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14
Q9Y6C9
P55957
1
relocalization
up-regulates
0.303
Mtch2/mimp (mitochondrial carrier homologue 2/met-induced mitochondrial protein), a novel truncated bid (tbid)-interacting protein, is a surface-exposed outer mitochondrial membrane protein that facilitates the recruitment of tbid to mitochondria
SIGNOR-165081
Q8IW41
Q9UKI8
0
phosphorylation
up-regulates activity
0.2
We established that TLK1 phosphorylates MK5 on three residues (S160, S354 and S386), resulting in MK5 activation, and additionally, mobility shifts of MK5 also supported its phosphorylation by TLK1 in transfected HEK 293 cells.
SIGNOR-276747
Q13164
Q00535
0
phosphorylation
up-regulates activity
0.2
CDK5 directly phosphorylated ERK5 at Thr732 and modulated the ERK5\u2013AP-1 signaling axis.
SIGNOR-279364
Q15075
Q9H8W4
2
binding
up-regulates activity
0.248
In yeast two-hybrid analysis we identified Phafin2 as a novel interactor of the endosomal-tethering protein EEA1, and Phafin2 colocalized strongly with EEA1 in microdomains of the endosome membrane. Our results suggest that Phafin2 controls receptor trafficking and fluid-phase transport through early endosomes by facilitating endosome fusion in concert with EEA1.
SIGNOR-261276
P35226
Q9Y243
0
phosphorylation
up-regulates activity
0.258
the polycomb group silencing protein Bmi1 can be phosphorylated by AKT, which enhances its oncogenic potential in PCa. Overexpression of Bmi1 can act in combination with PTEN haploinsufficiency to induce invasive carcinogenic formation in the prostate
SIGNOR-249583
P29122
P06213
1
cleavage
up-regulates activity
0.2
Here we demonstrate that the two IR isoforms are similarly cleaved by furin, but when this furin-dependent maturation is inefficient, IR proforms move to the cell surface where the proprotein convertase PACE4 selectively supports IRB maturation.
SIGNOR-260366
P34903
Q8TAB3
2
binding
up-regulates quantity by stabilization
0.2
Here, we found that PCDH19 binds the alpha subunits of GABAAR and regulates its surface availability and currents in cultured hippocampal neurons. The PCDH19 gene (Xp22.1) encodes the cell-adhesion protein protocadherin-19 (PCDH19) and is responsible for a neurodevelopmental pathology characterized by female-limited epilepsy, cognitive impairment and autistic features, the pathogenic mechanisms of which remain to be elucidated. Here, we identified a new interaction between PCDH19 and GABAA receptor (GABAAR) alpha subunits in the rat brain. PCDH19 shRNA-mediated downregulation reduces GABAAR surface expression and affects the frequency and kinetics of miniature inhibitory postsynaptic currents (mIPSCs) in cultured hippocampal neurons. 
SIGNOR-267222
P15036
Q9UQM7
0
phosphorylation
down-regulates
0.2
Camkii caused ets-2 phosphorylation.Serine 246, 310, and 313 were the targets. Camkii to phosphorylates ets-2, thus altering ets-2 binding to its downstream promoters
SIGNOR-183596
Q9HD67
P43146
2
relocalization
up-regulates quantity
0.686
Here, we provide evidence for the involvement of the unconventional myosin X (Myo X) in netrin-1 function. We find that Myo X interacts with the netrin receptor deleted in colorectal cancer (DCC) and neogenin, a DCC-related protein. Expression of Myo X redistributes DCC to the cell periphery or to the tips of neurites, whereas its silencing prevents DCC distribution in neurites. Moreover, expression of DCC, but not neogenin, stimulates Myo X-mediated formation and elongation of filopodia, suggesting that Myo X function may be differentially regulated by DCC and neogenin.
