GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P41279	Q01970	1	phosphorylation	up-regulates activity	0.2	Additionally, we found that PAR1-induced Ca2+ signals are transduced through Tpl2, which activates phospholipase C\u03b23 by phosphorylation at Ser537.\|These findings raised the question whether Tpl2, which phosphorylates PLCbeta 3 at Ser537 (this report) regulates Ca 2+ signaling in thrombin stimulated cells through phosphorylation of PLCbeta 3 at this site.	SIGNOR-278519
P16220	P01189	1	transcriptional regulation	up-regulates quantity by expression	0.37	Transcriptional activation of the proopiomelanocortin gene by cyclic AMP-responsive element binding protein\|Further, expression of a dominant inhibitory mutant of CREB reduced cAMP stimulated transcription of the full length POMC promoter and the PTRE.	SIGNOR-268620
P18146	P68400	0	phosphorylation	down-regulates activity	0.464	Casein kinase II associates with Egr-1 and acts as a negative modulator of its DNA binding and transcription activities in NIH 3T3 cells. \| There are three CKII recognition sites (S376XXD, T389XE, and T516XXXD) in fragment 10.	SIGNOR-250858
Q5SQI0	Q9NY65	1	acetylation	up-regulates quantity by stabilization	0.244	Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.\|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules	SIGNOR-272250
P53350	Q9UNE7	0	ubiquitination	down-regulates quantity by destabilization	0.252	As indicated in xref , all three Plk1 fragments were ubiquitinated by CHIP, suggesting that CHIP targets multiple sites of Plk1 for ubiquitination.\|Mechanistically, CHIP mediated degradation of AR and Plk1 leads to enhanced efficacy of HSP90 inhibitors.	SIGNOR-278532
P30622	P42345	0	phosphorylation	up-regulates activity	0.567	By contrast to the phosphorylation of p150 Glued by PKA, inhibition of mTOR by rapamycin inhibited the ability of CLIP-170 to bind to microtubules, suggesting that phosphorylation by mTOR promotes CLIP-170 microtubule binding.\|The new study confirms this physical interaction in animal cells and suggests that mTOR phosphorylates CLIP-170 on some, but not all, of the sites that are phosphorylated in vivo.	SIGNOR-279231
O00429	Q08209	0	dephosphorylation	up-regulates activity	0.277	When mitochondrial depolarization is associated with sustained cytosolic Ca(2+) rise, it activates the cytosolic phosphatase calcineurin that normally interacts with Drp1. Calcineurin-dependent dephosphorylation of Drp1, and in particular of its conserved serine 637, regulates its translocation to mitochondria as substantiated by site directed mutagenesis.	SIGNOR-248676
P12931	Q969T9	1	phosphorylation	up-regulates activity	0.297	Using dominant-negative, constitutively active mutants, RNAi, and pharmacological studies, we demonstrated that phosphorylation of WBP2 at Tyr192 and Tyr231 could be regulated by c-Src and c-Yes kinases.We further showed that abrogating WBP2 phosphorylation impaired >60% of ERα reporter activity, putatively by blocking nuclear entry of WBP2 and its interaction with ERα.	SIGNOR-273567
O15259	P12931	0	phosphorylation	up-regulates activity	0.297	Src-induced tyrosine phosphorylation could be prevented by mutating the tyrosine residue at position 721 to phenylalanine ( C, lane 12) suggesting that Src kinase phosphorylates NPHP1 at tyrosine 721.	SIGNOR-279122
Q13315	Q16665	1	phosphorylation	up-regulates	0.432	Here we show that hypoxia results in ataxia telangiectasia mutated (atm)-dependent phosphorylation of hypoxia-inducible factor 1-alpha (hif-1_) on serine(696) and mediates downregulation of mtorc1 signaling. phosphorylation of hif-1_ by atm is required for its stability	SIGNOR-169999
P52565	P17612	0	phosphorylation	down-regulates	0.387	The results indicate that phosphorylation of gdi_ at ser174 by pka suppresses rhoa activity, providing a potential protective signaling mechanism for inflammatory injury.	SIGNOR-180576
Q15418	P16220	1	phosphorylation	up-regulates activity	0.747	The rsks phosphorylate the trascription factor creb at serine 133 to promote cell survival.	SIGNOR-72117
P53350	Q9Y2T1	1	phosphorylation	up-regulates activity	0.486	Plk1 phosphorylates axin2 at Ser311.	SIGNOR-277180
P10909	Q86TM6	0	polyubiquitination	down-regulates quantity by destabilization	0.32	We also report that the ER-associated ubiquitin ligase Hrd1/synoviolin can interact with, and ubiquitinate clusterin. The fact that cleaved endogenous clusterin appears, under certain conditions, to be subject to polyubiquitination (Figure 2C) and proteasomal degradation (1, 2) strongly suggests that it passed through the secretory pathway before reaching the cytosol.	SIGNOR-272629
P35070	O14672	0	cleavage	up-regulates activity	0.372	Like ADAM17, ADAM10 has also been implicated in the activation of specific EGFR ligands, especially EGF and betacellulin	SIGNOR-259839
P53350	Q8N137	1	phosphorylation	up-regulates activity	0.324	However, unlike NEK2, PLK1 phosphorylation enhances the microtubule stabilizing activity of centrobin [22].\|PLK1 phosphorylation of centrobin is critical for bipolar spindle formation.	SIGNOR-279551
P55075	P40426	0	transcriptional regulation	down-regulates quantity by repression	0.2	Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression. Our data support the model that Engrailed heterodimerized with Pbx might activate transcription, while Engrailed or Pbx proteins alone might repress transcription	SIGNOR-265779
P18846	Q13315	0	phosphorylation	up-regulates activity	0.359	Exposure to DNA damage further induced ATF1 phosphorylation on Ser-51 by ATM in a manner that required prior phosphorylation of the upstream CK residues.	SIGNOR-278909
P54829	Q13224	1	dephosphorylation	down-regulates activity	0.547	These previous results, together with the present findings, indicate that STEP61 dephosphorylates the NR2B subunit at its regulatory tyr1472 site, and dephosphorylation of this site leads to internalization of the NMDAR complex from neuronal surface membranes.	SIGNOR-265744
Q86Y07	Q96EV8	1	phosphorylation	down-regulates quantity by destabilization	0.2	We show that VRK2 phosphorylates Ser 297 and Ser 299 of dysbindin using in vitro kinase assay. In addition, we found that VRK2-mediated phosphorylation of dysbindin enhanced ubiquitination of dysbindin and consequently resulted in the decrease in its protein stability through western blotting.	SIGNOR-277403
Q14289	P49023	1	phosphorylation	down-regulates quantity by destabilization	0.94	P130Cas and paxillin can be phosphorylated by Fak or Pyk2, and bind directly to these kinases.	SIGNOR-279272
Q13164	P43354	1	phosphorylation	up-regulates activity	0.2	Activation of MEK, which in turns activates ERK5, does enhance the ERK5 induced nurr1 activity, while no increase is observed in the presence of a dn MEK5 or of the unphosphorylated ERK5 AEF, in which amino acids phosphorylated by MEK5 are mutated.\|The A/B domain of nurr1 is highly phosphorylated in the presence of ERK5 and mutations of two amino acids in this same domain decrease significantly the ERK5 mediated nurr1 transcriptional response.\|These data would suggest once again that the basal activity of ERK5 is responsible for the phosphorylation of nurr1.\|As shown in XREF_FIG, nurr1 A/B domain was significantly phosphorylated by ERK5, while the GST protein alone was not a substrate for this kinase.	SIGNOR-279215
O14757	Q9UKI8	1	phosphorylation	down-regulates	0.431	Chk1 phosphorylates tlk1 on serine 695 (s695) these findings identify an unprecedented functional co- operation between atm and chk1 in propagation of a checkpoint response during s phase and suggest that, through transient inhibition of tlk kinases, the atm_chk1_tlk pathway may regulate processes involved in chromatin assembly.	SIGNOR-99653
Q16539	Q9BY84	0	dephosphorylation	down-regulates	0.805	Mkp-7 binds to and inactivates p38 mapk and jnk/sapk, but not erk inhibited by dual specificity phosphatases, such as dusp1, dusp10, and dusp16(uniprot)	SIGNOR-108233
Q99801	P53671	0	phosphorylation	down-regulates activity	0.2	LIMK2 also downregulates NKX3.1 mRNA levels.\|While WT-NKX3.1 was efficiently phosphorylated, the S185A mutant showed no phosphorylation ( xref A), confirming that LIMK2 only phosphorylates the S185 site in NKX3.1.	SIGNOR-278951
P20393	P49841	0	phosphorylation	up-regulates	0.282	We show here that gsk3beta phosphorylates and stabilizes the orphan nuclear receptor rev-erbalpha, a negative component of the circadian clock.	SIGNOR-144570
