GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
O95292	Q92953	relocalization	up-regulates quantity	0.2	Confirmation that Kv2.1 and -2.2 bind VAPA and VAPB employed colocalization/redistribution, siRNA knockdown, and Förster resonance energy transfer (FRET)-based assays.\|As Kv2.1 accumulates on the surface it begins to bind ER VAPs and form the large and stable membrane junctions.	SIGNOR-262123
Q08289	P55040	binding	down-regulates activity	0.2	Two functions for Gem have been demonstrated, including inhibition of voltage-gated calcium channel activity and inhibition of Rho kinase-mediated cytoskeletal reorganization, such as stress fiber formation and neurite retraction. These functions for Gem have been ascribed to its interaction with the calcium channel Β subunit and Rho kinase Β, respectively.	SIGNOR-261720
Q01196	P28482	phosphorylation	up-regulates activity	0.2	We have identified four phosphorylation sites on AML1c that are necessary for transcriptional activity of AML1c in K562 and 293T cells (27).4 Mutation of these four sites (serine 276, serine 293, serine 303, and threonine 300) to alanine abolishes transcriptional activation, whereas mutation of these sites to aspartic acid (which mimics phosphorylation) results in a hyperactive protein. The presence of these mutations results in an increase in the amount of ubiquitinated AML1c in the matrix, and increases the half-life of this insoluble AML1c. One possible model to explain these observations is that phosphorylation might be necessary for the normal process of both proteasome degradation and transcriptional activation.	SIGNOR-138973
O94916	P06493	phosphorylation	up-regulates	0.2	High nacl-induced activation of cdk5 increases phosphorylation of the osmoprotective transcription factor tonebp/orebp at threonine 135, which contributes to its rapid nuclear localization. we performed in vitro kinase assays using the tonebp/orebp peptide containing t135 as substrate (figure 3b, right panel) and various recombinant kinases. The peptide is strongly phosphorylated by cdk5, less by cdk1.	SIGNOR-170882
P08559	Q13131	phosphorylation	up-regulates activity	0.2	AMPKα phosphorylates PDHA subunit on Ser295 and Ser314 to activate PDH complex	SIGNOR-276837
Q03164	P23759	binding	up-regulates	0.2	Carm1 specifically methylates multiple arginines in the n-terminus of pax7. Methylated pax7 directly binds the c-terminal cleavage forms of the trithorax proteins mll1/2 resulting in the recruitment of the ash2l:mll1/2:wdr5:rbbp5 histone h3k4 methyltransferase complex to regulatory enhancers and the proximal promoter of myf5.	SIGNOR-198626
P26640	Q2TAL8	transcriptional regulation	up-regulates quantity by expression	0.2	QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.	SIGNOR-269408
Q16875	Q9P1W9	phosphorylation	up-regulates quantity by stabilization	0.2	We used biochemical methods to determine that PIM2 can directly bind and change the phosphorylation of PFKFB3 at Ser478 to enhance PFKFB3 protein stability through the ubiquitin-proteasome pathway.	SIGNOR-277554
Q96BF3	P31749	phosphorylation	up-regulates activity	0.2	We observed that IGPR-1 is activated by shear stress and tensile force and that flow shear stress-mediated IGPR-1 activation modulates remodeling of endothelial cells. Mechanistically, shear stress stimulated activation of AKT Ser/Thr kinase 1 (AKT1), leading to phosphorylation of IGPR-1 at Ser-220.	SIGNOR-273481
P68400	Q9Y4K3	binding	up-regulates activity	0.2	Here, we show that somatic nuclear autoantigenic sperm protein (sNASP) binds to TRAF6 to prevent TRAF6 autoubiquitination in unstimulated macrophages. Following LPS stimulation, a complex consisting of sNASP, TRAF6, IRAK4, and casein kinase 2 (CK2) is formed. CK2 phosphorylates sNASP at serine 158, allowing sNASP to dissociate from TRAF6. Free TRAF6 is then autoubiquitinated, followed by activation of downstream signaling pathways.	SIGNOR-273656
P16104	P45984	phosphorylation	up-regulates	0.2	H2ax interacts with numerous proteins required for dna damage signaling and repair when phosphorylated on ser-140. Phosphorylation of ser-140 (h2ax139ph) in response to ionizing radiation is mediated by both atm and prkdc. Our data showed that h2ax is phosphorylated by uva-activated jnk.	SIGNOR-160210
P04155	O00170	transcriptional regulation	down-regulates quantity by repression	0.2	We show that XAP2 is recruited to the promoter of ERα regulated genes like the breast cancer marker gene pS2 or GREB1 and negatively regulate the expression of these genes in MCF-7 cells.	SIGNOR-259911
O60603	P59594	binding	up-regulates activity	0.2	S protein is a ligand for human TLR2. S protein utilizes toll-like receptor 2(TLR 2) to increase IL-8 production.Our results show that SARS S protein in a soluble form increased IL-8 production through hTLR2 ligand interaction.	SIGNOR-260972
O94759	P17252	phosphorylation	up-regulates activity	0.2	ROS production in endothelial cells or directly applying ROS induced PKC\u03b1 activation and phosphorylation of TRPM2 at Ser 39.\|ROS production in endothelial cells or directly applying ROS induced PKCalpha activation and phosphorylation of TRPM2 at Ser 39.	SIGNOR-280082
P16104	P35226	ubiquitination	up-regulates activity	0.2	In this process, BMI1 ubiquitinates histone H2A and \u03b3H2AX, thereby facilitating the repair of double-stranded DNA breaks through stimulating homologous recombination and non-homologous end joining.	SIGNOR-278744
P09651	P17252	phosphorylation	down-regulates	0.2	A survey of seven protein kinases showed that a1 was heavily phosphorylated by protein kinase c (pkc) and also was phosphorylated by casein kinase iiamino acid sequencing revealed that these sites were ser95, ser192, and ser199;phosphorylation at ser192 was more abundant than at ser95 and ser199. Phosphorylation by pkc inhibited the strand annealing activity of a1.	SIGNOR-32291