SIGNOR-268282
Q13233
Q13158
1
phosphorylation
down-regulates activity
0.503
The results clearly show that fadd phosphorylation at ser194 affects functions both upstream and downstream of the mekk1/mkk7/jnk1 pathway and is closely associated with chemosensitivity in prostate cancer cells
SIGNOR-123168
O60934
Q14676
2
binding
up-regulates
0.834
Mdc1 also undergoes phosphorylation by ck2 after dna damage to generate a phospho-motif on mdc1, which binds directly to nbs1.
SIGNOR-184141
P20339
Q99698
2
binding
down-regulates activity
0.266
Mauve interacts with Rab5, Msps, and gamma-tubulin|Mauve/LYST opposes Rab5, which promotes vesicle fusion affecting PCM recruitment
SIGNOR-266001
P20929
O00401
2
binding
up-regulates
0.352
Igf1-akt signaling, by inhibiting gsk3b, allows the interaction of n-wasp with the unphosphorylated nebulin;the consequent recruitment of n-wasp to the z-disk promotes actin nucleation and elongation of actin filaments.
SIGNOR-175671
P35790
Q92993
0
acetylation
up-regulates activity
0.2
Glucose deprivation induces the binding of choline kinase α2 (CHKα2) to lipid droplets, followed by a continuous PTMs to promote lipolysis of lipid droplets, which are in turn mediated by AMPK-dependent CHKα2 Serine 279 phosphorylation and KAT5-dependent CHKα2 Lysine 247 acetylation.
SIGNOR-267648
Q05655
Q01543
1
phosphorylation
down-regulates
0.346
We have previously demonstrated that in response to transforming growth factor _ (tgf_), fli-1 activity is repressed through a series of sequential posttranslational modifications, consisting of protein kinase c_ (pkc_)-induced thr312 phosphorylation, acetylation by p300/creb binding protein-associated factor, and detachment from the collagen promoter.
SIGNOR-172113
P35555
O95967
2
binding
down-regulates activity
0.393
Fibulin-4 and -5 are extracellular glycoproteins with essential non-compensatory roles in elastic fiber assembly. Both fibulins differentially bound N-terminal fibrillin-1, which strongly inhibited their binding to lysyl oxidase and tropoelastin.
SIGNOR-251860
P00519
Q05086
1
phosphorylation
down-regulates activity
0.273
Our results suggest that c-Abl protects p53 from HPV-E6-E6AP complex-mediated degradation by phosphorylating E6AP and impairing its E3 ligase activity
SIGNOR-260930
Q03113
P31391
2
binding
up-regulates activity
0.25
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.
SIGNOR-256959
P00533
P0DP24
1
phosphorylation
down-regulates
0.345
Phosphorylation of calmodulin by the epidermal-growth-factor-receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule.
SIGNOR-266319
Q01094
P06400
2
binding
down-regulates activity
0.921
E2f binds rb. E2f activation domain is the target for rb-induced repression. Rb can silence the 57 residue e2f activation domain. Rb can mask e2f residues involved in the activation process, possibly by mimicking a component of the transcriptional machinery
SIGNOR-37305
Q14209
P06400
2
binding
down-regulates
0.914
Cyclin-dependent kinase (cdk) phosphorylation of the retinoblastoma protein (rb) drives cell proliferation through rb complexes with e2f transcription factors and other regulatory proteins.
SIGNOR-197328
P84243
O14647
0
relocalization
up-regulates quantity
0.2
Non-homologous end-joining (NHEJ) is the dominant DSB repair pathway in human cells, but our understanding of how it operates in chromatin is limited. Here, we define a mechanism that plays a crucial role in regulating NHEJ in chromatin. This mechanism is initiated by DNA damage-associated poly(ADP-ribose) polymerase 1 (PARP1), which recruits the chromatin remodeler CHD2 through a poly(ADP-ribose)-binding domain. CHD2 in turn triggers rapid chromatin expansion and the deposition of histone variant H3.3 at sites of DNA damage.
SIGNOR-264527
P40763
P42224
1
transcriptional regulation
up-regulates quantity by expression
0.615
In summary, we report in this study that STAT1 expression is upregulated by nuclear EGFR, EGFRvIII and HER2, and that STAT3 synergizes with the three receptors to further enhance STAT1 expression. These novel findings establish a novel link between the mitogenic ErbB signaling pathway and the inflammatory pathway mediated by STAT1. The oncogenic transcription factor STAT3 binds to the STAT1 promoter and synergizes with nuclear EGFR to significantly enhance STAT1 gene expression.