Q9H1A4	P06493	0	phosphorylation	up-regulates	0.592	Apc activation is thought to depend on apc phosphorylation and cdc20 binding. We have identified 43 phospho_sites on apc of which at least 34 are mitosis specific. Of these, 32 sites are clustered in parts of apc1 and the tetratricopeptide repeat (tpr) subunits cdc27, cdc16, cdc23 and apc7. In vitro, at least 15 of the mitotic phospho_sites can be generated by cyclin_dependent kinase 1 (cdk1), and 3 by polo_like kinase 1 (plk1). Apc phosphorylation by cdk1, but not by plk1, is sufficient for increased cdc20 binding and apc activation	SIGNOR-119705
Q13131	Q16875	1	phosphorylation	up-regulates	0.399	Ipfk-2 was phosphorylated on the homologous serine (ser-461) and activated by ampk in vitro.	SIGNOR-89760
O75410	Q9UQB9	0	phosphorylation	up-regulates activity	0.399	Aurora-C interacts with and phosphorylates the transforming acidic coiled-coil 1 protein. The results demonstrated that TACC1 is phosphorylated by Aurora-C on a serine at position 228. although the patho-physiological meaning of TACC1 phosphorylation by Aurora-C in normal and in malignant somatic cells remains to be fully investigated, our observations suggest that Aurora-C has a role in the later stage of mitosis, when an interaction with TACC1 may be relevant for the correct progression of the cell cycle.	SIGNOR-262663
Q9UBN7	P27361	0	phosphorylation	up-regulates	0.426	Histone deacetylase 6 (hdac6) is well known for its ability to promote cell migrationextracellular signal-regulated kinase (erk) phosphorylates histone deacetylase 6 (hdac6) at serine 1035 to stimulate cell migrationwe have identified two novel erk-mediated phosphorylation sites: threonine 1031 and serine 1035 in hdac6. Both sites were phosphorylated by erk1	SIGNOR-202702
P10275	P50613	0	phosphorylation	down-regulates	0.377	Here, we show that the transcription factor tfiih, via its cdk7 kinase, phosphorylates the androgen receptor (ar) at position ar/s515. Strikingly, this phosphorylation is a key step for an accurate transactivation that includes the cyclic recruitment of the transcription machinery, the mdm2 e3 ligase, the subsequent ubiquitination of ar at the promoter of target genes and its degradation by the proteasome machinery	SIGNOR-170599
P45983	Q13363	1	phosphorylation	down-regulates	0.358	In this study, we found that c-jun nh2-terminal kinase 1 activation triggered ctbp phosphorylation on ser-422 and subsequent degradation,	SIGNOR-149721
P07197	Q00535	0	phosphorylation	down-regulates quantity	0.42	Converse to the effect of PKA overexpression, overexpression of CDK5 and its activator, p35, decreased the association between spinophilin and NF-M as well as the expression of NF-M.\|Moreover, CDK5 phosphorylates NF-M [ xref ], and this was also apparent in our data, given a dramatic molecular weight shift in the NF-M band following CDK5 overexpression.	SIGNOR-279683
Q16649	O15534	1	transcriptional regulation	down-regulates quantity by repression	0.346	E4BP4, a basic leucine zipper transcription factor, contains a DNA-binding domain closely related to DBP, HLF, and TEF, which are PAR proteins. Here, we show that the phase of e4bp4 mRNA rhythm is opposite to that of the dbp, hlf, and tef rhythms in the suprachiasmatic nucleus (SCN), the mammalian circadian center, and the liver. The protein levels of E4BP4 and DBP also fluctuate in almost the opposite phase. All PAR proteins activate, whereas E4BP4 suppresses the mPer1 promoter through the same sequence	SIGNOR-268056
P48735	P24752	0	acetylation	down-regulates activity	0.287	Mitochondrial acetyltransferase ACAT1 and deacetylase SIRT3 are responsible for acetylation and deacetylation, respectively, at K413 of mIDH2\|K413 acetylation inhibits mIDH2 by simultaneously attenuating dimer formation from monomers and destabilizing dimers for conversion to monomers	SIGNOR-267627
O43683	P40763	1	phosphorylation	up-regulates activity	0.251	This study showed that the BUB1 kinase drives the progression and proliferation of BCa by regulating the transcriptional activation of STAT3 signaling and may be an attractive candidate for therapeutic targeting in BCa.\|We further identified through a series of molecular and cell biological approaches that BUB1 interacted directly with STAT3 and mediated the phosphorylation of STAT3 at Ser727.	SIGNOR-280198
P38936	P01106	0	transcriptional regulation	down-regulates quantity by repression	0.779	C-myc also directly represses transcription of cdk kinase inhibitors including p27kip1, p21cip1, p15ink4b and p16ink4a	SIGNOR-102740
O15111	P06748	1	phosphorylation	up-regulates activity	0.2	S125A and a delta form lacking the aa 119-195 region completely abolished NPM phosphorylation by IKKalpha (XREF_FIG), suggesting that IKKalpha phosphorylates S125 of NPM.\|We found that TNFalpha treatment induced IKKalpha phosphorylation and increased NPM hexamers, which were correlated with increased NPM phosphorylation (XREF_FIG).	SIGNOR-279405
Q9NQU5	O43426	1	phosphorylation	up-regulates activity	0.2	We identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo.	SIGNOR-263022
P49757	P46531	1	ubiquitination	down-regulates quantity by destabilization	0.798	Mammalian numb proteins promote notch1 receptor ubiquitination and degradation of the notch1 intracellular domain	SIGNOR-99762
Q05655	P11413	1	phosphorylation	up-regulates	0.2	A pkc activator, significantly increased g6pd phosphorylation and activity, whereas single (s210a, t266a) and double (s210a/t266a) mutations at sites flanking the g6pd active site significantly inhibited phosphorylation, shifted the isoelectric point, and reduced enzyme activity.	SIGNOR-167053
Q9UIC8	P62714	1	methylation	up-regulates activity	0.661	Methylation of the carboxy-terminal Leu309 in a conserved TPDYFL309 motif of the C subunit has been shown to enhance the affinity of the PP2A core enzyme for some, but not all, regulatory subunits \|The PP2A core enzyme was methylated by a PP2A-specific leucine carboxyl methyltransferase (LCMT1)	SIGNOR-265751
P40763	P29597	0	phosphorylation	up-regulates	0.687	Since Jak-STAT pathway primarily activated in IL-15-me- diated cell proliferation, we tested whether it is also participates in IL-15-mediated proliferation of FAPs. Interestingly, we found the expression of phospho-Jak3 and phospho-Tyk2, as well as their downstream, phospho- STAT3 and phospho-STAT5, was significantly upregulated	SIGNOR-256255
Q14596	P49840	0	phosphorylation	down-regulates activity	0.322	The autophagy receptor NBR1 (neighbor of BRCA1 gene 1) binds UB/ubiquitin and the autophagosome-conjugated MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) proteins, thereby ensuring ubiquitinated protein degradation\|Here we show that NBR1 is a substrate of GSK3. NBR1 phosphorylation by GSK3 at Thr586 prevents the aggregation of ubiquitinated proteins and their selective autophagic degradation.	SIGNOR-261794
P63104	P17612	0	phosphorylation	down-regulates activity	0.566	Phosphorylation by pka leads to modulation of 14-3-3zeta dimerization and affect its interaction with partner proteins. Substitution of ser58 to ala completely abolished phosphorylation of 14-3-3zeta by pka.	SIGNOR-143373
P20823	Q12864	1	transcriptional regulation	up-regulates quantity by expression	0.313	The present study aims to identify the transcription factors which interact and regulate CDH17 promoter activity that might contribute to the up-regulation of CDH17 gene in human HCC\|we identified hepatic nuclear factor 1α (HNF1α) and caudal-related homeobox 2 (CDX2) binding sites at the proximal promoter region which modulate the CDH17 promoter activities in two HCC cell lines (Hep3B and MHCC97L)	SIGNOR-253970
Q9UJV3	Q5S007	1	ubiquitination	down-regulates quantity by destabilization	0.2	The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its localization, degradation, and toxicity.	SIGNOR-278763
P15336	P59595	0	transcriptional regulation	up-regulates quantity by expression	0.2	The transcription factors c-Fos, FosB, CREB-1, and ATF2 were all activated by the addition of SARS-CoV N protein to the sample well	SIGNOR-260727
Q96KB5	Q96EP1	0	polyubiquitination	down-regulates quantity by destabilization	0.346	CHFR ubiquitinates and degrades TOPK. Our in vivo ubiquitination assays revealed that the polyubiquitination of TOPK occurs only in the presence of full length CHFR but not with the ΔRING or Δcysteine-rich domain deletion mutants (Fig. 2a).	SIGNOR-271471
P04637	Q96S44	0	phosphorylation	up-regulates	0.76	The intrinsic transcriptional activity of p53 was up-regulated by a transient transfection of prpk to cos-7 cells. Prpk was shown to bind to p53 and to phosphorylate p53 at ser-15.	SIGNOR-157471
