IdA
string
IdB
string
labels
int64
mechanism
string
effect
string
score
float64
sentence
string
signor_id
string
P17252
O95644
1
phosphorylation
down-regulates activity
0.384
Protein kinase A negatively modulates the nuclear accumulation of NF-ATc1. | Here we show that overexpression of PKA causes phosphorylation and cytoplasmic accumulation of NF-ATc1 in direct opposition to calcineurin by phosphorylating Ser-245, Ser-269, and Ser-294 in the conserved serine-proline repeat domain, and that mutation of these serines blocks the effect of PKA. Activation of endogenous PKA is similarly able to promote phosphorylation of these sites on NF-ATc1 in two lymphoid cell lines.
SIGNOR-249175
Q05397
Q14247
1
phosphorylation
down-regulates activity
0.745
FAK directly phosphorylates cortactin at Y421 and Y466 and over-expression of cortactin Y421, Y466, and Y482 mutated to phenylalanine (3YF) prevented FAK-enhanced FA turnover and cell motility.|GFP-FAK re-expression in FAK-/- MEFs enhances FA turnover (XREF_FIG) and cortactin knockdown slows FA turnover (XREF_FIG).
SIGNOR-278283
O15409
Q8WXX7
1
transcriptional regulation
up-regulates quantity by expression
0.325
By interacting with CASK, TBR1 regulates several ASD candidate genes, such as GRIN2B, AUTS2 and RELN—all of which are recurrently mutated in ASD. In areas of the brain with overlapping expression patterns, such as in glutamatergic layer 6 neurons, the TBR1–FOXP2 interaction may result in co-ordinated regulation of common downstream targets.
SIGNOR-266832
Q63ZE4
P20823
0
transcriptional regulation
up-regulates quantity by expression
0.2
Luciferase reporter gene constructs containing the OAT5 (SLC22A10) and OAT7 (SLC22A9) promoter regions were transactivated by HNF-1 in HepG2 cells.
SIGNOR-268983
P12931
P11413
1
phosphorylation
up-regulates activity
0.274
Here, we show that tyrosine kinase c-Src interacts with and phosphorylates G6PD at Tyr 112. This phosphorylation enhances catalytic activity of G6PD by dramatically decreasing its Km value and increasing its Kcat value for substrate glucose-6-phosphate.
SIGNOR-277550
O95786
P62136
0
dephosphorylation
up-regulates activity
0.2
We identified PP1alpha and PP1gamma as primary phosphatases responsible for MDA5 and RIG-I dephosphorylation, leading to their activation.|endogenous RIG-I and MDA5 that interacted with PP1 exhibited markedly decreased phosphorylation levels at S8 and S88, respectively 
SIGNOR-264581
Q9HCP0
O75581
1
phosphorylation
up-regulates
0.545
Ck1gamma is associated with lrp6, which has multiple, modular ck1 phosphorylation sites. Wnt treatment induces the rapid ck1gamma-mediated phosphorylation of these sites within lrp6
SIGNOR-143029
P29350
Q14289
1
dephosphorylation
down-regulates
0.359
Raftk binds constitutively to the protein tyrosine phosphatase shptp1.SHPTP1 Plays a negative role in pyk2/raftk signaling by dephosphorylating raftk on tyr-402, thereby inhibiting the interaction of the sh2 domain of c-src with raftk
SIGNOR-71414
O75030
P49841
0
phosphorylation
up-regulates quantity by stabilization
0.435
We also show that the MITF protein was stabilized by Wnt signaling, through the novel C-terminal GSK3 phosphorylations identified here.
SIGNOR-276476
P24588
Q9UIJ5
0
palmitoylation
up-regulates activity
0.331
Here, we report that the recycling endosome-resident palmitoyl acyltransferase DHHC2 interacts with and palmitoylates AKAP79/150 to regulate these plasticity signaling mechanisms
SIGNOR-261289
P06493
Q01196
1
phosphorylation
up-regulates
0.341
Phosphorylation of runx1 on ser-303 by cdks leads its ubiquitin-mediated degradation during g2/m (19). We developed additional evidence that cdks phosphorylate ser-303 and found that ser-48 and ser-424 are also substrates of cdk1/cyclin b and cdk6/cyclin d3. Moreover, we demonstrated that phosphorylation of ser-48, ser-303, and ser-424 strengthens the ability of runx1 to activate transcription and to stimulate proliferation of the ba/f3 hematopoietic cell line (20).