SIGNOR-263650
P08238
O14727
2
binding
down-regulates
0.388
The present studies demonstrate that heat shock protein 90 (hsp90) forms a cytosolic complex with apaf-1 and thereby inhibits the formation of the active complex.
SIGNOR-81043
P19235
O60674
0
phosphorylation
up-regulates activity
0.812
JAK2 in turn phosphorylates several tyrosine residues on the EpoR-cytosolic domain and probably on JAK2 itself that serve as docking sites for SH2 or protein tyrosine binding domains of downstream signal transduction proteins such as STAT5, phosphatidylinositol 3-kinase, Shc, and tyrosine phosphatases SHP1 and SHP2
SIGNOR-251351
Q96LB2
P19086
2
binding
up-regulates activity
0.2
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.
SIGNOR-257326
Q5VWQ8
P49841
2
binding
up-regulates activity
0.311
DAB2IP activates GSK-3β and antagonizes Wnt-mediated EMT. GSK-3β appears to directly associate with DAB2IP. Because DAB2IP is not a phosphatase, the mechanism of GSK-3β activation by DAB2IP is likely mediated by a separate phosphatase associated within this complex. PP2A is critical for DAB2IP-mediated GSK-3β activation and MET responses.
SIGNOR-254752
Q9GZQ8
Q96A56
2
binding
up-regulates
0.297
Tp53inp1-lc3 interaction occurs via a functional lc3-interacting region (lir)
SIGNOR-196673
P19367
P31749
2
binding
up-regulates
0.445
The glucose dependence of the antiapoptotic effects of growth factors and akt plus a strong correlation between akt-regulated mitochondrial hexokinase association and apoptotic susceptibility suggest a major role for hexokinases in these effects.
SIGNOR-252495
Q14332
Q9ULT6
0
ubiquitination
down-regulates
0.292
Znrf3 is associated with the wnt receptor complex, and inhibits wntby promoting the turnover of frizzled and lrp6.
SIGNOR-197417
Q9Y6K9
Q9BVN2
0
null
up-regulates quantity by stabilization
0.308
NESCA interacts with the IKK complex by the N-terminal region of NEMO. This experiment revealed that the overexpression of NESCA completely abolished the TRAF6-mediated polyubiquitination of NEMO, as it appears by using either anti-HA (Fig. 5A) or anti-NEMO (Fig. 5B) antibodies on immunoprecipitated extracts.
SIGNOR-272775
P63092
P21918
2
binding
up-regulates activity
0.482
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0.
SIGNOR-256771
P00441
Q9NX47
0
ubiquitination
down-regulates quantity by destabilization
0.2
Mitochondrial ubiquitin ligase MITOL ubiquitinates mutant SOD1 and attenuates mutant SOD1-induced reactive oxygen species generation
SIGNOR-272982
P50148
Q9H2D6
2
binding
up-regulates activity
0.2
We show that the C-terminal Rho-specific DH-PH cassette of Trio is similarly activated by Galpha(q)
SIGNOR-256494
P47712
Q16539
0
phosphorylation
up-regulates activity
0.668
These results provide the first direct evidence that p38 kinase is responsible for cpla2 phosphorylation in sfllrn-stimulated platelets and is involved in the early phosphorylation of cpla2 in thrombin-stimulated platelets
SIGNOR-44673
Q08881
P42680
1
phosphorylation
up-regulates
0.407
Tec family protein tyrosine kinases (tfks) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. Further activation occurs within the sh3 domain via a transphosphorylation mechanism. Here, we could confirm that y223 is the only site in the btk-sh3 domain being detectably phosphorylated
SIGNOR-98090
Q96SB3
Q00535
0
phosphorylation
down-regulates quantity
0.396
CDK5 decreased the expression of both spinophilin (30%) and neurabin (64%).|This suggests that CDK5 phosphorylation of spinophilin at Ser17 is not responsible for the CDK5 dependent increase in the spinophilin and PP1 association.