Q9GZV5	P49841	0	phosphorylation	down-regulates quantity by destabilization	0.2	GSK3 destabilizes TAZ. TAZS58A/S62A but not the TAZ S66A mutant diminished phos- phorylation by GSK3 , suggesting that Ser-58 and Ser-62 are important for GSK3 phosphorylation, whereas the Ser-66 is not (Fig. 4D).	SIGNOR-277646
Q99683	P38936	1	phosphorylation	up-regulates	0.589	P21cip1 is phosphorylated in vitro by both ask1 and jnk1 at s98. /phosphorylation of p21cip1 at s98, which in vivo appears to be regulated by ask1, may therefore mediate negative feedback in the ask1 signaling pathway.	SIGNOR-153440
P04792	Q13976	0	phosphorylation	down-regulates	0.274	Purified pkg isoforms ia, ib, and ii all caused incorporation of phosphate in recombinant hsp27 at ser-78, ser-82, and thr-143, but not ser-15.These Studies indicate that hsp27 is a genuine substrate for pkg and that pkg may mediate inhibition of platelet aggregation through phosphorylation of hsp27 and subsequent prevent of actin polymerization	SIGNOR-186784
P41279	P31749	0	phosphorylation	up-regulates activity	0.558	Akt-dependent phosphorylation of Cot occurs exclusively on serines 400 and 413. Akt to phosphorylate Cot at two sites in the carboxy-terminal domain, at least one of which may promote binding of substrates or coactivators to Cot, or alternatively may relieve binding of a negative regulator.	SIGNOR-252572
P25098	P17252	0	phosphorylation	up-regulates activity	0.2	Phosphorylation of GRK2 by protein kinase C abolishes its inhibition by calmodulin. In vitro, GRK2 was preferentially phosphorylated by PKC isoforms alpha, gamma, and delta. Two-dimensional peptide mapping of PKCalpha-phosphorylated GRK2 showed a single site of phosphorylation, which was identified as serine 29 by HPLC-MS. A S29A mutant of GRK2 was not phosphorylated by PKC in vitro and showed no phorbol ester-stimulated phosphorylation when transfected into human embryonic kidney (HEK)293 cells.	SIGNOR-249058
Q9Y251	P18146	0	transcriptional regulation	up-regulates quantity by expression	0.37	Promoter CpG hypomethylation and transcription factor EGR1 hyperactivate heparanase expression in bladder cancer.	SIGNOR-254267
Q9UKX7	P28482	0	phosphorylation	down-regulates activity	0.2	Erk phosphorylates nup50 at ser221 and ser315 erk phosphorylation of the fg repeat region of nup50 reduced its affinity for importin-beta family proteins, importin-beta and transportin.	SIGNOR-188135
Q12913	P27361	1	dephosphorylation	down-regulates activity	0.459	Tumor suppressor density-enhanced phosphatase-1 (DEP-1) inhibits the RAS pathway by direct dephosphorylation of ERK1/2 kinases\|Pulldown and in vitro dephosphorylation assays confirmed our prediction and demonstrated an overall specificity of DEP-1 in targeting the phosphorylated tyrosine 204 of ERK1/2.	SIGNOR-248707
Q9UQL6	Q15139	0	phosphorylation	down-regulates activity	0.516	Here, we demonstrate that signaling by protein kinase C (PKC) is sufficient and, in some cases, necessary to drive nuclear export of class II HDAC5 in cardiomyocytes.	SIGNOR-249270
P04637	Q93009	0	deubiquitination	up-regulates	0.741	Hausp counteracts the destabilizing effect of mdm2 by direct deubiquitination of p53.	SIGNOR-139456
O43683	P33981	0	phosphorylation	up-regulates activity	0.695	After Cdk1 phosphorylates Bub1 S459, Mps1 then phosphorylates Bub1 T461 (b).	SIGNOR-278255
Q13153	Q92974	1	phosphorylation	down-regulates	0.353	We identify gef-h1 as a binding target and substrate for p21-activated kinase 1 (pak1), we show that phosphorylation of gef-h1 at ser(885) by pak1 induces 14-3-3 binding to the exchange factor and relocation of 14-3-3 to microtubules.	SIGNOR-187573
Q96EP1	P09874	1	polyubiquitination	down-regulates quantity by destabilization	0.427	Here, we show that checkpoint with Forkhead-associated (FHA) and RING finger domain protein (CHFR), an E3 ubiquitin ligase, is recruited to DSBs by poly(ADP-ribose) (PAR). Moreover, CHFR ubiquitinates PAR polymerase 1 (PARP1) and regulates chromatin-associated PARP1 in vivo. Moreover, the poly-ubiquitin chain on PARP1 could be recognized by both anti-K48 and K63-linked poly-ubiquitin chain antibodies, suggesting that CHFR mediates a mixed poly-ubiquitin chain linkage on PARP1. With MG132 treatment, ubiquitinated PARP1 was significantly accumulated (Figure 4D), suggesting that the ubiquitination of PARP1 is likely involved in protein degradation. Consistently, we found that following DNA damage, PARP1 quickly dissociated from the chromatin in the wild-type cells (Figure 4F). However, in the Chfr−/− cells, the dissociation of PARP1 from the chromatin was significantly delayed.	SIGNOR-271470
Q99683	P52564	1	phosphorylation	up-regulates activity	0.613	A MAP kinase kinase kinase (MAPKKK), termed ASK1, was identified that activated two different subgroups of MAP kinase kinases (MAPKK), SEK1 (or MKK4) and MKK3/MAPKK6 (or MKK6), which in turn activated stress-activated protein kinase (SAPK, also known as JNK; c-Jun amino-terminal kinase) and p38 subgroups of MAP kinases, respectively.	SIGNOR-45353
O94856	P16157	1	relocalization	up-regulates quantity	0.685	Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.	SIGNOR-266718
P22455	Q8WU20	1	phosphorylation	up-regulates activity	0.685	In this report, we demonstrate that FGF stimulation induces tyrosine phosphorylation of a novel lipid anchored docking protein, termed FRS2, that forms a complex with Grb2/Sos, thus linking FGF-receptor activation to the Ras/MAPK signaling pathway.	SIGNOR-242661
P05067	O60260	0	ubiquitination	down-regulates quantity	0.2	Similarly, in transgenic AD mice models, lentiviral parkin expression ubiquitinates Abeta to reduce its intracellular levels while preventing plaque deposition, and this is associated with induction of beclin dependent autophagy .\|Thus, parkin reduces Abeta levels by enhancing both UPS- and autophagy dependent clearance of Abeta.	SIGNOR-278709
Q13177	P35240	1	phosphorylation	down-regulates	0.512	Merlin contains a c-terminal serine 518, which is phosphorylated both by p21-activated kinase (pak) and protein kinase a (pka) (shaw et al., 2001;kissil et al., 2002;xiao et al., 2002;alfthan et al., 2004). Phosphorylation at this site is predicted to result in a more open conformation incapable of inhibiting cell growth,	SIGNOR-159768
P04637	P78527	0	phosphorylation	up-regulates	0.793	We demonstrate that phosphorylation of p53 at serines 15 and 37 impairs the ability of mdm2 to inhibit p53-dependent transactivation. We present evidence that these effects are most likely due to a conformational change induced upon phosphorylation of p53. Our studies provide a plausible mechanism by which the induction of p53 can be modulated by dna-pk (or other protein kinases with similar specificity) in response to dna damage.	SIGNOR-53030
P09619	Q12913	0	dephosphorylation	down-regulates activity	0.582	Primary sequence determinants responsible for site-selective dephosphorylation of the PDGF beta-receptor by the receptor-like protein tyrosine phosphatase DEP-1\|DEP-1 dephosphorylation of original and chimeric phospho-peptides spanning the preferred pY1021	SIGNOR-248704
P42574	Q13043	1	cleavage	up-regulates activity	0.617	In response to apoptotic stimuli, caspase cleavage of mst1 occurs at asp-326 and asp-349, resulting in the separation of its n-terminal kinase domain from the nes-containing c-terminal domain. Thus, caspase cleavage of mst1 serves two purposes: one is activation of mst1 kinase activity and the other is translocation of mst1 into the nucleus.	SIGNOR-109878
Q71U36	Q5SQI0	0	acetylation	up-regulates quantity by stabilization	0.268	Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.\|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules	SIGNOR-272251
P49841	O15294	1	phosphorylation	up-regulates activity	0.518	But OGT activity is modulated by GSK3beta (XREF_FIG) and GSK3beta activity is known to oscillate through Ser9 phoshorylation.\|Here, we found that OGT is phosphorylated at serines 3 or 4 by GSK3beta and that O GlcNAcylation of OGT also occurs on the same or neighboring serine residues, suggesting interacting phosphorylation and O GlcNAcylation events on OGT itself.	SIGNOR-279528
Q9Y243	P24666	0	dephosphorylation	down-regulates activity	0.2	Reduction in the levels of both LMW-PTP isoforms in vitro and in vivo increased tyrosine phosphorylation of IR and AktSer473 and increased IRS-1- and IRS-2-associated PI3-K activities in both liver and fat.\|Activated PI3-K stimulates Akt (or protein kinase B) that in turn phosphorylates and inactivates glycogen synthase kinase-3	SIGNOR-248457