SIGNOR-169322
Q15154
Q12798
1
relocalization
up-regulates
0.406
Rna silencing of pcm-1 leads to reduced assembly of centrin, pericentrin, and ninein at the centrosome
SIGNOR-94947
P51813
P56945
1
phosphorylation
up-regulates quantity
0.506
Recombinant Bmx kinase was found to effectively phosphorylate the wt CAS SH3 domain on Tyr-12 (Figure 2B). A novel phosphorylation site on CAS, Tyr-12 (Y12) within the ligand-binding hydrophobic pocket of the CAS SH3 domain, was identified and found to be enriched in Src-transformed cells and invasive human carcinoma cells. 
SIGNOR-276384
P31749
Q96GX5
1
phosphorylation
up-regulates activity
0.2
Here, we report that AKT phosphorylates MASTL at residue T299, which plays a critical role in its activation.
SIGNOR-277515
P15559
Q9Y4A8
0
transcriptional regulation
down-regulates quantity by repression
0.338
Deletion mutation analysis revealed that Nrf3 repression of NQO1 gene expression required heterodimerization and DNA binding domains but not transcriptional activation domain of Nrf3.
SIGNOR-268976
P08631
Q13444
1
phosphorylation
up-regulates
0.355
Hck, and to a lesser extent lck, phosphorylated the adam15. Deletion and point mutation analysis of the adam15 cytoplasmic domain confirmed the importance of the proline-rich motifs for grb2 and lck binding and indicated the regulatory nature of tyr(715) and tyr(735). These data demonstrate selective, phosphorylation-dependent interactions of adam15 with src family ptks and grb2, which highlight the potential for integration of adam functions and cellular signaling.
SIGNOR-112919
P55011
Q9UEW8
0
phosphorylation
up-regulates activity
0.6
This phosphorylation event activates PASK, which in turn phosphorylates and activates NKCC1
SIGNOR-264642
Q9Y6M1
P42345
0
phosphorylation
up-regulates activity
0.2
IGF2BP2 can be activated by mTOR and promotes its binding to IGF2 mRNA of IGF2 thereby leading to diabetes mellitus [ xref , xref ].|In addition, phosphorylation of IGF2BP2 in the linker region between RRM2 and KH1 by mTOR promotes its binding to the IGF leader 3 mRNA 5\u2032-UTR, enhancing the initiation of IGF2 translation through eIF-4E- and 5\u2032 cap-independent internal ribosomal entry [ xref ].
SIGNOR-280046
P04275
Q76LX8
0
cleavage
down-regulates activity
0.599
Proteolytic degradation of VWF by ADAMTS-13 downregulates the proinflammatory potential of VWF. 
SIGNOR-251966
P62714
Q12933
1
dephosphorylation
down-regulates activity
0.2
We show that the Thr117 residue in TRAF2 is phosphorylated following TNFalpha stimulation. This phosphorylation process is modulated by PP2A and is required for TRAF2 functional activity.
SIGNOR-248597
P11912
P06241
0
phosphorylation
up-regulates activity
0.596
Lyn and Fyn phosphorylated the CD79a cytoplasmic portion of the fusion proteins well, with >80% of phosphorylation occurring at Y182. CD79a and CD79b function as transducers of B cell antigen receptor signals via a cytoplasmic sequence, termed the immunoreceptor tyrosine-based activation motif (ITAM).
SIGNOR-251153
P11308
P04628
1
transcriptional regulation
up-regulates quantity by expression
0.2
Interestingly, our data showed that ERG drastically induced Wnt ligand gene expression.