SIGNOR-279453
Q86UR5
Q9UQM7
0
phosphorylation
up-regulates
0.347
Two serine residues in rim1 (ser-241 and ser-287) and one serine residue in rim2 (ser-335) were required for 14-3-3 binding. Incubation with ca2+/calmodulin-dependent protein kinase ii greatly stimulated the interaction of recombinant n-terminal rim but not the s241/287a mutant with 14-3-3,
SIGNOR-103890
Q16566
P16949
1
phosphorylation
down-regulates
0.49
Serine 16 of oncoprotein 18 is a major cytosolic target for the ca2+/calmodulin-dependent kinase-gr.
SIGNOR-34743
P46531
P24863
0
phosphorylation
down-regulates
0.48
Purified recombinant cycc:cdk8 phosphorylates the notch icd within the tad and pest domains, and expression of cycc:cdk8 strongly enhances notch icd hyperphosphorylation and pest-dependent degradation by the fbw7/sel10 ubiquitin ligase in vivo.
SIGNOR-130592
P14635
P38936
2
binding
down-regulates
0.829
P21-mediated degradation of cyclin b1 in response to dna damage is necessary for the maintenance of g2 cell cycle arrest.
SIGNOR-183498
P10163
Q96L73
0
transcriptional regulation
up-regulates quantity by expression
0.342
We here demonstrate that NSD1 could bind to the promoter regions of PRB4 and activate promoter activity by reducing the binding of H3K27me2 and increasing the binding of H3K36me2 on PRB4 promoter.
SIGNOR-268459
Q86X55
Q01196
1
methylation
down-regulates activity
0.282
We have found that PRMT4 is highly expressed in HSPCs, where it functions as an inhibitor of myeloid differentiation (Figure 7G). In these cells, PRMT4 methylates RUNX1 at R223, promoting the assembly of a DPF2-containing transcriptional co-repressive complex, and repressing transcription at the miR-223 locus.
SIGNOR-261967
P09651
Q13148
0
post transcriptional regulation
up-regulates
0.406
TDP-43 regulates the alternative splicing of hnRNP A1 to yield an aggregation-prone variant in amyotrophic lateral sclerosis
SIGNOR-262824
P12931
Q13224
1
phosphorylation
up-regulates activity
0.559
We have investigated the tyrosine phosphorylation of NMDA receptor subunits NR2A and NR2B by exogenous Src Phosphorylation-site specific antibodies identified NR2B Tyr1472 as a phosphorylation site for intrinsic PSD tyrosine kinases
SIGNOR-247180
Q9UPW6
Q15797
0
transcriptional regulation
up-regulates quantity
0.2
Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation
SIGNOR-268934
Q15746
Q05682
1
phosphorylation
down-regulates
0.641
Phosphorylation of caldesmon by myosin light chain kinase increases its binding affinity for phosphorylated myosin filaments.
SIGNOR-166049
P10070
Q6PHR2
0
phosphorylation
up-regulates activity
0.621
We show that ULK3 is able to phosphorylate three mammalian GLI proteins in vitro
SIGNOR-260798
O00548
P51608
0
transcriptional regulation
down-regulates quantity by repression
0.2
As the first step to reveal how MeCP2 phosphorylation may regulate Notch signaling, we conducted chromatin immunoprecipitation (ChIP) experiment to determine whether the phosphor-mutant MeCP2 protein has altered promoter occupancy at the promoters of Dll1 and Notch1. We found increased binding of the phosphor-mutant protein at the promoters of both Dll1 and Notch1 
SIGNOR-264674
Q96J02
Q9UBN4
1
ubiquitination
down-regulates activity
0.35
Ubiquitination of TRPV4 is dramatically increased by the HECT (homologous to E6-AP carboxyl terminus)-family ubiquitin ligase AIP4 without inducing degradation of this channel. Instead, AIP4 promotes the endocytosis of TRPV4 and decreases its amount at the plasma membrane.