O00311	Q9HAW4	1	phosphorylation	up-regulates activity	0.742	Cdc7 phosphorylates Claspin in a manner dependent on AP and inhibits N\u2013C interaction.\|Thus, Cdc7-ASK may activate DNA and PCNA bindings of Claspin through AP-mediated phosphorylation.	SIGNOR-279360
Q9NV92	P46934	1	relocalization	down-regulates activity	0.568	Ndfip1 is primarily localized in the Golgi apparatus where it recruits Nedd4-2 to mediate the degradation of mature hERG proteins during channel trafficking to the plasma membrane. Although Ndfip2 directs Nedd4-2 to the Golgi apparatus, it also recruits Nedd4-2 to the multivesicular bodies (MVBs), which may impair MVB function and impede the degradation of mature hERG proteins mediated by Nedd4-2.	SIGNOR-260995
P08648	P31249	0	transcriptional regulation	up-regulates quantity by expression	0.25	The homeobox transcription factor Hox D3 promotes integrin alpha5beta1 expression and function during angiogenesis.	SIGNOR-261649
Q06710	P01266	1	transcriptional regulation	up-regulates quantity by expression	0.458	The transcription factor Pax8 plays an important role in the expression of the differentiated phenotype of thyroid follicular cells. It has recently been shown that Pax8 is necessary for thyroglobulin (Tg) gene expression.	SIGNOR-251998
O75582	Q13541	1	phosphorylation	down-regulates activity	0.671	In response to UV-B irradiation, the translation factor 4E-BP1 (eukaryotic initiation factor 4E [eIF4E]-binding protein 1) was phosphorylated at Thr36, Thr45, Ser64 and Thr69. Using either p38 MAPK inhibitors or the MSK inhibitor H89, UV-B-irradiation-induced phosphorylation was blocked [43]. 4E-BP1 binds to eIF4E in resting cells to prevent formation of a functional eIF4F complex, which is essential for cap-dependent initiation of translation. Phosphorylation of 4E-BP1 leads to dissociation from eIF4E	SIGNOR-262992
Q9BQE3	Q8NG68	0	tyrosination	down-regulates	0.473	Tubulin tyrosine ligase (ttl) adds a c-terminal tyr to __tubulin as part of a tyrosination/detyrosination cycle present in most eukaryotic cells. / ttl inhibits spontaneous tubulin polymerization	SIGNOR-176918
P06239	Q9H4E7	1	phosphorylation	up-regulates activity	0.5	In vitro kinase assays indeed demonstrated that Lck can phosphorylate wild-type IBP but not the Y210F mutant. IBP Binds PI(3,4,5)P3 upon Phosphorylation by Lck	SIGNOR-251372
P17480	P01106	0	transcriptional regulation	up-regulates quantity by expression	0.356	MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation\|MAD1 repressed and c-MYC activated rDNA transcription in nuclear run-on assays. Repression of rDNA transcription by MAD1 was associated with its ability to interact directly with the promoter of upstream binding factor (UBF), an rDNA regulatory factor. Conversely, c-MYC activated transcription from the UBF promoter.	SIGNOR-269644
Q13304	P25098	0	phosphorylation	down-regulates activity	0.2	As depicted in Fig. 8 A and B, GRK2 silencing resulted in up-regulation of GPR17 and down-regulation of the mature markers CNPase and MBP, indicating a shift of cells toward a less differentiated stage.Having established that, in primary cultured OPCs, LTD 4 mediated desensitization of GPR17 through the primary recruitment of GRK2, we then asked whether GRK2 pharmacological inhibition had any effects on cysLT promoted cell maturation.\|These data demonstrate that LTD 4 -induced GPR17 phosphorylation is preferentially mediated by GRK2 and only partially by GRK5, whereas UDP-glucose-mediated receptor phosphorylation exclusively requires the GRK5 isoform.We examined the involvement of GRK2 and GRK5 in agonist induced desensitization of GPR17.	SIGNOR-279999
P67775	P24071	1	dephosphorylation	up-regulates activity	0.323	Furthermore, FcalphaRI activation is induced by protein phosphatase 2A (PP2A) after it dephosphorylates a single serine residue (S263) in the FcalphaRI intracellular tail	SIGNOR-264858
Q12857	Q9HD90	1	transcriptional regulation	up-regulates quantity	0.2	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268891
Q8NEV1	Q99250	1	phosphorylation	up-regulates activity	0.2	We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. \| inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G.	SIGNOR-275755
P10275	P49841	0	phosphorylation	down-regulates activity	0.649	Glycogen synthase kinase-3 beta is involved in the phosphorylation and suppression of androgen receptor activity.\|In particular, we showed that glycogen synthase kinase-3 beta phosphorylates the androgen receptor, thereby inhibiting androgen receptor-driven transcription.	SIGNOR-279334
P15259	Q8IXJ6	0	deacetylation	up-regulates activity	0.2	Here we report that PGAM is acetylated at lysine 100 (K100), an active site residue that is invariably conserved from bacteria, to yeast, plant, and mammals. K100 acetylation is detected in fly, mouse, and human cells and in multiple tissues and decreases PGAM2 activity. The cytosolic protein deacetylase sirtuin 2 (SIRT2) deacetylates and activates PGAM2.	SIGNOR-266518
P27361	Q02447	1	phosphorylation	up-regulates	0.299	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.	SIGNOR-157276
P52564	Q15759	1	phosphorylation	up-regulates	0.702	The p38 mapkinasekinasemkk6 is identified as a common activator of p38 alpha, p38 beta 2, and p38 gamma mapkinaseisoforms.	SIGNOR-54947
Q9Y6X2	P40763	1	sumoylation	down-regulates	0.731	Stat3 mediated signaling pathways can be inhibited by pias3 (protein inhibitor of activated stat3), which was recently found to regulate protein stability and function by its sumo (small-ubiquitin like modifiers) ligase activity in promoting sumoylation of important nuclear proteins.	SIGNOR-124723
P01178-PRO_0000020495	P16519	0	cleavage	up-regulates quantity	0.2	Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension.	SIGNOR-270335
Q15154	P41208	1	relocalization	up-regulates	0.531	Rna silencing of pcm-1 leads to reduced assembly of centrin, pericentrin, and ninein at the centrosome	SIGNOR-94990
P08581	P46940	1	phosphorylation	up-regulates activity	0.272	IQGAP1 was phosphorylated exclusively on Tyr-1510 under conditions with enhanced MET or c-Src signaling, including in human lung cancer cell lines. This phosphorylation was significantly reduced by chemical inhibitors of MET or c-Src or by siRNA-mediated knockdown of MET.	SIGNOR-277532
Q53ET0	Q9Y4K3	0	ubiquitination	down-regulates quantity	0.307	Consistently, TRAF6 reduced G6pase gene expression or reporter activity induced by wild-type CRTC1 and CRTC2 but not TRAF6-interaction-defective CRTC1 and CRTC2 (XREF_FIG and XREF_SUPPLEMENTARY).\|Indeed, TRAF6, the E3 ubiquitin ligase activated by IL-1beta associates with and ubiquitinates CRTC2.	SIGNOR-278725
P11362	P00338	1	phosphorylation	up-regulates	0.366	We found that the oncogenic receptor tyrosine kinase fgfr1 directly phosphorylates ldh-a. Phosphorylation at y10 and y83 enhances ldh-a activity by enhancing the formation of active, tetrameric ldh-a and the binding of ldh-a substrate nadh, respectively.	SIGNOR-176730
P60709	P12277	0	relocalization	up-regulates quantity	0.292	In summary, data presented here strongly suggest that locally generated ATP is an important regulator for actin-based cytoskeletal dynamics involved in cell extension and motility and that CK-B is a controlling enzyme in the compartmentalization of ATP availability. CK-B co-localizes with cortical actin and facilitates spreading of astrocytes	SIGNOR-265791
Q13285	P11511	1	transcriptional regulation	up-regulates quantity by expression	0.479	The in vivo existence of an SF-1 corepressor complex consisting of DAX-1, RNF31, and SMRT at the steroidogenic promoters of the human StAR and CYP19 genes. We demonstrate that RNF31 is necessary for the stable association of the DAX-1 corepressor complex with chromatin-bound SF-1, thereby inhibiting the recruitment of coactivators and Pol II and controlling basal transcription levels of SF-1 target genes.	SIGNOR-271787
Q01082	P68400	0	phosphorylation	down-regulates	0.334	We show here that the short c-terminal splice variant of betaii-spectrin (betaiisigma2) is a substrate for phosphorylation. In vitro, protein kinase ck2 phosphorylates ser-2110 and thr-2159 / phosphorylation of ?II?2 C-terminal fragment inhibits its interaction with ?II N-terminal fragment.	SIGNOR-150471
Q6UUV7	P57059	0	phosphorylation	down-regulates	0.418	These results suggested that sik1 could phosphorylate all torcs and thereby repress their transactivation activities.	SIGNOR-147703

