Rbx (RING box protein) or ROC (Regulator of cullins) or Hrt that is a component of SCF E3 ubiquitin ligase. Indeed, like ROC1/Rbx1/Hrt1, SAG binds to Cul1 and SAG-Cul1 complex has ubiquitin ligase activity to promote poly-ubiquitination of E2/Cdc34.

SIGNOR-271444

O14976

Q00610

1

phosphorylation

up-regulates activity

0.857

Clathrin heavy chain (CHC) was phosphorylated at T606 by its association partner cyclin G-associated kinase (GAK). This phosphorylation was required for proper cell proliferation and tumor growth of cells implanted into nude mice.

SIGNOR-275448

P01042

P30411

1

binding

up-regulates activity

0.857

BK binds receptor B2 (B2R) and triggers inflammation, edema, and symptoms of anaphylaxis.

SIGNOR-263554

O43557

Q92956

1

binding

up-regulates

0.857

A member of the tumor necrosis factor (tnf) superfamily, human tnfsf14 (htnfsf14)/hvem-l (herpes virus entry mediator ligand) was isolated as a cellular ligand for hvem/tr2 and human lymphotoxin beta receptor (ltbetar). Tnfsf14 induces apoptosis and suppresses tumor formation

SIGNOR-79328

P04141

P15509

1

binding

up-regulates

0.857

We have determined the nmr structure of a ligand-binding domain of the granulocyte colony-stimulating factor (g-csf) receptor comparisons between the spectra of the 15n-labelled domain with and without g-csf indicate that the major ligand-recognition site is on the fg loop just upstream of the wsxws sequence.

SIGNOR-72458

P01303

P25929

1

binding

up-regulates

0.857

Analogs of npy and pyy have been synthesized that contain a proline residue in position 34 of the molecule, i.e., [leu31, pro34]npy (fuhlendorff et al., 1990) or [pro34]pyy (grandt et al., 1994b), and are much more potent at y1 than y2receptors.

SIGNOR-56522

O14757

P30304

1

phosphorylation

down-regulates

0.857

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-163134

O14490

Q9Y566

1

relocalization

up-regulates activity

0.857

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-264586

Q9UM47

Q06330

1

binding

up-regulates

0.857

Both notch 1 and notch 3 ics displace the co-repressor smrt from the dna-binding protein rbp-j kappa on the hes promoter. The latter observation suggests that both notch 3 ic and notch 1 ic can access rbp-j kappa in vivo, and that the difference in activation capacity instead stems from structural differences in the two ics when positioned on rbp-j kappa.

SIGNOR-86128

O60934

Q13315

2

binding

up-regulates

0.856

Nbs1 can also immobilize atm at the site of the dsb via direct binding of atm to a c-terminal atm interaction motif on nbs1 . the mre11/rad50/nbs1 (mrn) complex maintains genomic stability by bridging dna ends and initiating dna damage signaling through activation of the atm

SIGNOR-134508

Q96KS0

Q16665

1

hydroxylation

down-regulates quantity by destabilization

0.856

There are three EglN family members in humans and mice (EglN1, EglN2, and EglN3). Their enzymatic activity requires oxygen, ascorbic acid, iron, and α-ketoglutarate (α-KG). Under hypoxic conditions, EglNs lose their activity and fail to hydroxylate HIFα, which leads to HIFα stabilization

SIGNOR-261999

Q13315

O60934

2

phosphorylation

up-regulates

0.856

In this report, we showed that atm phosphorylates a p95 peptide (ser-343) and a mre11 peptide (ser-264) in vitro, suggesting that atm may regulate the function of p95?Mre11? Rad50 repair complex in response to dna damage.