SIGNOR-272624
Q9H6E5
Q05655
0
phosphorylation
up-regulates activity
0.2
PKCdelta associates with and directly phosphorylates Star-PAP.
SIGNOR-279385
Q01484
P11532
1
relocalization
up-regulates quantity
0.53
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-266712
P50613
P21127
1
phosphorylation
up-regulates activity
0.335
We conclude that CDK7 phsphorylates Cdk11, dependent on the conserved Thr219 residue in the CDK11 T loop, and it is therefore likely to be a genuine Cdk11 activating kinase
SIGNOR-245871
Q15759
P05787
1
phosphorylation
up-regulates
0.427
Keratin 8 (k8) serine 73 occurs within a relatively conserved type ii keratin motif . Here we show that ser-73 is exclusively phosphorylated in vitro by p38 mitogen-activated protein kinase. The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing keratin mutations can modulate keratin phosphorylation and organization, which may affect disease pathogenesis.
SIGNOR-114063
P06493
Q96JH7
1
phosphorylation
down-regulates activity
0.537
We clarified that VCIP135, an essential factor in both p97 membrane fusion pathways, is phosphorylated on Threonine-760 and Serine-767 by Cdc2 at mitosis and that this phosphorylated VCIP135 does not bind to p97. 
SIGNOR-265038
P08922
P18031
0
dephosphorylation
down-regulates
0.374
In an approach to gain insight into the sequence-dependent dephosphorylation of multiple phosphotyrosyl-containing peptides by the phosphatases shp-1 and ptp1b, we applied a chromatographic technique for the analysis of the dephosphorylation products.
SIGNOR-154199
P15172
P06400
2
transcriptional regulation
up-regulates quantity by expression
0.394
Here we report that, at the onset of differentiation, activation by MyoD of the Rb, p21, and cyclin D3 genes occurs in the absence of new protein synthesis and with the requirement of the p300 transcriptional coactivator.
SIGNOR-238532
P35222
P25054
2
binding
down-regulates quantity
0.921
Apc binds to both b-catenin and axin, and could shuttle b-catenin from the plasma membrane and nucleus to the cytoplasmic axin complex. APC cooperates with Axin to promote the phosphorylation of _-catenin by GSK3 [which requires priming phosphorylation by casein kinase 1, _-isoform (CK1_)].
SIGNOR-177230
Q9NZ72
P49840
0
phosphorylation
up-regulates activity
0.252
Altogether, these results indicate that CDK5 phosphorylates similarly serines 68 and 73, whereas ERK2 targets mostly serine 68 and GSK-3beta mostly serine 60.|This observation may support the hypothesis of a specific localization of stathmin 3 depending on its phosphorylation by GSK-3beta
SIGNOR-264883
Q13153
Q15831
0
phosphorylation
down-regulates
0.247
Lkb1 suppresses p21-activated kinase-1 (pak1) by phosphorylation of thr109 in the p21-binding domain.
SIGNOR-164814
Q13526
P46531
2
binding
up-regulates
0.384
Prolyl-isomerase pin1 interacts with notch1 and affects notch1 activation. Pin1 potentiates notch1 cleavage by gamma-secretase, leading to an increased release of the active intracellular domain and ultimately enhancing notch1. pin1 potentiates notch1 cleavage by gamma-secretase
SIGNOR-183461
P01112
P49354
0
null
up-regulates activity
0.413
Major investments have been made to target Ras through indirect routes. Inhibition of farnesyl transferase to block Ras maturation has failed in large clinical trials.
SIGNOR-242568
Q15637
P35637
2
binding
down-regulates
0.561
We speculate that zfm1 may inhibit transcription driven by the ntds of tls
SIGNOR-58967
Q13557
P51787
1
phosphorylation
down-regulates activity
0.2
CaMKII regulates KCNQ1 at S484 during sustained β-AR stimulation to inhibit IKs. The ability of CaMKII to inhibit IKs may contribute to arrhythmogenicity during HF.