SIGNOR-261597
O75592
P46060
0
relocalization
down-regulates quantity by destabilization
0.315
SUMOylated RanGAP1 Inhibits MYCBP2 Activity and Mediates Its Transport to the Nucleus. Surprisingly, we did not find MYCBP2-dependent ubiquitylation of SUMOylated RanGAP1 but instead a strong inhibition of the ubiquitin ligase activity of MYCBP2 in the presence of SUMOylated RanGAP1, as determined by the presence of ubiquitylated proteins. this effect was specific for SUMOylated RanGAP1, because the unmodified form of RanGAP1 did not affect MYCBP2-dependent protein ubiquitylation. , SUMOylated RanGAP1 inhibited the ubiquitin ligase activity of MYCBP2, and it is tempting to speculate that SUMOylated RanGAP1 inhibits the ubiquitin ligase activity of MYCBP2 to ensure MYCBP2 silencing during its transport to the nucleus
SIGNOR-261203
P01106
P17480
1
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
O15234
O95271
0
ADP-ribosylation
down-regulates quantity by destabilization
0.2
Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation.
SIGNOR-263383
Q9H4B4
Q16143
1
phosphorylation
down-regulates activity
0.38
Polo-like kinase (plk) family (plk1, plk2, and plk3) phosphorylate alpha-syn and beta-syn specifically at ser-129 and ser-118, respectively. Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation.
SIGNOR-189057
P42345
O95163
1
phosphorylation
up-regulates activity
0.2
Human ELP1 S1174 phosphorylation was triggered by insulin treatment, as shown by the specific phosphorylated (p)ELP1 (S1174) antibody, and addition of a phosphorylation-mutant variant of the ELP1 protein (ELP1(S1174A)) to ELP1-depleted BRAFV600E melanoma cells failed to rescue cell survival |In line with these findings, mTORC2 activity, but not mTORC1, was required for the insulin-induced phosphorylation of Elp1 S1174
SIGNOR-275541
P19021
P01178-PRO_0000020495
1
cleavage
up-regulates activity
0.2
Nevertheless, overall the results of this study show that peptide sequence recognition is an important aspect of the interactions of the prohormone substrates prooxytocin (3d) and procalcitonin (7e) with PAM, which is mirrored in the potency of analogous peptidomimetic glycolate inhibitors of the enzyme.
SIGNOR-268551
O15297
Q13315
1
dephosphorylation
down-regulates
0.488
The negative regulator wip1 plays an important role in inhibiting atm, resulting in a pulse of atm activity.
SIGNOR-185135
P00533
Q16539
0
phosphorylation
down-regulates
0.508
In conclusion, the use of pharmacological agents suggests that p38 mapk is the enzyme involved in egfr phosphorylation, as well as internalization, following exposure of cells to various stress-inducing conditions.
SIGNOR-149089
P04049
O75914
0
phosphorylation
up-regulates
0.556
The protein kinase pak3 positively regulates raf-1 activity through phosphorylation of serine 338.
SIGNOR-62043
Q5VWQ8
P01112
1
gtpase-activating protein
down-regulates activity
0.6
The GAP domain of DAB2IP is homologous to other Ras-GAPs, such as GAP120 and neurofibromin (NF1), and can stimulate the GTPase activity of RAS proteins both in vitro and in cancer cell lines. DAB2IP is able to stimulate in vitro and in vivo the GTPase activity of RAS proteins (H-Ras, K-Ras, and N-Ras) facilitating GTP hydrolysis to GDP.
SIGNOR-254745
Q8TEU7
P01112
1
guanine nucleotide exchange factor
up-regulates
0.336
Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras.
SIGNOR-183796
P17252
P08670
1
phosphorylation
down-regulates quantity by destabilization
0.284
We reported that stoichiometric phosphorylation by either cAMP-dependent protein kinase or protein kinase C induces disassembly of vimentin filaments. In the present work, we attempted to identify the sites of vimentin phosphorylated by each protein kinase. Sequential analysis of the purified phosphopeptides, together with the known primary sequence, revealed that Ser-8, Ser-9, Ser-20, Ser-25, Ser-33, and Ser-41 were specifically phosphorylated by protein kinase C, whereas Ser-46 was phosphorylated preferentially by cAMP-dependent protein kinase. Both kinases reacted with Ser-6, Ser-24, Ser-38, Ser-50, and Ser-65.