P41279

Q01970

1

phosphorylation

up-regulates activity

0.2

Additionally, we found that PAR1-induced Ca2+ signals are transduced through Tpl2, which activates phospholipase C\u03b23 by phosphorylation at Ser537.|These findings raised the question whether Tpl2, which phosphorylates PLCbeta 3 at Ser537 (this report) regulates Ca 2+ signaling in thrombin stimulated cells through phosphorylation of PLCbeta 3 at this site.

SIGNOR-278519

P16220

P01189

1

transcriptional regulation

up-regulates quantity by expression

0.37

Transcriptional activation of the proopiomelanocortin gene by cyclic AMP-responsive element binding protein|Further, expression of a dominant inhibitory mutant of CREB reduced cAMP stimulated transcription of the full length POMC promoter and the PTRE.

SIGNOR-268620

P18146

P68400

0

phosphorylation

down-regulates activity

0.464

Casein kinase II associates with Egr-1 and acts as a negative modulator of its DNA binding and transcription activities in NIH 3T3 cells. | There are three CKII recognition sites (S376XXD, T389XE, and T516XXXD) in fragment 10.

SIGNOR-250858

Q5SQI0

Q9NY65

1

acetylation

up-regulates quantity by stabilization

0.244

Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules

SIGNOR-272250

P53350

Q9UNE7

0

ubiquitination

down-regulates quantity by destabilization

0.252

As indicated in xref , all three Plk1 fragments were ubiquitinated by CHIP, suggesting that CHIP targets multiple sites of Plk1 for ubiquitination.|Mechanistically, CHIP mediated degradation of AR and Plk1 leads to enhanced efficacy of HSP90 inhibitors.

SIGNOR-278532

P30622

P42345

0

phosphorylation

up-regulates activity

0.567

By contrast to the phosphorylation of p150 Glued by PKA, inhibition of mTOR by rapamycin inhibited the ability of CLIP-170 to bind to microtubules, suggesting that phosphorylation by mTOR promotes CLIP-170 microtubule binding.|The new study confirms this physical interaction in animal cells and suggests that mTOR phosphorylates CLIP-170 on some, but not all, of the sites that are phosphorylated in vivo.

SIGNOR-279231

O00429

Q08209

0

dephosphorylation

up-regulates activity

0.277

When mitochondrial depolarization is associated with sustained cytosolic Ca(2+) rise, it activates the cytosolic phosphatase calcineurin that normally interacts with Drp1. Calcineurin-dependent dephosphorylation of Drp1, and in particular of its conserved serine 637, regulates its translocation to mitochondria as substantiated by site directed mutagenesis.

SIGNOR-248676

P12931

Q969T9

1

phosphorylation

up-regulates activity

0.297

Using dominant-negative, constitutively active mutants, RNAi, and pharmacological studies, we demonstrated that phosphorylation of WBP2 at Tyr192 and Tyr231 could be regulated by c-Src and c-Yes kinases.We further showed that abrogating WBP2 phosphorylation impaired >60% of ERα reporter activity, putatively by blocking nuclear entry of WBP2 and its interaction with ERα.

SIGNOR-273567

O15259

P12931

0

phosphorylation

up-regulates activity

0.297

Src-induced tyrosine phosphorylation could be prevented by mutating the tyrosine residue at position 721 to phenylalanine ( C, lane 12) suggesting that Src kinase phosphorylates NPHP1 at tyrosine 721.

SIGNOR-279122

Q13315

Q16665

1

phosphorylation

up-regulates

0.432

Here we show that hypoxia results in ataxia telangiectasia mutated (atm)-dependent phosphorylation of hypoxia-inducible factor 1-alpha (hif-1_) on serine(696) and mediates downregulation of mtorc1 signaling. phosphorylation of hif-1_ by atm is required for its stability

SIGNOR-169999

P52565

P17612

0

phosphorylation

down-regulates

0.387

The results indicate that phosphorylation of gdi_ at ser174 by pka suppresses rhoa activity, providing a potential protective signaling mechanism for inflammatory injury.

SIGNOR-180576

Q15418

P16220

1

phosphorylation

up-regulates activity

0.747

The rsks phosphorylate the trascription factor creb at serine 133 to promote cell survival.

SIGNOR-72117

P53350

Q9Y2T1

1

phosphorylation

up-regulates activity

0.486

Plk1 phosphorylates axin2 at Ser311.

SIGNOR-277180

P10909

Q86TM6

0

polyubiquitination

down-regulates quantity by destabilization

0.32

We also report that the ER-associated ubiquitin ligase Hrd1/synoviolin can interact with, and ubiquitinate clusterin. The fact that cleaved endogenous clusterin appears, under certain conditions, to be subject to polyubiquitination (Figure 2C) and proteasomal degradation (1, 2) strongly suggests that it passed through the secretory pathway before reaching the cytosol.

SIGNOR-272629

P35070

O14672

0

cleavage

up-regulates activity

0.372

Like ADAM17, ADAM10 has also been implicated in the activation of specific EGFR ligands, especially EGF and betacellulin

SIGNOR-259839

P53350

Q8N137

1

phosphorylation

up-regulates activity

0.324

However, unlike NEK2, PLK1 phosphorylation enhances the microtubule stabilizing activity of centrobin [22].|PLK1 phosphorylation of centrobin is critical for bipolar spindle formation.

SIGNOR-279551

P55075

P40426

0

transcriptional regulation

down-regulates quantity by repression

0.2

Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression. Our data support the model that Engrailed heterodimerized with Pbx might activate transcription, while Engrailed or Pbx proteins alone might repress transcription

SIGNOR-265779

P18846

Q13315

0

phosphorylation

up-regulates activity

0.359

Exposure to DNA damage further induced ATF1 phosphorylation on Ser-51 by ATM in a manner that required prior phosphorylation of the upstream CK residues.

SIGNOR-278909

P54829

Q13224

1

dephosphorylation

down-regulates activity

0.547

These previous results, together with the present findings, indicate that STEP61 dephosphorylates the NR2B subunit at its regulatory tyr1472 site, and dephosphorylation of this site leads to internalization of the NMDAR complex from neuronal surface membranes.

SIGNOR-265744

Q86Y07

Q96EV8

1

phosphorylation

down-regulates quantity by destabilization

0.2

We show that VRK2 phosphorylates Ser 297 and Ser 299 of dysbindin using in vitro kinase assay. In addition, we found that VRK2-mediated phosphorylation of dysbindin enhanced ubiquitination of dysbindin and consequently resulted in the decrease in its protein stability through western blotting.

SIGNOR-277403

Q14289

P49023

1

phosphorylation

down-regulates quantity by destabilization

0.94

P130Cas and paxillin can be phosphorylated by Fak or Pyk2, and bind directly to these kinases.

SIGNOR-279272

Q13164

P43354

1

phosphorylation

up-regulates activity

0.2

Activation of MEK, which in turns activates ERK5, does enhance the ERK5 induced nurr1 activity, while no increase is observed in the presence of a dn MEK5 or of the unphosphorylated ERK5 AEF, in which amino acids phosphorylated by MEK5 are mutated.|The A/B domain of nurr1 is highly phosphorylated in the presence of ERK5 and mutations of two amino acids in this same domain decrease significantly the ERK5 mediated nurr1 transcriptional response.|These data would suggest once again that the basal activity of ERK5 is responsible for the phosphorylation of nurr1.|As shown in XREF_FIG, nurr1 A/B domain was significantly phosphorylated by ERK5, while the GST protein alone was not a substrate for this kinase.

SIGNOR-279215

O14757

Q9UKI8

1

phosphorylation

down-regulates

0.431

Chk1 phosphorylates tlk1 on serine 695 (s695) these findings identify an unprecedented functional co- operation between atm and chk1 in propagation of a checkpoint response during s phase and suggest that, through transient inhibition of tlk kinases, the atm_chk1_tlk pathway may regulate processes involved in chromatin assembly.

SIGNOR-99653

Q16539

Q9BY84

0

dephosphorylation

down-regulates

0.805

Mkp-7 binds to and inactivates p38 mapk and jnk/sapk, but not erk inhibited by dual specificity phosphatases, such as dusp1, dusp10, and dusp16(uniprot)

SIGNOR-108233

Q99801

P53671

0

phosphorylation

down-regulates activity

0.2

LIMK2 also downregulates NKX3.1 mRNA levels.|While WT-NKX3.1 was efficiently phosphorylated, the S185A mutant showed no phosphorylation ( xref A), confirming that LIMK2 only phosphorylates the S185 site in NKX3.1.

SIGNOR-278951

P20393

P49841

0

phosphorylation

up-regulates

0.282

We show here that gsk3beta phosphorylates and stabilizes the orphan nuclear receptor rev-erbalpha, a negative component of the circadian clock.