O14649	P17612	phosphorylation	up-regulates activity	0.2	Mutation of the ser393 to alanine, which can neither be phosphorylated nor mimic a phosphorylated residue, resulted in the channel failing to pass current all of our findings support the conclusion that camp-dependent protein kinase is responsible for the phosphorylation of the terminal serine in both k2p3.1 and k2p9.1.	SIGNOR-172430
Q6J4K2	P17612	phosphorylation	up-regulates activity	0.2	However, the PDE2-inhibitory effect is eliminated when the mitochondrial S258A NCLX mutant that mimics a non-PKA phosphorylated state of NCLX is expressed. Altogether, our findings indicate that NCLX is regulated by the mitochondrial PDE2A2 form.\|We show that caffeine, by inhibiting PDE2, enhances PKA phosphorylation leading to mitochondrial NCLX activation, thereby reducing neuronal excitotoxicity and enhancing learning in mice. \|Moreover, PDE2 acts by diminishing mitochondrial cAMP, thus promoting NCLX phosphorylation at its PKA site.	SIGNOR-275727
P35367	Q13976	phosphorylation	down-regulates	0.2	Ser396 and ser398 are also potential phosphorylation sites for capk, cgmp-dependent protein kinase, and camk ii. Elevation of intracellular camp content has been shown to attenuate histamine-induced accumulation of ip in c6 glioma cells (peakman and hill, 1994) and in ddt1 mf-2 smooth muscle cells (sipma et al., 1995	SIGNOR-66019
O43156	P68400	phosphorylation	down-regulates	0.2	Here we report that tel2 and tti1 are targeted for degradation within mtorc1 by the scffbxo9 ubiquitin ligase to adjust mtor signalling to growth factor availability. This process is primed by ck2, which translocates to the cytoplasm to mediate mtorc1-specific phosphorylation of tel2/tti1	SIGNOR-200240
Q16543	O75385	phosphorylation	down-regulates activity	0.2	Serine/Threonine Kinase Unc-51-like Kinase-1 (Ulk1) Phosphorylates the Co-chaperone Cell Division Cycle Protein 37 (Cdc37) and Thereby Disrupts the Stability of Cdc37 Client Proteins.\|Ulk1-mediated phosphorylation of Ser-339 in Cdc37 compromised the recruitment of client kinases to a complex comprising Cdc37 and heat shock protein 90 (Hsp90) but only modestly affected Cdc37 binding to Hsp90.	SIGNOR-280158
P09917	Q9UQM7	phosphorylation	up-regulates activity	0.2	Phosphorylation of serine 271 on 5-lipoxygenase and its role in nuclear export\|We report here that 5-LO is constitutively phosphorylated on Ser-271 in transfected NIH 3T3 cells. This residue is nested in a classical nuclear export sequence, and phosphorylated Ser-271 5-LO was exclusively found in the nucleus by immunofluorescence and by fractionation techniques\|Nuclear export of 5-LO can also be induced by KN-93, an inhibitor of Ca2+/calmodulin-dependent kinase II, and the effects of SB 203,580 plus KN-93 are additive. Finally, HeLa cells, which lack nuclear 5-LO, also lack constitutive phosphorylation of Ser-271. Taken together, these results indicate that the phosphorylation of Ser-271 serves to inhibit the nuclear export of 5-LO.	SIGNOR-264408
Q86UC2	P28482	phosphorylation	up-regulates activity	0.2	ERK1/2 phosphorylate RSPH3. the extent of radiolabeled phosphate incorporation into RSPH3 T286A was much less than that into wild-type RSPH3, suggesting that threonine 286 is the major ERK1/2 phosphorylation site in cells. ERK2 also phosphorylates RSPH3 on threonine 243 to a lesser extent. Phosphorylation of the double mutant T243V/T286A RSPH3 was no more than 20% that of wild-type RSPH3 (Fig. 4, C and D). inhibiting ERK1/2 activity appears to negatively regulate the AKAP function of RSPH3.	SIGNOR-262839
O95817	Q8NEZ5	binding	down-regulates quantity by destabilization	0.2	We further demonstrated BAG3, a HSP70 co-chaperone, is a bona fide substrate of SCFFBXO22. FBXO22 mediates BAG3 ubiquitination and degradation that requires ERK-dependent BAG3 phosphorylation at S377.	SIGNOR-277319
O60603	P03217	post transcriptional regulation	down-regulates quantity by repression	0.2	The RNA degradation induced by EBV BGLF5 can affect immunologically relevant proteins, including TLR2. Alkaline exonuclease involved in host shutoff, downregulates TLR2.	SIGNOR-266741
Q9P0K8	Q9HC98	phosphorylation	up-regulates activity	0.2	Additionally, we found that NEK6 phosphorylated FOXJ2 at Thr23 and Ser254 ( xref , lanes 3 and 5), and NCOA5 at Ser21 and Ser151 ( xref , lanes 3 and 4).	SIGNOR-278965
Q96QB1	Q00535	phosphorylation	up-regulates activity	0.2	The CDK5 kinase phosphorylates four serines in DLC1 located N-terminal to the Rho-GAP domain. When not phosphorylated, this N-terminal region functions as an autoinhibitory domain that places DLC1 in a closed, inactive conformation by efficiently binding to the Rho-GAP domain. CDK5 phosphorylation reduces this binding and orchestrates the coordinate activation DLC1, including its localization to focal adhesions, its Rho-GAP activity, and its ability to bind tensin and talin.	SIGNOR-276444
Q13315	P48729	phosphorylation	down-regulates quantity by destabilization	0.2	Mechanistically, CK1α phosphorylates the serine residue S1270 and modulates the protein abundance of ataxia telangiectasia mutated (ATM), a primary initiator of DNA double-strand break (DSB)-response signaling, which is compromised in ENZA-resistant cells and patients. Inhibition of CK1α stabilizes ATM, resulting in the restoration of DSB signaling, and thus increases ENZA-induced cell death and growth arrest.	SIGNOR-277918
Q9Y6N7	Q14938	transcriptional regulation	up-regulates quantity	0.2	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268907