SIGNOR-73432

O96017

P30307

1

phosphorylation

down-regulates activity

0.856

Activated chk2 in turn phosphorylates cdc25c at serine-216 contributing to the g2/m checkpoints. Cds1 phosphorylates and inactivates cdc25 in vitro|CDC25C is phosphorylated on Ser 216 throughout interphase, but not in mitosis. This creates a binding site for 14‐3‐3 proteins | It has been suggested that 14‐3‐3 protein binding is responsible for retaining Cdc25C in the cytoplasm during interphase, thereby contributing to the prevention of premature initiation of mitotic events

SIGNOR-102779

P31321

P17612

1

binding

down-regulates activity

0.856

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-258753

Q9NP77

P24928

1

dephosphorylation

up-regulates activity

0.855

Phosphorylation of serine-2 (S2) and serine-5 (S5) of the C-terminal domain (CTD) of RNA polymerase II (RNAP II) is a dynamic process that regulates the transcription cycle and coordinates recruitment of RNA processing factors. The Fcp1 CTD phosphatase catalyzes dephosphorylation of S2-P.| Depletion of Ssu72 impairs transcription in vitro

SIGNOR-248815

P30304

P14635

1

dephosphorylation

up-regulates activity

0.855

Cdc25A dephosphorylates and activates CyclinE\u2013Cdk2, CyclinA\u2013Cdk2 and CyclinB\u2013Cdk1, whereas Cdc25B and Cdc25C primarily target CyclinB\u2013Cdk1 [4,5] .

SIGNOR-277137

Q00534

P46527

1

phosphorylation

up-regulates

0.855

Phosphorylation on ser-10 is the major site of phosphorylation in resting cells, takes place at the g(0)-g1 phase and leads to protein stability.p27(kip1) was phosphorylated by v-cyclin-cdk6 predominantly on ser10, which enhances its cytoplasmic localization.

SIGNOR-140401

P27361

Q16828

2

phosphorylation

down-regulates

0.855

Phosphorylation of serines 159 and 197 by erk1/2 enhances proteasomal degradation of mkp-3

SIGNOR-132975

Q9H492

Q9NT62

1

binding

up-regulates

0.855

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-191543

P31948

P08238

1

binding

down-regulates activity

0.855

Hsp90 chaperone cycle is tightly regulated by another group of proteins referred to as ‘co-chaperones'. Their stability does not depend on Hsp90 function but they interact with distinct Hsp90 conformational states, providing directionality to the Hsp90 cycle4. Furthermore, certain co-chaperones, such as HOP and Cdc37p50 inhibit the Hsp90 chaperone cycle, assisting in delivery of distinct sets of client proteins (steroid hormone receptors and kinases, respectively) to the Hsp90 chaperone machine.

SIGNOR-261412

Q16828

P27361

2

dephosphorylation

down-regulates

0.855

P-erk1/2 proteins were efficiently dephosphorylated in vitro by protein phosphatases 1 and 2a (pp1/2a) and mapk phosphatase 3 (mkp3).

SIGNOR-103149

P52333

P42229

1

phosphorylation

up-regulates

0.854

For these assays, coexpression of wt jak3 with stat5a was found to result in tyrosine phosphorylation of stat5a (lane 2) mediated by jak3, since stat5a coexpressed with the kinase-inactive k855a mutant form of jak3 was not tyrosine phosphorylated.

SIGNOR-182817

P01111

P15056

1

binding

up-regulates activity

0.854

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-175219

P61088

Q13404

1

binding

up-regulates activity

0.854

Ubc13, the partner of rnf8 and rnf168, usually cooperates with an e2-like protein, uev1 (also known as ube2v1) or mms2 (also known as ube2v2), for the synthesis of lys63-linked polyubiquitin chains.

SIGNOR-166177

P01137

P37173

1

binding

up-regulates activity

0.853

A cdna encoding the tgf-beta type ii receptor protein has been isolated by an expression cloning strategy. The cloned cdna, when transfected into cos cells, leads to overexpression of an approximately 80 kd protein that specifically binds radioiodinated tgf-beta 1. Excess tgf-beta 1 competes for binding of radioiodinated tgf-beta 1 in a dose-dependent manner and is more effective than tgf-beta 2.

