GleghornLab/Signor_3class · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels int64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
O14733	Q9Y2U5	0	phosphorylation	up-regulates activity	0.603	MEKK2 can phosphorylate and activate MAP2K proteins MKK7 and MEK5, thereby promoting activation of JNK and ERK5, respectively [ xref ].	SIGNOR-279212
P67775	Q96HP0	1	phosphorylation	down-regulates activity	0.2	Akt and PP2A reciprocally regulate the guanine nucleotide exchange factor Dock6 to control axon growth of sensory neurons\|At later developmental stages, the abundance of the kinase Akt increased, resulting in the binding of Akt to Dock6 and the phosphorylation of Dock6 at Ser(1194). \| In dorsal root ganglion neurons from mice lacking Dock6, reintroduction of Dock6 with a nonphosphorylatable S1194A mutation rescued axon extension but not branch number, whereas reintroduction of Dock6 with a phosphomimetic S1194E mutation resulted in premature branching	SIGNOR-275669
O76050	Q8NE35	1	ubiquitination	up-regulates activity	0.47	If Neurl1 interacts and modulates the activity of CPEB3 and increases the translation of GluA1 and GluA2 mRNAs, this effect would be blocked if we abolished the interaction between CPEB3 and Neurl1.\|Neurl1 Interacts with and Ubiquitinates a Translational Regulator of GluA1 and GluA2 : the Cytoplasmic Polyadenylation Element Binding Protein 3.	SIGNOR-278588
P11021	Q9NZJ5	2	binding	down-regulates activity	0.726	In the stressed ER, protein chaperone GRP78 binds to unfolded proteins and dissociates from the luminal domain of PERK, leading to oligomerization and activation of PERK by autophosphorylation.	SIGNOR-260164
P51812	Q99683	1	phosphorylation	down-regulates activity	0.2	We provide evidence to show that RSK2 inhibits ASK1 by phosphorylating S83, T1109, and T1326 through a novel mechanism in which phospho-T1109/T1326 inhibits ATP binding to ASK1, while phospho-S83 attenuates ASK1 substrate MKK6 binding.	SIGNOR-276463
Q14863	O14965	0	phosphorylation	down-regulates activity	0.2	Here, we report that Aurora kinase A phosphorylates mPOU at Ser197 and inhibit its DNA-binding ability.	SIGNOR-273546
Q99558	P19634	1	phosphorylation	up-regulates activity	0.307	The Nck-interacting kinase (NIK) phosphorylates the Na+-H+ exchanger NHE1 and regulates NHE1 activation by platelet-derived growth factor.\|We now show that NIK binds to and divergently activates the plasma membrane Na(+)-H(+) exchanger NHE1.	SIGNOR-279632
P08047	Q05513	0	phosphorylation	up-regulates	0.484	Here we have used a variety of approaches to identify 3 amino acids (thr668, ser670, and thr681) in the zinc finger domain of sp1 that are modified by pkc-zeta angiotensin ii, which activates pkc-? Phosphorylation (at thr410) via the angiotensin ii type 1 receptor, stimulates sp1 phosphorylation and increases sp1 binding to the platelet-derived growth factor-d promoter.	SIGNOR-160774
P14091	P01023	1	cleavage	down-regulates quantity by destabilization	0.38	Disruption of structural and functional integrity of alpha 2-macroglobulin by cathepsin E\|Analysis of the N-terminal amino-acid sequences of these proteins revealed that alpha 2M was selectively cleaved at the Phe811-Leu812 bond in about 100mer downstream of the bait region.	SIGNOR-266977
P04792	P49137	0	phosphorylation	down-regulates	0.809	Notably mk2 is well known to play an important role in actin filament remodellng by phosphorylating hsp27.	SIGNOR-94021
Q9UQM7	P49593	0	dephosphorylation	down-regulates	0.331	Ppm1f specifically dephosphorylates the phospho-thr-286 in autophosphorylated camkii substrate and thus deactivates the camkii in vitro.	SIGNOR-124309
P35222	P35579	0	transcriptional regulation	up-regulates quantity by expression	0.274	Nuclear MYH9 bound to the CTNNB1 promoter through its DNA-binding domain, and interacted with myosin light chain 9, β-actin and RNA polymerase II to promote CTNNB1 transcription, which conferred resistance to anoikis in GC cells in vitro and in vivo.	SIGNOR-278896
P15923	P41134	2	binding	down-regulates activity	0.634	All three Ids bound with high affinity to E proteins .Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo.	SIGNOR-241107
Q96AP0	P35244	2	binding	down-regulates activity	0.2	The current model for how telomeres repress ATR signaling proposes that POT1/TPP1 prevents the binding of RPA to the single-stranded telomeric DNA	SIGNOR-263329
O75385	Q8NEB9	1	phosphorylation	up-regulates activity	0.713	In the nucleation step of autophagy, The ULK1 complex phosphorylates and activates the Beclin-1-VPS34 complex.	SIGNOR-279670
P53350	Q9Y5T5	1	phosphorylation	up-regulates activity	0.344	Plk1 phosphorylates and activates Usp16. In vitro phosphorylation of Usp16 with single (S330A, S386A, or S486A) or collective 3A (S330A/S386A/S486A) mutation showed that Plk1 phosphorylated Usp16 at all three sites (Fig. S2 D).	SIGNOR-274015
Q9Y4K3	P14778	1	ubiquitination	down-regulates quantity by destabilization	0.9	We found that of all TRAFs and E3 ligases examined, TRAF6 preferentially ubiquitinated IL-1R1.	SIGNOR-278576
P06493	Q9BYG3	1	phosphorylation	up-regulates activity	0.28	The forkhead-associated (FHA) domain of human Ki67 interacts with the human nucleolar protein hNIFK, recognizing a 44-residue fragment, hNIFK226-269, phosphorylated at Thr234. Here we show that high-affinity binding requires sequential phosphorylation by two kinases, CDK1 and GSK3, yielding pThr238, pThr234 and pSer230. phosphorylation of Thr234 by GSK3 proceeds only after Thr238 is already phosphorylated by CDK1.	SIGNOR-262696
P99999	P53701	0	chemical modification	up-regulates activity	0.44	Cytochrome c oxidase catalyzes the reduction of molecular oxygen to water, a process in which four electrons, four protons, and one molecule of oxygen are consumed. The reaction is coupled to the pumping of four additional protons across the membrane. According to the currently accepted concept, the pumping of all four protons occurs after the binding of oxygen to the reduced enzyme and is exclusively coupled to the last two electron transfer steps.	SIGNOR-280296
Q9UJ99	P35222	2	binding	up-regulates activity	0.332	At its C-terminus, cadherin interacts with Î²-catenin, which dynamically associates with Î±-catenin, a direct binding partner of filamentous actin	SIGNOR-265860
P84022	Q96PZ7	2	binding	up-regulates activity	0.2	CSMD1 co-immunoprecipitated with SMAD3, confirming our results that CSMD1 interacts with Smad3 in A375 cells. CSMD1 interacts with Smad3 and induces phosphorylation (p-Smad3). Phosphorylated Smad3 promotes Smad2 phosphorylation and Smad2/3/4 complex formation.	SIGNOR-265151
P55199	Q96CJ1	2	binding	up-regulates	0.746	The eaf1-related eaf2 protein is also a positive regulator of ell elongation activity	SIGNOR-138540
O43306	P08754	2	binding	down-regulates activity	0.511	Types V and VI adenylyl cyclase are most sensitive to inhibition by Gnai1, Gnai2, and Gnai3	SIGNOR-278079
P12644	P19838	0	transcriptional regulation	down-regulates quantity by repression	0.2	The effect of TNF-alpha on the Bmp4 promoter is mediated through NF-kB.	SIGNOR-266086
Q86UY5	P49674	2	binding	up-regulates quantity	0.2	We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.	SIGNOR-273761
O60353	O14640	2	binding	up-regulates activity	0.678	When canonical wnts bind to their respective fzd receptors, heterotrimeric g-proteins and dsh get activated and lead to the recruitment of axin to the fzd co-receptor lrp.	SIGNOR-198828