SIGNOR-248880
Q02779
P15923
1
phosphorylation
down-regulates
0.2
Mlk2 inhibits e47 transactivation activity on the trkb promote
SIGNOR-161544
Q7Z6Z7
Q13105
1
ubiquitination
down-regulates quantity by destabilization
0.327
Previously, we reported that K48 linked polyubiquitination of Miz1 by Mule triggers its proteasomal degradation, thereby relieving Miz1 suppression on TNF induced JNK activation and apoptosis.
SIGNOR-278697
P45983
P17535
1
phosphorylation
up-regulates
0.796
Menin binds the jun family transcription factor jund and inhibits its transcriptional activity. The menin-jund interaction blocks jun n-terminal kinase (jnk)-mediated jund phosphorylation and suppresses jund-induced transcription. We found a role for phosphorylation of the ser100 residue of jund;jund phosphorylation were prevented by inhibitors of calcium, calmodulin, or erk1/2 kinase.
SIGNOR-196038
Q9H2G2
P04637
1
phosphorylation
up-regulates activity
0.256
The Ste20 like kinase SLK promotes p53 transactivation and apoptosis.|Thus SLK induces p53 phosphorylation and transactivation, which enhances apoptosis after in vitro ischemia-reperfusion injury.
SIGNOR-279285
P09622
Q9Y572
0
phosphorylation
up-regulates activity
0.2
Here, we show that RIP3 activates the pyruvate dehydrogenase complex (PDC, also known as PDH), the rate-limiting enzyme linking glycolysis to aerobic respiration, by directly phosphorylating the PDC E3 subunit (PDC-E3) on T135.
SIGNOR-266372
P10275
P16591
0
phosphorylation
up-regulates
0.259
Fer is required for il-6 mediated ar activation by phosphorylating ar tyrosine 223 and binding via its sh2 domain.
SIGNOR-194749
P67775
Q9BXL7
1
dephosphorylation
down-regulates activity
0.309
NF-kappaB activation is triggered by PKCtheta-dependent phosphorylation of Carma1 after TCR/CD28 co-stimulation. PKCtheta-phosphorylated Carma1 was suggested to function as a molecular scaffold that recruits preassembled Bcl10-Malt1 complexes to the membrane|we demonstrate that PP2A removes PKCtheta-dependent phosphorylation of Ser645 in Carma1, and show that maintenance of this phosphorylation is correlated with increased T-cell activation.
SIGNOR-248650
P25440
P62805
0
relocalization
up-regulates activity
0.2
Thus, the TIP60 HAT complex is recruited to MYC-target genes and, probably with other other HATs, contributes to histone acetylation in response to mitogenic signals.
SIGNOR-262062
O95155
P54252
1
polyubiquitination
down-regulates quantity by destabilization
0.578
Mammalian E4B (UFD2a), a ubiquitin chain assembly factor (E4), copurified with the polyubiquitylation activity for ataxin-3. E4B interacted with, and thereby mediated polyubiquitylation of, ataxin-3.  Collectively, these data suggest that E4B promotes the degradation of ataxin-3, and that this effect surmounts the stabilization of ataxin-3 conferred by expansion of the polyglutamine tract.
SIGNOR-271502
P36873
P50750
1
dephosphorylation
up-regulates
0.2
Pp1 is an activator of cdk9. Pp1 dephosphorylates cdk9 thr186.
SIGNOR-173454
Q13363
P45983
0
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
Q13309
P01106
1
ubiquitination
down-regulates quantity
0.736
The F-box protein Skp2 mediates c-Myc ubiquitylation by binding to the MB2 domain
SIGNOR-243548
P18887
P68400
0
phosphorylation
up-regulates
0.395
Xrcc1 phosphorylation by ck2 is required for its stability and efficient dna repair
SIGNOR-165419
P04637
O14920
0
phosphorylation
up-regulates activity
0.52
Here , we show that IKKbeta modulates the activity of p53 in response to glutamine depletion to promote cancer cell adaptation .|Taken together, these results indicate that IKK\u03b2 phosphorylates p53 on Ser392 as an early response to glutamine deprivation and possibly later facilitates its phosphorylation at Ser15 and transcriptional activity.