SIGNOR-236080

P62942

P36897

1

binding

down-regulates activity

0.853

Blocking fkbp12/type i receptor interaction with fk506 nonfunctional derivatives enhances the ligand activity, indicating that fkbp12 binding is inhibitory to the signaling pathways of the tgf beta family ligands

SIGNOR-236142

O14920

P19838

1

phosphorylation

down-regulates quantity by destabilization

0.853

Ikkbeta phosphorylates p105 resulting in its degradation, which releases tpl2 resulting in activation of the pro-proliferative map kinase- pathway.

SIGNOR-70473

P35225

P78552

1

binding

up-regulates

0.853

It is now known that this alternate receptor is a heterodimer, the type ii il-4 receptor or the il-13 receptor, which is comprised of IL-4R And IL-13R1.

SIGNOR-100750

P40933

P31785

1

binding

up-regulates

0.853

The common gamma-chain (gamma(c)) is an indispensable subunit of the functional receptor complexes for il-4, il-7, il-9, and il-15 as well as il-2. Here we show that the gamma(c) is also shared with the il-21r complex.

SIGNOR-108815

P01019

P30556

1

binding

up-regulates activity

0.852

AT(1) receptor (AngII type-1 receptor), a G-protein-coupled receptor, mediates most of the physiological and pathophysiological actions of AngII, and this receptor is predominantly expressed in cardiovascular cells, such as VSMCs (vascular smooth muscle cells)

SIGNOR-252293

P61586

Q16512

1

binding

up-regulates activity

0.852

PKNs bind to human pyrin and phosphorylate S208 and S242. Pyrin forms an inflammasome when mutant or in response to bacterial modification of the GTPase RhoA. We found that RhoA activated the serine-threonine kinases PKN1 and PKN2 that bind and phosphorylate pyrin. Phosphorylated pyrin bound to 14-3-3 proteins, regulatory proteins that in turn blocked the pyrin inflammasome.

SIGNOR-275465

P46020

P15735

1

binding

down-regulates activity

0.852

Phk is among the most complex of the protein kinases so far elucidated. It has one catalytic (gamma) subunit and three different regulatory (alpha, beta, and delta) subunits, a molecular mass of 1.3 X 106 daltons, and each holoenzyme molecule is presumed to contain four molecules of each subunit. The three regulatory subunits inhibit the phosphotransferase activity of the gamma subunit.

SIGNOR-267407

Q13253

P18075

1

binding

down-regulates activity

0.852

We report the crystal structure of the antagonist Noggin bound to BMP-7, which shows that Noggin inhibits BMP signalling by blocking the molecular interfaces of the binding epitopes for both type I and type II receptors.

SIGNOR-256484

Q13535

P54132

1

phosphorylation

up-regulates activity

0.852

It is noteworthy that an active BLM seems to be unnecessary to the activation of BRCA1, either after gamma-rays or HU, even though BRCA1 and BLM helicase are activated by ATR in response to stalled replication, and despite the fact that they colocalize after replication arrest.|These results show that BLM phosphorylation by ATR after replication fork arrest is not important for its relocalization.

SIGNOR-278978

Q13043

Q7L9L4

1

phosphorylation

up-regulates

0.851

Mob1, which forms a complex with lats1/2, is also phosphorylated by mst1/2, resulting in an enhanced lats1/2mob1 interaction.

SIGNOR-175841

Q9UQK1

P13807

1

binding

up-regulates

0.851

In the liver, PTG and PPP1R3B(GL)are expressed at roughly equivalent levels [55], and they jointly promote hepatic glycogen mobilization and storage. PTG overexpression significantly increased glycogen content, mainly due to its ability to promote the redistribution of PP1 and glycogen synthase to glycogen granules, significantly increasing GS activity and glycogen synthesis (Figure 2)

SIGNOR-271733

Q02410

O14936

1

binding

up-regulates activity

0.851

Interaction with Munc18 increases Mint1 binding to CASK.