SIGNOR-144570

Q9H1A4

P06493

0

phosphorylation

up-regulates

0.592

Apc activation is thought to depend on apc phosphorylation and cdc20 binding. We have identified 43 phospho_sites on apc of which at least 34 are mitosis specific. Of these, 32 sites are clustered in parts of apc1 and the tetratricopeptide repeat (tpr) subunits cdc27, cdc16, cdc23 and apc7. In vitro, at least 15 of the mitotic phospho_sites can be generated by cyclin_dependent kinase 1 (cdk1), and 3 by polo_like kinase 1 (plk1). Apc phosphorylation by cdk1, but not by plk1, is sufficient for increased cdc20 binding and apc activation

SIGNOR-119705

Q13131

Q16875

1

phosphorylation

up-regulates

0.399

Ipfk-2 was phosphorylated on the homologous serine (ser-461) and activated by ampk in vitro.

SIGNOR-89760

O75410

Q9UQB9

0

phosphorylation

up-regulates activity

0.399

Aurora-C interacts with and phosphorylates the transforming acidic coiled-coil 1 protein. The results demonstrated that TACC1 is phosphorylated by Aurora-C on a serine at position 228. although the patho-physiological meaning of TACC1 phosphorylation by Aurora-C in normal and in malignant somatic cells remains to be fully investigated, our observations suggest that Aurora-C has a role in the later stage of mitosis, when an interaction with TACC1 may be relevant for the correct progression of the cell cycle.

SIGNOR-262663

Q9UBN7

P27361

0

phosphorylation

up-regulates

0.426

Histone deacetylase 6 (hdac6) is well known for its ability to promote cell migrationextracellular signal-regulated kinase (erk) phosphorylates histone deacetylase 6 (hdac6) at serine 1035 to stimulate cell migrationwe have identified two novel erk-mediated phosphorylation sites: threonine 1031 and serine 1035 in hdac6. Both sites were phosphorylated by erk1

SIGNOR-202702

P10275

P50613

0

phosphorylation

down-regulates

0.377

Here, we show that the transcription factor tfiih, via its cdk7 kinase, phosphorylates the androgen receptor (ar) at position ar/s515. Strikingly, this phosphorylation is a key step for an accurate transactivation that includes the cyclic recruitment of the transcription machinery, the mdm2 e3 ligase, the subsequent ubiquitination of ar at the promoter of target genes and its degradation by the proteasome machinery

SIGNOR-170599

P45983

Q13363

1

phosphorylation

down-regulates

0.358

In this study, we found that c-jun nh2-terminal kinase 1 activation triggered ctbp phosphorylation on ser-422 and subsequent degradation,

SIGNOR-149721

P07197

Q00535

0

phosphorylation

down-regulates quantity

0.42

Converse to the effect of PKA overexpression, overexpression of CDK5 and its activator, p35, decreased the association between spinophilin and NF-M as well as the expression of NF-M.|Moreover, CDK5 phosphorylates NF-M [ xref ], and this was also apparent in our data, given a dramatic molecular weight shift in the NF-M band following CDK5 overexpression.

SIGNOR-279683

Q16649

O15534

1

transcriptional regulation

down-regulates quantity by repression

0.346

E4BP4, a basic leucine zipper transcription factor, contains a DNA-binding domain closely related to DBP, HLF, and TEF, which are PAR proteins. Here, we show that the phase of e4bp4 mRNA rhythm is opposite to that of the dbp, hlf, and tef rhythms in the suprachiasmatic nucleus (SCN), the mammalian circadian center, and the liver. The protein levels of E4BP4 and DBP also fluctuate in almost the opposite phase. All PAR proteins activate, whereas E4BP4 suppresses the mPer1 promoter through the same sequence

SIGNOR-268056

P48735

P24752

0

acetylation

down-regulates activity

0.287

Mitochondrial acetyltransferase ACAT1 and deacetylase SIRT3 are responsible for acetylation and deacetylation, respectively, at K413 of mIDH2|K413 acetylation inhibits mIDH2 by simultaneously attenuating dimer formation from monomers and destabilizing dimers for conversion to monomers

SIGNOR-267627

O43683

P40763

1

phosphorylation

up-regulates activity

0.251

This study showed that the BUB1 kinase drives the progression and proliferation of BCa by regulating the transcriptional activation of STAT3 signaling and may be an attractive candidate for therapeutic targeting in BCa.|We further identified through a series of molecular and cell biological approaches that BUB1 interacted directly with STAT3 and mediated the phosphorylation of STAT3 at Ser727.

SIGNOR-280198

P38936

P01106

0

transcriptional regulation

down-regulates quantity by repression

0.779

C-myc also directly represses transcription of cdk kinase inhibitors including p27kip1, p21cip1, p15ink4b and p16ink4a

SIGNOR-102740

O15111

P06748

1

phosphorylation

up-regulates activity

0.2

S125A and a delta form lacking the aa 119-195 region completely abolished NPM phosphorylation by IKKalpha (XREF_FIG), suggesting that IKKalpha phosphorylates S125 of NPM.|We found that TNFalpha treatment induced IKKalpha phosphorylation and increased NPM hexamers, which were correlated with increased NPM phosphorylation (XREF_FIG).

SIGNOR-279405

Q9NQU5

O43426

1

phosphorylation

up-regulates activity

0.2

We identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo.

SIGNOR-263022

P49757

P46531

1

ubiquitination

down-regulates quantity by destabilization

0.798

Mammalian numb proteins promote notch1 receptor ubiquitination and degradation of the notch1 intracellular domain

SIGNOR-99762

Q05655

P11413

1

phosphorylation

up-regulates

0.2

A pkc activator, significantly increased g6pd phosphorylation and activity, whereas single (s210a, t266a) and double (s210a/t266a) mutations at sites flanking the g6pd active site significantly inhibited phosphorylation, shifted the isoelectric point, and reduced enzyme activity.

SIGNOR-167053

Q9UIC8

P62714

1

methylation

up-regulates activity

0.661

Methylation of the carboxy-terminal Leu309 in a conserved TPDYFL309 motif of the C subunit has been shown to enhance the affinity of the PP2A core enzyme for some, but not all, regulatory subunits |The PP2A core enzyme was methylated by a PP2A-specific leucine carboxyl methyltransferase (LCMT1)

SIGNOR-265751

P40763

P29597

0

phosphorylation

up-regulates

0.687

Since Jak-STAT pathway primarily activated in IL-15-me- diated cell proliferation, we tested whether it is also participates in IL-15-mediated proliferation of FAPs. Interestingly, we found the expression of phospho-Jak3 and phospho-Tyk2, as well as their downstream, phospho- STAT3 and phospho-STAT5, was significantly upregulated

SIGNOR-256255

Q14596

P49840

0

phosphorylation

down-regulates activity

0.322

The autophagy receptor NBR1 (neighbor of BRCA1 gene 1) binds UB/ubiquitin and the autophagosome-conjugated MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) proteins, thereby ensuring ubiquitinated protein degradation|Here we show that NBR1 is a substrate of GSK3. NBR1 phosphorylation by GSK3 at Thr586 prevents the aggregation of ubiquitinated proteins and their selective autophagic degradation.

SIGNOR-261794

P63104

P17612

0

phosphorylation

down-regulates activity

0.566

Phosphorylation by pka leads to modulation of 14-3-3zeta dimerization and affect its interaction with partner proteins. Substitution of ser58 to ala completely abolished phosphorylation of 14-3-3zeta by pka.

SIGNOR-143373

P20823

Q12864

1

transcriptional regulation

up-regulates quantity by expression

0.313

The present study aims to identify the transcription factors which interact and regulate CDH17 promoter activity that might contribute to the up-regulation of CDH17 gene in human HCC|we identified hepatic nuclear factor 1α (HNF1α) and caudal-related homeobox 2 (CDX2) binding sites at the proximal promoter region which modulate the CDH17 promoter activities in two HCC cell lines (Hep3B and MHCC97L)

SIGNOR-253970

Q9UJV3

Q5S007

1

ubiquitination

down-regulates quantity by destabilization

0.2

The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its localization, degradation, and toxicity.

SIGNOR-278763

P15336

P59595

0

transcriptional regulation

up-regulates quantity by expression

0.2

The transcription factors c-Fos, FosB, CREB-1, and ATF2 were all activated by the addition of SARS-CoV N protein to the sample well

SIGNOR-260727

Q96KB5

Q96EP1

0

polyubiquitination

down-regulates quantity by destabilization

0.346

CHFR ubiquitinates and degrades TOPK. Our in vivo ubiquitination assays revealed that the polyubiquitination of TOPK occurs only in the presence of full length CHFR but not with the ΔRING or Δcysteine-rich domain deletion mutants (Fig. 2a).

SIGNOR-271471

P04637

Q96S44

0

phosphorylation

up-regulates

0.76

The intrinsic transcriptional activity of p53 was up-regulated by a transient transfection of prpk to cos-7 cells. Prpk was shown to bind to p53 and to phosphorylate p53 at ser-15.