Q9BWW4	P06239	phosphorylation	up-regulates activity	0.2	The Src tyrosine kinase inhibitor PP2 blocked the nuclear translocation of Ssdp1. Western blot analysis showed that co-expression of Ssdp1 and Lck in 293T cells induces Ssdp1 phosphorylation. Mutation of the Ssdp1 N terminal tyrosine residues 23 and 25 markedly reduced both the phosphorylation and the nuclear localization of Ssdp1. Lck enhanced the transcriptional activity of Ssdp1 in the context of known components of a LIM-homeodomain (LIM-HD)/cofactor complex.	SIGNOR-273648
P03372	Q9H3C7	binding	down-regulates activity	0.2	We further demonstrate that GGNBP2 protein physically interacts with ERα, inhibits E2-induced activation of estrogen response element-driven reporter activity, and attenuates ER target gene expression in T47D cells.	SIGNOR-269076
P50549	Q13535	phosphorylation	up-regulates quantity by stabilization	0.2	Collectively, the results described above indicate that ATR phosphorylates ETV1 and stabilizes it from proteolytic degradation.	SIGNOR-279355
P68431	O94953	demethylation	down-regulates activity	0.2	The KDM4 family of Jumonj domain histone demethylases specifically target di- and tri-methylated lysine 9 on histone H3 (H3K9me3), removing a modification central to defining heterochromatin and gene repression. The majority of studies regarding its function describe it as an activator that removes repressive H3K9me3 and H3K9me2 at or near regulated promoters in order to facilitate expression of the indicated pathways.	SIGNOR-263734
P25098	P62166	binding	down-regulates activity	0.2	Here we show that the neuronal calcium sensor-1 (NCS-1) can mediate desensitization of D2 dopamine receptors. Analysis of D2 receptors expressed in human embryonic kidney 293 cells indicates that NCS-1 attenuates agonist-induced receptor internalization via a mechanism that involves a reduction in D2 receptor phosphorylation. Coimmunoprecipitation experiments from striatal neurons reveal that NCS-1 is found in association with both the D2 receptor and G-protein-coupled receptor kinase 2, a regulator of D2 receptor desensitization.	SIGNOR-263965
Q00987	Q9NQU5	phosphorylation	up-regulates activity	0.2	We also showed that PAK6 phosphorylates Mdm2 on Thr-158 and Ser-186, which is critical for AR ubiquitin-mediated degradation.	SIGNOR-276428
P68431	P83916	binding	up-regulates activity	0.2	A core characteristic of heterochromatin is its association with heterochromatin protein 1 (HP1) proteins, a highly conserved family of chromosomal proteins that bind to di- and trimethylated H3K9 via a conserved N-terminal domain called the chromodomain (CD) HP1 proteins are a highly conserved family of eukaryotic proteins that bind to methylated histone H3 lysine 9 (H3K9) and are required for heterochromatic gene silencing.	SIGNOR-264493
P40763	Q13188	phosphorylation	down-regulates activity	0.2	Hippo pathway component MST2 kinase phosphorylates STAT3 at T622, which is located in the SH2 domain of STAT3. This phosphorylation blocks the SH2 domain in one STAT3 molecule to bind with the phosphorylated Y705 site in another STAT3 molecule, which further counteracts IL6-induced STAT3 dimerization and activation.	SIGNOR-277599
P17252	Q9NPB6	binding	up-regulates activity	0.2	The Par complex member Par-6, previously thought to inhibit aPKC, is a potent activator of aPKC in our assays. Par-6 and aPKC interact via PB1 domain heterodimerization, and this interaction activates aPKC by displacing the pseudosubstrate, although full activity requires the Par-6 CRIB-PDZ domains.	SIGNOR-227489
Q8N752	Q9H4H8	binding	up-regulates quantity	0.2	We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.	SIGNOR-273757
P11912	Q9NRF2	dephosphorylation	down-regulates activity	0.2	SHP-1 is recruited by the phosphorylated ITIM-bearing receptors such as CD22 and it dephosphorylates proximal BCR signaling molecules such as CD79, SYK, BLNK.	SIGNOR-268457
P48539	P35398	transcriptional regulation	up-regulates quantity by expression	0.2	RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.	SIGNOR-266848
P31751	O60858	polyubiquitination	down-regulates quantity by destabilization	0.2	Here, we demonstrate that overexpression of RFP2 in cells induced apoptosis through proteasomal degradation of MDM2 and AKT. We observed that RFP2 formed a complex with MDM2, a negative regulator of the p53 tumor suppressor, and AKT, a regulator of apoptosis inhibition at the cellular level. Additionally, we found that the interaction of RFP2 with MDM2 and AKT resulted in ubiquitination and proteasomal degradation of MDM2 and AKT in vivo and in vitro.	SIGNOR-271853
Q9UK17	P06241	phosphorylation	up-regulates activity	0.2	These results indicate that Y108 (for Src-family kinases) and Y136 (for EGFR kinase) are involved in the tyrosine phosphorylation of hKv4.3 channels.	SIGNOR-276396
Q9UHD2	P06239	phosphorylation	down-regulates activity	0.2	The Src family kinases (SFKs) Lck, Hck, and Fgr directly phosphorylate TBK1 at Tyr354/394, to prevent TBK1 dimerization and activation.	SIGNOR-276724
O43623	O96013	phosphorylation	up-regulates quantity by stabilization	0.2	P21 activated kinase 4 (PAK4) directly phosphorylates Slug, resulting in pro malignant Slug stabilization.	SIGNOR-280057
P18846	Q00526	phosphorylation	up-regulates	0.2	Cyclin-dependent kinase 3-mediated activating transcription factor 1 phosphorylation enhances cell transformationwe found that cdk3 phosphorylates activating transcription factor 1 (atf1) at serine 63 and enhances the transactivation and transcriptional activities of atf1.	SIGNOR-180920