SIGNOR-275479
Q8IZL2
Q99466
2
binding
up-regulates
0.86
We show here identification of two new members of human mam family (human mastermind-2 (hmam-2) and human mastermind-3 (hmam-3)), which retain characteristics similar to human mastermind-1 (hmam-1) and drosophila mastermind. Both hmam-2 and hmam-3 stabilize and participate in the dna-binding complex rbp-j/cbf-1 protein and the notch intracellular domains that serve as intermediates of the signaling. Both hmam-2 and hmam-3 enhanced the activation of transcription from a target promoter by notch signaling. However, we also show evidence that the activation of the target promoter by notch3 and notch4 is more efficiently potentiated by hmam-2 than by hmam-1 or -3.
SIGNOR-94279
Q96A56
Q9GZQ8
2
binding
up-regulates
0.297
Tp53inp1-lc3 interaction occurs via a functional lc3-interacting region (lir)
SIGNOR-196673
Q92949
O75602
1
transcriptional regulation
up-regulates quantity by expression
0.447
FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).
SIGNOR-266935
P21860
Q96JA1
0
ubiquitination
down-regulates
0.434
We report upregulation of lrig1 transcript and protein upon egf stimulation, and physical association of the encoded protein with the four egfr orthologs of mammals. Upregulation of lrig1 is followed by enhanced ubiquitylation and degradation of egfr. The underlying mechanism involves recruitment of c-cbl, an e3 ubiquitin ligase that simultaneously ubiquitylates egfr and lrig1 and sorts them for degradation.
SIGNOR-139951
Q13485
O15198
0
phosphorylation
up-regulates
0.685
Whereas alk5 signalling is mediated by phosphorylation of smad2 and smad3 proteins, alk1 signalling is mediated by smad1, smad5, and smad8. Activated smads form a complex with the common smad (co-smad; smad4 in mammals) and shuttle into the nucleus.
SIGNOR-168740
P17302
P78415
0
transcriptional regulation
down-regulates quantity by repression
0.278
Irx3 directly represses Cx43 transcription 
SIGNOR-266044
Q8WXD0
P04090
2
binding
up-regulates
0.708
Lgr7 and lgr8, are capable of mediating the action of relaxin through an adenosine 3',5'-monophosphate (camp)-dependent pathway.
SIGNOR-114585
Q00535
Q8NER1
1
phosphorylation
up-regulates activity
0.2
TNF-alpha overexpression increased Cdk5-mediated phosphorylation of TRPV1 at T407.|These results suggest that the activation of Cdk5 by p35 enhances the response of TRPV1 to capsaicin, probably by phosphorylation of the channel [34].
SIGNOR-278437
Q06418
Q13191
2
phosphorylation
up-regulates activity
0.35
To test whether phosphorylation of Cbl-b at Tyr133 and/or Tyr363 by Tyro3 is important for its ubiquitin ligase function, we examined the ubiquitination of the Cbl-b mutants and Tyro3.
SIGNOR-279577
P27361
P49715
1
phosphorylation
down-regulates
0.371
Ccaat/enhancer-binding protein alpha (c/ebpalpha) is one of the key transcription factors that mediate lineage specification and differentiation of multipotent myeloid progenitors into mature granulocytes.Here we report that inducers of monocyte differentiation inhibit the alternate cell fate choice, that of granulopoiesis, through inhibition of c/ebpalpha. This inhibition is mediated by extracellular signal-regulated kinases 1 and/or 2 (erk1/2), which interact with c/ebpalpha through an fxfp docking site and phosphorylate serine 21.
SIGNOR-120570
P37840
P53355
0
phosphorylation
up-regulates quantity
0.27
We demonstrated that DAPK1 directly phosphorylates \u03b1-synuclein at Ser129, and induces the formation of insoluble \u03b1-synuclein aggregates.
SIGNOR-278440
P30307
P53350
0
phosphorylation
up-regulates
0.804
The nuclear accumulation of active m-phase promoting factor (mpf) during prophase is thought to be essential for coordinating m-phase events in vertebrate cells. The protein phosphatase cdc25c, an activator of mpf, enters the nucleus to keep mpf active in the nucleus during prophase. these results suggest that plk1 phosphorylates cdc25c on ser198 and regulates nuclear translocation of cdc25c during prophase.
