GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels float64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q9ULV8	P07949	1	ubiquitination	down-regulates quantity by destabilization	0.368	Here we show that Cbl-c binds wild-type and MEN2A isoforms of the receptor tyrosine kinase, RET, and that Cbl-c enhances ubiquitination and degradation of activated RET.\|We show that Cbl-c negatively regulates RET by ubiquitinating and downregulating the activated RTK while Enigma positively regulates activated RET by preventing Cbl-c binding to RET and thus preventing RET ubiquitination and degradation while promoting RET mitogenic signaling.	SIGNOR-278674
Q13882	Q6P1J9	1	phosphorylation	down-regulates activity	0.368	PTK6 impairs the coactivator function of parafibromin.\|To study the functional consequence of parafibromin phosphorylation by PTK6, we examined the effect of PTK6 inhibition on Wnt signal activation.	SIGNOR-279273
Q96NI6	Q13332	1	binding	up-regulates activity	0.368	SALM5 trans-synaptically interacts with LAR-RPTPs in a splicing-dependent manner to regulate synapse development. we identified LAR-RPTPs as novel ligands of SALM5 that mediates SALM5-dependent presynaptic differentiation in a splicing-dependent manner. Our data indicate that SALM5 interacts with all three known LAR-RPTPs—LAR, PTPδ, and PTPσ (Fig. 1).	SIGNOR-264088
Q8TAS1	P46527	1	phosphorylation	up-regulates	0.367	Hkis is a nuclear protein that binds the c-terminal domain of p27(kip1) and phosphorylates it on s10 in vitro and in vivo, promoting its nuclear export to the cytoplasm.Phosphorylation at serine 10, a major phosphorylation site of p27(kip1), increases its protein stability	SIGNOR-90274
Q06124	Q99683	1	dephosphorylation	up-regulates	0.367	Previously we have shown that tyrosine 718 of ask1 when phosphorylated is critical for socs1 binding and socs1-mediated degradation of ask1we identified jak2 and shp2 as a tyr-718-specific kinase and phosphatase, respectively.	SIGNOR-184604
O15287	Q13813	1	null	up-regulates quantity by stabilization	0.367	In FA cells, deficiencies in FA proteins lead to decreased stability of alphaRIISp \|These results demonstrate that one of the FA proteins, FANCG, contains a motif that interacts directly with the SH3 domain of alphaIISp. We propose that this binding of FANCG to alphaIISp may be important for the stability of alphaIISp in cells and the role alphaIISp plays in the DNA repair process.\|	SIGNOR-263275
P06241	Q15700	1	phosphorylation	up-regulates activity	0.367	Recombinant PSD-93 was phosphorylated by Fyn in vitro, and Tyr-384 was identified as a major phosphorylation site. In COS7 cells, exogenously expressed PSD-93 was phosphorylated, dependent on its membrane localization. In addition, tyrosine-phosphorylated PSD-93 was able to bind to Csk, a negative regulator of Src family kinases, in vitro as well as in a brain lysate.	SIGNOR-262874
P28482	Q9NZV8	1	phosphorylation	up-regulates activity	0.367	We determined that the Kv4.2 C-terminal cytoplasmic domain is an effective ERK2 substrate, and that it is phosphorylated at three sites: Thr(602), Thr(607), and Ser(616). Phosphorylation of the Kv4.2 channel by ERK during LTP induction may lead to increased excitability and membrane depolarization of neurons, which would increase the magnitude of the calcium influx and the probability of triggering LTP.	SIGNOR-262935
Q8IYU2	P63000	1	ubiquitination	down-regulates quantity by destabilization	0.367	The CNF1 toxin of pathogenic Escherichia coli addresses Rac1 to ubiquitin-proteasome system (UPS). We report the essential role of the tumor suppressor HACE1, a HECT-domain containing E3 ubiquitin-ligase, in the targeting of Rac1 to UPS. HACE1 binds preferentially GTP-bound Rac1 and catalyzes its polyubiquitylation	SIGNOR-255538
P12931	Q9UK53	1	phosphorylation	down-regulates activity	0.367	Src Decreases the Stability and Level of ING1.\|This study, as well as a previous report identifying Ser-126 of ING1 as a kinase target, confirm that ING1 stability is also regulated by phosphorylation. However, the mechanism may be complex since phosphorylation of Ser-126 stabilizes the protein while phosphorylation by Src reduces ING1 stability and causes a relocalization of ING1 from the nucleus to the cytoplasm.	SIGNOR-279760
Q5S007	P46459	1	phosphorylation	up-regulates activity	0.367	LRRK2 phosphorylates full-length NSF at threonine 645 in the ATP binding pocket of D2 domain. Functionally, NSF phosphorylated by LRRK2 displays enhanced ATPase activity and increased rate of SNARE complex disassembling.	SIGNOR-277196
Q14526	P40763	1	binding	down-regulates quantity by repression	0.367	HIC1 interacts with the DNA binding domain of STAT3 and suppresses the binding of STAT3 to its target gene promoters. HIC1 C-terminal domain binds to STAT3. HIC1 mutant defective in STAT3 interaction reduced its repressive effect on STAT3 DNA binding activity, the reporter activity and gene expression of the VEGF and c-Myc genes, and cell growth in MDA-MB 231 cells.	SIGNOR-254246
P31749	Q12906	1	phosphorylation	up-regulates activity	0.367	Upon T cell activation, NF90 translocates from the nucleus into the cytoplasm, where it binds to the AU-rich element-containing 3' untranslated regions of IL-2 mRNA and stabilizes it.\|Our previous work showed that CD28 costimulation of T cells activated AKT to phosphorylate NF90 at Ser647 and caused NF90 to undergo nuclear export and stabilize IL-2 mRNA.	SIGNOR-252512
Q92466	Q01094	1	binding	up-regulates	0.367	We show that ddb, a putative dna repair protein, associates with the activation domain of e2f1 / expression of ddb specifically stimulated e2f1-activated transcription	SIGNOR-54102
P49841	Q9Y6R4	1	binding	down-regulates	0.367	Gsk3beta binding to mekk4 blocks mekk4 dimerization that is required for mekk4 activation, effectively inhibiting mekk4 stimulation of the jnk and p38 mapk pathways	SIGNOR-157541
Q15349	P22736	1	phosphorylation	down-regulates activity	0.367	Phosphorylation of a residue in the DNA-binding region (Ser-350 of NGFI-B and 354 of Nur77) has been described in detail to have effect on the transcriptional function of the protein [11, 24]. Growth-related kinase pp90rsk, but not ERK1 (pp44mapk), was shown to phosphorylate recombinant Nur77 in vitro in the DNA binding domain, but not the amino-terminus, using an immune complex kinase as- say [11].	SIGNOR-249429
Q05655	Q13501	1	phosphorylation	up-regulates activity	0.367	Data presented here suggested that Vps34 stimulates tumor development mainly through PKC-\u03b4- activation of p62.\|In conclusion, elevation of Vps34 results in tumor progression via the PKC-\u03b4-phosphorylation of p62 at S349 and PKC-\u03b4 involved phosphorylation of Raf 1 at Y340/341.\|Vps34 induces PKC-\u03b4-dependent phosphorylation of p62.	SIGNOR-280086
Q96NX9	P15173	1	transcriptional regulation	down-regulates quantity by repression	0.367	We confirmed Dach2 is a Mgn transcriptional repressor that mediates HDAC-dependent regulation by (i) overexpressing Dach2 in myotubes harboring the 133-bp Mgn promoter and (ii) rescuing TSA-mediated Mgn repression by Dach2 knockdown.	SIGNOR-261579
Q9HC98	P23443	1	phosphorylation	up-regulates activity	0.367	Here we demonstrate that in addition to phosphorylating S6K1 and SGK1 at their hydrophobic motif, NEK6 also phosphorylates S6K1 at two other sites and phosphorylates SGK1 at one other site in vitro. Analysis of the peptides phosphorylated by NEK6 (Fig 2), performed in the present study has confirmed this, and identified two novel sites on S6K1 (Ser53 and Ser403) as major sites of NEK6 phosphorylation.	SIGNOR-262953
P49841	Q92993	1	phosphorylation	up-regulates	0.367	We demonstrate that gsk-3 phosphorylates serine 86 of the p53-acetyltransferase tip60. A tip60(s86a) mutant was less active to induce p53 k120 acetylation, histone 4 acetylation, and expression of puma	SIGNOR-174049
P54646	P41235	1	phosphorylation	down-regulates quantity by destabilization	0.367	AMPK directly phosphorylates HNF4alpha and represses its transcriptional activity. AMPK-mediated phosphorylation of HNF4alpha on serine 304 had a 2-fold effect, reducing the ability of the transcription factor to form homodimers and bind DNA and increasing its degradation rate in vivo. Phosphorylation of HNF4α on Ser-304 reduces protein stability.	SIGNOR-250322
O60674	Q99683	1	phosphorylation	down-regulates quantity by destabilization	0.367	Furthermore, JAK2, but not JAK1, directly bound to and phosphorylated ASK1 at Tyr-718, leading to an enhanced association of ASK1 with SOCS1 and subsequent ASK1 degradation.	SIGNOR-276145