P05108	Q9NTG7	deacetylation	up-regulates quantity by stabilization	0.2	Resveratrol stimulates cortisol biosynthesis by activating SIRT-dependent deacetylation of P450scc.\|Stable overexpression of SIRT3 abrogates the cellular content of acetylated P450scc, concomitant with an increase in P450scc protein expression and cortisol secretion. Mutation of K148 and K149 to alanine stabilizes the expression of P450scc and results in a 1.5-fold increase in pregnenolone biosynthesis.	SIGNOR-268718
P60321	Q99619	binding	down-regulates quantity by destabilization	0.2	We have identified SPRY domain-containing SOCS (suppressor of cytokine signaling) box protein 2 (SPSB2) as a novel negative regulator that recruits an E3 ubiquitin ligase complex to polyubiquitinate iNOS, resulting in its proteasomal degradation. A cell-free ubiquitination assay was established to demonstrate SPSB2-dependent ubiquitination of iNOS. LPS/IFN-γ–stimulated macrophage lysates from Spsb2−/− mice were used as a source of iNOS and incubated with ubiquitin and a trimeric SPSB2/elongin BC complex in the presence of E1 and E2 (UbcH5a) enzymes, Rbx2, and Cullin5 for various times.	SIGNOR-271901
P04001	Q92753	transcriptional regulation	up-regulates quantity by expression	0.2	These observations indicate that RORβ is required for the induction of S opsin and support the conclusion that RORβ regulates Opn1sw transcription in a direct manner through ROREs within its proximal promoter region. In addition, they explain the greatly diminished expression of Opn1sw observed in the retina of RORβ-/- mice.	SIGNOR-266851
P14210	P08047	transcriptional regulation	up-regulates quantity by expression	0.2	Furthermore, in transient cotransfection assays, overexpression of Sp1 and/or Sp3 stimulated HGF promoter activity independently and additively through binding to the Sp1 binding site in the HGF gene promoter region.	SIGNOR-251739
Q6NXT1	Q05655	phosphorylation	up-regulates activity	0.2	The mechanism by which phosphorylation of Ankrd54 by PKC\u03b4 enhances cytoplasmic accumulation of Ankrd54 and its interaction with Lyn remains to be determined.\|This revealed, in agreement with the biochemical analysis, that PKCdelta significantly promotes cytoplasmic accumulation of Ankrd54.	SIGNOR-279259
P78357	Q05655	phosphorylation	down-regulates activity	0.2	Inhibition of PKCdelta increased p190 activity, while PKCdelta overexpression diminished p190 activity.\|We further show that PKC\u03b4 was able to phosphorylate and bind distinct domains of p190.	SIGNOR-279260
P55211	Q6UXS9	cleavage	up-regulates	0.2	Caspase-12 specifically cleaves and activates procaspase-9 in cytosolic extracts. Results suggest that caspase-12 can activate caspase-9 without involvement of cytochromec.	SIGNOR-90318
P23246	P49840	phosphorylation	down-regulates	0.2	Psf is directly phosphorylated by gsk3, thus promoting interaction of psf with trap150, which prevents psf from binding cd45 pre-mrna. / threonine phosphorylation of psf by gsk3 primarily occurs on residue t687	SIGNOR-168385
Q01860	Q6U7Q0	transcriptional regulation	up-regulates quantity by expression	0.2	Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays revealed that Zfp322a binds to Pou5f1 and Nanog promoters and regulates their transcription.	SIGNOR-264900
Q13131	Q13554	phosphorylation	up-regulates	0.2	These data indicate that the camkks function in intact cells as ampkks, predicting wider roles for these kinases in regulating ampk activity in vivo.	SIGNOR-138360
P68431	P51812	phosphorylation	down-regulates activity	0.2	Phosphorylation at ser-11 (h3s10ph) by rps6ka4 and rps6ka5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or uv irradiation and result in the activation of genes, such as c-fos and c-jun.	SIGNOR-119229
Q6DN90	O95819	phosphorylation	up-regulates activity	0.2	Together, our results provide compelling evidence that MAP4K4 promotes FA dynamics by regulating IQSEC1 and Arf6 pathway and controlling endocytosis of integrin.\|Upon targeting to FAs via MTs, MAP4K4 can bind and phosphorylate IQSEC1, which in turn activates Arf6 and endocytosis, leading to turnover of FAs.	SIGNOR-280020
P26367	O00330	binding	down-regulates activity	0.2	In the heterologous cell line BHK-21, Pdx1 inhibited by 60 to 80% the activation of the alpha-cell specific element G1 conferred by Pax-6 and/or Cdx-2/3. Although Pdx1 could bind three AT-rich motifs within G1, two of which are binding sites for Pax-6 and Cdx-2/3, the affinity of Pdx1 for G1 was much lower as compared to Pax-6. In addition, Pdx1 inhibited Pax-6 mediated activation through G3, to which Pdx1 was unable to bind. Moreover, a mutation impairing DNA binding of Pdx1 had no effect on its inhibition on Cdx-2/3. Since Pdx1 interacts directly with Pax-6 and Cdx-2/3 forming heterodimers, we suggest that Pdx1 inhibits glucagon gene transcription through protein to protein interactions with Pax-6 and Cdx-2/3.	SIGNOR-254903
Q9UGP8	P67870	phosphorylation	up-regulates activity	0.2	Sec63 was identified as a novel substrate and binding partner of protein kinase CK2. We identified serine 574, serine 576 and serine 748 as CK2 phosphorylation sites. Phosphorylation of Sec63 by CK2 enhanced its binding to Sec62.	SIGNOR-265270
O43781	P18848	transcriptional regulation	down-regulates quantity by repression	0.2	Interestingly, the promoter activity of Dyrk3 was negatively regulated by ATF4, indicating a double-negative feedback loop.	SIGNOR-275453
Q16206	Q05655	phosphorylation	up-regulates	0.2	Tnox is phosphorylated by protein kinase c_ (pkc_) both in vitro and in vivo. Replacement of serine-504 with alanine significantly reduces phosphorylation by pkc_. C. overexpression of the s504a tnox mutant leads to diminished cell proliferation and migration, reflecting reduced stability of the unphosphorylatable tnox mutant protein.	SIGNOR-197706