P12931	Q9UL51	1	phosphorylation	up-regulates activity	0.267	We identified a highly conserved tyrosine residue in the C-linker of HCN channels (Tyr476 in HCN2) that confers modulation by Src. Replacement of this tyrosine by phenylalanine in HCN2 or HCN4 abolished sensitivity to Src inhibitors. Mass spectrometry confirmed that Tyr476 is phosphorylated by Src. Our results have functional implications for HCN channel gating. Furthermore, they indicate that tyrosine phosphorylation contributes in vivo to the fine tuning of HCN channel activity.	SIGNOR-263199
P19784	Q92769	1	phosphorylation	up-regulates activity	0.39	HDAC2 is phosphorylated uniquely by protein kinase CK2 in vitro. Studies using unfractionated cell extracts with CK2 inhibitors suggest that protein kinase CK2 is the major source of HDAC2 kinase. Finally, and perhaps most interesting, HDAC2 phosphorylation promotes enzymatic activity, selectively regulates complex formation, but has no effect on transcriptional repression. \| Since our data suggest that protein kinase CK2 is the major kinase responsible for HDAC2 phosphorylation, and because Ser422 and Ser424, but not Ser411, lie within CK2 recognition sequences, we believe that Ser394, Ser422, and Ser424 constitute the three phosphorylated residues in HDAC2.	SIGNOR-251001
P05556	Q9Y5I0	2	binding	up-regulates activity	0.2	The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion.	SIGNOR-265672
P49411	Q9BXM7	0	phosphorylation	down-regulates activity	0.2	PINK1 interacts with the autophagy effector TUFm and phosphorylates TUFm at Ser222. These results indicated that p222-hTUFm sequestered more monomer Atg5 and reduced the conjugated Atg5-Atg12 complex to subdue mitophagy.	SIGNOR-266382
Q14332	P56704	2	binding	up-regulates	0.753	It was also shown that wnt5a inhibits the beta-catenin pathway by competing with wnt3a for binding to fz2, and that the impairment of clathrin-mediated internalization does not affect this wnt5a inhibitory action.	SIGNOR-189117
Q93009	Q00987	1	deubiquitination	up-regulates	0.77	Subsequently, hausp was shown to deubiquitinate mdm2 and mdmx, thereby stabilizing these proteins.	SIGNOR-139450
P27816	Q9P0L2	0	phosphorylation	down-regulates activity	0.437	Here we show that p110mark phosphorylates analogous KXGS sites in the microtubule binding domains of the neuronal MAP2 and the ubiquitous MAP4. Phosphorylation in vitro leads to the dissociation of MAP2 and MAP4 from microtubules and to a pronounced increase in dynamic instability.	SIGNOR-250171
P00749	Q03405	2	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
Q5T6F0	P43360	2	binding	down-regulates quantity by destabilization	0.2	The CRL4‐DCAF12 E3 ubiquitin ligase degrades MAGE‐A3/6	SIGNOR-272255
Q9NYB9	Q6T4R5	2	binding	up-regulates activity	0.2	NHS may preferentially bind one or more Abi's in vivo, and it is also likely that specificity is governed by spatiotemporal expression of both proteins. Abi2 is highly expressed in the lens and plays a pivotal role in the development of the anterior and posterior sutures. This suggests that an NHS–Abi2 interaction may be physiologically important for lens development and that null mutations in the NHS gene could cause congenital cataract by disruption of this interaction and the actin cytoskeleton.	SIGNOR-253579
P10242	Q9UBE8	0	phosphorylation	down-regulates activity	0.714	Furthermore, the downregulation of c-Myb by NLK overexpression could be inhibited in cells that had been treated with the 26S proteasome inhibitor MG132 but not in those treated with DMSO ( ).\|HIPK2 and NLK directly bind to c-Myb, and NLK phosphorylates c-Myb at multiple sites, resulting in its ubiquitination and proteasome-dependent degradation [32].	SIGNOR-280049
P00533	Q13315	1	phosphorylation	up-regulates activity	0.399	Here, we show that upon irradiation stimulation, ATM associates with and is phosphorylated by epidermal growth factor receptor (EGFR) at Tyr370 (Y370) at the site of DNA double-strand breaks.	SIGNOR-276872
Q9BYG3	P06493	0	phosphorylation	up-regulates activity	0.28	The forkhead-associated (FHA) domain of human Ki67 interacts with the human nucleolar protein hNIFK, recognizing a 44-residue fragment, hNIFK226-269, phosphorylated at Thr234. Here we show that high-affinity binding requires sequential phosphorylation by two kinases, CDK1 and GSK3, yielding pThr238, pThr234 and pSer230. phosphorylation of Thr234 by GSK3 proceeds only after Thr238 is already phosphorylated by CDK1.	SIGNOR-262696
O15393	P14210	1	transcriptional regulation	up-regulates quantity by expression	0.2	we identified pro-hepatocyte growth factor (HGF) as a TMPRSS2 substrate and confirmed that HGF and it’s cognate receptor c-Met are activated in prostate cancers expressing TMPRSS2, a finding that also associated with the acquisition of a pro-invasive mesenchymal gene expression program.	SIGNOR-263657
P15172	P26651	0	post transcriptional regulation	down-regulates quantity by destabilization	0.292	The TTP binding site in the 3â€² UTR of MyoD would permit TTP-mediated mRNA decay	SIGNOR-253597
O60260	Q03135	1	ubiquitination	down-regulates quantity	0.2	Parkin induces the degradation of cav-1 through the proteasome dependent pathway.\|We also demonstrated that WT parkin ubiquitinates cav-1 for degradation.	SIGNOR-278710
Q9Y618	Q96T58	2	binding	up-regulates	0.467	Sharp is a potent transcriptional repressor whose repression domain (rd) interacts directly with smrt	SIGNOR-107260
P24941	P20248	1	phosphorylation	up-regulates	0.977	Here we present evidence from in vitro and in vivo assay systems that the degradation of human cyclin a can be inhibited by kinase-inactive mutants of cdk2 and cdc2cdk2 can phosphorylate cyclin a on ser-154	SIGNOR-74466
P01137	P62736	1	transcriptional regulation	up-regulates quantity by expression	0.419	A TGF-β1 response element that has a sequence different to that known for Smad binding has been identified in the α- SM actin promoter and seems to be essential for expression of α-SM actin in both SM cells 72 and myofibroblasts73 . How TGF-β1 activates expression of α-SM actin through this TGF-β1 control element is, as yet, unknown	SIGNOR-277681
P49116	Q13131	0	phosphorylation	down-regulates	0.2	Tr4 transactivation is inhibited via phosphorylation bymetformin-induced amp-activated protein kinase (ampk) at the amino acid serine 351, which results in the suppression of scd1 gene expression	SIGNOR-173118
P17252	Q8WZ42	1	phosphorylation	up-regulates activity	0.271	In summary, titin is a PKC substrate with PKCalpha phosphorylating predominately the full-length titin molecule.\|Mechanical experiments with skinned LV myocardium revealed that PKCalpha significantly increases titin based passive tension, an effect that is reversed by PP1.	SIGNOR-278382
P23443	Q9BPZ7	1	phosphorylation	down-regulates activity	0.565	Consistently, we detected in vivo Sin1 phosphorylation triggered by S6K1 and to a lesser extent, Akt1, but not other characterized AGC kinases (XREF_FIG and XREF_SUPPLEMENTARY).\|Here we report that phosphorylation of Sin1 at Thr 86 and Thr 398 suppresses mTORC2 kinase activity by dissociating Sin1 from mTORC2.	SIGNOR-279568
Q13485	O14980	0	relocalization	down-regulates	0.3	We demonstrate that inhibition of crm1-mediated nuclear export by treatment of cells with leptomycin b results in endogenous smad4 accumulating very rapidly in the nucleus.	SIGNOR-84247
Q13642	Q06587	2	binding	up-regulates	0.357	The polycombprotein ring1 interacts with the lim domains of kyot2 in yeast and mammalian cells. The interaction between kyot2 and ring1 was detected both in vitro and in vivo	SIGNOR-123150