P67775	Q13043	1	dephosphorylation	down-regulates	0.367	Rassf1a apparently protects mst1/2 against inactivation by pp2a , the phosphatases that dephosphorylate the stimulatory thr-183 and thr-180 of mst1 andmst2, respectively.	SIGNOR-201270
P63279	P35712	1	sumoylation	down-regulates activity	0.367	We show that SOX6 is modified in vitro and in vivo by small ubiquitin‐related modifier (SUMO) on two distinct sites. Mutation of both sites abolished SOX6 sumoylation and increased SOX6 transcriptional activity. SUMO dependent repression of SOX6 transcription was promoted by UBC9 whereas siRNA to UBC9, cotransfection of inactive UBC9 or a SUMO protease increased SOX6 transcriptional activity.	SIGNOR-256130
P35452	O75444	1	binding	down-regulates activity	0.367	Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf.	SIGNOR-221887
Q13233	P46531	1	phosphorylation	down-regulates activity	0.367	As a result, MEKK1 suppresses the Notch1 intracellular domain protein stability and transcriptional activity.\|We confirmed that MEKK1 binds to Notch1 intracellular domain and phosphorylates the Notch1 intracellular domain Threonine 2512 residue.	SIGNOR-279628
Q13153	Q70Z35	1	phosphorylation	down-regulates activity	0.367	P21-activated Kinases (PAKs) Mediate the Phosphorylation of PREX2 Protein to Initiate Feedback Inhibition of Rac1 GTPase. PAK-mediated phosphorylation of PREX2 reduced GEF activity toward Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ.	SIGNOR-277181
Q969H0	Q16204	1	binding	down-regulates	0.367	Fbxw7 interacts with and targets ccdc6 for ubiquitin-mediated proteasomal degradation	SIGNOR-199279
P24941	Q8IZL8	1	phosphorylation	up-regulates	0.367	We identified ser(477) and ser(991) of pelp1 as cdk phosphorylation sites. we conclude that pelp1 is a novel substrate of interphase cdks and that its phosphorylation is important for the proper function of pelp1 in modulating hormone-driven cell cycle progression and also for optimal e2f transactivation function.	SIGNOR-167766
Q15831	Q9NRH2	1	phosphorylation	up-regulates activity	0.367	We demonstrate that LKB1 activates SNRK by phosphorylating the T‐loop residue (Thr173)	SIGNOR-260824
Q7KZI7	Q9BXM7	1	phosphorylation	up-regulates activity	0.367	MARK2 phosphorylated and activated the cleaved form of PINK1 (DeltaN-PINK1	SIGNOR-278975
Q16539	Q13950	1	phosphorylation	up-regulates activity	0.367	Mechanistic analysis revealed that the TAK1–MKK3/6–p38 MAPK axis phosphorylated Runx2, promoting its association with the coactivator CREB-binding protein (CBP), which was required to regulate osteoblast genetic programs. These findings reveal an in vivo function for p38β and establish that MAPK signaling is essential for bone formation in vivo.	SIGNOR-255777
Q13464	P08670	1	phosphorylation	down-regulates activity	0.367	We found that vimentin, the most widely expressed intermediate filament protein, served as an excellent substrate for Rho-associated kinase (Rho-kinase) and that vimentin phosphorylated by Rho-kinase lost its ability to form filaments in vitro. Two amino-terminal sites on vimentin, Ser38 and Ser71, were identified as the major phosphorylation sites for Rho-kinase, and Ser71 was the most favored and unique phosphorylation site for Rho-kinase in vitro.	SIGNOR-248998
P28482	Q53EZ4	1	phosphorylation	down-regulates	0.367	Upon mitotic entry, centrosome dissociation of cep55 is triggered by erk2/cdk1-dependent phosphorylation at s425 and s428. S425/428 phosphorylation is required for interaction with plk1, enabling phosphorylation of cep55 at s436. enabling it to relocate to the midbody to function in mitotic exit and cytokinesis.	SIGNOR-140890
Q12955	P11532	1	relocalization	up-regulates quantity	0.367	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-266715
P27361	Q16204	1	phosphorylation	up-regulates activity	0.367	We have characterized the H4(D10S170) gene product, showing that it is a ubiquitously expressed 55 KDa nuclear and cytosolic protein that is phosphorylated following serum stimulation. This phosphorylation was found to depend on mitogen-activated protein kinase (MAPK) Erk1/2 activity and to be associated to the relocation of H4(D10S170) from the nucleus to the cytosol. S244 is the major target residue of ERK1	SIGNOR-276003
P08246	P12259	1	cleavage	up-regulates activity	0.366	Human neutrophil elastase activates human factor V but inactivates thrombin-activated human factor V\|NH2-terminal sequence analysis of F.V treated with HNE indicated cleavage at Ile819 and Ile1484 under conditions during which the procofactor expressed enhanced cofactor activity in the prothrombinase complex.	SIGNOR-263637
Q15418	P30304	1	phosphorylation	down-regulates	0.366	Rsk promotes g2/m transition through activating phosphorylation of cdc25a and cdc25b rsk is likely to be more active in mitotic cells than in interphase cells, as evidenced by the phosphorylation status of t359/s363 in rsk. Together, these findings indicate that rsk promotes g2/m transition in mammalian cells through activating phosphorylation of cdc25a and cdc25b.	SIGNOR-202117
P17252	P14136	1	phosphorylation	down-regulates activity	0.366	Glial fibrillary acidic protein (GFAP), the intermediate filament component of astroglial cells, can serve as an excellent substrate for both cAMP-dependent protein kinase and protein kinase C, in vitro. GFAP phosphorylated by each protein kinase does not polymerize, and the filaments that do polymerize tend to depolymerize after phosphorylation. Dephosphorylation of phospho-GFAP by phosphatase led to a recovery of the polymerization competence of GFAP. Most of the phosphorylation sites for cAMP-dependent protein kinase and protein kinase C on GFAP are the same, Ser-8, Ser-13, and Ser-34. cAMP-dependent protein kinase has one additional phosphorylation site, Thr-7.	SIGNOR-248862
Q15208	Q96QF0	1	phosphorylation	up-regulates activity	0.366	We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation.	SIGNOR-263036
P17252	Q16760	1	phosphorylation	down-regulates activity	0.366	The plasma membrane translocation of diacylglycerol kinase delta1 is negatively regulated by conventional protein kinase C-dependent phosphorylation at Ser-22 and Ser-26 within the pleckstrin homology domain.	SIGNOR-249265
P50613	Q13285	1	phosphorylation	up-regulates	0.366	In conclusion, our results indicate that cdk7, as part of the cak complex and tfiih, phosphorylates sf1 at s203 followed by increased transcriptional activity of sf1	SIGNOR-157952
P11362	P00338	1	phosphorylation	up-regulates	0.366	We found that the oncogenic receptor tyrosine kinase fgfr1 directly phosphorylates ldh-a. Phosphorylation at y10 and y83 enhances ldh-a activity by enhancing the formation of active, tetrameric ldh-a and the binding of ldh-a substrate nadh, respectively.	SIGNOR-176730
Q9BV47	P04637	1	dephosphorylation	down-regulates activity	0.366	Dual-specificity phosphatase 26 is a novel p53 phosphatase and inhibits p53 tumor suppressor functions in human neuroblastoma\|Inhibiting DUSP26 expression in the IMR-32 neuroblastoma cell line enhanced doxorubicin-induced p53 phosphorylation at Ser20 and Ser37, p21, Puma, Bax expression as well as apoptosis	SIGNOR-248765
P49137	O95816	1	phosphorylation	up-regulates	0.366	We provided definite evidence that mapkapk2 phosphorylates bag2 at ser 20 in vitro and in vivo. These results demonstrate that bag2 is a novel component of the p38 mapk signaling pathways.	SIGNOR-126953
P01116	Q13233	1	binding	up-regulates	0.366	Mitogen-activated protein kinase kinase kinase (mekk1) is a serine-threonine kinase that regulates sequential protein kinase pathways involving stress-activated protein kinases and mitogen-activated protein kinases. Mekk1 is activated in response to growth factor stimulation of cells and by expression of activated ras. mekk1 directly binds ras.GTP. Thus, ras interacts with protein kinases of both the raf and mekk families.	SIGNOR-32620
Q00535	P35712	1	phosphorylation	down-regulates quantity	0.366	GST-Sox6 was phosphorylated in vitro by Cdk5 and p35 (XREF_FIG).\|Inhibition of Cdk5 activity by DN Cdk5 and roscovitine increases the Sox6 expression in primary cortical neurons.	SIGNOR-279365
Q9Y6D6	P61204	1	guanine nucleotide exchange factor	up-regulates activity	0.366	Brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1) is an approximately 200-kDa brefeldin A-inhibited guanine nucleotide-exchange protein that preferentially activates ADP-ribosylation factor 1 (ARF1) and ARF3.	SIGNOR-272148