Q9GZY8	O94806	phosphorylation	up-regulates activity	0.2	The mitochondrial fission factor (MFF), the main mitochondrial receptor for the Dynamin-related protein 1 (DRP1), is directly phosphorylated by Protein Kinase D (PKD) specifically during mitosis. PKD-dependent MFF phosphorylation is required and sufficient for mitochondrial fission in mitotic but not in interphasic cells.\|PKD directly phosphorylates MFF on serines 155, 172, and 275	SIGNOR-275945
P16401	P49841	phosphorylation	up-regulates	0.2	We found that threonine 10 of h1.5 can be phosphorylated by glycogen synthase kinase-3 in vitro. We have generated an antiserum specific for human h1.5 phosphorylated at threonine 10. Immunofluorescence labeling of hela cells with this antiserum revealed that the phosphorylation at this site appears in prometaphase and disappears in telophase, and that this hyperphosphorylated form of h1.5 is mainly chromatin-bound in metaphase when chromatin condensation is maximal.	SIGNOR-183325
O15084	Q13557	phosphorylation	down-regulates activity	0.2	We provide evidence for a dual kinase-mediated regulation of the PITK holoenzyme whereby PITK phosphorylation at S1017 is catalyzed by calcium/calmodulin-dependent kinase II-delta (CaMKIIdelta), promoting the subsequent phosphorylation of S1013 by glycogen synthase kinase-3 (GSK3) in vitro.\|the phosphorylation of PITK at these specific residues altered PP1 binding and subsequent PITK-directed dephosphorylation of hnRNP K	SIGNOR-264793
Q15811	Q96CN9	relocalization	up-regulates activity	0.2	GFP-GCC88 was immunoprecipitated by both the short and long form of ITSN-1 but not with FLAG-Rheb (Figure 4A). These data demonstrate that both GCC88 and ITSN-1 are part of a complex. We propose that GCC88 recruits ITSN-1-L to the TGN, which in turn activates Cdc42 at the trans-face of the Golgi (Figure 9A).	SIGNOR-260600
Q96F24	P42345	phosphorylation	up-regulates activity	0.2	Human NRBF2 is phosphorylated by MTORC1 at S113 and S120. Upon nutrient starvation or MTORC1 inhibition, NRBF2 phosphorylation is diminished. Phosphorylated NRBF2 preferentially interacts with PIK3C3/PIK3R4. Suppression of NRBF2 phosphorylation by MTORC1 inhibition alters its binding preference from PIK3C3/PIK3R4 to ATG14/BECN1, leading to increased autophagic PtdIns3K complex assembly, as well as enhancement of ULK1 protein complex association.	SIGNOR-265875
Q9UGI0	P31749	phosphorylation	up-regulates activity	0.2	Our findings also identify an essential role for activation of Trabid by AKT-mediated phosphorylation at Ser78/Thr117 in negatively regulating Twist1 signaling, which further provides insights into the mechanisms by which Trabid regulates Twist1 ubiquitination.	SIGNOR-273484
Q9Y4G8	O14920	phosphorylation	down-regulates quantity by destabilization	0.2	Taken together, these results indicate that IKK\u03b2-dependent phosphorylation of RAPGEF2 is required for RAPGEF2 degradation induced by HGF and mediated by \u03b2TrCP.	SIGNOR-279807
P09211	Q05513	phosphorylation	up-regulates activity	0.2	Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently	SIGNOR-276017
P54274	P68400	phosphorylation	up-regulates	0.2	Regulation of telomeric repeat binding factor 1 binding to telomeres by casein kinase 2-mediated phosphorylation. Mapping of the ck2 target site identified threonine 122 as a substrate in trf1. A threonine to alanine change at this position led to a diminished dna binding due to reduced dimerization of trf1.	SIGNOR-178034
P19447	P68400	phosphorylation	down-regulates activity	0.2	Phosphorylation of S751 by CKII inhibits 5′ incision.	SIGNOR-276013
P46527	P49792	relocalization	down-regulates quantity	0.2	RanBP2 can increase the sumoylation of p27kip1. In our study, the target protein p27kip1 mainly acts as a tumor-suppressor gene in the nucleus, RanBP2 and SUMO1 act as oncogenes by promoting the nuclear-cytoplasmic translocation and debilitate the G1-arrest brought by p27kip1 accumulation in the nucleus.	SIGNOR-259115
Q13671	P55196	binding	up-regulates activity	0.2	Rit and Rin were found to interact with the known Ras binding proteins RalGDS, Rlf, and AF-6/Canoe. These interactions were GTP and effector domain dependent and suggest that RalGDS, Rlf, and AF-6 are Rit and Rin effectors.	SIGNOR-220926
O43318	Q13555	phosphorylation	up-regulates	0.2	Camkii interacts with and phosphorylates tak1.	SIGNOR-96422
O94826	Q13627	phosphorylation	up-regulates activity	0.2	Phosphorylation of TOM70 Ser91 by DYRK1A stimulates interaction of TOM70 with the core TOM translocase.	SIGNOR-279994
Q9P0L9	P17612	phosphorylation	up-regulates activity	0.2	PKD2L1 channel activation by PKA phosphorylation. In this study, we observed the activity of PKD2L1 channel increased by the downstream cascades of β2AR and found the clustered phosphorylation sites, Ser-682, Ser-685, and Ser-686 that are significant in the channel regulation by phosphorylation.	SIGNOR-273562
P48729	Q9BQN1	binding	up-regulates quantity	0.2	We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.	SIGNOR-273752
Q71DI3	Q9UIF8	binding	down-regulates activity	0.2	The BAZ2B bromodomain has been shown to bind to acetylated H3K14 (H3K14ac), whose presence at promoter regions is generally associated with gene activation. This suggests a potential role for BAZ2B in transcriptional activation.	SIGNOR-266623
Q9BX84	P63244	binding	down-regulates activity	0.2	We identified RACK1 as the first TRPM6-associated protein and demonstrated that RACK1 inhibits TRPM6 channel activity depending on the phosphorylation state T1851 in the α-kinase domain.	SIGNOR-260921
O43524	O43638	transcriptional regulation	down-regulates quantity by repression	0.2	Fkhl18 suppressed the transcriptional activity of FoxO3a and FoxO4.	SIGNOR-261610