O00399	P06493	0	phosphorylation	up-regulates activity	0.307	Here, we show that the p27/p25 heterodimer undergoes mitotic phosphorylation by cyclin‐dependent kinase 1 (Cdk1) at a single site, p27 Thr186, to generate an anchoring site for polo‐like kinase 1 (Plk1) at kinetochores.	SIGNOR-264777
P36873	P31749	1	dephosphorylation	down-regulates activity	0.383	Here, we identify PP1 as a serine/threonine phosphatase that associates with and dephosphorylates AKT in breast cancer cells\|The heat shock protein 90 inhibitor geldanamycin and the ErbB inhibitor ZD1839 promote rapid PP1 phosphatase-dependent inactivation of AKT in ErbB2 overexpressing breast cancer cells	SIGNOR-252605
Q92917	O60231	2	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
P10636	O00141	0	phosphorylation	down-regulates	0.331	Second, sgk1 indirectly depolymerized mts through the phosphorylation of tau at ser214	SIGNOR-161288
P09874	Q9H0A0	0	acetylation	up-regulates quantity by stabilization	0.2	MORC2 directly interacts with PARP1. MORC2 mediates the interaction between PARP1 and NAT10 and thereby promotes NAT10-mediated PARP1 acetylation at K949, which blocks CHFR-mediated ubiquitination and degradation of PARP1.	SIGNOR-273715
Q9HC16	P17612	0	phosphorylation	up-regulates	0.324	Here we show that pka binds and specifically phosphorylates a3g at thr32 in vitro and in vivo. This phosphorylation event reduces the binding of a3g to vif and its subsequent ubiquitination and degradation, and thus promotes a3g antiviral activity.	SIGNOR-181526
P14921	Q93084	1	transcriptional regulation	up-regulates quantity by expression	0.326	Ets-1 was able to transactivate the SERCA3 promoter in MoBr 204 as cotransfection of an Ets-1 expression vector increased the activity of the −97/+301-Luc construct by 6-fold.	SIGNOR-261601
O75460	P17861	1	phosphorylation	up-regulates activity	0.647	IRE1\u03b1 phosphorylates and activates the XBP1 transcription factor XBP1 via its kinase activity.	SIGNOR-279712
Q14258	Q9UKV5	1	polyubiquitination	down-regulates quantity by destabilization	0.364	We further demonstrate that TRIM25 ubiquitylates gp78 and that overexpression of TRIM25 accelerates the degradation of gp78. Our data suggest that TRIM25 not only cooperates with gp78 in polyubiquitylation of AMF but also gauges the steady-state level of gp78.	SIGNOR-272176
Q969F8	Q15726	2	binding	up-regulates	0.806	Here we show that kiss-1 (refs 1, 4) encodes a carboxy-terminally amidated peptide with 54 amino-acid residues, which we have isolated from human placenta as the endogenous ligand of an orphan g-protein-coupled receptor (hot7t175) and have named 'metastin'	SIGNOR-108480
P58753	Q9NWF9	0	ubiquitination	down-regulates quantity by destabilization	0.387	Triad3A promotes proteolytic degradation of adapter proteins. A, Triad3A promotes down-regulation of TIRAP, TRIF, and RIP1 proteins.	SIGNOR-271607
P46527	O00141	0	phosphorylation	down-regulates	0.469	Activated sgk1 and p27 phosphorylation at t157, and both were inhibited by short-term rapamycin treatment and by sgk1 shrna.	SIGNOR-179117
O00712	Q14938	1	transcriptional regulation	up-regulates quantity	0.42	We report that, in the absence of Nfia or Nfib, there is a marked reduction in the spinal cord expression of NFIX, and that NFIB can transcriptionally activate Nfix expression in vitro. These data demonstrate that NFIX is part of the downstream transcriptional program through which NFIA and NFIB coordinate gliogenesis within the spinal cord.	SIGNOR-268870
P29353	Q02763	2	binding	up-regulates activity	0.58	Our results identified a novel interaction between Tie2 with the adapter molecule ShcA and suggested that this interaction may play a role in the regulation of migration and three-dimensional organization of endothelial cells induced by angiopoietin-1. Furthermore, Tyr-1101 of Tie2 was identified as the primary binding site for the SH2 domain of ShcA.	SIGNOR-242573
Q14469	P37231	1	transcriptional regulation	down-regulates quantity by repression	0.248	CREB inhibits hepatic PPAR-gamma expression in the fasted state by stimulating the expression of the Hairy Enhancer of Split (HES-1) gene, a transcriptional repressor that is shown here to be a mediator of fasting lipid metabolism in vivo	SIGNOR-253584
Q13115	P27361	1	dephosphorylation	down-regulates activity	0.709	Dephosphorylation and Inactivation of ERKs\|ERK1 phosphorylated on either threonine (ERK1Y204F) or tyrosine alone (ERK1T202A) was utilized as a substrate for HVH2. Threonine 202 and tyrosine 204 in ERK1 (53) correspond to threonine 183 and tyrosine 185 in ERK2 which are the activation-phosphorylation sites by MEK(14, 15, 16). ERK1, a kinase-deficient mutant, was phosphorylated on both threonine and tyrosine by MEK2 (Fig. 3B). ERK1T202A, having threonine 202 substituted by an alanine, was phosphorylated only on tyrosine while ERK1Y204F, having tyrosine 204 substituted by a phenylalanine, was phosphorylated only on threonine (Fig. 3B). GST-HVH2 dephosphorylated all three ERK1 mutants (Fig. 3A), suggesting that double phosphorylations of adjacent threonine and tyrosine were not a prerequisite for HVH2 recognition. However, HVH2 dephosphorylated ERK1* and ERK1T202A more efficiently than ERK1Y204F (Fig. 3A), indicating that HVH2 preferred phosphotyrosine over phosphothreonine. Interestingly, MEK also phosphorylated tyrosine residues more efficiently than threonine residues of ERK	SIGNOR-248716
P31751	O43524	1	phosphorylation	down-regulates activity	0.751	Akt-dependent phosphorylation of foxo3a (thr32, ser253, and ser315 for human foxo3) enhances foxo3a/14-3-3 Interaction and promotes foxo3a nuclear export to the cytoplasm, resulting in the repression of foxo3a transcriptional function akt phosphorylates members of the foxo factors (forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localisation. In particular, akt phosphorylates foxo1 on thr24, ser256 and ser319. Foxo 3alfa and foxo4 are phosphorylated on equivalent sites.	SIGNOR-236671
Q7Z2Z2	Q9Y3A5	2	binding	up-regulates	0.2	Sbds stimulates 60s-dependent gtp hydrolysis by efl1	SIGNOR-173533
Q7KZI7	Q6WKZ4	1	phosphorylation	up-regulates quantity	0.341	We have now found that MARK2 phosphorylates Rab11-FIP1B/C at serine 234 in a consensus site similar to that previously identified in Rab11-FIP2.	SIGNOR-273676
O60341	Q9HCU9	2	binding	up-regulates activity	0.257	Our results have showed that BRMS1 together with LSD1 are required for inhibition of breast cancer cell migration and invasion. Collectively, these findings demonstrate that BRMS1 executes transcriptional suppression of breast cancer metastasis by associating with the LSD1 and thus can be targeted for breast cancer therapy.	SIGNOR-266409
Q9Y6Q9	O15111	0	phosphorylation	up-regulates	0.395	Herein, we report the successful identification of six functional in vivo src-3 phosphorylation sites.	SIGNOR-196953
Q02447	P28482	0	phosphorylation	up-regulates	0.305	Here, we show that sp3, which, as sp1, belongs to the gc-rich binding transcription factor family, is also phosphorylated by erk in vitro on serine 73. in the inducible cell lines, expression of wild-type form of sp3 increases vegf production whereas the s73a form has a reduced potential reflecting its lower transcriptional activity.	SIGNOR-157272
P11137	Q9P0L2	0	phosphorylation	down-regulates activity	0.418	Here we show that p110mark phosphorylates analogous KXGS sites in the microtubule binding domains of the neuronal MAP2 and the ubiquitous MAP4. Phosphorylation in vitro leads to the dissociation of MAP2 and MAP4 from microtubules and to a pronounced increase in dynamic instability.	SIGNOR-250166