SIGNOR-278516
Q86X55
P23759
1
methylation
up-regulates
0.421
Carm1 specifically methylates Pax7 at multiple arginine residues in the N terminus of Pax7
SIGNOR-255898
Q13315
Q8N0Z6
1
phosphorylation
up-regulates activity
0.538
Here we report a new pathway in which ATM kinase signals the DNA damage response by targeting the transcriptional cofactor Strap. ATM phosphorylates Strap at a serine residue, stabilizing nuclear Strap and facilitating formation of a stress-responsive co-activator complex.
SIGNOR-262645
Q13315
Q9HAU4
1
phosphorylation
up-regulates activity
0.2
Using biochemical approaches and MS analysis, we show that upon the onset of the DNA-damage response, SMURF2 becomes phosphorylated at Ser384 by ataxia telangiectasia mutated (ATM) serine/threonine kinase, and this phosphorylation is required for its interaction with RNF20.
SIGNOR-277534
Q9Y2T7
P31751
0
phosphorylation
up-regulates quantity by stabilization
0.2
In this context, YBX2 is a dual substrate for both AMPK and Akt2. The phosphorylation at Thr115 by AMPK or at Ser137 by Akt2 facilitates YBX2 accumulation in brown adipocytes by decreasing ubiquitination-mediated degradation. 
SIGNOR-277869
O75717
Q13535
0
phosphorylation
up-regulates activity
0.539
And-1 is phosphorylated at T826 by ATR following replication stress, and this phosphorylation is required for And-1 to accumulate at the damage sites, where And-1 promotes the interaction between Claspin and Chk1, thereby stimulating efficient Chk1 activation by ATR.
SIGNOR-262664
P27361
Q15672
1
phosphorylation
up-regulates
0.328
Phosphorylation of serine 68 of twist1 by mapks stabilizes twist1 protein and promotes breast cancer cell invasiveness. this ser 68 is phosphorylated by p38, c-jun n-terminal kinases (jnk), and extracellular signal-regulated kinases1/2 in vitro
SIGNOR-173413
P55211
Q9Y243
0
phosphorylation
down-regulates
0.518
Akt phosphorylated recombinant casp9 in vitro on serine-196 and inhibited its protease activity
SIGNOR-61565
Q53EL6
P31749
0
phosphorylation
down-regulates
0.435
Both akt and p70(s6k) phosphorylate pdcd4, allowing for binding of the e3-ubiquitin ligase beta-trcp and consequently ubiquitylation.
SIGNOR-252505
P31749
P15056
1
phosphorylation
down-regulates activity
0.458
Akt phosphorylates both S364 and S428. Akt downregulates B-Raf activity in vivo
SIGNOR-251472
Q13315
P55957
1
phosphorylation
down-regulates activity
0.463
Taken together, these results are consistent with the idea that at low levels of DNA damage ATM phosphorylates Bid to keep it away from the mitochondria resulting in low levels of ROS.|Thus, Bid accumulation at the mitochondria, which is negatively regulated by ATM, triggers a metabolic change in mitochondria that includes an increase in ROS and perhaps changes in other metabolites that signal back to the nucleus to regulate gene transcription leading to cell cycle progression (XREF_FIG).
SIGNOR-279790
Q15796
Q13705
0
phosphorylation
up-regulates activity
0.776
It has been suggested that binding of myostatin to the ActRIIB results in the phosphorylation of two serine residues of Smad2 or Smad3 at COOH domains
SIGNOR-254984
Q9UJW0
Q01484
0
relocalization
up-regulates quantity
0.625
We present evidence for an ankyrin-based mechanism for sarcolemmal localization of dystrophin and beta-DG. Ankyrin-B thus is an adaptor required for sarcolemmal localization of dystrophin, as well as dynactin-4.
SIGNOR-266713
Q13315
Q96SD1
1
phosphorylation
up-regulates
0.619
The artemis nuclease is defective in radiosensitive severe combined immunodeficiency patients and is required for the repair of a subset of ionising radiation induced dna double-strand breaks (dsbs) in an atm and dna-pk dependent process. Here, we show that artemis phosphorylation by atm and dna-pk in vitro is primarily attributable to s503, s516 and s645 and demonstrate atm dependent phosphorylation at serine 645 in vivo
SIGNOR-148315
O60315
P50222
1
transcriptional regulation
down-regulates quantity by repression
0.318
ZEB2 represses GAX transcription through multiple up- stream consensus binding sites.