P69905	P15169	cleavage	down-regulates activity	0.2	Both human plasma carboxypeptidase N (CPN) and membrane-bound carboxypeptidase M (CPM) released the C-terminal arginine (alpha-Arg141) of the alpha chain of human adult hemoglobin. Thus, the hydrolysis of hemoglobin by CPM and CPN demonstrated the contribution of the alpha-Arg141 residue to sustaining the tetrameric structure of hemoglobin and its normal oxygen affinity and vasoactivity.	SIGNOR-256508
Q12800	P27361	phosphorylation	down-regulates	0.2	We previously established that phosphorylation of lsf in early g1 at ser-291 and ser-309 inhibits its transcriptional activity and that dephosphorylation later in g1 is required for its reactivation. At the peak activities of erk and cyclin c/cdk2 in early g1, lsf is efficiently phosphorylated on ser-291 and ser-309.	SIGNOR-184176
P52292	P0DTC6	binding	down-regulates activity	0.2	The results from Figure 1C suggest that ORF6 inhibits IFN-β production through IRF3 or a component downstream of IRF3. Thus, we examined the effect of ORF6 on IRF3 nuclear translocation. Upon poly(I:C) treatment, IRF3 translocated to the cell nucleus in the absence of ORF6, whereas the expression of ORF6 blocked its nuclear translocation (Figure 2D). Karyopherin α 1–6 (KPNA1–6) are importing factors for nuclear translocation of cargos, including IRF3, IRF7, and STAT1 (Chook and Blobel, 2001). Co-immunoprecipitation showed that ORF6 selectively interacted with KPNA2, but not the other KPNAs (Figure 2E), suggesting that ORF6 inhibits IFN-β production by binding to KPNA2 to block IRF3 nuclear translocation (Figure 2F).	SIGNOR-262513
P52292	Q19QW5	relocalization	down-regulates activity	0.2	Taken together, these data support a direct interaction between KPNA2 and ORF6 in the context of virus infection.\|SARS-CoV, but not SARSdeltaORF6, retains KPNA2 at the ER/Golgi membrane.	SIGNOR-260272
Q9NZQ7	Q9Y2A9	glycosylation	up-regulates activity	0.2	These results further suggested that B3GNT3 mediates PD-L1 and PD-1 interaction through N-linked glycosylation instead of O-linked glycosylation	SIGNOR-275389
Q13586	Q13131	phosphorylation	down-regulates activity	0.2	STIM1 is a novel exercise‐regulated AMPK substrate. Phosphorylation of STIM1 by AMPK suppresses SOCE	SIGNOR-277299
Q03135	O60260	ubiquitination	down-regulates quantity	0.2	Parkin induces the degradation of cav-1 through the proteasome dependent pathway.\|We also demonstrated that WT parkin ubiquitinates cav-1 for degradation.	SIGNOR-278710
P10912	P54764	phosphorylation	up-regulates activity	0.2	EphA4 binds to growth hormone receptor at both its extracellular and intracellular domains and phosphorylates growth hormone receptor when stimulated with a ligand.\|These findings suggest that EphA4 activates not only GHR, as shown above, but also JAK2 by direct phosphorylation.	SIGNOR-279461
P05771	P54792	binding	up-regulates	0.2	Taken together, these results suggest that site-specific dvl2 phosphorylation is required for dvl2 association with pkc_. This interaction is likely to be one of the mechanisms essential for wnt3a-dependent neurite outgrowth.	SIGNOR-199457
P49841	Q9UK32	phosphorylation	down-regulates activity	0.2	Moreover, RSK4 stabilized Beta-catenin in the presence of GSK-3Beta WT but not RSK4 stabilizes Beta-catenin through phosphorylation of GSK-3Beta (Ser9) in ESCC cells\|GSK-3Beta S9A in ESCC cells, which was similar to overexpression of GSK3Beta S9D\|	SIGNOR-275801
Q15652	P22415	binding	up-regulates activity	0.2	We show that, by direct interaction with USF-1, JMJD1C is recruited to lipogenic promoters. We also show that JMJD1C is phosphorylated at T505 by mammalian target of rapamyci (mTOR) to be recruited to lipogenic genes in response to insulin/feeding.	SIGNOR-265167
Q5XUX0	P12830	binding	down-regulates quantity by destabilization	0.2	Here we show that the low levels of FBXO31 are maintained through proteasomal degradation by anaphase-promoting complex/cyclosome (APC/C). We find that the APC/C coactivators CDH1 and CDC20 bind to a destruction-box (D-box) motif present in FBXO31 to promote its polyubiquitination and degradation in a cell-cycle-regulated manner, which requires phosphorylation of FBXO31 on serine-33 by the prosurvival kinase AKT.	SIGNOR-277377
Q02447	P62136	dephosphorylation	down-regulates activity	0.2	Transcription factors Sp1 and Sp3 activate alpha-ENaC2 transcription through a GC-rich element (Sp1-binding site) in the promoter. Sp1 and Sp3 are essential for alpha-ENaC2 transcription in lung epithelial cells and that dephosphorylation of the Sp transcription factors by PP1 suppresses alpha-ENaC2 expression.	SIGNOR-251953
P09471	P25103	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257249
P27816	O14757	phosphorylation	down-regulates quantity by destabilization	0.2	MAP4 is a novel target of FBXW7 via the phosphorylated threonine T521 modified by CHEK1 in ESCC. The threonine T521 of MAP4, which was phosphorylated by CHEK1, played a key role in the FBXW7-related degradation system.	SIGNOR-277846
Q9UJT1	Q14980	binding	up-regulates	0.2	Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules.	SIGNOR-117159
Q9UHC6	Q6ZVD7	transcriptional regulation	down-regulates quantity by repression	0.2	In this study we performed chromatin immunoprecipitation coupled to shotgun cloning to discover novel STOX1A target genes. Our results show that CNTNAP2, a member of the neurexin family, is directly downregulated by STOX1A.	SIGNOR-269065
Q01668	Q9UJD0	binding	up-regulates activity	0.2	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-264357
P0C0S8	O75582	phosphorylation	up-regulates	0.2	We found that msk1 phosphorylated histone h2a on serine 1, and mutation of serine 1 to alanine blocked the inhibition of transcription by msk1.	SIGNOR-123383