Q96AX9	Q13224	1	ubiquitination	down-regulates quantity	0.366	Mib2 is localized to the PSD of dendrites in hippocampal neurons and directly ubiquitinates GluN2B in a manner dependent on the non receptor tyrosine kinase Fyn.\|These findings suggest that Mib2 mediates proteasome dependent degradation of GluN2B subunits, which may provide a reciprocal mechanism to SCF Fbx2 regulation of GluN2A.	SIGNOR-278762
Q5H8C1	Q6UXI9	1	transcriptional regulation	up-regulates quantity by expression	0.366	The loss of QBRICK significantly diminished the expression of nephronectin, an integrin α8β1 ligand necessary for renal development. In vivo, nephronectin associated with QBRICK and localized at the sublamina densa region, where QBRICK was also located. Collectively, these findings indicate that QBRICK facilitates the integrin α8β1-dependent interactions of cells with basement membranes by regulating the basement membrane assembly of nephronectin and explain why renal defects occur in Fraser syndrome.	SIGNOR-253308
P48730	Q9GZV5	1	phosphorylation	down-regulates	0.366	LATS1/2-mediated phosphorylation of a conserved serine in this region (Ser311 in human TAZ; Ser397 in human YAP) primes for further phosphorylation by CK1_/_ kinases (Ser314 on human TAZ; Ser400/403 in human YAP)	SIGNOR-234438
P68400	Q16623	1	phosphorylation	up-regulates	0.366	In this report, we show that syntaxin-1a is phosphorylated in vitro by cki on thr21. Casein kinase ii (ckii) has been shown previously to phosphorylate syntaxin-1a in vitro and we have identified ser14 as the ckii phosphorylation site. the phosphorylation of syntaxin-1a by ckii enhances its capacity to associate with synaptotagmin [21]. Therefore, phosphorylation of ser14 by ckii suggests an important role for this residue in regulating the interaction between syntaxin-1a and synaptotagmin	SIGNOR-114840
Q9UHD2	A5D8V6	1	phosphorylation	down-regulates activity	0.366	We have identified that TBK1 may target and phosphorylate VPS37C, a structural component of ESCRT-I complex, and serve as a ratelimiting factor in the control of PTAP-dependent (HIV-1, MLV/p6, and EIAV/PTAP), but not PPPY-dependent (MLV, EIAV/PPPY) retrovirus budding, independent of its role in IFN-I signaling.	SIGNOR-279768
Q9BV47	Q13158	1	dephosphorylation	down-regulates activity	0.366	This multi-functionality of fadd may depend primarily on its subcellular location. Fadd shuttles between the cytosol and the nucleus and this signal is unclear;however, fadd trafficking requires phosphorylation of the protein on ser194dusp26 suppresses cell proliferation by fadd dephosphorylation	SIGNOR-204559
Q05655	Q09472	1	phosphorylation	down-regulates	0.366	Inhibition of histone acetyltransferase function of p300 by pkcdeltawe found that pkcdelta but not classical pkc, specifically phosphorylates p300 at serine 89 in vitro and in vivo. This phosphorylation causes inhibition of p300 intrinsic hat activity.	SIGNOR-94263
Q96GD4	P54274	1	phosphorylation	up-regulates activity	0.366	Our data indicate that AURKB can phosphorylate the integral telomere DNA-binding Shelterin protein TERF1 at S404 (within the DNA-binding domain) in vitro .	SIGNOR-279440
Q13153	Q9Y6X9	1	phosphorylation	up-regulates activity	0.366	We demonstrate that PAK1-mediated MORC2 phosphorylation promotes cell cycle progression, defective phosphorylation of MORC2-S677A results in attenuated cell proliferation and tumorigenicity of gastric cancer cells, which is significantly enhanced in overexpression of phospho-mimic MORC2-S677E form, suggesting the importance of MORC2 phosphorylation in tumorigenesis.	SIGNOR-273714
Q9UHC7	Q8N726	1	polyubiquitination	down-regulates quantity by destabilization	0.366	Biochemical analyses confirmed that MKRN1 targets p14ARF for ubiquitination and subsequent proteasome-dependent degradation.The Skp1-Cul1-F-box-protein44 (SCF(FBXO44)) complex ubiquitinates full-length BRCA1 in vitro.	SIGNOR-272036
P06241	Q96J02	1	phosphorylation	down-regulates activity	0.366	Tyrosine phosphorylation of Itch appears to reduce its interaction with its substrate JunB. The turnover of JunB is accelerated in Fyn-deficient T cells, which is further reconstituted by Itch Tyr371 mutation	SIGNOR-245332
P06241	Q12913	1	phosphorylation	up-regulates activity	0.366	We demonstrate here that DEP-1 is phosphorylated in a Src- and Fyn-dependent manner on Y1311 and Y1320, which bind the Src SH2 domain. This allows DEP-1-catalyzed dephosphorylation of Src inhibitory Y529 and favors the VEGF-induced phosphorylation of Src substrates VE-cadherin and Cortactin.	SIGNOR-276372
Q5T447	Q9UDY8	1	polyubiquitination	up-regulates quantity by stabilization	0.366	HECTD3 promotes MALT1 ubiquitination with nondegradative polyubiquitin chains by direct interacting with the MALT1 through its N-terminal destruction of cyclin domain. HECTD3 does not target MALT1 for degradation but stabilize it.	SIGNOR-272096
O75309	P35222	1	binding	up-regulates activity	0.366	At its C-terminus, cadherin interacts with Î²-catenin, which dynamically associates with Î±-catenin, a direct binding partner of filamentous actin	SIGNOR-265855
P17612	Q14344	1	phosphorylation	down-regulates activity	0.366	PKA directly phosphorylates Galpha(13). Galpha(13)-T203A mutant (in COS-7 cells) could not be phosphorylated by PKA. PKA blocks Rho activation by phosphorylation of Galpha(13) Thr(203).	SIGNOR-249985
O00213	Q63HK5	1	relocalization	up-regulates activity	0.366	We carried out yeast two-hybrid studies with a PTB domain of FE65, focusing on those genes that might be involved in nuclear signaling, and identified and validated Teashirt proteins as FE65 interacting proteins in neurons. Using reporter systems, we observed that FE65 could simultaneously recruit SET, a component of the inhibitor of acetyl transferase, and Teashirt, which in turn recruited histone deacetylases, to produce a powerful gene-silencing complex.	SIGNOR-264813
P49674	Q9GZV5	1	phosphorylation	down-regulates	0.366	LATS1/2-mediated phosphorylation of a conserved serine in this region (Ser311 in human TAZ; Ser397 in human YAP) primes for further phosphorylation by CK1_/_ kinases (Ser314 on human TAZ; Ser400/403 in human YAP)	SIGNOR-230747
P84022	Q06710	1	binding	down-regulates activity	0.366	DNA Binding Activity of Pax8 to the NIS Promoter Is Reduced by Smad3. TGF-Î² decreases Pax8 DNA binding to the NIS promoter and also found a physical interaction between Pax8 and Smad3.	SIGNOR-251992
P12931	P41235	1	phosphorylation	down-regulates	0.365	Here we show that c-src phosphorylates human hnf4_ on three tyrosines phosphomimetic mutants in the lbd decrease p1-hnf4_ protein stability, nuclear localization and transactivation function.	SIGNOR-195896
P11309	P61073	1	phosphorylation	up-regulates quantity	0.365	Pim-1 and Pim-3 enhance phosphorylation and cell surface expression of CXCR4.\|When the in vitro phosphorylated fragments were detected with the anti-phospho (Ser339)-CXCR4 antibody, it became evident that both Pim-1 and Pim-3, but not Pim-2 can phosphorylate CXCR4 on Ser339 (XREF_FIG).	SIGNOR-278450
Q9HCJ2	P78352	1	binding	up-regulates activity	0.365	A possible function for the NGL–PSD-95 interaction is to couple trans-synaptic adhesion events to the recruitment of PSD-95 and other PSD-95-associated postsynaptic proteins. PSD-95 and liprin-α may be key synaptic scaffolding proteins that couple trans-synaptic adhesions to the assembly of synaptic proteins/vesicles	SIGNOR-264050
Q16512	P29966	1	phosphorylation	down-regulates activity	0.365	PRK1 phosphorylates MARCKS at the PKC sites: serine 152, serine 156 and serine 163.	SIGNOR-249671
O14920	P20749	1	phosphorylation	up-regulates activity	0.365	Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3. Phosphorylation by Erk2 and IKK1/2 of Ser114 and Ser446 converts Bcl3 into a transcriptional coregulator by facilitating its recruitment to DNA.	SIGNOR-277364
Q9UKC9	O00459	1	binding	down-regulates quantity by destabilization	0.365	FBXL2 binds p85α and p85β. p85β is targeted for ubiquitylation and degradation by SCF FBXL2.	SIGNOR-272111
Q8NEZ5	O43474	1	ubiquitination	down-regulates quantity by destabilization	0.365	F-box protein FBXO22 mediates polyubiquitination and degradation of KLF4 to promote hepatocellular carcinoma progression	SIGNOR-273444
P23470	P06213	1	dephosphorylation	up-regulates activity	0.365	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-254703
Q14289	Q14247	1	phosphorylation	up-regulates activity	0.365	In conclusion, these data suggest that Pyk2 phosphorylates cortactin on tyrosine residues Y421, Y466, and Y482.\|To confirm the direct and indirect effects of Pyk2 on cortactin phosphorylation, we used cells overexpressing Arg YFP and treated with Pyk2 siRNA or a nonsilencing siRNA.	SIGNOR-278344