P41240	Q92793	2	binding	up-regulates	0.535	Here we present cbp--a transmembrane phosphoprotein that is ubiquitously expressed and binds specifically to the sh2 domain of csk. Cbp is involved in the membrane localization of csk and in the csk-mediated inhibition of c-src.	SIGNOR-77139
P68400	P06744	1	phosphorylation	down-regulates activity	0.333	It is known that human PGI/AMF is phosphorylated at Ser(185) by protein kinase CK2 (CK2) \| These results demonstrate that phosphorylation affects the allosteric kinetic properties of the enzyme, resulting in a less active form of PGI, whereas non-phosphorylated protein species retain cytokine activity.	SIGNOR-250869
Q16236	P09601	1	transcriptional regulation	up-regulates quantity by expression	0.679	In both models, the inducer-modified and Nrf2-bound Keap1 is inactivated and, consequently, newly synthesized Nrf2 proteins bypass Keap1 and translocate into the nucleus, bind to the ARE and drive the expression of Nrf2 target genes such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase (GCL) and glutathione S transferases (GSTs).	SIGNOR-256276
P52564	P46108	1	phosphorylation	up-regulates	0.2	Mapkk6 was shown to phosphorylate and specifically activate the p38/mpk2 sub-family of the mitogen-activated protein kinase superfamily.	SIGNOR-42384
Q92922	P51531	2	binding	up-regulates	0.911	The remodeling activity of brg1 and hbrm is stimulated by baf170/baf155 and is further stimulated when ini1 is added.	SIGNOR-65432
P10415	P01241	0	transcriptional regulation	up-regulates quantity by expression	0.2	Autocrine hGH increased the transcription and subsequent mRNA level and protein expression of c-Myc, Cyclin D1, and Bcl-2 in human mammary epithelial cells	SIGNOR-261628
P07900	Q9P278	2	binding	down-regulates activity	0.411	FNIP1 and FNIP2 facilitate FLCN binding to Hsp90 chaperone. Our results suggest that FNIP1 is a potent inhibitor of Hsp90 ATPase activity, as 200 nM of FNIP1 inhibits Hsp90 ATPase activity by 50-fold. FNIP2 also has shown inhibitory activity towards Hsp90; however, it required 1.6 μM of FNIP2 to inhibit the ATPase activity by eightfold. Although we use the term ‘inhibition' here, FNIPs seem only to be slowing the chaperone cycle.	SIGNOR-261414
P06213	Q9Y4H2	1	phosphorylation	down-regulates activity	0.757	Tyr624 and Tyr628 are involved in the interaction between the IR and the KRLB domain of IRS-2, including tyrosine phosphorylation, and Tyr628 seems to be more important than Tyr624 in this process. the binding between the insulin receptor and the KRLB domain of IRS-2 results in tyrosine phosphorylation of the KRLB domain, and this leads to decreased binding of IRS-2 to the insulin receptor.	SIGNOR-251319
Q9HBE4	P31785	2	binding	up-regulates	0.61	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-108858
P35367	Q9UQM7	0	phosphorylation	down-regulates	0.282	As we have shown previously, human h1r can be phosphorylated in vitro by several kinases includingpka, pkc, pkg, and camk ii in summary, these data suggest that thr140, thr142, ser396, ser398, and thr478 can be phosphorylated by the kinases described above (table 2).	SIGNOR-124348
Q13315	Q96S59	1	phosphorylation	up-regulates activity	0.439	We demonstrate that ATM phosphorylates RanBP9 in response to Ionizing Radiation and mediates its nuclear accumulation.	SIGNOR-279005
P33981	O43683	1	phosphorylation	up-regulates activity	0.695	After Cdk1 phosphorylates Bub1 S459, Mps1 then phosphorylates Bub1 T461 (b).	SIGNOR-278255
O75592	Q8TEK3	0	transcriptional regulation	down-regulates quantity by repression	0.2	Overexpression of DOT1L decreased the expression of HECTD4 and MYCBP2 in LNCaP, C42B, and 22rv1 cells (Supplementary Fig. 5c), suggesting that DOT1L plays a role in repressing these targets either directly or indirectly.	SIGNOR-267151
P06493	P04626	0	phosphorylation	down-regulates	0.274	Phosphorylation on tyrosine-15 of p34(cdc2) by erbb2 inhibits p34(cdc2) activation and is involved in resistance to taxol-induced apoptosis	SIGNOR-88671
O14641	Q13145	2	binding	up-regulates	0.516	Bmp-2 mediates phosphorylated smad1 (psmad1) or, with loss of bmprii, psmad3-dependent recruitment of disheveled (dvl) to promote rhoa-rac1 signaling necessary for motility.	SIGNOR-23037
Q9Y4K3	Q86UT6	2	binding	down-regulates activity	0.472	Immunoprecipitation experiments showed that NLRX1 interacted with TRAF6 and TRAF3, but not with TRAF2 or TRAF5. These results further suggest that NLRX1 specifically inhibits TLR-induced TRAF6-dependent NF-kB signaling through targeting TRAF6.	SIGNOR-260364
Q96P48	P60953	1	gtpase-activating protein	down-regulates activity	0.531	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-260452
O15392	Q16254	0	transcriptional regulation	down-regulates quantity by repression	0.334	This TGF-beta response is triggered through a Smad2/3-dependent hypophosphorylation of Rb and the subsequent association of the Rb/E2F4 repressive complex to CDE/CHR elements in the proximal region of the survivin promoter.	SIGNOR-271678
P17252	Q13255	1	phosphorylation	down-regulates activity	0.385	Furthermore, we demonstrate that the selectivity of PKC action on receptor signaling rests on phosphorylation of a threonine residue located in the G protein-interacting domain of the receptor. Modification at Thr(695) selectively disrupts mGluR1alpha-G(q/11) interaction without affecting signaling through G(s).	SIGNOR-249043
P12004	P38936	2	binding	down-regulates	0.765	P21 exerts its effect on the cell cycle not only by inhibiting cyclin/cdk complexes, but also by inhibiting proliferating cell nuclear antigen (pcna)	SIGNOR-191939
P48357	P41159	2	binding	up-regulates	0.814	Both ob-ra and ob-rb bind leptin with the same affinity, whereas only ob-rb can elicit intracellular response	SIGNOR-55656
O75116	Q09472	1	phosphorylation	up-regulates activity	0.297	Nuclear Rho kinase, ROCK2, targets p300 acetyltransferase.\|p300 acetyltransferase activity is dependent on its phosphorylation status in cells, and p300 phosphorylation by ROCK2 results in an increase in its acetyltransferase activity in vitro.	SIGNOR-279482
Q13950	Q92793	2	binding	up-regulates	0.406	Mechanistic analysis revealed that the tak1-mkk3/6-p38 mapk axis phosphory-lated runx2, promoting its association with the coac-tivator creb-binding protein (cbp), which is re-quired to regulate osteoblast genetic programs.	SIGNOR-166170
Q00535	P04150	1	phosphorylation	down-regulates activity	0.481	Cdk5 phosphorylated gr at multiple serines, including ser203 and ser211 of its n-terminal domain, and suppressed the transcriptional activity of this receptor on glucocorticoid-responsive promoters by attenuating attraction of transcriptional cofactors to dna.\| the effect of CDK5 on GR-induced transcriptional activity is specific to gene promoter, and possibly, to tissue	SIGNOR-154405
O15530	Q14680	0	phosphorylation	down-regulates activity	0.267	The results showed that MPK38 interacted with and inhibited PDK1 activity via Thr(354) phosphorylation.	SIGNOR-276414
Q13188	P04049	2	binding	down-regulates	0.36	Raf-1 prevents dimerization and phosphorylation of the activation loop of mst2 independently of its protein kinase activity.Raf-1 counteracts apoptosis by suppressing the activation of mammalian sterile 20-like kinase (mst2)	SIGNOR-132824
P35659	P68400	0	phosphorylation	up-regulates	0.35	Dek is phosphorylated by the protein kinase ck2 in vitro and in vivo on ser32	SIGNOR-125912

