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P55072
P26045
0
dephosphorylation
down-regulates activity
0.478
Identification of VCP as a substrate of PTPH1in vivo.|The tyrosines (Tyr796 and Tyr805) at the C terminus of VCP have been reported to be the major sites of phosphorylation, with Tyr805 accounting for more than 90% of the tyrosine phosphorylation on the protein |The Y796F/Y805F VCP mutant was not associated with any of the PTPH1 constructs.
SIGNOR-248460
Q13153
P27361
0
phosphorylation
down-regulates
0.337
Activated erk can phosphorylate t292 in the prs, and this blocks the ability of pak to phosphorylate s298 and of rac-pak signaling to enhance mek1-erk complex formation.
SIGNOR-123074
Q13158
P53350
0
phosphorylation
down-regulates activity
0.459
Fas-associated death domain-containing protein (FADD) was first identified as an adapter molecule involved in formation of a death-inducing signaling complex upon Fas stimulation| Plk1 phosphorylates fadd at ser-194 in response to treatment with taxol Phosphorylation by polo-like kinase 1 induces the tumor-suppressing activity of FADD
SIGNOR-168204
Q07955
P21127
0
phosphorylation
up-regulates activity
0.283
In comparison, CLK1 expression leads to speckle dissolution and diffuse GFP-SRSF1 localization in the nucleus.|We showed that CLK1 phosphorylates SRSF1 at approximately 18 sites inducing a gel shift from 35 to about 38 kDa on SDS-PAGE (XREF_FIG, upper panel).
SIGNOR-279499
P52945
P01308
1
transcriptional regulation
up-regulates quantity by expression
0.643
In conclusion, Pdx1 confers the expression of pancreatic β-cell-specific genes, such as genes encoding insulin, islet amyloid polypeptide, Glut2, and Nkx6.1.
SIGNOR-255541
Q13873
P36894
2
phosphorylation
up-regulates
0.631
Bmp ligands bind to the bmp receptors bmpr1 and bmpr2, and bmpr2 then phosphorylates and activates bmpr1.
SIGNOR-180545
P04629
P06241
0
phosphorylation
up-regulates activity
0.254
Here, we demonstrate that Fyn can directly phosphorylate the intracellular domain of TrkA and that its kinase activity towards Trk is increased by GPCR stimulation ( Fig. 4 ).
SIGNOR-279410
P28482
P31749
0
phosphorylation
up-regulates activity
0.533
AKT1 stimulated PLD activity via activation of ERK.|AKT1 actually phosphorylated ERK2 as a substrate (K(m) 1 \u03bcm).
SIGNOR-279136
Q92585
Q99466
2
binding
up-regulates
0.71
Maml1 binds to the ankyrin repeat domain of all four mammalian notch receptors, forms a dna-binding complex with icn and rbp-jkappa, and amplifies notch-induced transcription of hes4
SIGNOR-84916
Q09472
Q9UPU5
0
deubiquitination
up-regulates quantity by stabilization
0.271
In this study, several cancer-related proteins (Bax, p300, E2F4 and securin) have been proven to be substrates of ubiquitin-specific peptidase 24 (USP24), and relevance has been shown between USP24 and its substrates in samples from clinical lung cancer patients. |Knockdown of USP24 decreases Bax and p300 levels
SIGNOR-275607
Q7L591
P62993
2
binding
up-regulates activity
0.554
An adaptor protein Dok-3 mediates the suppressive function of LYN. The Dok-3 phosphorylated by LYN upon BCR stimulation forms a complex with GRB2, which allows it to enter into the signalosome and associate with activation of SHIP protein. This translocation facilitates the efficient inhibition of PLCc2 and SYK from activation, subsequently resulting in the suppression of downstream Ca2+ signaling.
SIGNOR-268448
P49841
P46527
1
phosphorylation
up-regulates quantity by stabilization
0.389
GSK-3\u03b2 phosphorylates p27 Kip1 at S160 and S161, resulting in increased p27 Kip1 stability [ xref ].