SIGNOR-115993
O43293
P40429
1
phosphorylation
up-regulates
0.402
Zipk phosphorylates l13a in vitro / l13a is phosphorylated on ser77 in vitro
SIGNOR-182117
P06493
Q14CS0
1
phosphorylation
down-regulates activity
0.2
At mitosis, Cdc2 kinase phosphorylates p47 on Serine-140 and p37 on Serine-56 and Threonine-59, respectively. The phosphorylated p47 and p37 are unable to bind to Golgi membranes, resulting in mitotic inhibition of the p97/p47 and the p97/p37 pathways, respectively.
SIGNOR-265041
P11171
Q12959
1
relocalization
up-regulates activity
0.472
Together, our results demonstrate that in addition to the N-terminal targeting domain, the alternatively spliced I3 insertion plays a critical role in recruiting hDlg to the lateral membrane in epithelial cells via its interaction with protein 4.1R.
SIGNOR-266011
Q8TEB1
Q17RS7
2
binding
down-regulates quantity by destabilization
0.2
(WDR23) isoforms differentially ubiquitinate (GEN1). In the presence of the necessary components for a successful ubiquitination reaction (CUL4A-DDB1-WDR23 complex, UBE1, UBE2D1, ubiquitin, and ATP) GEN1 receives the addition of ubiquitin in a time dependent manner.
SIGNOR-272258
Q99626
Q9HAW8
1
transcriptional regulation
up-regulates quantity by expression
0.257
Using gel shift and functional assays, HNF1alpha was demonstrated to bind to and activate the UGT1A8, -1A9, and -1A10 promoters. In contrast, Cdx2 bound to and activated the UGT1A8 and -1A10 promoters but could not activate the UGT1A9 promoter.
SIGNOR-253968
P08754
P41595
2
binding
up-regulates activity
0.265
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.
SIGNOR-256886
Q04206
Q9Y2K7
0
demethylation
down-regulates
0.459
Fbxl11 and nsd1 have opposite effects on nf-kb; both bind to p65 subunit after activation of nf-kb. / nsd1 activates nf-kb and reverses the inhibitory effect of fbxl11 / these data confirm that fbxl11 and nsd1 constitute an enzyme pair that methylates and demethylates p65 on k218 and 221 in response to cytokine stimulation.
SIGNOR-163384
Q9Y6R4
P46734
1
phosphorylation
up-regulates activity
0.639
These results, therefore, suggest that mtk1 directly phosphorylates and activates mkk3, mkk6 and sek1.
SIGNOR-50891
O43768
Q96GX5
0
phosphorylation
up-regulates activity
0.732
We identified cyclic adenosine monophosphate€“regulated phosphoprotein 19 (Arpp19) and -Endosulfine as two substrates of Gwl that, when phosphorylated by this kinase, associate with and inhibit PP2A, thus promoting mitotic entry.
SIGNOR-243690
Q07352
Q15418
0
phosphorylation
down-regulates activity
0.2
These results indicate that RSK1 directly phosphorylates the C-terminus of ZFP36L1 downstream of ERK, and inhibits the Messenger RNA destabilization activity of ZFP36L1.|These results indicate that RSK1 directly phosphorylates the C-terminus of ZFP36L1 downstream of ERK, and inhibits the mRNA destabilization activity of ZFP36L1.
SIGNOR-279280
Q9NXA8
P54868
1
post translational modification
up-regulates activity
0.343
We demonstrate that SIRT5 regu-lates succinylation of the rate-limiting ketogenicenzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2(HMGCS2) both in vivo and in vitro.|Succinylation of Lysine Residues within the SubstrateBinding Pocket Inhibits HMGCS2 Activity|Here, we use a label-freequantitative proteomic approach to characterizethe lysine succinylome in liver mitochondria and itsregulation by the desuccinylase SIRT5
SIGNOR-267641
Q09472
Q10571
2
binding
up-regulates
0.342
Our results indicate that mn1 is a transcription coactivator rather than a sequence-specific transcription factor, and that it may stimulate rar/rxr-mediated transcription through interaction with p160 and p300.