O14733

Q9Y2U5

0

phosphorylation

up-regulates activity

0.603

MEKK2 can phosphorylate and activate MAP2K proteins MKK7 and MEK5, thereby promoting activation of JNK and ERK5, respectively [ xref ].

SIGNOR-279212

P67775

Q96HP0

1

phosphorylation

down-regulates activity

0.2

Akt and PP2A reciprocally regulate the guanine nucleotide exchange factor Dock6 to control axon growth of sensory neurons|At later developmental stages, the abundance of the kinase Akt increased, resulting in the binding of Akt to Dock6 and the phosphorylation of Dock6 at Ser(1194). | In dorsal root ganglion neurons from mice lacking Dock6, reintroduction of Dock6 with a nonphosphorylatable S1194A mutation rescued axon extension but not branch number, whereas reintroduction of Dock6 with a phosphomimetic S1194E mutation resulted in premature branching

SIGNOR-275669

O76050

Q8NE35

1

ubiquitination

up-regulates activity

0.47

If Neurl1 interacts and modulates the activity of CPEB3 and increases the translation of GluA1 and GluA2 mRNAs, this effect would be blocked if we abolished the interaction between CPEB3 and Neurl1.|Neurl1 Interacts with and Ubiquitinates a Translational Regulator of GluA1 and GluA2 : the Cytoplasmic Polyadenylation Element Binding Protein 3.

SIGNOR-278588

P11021

Q9NZJ5

2

binding

down-regulates activity

0.726

In the stressed ER, protein chaperone GRP78 binds to unfolded proteins and dissociates from the luminal domain of PERK, leading to oligomerization and activation of PERK by autophosphorylation.

SIGNOR-260164

P51812

Q99683

1

phosphorylation

down-regulates activity

0.2

We provide evidence to show that RSK2 inhibits ASK1 by phosphorylating S83, T1109, and T1326 through a novel mechanism in which phospho-T1109/T1326 inhibits ATP binding to ASK1, while phospho-S83 attenuates ASK1 substrate MKK6 binding.

SIGNOR-276463

Q14863

O14965

0

phosphorylation

down-regulates activity

0.2

Here, we report that Aurora kinase A phosphorylates mPOU at Ser197 and inhibit its DNA-binding ability.

SIGNOR-273546

Q99558

P19634

1

phosphorylation

up-regulates activity

0.307

The Nck-interacting kinase (NIK) phosphorylates the Na+-H+ exchanger NHE1 and regulates NHE1 activation by platelet-derived growth factor.|We now show that NIK binds to and divergently activates the plasma membrane Na(+)-H(+) exchanger NHE1.

SIGNOR-279632

P08047

Q05513

0

phosphorylation

up-regulates

0.484

Here we have used a variety of approaches to identify 3 amino acids (thr668, ser670, and thr681) in the zinc finger domain of sp1 that are modified by pkc-zeta angiotensin ii, which activates pkc-? Phosphorylation (at thr410) via the angiotensin ii type 1 receptor, stimulates sp1 phosphorylation and increases sp1 binding to the platelet-derived growth factor-d promoter.

SIGNOR-160774

P14091

P01023

1

cleavage

down-regulates quantity by destabilization

0.38

Disruption of structural and functional integrity of alpha 2-macroglobulin by cathepsin E|Analysis of the N-terminal amino-acid sequences of these proteins revealed that alpha 2M was selectively cleaved at the Phe811-Leu812 bond in about 100mer downstream of the bait region.

SIGNOR-266977

P04792

P49137

0

phosphorylation

down-regulates

0.809

Notably mk2 is well known to play an important role in actin filament remodellng by phosphorylating hsp27.

SIGNOR-94021

Q9UQM7

P49593

0

dephosphorylation

down-regulates

0.331

Ppm1f specifically dephosphorylates the phospho-thr-286 in autophosphorylated camkii substrate and thus deactivates the camkii in vitro.

SIGNOR-124309

P35222

P35579

0

transcriptional regulation

up-regulates quantity by expression

0.274

Nuclear MYH9 bound to the CTNNB1 promoter through its DNA-binding domain, and interacted with myosin light chain 9, β-actin and RNA polymerase II to promote CTNNB1 transcription, which conferred resistance to anoikis in GC cells in vitro and in vivo.

SIGNOR-278896

P15923

P41134

2

binding

down-regulates activity

0.634

All three Ids bound with high affinity to E proteins .Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo.

SIGNOR-241107

Q96AP0

P35244

2

binding

down-regulates activity

0.2

The current model for how telomeres repress ATR signaling proposes that POT1/TPP1 prevents the binding of RPA to the single-stranded telomeric DNA

SIGNOR-263329

O75385

Q8NEB9

1

phosphorylation

up-regulates activity

0.713

In the nucleation step of autophagy, The ULK1 complex phosphorylates and activates the Beclin-1-VPS34 complex.

SIGNOR-279670

P53350

Q9Y5T5

1

phosphorylation

up-regulates activity

0.344

Plk1 phosphorylates and activates Usp16. In vitro phosphorylation of Usp16 with single (S330A, S386A, or S486A) or collective 3A (S330A/S386A/S486A) mutation showed that Plk1 phosphorylated Usp16 at all three sites (Fig. S2 D).

SIGNOR-274015

Q9Y4K3

P14778

1

ubiquitination

down-regulates quantity by destabilization

0.9

We found that of all TRAFs and E3 ligases examined, TRAF6 preferentially ubiquitinated IL-1R1.

SIGNOR-278576

P06493

Q9BYG3

1

phosphorylation

up-regulates activity

0.28

The forkhead-associated (FHA) domain of human Ki67 interacts with the human nucleolar protein hNIFK, recognizing a 44-residue fragment, hNIFK226-269, phosphorylated at Thr234. Here we show that high-affinity binding requires sequential phosphorylation by two kinases, CDK1 and GSK3, yielding pThr238, pThr234 and pSer230. phosphorylation of Thr234 by GSK3 proceeds only after Thr238 is already phosphorylated by CDK1.

SIGNOR-262696

P99999

P53701

0

chemical modification

up-regulates activity

0.44

Cytochrome c oxidase catalyzes the reduction of molecular oxygen to water, a process in which four electrons, four protons, and one molecule of oxygen are consumed. The reaction is coupled to the pumping of four additional protons across the membrane. According to the currently accepted concept, the pumping of all four protons occurs after the binding of oxygen to the reduced enzyme and is exclusively coupled to the last two electron transfer steps.

SIGNOR-280296

Q9UJ99

P35222

2

binding

up-regulates activity

0.332

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

SIGNOR-265860

P84022

Q96PZ7

2

binding

up-regulates activity

0.2

CSMD1 co-immunoprecipitated with SMAD3, confirming our results that CSMD1 interacts with Smad3 in A375 cells. CSMD1 interacts with Smad3 and induces phosphorylation (p-Smad3). Phosphorylated Smad3 promotes Smad2 phosphorylation and Smad2/3/4 complex formation.

SIGNOR-265151

P55199

Q96CJ1

2

binding

up-regulates

0.746

The eaf1-related eaf2 protein is also a positive regulator of ell elongation activity

SIGNOR-138540

O43306

P08754

2

binding

down-regulates activity

0.511

Types V and VI adenylyl cyclase are most sensitive to inhibition by Gnai1, Gnai2, and Gnai3

SIGNOR-278079

P12644

P19838

0

transcriptional regulation

down-regulates quantity by repression

0.2

The effect of TNF-alpha on the Bmp4 promoter is mediated through NF-kB.

SIGNOR-266086

Q86UY5

P49674

2

binding

up-regulates quantity

0.2

We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.

SIGNOR-273761

O60353

O14640

2

binding

up-regulates activity

0.678

When canonical wnts bind to their respective fzd receptors, heterotrimeric g-proteins and dsh get activated and lead to the recruitment of axin to the fzd co-receptor lrp.