SIGNOR-278938
P08069
P05019
2
binding
up-regulates activity
0.956
Binding of IGF1 to its receptor leads to activation of its intrinsic tyrosine kinase and autophosphorylation, thus generating docking sites for insulin receptor substrate (IRS), which is also phosphorylated by the IGF1 receptor.
SIGNOR-175662
P28482
C9JLW8
1
phosphorylation
down-regulates activity
0.2
When phosphorylated by ERK, MCRIP1 dissociates from CtBP, allowing CtBP to interact with ZEB1. In this manner, the CtBP co-repressor complex is recruited to, and silences, the E-cadherin promoter by inducing chromatin modifications.| While substitution of S4 or S18 with Ala did not affect the phosphorylation of MCRIP1 by ERK, substitution of either S21 or T30 significantly reduced MCRIP1 phosphorylation
SIGNOR-264774
P17600
Q13153
0
phosphorylation
up-regulates activity
0.349
Synapsin I is phosphorylated at Ser603 by p21-activated kinases. the Ser603 residue must be one of the pivotal sites for the release
SIGNOR-250235
P03956
Q8TF68
0
transcriptional regulation
up-regulates quantity by expression
0.307
Luciferase activity driven by the MMP-1 promoter also increased by 2.5- to 3-fold. In contrast, CIZ had no effect on the luciferase activity from the MMP-1 promoter that was mutated at the CIZ binding consensus sequence. These results show that the CIZ transactivates the MMP-1 promoter through this sequence.
SIGNOR-266229
P45984
Q9UQF2
2
phosphorylation
up-regulates activity
0.769
Recruitment of jnk to jip1 and jnk-dependent jip1 phosphorylation regulates jnk module dynamics and activation it was observed that phosphorylation by jnk of jip1 on thr-103 and not other phosphorylated jip1 residues is necessary for the regulation of dlk association with jip1, dlk activation, and subsequent module activation.
SIGNOR-101201
Q8TEA8
O75419
2
binding
up-regulates activity
0.504
The DNA unwinding element (DUE)-binding protein (DUE-B) binds to replication origins coordinately with the minichromosome maintenance (MCM) helicase and the helicase activator Cdc45 in vivo, and loads Cdc45 onto chromatin in Xenopus egg extracts. In egg extracts alanine mutation of the DUE-B C-terminal phosphorylation sites blocks Cdc45 loading and inhibits DNA replication. The effects of DUE-B C-terminal phosphorylation reveal a novel S phase kinase regulatory mechanism for Cdc45 loading and MCM helicase activation.
SIGNOR-273973
P10276
P10827
2
binding
up-regulates
0.432
We report that the retinoic acid receptors (rars), a distinct class of nuclear receptors, are also efficient heterodimer partners for trs.
SIGNOR-133231
P33981
P24941
0
phosphorylation
up-regulates quantity by stabilization
0.411
Cdk2 phosphorylates Mps1 at T468, attenuating the function of a degradation signal found in amino acids 420\u2013507 (encoded by exons 12 and 13) and allowing the accumulation of a centrosomal pool of Mps1 that represents no more than 10% of total cellular Mps1 ( xref ).
SIGNOR-279398
Q9UN70
Q9Y5H9
2
binding
up-regulates activity
0.2
The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.
SIGNOR-265674
Q14653
P49841
0
phosphorylation
up-regulates activity
0.346
Invitro, both GSK3alpha and GSK3beta phosphorylate IRF3 at the linker region.
SIGNOR-279182
P36897
Q9HCE7
0
polyubiquitination
down-regulates quantity by destabilization
0.694
Here we show that Smurf1, an E3 ubiquitin ligase for bone morphogenetic protein-specific Smads, also interacts with Smad7 and induces Smad7 ubiquitination and translocation into the cytoplasm. In addition, Smurf1 associates with TbetaR-I via Smad7, with subsequent enhancement of turnover of TbetaR-I and Smad7. 
SIGNOR-272943
P17612
P48058
1
phosphorylation
up-regulates
0.429
We found that pka phosphorylation of the ampa receptor subunits glur4 and glur1 directly controlled the synaptic incorporation of ampa receptors in organotypic slices from rat hippocampus.