Q00535	Q9NQT8	1	phosphorylation	down-regulates activity	0.365	Overexpression of Cdk5 or its activator p35 promoted and inhibition of Cdk5 activity prevented the KIF13B-TRPV1 association, indicating that Cdk5 promotes TRPV1 anterograde transport by mediating the motor-cargo association. Cdk5 phosphorylates KIF13B at Thr-506, a residue located in the FHA domain. T506A mutation reduced the motor-cargo interaction and the cell-permeable TAT-T506 peptide, targeting to the Thr-506, decreased TRPV1 surface localization, demonstrating the essential role of Thr-506 phosphorylation in TRPV1 transport.	SIGNOR-262737
Q92993	P15172	1	binding	up-regulates activity	0.365	Tip60 regulates myoblast differentiation by enhancing the transcriptional activity of MyoD via their physical interactions.	SIGNOR-237675
Q86UR5	Q01668	1	binding	up-regulates activity	0.365	Here, we report an interaction of the C2B domain of RIM2α and RIM3γ with the C-terminus of the pore-forming α-subunit of CaV1.3 channels (CaV1.3α1), which mediate stimulus-secretion coupling at the ribbon synapses of cochlear inner hair cells (IHCs). In conclusion, we propose that RIM2α and RIM3γ directly interact with the C-terminus of the pore-forming subunit of CaV1.3 Ca2+ channels and positively regulate their plasma membrane expression in HEK293 cells.	SIGNOR-264358
O15409	P78509	1	transcriptional regulation	up-regulates quantity by expression	0.365	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-266833
P57086	P28698	1	binding	up-regulates activity	0.365	Co-immunoprecipitation and yeast two-hybrid analyses demonstrate that MZF1B and RAZ1 associate in vitro via a SCAN box-dependent mechanism. The interaction between MZF1B and RAZ1 might be necessary for mediating MZF1B function	SIGNOR-221561
P48736	P12931	1	phosphorylation	up-regulates activity	0.365	PI3Kγ mediated phosphorylation of Src enhances Src activity protein kinase activity of PI3K phosphorylates serine residue 70 on Src to enhance its activity and induce EGFR transactivation following βAR stimulation.	SIGNOR-277225
Q05397	P49841	1	phosphorylation	up-regulates activity	0.365	Inhibition of FAK by its small molecule inhibitor attenuated IL-33-induced tyrosine 216 phosphorylation of GSK3beta in a both time- and dose dependent manner (XREF_FIG).\|The current study indicates that FAK activated GSK3beta modulates ST2L internalization and signaling.	SIGNOR-278986
P23760	P22455	1	transcriptional regulation	up-regulates quantity by expression	0.365	FGFR4 is a transcriptional target of PAX3 and the PAX3-FOXO1 fusion protein found in ARMS.	SIGNOR-251572
P17676	P49675	1	transcriptional regulation	up-regulates quantity by expression	0.365	Electrophoretic mobility shift assay demonstrated that this region of the StAR promoter was bound by C/EBPalpha, C/EBPbeta, and CREB. Forced expression of either C/EBPalpha or C/EBPbeta alone was sufficient to up-regulate StAR promoter activity whereas PGE(2) was needed to induce StAR promoter activity in CREB-overexpressed cells.	SIGNOR-254046
Q02156	Q92993	1	phosphorylation	up-regulates activity	0.365	At least two TIP60 residues, Thr298 and Ser300, can be targeted in vitro by PKCepsilon.\|In vitro, protein kinase C epsilon phosphorylates Tat-interactive protein 60 kDa on at least two sites within the acetyltransferase domain.	SIGNOR-279309
Q99623	P15172	1	binding	down-regulates	0.365	Phb2 interacts with both myod and mef2, and represses both myod- and mef2-dependent gene transcription. Furthermore, binding of phb2 to both myod and mef2 significantly decreases upon myogenic differentiation.	SIGNOR-235843
P68400	Q01105-2	1	phosphorylation	down-regulates	0.365	Ckii-mediated phosphorylation at ser9 hinders nuclear import of set	SIGNOR-200798
P63279	P01100	1	sumoylation	down-regulates activity	0.365	We report here that lysine 265 of c-Fos is conjugated by the peptidic posttranslational modifiers SUMO-1, SUMO-2, and SUMO-3 and that c-Jun can be sumoylated on lysine 257 as well as on the previously described lysine 229. Sumoylation of c-Fos preferentially occurs in the context of c-Jun/c-Fos heterodimers.\|Inhibition of c-Fos and c-Jun sumoylation stimulates AP-1-dependent transcription activity.	SIGNOR-263013
Q05086	O43166	1	polyubiquitination	down-regulates quantity by destabilization	0.365	the purified E6AP enhanced the ubiquitination and degradation of E6TP1 in the presence of E6 in vitro. Additionally, the expression of a dominant-negative E6AP mutant (C833A) in cells inhibited the E6-induced degradation of E6TP1. These findings demonstrate that the E6-induced decrease in the levels of E6TP1 protein involves the E6AP-mediated ubiquitination followed by proteasome-dependent degradation.	SIGNOR-272608
P17612	Q9Y6Q9	1	phosphorylation	up-regulates	0.364	Herein, we report the successful identification of six functional in vivo src-3 phosphorylation sites.	SIGNOR-129349
P06454	P55211	1	binding	down-regulates	0.364	PHAP proteins promoted caspase-9 activation after apoptosome formation, whereas ProT negatively regulated caspase-9 activation by inhibiting apoptosome formation.	SIGNOR-259079
O43711	P14921	1	binding	down-regulates activity	0.364	We show that the cortical thymic maturation arrest in T-lineage ALLs that overexpress TLX1 or TLX3 is due to binding of TLX1/TLX3 to ETS1, leading to repression of T cell receptor (TCR) α enhanceosome activity and blocked TCR-Jα rearrangement.	SIGNOR-259098
P17252	P29350	1	phosphorylation	down-regulates	0.364	Protein kinase calpha therefore critically and negatively regulates shp-1 function, forming part of a mechanism to retain shp-1 in a basal active state through interaction with its sh2 domains, and phosphorylating its c-terminal ser591 upon cellular activation	SIGNOR-126876
P28482	Q15788	1	phosphorylation	up-regulates	0.364	Furthermore, erk-2 phosphorylated threonine 1179 and serine 1185 (and to a lesser extent, serine 395) in vitro, suggesting the importance of this pathway for src-1 regulation. Treatment of cells expressing src-1 with epidermal growth factor enhanced the ligand-dependent, progesterone receptor-mediated activation of a target reporter gene.	SIGNOR-74880
P17252	Q96KS0	1	phosphorylation	down-regulates	0.364	Thus, recombinant phd1 was examined for in vitro phosphorylation using protein kinase a, protein kinase calpha, casein kinase i and ii and erk2. The protein was most strongly phosphorylated by protein kinase calpha, and the phosphorylation sites were found to be ser-132, ser-226 and ser-234.Mutation Of ser-132 or ser-234 to asp or glu diminished the enzymatic activity to 25-60%, while mutation of ser-226 scarcely influenced the activity.	SIGNOR-180203
P16298	Q92934	1	dephosphorylation	up-regulates activity	0.364	Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD\|Calcineurin was found to dephosphorylate BAD, a pro-apoptotic member of the Bcl-2 family, thus enhancing BAD heterodimerization with Bcl-xL and promoting apoptosis.	SIGNOR-248384
P17252	P49802	1	phosphorylation	down-regulates activity	0.364	TNF-α rapidly increases the concentration of functionally active RGS7 protein through two mechanisms. TNF-induced dephosphorylation of serine 434 liberates RGS7 from 14-3-3 binding and inhibition. , PKC α catalyzes the incorporation of phosphate into a truncation of RGS7 fused to maltose-binding protein (MBP.RGS7315–469).	SIGNOR-263165
P51812	P05114	1	phosphorylation	down-regulates activity	0.364	We report here that the NBD of the HMGN1 and -N2 protein family is highly and specifically phosphorylated during mitosis and that this phosphorylation has a major functional consequence: it abolishes the interaction of the proteins with its chromatin targets.	SIGNOR-249100
Q96P31	P43403	1	binding	up-regulates activity	0.364	Tyrosine phosphorylation of SPAP2a by c-Src and in vitro. Tyrosine-phosphorylated SPAP2 is specifically associated with SH2 domain-containing tyrosine kinases Syk and Zap70 and SH2 domain-containing tyrosine phosphatases SHP-1 and SHP-2. Site-specific mutagenesis studies revealed that tyrosyl residues 650 and 662 embedded in the ITIMs are responsible for the binding of Syk and Zap70 while tyrosyl residues 692 and 722 embedded in the ITIMs are involved in interactions with SHP-1 and SHP-2.	SIGNOR-274012
P63241	P04637	1	transcriptional regulation	up-regulates quantity by expression	0.364	eIF5A regulated p53 protein expression. Further analysis by reverse transcription PCR showed eIF5A-activated p53 transcription. The effect of eIF5A on p53 transcriptional activity was further demonstrated by the increasing expressions of p21 and Bax, well known target genes of p53.	SIGNOR-266375