O95292

Q92953

0

relocalization

up-regulates quantity

0.2

Confirmation that Kv2.1 and -2.2 bind VAPA and VAPB employed colocalization/redistribution, siRNA knockdown, and Förster resonance energy transfer (FRET)-based assays.|As Kv2.1 accumulates on the surface it begins to bind ER VAPs and form the large and stable membrane junctions.

SIGNOR-262123

Q08289

P55040

0

binding

down-regulates activity

0.2

Two functions for Gem have been demonstrated, including inhibition of voltage-gated calcium channel activity and inhibition of Rho kinase-mediated cytoskeletal reorganization, such as stress fiber formation and neurite retraction. These functions for Gem have been ascribed to its interaction with the calcium channel Β subunit and Rho kinase Β, respectively.

SIGNOR-261720

Q01196

P28482

0

phosphorylation

up-regulates activity

0.2

We have identified four phosphorylation sites on AML1c that are necessary for transcriptional activity of AML1c in K562 and 293T cells (27).4 Mutation of these four sites (serine 276, serine 293, serine 303, and threonine 300) to alanine abolishes transcriptional activation, whereas mutation of these sites to aspartic acid (which mimics phosphorylation) results in a hyperactive protein. The presence of these mutations results in an increase in the amount of ubiquitinated AML1c in the matrix, and increases the half-life of this insoluble AML1c. One possible model to explain these observations is that phosphorylation might be necessary for the normal process of both proteasome degradation and transcriptional activation.

SIGNOR-138973

O94916

P06493

0

phosphorylation

up-regulates

0.2

High nacl-induced activation of cdk5 increases phosphorylation of the osmoprotective transcription factor tonebp/orebp at threonine 135, which contributes to its rapid nuclear localization. we performed in vitro kinase assays using the tonebp/orebp peptide containing t135 as substrate (figure 3b, right panel) and various recombinant kinases. The peptide is strongly phosphorylated by cdk5, less by cdk1.

SIGNOR-170882

P08559

Q13131

0

phosphorylation

up-regulates activity

0.2

AMPKα phosphorylates PDHA subunit on Ser295 and Ser314 to activate PDH complex

SIGNOR-276837

Q03164

P23759

0

binding

up-regulates

0.2

Carm1 specifically methylates multiple arginines in the n-terminus of pax7. Methylated pax7 directly binds the c-terminal cleavage forms of the trithorax proteins mll1/2 resulting in the recruitment of the ash2l:mll1/2:wdr5:rbbp5 histone h3k4 methyltransferase complex to regulatory enhancers and the proximal promoter of myf5.

SIGNOR-198626

P26640

Q2TAL8

0

transcriptional regulation

up-regulates quantity by expression

0.2

QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.

SIGNOR-269408

Q16875

Q9P1W9

0

phosphorylation

up-regulates quantity by stabilization

0.2

We used biochemical methods to determine that PIM2 can directly bind and change the phosphorylation of PFKFB3 at Ser478 to enhance PFKFB3 protein stability through the ubiquitin-proteasome pathway.

SIGNOR-277554

Q96BF3

P31749

0

phosphorylation

up-regulates activity

0.2

We observed that IGPR-1 is activated by shear stress and tensile force and that flow shear stress-mediated IGPR-1 activation modulates remodeling of endothelial cells. Mechanistically, shear stress stimulated activation of AKT Ser/Thr kinase 1 (AKT1), leading to phosphorylation of IGPR-1 at Ser-220.

SIGNOR-273481

P68400

Q9Y4K3

0

binding

up-regulates activity

0.2

Here, we show that somatic nuclear autoantigenic sperm protein (sNASP) binds to TRAF6 to prevent TRAF6 autoubiquitination in unstimulated macrophages. Following LPS stimulation, a complex consisting of sNASP, TRAF6, IRAK4, and casein kinase 2 (CK2) is formed. CK2 phosphorylates sNASP at serine 158, allowing sNASP to dissociate from TRAF6. Free TRAF6 is then autoubiquitinated, followed by activation of downstream signaling pathways.