SIGNOR-97550
Q15303
P42229
1
phosphorylation
up-regulates activity
0.811
ERBB4 directly activates STAT5A, in part, through phosphorylation of STAT5A at the regulatory Tyr-694.|ERBB4/HER4 potentiates STAT5A transcriptional activity by regulating novel STAT5A serine phosphorylation events.
SIGNOR-279711
P53355
Q86YT6
0
polyubiquitination
down-regulates quantity by destabilization
0.437
Transient expression of DIP-1 in HeLa cells antagonizes the anti-apoptotic function of DAPK to promote a caspase-dependent apoptosis. These studies also demonstrate that DAPK is an in vitro and in vivo target for ubiquitination by DIP-1, thereby providing a mechanism by which DAPK activities can be regulated through proteasomal degradation.
SIGNOR-272602
P10147
P32246
2
binding
up-regulates activity
0.71
The investigators showed that myoblasts constitutively express receptors for CCL2 (CCR2), CCL3 (CCR1 and CCR5), and CCL4 (CCR5), and that stimulation with either CCL2 or CCL4 was sufficient to promote myoblast proliferation. 
SIGNOR-255114
Q9H2D6
P53350
0
phosphorylation
up-regulates
0.335
Here we show that tara is a novel polo-like kinase 1 (plk1) target protein. Plk1 interacts with and phosphorylates tara in vivo and in vitro. Actually, the thr-457 in tara was a bona fide in vivo phosphorylation site for plk1. Interestingly, we found that the centrosomal localization of tara depended on the thr-457 phosphorylation and the kinase activity of plk1
SIGNOR-198353
Q14118
Q9P2S2
2
binding
up-regulates activity
0.262
The DGC is potentially recruited to the postsynaptic membrane though a direct neurexin–dystroglycan interaction and an indirect interaction with NL2 via the synaptic scaffolding protein S-SCAM.
SIGNOR-265460
P61586
Q03113
2
binding
up-regulates
0.558
Ga12/13 recruitment of rho-gefs causes rhoa activation and f-actin assembly, which promotes lats1/lat2 inactivation by an unknown, but myosin-independent mechanism.
SIGNOR-192108
P42684
Q13671
2
phosphorylation
up-regulates activity
0.615
These findings suggested that RIN1 is phosphorylated by both ABL1 and ABL2.
SIGNOR-279676
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
P62993
P09619
2
binding
up-regulates
0.68
A pathway leading to activation of the gtp-binding protein ras involves the adaptor molecule grb2. Here we show that tyr-716, a novel autophosphorylation site in the pdgf beta-receptor kinase insert, mediates direct binding of grb2 in vitro and in vivo.
SIGNOR-34765
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
Q9BY11
O96013
0
phosphorylation
up-regulates activity
0.295
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-263023
P00533
P03372
1
phosphorylation
up-regulates
0.59
Activation of estrogen receptor-alpha (eralpha) by growth factors in the absence of estrogen is a well-documented phenomenon.Egfr tyrosine kinase in vitro stimulated the phosphorylation of recombinant er
SIGNOR-115734
P24394
P35568
1
phosphorylation
up-regulates
0.566
Irs-1 and a homologous protein, irs-2 (also known as 4-phosphotyrosine substrate), are recruited to phosphorylated y497 of IL-4R After ligand binding, leading to phosphorylation and activation of irs-1 and irs-2.
SIGNOR-100768
Q96L34
P10636
1
phosphorylation
down-regulates activity
0.419
AMPK phosphorylation inhibits tau binding of microtubules. In order to study further the phosphorylation of tau by AMPK, we compared phosphorylation of tau by MARK4 or AMPK using a panel of phospho-tau antibodies (Figure 2A). Five phosphorylation sites common to both kinases were identified (Thr231, Ser262, Ser356, Ser396 and Ser422). In addition, AMPK, but not MARK4, was capable of phosphorylating Ser214 (Figure 2A).