SIGNOR-198828

P12931

Q9UL51

1

phosphorylation

up-regulates activity

0.267

We identified a highly conserved tyrosine residue in the C-linker of HCN channels (Tyr476 in HCN2) that confers modulation by Src. Replacement of this tyrosine by phenylalanine in HCN2 or HCN4 abolished sensitivity to Src inhibitors. Mass spectrometry confirmed that Tyr476 is phosphorylated by Src. Our results have functional implications for HCN channel gating. Furthermore, they indicate that tyrosine phosphorylation contributes in vivo to the fine tuning of HCN channel activity.

SIGNOR-263199

P19784

Q92769

1

phosphorylation

up-regulates activity

0.39

HDAC2 is phosphorylated uniquely by protein kinase CK2 in vitro. Studies using unfractionated cell extracts with CK2 inhibitors suggest that protein kinase CK2 is the major source of HDAC2 kinase. Finally, and perhaps most interesting, HDAC2 phosphorylation promotes enzymatic activity, selectively regulates complex formation, but has no effect on transcriptional repression. | Since our data suggest that protein kinase CK2 is the major kinase responsible for HDAC2 phosphorylation, and because Ser422 and Ser424, but not Ser411, lie within CK2 recognition sequences, we believe that Ser394, Ser422, and Ser424 constitute the three phosphorylated residues in HDAC2.

SIGNOR-251001

P05556

Q9Y5I0

2

binding

up-regulates activity

0.2

The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion.

SIGNOR-265672

P49411

Q9BXM7

0

phosphorylation

down-regulates activity

0.2

PINK1 interacts with the autophagy effector TUFm and phosphorylates TUFm at Ser222. These results indicated that p222-hTUFm sequestered more monomer Atg5 and reduced the conjugated Atg5-Atg12 complex to subdue mitophagy.

SIGNOR-266382

Q14332

P56704

2

binding

up-regulates

0.753

It was also shown that wnt5a inhibits the beta-catenin pathway by competing with wnt3a for binding to fz2, and that the impairment of clathrin-mediated internalization does not affect this wnt5a inhibitory action.

SIGNOR-189117

Q93009

Q00987

1

deubiquitination

up-regulates

0.77

Subsequently, hausp was shown to deubiquitinate mdm2 and mdmx, thereby stabilizing these proteins.

SIGNOR-139450

P27816

Q9P0L2

0

phosphorylation

down-regulates activity

0.437

Here we show that p110mark phosphorylates analogous KXGS sites in the microtubule binding domains of the neuronal MAP2 and the ubiquitous MAP4. Phosphorylation in vitro leads to the dissociation of MAP2 and MAP4 from microtubules and to a pronounced increase in dynamic instability.

SIGNOR-250171

P00749

Q03405

2

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

Q5T6F0

P43360

2

binding

down-regulates quantity by destabilization

0.2

The CRL4‐DCAF12 E3 ubiquitin ligase degrades MAGE‐A3/6

SIGNOR-272255

Q9NYB9

Q6T4R5

2

binding

up-regulates activity

0.2

NHS may preferentially bind one or more Abi's in vivo, and it is also likely that specificity is governed by spatiotemporal expression of both proteins. Abi2 is highly expressed in the lens and plays a pivotal role in the development of the anterior and posterior sutures. This suggests that an NHS–Abi2 interaction may be physiologically important for lens development and that null mutations in the NHS gene could cause congenital cataract by disruption of this interaction and the actin cytoskeleton.

SIGNOR-253579

P10242

Q9UBE8

0

phosphorylation

down-regulates activity

0.714

Furthermore, the downregulation of c-Myb by NLK overexpression could be inhibited in cells that had been treated with the 26S proteasome inhibitor MG132 but not in those treated with DMSO ( ).|HIPK2 and NLK directly bind to c-Myb, and NLK phosphorylates c-Myb at multiple sites, resulting in its ubiquitination and proteasome-dependent degradation [32].

SIGNOR-280049

P00533

Q13315

1

phosphorylation

up-regulates activity

0.399

Here, we show that upon irradiation stimulation, ATM associates with and is phosphorylated by epidermal growth factor receptor (EGFR) at Tyr370 (Y370) at the site of DNA double-strand breaks.

SIGNOR-276872

Q9BYG3

P06493

0

phosphorylation

up-regulates activity

0.28

The forkhead-associated (FHA) domain of human Ki67 interacts with the human nucleolar protein hNIFK, recognizing a 44-residue fragment, hNIFK226-269, phosphorylated at Thr234. Here we show that high-affinity binding requires sequential phosphorylation by two kinases, CDK1 and GSK3, yielding pThr238, pThr234 and pSer230. phosphorylation of Thr234 by GSK3 proceeds only after Thr238 is already phosphorylated by CDK1.

SIGNOR-262696

O15393

P14210

1

transcriptional regulation

up-regulates quantity by expression

0.2

we identified pro-hepatocyte growth factor (HGF) as a TMPRSS2 substrate and confirmed that HGF and it’s cognate receptor c-Met are activated in prostate cancers expressing TMPRSS2, a finding that also associated with the acquisition of a pro-invasive mesenchymal gene expression program.

SIGNOR-263657

P15172

P26651

0

post transcriptional regulation

down-regulates quantity by destabilization

0.292

The TTP binding site in the 3â€² UTR of MyoD would permit TTP-mediated mRNA decay

SIGNOR-253597

O60260

Q03135

1

ubiquitination

down-regulates quantity

0.2

Parkin induces the degradation of cav-1 through the proteasome dependent pathway.|We also demonstrated that WT parkin ubiquitinates cav-1 for degradation.

SIGNOR-278710

Q9Y618

Q96T58

2

binding

up-regulates

0.467

Sharp is a potent transcriptional repressor whose repression domain (rd) interacts directly with smrt

SIGNOR-107260

P24941

P20248

1

phosphorylation

up-regulates

0.977

Here we present evidence from in vitro and in vivo assay systems that the degradation of human cyclin a can be inhibited by kinase-inactive mutants of cdk2 and cdc2cdk2 can phosphorylate cyclin a on ser-154

SIGNOR-74466

P01137

P62736

1

transcriptional regulation

up-regulates quantity by expression

0.419

A TGF-β1 response element that has a sequence different to that known for Smad binding has been identified in the α- SM actin promoter and seems to be essential for expression of α-SM actin in both SM cells 72 and myofibroblasts73 . How TGF-β1 activates expression of α-SM actin through this TGF-β1 control element is, as yet, unknown

SIGNOR-277681

P49116

Q13131

0

phosphorylation

down-regulates

0.2

Tr4 transactivation is inhibited via phosphorylation bymetformin-induced amp-activated protein kinase (ampk) at the amino acid serine 351, which results in the suppression of scd1 gene expression

SIGNOR-173118

P17252

Q8WZ42

1

phosphorylation

up-regulates activity

0.271

In summary, titin is a PKC substrate with PKCalpha phosphorylating predominately the full-length titin molecule.|Mechanical experiments with skinned LV myocardium revealed that PKCalpha significantly increases titin based passive tension, an effect that is reversed by PP1.

SIGNOR-278382

P23443

Q9BPZ7

1

phosphorylation

down-regulates activity

0.565

Consistently, we detected in vivo Sin1 phosphorylation triggered by S6K1 and to a lesser extent, Akt1, but not other characterized AGC kinases (XREF_FIG and XREF_SUPPLEMENTARY).|Here we report that phosphorylation of Sin1 at Thr 86 and Thr 398 suppresses mTORC2 kinase activity by dissociating Sin1 from mTORC2.

SIGNOR-279568

Q13485

O14980

0

relocalization

down-regulates

0.3

We demonstrate that inhibition of crm1-mediated nuclear export by treatment of cells with leptomycin b results in endogenous smad4 accumulating very rapidly in the nucleus.

SIGNOR-84247

Q13642

Q06587

2

binding

up-regulates

0.357

The polycombprotein ring1 interacts with the lim domains of kyot2 in yeast and mammalian cells. The interaction between kyot2 and ring1 was detected both in vitro and in vivo

SIGNOR-123150

O00399

P06493

0

phosphorylation

up-regulates activity

0.307

Here, we show that the p27/p25 heterodimer undergoes mitotic phosphorylation by cyclin‐dependent kinase 1 (Cdk1) at a single site, p27 Thr186, to generate an anchoring site for polo‐like kinase 1 (Plk1) at kinetochores.