Q9ULV8

P07949

1

ubiquitination

down-regulates quantity by destabilization

0.368

Here we show that Cbl-c binds wild-type and MEN2A isoforms of the receptor tyrosine kinase, RET, and that Cbl-c enhances ubiquitination and degradation of activated RET.|We show that Cbl-c negatively regulates RET by ubiquitinating and downregulating the activated RTK while Enigma positively regulates activated RET by preventing Cbl-c binding to RET and thus preventing RET ubiquitination and degradation while promoting RET mitogenic signaling.

SIGNOR-278674

Q13882

Q6P1J9

1

phosphorylation

down-regulates activity

0.368

PTK6 impairs the coactivator function of parafibromin.|To study the functional consequence of parafibromin phosphorylation by PTK6, we examined the effect of PTK6 inhibition on Wnt signal activation.

SIGNOR-279273

Q96NI6

Q13332

1

binding

up-regulates activity

0.368

SALM5 trans-synaptically interacts with LAR-RPTPs in a splicing-dependent manner to regulate synapse development. we identified LAR-RPTPs as novel ligands of SALM5 that mediates SALM5-dependent presynaptic differentiation in a splicing-dependent manner. Our data indicate that SALM5 interacts with all three known LAR-RPTPs—LAR, PTPδ, and PTPσ (Fig. 1).

SIGNOR-264088

Q8TAS1

P46527

1

phosphorylation

up-regulates

0.367

Hkis is a nuclear protein that binds the c-terminal domain of p27(kip1) and phosphorylates it on s10 in vitro and in vivo, promoting its nuclear export to the cytoplasm.Phosphorylation at serine 10, a major phosphorylation site of p27(kip1), increases its protein stability

SIGNOR-90274

Q06124

Q99683

1

dephosphorylation

up-regulates

0.367

Previously we have shown that tyrosine 718 of ask1 when phosphorylated is critical for socs1 binding and socs1-mediated degradation of ask1we identified jak2 and shp2 as a tyr-718-specific kinase and phosphatase, respectively.

SIGNOR-184604

O15287

Q13813

1

null

up-regulates quantity by stabilization

0.367

In FA cells, deficiencies in FA proteins lead to decreased stability of alphaRIISp |These results demonstrate that one of the FA proteins, FANCG, contains a motif that interacts directly with the SH3 domain of alphaIISp. We propose that this binding of FANCG to alphaIISp may be important for the stability of alphaIISp in cells and the role alphaIISp plays in the DNA repair process.|

SIGNOR-263275

P06241

Q15700

1

phosphorylation

up-regulates activity

0.367

Recombinant PSD-93 was phosphorylated by Fyn in vitro, and Tyr-384 was identified as a major phosphorylation site. In COS7 cells, exogenously expressed PSD-93 was phosphorylated, dependent on its membrane localization. In addition, tyrosine-phosphorylated PSD-93 was able to bind to Csk, a negative regulator of Src family kinases, in vitro as well as in a brain lysate.

SIGNOR-262874

P28482

Q9NZV8

1

phosphorylation

up-regulates activity

0.367

We determined that the Kv4.2 C-terminal cytoplasmic domain is an effective ERK2 substrate, and that it is phosphorylated at three sites: Thr(602), Thr(607), and Ser(616). Phosphorylation of the Kv4.2 channel by ERK during LTP induction may lead to increased excitability and membrane depolarization of neurons, which would increase the magnitude of the calcium influx and the probability of triggering LTP.

SIGNOR-262935

Q8IYU2

P63000

1

ubiquitination

down-regulates quantity by destabilization

0.367

The CNF1 toxin of pathogenic Escherichia coli addresses Rac1 to ubiquitin-proteasome system (UPS). We report the essential role of the tumor suppressor HACE1, a HECT-domain containing E3 ubiquitin-ligase, in the targeting of Rac1 to UPS. HACE1 binds preferentially GTP-bound Rac1 and catalyzes its polyubiquitylation

SIGNOR-255538

P12931

Q9UK53

1

phosphorylation

down-regulates activity

0.367

Src Decreases the Stability and Level of ING1.|This study, as well as a previous report identifying Ser-126 of ING1 as a kinase target, confirm that ING1 stability is also regulated by phosphorylation. However, the mechanism may be complex since phosphorylation of Ser-126 stabilizes the protein while phosphorylation by Src reduces ING1 stability and causes a relocalization of ING1 from the nucleus to the cytoplasm.

SIGNOR-279760

Q5S007

P46459

1

phosphorylation

up-regulates activity

0.367

LRRK2 phosphorylates full-length NSF at threonine 645 in the ATP binding pocket of D2 domain. Functionally, NSF phosphorylated by LRRK2 displays enhanced ATPase activity and increased rate of SNARE complex disassembling.

SIGNOR-277196

Q14526

P40763

1

binding

down-regulates quantity by repression

0.367

HIC1 interacts with the DNA binding domain of STAT3 and suppresses the binding of STAT3 to its target gene promoters. HIC1 C-terminal domain binds to STAT3. HIC1 mutant defective in STAT3 interaction reduced its repressive effect on STAT3 DNA binding activity, the reporter activity and gene expression of the VEGF and c-Myc genes, and cell growth in MDA-MB 231 cells.

SIGNOR-254246

P31749

Q12906

1

phosphorylation

up-regulates activity

0.367

Upon T cell activation, NF90 translocates from the nucleus into the cytoplasm, where it binds to the AU-rich element-containing 3' untranslated regions of IL-2 mRNA and stabilizes it.|Our previous work showed that CD28 costimulation of T cells activated AKT to phosphorylate NF90 at Ser647 and caused NF90 to undergo nuclear export and stabilize IL-2 mRNA.

SIGNOR-252512

Q92466

Q01094

1

binding

up-regulates

0.367

We show that ddb, a putative dna repair protein, associates with the activation domain of e2f1 / expression of ddb specifically stimulated e2f1-activated transcription

SIGNOR-54102

P49841

Q9Y6R4

1

binding

down-regulates

0.367

Gsk3beta binding to mekk4 blocks mekk4 dimerization that is required for mekk4 activation, effectively inhibiting mekk4 stimulation of the jnk and p38 mapk pathways

SIGNOR-157541

Q15349

P22736

1

phosphorylation

down-regulates activity

0.367

Phosphorylation of a residue in the DNA-binding region (Ser-350 of NGFI-B and 354 of Nur77) has been described in detail to have effect on the transcriptional function of the protein [11, 24]. Growth-related kinase pp90rsk, but not ERK1 (pp44mapk), was shown to phosphorylate recombinant Nur77 in vitro in the DNA binding domain, but not the amino-terminus, using an immune complex kinase as- say [11].

SIGNOR-249429

Q05655

Q13501

1

phosphorylation

up-regulates activity

0.367

Data presented here suggested that Vps34 stimulates tumor development mainly through PKC-\u03b4- activation of p62.|In conclusion, elevation of Vps34 results in tumor progression via the PKC-\u03b4-phosphorylation of p62 at S349 and PKC-\u03b4 involved phosphorylation of Raf 1 at Y340/341.|Vps34 induces PKC-\u03b4-dependent phosphorylation of p62.

SIGNOR-280086

Q96NX9

P15173

1

transcriptional regulation

down-regulates quantity by repression

0.367

We confirmed Dach2 is a Mgn transcriptional repressor that mediates HDAC-dependent regulation by (i) overexpressing Dach2 in myotubes harboring the 133-bp Mgn promoter and (ii) rescuing TSA-mediated Mgn repression by Dach2 knockdown.

SIGNOR-261579

Q9HC98

P23443

1

phosphorylation

up-regulates activity

0.367

Here we demonstrate that in addition to phosphorylating S6K1 and SGK1 at their hydrophobic motif, NEK6 also phosphorylates S6K1 at two other sites and phosphorylates SGK1 at one other site in vitro. Analysis of the peptides phosphorylated by NEK6 (Fig 2), performed in the present study has confirmed this, and identified two novel sites on S6K1 (Ser53 and Ser403) as major sites of NEK6 phosphorylation.

SIGNOR-262953

P49841

Q92993

1

phosphorylation

up-regulates

0.367

We demonstrate that gsk-3 phosphorylates serine 86 of the p53-acetyltransferase tip60. A tip60(s86a) mutant was less active to induce p53 k120 acetylation, histone 4 acetylation, and expression of puma

SIGNOR-174049

P54646

P41235

1

phosphorylation

down-regulates quantity by destabilization

0.367

AMPK directly phosphorylates HNF4alpha and represses its transcriptional activity. AMPK-mediated phosphorylation of HNF4alpha on serine 304 had a 2-fold effect, reducing the ability of the transcription factor to form homodimers and bind DNA and increasing its degradation rate in vivo. Phosphorylation of HNF4α on Ser-304 reduces protein stability.