SIGNOR-268951
P28482
P17676
1
phosphorylation
up-regulates
0.716
Phosphorylation of cebpb at thr(235) peaked at 16 hours in il-1beta-stimulated cells. The mek inhibitor u0126 inhibited this phosphorylation and reduced mmp-1 gene induction.
SIGNOR-187798
P31749
Q15257
0
dephosphorylation
down-regulates
0.2
Consistent with previous reports (2830), we found that expression of sv40st, suppression of either pp2a c or b resulted in elevated levels of akt phosphorylation (ser473)
SIGNOR-252607
O14920
P42771
1
phosphorylation
down-regulates
0.396
Ikkbeta specifically binds to p16 and phosphorylates ser8 of p16 phosphorylation at ser8 of p16 brings about a significant loss of its cyclin-dependent kinase (cdk) 4-inhibitory activity
SIGNOR-163801
P17947
O15550
0
transcriptional regulation
down-regulates quantity by repression
0.252
Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase
SIGNOR-260036
Q9HCE7
Q12778
0
transcriptional regulation
up-regulates quantity
0.248
FoxO factors are required for the transcriptional regulation of the ubiquitin ligases atrogin-1, also called muscle atrophy F-box (MAFbx) and muscle ring finger 1 (MuRF1), leading to the ubiquitylation of myosin and other muscle proteins (see below), and their degradation via the proteasome
SIGNOR-256268
Q96J02
O15350
1
ubiquitination
down-regulates quantity by destabilization
0.566
Collectively, our present findings suggest that MDM2 promotes Itch-mediated degradation of p73 through the interaction with Itch in HeLa cells
SIGNOR-278699
P46531
O00629
0
relocalization
up-regulates
0.287
Nicd binds via one of its four potential nuclear localization signals to importins alfa3, alfa4, and alfa7.
SIGNOR-165314
O94986
P24941
1
relocalization
up-regulates activity
0.278
Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome.
SIGNOR-271724
P14618
Q9P1W9
0
phosphorylation
up-regulates quantity by stabilization
0.37
Here, we identified the protein-serine/threonine kinase PIM2, a known oncogene, as a novel binding partner of PKM2. The interaction between PIM2 and PKM2 was confirmed by multiple biochemical approaches in vitro and in cultured cells. Importantly, we found that PIM2 could directly phosphorylate PKM2 on the Thr-454 residue, resulting in an increase of PKM2 protein levels. Compared with wild type, PKM2 with the phosphorylation-defective mutation displayed a reduced effect on glycolysis
SIGNOR-267472
P78352
Q02156
0
phosphorylation
up-regulates quantity
0.285
PKCepsilon directly phosphorylated PSD-95 and JNK1 in vitro Inhibiting PKCepsilon, JNK, or calcium/calmodulin dependent kinase II activity prevented the effects of PKCepsilon activators on PSD-95 phosphorylation.|These results indicate that PKCepsilon promotes synaptogenesis by activating PSD-95 phosphorylation directly through JNK1 and calcium/calmodulin dependent kinase II and also by inducing expression of PSD-95 and synaptophysin.
SIGNOR-280087
P19474
P49915
1
ubiquitination
down-regulates
0.326
Cytoplasmic sequestration of gmps requires ubiquitylation by trim21, a ubiquitin ligase associated with autoimmune disease.
SIGNOR-204478
Q13315
Q96J02
1
phosphorylation
up-regulates activity
0.264
Here we uncover ATM as a novel positive modulator of ITCH E3-ubiquitin ligase activity. A single residue on ITCH protein, S161, which is part of an ATM SQ consensus motif, is required for ATM-dependent activation of ITCH.
SIGNOR-276488
O43293
O14950
1
phosphorylation
up-regulates
0.511
Hzipk phosphorylated the regulatory light chain of myosin ii (mrlc) at both ser19 and thr18 in vitro. Phosphorylation of mrlc is required to generate the driving force in the migration of the cells but not necessary for localization of myosin ii at the leading edge.