SIGNOR-264777

P36873

P31749

1

dephosphorylation

down-regulates activity

0.383

Here, we identify PP1 as a serine/threonine phosphatase that associates with and dephosphorylates AKT in breast cancer cells|The heat shock protein 90 inhibitor geldanamycin and the ErbB inhibitor ZD1839 promote rapid PP1 phosphatase-dependent inactivation of AKT in ErbB2 overexpressing breast cancer cells

SIGNOR-252605

Q92917

O60231

2

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

P10636

O00141

0

phosphorylation

down-regulates

0.331

Second, sgk1 indirectly depolymerized mts through the phosphorylation of tau at ser214

SIGNOR-161288

P09874

Q9H0A0

0

acetylation

up-regulates quantity by stabilization

0.2

MORC2 directly interacts with PARP1. MORC2 mediates the interaction between PARP1 and NAT10 and thereby promotes NAT10-mediated PARP1 acetylation at K949, which blocks CHFR-mediated ubiquitination and degradation of PARP1.

SIGNOR-273715

Q9HC16

P17612

0

phosphorylation

up-regulates

0.324

Here we show that pka binds and specifically phosphorylates a3g at thr32 in vitro and in vivo. This phosphorylation event reduces the binding of a3g to vif and its subsequent ubiquitination and degradation, and thus promotes a3g antiviral activity.

SIGNOR-181526

P14921

Q93084

1

transcriptional regulation

up-regulates quantity by expression

0.326

Ets-1 was able to transactivate the SERCA3 promoter in MoBr 204 as cotransfection of an Ets-1 expression vector increased the activity of the −97/+301-Luc construct by 6-fold.

SIGNOR-261601

O75460

P17861

1

phosphorylation

up-regulates activity

0.647

IRE1\u03b1 phosphorylates and activates the XBP1 transcription factor XBP1 via its kinase activity.

SIGNOR-279712

Q14258

Q9UKV5

1

polyubiquitination

down-regulates quantity by destabilization

0.364

We further demonstrate that TRIM25 ubiquitylates gp78 and that overexpression of TRIM25 accelerates the degradation of gp78. Our data suggest that TRIM25 not only cooperates with gp78 in polyubiquitylation of AMF but also gauges the steady-state level of gp78.

SIGNOR-272176

Q969F8

Q15726

2

binding

up-regulates

0.806

Here we show that kiss-1 (refs 1, 4) encodes a carboxy-terminally amidated peptide with 54 amino-acid residues, which we have isolated from human placenta as the endogenous ligand of an orphan g-protein-coupled receptor (hot7t175) and have named 'metastin'

SIGNOR-108480

P58753

Q9NWF9

0

ubiquitination

down-regulates quantity by destabilization

0.387

Triad3A promotes proteolytic degradation of adapter proteins. A, Triad3A promotes down-regulation of TIRAP, TRIF, and RIP1 proteins.

SIGNOR-271607

P46527

O00141

0

phosphorylation

down-regulates

0.469

Activated sgk1 and p27 phosphorylation at t157, and both were inhibited by short-term rapamycin treatment and by sgk1 shrna.

SIGNOR-179117

O00712

Q14938

1

transcriptional regulation

up-regulates quantity

0.42

We report that, in the absence of Nfia or Nfib, there is a marked reduction in the spinal cord expression of NFIX, and that NFIB can transcriptionally activate Nfix expression in vitro. These data demonstrate that NFIX is part of the downstream transcriptional program through which NFIA and NFIB coordinate gliogenesis within the spinal cord.

SIGNOR-268870

P29353

Q02763

2

binding

up-regulates activity

0.58

Our results identified a novel interaction between Tie2 with the adapter molecule ShcA and suggested that this interaction may play a role in the regulation of migration and three-dimensional organization of endothelial cells induced by angiopoietin-1. Furthermore, Tyr-1101 of Tie2 was identified as the primary binding site for the SH2 domain of ShcA.

SIGNOR-242573

Q14469

P37231

1

transcriptional regulation

down-regulates quantity by repression

0.248

CREB inhibits hepatic PPAR-gamma expression in the fasted state by stimulating the expression of the Hairy Enhancer of Split (HES-1) gene, a transcriptional repressor that is shown here to be a mediator of fasting lipid metabolism in vivo

SIGNOR-253584

Q13115

P27361

1

dephosphorylation

down-regulates activity

0.709

Dephosphorylation and Inactivation of ERKs|ERK1 phosphorylated on either threonine (ERK1*Y204F) or tyrosine alone (ERK1*T202A) was utilized as a substrate for HVH2. Threonine 202 and tyrosine 204 in ERK1 (53) correspond to threonine 183 and tyrosine 185 in ERK2 which are the activation-phosphorylation sites by MEK(14, 15, 16). ERK1*, a kinase-deficient mutant, was phosphorylated on both threonine and tyrosine by MEK2 (Fig. 3B). ERK1*T202A, having threonine 202 substituted by an alanine, was phosphorylated only on tyrosine while ERK1*Y204F, having tyrosine 204 substituted by a phenylalanine, was phosphorylated only on threonine (Fig. 3B). GST-HVH2 dephosphorylated all three ERK1* mutants (Fig. 3A), suggesting that double phosphorylations of adjacent threonine and tyrosine were not a prerequisite for HVH2 recognition. However, HVH2 dephosphorylated ERK1* and ERK1*T202A more efficiently than ERK1*Y204F (Fig. 3A), indicating that HVH2 preferred phosphotyrosine over phosphothreonine. Interestingly, MEK also phosphorylated tyrosine residues more efficiently than threonine residues of ERK

SIGNOR-248716

P31751

O43524

1

phosphorylation

down-regulates activity

0.751

Akt-dependent phosphorylation of foxo3a (thr32, ser253, and ser315 for human foxo3) enhances foxo3a/14-3-3 Interaction and promotes foxo3a nuclear export to the cytoplasm, resulting in the repression of foxo3a transcriptional function akt phosphorylates members of the foxo factors (forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localisation. In particular, akt phosphorylates foxo1 on thr24, ser256 and ser319. Foxo 3alfa and foxo4 are phosphorylated on equivalent sites.

SIGNOR-236671

Q7Z2Z2

Q9Y3A5

2

binding

up-regulates

0.2

Sbds stimulates 60s-dependent gtp hydrolysis by efl1

SIGNOR-173533

Q7KZI7

Q6WKZ4

1

phosphorylation

up-regulates quantity

0.341

We have now found that MARK2 phosphorylates Rab11-FIP1B/C at serine 234 in a consensus site similar to that previously identified in Rab11-FIP2.

SIGNOR-273676

O60341

Q9HCU9

2

binding

up-regulates activity

0.257

Our results have showed that BRMS1 together with LSD1 are required for inhibition of breast cancer cell migration and invasion. Collectively, these findings demonstrate that BRMS1 executes transcriptional suppression of breast cancer metastasis by associating with the LSD1 and thus can be targeted for breast cancer therapy.

SIGNOR-266409

Q9Y6Q9

O15111

0

phosphorylation

up-regulates

0.395

Herein, we report the successful identification of six functional in vivo src-3 phosphorylation sites.

SIGNOR-196953

Q02447

P28482

0

phosphorylation

up-regulates

0.305

Here, we show that sp3, which, as sp1, belongs to the gc-rich binding transcription factor family, is also phosphorylated by erk in vitro on serine 73. in the inducible cell lines, expression of wild-type form of sp3 increases vegf production whereas the s73a form has a reduced potential reflecting its lower transcriptional activity.

SIGNOR-157272

P11137

Q9P0L2

0

phosphorylation

down-regulates activity

0.418

Here we show that p110mark phosphorylates analogous KXGS sites in the microtubule binding domains of the neuronal MAP2 and the ubiquitous MAP4. Phosphorylation in vitro leads to the dissociation of MAP2 and MAP4 from microtubules and to a pronounced increase in dynamic instability.