SIGNOR-250322

O60674

Q99683

1

phosphorylation

down-regulates quantity by destabilization

0.367

Furthermore, JAK2, but not JAK1, directly bound to and phosphorylated ASK1 at Tyr-718, leading to an enhanced association of ASK1 with SOCS1 and subsequent ASK1 degradation.

SIGNOR-276145

P67775

Q13043

1

dephosphorylation

down-regulates

0.367

Rassf1a apparently protects mst1/2 against inactivation by pp2a , the phosphatases that dephosphorylate the stimulatory thr-183 and thr-180 of mst1 andmst2, respectively.

SIGNOR-201270

P63279

P35712

1

sumoylation

down-regulates activity

0.367

We show that SOX6 is modified in vitro and in vivo by small ubiquitin‐related modifier (SUMO) on two distinct sites. Mutation of both sites abolished SOX6 sumoylation and increased SOX6 transcriptional activity. SUMO dependent repression of SOX6 transcription was promoted by UBC9 whereas siRNA to UBC9, cotransfection of inactive UBC9 or a SUMO protease increased SOX6 transcriptional activity.

SIGNOR-256130

P35452

O75444

1

binding

down-regulates activity

0.367

Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf.

SIGNOR-221887

Q13233

P46531

1

phosphorylation

down-regulates activity

0.367

As a result, MEKK1 suppresses the Notch1 intracellular domain protein stability and transcriptional activity.|We confirmed that MEKK1 binds to Notch1 intracellular domain and phosphorylates the Notch1 intracellular domain Threonine 2512 residue.

SIGNOR-279628

Q13153

Q70Z35

1

phosphorylation

down-regulates activity

0.367

P21-activated Kinases (PAKs) Mediate the Phosphorylation of PREX2 Protein to Initiate Feedback Inhibition of Rac1 GTPase. PAK-mediated phosphorylation of PREX2 reduced GEF activity toward Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ.

SIGNOR-277181

Q969H0

Q16204

1

binding

down-regulates

0.367

Fbxw7 interacts with and targets ccdc6 for ubiquitin-mediated proteasomal degradation

SIGNOR-199279

P24941

Q8IZL8

1

phosphorylation

up-regulates

0.367

We identified ser(477) and ser(991) of pelp1 as cdk phosphorylation sites. we conclude that pelp1 is a novel substrate of interphase cdks and that its phosphorylation is important for the proper function of pelp1 in modulating hormone-driven cell cycle progression and also for optimal e2f transactivation function.

SIGNOR-167766

Q15831

Q9NRH2

1

phosphorylation

up-regulates activity

0.367

We demonstrate that LKB1 activates SNRK by phosphorylating the T‐loop residue (Thr173)

SIGNOR-260824

Q7KZI7

Q9BXM7

1

phosphorylation

up-regulates activity

0.367

MARK2 phosphorylated and activated the cleaved form of PINK1 (DeltaN-PINK1

SIGNOR-278975

Q16539

Q13950

1

phosphorylation

up-regulates activity

0.367

Mechanistic analysis revealed that the TAK1–MKK3/6–p38 MAPK axis phosphorylated Runx2, promoting its association with the coactivator CREB-binding protein (CBP), which was required to regulate osteoblast genetic programs. These findings reveal an in vivo function for p38β and establish that MAPK signaling is essential for bone formation in vivo.

SIGNOR-255777

Q13464

P08670

1

phosphorylation

down-regulates activity

0.367

We found that vimentin, the most widely expressed intermediate filament protein, served as an excellent substrate for Rho-associated kinase (Rho-kinase) and that vimentin phosphorylated by Rho-kinase lost its ability to form filaments in vitro. Two amino-terminal sites on vimentin, Ser38 and Ser71, were identified as the major phosphorylation sites for Rho-kinase, and Ser71 was the most favored and unique phosphorylation site for Rho-kinase in vitro.

SIGNOR-248998

P28482

Q53EZ4

1

phosphorylation

down-regulates

0.367

Upon mitotic entry, centrosome dissociation of cep55 is triggered by erk2/cdk1-dependent phosphorylation at s425 and s428. S425/428 phosphorylation is required for interaction with plk1, enabling phosphorylation of cep55 at s436. enabling it to relocate to the midbody to function in mitotic exit and cytokinesis.

SIGNOR-140890

Q12955

P11532

1

relocalization

up-regulates quantity

0.367

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-266715

P27361

Q16204

1

phosphorylation

up-regulates activity

0.367

We have characterized the H4(D10S170) gene product, showing that it is a ubiquitously expressed 55 KDa nuclear and cytosolic protein that is phosphorylated following serum stimulation. This phosphorylation was found to depend on mitogen-activated protein kinase (MAPK) Erk1/2 activity and to be associated to the relocation of H4(D10S170) from the nucleus to the cytosol. S244 is the major target residue of ERK1

SIGNOR-276003

P08246

P12259

1

cleavage

up-regulates activity

0.366

Human neutrophil elastase activates human factor V but inactivates thrombin-activated human factor V|NH2-terminal sequence analysis of F.V treated with HNE indicated cleavage at Ile819 and Ile1484 under conditions during which the procofactor expressed enhanced cofactor activity in the prothrombinase complex.

SIGNOR-263637

Q15418

P30304

1

phosphorylation

down-regulates

0.366

Rsk promotes g2/m transition through activating phosphorylation of cdc25a and cdc25b rsk is likely to be more active in mitotic cells than in interphase cells, as evidenced by the phosphorylation status of t359/s363 in rsk. Together, these findings indicate that rsk promotes g2/m transition in mammalian cells through activating phosphorylation of cdc25a and cdc25b.

SIGNOR-202117

P17252

P14136

1

phosphorylation

down-regulates activity

0.366

Glial fibrillary acidic protein (GFAP), the intermediate filament component of astroglial cells, can serve as an excellent substrate for both cAMP-dependent protein kinase and protein kinase C, in vitro. GFAP phosphorylated by each protein kinase does not polymerize, and the filaments that do polymerize tend to depolymerize after phosphorylation. Dephosphorylation of phospho-GFAP by phosphatase led to a recovery of the polymerization competence of GFAP. Most of the phosphorylation sites for cAMP-dependent protein kinase and protein kinase C on GFAP are the same, Ser-8, Ser-13, and Ser-34. cAMP-dependent protein kinase has one additional phosphorylation site, Thr-7.

SIGNOR-248862

Q15208

Q96QF0

1

phosphorylation

up-regulates activity

0.366

We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation.

SIGNOR-263036

P17252

Q16760

1

phosphorylation

down-regulates activity

0.366

The plasma membrane translocation of diacylglycerol kinase delta1 is negatively regulated by conventional protein kinase C-dependent phosphorylation at Ser-22 and Ser-26 within the pleckstrin homology domain.

SIGNOR-249265

P50613

Q13285

1

phosphorylation

up-regulates

0.366

In conclusion, our results indicate that cdk7, as part of the cak complex and tfiih, phosphorylates sf1 at s203 followed by increased transcriptional activity of sf1

SIGNOR-157952

P11362

P00338

1

phosphorylation

up-regulates

0.366

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

SIGNOR-176730

Q9BV47

P04637

1

dephosphorylation

down-regulates activity

0.366

Dual-specificity phosphatase 26 is a novel p53 phosphatase and inhibits p53 tumor suppressor functions in human neuroblastoma|Inhibiting DUSP26 expression in the IMR-32 neuroblastoma cell line enhanced doxorubicin-induced p53 phosphorylation at Ser20 and Ser37, p21, Puma, Bax expression as well as apoptosis

SIGNOR-248765

P49137

O95816

1

phosphorylation

up-regulates

0.366

We provided definite evidence that mapkapk2 phosphorylates bag2 at ser 20 in vitro and in vivo. These results demonstrate that bag2 is a novel component of the p38 mapk signaling pathways.

SIGNOR-126953

P01116

Q13233

1

binding

up-regulates

0.366

Mitogen-activated protein kinase kinase kinase (mekk1) is a serine-threonine kinase that regulates sequential protein kinase pathways involving stress-activated protein kinases and mitogen-activated protein kinases. Mekk1 is activated in response to growth factor stimulation of cells and by expression of activated ras. mekk1 directly binds ras.GTP. Thus, ras interacts with protein kinases of both the raf and mekk families.

SIGNOR-32620

Q00535

P35712

1

phosphorylation

down-regulates quantity

0.366

GST-Sox6 was phosphorylated in vitro by Cdk5 and p35 (XREF_FIG).|Inhibition of Cdk5 activity by DN Cdk5 and roscovitine increases the Sox6 expression in primary cortical neurons.

SIGNOR-279365

Q9Y6D6

P61204

1

guanine nucleotide exchange factor

up-regulates activity

0.366

Brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1) is an approximately 200-kDa brefeldin A-inhibited guanine nucleotide-exchange protein that preferentially activates ADP-ribosylation factor 1 (ARF1) and ARF3.

SIGNOR-272148

Q96AX9

Q13224

1

ubiquitination

down-regulates quantity

0.366

Mib2 is localized to the PSD of dendrites in hippocampal neurons and directly ubiquitinates GluN2B in a manner dependent on the non receptor tyrosine kinase Fyn.|These findings suggest that Mib2 mediates proteasome dependent degradation of GluN2B subunits, which may provide a reciprocal mechanism to SCF Fbx2 regulation of GluN2A.