SIGNOR-273935
Q16654
P08559
1
phosphorylation
down-regulates
0.686
Mammalian pyruvate dehydrogenase (?2_2) (e1) is regulated by phosphorylation-dephosphorylation, catalyzed by the e1-kinase and the phospho-e1-phosphatase.
SIGNOR-33201
P45983
Q9UQF2
2
phosphorylation
up-regulates activity
0.879
After mapping JNK-dependent JIP1 phosphorylation sites and testing their functional significance, it was observed that phosphorylation by JNK of JIP1 on Thr-103 and not other phosphorylated JIP1 residues is necessary for the regulation of DLK association with JIP1, DLK activation, and subsequent module activation. The data presented corroborates our previous observations using endogenous proteins, demonstrates that JNK binding to JIP1 is necessary for module activation, and shows that activation of JIP1-JNK module dynamics requires phosphorylation of JIP1 on Thr-103 by JNK. and Thr-205 are phosphorylated directly by JNK after JNK binds to JIP1.
SIGNOR-250128
O96017
P33981
2
phosphorylation
up-regulates
0.292
Phosphorylation at ttk/hmps1 thr288 is enhanced by chk2 in vitro and in vivo after ir
SIGNOR-242665
Q6IMN6
P01178
1
post transcriptional regulation
up-regulates quantity by stabilization
0.2
Transcriptional and post-transcriptional regulation of oxytocin and vasopressin gene expression by CREB3L1 and CAPRIN2|Altogether, the data indicate that CAPRIN2 binds Oxt mRNA |Therefore, we propose that CAPRIN2 facilitates post-transcriptional modifications that increase Oxt transcript stability.
SIGNOR-268556
Q14790
Q9H4B4
0
phosphorylation
up-regulates activity
0.338
Furthermore, we identify caspase-8 as a new substrate for Plk3. Phosphorylation occurs on T273 and results in stimulation of caspase-8 proapoptotic function.
SIGNOR-272995
P02647
P02649
1
relocalization
up-regulates activity
0.738
ApoA-I stimulates apoE secretion in mature human adipocytes. The regulation of apoE secretion by apoA-I, is neither dependent upon an increase in gene transcription, nor upon increased release from the Golgi. It may therefore be assumed that, in macrophage models, apoE is stored mainly in the cytoplasm and/or on the cell surface, with apoA-I enabling secretion of this cytoplasmic pool
SIGNOR-252105
P30874
P63096
2
binding
up-regulates activity
0.582
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-256684
Q02747
P25092
2
binding
up-regulates
0.771
Guanylins activate two receptors, gc-c and ok-gc, which are expressed in intestine and/or kidney
SIGNOR-78096
Q96QT6
Q04726
2
binding
up-regulates activity
0.2
We have cloned and characterized a new member of the PHD zinc finger family called Pf1 that interacts with two global transcription corepressors: mSin3A and TLE. Pf1 interacts with TLE. The Groucho/TLE proteins are members of an abundant corepressor family, and we hypothesized that Pf1 might interact with TLE family members. Together, these data suggest that in the absence of interactions with mSin3A, Gal4-Pf1 (102–273 L212P/A216P)-dependent repression can be attributed to interaction with endogenous TLE.
SIGNOR-266993
O00308
P60484
1
ubiquitination
down-regulates quantity by destabilization
0.632
We have shown that WWP2 interacts with and ubiquitylates PTEN, promoting its degradation.
SIGNOR-278650
P54756
O43921
2
binding
up-regulates
0.818
Ephrin-a ligands (named ephrin-a1_ephrin-a5) are anchored in the plasma membrane through a gpi-linkage, and each can bind any of the epha subclass of receptors (epha1_epha8)
SIGNOR-65416
P32238
P06307
2
binding
up-regulates
0.786
Cck8 interacts with nanomolar affinities with two different receptors designated cck-a and cck-b
SIGNOR-68474
P17096
Q9H2X6
0
phosphorylation
down-regulates
0.493
Here, we found that hipk2 phosphorylates hmga1a at ser-35, thr-52, and thr-77, and hmga1b at thr-41 and thr-66. In addition, we demonstrated that cdc2, which is known to phosphorylate hmga1 proteins, could induce the phosphorylation of hmga1 proteins at the same ser/thr sites. we found that the hipk2-phosphorylated hmga1a reduced the binding affinity of hmga1a to human germ line promoter, and the drop in binding affinity induced by hipk2 phosphorylation was lower than that introduced by cdc2 phosphorylation.