SIGNOR-16043
Q13627
P40763
1
phosphorylation
up-regulates activity
0.265
DYRK1A overexpression promotes STAT3 activity by phosphorylating STAT3 at Ser727 and contributes to reduced neuronal production and increased astroglial generation in DS.
SIGNOR-279992
P54646
Q92574
1
phosphorylation
up-regulates
0.551
Under energy starvation conditions, the amp-activated protein kinase (ampk) phosphorylates tsc2 and enhances its activity.
SIGNOR-119541
P28482
P17480
1
phosphorylation
down-regulates
0.394
Erk1/2 was found to phosphorylate the architectural transcription factor ubf at amino acids 117 and 201 within hmg boxes 1 and 2, preventing their interaction with dna
SIGNOR-112809
P67775
P31749
1
dephosphorylation
down-regulates activity
0.893
Protein phosphatase 2A negatively regulates insulin's metabolic signaling pathway by inhibiting Akt (protein kinase B) activity in 3T3-L1 adipocytes
SIGNOR-252614
O75874
Q12778
0
transcriptional regulation
up-regulates quantity by expression
0.258
We identify FOXOs as transcriptional activators of IDH1. FOXOs promote IDH1 expression and thereby maintain the cytosolic levels of α-ketoglutarate and NADPH.
SIGNOR-260101
P31269
P11309
1
transcriptional regulation
up-regulates quantity by expression
0.2
Thus Pim1 appears to be a direct transcriptional target of HOXA9 and a mediator of its antiapoptotic and proproliferative effects in early cells. 
SIGNOR-261632
Q14653
P13288
0
phosphorylation
down-regulates activity
0.2
BGLF4 kinase interacts physically with and phosphorylates IRF3, which is the initial activator of transcription in the innate immune response. BGLF4 suppresses IRF3-dependent transcriptional activation. Data here suggest that Ser123, Ser173, and Thr180 contribute additively to the BGLF4-mediated repression of the IRF3 transactivation activity.
SIGNOR-266647
P06493
Q9BZB8
1
phosphorylation
up-regulates activity
0.581
Combined, our results suggest that XGef is involved in XRINGO and CDK1 mediated activation of CPEB and that an XGef, XRINGO, ERK2, and CPEB complex forms in ovo to facilitate this process.|Notably, specific inhibition of XRINGO and CDK1 activity in CPEB phosphorylation-competent extracts completely blocks phosphorylation of CPEB, which suggests that XRINGO and CDK1 directly phosphorylates CPEB.
SIGNOR-280205
P37840
P67775
0
dephosphorylation
down-regulates activity
0.332
α-Synuclein (α-Syn) is a key protein that accumulates as hyperphosphorylated aggregates in pathologic hallmark features of Parkinson's disease (PD) and other neurodegenerative disorders. Phosphorylation of this protein at serine 129 is believed to promote its aggregation and neurotoxicity, suggesting that this post-translational modification could be a therapeutic target. Here, we demonstrate that phosphoprotein phosphatase 2A (PP2A) dephosphorylates α-Syn at serine 129
SIGNOR-248635
P60953
Q8NF50
0
guanine nucleotide exchange factor
up-regulates activity
0.767
Recently, DOCK8 was identified as a guanine-nucleotide exchange factor (GEF) for Cdc42 activation and has been associated with human mental retardation. 
SIGNOR-268412
Q9HCK8
P04818
1
transcriptional regulation
up-regulates quantity by expression
0.283
In order to identify CHD8 target genes, we performed a transcriptomic analysis of CHD8-depleted cells, finding out that CHD8 controls the expression of cyclin E2 (CCNE2) and thymidylate synthetase (TYMS), two genes expressed in the G1/S transition of the cell cycle. CHD8 was also able to co-activate the CCNE2 promoter in transient transfection experiments. Chromatin immunoprecipitation experiments demonstrated that CHD8 binds directly to the 5' region of both CCNE2 and TYMS genes.
SIGNOR-268805
O43521
P45984
0
phosphorylation
up-regulates activity
0.637
JNKs specifically phosphorylate BIMEL at Ser55, 65, and/or 73. several observations demonstrate that the phosphorylation of BIMEL is a physiologically important mechanism for enhancing its proapoptotic activity.