SIGNOR-157471

Q9GZV5

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.2

GSK3 destabilizes TAZ. TAZS58A/S62A but not the TAZ S66A mutant diminished phos- phorylation by GSK3 , suggesting that Ser-58 and Ser-62 are important for GSK3 phosphorylation, whereas the Ser-66 is not (Fig. 4D).

SIGNOR-277646

Q99683

P38936

1

phosphorylation

up-regulates

0.589

P21cip1 is phosphorylated in vitro by both ask1 and jnk1 at s98. /phosphorylation of p21cip1 at s98, which in vivo appears to be regulated by ask1, may therefore mediate negative feedback in the ask1 signaling pathway.

SIGNOR-153440

P04792

Q13976

0

phosphorylation

down-regulates

0.274

Purified pkg isoforms ia, ib, and ii all caused incorporation of phosphate in recombinant hsp27 at ser-78, ser-82, and thr-143, but not ser-15.These Studies indicate that hsp27 is a genuine substrate for pkg and that pkg may mediate inhibition of platelet aggregation through phosphorylation of hsp27 and subsequent prevent of actin polymerization

SIGNOR-186784

P41279

P31749

0

phosphorylation

up-regulates activity

0.558

Akt-dependent phosphorylation of Cot occurs exclusively on serines 400 and 413. Akt to phosphorylate Cot at two sites in the carboxy-terminal domain, at least one of which may promote binding of substrates or coactivators to Cot, or alternatively may relieve binding of a negative regulator.

SIGNOR-252572

P25098

P17252

0

phosphorylation

up-regulates activity

0.2

Phosphorylation of GRK2 by protein kinase C abolishes its inhibition by calmodulin. In vitro, GRK2 was preferentially phosphorylated by PKC isoforms alpha, gamma, and delta. Two-dimensional peptide mapping of PKCalpha-phosphorylated GRK2 showed a single site of phosphorylation, which was identified as serine 29 by HPLC-MS. A S29A mutant of GRK2 was not phosphorylated by PKC in vitro and showed no phorbol ester-stimulated phosphorylation when transfected into human embryonic kidney (HEK)293 cells.

SIGNOR-249058

Q9Y251

P18146

0

transcriptional regulation

up-regulates quantity by expression

0.37

Promoter CpG hypomethylation and transcription factor EGR1 hyperactivate heparanase expression in bladder cancer.

SIGNOR-254267

Q9UKX7

P28482

0

phosphorylation

down-regulates activity

0.2

Erk phosphorylates nup50 at ser221 and ser315 erk phosphorylation of the fg repeat region of nup50 reduced its affinity for importin-beta family proteins, importin-beta and transportin.

SIGNOR-188135

Q12913

P27361

1

dephosphorylation

down-regulates activity

0.459

Tumor suppressor density-enhanced phosphatase-1 (DEP-1) inhibits the RAS pathway by direct dephosphorylation of ERK1/2 kinases|Pulldown and in vitro dephosphorylation assays confirmed our prediction and demonstrated an overall specificity of DEP-1 in targeting the phosphorylated tyrosine 204 of ERK1/2.

SIGNOR-248707

Q9UQL6

Q15139

0

phosphorylation

down-regulates activity

0.516

Here, we demonstrate that signaling by protein kinase C (PKC) is sufficient and, in some cases, necessary to drive nuclear export of class II HDAC5 in cardiomyocytes.

SIGNOR-249270

P04637

Q93009

0

deubiquitination

up-regulates

0.741

Hausp counteracts the destabilizing effect of mdm2 by direct deubiquitination of p53.

SIGNOR-139456

O43683

P33981

0

phosphorylation

up-regulates activity

0.695

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

SIGNOR-278255

Q13153

Q92974

1

phosphorylation

down-regulates

0.353

We identify gef-h1 as a binding target and substrate for p21-activated kinase 1 (pak1), we show that phosphorylation of gef-h1 at ser(885) by pak1 induces 14-3-3 binding to the exchange factor and relocation of 14-3-3 to microtubules.

SIGNOR-187573

Q96EP1

P09874

1

polyubiquitination

down-regulates quantity by destabilization

0.427

Here, we show that checkpoint with Forkhead-associated (FHA) and RING finger domain protein (CHFR), an E3 ubiquitin ligase, is recruited to DSBs by poly(ADP-ribose) (PAR). Moreover, CHFR ubiquitinates PAR polymerase 1 (PARP1) and regulates chromatin-associated PARP1 in vivo. Moreover, the poly-ubiquitin chain on PARP1 could be recognized by both anti-K48 and K63-linked poly-ubiquitin chain antibodies, suggesting that CHFR mediates a mixed poly-ubiquitin chain linkage on PARP1. With MG132 treatment, ubiquitinated PARP1 was significantly accumulated (Figure 4D), suggesting that the ubiquitination of PARP1 is likely involved in protein degradation. Consistently, we found that following DNA damage, PARP1 quickly dissociated from the chromatin in the wild-type cells (Figure 4F). However, in the Chfr−/− cells, the dissociation of PARP1 from the chromatin was significantly delayed.

SIGNOR-271470

Q99683

P52564

1

phosphorylation

up-regulates activity

0.613

A MAP kinase kinase kinase (MAPKKK), termed ASK1, was identified that activated two different subgroups of MAP kinase kinases (MAPKK), SEK1 (or MKK4) and MKK3/MAPKK6 (or MKK6), which in turn activated stress-activated protein kinase (SAPK, also known as JNK; c-Jun amino-terminal kinase) and p38 subgroups of MAP kinases, respectively.

SIGNOR-45353

O94856

P16157

1

relocalization

up-regulates quantity

0.685

Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.

SIGNOR-266718

P22455

Q8WU20

1

phosphorylation

up-regulates activity

0.685

In this report, we demonstrate that FGF stimulation induces tyrosine phosphorylation of a novel lipid anchored docking protein, termed FRS2, that forms a complex with Grb2/Sos, thus linking FGF-receptor activation to the Ras/MAPK signaling pathway.

SIGNOR-242661

P05067

O60260

0

ubiquitination

down-regulates quantity

0.2

Similarly, in transgenic AD mice models, lentiviral parkin expression ubiquitinates Abeta to reduce its intracellular levels while preventing plaque deposition, and this is associated with induction of beclin dependent autophagy .|Thus, parkin reduces Abeta levels by enhancing both UPS- and autophagy dependent clearance of Abeta.

SIGNOR-278709

Q13177

P35240

1

phosphorylation

down-regulates

0.512

Merlin contains a c-terminal serine 518, which is phosphorylated both by p21-activated kinase (pak) and protein kinase a (pka) (shaw et al., 2001;kissil et al., 2002;xiao et al., 2002;alfthan et al., 2004). Phosphorylation at this site is predicted to result in a more open conformation incapable of inhibiting cell growth,

SIGNOR-159768

P04637

P78527

0

phosphorylation

up-regulates

0.793

We demonstrate that phosphorylation of p53 at serines 15 and 37 impairs the ability of mdm2 to inhibit p53-dependent transactivation. We present evidence that these effects are most likely due to a conformational change induced upon phosphorylation of p53. Our studies provide a plausible mechanism by which the induction of p53 can be modulated by dna-pk (or other protein kinases with similar specificity) in response to dna damage.

SIGNOR-53030

P09619

Q12913

0

dephosphorylation

down-regulates activity

0.582

Primary sequence determinants responsible for site-selective dephosphorylation of the PDGF beta-receptor by the receptor-like protein tyrosine phosphatase DEP-1|DEP-1 dephosphorylation of original and chimeric phospho-peptides spanning the preferred pY1021

SIGNOR-248704

P42574

Q13043

1

cleavage

up-regulates activity

0.617

In response to apoptotic stimuli, caspase cleavage of mst1 occurs at asp-326 and asp-349, resulting in the separation of its n-terminal kinase domain from the nes-containing c-terminal domain. Thus, caspase cleavage of mst1 serves two purposes: one is activation of mst1 kinase activity and the other is translocation of mst1 into the nucleus.

SIGNOR-109878

Q71U36

Q5SQI0

0

acetylation

up-regulates quantity by stabilization

0.268

Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules

SIGNOR-272251

P49841

O15294

1

phosphorylation

up-regulates activity

0.518

But OGT activity is modulated by GSK3beta (XREF_FIG) and GSK3beta activity is known to oscillate through Ser9 phoshorylation.|Here, we found that OGT is phosphorylated at serines 3 or 4 by GSK3beta and that O GlcNAcylation of OGT also occurs on the same or neighboring serine residues, suggesting interacting phosphorylation and O GlcNAcylation events on OGT itself.

SIGNOR-279528

Q9Y243

P24666

0

dephosphorylation

down-regulates activity

0.2

Reduction in the levels of both LMW-PTP isoforms in vitro and in vivo increased tyrosine phosphorylation of IR and AktSer473 and increased IRS-1- and IRS-2-associated PI3-K activities in both liver and fat.|Activated PI3-K stimulates Akt (or protein kinase B) that in turn phosphorylates and inactivates glycogen synthase kinase-3

SIGNOR-248457

O00311

Q9HAW4

1

phosphorylation

up-regulates activity

0.742

Cdc7 phosphorylates Claspin in a manner dependent on AP and inhibits N\u2013C interaction.|Thus, Cdc7-ASK may activate DNA and PCNA bindings of Claspin through AP-mediated phosphorylation.