SIGNOR-158620
Q96IZ0
P19544
2
binding
down-regulates activity
0.501
We identified par-4 (for prostate apoptosis response) as a WT1-interacting protein that itself functions as a transcriptional repressor. Functionally, par-4 inhibited transcription activated by WT1
SIGNOR-240596
Q15831
Q13315
0
phosphorylation
up-regulates
0.571
We demonstrate that both dna-pk and atm efficiently phosphorylate lkb1 at thr-366 in vitro and provide evidence that atm mediates this phosphorylation in vivo.
SIGNOR-92873
O15068
P61586
1
guanine nucleotide exchange factor
up-regulates activity
0.619
We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).
SIGNOR-260559
Q13131
P14859
1
phosphorylation
down-regulates
0.2
Mitosis-specific phosphorylation site in the homeodomain of oct-1 was phosphorylated in vitro by protein kinase a. Pka-mediated phosphorylation event was identified in the cns-specific pou domain protein brn-2/n-oct-3/pou3f2 (nieto et al. 2007). In this case, the modification, at a position homologous to oct1 s385, was found to alter binding specificity for complex dimeric sites.
SIGNOR-53254
P05412
P63244
1
null
up-regulates quantity by expression
0.2
In turn, c-Jun induces expression of RACK1, which is required for JNK activation by PKC, pointing to a c-Jun/RACK1/PKC/JNK feedback loop.
SIGNOR-278066
O14733
O43318
0
phosphorylation
up-regulates activity
0.645
Upon TNFα stimulation, MEKK1, ASK1, and TAK1 phosphorylate and activate MKK7, which in turn activates JNK
SIGNOR-274146
P00519
Q9P0J1
1
phosphorylation
down-regulates activity
0.268
Here we report that phosphorylation at another tyrosine residue, Tyr-94, inhibits PDP1 by reducing the binding ability of PDP1 to lipoic acid, which is covalently attached to the L2 domain of dihydrolipoyl acetyltransferase (E2) to recruit PDP1 to PDC. We found that multiple oncogenic tyrosine kinases directly phosphorylated PDP1 at Tyr-94, and Tyr-94 phosphorylation of PDP1 was common in diverse human cancer cells and primary leukemia cells from patients. 
SIGNOR-276641
P52926
Q66K89
2
binding
down-regulates
0.371
Here we show that hmga2 associates with the e1a-regulated transcriptional repressor p120(e4f), interfering with p120(e4f) binding to the cyclin a promoter
SIGNOR-119537
Q13131
P49116
1
phosphorylation
down-regulates
0.2
Tr4 transactivation is inhibited via phosphorylation bymetformin-induced amp-activated protein kinase (ampk) at the amino acid serine 351, which results in the suppression of scd1 gene expression
SIGNOR-173118
P63027
O60641
2
binding
up-regulates quantity
0.63
 the monomeric adaptor proteins AP180/CALM and stonin-2 are required for the efficient retrieval of synaptobrevin II (sybII) and synaptotagmin-1 respectively. Furthermore, recent studies have revealed that sybII and synaptotagmin-1 interact with other SV cargoes to ensure a high fidelity of retrieval.
SIGNOR-264112
O00141
P15056
1
phosphorylation
down-regulates activity
0.344
Serum- and glucocorticoid-inducible kinase SGK phosphorylates and negatively regulates B-Raf.|We observed that SGK inhibits B-Raf activity.
SIGNOR-279110
Q05655
P29474
1
phosphorylation
down-regulates activity
0.568
The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites
SIGNOR-251631
P04637
Q00987
0
ubiquitination
down-regulates quantity by destabilization
0.968
The E3 ubiquitin ligase, MDM2, uses a dual-site mechanism to ubiquitinate and degrade the tumor suppressor protein p53, involving interactions with the N-terminal hydrophobic pocket and the acidic domain of MDM2.