SIGNOR-264041

P22223

P35222

1

binding

up-regulates activity

0.851

At its C-terminus, cadherin interacts with Î²-catenin, which dynamically associates with Î±-catenin, a direct binding partner of filamentous actin

SIGNOR-265865

P27986

P42338

1

binding

up-regulates activity

0.851

Signal transduction pathways triggered by Tie2 have been extensively examined. Tyr-1101of Tie2 directly associates in a phosphotyrosine (pTyr)-dependent manner with the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase, which in turn activate PI 3-kinase, leading to cell motility and survival

SIGNOR-242640

P06241

P35222

1

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

Q86YC2

P38398

1

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

O14757

P30307

1

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

Q13188

Q9H8S9

1

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

O00206

Q8IUC6

1

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

P31749

P46527

1

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

P04626

P62993

1

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

P46937

Q99594

1

binding

up-regulates

0.85

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

SIGNOR-201471

P42345

O75385

1

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

P42345

O00141

1

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

Q9P1A6

Q9UPX8

1

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

Q8IZI9

Q8IU57

1

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

P20783

Q16288

1

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

Q96EP0

Q9Y6K9

1

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

O14763

Q13158

1

binding

up-regulates

0.849

Fadd binds to ligated trailr1 or trail-r2

SIGNOR-98565

Q9Y2X7

Q15052

1

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

P24941

Q08999

1

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

O00468

O75096

1

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

Q9NR50

P20042

1

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

Q9Y6K9

P25963

1

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

Q99836

P51617

1

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

Q92934

Q07817

2

binding

down-regulates activity

0.848

Bad binds more strongly to Bcl-x, than Bcl-2 in mammalian cells, and it reversed the death repressor activity of Bcl-x,, but not that of Bcl-2. When Bad dimerized with Bcl-x,, Bax was displaced and apoptosis was restored.

SIGNOR-249617

Q07817

Q92934

2

binding

up-regulates activity

0.848

Bad dimerizes with bcl-xl at the mitochondrial membrane where it exert its killing effects. Phosphorylation of bad promotes its binding to 14-3-3 protein, which may sequester bad from bcl-xl, thus promoting cell cells survival.

SIGNOR-81125

Q13951

Q01196

1

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

Q92917

O60231

1

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

Q96GD4

O14777

1

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

Q9Y2T1

P35222

1

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

Q15811

P60953

1

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

P29459

P29460

1

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

P20936

P01112

1

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

Q8IZI9

Q08334

1

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

O15111

Q04206

1

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

P45974

P0CG48

1

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

P01116

P04049

1

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

Q9NT62

O95166

1

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

Q96JC9

P55199

1

binding

up-regulates

0.847

Positive regulation of ell elongation activity depends on stable binding of eaf1 to the ell n terminus

SIGNOR-138516

P19883

P08476

1

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

P01137

P36897

1

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

Q13315

Q14676

1

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

Q92569

P42336

1

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

Q02224

O60566

1

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

Q9NS91

P12004

1

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

Q15788

P03372

1

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

Q13315

O14757

1

phosphorylation

up-regulates

0.845

Atr (predominantly) or atm (to a lesser extent) phosphorylates chk1 at ser317/345, directly leading to activation.

SIGNOR-163106

P38398

Q9BXW9

1

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

Q9BXL7

O95999

1

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

P61970

P37198

1

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

P51955

Q13257

1

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

P01374

P36941

1

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

P04629

P29353

1

binding

up-regulates

0.844

Autophosphorylated trka binds directly to plc?, Abl, and shc.

SIGNOR-75408

P25942

Q12933

1

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

P01111

P42336

1

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

Q9Y4P1

P60520

1

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