SIGNOR-250134
Q9BX84
Q96QT4
1
phosphorylation
down-regulates quantity
0.498
We found TRPM6 and TRPM7 both autophosphorylate threonine residues, but only TRPM6 crossphosphorylates TRPM7, and not the reverse .
SIGNOR-279770
P36897
P63000
1
null
up-regulates activity
0.28
Thus, TGF-_1 rapidly stimulates activity of both RhoA and Rac1 and this activation requires ALK5/T_RI kinase activity.
SIGNOR-227496
Q9UII4
P22392
1
ubiquitination
up-regulates quantity by stabilization
0.307
HERC5 is required for ubiquitination of Nm23B. In summary, Nm23B ubiquitination is mediated by HERC5. Stable Nm23B protein in presence of HERC5 as well as proteasome-independent ubiquitination suggest that ubiquitination of Nm23B serves a different purpose than marking it for degradation.
SIGNOR-271778
Q00987
P35790
0
phosphorylation
down-regulates quantity by destabilization
0.274
The data presented here provides evidence for a molecular mechanism by which CKI-dependent phosphorylation of Mdm2 at multiple sites triggers SCF \u03b2-TRCP -mediated Mdm2 destruction ( xref ).
SIGNOR-279606
Q14896
P17612
0
phosphorylation
up-regulates
0.275
Phosphorylation of cmybp-c by pka speeds actomyosin interactions and contributes to increased cardiac contractility following _-adrenergic stimulation.7, 8 phosphorylation by pka is essential for proper cardiac function /for the human isoform, three pka sites were previously identified (ser275, ser284, and ser304) /our results indicate that pka phosphorylates up to four sites in both the murine and human m-domains including a novel site not previously described for either protein (ser307 for mouse and ser311 for human).
SIGNOR-163760
O15105
Q96EB6
0
deacetylation
down-regulates
0.441
Sirt1 reversed acetyl-transferase (p300)-mediated acetylation of two lysine residues (lys-64 and -70) on smad7. sirt1-mediated deacetylation of smad7 enhanced smad ubiquitination regulatory factor 1 (smurf1)-mediated ubiquitin proteasome degradation, which contributed to the low expression of smad7 in sirt1-overexpressing mesangial cells.
SIGNOR-150595
P37231
Q00987
0
ubiquitination
down-regulates quantity by destabilization
0.389
 Here, we found that nuclear EGFR induced phosphorylation of PPARγ at Tyr-74 leading to PPARγ ubiquitination and degradation by mouse double minute 2 (MDM2) ubiquitin ligase. 
SIGNOR-277191
Q6VVB1
P35573
1
ubiquitination
down-regulates quantity by destabilization
0.56
The E3 ubiquitin ligase Malin interacts with and promotes the ubiquitination of AGL.
SIGNOR-271669
Q00535
P49023
1
phosphorylation
up-regulates activity
0.377
Thus, phosphorylation of paxillin is involved in NGF-induced neurite extension of PC-12 cells, probably through regulating focal adhesion organization.|cdk5 and p38MAPK phosphorylates Ser 85 on paxillin in vitro.
SIGNOR-278921
Q9Y314
P67775
1
ubiquitination
down-regulates quantity by destabilization
0.338
 NOSIP mediates the monoubiquitination of the PP2A catalytic subunit and the loss of NOSIP results in an increase in PP2A activity in craniofacial tissue in NOSIP knockout mice. 
SIGNOR-271498
Q86UR1
P10415
1
null
down-regulates activity
0.2
BH3-only proteins containing only a single BH domain and including Puma, Noxa, Bid and Bad as well as other factors are particularly important for such neutralisation, binding and regulating the anti-apoptotic Bcl-2 proteins to promote apoptosis
SIGNOR-209684
Q8TD19
Q8TDX7
1
phosphorylation
up-regulates activity
0.715
Nercc1 catalyzes the phosphorylation of nek6 (ser206) and the equivalent site on nek7 (ser195), resulting in a 20-25-fold activation of nek6/7 kinase activity
SIGNOR-103030
O15054
Q16665
0
transcriptional regulation
up-regulates quantity by expression
0.266
To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.
SIGNOR-271571