SIGNOR-196116
P30305
Q8TDC3
0
phosphorylation
down-regulates
0.506
Hssad1 specifically phosphorylated wee1a, cdc25-c, and -b on ser-642, ser-216, and ser-361 in vitro, respectivelyphosphorylation of cdc25 triggers cell-cycle arrest by the sequestration of cdc25 by 14-3-3
SIGNOR-124839
Q09472
Q9UK32
0
phosphorylation
down-regulates activity
0.253
Figure 2G shows that Ser89 phosphorylation of p300, an event that inhibits p300’s acetyltransferase activity (13), was decreased in RSK4-silenced A549 and T24 cells. Consequently, RSK4 may regulate the activity of the NFκB pathway by direct phosphorylation of p300, as recombinant RSK4 phosphorylates p300 on Ser89 in vitro 
SIGNOR-275796
Q5JUK2
P10721
1
transcriptional regulation
up-regulates quantity by expression
0.346
Our results suggest that SOHLH1 and SOHLH2 directly stimulate Kit transcription in postnatal spermatogonia, thus activating the signaling involved in spermatogonia differentiation and spermatogenetic progression.
SIGNOR-266205
Q13085
Q13131
0
phosphorylation
down-regulates activity
0.7
We have isolated and purified from rat livers a novel kinase that phosphorylates and inactivates the carboxylase Ser1200 isphosphorylated by both CAMP-dependent protein kinase and AMP-activated protein kinase
SIGNOR-250400
P43115
P16520
2
binding
up-regulates
0.498
Ep3 receptor signals are primarily involved in adenylyl cyclase via g(i) activation, and in ca(2+)-mobilization through g(beta)(gamma) from g(i)
SIGNOR-88192
Q14005
P19784
0
phosphorylation
up-regulates activity
0.326
We now show that N-terminal to the NLS domain of pro-IL-16 are protein kinase CK2 substrate and cdc2 kinase substrate sites which, along with the NLS, constitute a dual phosphorylation-regulated CcN motif which regulates nuclear localization of pro-IL-16. In addition, we demonstrate that mutation of either site is associated with impairment of the N-terminal domain's ability to induce G(0)/G(1) cell cycle arrest. | Thus, we confirm that the N-terminal (42SLNEE46) sequence of pro-IL-16 is in fact a site for protein kinase CK2 phosphorylation.
SIGNOR-251009
Q99963
Q8WWB3
2
binding
up-regulates activity
0.308
DYDC1 and SH3P13 interact in vitro and in vivo. We recently demonstrated that SH3P13, a BAR domain-containing protein, assists in regulatingclathrin-coated vesicle traffic that is crucial for acrosome biogenesis during spermatogenesis
SIGNOR-263882
Q8N0W4
Q9Y4C0
2
binding
up-regulates activity
0.767
Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)
SIGNOR-264165
P31941
Q13617
0
ubiquitination
down-regulates quantity by destabilization
0.251
Human Papillomavirus 16 E7 Stabilizes APOBEC3A Protein by Inhibiting Cullin 2-Dependent Protein Degradation|Here, we report that the HPV oncoprotein E7 stabilizes the APOBEC3A (A3A) protein in human keratinocytes by inhibiting ubiquitin-dependent protein degradation in a cullin-dependent manner.
SIGNOR-261325
Q9UHD2
Q9Y2E6
0
ubiquitination
down-regulates
0.584
Nlrp4 negatively regulates type i interferon signaling by targeting the kinase tbk1 for degradation via the ubiquitin ligase dtx4
SIGNOR-71565
P35222
Q9H6I2
2
binding
down-regulates
0.686
Two additional sox proteins, xsox17alfa and xsox3 , likewise bind to beta-catenin and inhibit its tcf-mediated signaling activity
SIGNOR-72006
Q9UJP4
Q96GD4
2
binding
up-regulates activity
0.507
KLHL21 directly binds to Aurora B and mediates ubiquitination of Aurora B in vitro. In contrast to KLHL9 and KLHL13, KLHL21 localizes to midzone microtubules in anaphase and recruits Aurora B and Cul3 to this region. Together, our results suggest that different Cul3 adaptors nonredundantly regulate Aurora B during mitosis, possibly by ubiquitinating different pools of Aurora B at distinct subcellular localizations.