SIGNOR-250166

P41240

Q92793

2

binding

up-regulates

0.535

Here we present cbp--a transmembrane phosphoprotein that is ubiquitously expressed and binds specifically to the sh2 domain of csk. Cbp is involved in the membrane localization of csk and in the csk-mediated inhibition of c-src.

SIGNOR-77139

P68400

P06744

1

phosphorylation

down-regulates activity

0.333

It is known that human PGI/AMF is phosphorylated at Ser(185) by protein kinase CK2 (CK2) | These results demonstrate that phosphorylation affects the allosteric kinetic properties of the enzyme, resulting in a less active form of PGI, whereas non-phosphorylated protein species retain cytokine activity.

SIGNOR-250869

Q16236

P09601

1

transcriptional regulation

up-regulates quantity by expression

0.679

In both models, the inducer-modified and Nrf2-bound Keap1 is inactivated and, consequently, newly synthesized Nrf2 proteins bypass Keap1 and translocate into the nucleus, bind to the ARE and drive the expression of Nrf2 target genes such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase (GCL) and glutathione S transferases (GSTs).

SIGNOR-256276

P52564

P46108

1

phosphorylation

up-regulates

0.2

Mapkk6 was shown to phosphorylate and specifically activate the p38/mpk2 sub-family of the mitogen-activated protein kinase superfamily.

SIGNOR-42384

Q92922

P51531

2

binding

up-regulates

0.911

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

SIGNOR-65432

P10415

P01241

0

transcriptional regulation

up-regulates quantity by expression

0.2

Autocrine hGH increased the transcription and subsequent mRNA level and protein expression of c-Myc, Cyclin D1, and Bcl-2 in human mammary epithelial cells

SIGNOR-261628

P07900

Q9P278

2

binding

down-regulates activity

0.411

FNIP1 and FNIP2 facilitate FLCN binding to Hsp90 chaperone. Our results suggest that FNIP1 is a potent inhibitor of Hsp90 ATPase activity, as 200 nM of FNIP1 inhibits Hsp90 ATPase activity by 50-fold. FNIP2 also has shown inhibitory activity towards Hsp90; however, it required 1.6 μM of FNIP2 to inhibit the ATPase activity by eightfold. Although we use the term ‘inhibition' here, FNIPs seem only to be slowing the chaperone cycle.

SIGNOR-261414

P06213

Q9Y4H2

1

phosphorylation

down-regulates activity

0.757

Tyr624 and Tyr628 are involved in the interaction between the IR and the KRLB domain of IRS-2, including tyrosine phosphorylation, and Tyr628 seems to be more important than Tyr624 in this process. the binding between the insulin receptor and the KRLB domain of IRS-2 results in tyrosine phosphorylation of the KRLB domain, and this leads to decreased binding of IRS-2 to the insulin receptor.

SIGNOR-251319

Q9HBE4

P31785

2

binding

up-regulates

0.61

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-108858

P35367

Q9UQM7

0

phosphorylation

down-regulates

0.282

As we have shown previously, human h1r can be phosphorylated in vitro by several kinases includingpka, pkc, pkg, and camk ii in summary, these data suggest that thr140, thr142, ser396, ser398, and thr478 can be phosphorylated by the kinases described above (table 2).

SIGNOR-124348

Q13315

Q96S59

1

phosphorylation

up-regulates activity

0.439

We demonstrate that ATM phosphorylates RanBP9 in response to Ionizing Radiation and mediates its nuclear accumulation.

SIGNOR-279005

P33981

O43683

1

phosphorylation

up-regulates activity

0.695

After Cdk1 phosphorylates Bub1 S459, Mps1 then phosphorylates Bub1 T461 (b).

SIGNOR-278255

O75592

Q8TEK3

0

transcriptional regulation

down-regulates quantity by repression

0.2

Overexpression of DOT1L decreased the expression of HECTD4 and MYCBP2 in LNCaP, C42B, and 22rv1 cells (Supplementary Fig. 5c), suggesting that DOT1L plays a role in repressing these targets either directly or indirectly.

SIGNOR-267151

P06493

P04626

0

phosphorylation

down-regulates

0.274

Phosphorylation on tyrosine-15 of p34(cdc2) by erbb2 inhibits p34(cdc2) activation and is involved in resistance to taxol-induced apoptosis

SIGNOR-88671

O14641

Q13145

2

binding

up-regulates

0.516

Bmp-2 mediates phosphorylated smad1 (psmad1) or, with loss of bmprii, psmad3-dependent recruitment of disheveled (dvl) to promote rhoa-rac1 signaling necessary for motility.

SIGNOR-23037

Q9Y4K3

Q86UT6

2

binding

down-regulates activity

0.472

Immunoprecipitation experiments showed that NLRX1 interacted with TRAF6 and TRAF3, but not with TRAF2 or TRAF5. These results further suggest that NLRX1 specifically inhibits TLR-induced TRAF6-dependent NF-kB signaling through targeting TRAF6.

SIGNOR-260364

Q96P48

P60953

1

gtpase-activating protein

down-regulates activity

0.531

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-260452

O15392

Q16254

0

transcriptional regulation

down-regulates quantity by repression

0.334

This TGF-beta response is triggered through a Smad2/3-dependent hypophosphorylation of Rb and the subsequent association of the Rb/E2F4 repressive complex to CDE/CHR elements in the proximal region of the survivin promoter.

SIGNOR-271678

P17252

Q13255

1

phosphorylation

down-regulates activity

0.385

Furthermore, we demonstrate that the selectivity of PKC action on receptor signaling rests on phosphorylation of a threonine residue located in the G protein-interacting domain of the receptor. Modification at Thr(695) selectively disrupts mGluR1alpha-G(q/11) interaction without affecting signaling through G(s).

SIGNOR-249043

P12004

P38936

2

binding

down-regulates

0.765

P21 exerts its effect on the cell cycle not only by inhibiting cyclin/cdk complexes, but also by inhibiting proliferating cell nuclear antigen (pcna)

SIGNOR-191939

P48357

P41159

2

binding

up-regulates

0.814

Both ob-ra and ob-rb bind leptin with the same affinity, whereas only ob-rb can elicit intracellular response

SIGNOR-55656

O75116

Q09472

1

phosphorylation

up-regulates activity

0.297

Nuclear Rho kinase, ROCK2, targets p300 acetyltransferase.|p300 acetyltransferase activity is dependent on its phosphorylation status in cells, and p300 phosphorylation by ROCK2 results in an increase in its acetyltransferase activity in vitro.

SIGNOR-279482

Q13950

Q92793

2

binding

up-regulates

0.406

Mechanistic analysis revealed that the tak1-mkk3/6-p38 mapk axis phosphory-lated runx2, promoting its association with the coac-tivator creb-binding protein (cbp), which is re-quired to regulate osteoblast genetic programs.

SIGNOR-166170

Q00535

P04150

1

phosphorylation

down-regulates activity

0.481

Cdk5 phosphorylated gr at multiple serines, including ser203 and ser211 of its n-terminal domain, and suppressed the transcriptional activity of this receptor on glucocorticoid-responsive promoters by attenuating attraction of transcriptional cofactors to dna.| the effect of CDK5 on GR-induced transcriptional activity is specific to gene promoter, and possibly, to tissue

SIGNOR-154405

O15530

Q14680

0

phosphorylation

down-regulates activity

0.267

The results showed that MPK38 interacted with and inhibited PDK1 activity via Thr(354) phosphorylation.

SIGNOR-276414

Q13188

P04049

2

binding

down-regulates

0.36

Raf-1 prevents dimerization and phosphorylation of the activation loop of mst2 independently of its protein kinase activity.Raf-1 counteracts apoptosis by suppressing the activation of mammalian sterile 20-like kinase (mst2)

SIGNOR-132824

P35659

P68400

0

phosphorylation

up-regulates

0.35

Dek is phosphorylated by the protein kinase ck2 in vitro and in vivo on ser32

SIGNOR-125912