SIGNOR-278762

Q5H8C1

Q6UXI9

1

transcriptional regulation

up-regulates quantity by expression

0.366

The loss of QBRICK significantly diminished the expression of nephronectin, an integrin α8β1 ligand necessary for renal development. In vivo, nephronectin associated with QBRICK and localized at the sublamina densa region, where QBRICK was also located. Collectively, these findings indicate that QBRICK facilitates the integrin α8β1-dependent interactions of cells with basement membranes by regulating the basement membrane assembly of nephronectin and explain why renal defects occur in Fraser syndrome.

SIGNOR-253308

P48730

Q9GZV5

1

phosphorylation

down-regulates

0.366

LATS1/2-mediated phosphorylation of a conserved serine in this region (Ser311 in human TAZ; Ser397 in human YAP) primes for further phosphorylation by CK1_/_ kinases (Ser314 on human TAZ; Ser400/403 in human YAP)

SIGNOR-234438

P68400

Q16623

1

phosphorylation

up-regulates

0.366

In this report, we show that syntaxin-1a is phosphorylated in vitro by cki on thr21. Casein kinase ii (ckii) has been shown previously to phosphorylate syntaxin-1a in vitro and we have identified ser14 as the ckii phosphorylation site. the phosphorylation of syntaxin-1a by ckii enhances its capacity to associate with synaptotagmin [21]. Therefore, phosphorylation of ser14 by ckii suggests an important role for this residue in regulating the interaction between syntaxin-1a and synaptotagmin

SIGNOR-114840

Q9UHD2

A5D8V6

1

phosphorylation

down-regulates activity

0.366

We have identified that TBK1 may target and phosphorylate VPS37C, a structural component of ESCRT-I complex, and serve as a ratelimiting factor in the control of PTAP-dependent (HIV-1, MLV/p6, and EIAV/PTAP), but not PPPY-dependent (MLV, EIAV/PPPY) retrovirus budding, independent of its role in IFN-I signaling.

SIGNOR-279768

Q9BV47

Q13158

1

dephosphorylation

down-regulates activity

0.366

This multi-functionality of fadd may depend primarily on its subcellular location. Fadd shuttles between the cytosol and the nucleus and this signal is unclear;however, fadd trafficking requires phosphorylation of the protein on ser194dusp26 suppresses cell proliferation by fadd dephosphorylation

SIGNOR-204559

Q05655

Q09472

1

phosphorylation

down-regulates

0.366

Inhibition of histone acetyltransferase function of p300 by pkcdeltawe found that pkcdelta but not classical pkc, specifically phosphorylates p300 at serine 89 in vitro and in vivo. This phosphorylation causes inhibition of p300 intrinsic hat activity.

SIGNOR-94263

Q96GD4

P54274

1

phosphorylation

up-regulates activity

0.366

Our data indicate that AURKB can phosphorylate the integral telomere DNA-binding Shelterin protein TERF1 at S404 (within the DNA-binding domain) in vitro .

SIGNOR-279440

Q13153

Q9Y6X9

1

phosphorylation

up-regulates activity

0.366

We demonstrate that PAK1-mediated MORC2 phosphorylation promotes cell cycle progression, defective phosphorylation of MORC2-S677A results in attenuated cell proliferation and tumorigenicity of gastric cancer cells, which is significantly enhanced in overexpression of phospho-mimic MORC2-S677E form, suggesting the importance of MORC2 phosphorylation in tumorigenesis.

SIGNOR-273714

Q9UHC7

Q8N726

1

polyubiquitination

down-regulates quantity by destabilization

0.366

Biochemical analyses confirmed that MKRN1 targets p14ARF for ubiquitination and subsequent proteasome-dependent degradation.The Skp1-Cul1-F-box-protein44 (SCF(FBXO44)) complex ubiquitinates full-length BRCA1 in vitro.

SIGNOR-272036

P06241

Q96J02

1

phosphorylation

down-regulates activity

0.366

Tyrosine phosphorylation of Itch appears to reduce its interaction with its substrate JunB. The turnover of JunB is accelerated in Fyn-deficient T cells, which is further reconstituted by Itch Tyr371 mutation

SIGNOR-245332

P06241

Q12913

1

phosphorylation

up-regulates activity

0.366

We demonstrate here that DEP-1 is phosphorylated in a Src- and Fyn-dependent manner on Y1311 and Y1320, which bind the Src SH2 domain. This allows DEP-1-catalyzed dephosphorylation of Src inhibitory Y529 and favors the VEGF-induced phosphorylation of Src substrates VE-cadherin and Cortactin.

SIGNOR-276372

Q5T447

Q9UDY8

1

polyubiquitination

up-regulates quantity by stabilization

0.366

HECTD3 promotes MALT1 ubiquitination with nondegradative polyubiquitin chains by direct interacting with the MALT1 through its N-terminal destruction of cyclin domain. HECTD3 does not target MALT1 for degradation but stabilize it.

SIGNOR-272096

O75309

P35222

1

binding

up-regulates activity

0.366

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

SIGNOR-265855

P17612

Q14344

1

phosphorylation

down-regulates activity

0.366

PKA directly phosphorylates Galpha(13). Galpha(13)-T203A mutant (in COS-7 cells) could not be phosphorylated by PKA. PKA blocks Rho activation by phosphorylation of Galpha(13) Thr(203).

SIGNOR-249985

O00213

Q63HK5

1

relocalization

up-regulates activity

0.366

We carried out yeast two-hybrid studies with a PTB domain of FE65, focusing on those genes that might be involved in nuclear signaling, and identified and validated Teashirt proteins as FE65 interacting proteins in neurons. Using reporter systems, we observed that FE65 could simultaneously recruit SET, a component of the inhibitor of acetyl transferase, and Teashirt, which in turn recruited histone deacetylases, to produce a powerful gene-silencing complex.

SIGNOR-264813

P49674

Q9GZV5

1

phosphorylation

down-regulates

0.366

LATS1/2-mediated phosphorylation of a conserved serine in this region (Ser311 in human TAZ; Ser397 in human YAP) primes for further phosphorylation by CK1_/_ kinases (Ser314 on human TAZ; Ser400/403 in human YAP)

SIGNOR-230747

P84022

Q06710

1

binding

down-regulates activity

0.366

DNA Binding Activity of Pax8 to the NIS Promoter Is Reduced by Smad3. TGF-Î² decreases Pax8 DNA binding to the NIS promoter and also found a physical interaction between Pax8 and Smad3.

SIGNOR-251992

P12931

P41235

1

phosphorylation

down-regulates

0.365

Here we show that c-src phosphorylates human hnf4_ on three tyrosines phosphomimetic mutants in the lbd decrease p1-hnf4_ protein stability, nuclear localization and transactivation function.

SIGNOR-195896

P11309

P61073

1

phosphorylation

up-regulates quantity

0.365

Pim-1 and Pim-3 enhance phosphorylation and cell surface expression of CXCR4.|When the in vitro phosphorylated fragments were detected with the anti-phospho (Ser339)-CXCR4 antibody, it became evident that both Pim-1 and Pim-3, but not Pim-2 can phosphorylate CXCR4 on Ser339 (XREF_FIG).

SIGNOR-278450

Q9HCJ2

P78352

1

binding

up-regulates activity

0.365

A possible function for the NGL–PSD-95 interaction is to couple trans-synaptic adhesion events to the recruitment of PSD-95 and other PSD-95-associated postsynaptic proteins. PSD-95 and liprin-α may be key synaptic scaffolding proteins that couple trans-synaptic adhesions to the assembly of synaptic proteins/vesicles

SIGNOR-264050

Q16512

P29966

1

phosphorylation

down-regulates activity

0.365

PRK1 phosphorylates MARCKS at the PKC sites: serine 152, serine 156 and serine 163.

SIGNOR-249671

O14920

P20749

1

phosphorylation

up-regulates activity

0.365

Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3. Phosphorylation by Erk2 and IKK1/2 of Ser114 and Ser446 converts Bcl3 into a transcriptional coregulator by facilitating its recruitment to DNA.

SIGNOR-277364

Q9UKC9

O00459

1

binding

down-regulates quantity by destabilization

0.365

FBXL2 binds p85α and p85β. p85β is targeted for ubiquitylation and degradation by SCF FBXL2.

SIGNOR-272111

Q8NEZ5

O43474

1

ubiquitination

down-regulates quantity by destabilization

0.365

F-box protein FBXO22 mediates polyubiquitination and degradation of KLF4 to promote hepatocellular carcinoma progression

SIGNOR-273444

P23470

P06213

1

dephosphorylation

up-regulates activity

0.365

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-254703

Q14289

Q14247

1

phosphorylation

up-regulates activity

0.365

In conclusion, these data suggest that Pyk2 phosphorylates cortactin on tyrosine residues Y421, Y466, and Y482.|To confirm the direct and indirect effects of Pyk2 on cortactin phosphorylation, we used cells overexpressing Arg YFP and treated with Pyk2 siRNA or a nonsilencing siRNA.