SIGNOR-271848
P20823
Q9HAW8
1
transcriptional regulation
up-regulates quantity by expression
0.251
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-253971
Q04206
Q05513
0
phosphorylation
up-regulates
0.555
Rela is phosphorylated at: ser276 by the catalytic subunit of protein kinase a (pkac), msk1 and msk2; at ser311 by the atypical pkczeta; at ser468 by ikkbeta, ikkepsilon and glycogen-synthase kinase-3beta (gsk3beta); at ser529 by ck2; and at ser536 by ikkbeta, ikkalfa, ikkepsilon, nf-kb activating kinase (nak, also known as tank-binding kinase-1 tbk1)) and rsk1 (also known as p90 ribosomal protein s6 kinase (p90s6k)
SIGNOR-151432
O14757
Q96AV8
1
phosphorylation
down-regulates activity
0.387
Chk1 inhibits the transcriptional repressor function of E2F7 and E2F8 to promote cell cycle progression and prevent apoptosis.|Here, we demonstrate that Chk1 phosphorylates both E2F7 and E2F8 in response to DNA damage.
SIGNOR-279692
Q9P212
P62834
2
binding
up-regulates quantity
0.491
 The SUR1 subunit of KATP channels recruits Epac2 to the plasma membrane where a signaling complex comprised of Epac2, Rap1 and PLC-ε is formed. Rap1 is activated by Epac2, and the activated form of Rap1 binds to and activates PLC-ε.
SIGNOR-278142
Q14703
Q12772
1
cleavage
up-regulates activity
0.594
We present evidence that SKI-1 processes peptides mimicking the cleavage sites of the SKI-1 prosegment, pro-brain-derived neurotrophic factor, and the sterol regulatory element-binding protein SREBP-2
SIGNOR-267496
P52630
Q5T197
0
ubiquitination
down-regulates activity
0.448
DCST1 promotes ubiquitination of STAT2.|The ability of DCST1 to degrade STAT2 levels was visible both in the presence and absence of IFNbetastimulation.|In our study, DCST1 was found to interact with and promote ubiquitination of STAT2, leading to reduced STAT2 expression and attenuated activation of the ISG induction pathway.
SIGNOR-278747
P12931
Q04760
1
phosphorylation
up-regulates activity
0.2
We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D).
SIGNOR-276189
Q13224
Q13554
0
phosphorylation
up-regulates activity
0.606
By peptide mapping, automated sequencing, and mass spectrometry, we identified the major site of phosphorylation on the fusion protein as Ser-383, corresponding to Ser-1303 of full-length NR2B. The Km for phosphorylation of this site in the fusion protein was approximately 50 nM, much lower than that of other known substrates for CaM kinase II, suggesting that the receptor is a high affinity substrate. We show that serine 1303 in the full-length NR2B and/or the cognate site in NR2A is a major site of phosphorylation of the receptor both in the postsynaptic density fraction and in living hippocampal neurons.
SIGNOR-250688
Q9H8V3
P41743
0
phosphorylation
up-regulates
0.474
Our data support a model in which pkc?-Mediated phosphorylation regulates ect2 binding to the oncogenic pkc?-Par6 complex thereby activating rac1 activity and driving transformed growth and invasion.
SIGNOR-170790
P31749
O15327
0
dephosphorylation
down-regulates activity
0.374
Further, we show that INPP4B but not PTEN is able to reduce tyrosine phosphorylation of Akt1 and both the lipid and PTP activity of INPP4B likely contribute to the reduction of Akt1 phosphorylation.|Further, we show that INPP4B but not PTEN is able to reduce tyrosine phosphorylation of Akt1 and both the lipid and protein tyrosine phosphatase activity of INPP4B likely contribute to the reduction of Akt1 phosphorylation.