SIGNOR-279360

Q9NV92

P46934

1

relocalization

down-regulates activity

0.568

Ndfip1 is primarily localized in the Golgi apparatus where it recruits Nedd4-2 to mediate the degradation of mature hERG proteins during channel trafficking to the plasma membrane. Although Ndfip2 directs Nedd4-2 to the Golgi apparatus, it also recruits Nedd4-2 to the multivesicular bodies (MVBs), which may impair MVB function and impede the degradation of mature hERG proteins mediated by Nedd4-2.

SIGNOR-260995

P08648

P31249

0

transcriptional regulation

up-regulates quantity by expression

0.25

The homeobox transcription factor Hox D3 promotes integrin alpha5beta1 expression and function during angiogenesis.

SIGNOR-261649

Q06710

P01266

1

transcriptional regulation

up-regulates quantity by expression

0.458

The transcription factor Pax8 plays an important role in the expression of the differentiated phenotype of thyroid follicular cells. It has recently been shown that Pax8 is necessary for thyroglobulin (Tg) gene expression.

SIGNOR-251998

O75582

Q13541

1

phosphorylation

down-regulates activity

0.671

In response to UV-B irradiation, the translation factor 4E-BP1 (eukaryotic initiation factor 4E [eIF4E]-binding protein 1) was phosphorylated at Thr36, Thr45, Ser64 and Thr69. Using either p38 MAPK inhibitors or the MSK inhibitor H89, UV-B-irradiation-induced phosphorylation was blocked [43]. 4E-BP1 binds to eIF4E in resting cells to prevent formation of a functional eIF4F complex, which is essential for cap-dependent initiation of translation. Phosphorylation of 4E-BP1 leads to dissociation from eIF4E

SIGNOR-262992

Q9BQE3

Q8NG68

0

tyrosination

down-regulates

0.473

Tubulin tyrosine ligase (ttl) adds a c-terminal tyr to __tubulin as part of a tyrosination/detyrosination cycle present in most eukaryotic cells. / ttl inhibits spontaneous tubulin polymerization

SIGNOR-176918

P06239

Q9H4E7

1

phosphorylation

up-regulates activity

0.5

In vitro kinase assays indeed demonstrated that Lck can phosphorylate wild-type IBP but not the Y210F mutant. IBP Binds PI(3,4,5)P3 upon Phosphorylation by Lck

SIGNOR-251372

P17480

P01106

0

transcriptional regulation

up-regulates quantity by expression

0.356

MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation|MAD1 repressed and c-MYC activated rDNA transcription in nuclear run-on assays. Repression of rDNA transcription by MAD1 was associated with its ability to interact directly with the promoter of upstream binding factor (UBF), an rDNA regulatory factor. Conversely, c-MYC activated transcription from the UBF promoter.

SIGNOR-269644

Q13304

P25098

0

phosphorylation

down-regulates activity

0.2

As depicted in Fig. 8 A and B, GRK2 silencing resulted in up-regulation of GPR17 and down-regulation of the mature markers CNPase and MBP, indicating a shift of cells toward a less differentiated stage.Having established that, in primary cultured OPCs, LTD 4 mediated desensitization of GPR17 through the primary recruitment of GRK2, we then asked whether GRK2 pharmacological inhibition had any effects on cysLT promoted cell maturation.|These data demonstrate that LTD 4 -induced GPR17 phosphorylation is preferentially mediated by GRK2 and only partially by GRK5, whereas UDP-glucose-mediated receptor phosphorylation exclusively requires the GRK5 isoform.We examined the involvement of GRK2 and GRK5 in agonist induced desensitization of GPR17.

SIGNOR-279999

P67775

P24071

1

dephosphorylation

up-regulates activity

0.323

Furthermore, FcalphaRI activation is induced by protein phosphatase 2A (PP2A) after it dephosphorylates a single serine residue (S263) in the FcalphaRI intracellular tail

SIGNOR-264858

Q12857

Q9HD90

1

transcriptional regulation

up-regulates quantity

0.2

For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)

SIGNOR-268891

Q8NEV1

Q99250

1

phosphorylation

up-regulates activity

0.2

We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G.

SIGNOR-275755

P10275

P49841

0

phosphorylation

down-regulates activity

0.649

Glycogen synthase kinase-3 beta is involved in the phosphorylation and suppression of androgen receptor activity.|In particular, we showed that glycogen synthase kinase-3 beta phosphorylates the androgen receptor, thereby inhibiting androgen receptor-driven transcription.

SIGNOR-279334

P15259

Q8IXJ6

0

deacetylation

up-regulates activity

0.2

Here we report that PGAM is acetylated at lysine 100 (K100), an active site residue that is invariably conserved from bacteria, to yeast, plant, and mammals. K100 acetylation is detected in fly, mouse, and human cells and in multiple tissues and decreases PGAM2 activity. The cytosolic protein deacetylase sirtuin 2 (SIRT2) deacetylates and activates PGAM2.

SIGNOR-266518

P27361

Q02447

1

phosphorylation

up-regulates

0.299

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.

SIGNOR-157276

P52564

Q15759

1

phosphorylation

up-regulates

0.702

The p38 mapkinasekinasemkk6 is identified as a common activator of p38 alpha, p38 beta 2, and p38 gamma mapkinaseisoforms.

SIGNOR-54947

Q9Y6X2

P40763

1

sumoylation

down-regulates

0.731

Stat3 mediated signaling pathways can be inhibited by pias3 (protein inhibitor of activated stat3), which was recently found to regulate protein stability and function by its sumo (small-ubiquitin like modifiers) ligase activity in promoting sumoylation of important nuclear proteins.

SIGNOR-124723

P01178-PRO_0000020495

P16519

0

cleavage

up-regulates quantity

0.2

Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension.

SIGNOR-270335

Q15154

P41208

1

relocalization

up-regulates

0.531

Rna silencing of pcm-1 leads to reduced assembly of centrin, pericentrin, and ninein at the centrosome

SIGNOR-94990

P08581

P46940

1

phosphorylation

up-regulates activity

0.272

IQGAP1 was phosphorylated exclusively on Tyr-1510 under conditions with enhanced MET or c-Src signaling, including in human lung cancer cell lines. This phosphorylation was significantly reduced by chemical inhibitors of MET or c-Src or by siRNA-mediated knockdown of MET.

SIGNOR-277532

Q53ET0

Q9Y4K3

0

ubiquitination

down-regulates quantity

0.307

Consistently, TRAF6 reduced G6pase gene expression or reporter activity induced by wild-type CRTC1 and CRTC2 but not TRAF6-interaction-defective CRTC1 and CRTC2 (XREF_FIG and XREF_SUPPLEMENTARY).|Indeed, TRAF6, the E3 ubiquitin ligase activated by IL-1beta associates with and ubiquitinates CRTC2.

SIGNOR-278725

P11362

P00338

1

phosphorylation

up-regulates

0.366

We found that the oncogenic receptor tyrosine kinase fgfr1 directly phosphorylates ldh-a. Phosphorylation at y10 and y83 enhances ldh-a activity by enhancing the formation of active, tetrameric ldh-a and the binding of ldh-a substrate nadh, respectively.

SIGNOR-176730

P60709

P12277

0

relocalization

up-regulates quantity

0.292

In summary, data presented here strongly suggest that locally generated ATP is an important regulator for actin-based cytoskeletal dynamics involved in cell extension and motility and that CK-B is a controlling enzyme in the compartmentalization of ATP availability. CK-B co-localizes with cortical actin and facilitates spreading of astrocytes

SIGNOR-265791

Q13285

P11511

1

transcriptional regulation

up-regulates quantity by expression

0.479

The in vivo existence of an SF-1 corepressor complex consisting of DAX-1, RNF31, and SMRT at the steroidogenic promoters of the human StAR and CYP19 genes. We demonstrate that RNF31 is necessary for the stable association of the DAX-1 corepressor complex with chromatin-bound SF-1, thereby inhibiting the recruitment of coactivators and Pol II and controlling basal transcription levels of SF-1 target genes.

SIGNOR-271787

Q01082

P68400

0

phosphorylation

down-regulates

0.334

We show here that the short c-terminal splice variant of betaii-spectrin (betaiisigma2) is a substrate for phosphorylation. In vitro, protein kinase ck2 phosphorylates ser-2110 and thr-2159 / phosphorylation of ?II?2 C-terminal fragment inhibits its interaction with ?II N-terminal fragment.

SIGNOR-150471

Q6UUV7

P57059

0

phosphorylation

down-regulates

0.418

These results suggested that sik1 could phosphorylate all torcs and thereby repress their transactivation activities.

SIGNOR-147703