SIGNOR-97899
P02649
Q99523
2
binding
up-regulates quantity
0.427
Here, we identified the pro-neurotrophin receptor sortilin as major endocytic pathway for clearance of APOE/Aβ complexes in neurons. Sortilin binds APOE with high affinity. Lack of receptor expression in mice results in accumulation of APOE and of Aβ in the brain and in aggravated plaque burden. Sortilin interacts with all human APOE isoforms.
SIGNOR-273721
P08754
Q9NQS5
2
binding
up-regulates activity
0.277
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.
SIGNOR-256847
Q96EB6
Q9Y618
1
null
up-regulates
0.494
In differentiated adipocyte cell lines, SIRT1 inhibits adipogenesis and enhances fat mobilization through lipolysis by suppressing the activity of PPARγ. SIRT1 achieves this by promoting the assembly of a corepressor complex, involving NCoR1 and SMRT, on the promoters of PPARγ target genes to repress their transcription.
SIGNOR-253506
O14578
Q96GD4
0
phosphorylation
down-regulates activity
0.283
Finally, Aurora B phosphorylates CIT-K to control its localization and interaction with central spindle partners.|Together these findings indicate that CIT-K is an Aurora B substrate and that Aurora B phosphorylation at S699 dampens the association of CIT-K with KIF23 and the chromosomal passenger complex in order to reduce CIT-K accumulation at the spindle midzone in early cytokinesis.
SIGNOR-279140
Q02156
Q96A00
1
phosphorylation
up-regulates activity
0.261
A major kinase for GPCR‐induced CPI‐17 phosphorylation is PKC which is activated by the PLCbeta‐produced signaling messenger diacylglycerol (DAG). It phosphorylates CPI‐17 at Thr38 residue that directly docks at the active site of MLCP, thereby inhibiting its activity and promoting an increase of phosphorylation of myosin and of other MLCP.
SIGNOR-249258
P19838
P12644
1
transcriptional regulation
down-regulates quantity by repression
0.2
 The effect of TNF-alpha on the Bmp4 promoter is mediated through NF-kB.
SIGNOR-266086
P23246
P07101
1
transcriptional regulation
down-regulates quantity by repression
0.2
It has been reported that DJ-1 is a neuroprotective transcriptional co-activator that sequesters a transcriptional co-repressor polypyrimidine tract-binding protein-associated splicing factor (PSF) from the TH gene promoter.
SIGNOR-271697
P18075
Q13253
2
binding
down-regulates activity
0.852
We report the crystal structure of the antagonist Noggin bound to BMP-7, which shows that Noggin inhibits BMP signalling by blocking the molecular interfaces of the binding epitopes for both type I and type II receptors.
SIGNOR-256484
P84022
P15172
2
binding
down-regulates activity
0.731
We show that the TGF-beta intracellular effector Smad3, but not Smad2, mediates the inhibition of myogenic differentiation in MyoD-expressing C3H10T1/2 cells and C2C12 myoblasts by repressing the activity of the MyoD family of transcriptional factors.
SIGNOR-252071
Q96D59
Q07817
1
ubiquitination
down-regulates quantity by destabilization
0.385
As an E3 ligase, RNF183 ubiquitinates Bcl-xL, causing its degradation and subsequent apoptosis.
SIGNOR-278595
Q13950
P56524
0
deacetylation
down-regulates activity
0.524
HDAC4 and HDAC5 deacetylate Runx2, allowing the protein to undergo Smurf-mediated degradation
SIGNOR-227547
Q8N8S7
Q70E73
2
binding
up-regulates activity
0.544
Here we show that Lpd is a substrate of Abl kinases and binds to the Abl SH2 domain. Phosphorylation of Lpd positively regulates the interaction between Lpd and Ena/VASP proteins.
SIGNOR-268425