SIGNOR-277106
P35638
P18850
0
transcriptional regulation
up-regulates quantity by expression
0.658
Apart from ER protein chaperones, ATF6 also induces the expression of CHOP and XBP1, thereby connecting the three UPR branches into an integrated signaling network
SIGNOR-260180
Q13546
Q6WCQ1
1
phosphorylation
up-regulates activity
0.2
Under such conditions, RIP1 phosphorylates and activates RIP3, which in turn phosphorylates its downstream substrate MLKL, leading to plasma membrane rupture and necrosis( xref ).
SIGNOR-279755
Q9P2Y5
P42345
0
phosphorylation
up-regulates activity
0.408
MTOR phosphorylates UVRAG at serine 550 and serine 571
SIGNOR-276919
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
P42226
P23771
1
null
up-regulates
0.662
GATA-3 plays a central role in regulating Th1 and Th2 cell differentiation. Upon interleukin (IL)-4 binding to its receptor, GATA-3 is induced through the action of Stat6
SIGNOR-254299
Q8N668
P10909
2
binding
down-regulates quantity by destabilization
0.392
CLU-2 is a ubiquitin binding protein (UBP) that enhances proteasome activity. sCLU promotes degradation of COMMD1. sCLU interacts with the SCF-βTrCP E3 ligase complex, serving as a scaffolding chaperone to form a multimeric protein complex that facilitates COMMD1 and I-κB ubiquitination and proteasomal degradation.
SIGNOR-271432
P08581
P23470
0
dephosphorylation
down-regulates activity
0.317
PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.
SIGNOR-254712
P61586
Q8N5V2
0
guanine nucleotide exchange factor
up-regulates activity
0.675
We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).
SIGNOR-260562
P17612
Q9UQL6
1
phosphorylation
up-regulates activity
0.2
PKA/Cdk5-mediated phosphorylation of HDAC5 at Ser279 within the NLS promotes nuclear localization of HDAC5 and interaction with the nuclear corepressor complex
SIGNOR-198658
P10144
P11717
2
binding
up-regulates
0.407
The serine proteinase granzyme b is crucial for the rapid induction of target cell apoptosis by cytotoxic t cells. We now present evidence that this receptor is the cation-independent mannose 6-phosphate/insulin-like growth factor receptor (ci-mpr). Inhibition of the granzyme b ci-mpr interaction prevented granzyme b cell surface binding, uptake, and the induction of apoptosis.
SIGNOR-84314
Q15628
O00463
2
binding
up-regulates
0.607
Upon stimulation of the tumor necrosis factor receptor1 (tnfr1), tnf-receptor-associated death domain (tradd) provides a scaffold for the assembly of complex i at the plasma membrane by binding receptor interacting protein 1 (rip1), tnfreceptor-associated factor 2 ,traf2.
SIGNOR-187058
P46527
P11309
0
phosphorylation
down-regulates activity
0.382
We show, herein, that all the pim family members (pim1, pim2, and pim3) bind to and directly phosphorylate the cyclin-dependent kinase inhibitor p27(kip1) at threonine-157 and threonine-198 residues in cells and in vitro.|Pim kinases promote cell cycle progression and tumorigenesis by down-regulating p27(Kip1) expression at both transcriptional and posttranslational levels.
SIGNOR-179300
P00519
Q6NUN9
1
phosphorylation
up-regulates activity
0.313
C-Abl-mediated phosphorylation of PARIS at Y137 (within the Krüppel-associated box domain) drives its association with KAP1 and the repression of genes with diverse functions in pathways such as chromatin remodelling and p53-dependent cell death.
SIGNOR-277626
P13051
P49840
0
phosphorylation
down-regulates quantity by destabilization
0.2
Here we show that glycogen synthase kinase 3 (GSK-3) interacts with and phosphorylates UNG2 at Thr60 and that Thr60 phosphorylation requires a Ser64 priming phosphorylation event.|phosphorylation of Thr60 and Ser64 creates a cyclin E/c-Myc-like phosphodegron that promotes polyubiquitylation and proteasome-mediated degradation
SIGNOR-264886