SIGNOR-278344

Q00535

Q9NQT8

1

phosphorylation

down-regulates activity

0.365

Overexpression of Cdk5 or its activator p35 promoted and inhibition of Cdk5 activity prevented the KIF13B-TRPV1 association, indicating that Cdk5 promotes TRPV1 anterograde transport by mediating the motor-cargo association. Cdk5 phosphorylates KIF13B at Thr-506, a residue located in the FHA domain. T506A mutation reduced the motor-cargo interaction and the cell-permeable TAT-T506 peptide, targeting to the Thr-506, decreased TRPV1 surface localization, demonstrating the essential role of Thr-506 phosphorylation in TRPV1 transport.

SIGNOR-262737

Q92993

P15172

1

binding

up-regulates activity

0.365

Tip60 regulates myoblast differentiation by enhancing the transcriptional activity of MyoD via their physical interactions.

SIGNOR-237675

Q86UR5

Q01668

1

binding

up-regulates activity

0.365

Here, we report an interaction of the C2B domain of RIM2α and RIM3γ with the C-terminus of the pore-forming α-subunit of CaV1.3 channels (CaV1.3α1), which mediate stimulus-secretion coupling at the ribbon synapses of cochlear inner hair cells (IHCs). In conclusion, we propose that RIM2α and RIM3γ directly interact with the C-terminus of the pore-forming subunit of CaV1.3 Ca2+ channels and positively regulate their plasma membrane expression in HEK293 cells.

SIGNOR-264358

O15409

P78509

1

transcriptional regulation

up-regulates quantity by expression

0.365

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-266833

P57086

P28698

1

binding

up-regulates activity

0.365

Co-immunoprecipitation and yeast two-hybrid analyses demonstrate that MZF1B and RAZ1 associate in vitro via a SCAN box-dependent mechanism. The interaction between MZF1B and RAZ1 might be necessary for mediating MZF1B function

SIGNOR-221561

P48736

P12931

1

phosphorylation

up-regulates activity

0.365

PI3Kγ mediated phosphorylation of Src enhances Src activity protein kinase activity of PI3K phosphorylates serine residue 70 on Src to enhance its activity and induce EGFR transactivation following βAR stimulation.

SIGNOR-277225

Q05397

P49841

1

phosphorylation

up-regulates activity

0.365

Inhibition of FAK by its small molecule inhibitor attenuated IL-33-induced tyrosine 216 phosphorylation of GSK3beta in a both time- and dose dependent manner (XREF_FIG).|The current study indicates that FAK activated GSK3beta modulates ST2L internalization and signaling.

SIGNOR-278986

P23760

P22455

1

transcriptional regulation

up-regulates quantity by expression

0.365

FGFR4 is a transcriptional target of PAX3 and the PAX3-FOXO1 fusion protein found in ARMS.

SIGNOR-251572

P17676

P49675

1

transcriptional regulation

up-regulates quantity by expression

0.365

Electrophoretic mobility shift assay demonstrated that this region of the StAR promoter was bound by C/EBPalpha, C/EBPbeta, and CREB. Forced expression of either C/EBPalpha or C/EBPbeta alone was sufficient to up-regulate StAR promoter activity whereas PGE(2) was needed to induce StAR promoter activity in CREB-overexpressed cells.

SIGNOR-254046

Q02156

Q92993

1

phosphorylation

up-regulates activity

0.365

At least two TIP60 residues, Thr298 and Ser300, can be targeted in vitro by PKCepsilon.|In vitro, protein kinase C epsilon phosphorylates Tat-interactive protein 60 kDa on at least two sites within the acetyltransferase domain.

SIGNOR-279309

Q99623

P15172

1

binding

down-regulates

0.365

Phb2 interacts with both myod and mef2, and represses both myod- and mef2-dependent gene transcription. Furthermore, binding of phb2 to both myod and mef2 significantly decreases upon myogenic differentiation.

SIGNOR-235843

P68400

Q01105-2

1

phosphorylation

down-regulates

0.365

Ckii-mediated phosphorylation at ser9 hinders nuclear import of set

SIGNOR-200798

P63279

P01100

1

sumoylation

down-regulates activity

0.365

We report here that lysine 265 of c-Fos is conjugated by the peptidic posttranslational modifiers SUMO-1, SUMO-2, and SUMO-3 and that c-Jun can be sumoylated on lysine 257 as well as on the previously described lysine 229. Sumoylation of c-Fos preferentially occurs in the context of c-Jun/c-Fos heterodimers.|Inhibition of c-Fos and c-Jun sumoylation stimulates AP-1-dependent transcription activity.

SIGNOR-263013

Q05086

O43166

1

polyubiquitination

down-regulates quantity by destabilization

0.365

the purified E6AP enhanced the ubiquitination and degradation of E6TP1 in the presence of E6 in vitro. Additionally, the expression of a dominant-negative E6AP mutant (C833A) in cells inhibited the E6-induced degradation of E6TP1. These findings demonstrate that the E6-induced decrease in the levels of E6TP1 protein involves the E6AP-mediated ubiquitination followed by proteasome-dependent degradation.

SIGNOR-272608

P17612

Q9Y6Q9

1

phosphorylation

up-regulates

0.364

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

SIGNOR-129349

P06454

P55211

1

binding

down-regulates

0.364

PHAP proteins promoted caspase-9 activation after apoptosome formation, whereas ProT negatively regulated caspase-9 activation by inhibiting apoptosome formation.

SIGNOR-259079

O43711

P14921

1

binding

down-regulates activity

0.364

We show that the cortical thymic maturation arrest in T-lineage ALLs that overexpress TLX1 or TLX3 is due to binding of TLX1/TLX3 to ETS1, leading to repression of T cell receptor (TCR) α enhanceosome activity and blocked TCR-Jα rearrangement.

SIGNOR-259098

P17252

P29350

1

phosphorylation

down-regulates

0.364

Protein kinase calpha therefore critically and negatively regulates shp-1 function, forming part of a mechanism to retain shp-1 in a basal active state through interaction with its sh2 domains, and phosphorylating its c-terminal ser591 upon cellular activation

SIGNOR-126876

P28482

Q15788

1

phosphorylation

up-regulates

0.364

Furthermore, erk-2 phosphorylated threonine 1179 and serine 1185 (and to a lesser extent, serine 395) in vitro, suggesting the importance of this pathway for src-1 regulation. Treatment of cells expressing src-1 with epidermal growth factor enhanced the ligand-dependent, progesterone receptor-mediated activation of a target reporter gene.

SIGNOR-74880

P17252

Q96KS0

1

phosphorylation

down-regulates

0.364

Thus, recombinant phd1 was examined for in vitro phosphorylation using protein kinase a, protein kinase calpha, casein kinase i and ii and erk2. The protein was most strongly phosphorylated by protein kinase calpha, and the phosphorylation sites were found to be ser-132, ser-226 and ser-234.Mutation Of ser-132 or ser-234 to asp or glu diminished the enzymatic activity to 25-60%, while mutation of ser-226 scarcely influenced the activity.

SIGNOR-180203

P16298

Q92934

1

dephosphorylation

up-regulates activity

0.364

Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD|Calcineurin was found to dephosphorylate BAD, a pro-apoptotic member of the Bcl-2 family, thus enhancing BAD heterodimerization with Bcl-xL and promoting apoptosis.

SIGNOR-248384

P17252

P49802

1

phosphorylation

down-regulates activity

0.364

TNF-α rapidly increases the concentration of functionally active RGS7 protein through two mechanisms. TNF-induced dephosphorylation of serine 434 liberates RGS7 from 14-3-3 binding and inhibition. , PKC α catalyzes the incorporation of phosphate into a truncation of RGS7 fused to maltose-binding protein (MBP.RGS7315–469).

SIGNOR-263165

P51812

P05114

1

phosphorylation

down-regulates activity

0.364

We report here that the NBD of the HMGN1 and -N2 protein family is highly and specifically phosphorylated during mitosis and that this phosphorylation has a major functional consequence: it abolishes the interaction of the proteins with its chromatin targets.

SIGNOR-249100

Q96P31

P43403

1

binding

up-regulates activity

0.364

Tyrosine phosphorylation of SPAP2a by c-Src and in vitro. Tyrosine-phosphorylated SPAP2 is specifically associated with SH2 domain-containing tyrosine kinases Syk and Zap70 and SH2 domain-containing tyrosine phosphatases SHP-1 and SHP-2. Site-specific mutagenesis studies revealed that tyrosyl residues 650 and 662 embedded in the ITIMs are responsible for the binding of Syk and Zap70 while tyrosyl residues 692 and 722 embedded in the ITIMs are involved in interactions with SHP-1 and SHP-2.

SIGNOR-274012

P63241

P04637

1

transcriptional regulation

up-regulates quantity by expression

0.364

eIF5A regulated p53 protein expression. Further analysis by reverse transcription PCR showed eIF5A-activated p53 transcription. The effect of eIF5A on p53 transcriptional activity was further demonstrated by the increasing expressions of p21 and Bax, well known target genes of p53.

SIGNOR-266375