SIGNOR-273656

P16104

P45984

0

phosphorylation

up-regulates

0.2

H2ax interacts with numerous proteins required for dna damage signaling and repair when phosphorylated on ser-140. Phosphorylation of ser-140 (h2ax139ph) in response to ionizing radiation is mediated by both atm and prkdc. Our data showed that h2ax is phosphorylated by uva-activated jnk.

SIGNOR-160210

P04155

O00170

0

transcriptional regulation

down-regulates quantity by repression

0.2

We show that XAP2 is recruited to the promoter of ERα regulated genes like the breast cancer marker gene pS2 or GREB1 and negatively regulate the expression of these genes in MCF-7 cells.

SIGNOR-259911

O60603

P59594

0

binding

up-regulates activity

0.2

S protein is a ligand for human TLR2. S protein utilizes toll-like receptor 2(TLR 2) to increase IL-8 production.Our results show that SARS S protein in a soluble form increased IL-8 production through hTLR2 ligand interaction.

SIGNOR-260972

O94759

P17252

0

phosphorylation

up-regulates activity

0.2

ROS production in endothelial cells or directly applying ROS induced PKC\u03b1 activation and phosphorylation of TRPM2 at Ser 39.|ROS production in endothelial cells or directly applying ROS induced PKCalpha activation and phosphorylation of TRPM2 at Ser 39.

SIGNOR-280082

P16104

P35226

0

ubiquitination

up-regulates activity

0.2

In this process, BMI1 ubiquitinates histone H2A and \u03b3H2AX, thereby facilitating the repair of double-stranded DNA breaks through stimulating homologous recombination and non-homologous end joining.

SIGNOR-278744

P09651

P17252

0

phosphorylation

down-regulates

0.2

A survey of seven protein kinases showed that a1 was heavily phosphorylated by protein kinase c (pkc) and also was phosphorylated by casein kinase iiamino acid sequencing revealed that these sites were ser95, ser192, and ser199;phosphorylation at ser192 was more abundant than at ser95 and ser199. Phosphorylation by pkc inhibited the strand annealing activity of a1.

SIGNOR-32291

O14649

P17612

0

phosphorylation

up-regulates activity

0.2

Mutation of the ser393 to alanine, which can neither be phosphorylated nor mimic a phosphorylated residue, resulted in the channel failing to pass current all of our findings support the conclusion that camp-dependent protein kinase is responsible for the phosphorylation of the terminal serine in both k2p3.1 and k2p9.1.

SIGNOR-172430

Q6J4K2

P17612

0

phosphorylation

up-regulates activity

0.2

However, the PDE2-inhibitory effect is eliminated when the mitochondrial S258A NCLX mutant that mimics a non-PKA phosphorylated state of NCLX is expressed. Altogether, our findings indicate that NCLX is regulated by the mitochondrial PDE2A2 form.|We show that caffeine, by inhibiting PDE2, enhances PKA phosphorylation leading to mitochondrial NCLX activation, thereby reducing neuronal excitotoxicity and enhancing learning in mice. |Moreover, PDE2 acts by diminishing mitochondrial cAMP, thus promoting NCLX phosphorylation at its PKA site.

SIGNOR-275727

P35367

Q13976

0

phosphorylation

down-regulates

0.2

Ser396 and ser398 are also potential phosphorylation sites for capk, cgmp-dependent protein kinase, and camk ii. Elevation of intracellular camp content has been shown to attenuate histamine-induced accumulation of ip in c6 glioma cells (peakman and hill, 1994) and in ddt1 mf-2 smooth muscle cells (sipma et al., 1995

SIGNOR-66019

O43156

P68400

0

phosphorylation

down-regulates

0.2

Here we report that tel2 and tti1 are targeted for degradation within mtorc1 by the scffbxo9 ubiquitin ligase to adjust mtor signalling to growth factor availability. This process is primed by ck2, which translocates to the cytoplasm to mediate mtorc1-specific phosphorylation of tel2/tti1

SIGNOR-200240

Q16543

O75385

0

phosphorylation

down-regulates activity

0.2

Serine/Threonine Kinase Unc-51-like Kinase-1 (Ulk1) Phosphorylates the Co-chaperone Cell Division Cycle Protein 37 (Cdc37) and Thereby Disrupts the Stability of Cdc37 Client Proteins.|Ulk1-mediated phosphorylation of Ser-339 in Cdc37 compromised the recruitment of client kinases to a complex comprising Cdc37 and heat shock protein 90 (Hsp90) but only modestly affected Cdc37 binding to Hsp90.

SIGNOR-280158

P09917

Q9UQM7

0

phosphorylation

up-regulates activity

0.2

Phosphorylation of serine 271 on 5-lipoxygenase and its role in nuclear export|We report here that 5-LO is constitutively phosphorylated on Ser-271 in transfected NIH 3T3 cells. This residue is nested in a classical nuclear export sequence, and phosphorylated Ser-271 5-LO was exclusively found in the nucleus by immunofluorescence and by fractionation techniques|Nuclear export of 5-LO can also be induced by KN-93, an inhibitor of Ca2+/calmodulin-dependent kinase II, and the effects of SB 203,580 plus KN-93 are additive. Finally, HeLa cells, which lack nuclear 5-LO, also lack constitutive phosphorylation of Ser-271. Taken together, these results indicate that the phosphorylation of Ser-271 serves to inhibit the nuclear export of 5-LO.

SIGNOR-264408

Q86UC2

P28482

0

phosphorylation

up-regulates activity

0.2

ERK1/2 phosphorylate RSPH3. the extent of radiolabeled phosphate incorporation into RSPH3 T286A was much less than that into wild-type RSPH3, suggesting that threonine 286 is the major ERK1/2 phosphorylation site in cells. ERK2 also phosphorylates RSPH3 on threonine 243 to a lesser extent. Phosphorylation of the double mutant T243V/T286A RSPH3 was no more than 20% that of wild-type RSPH3 (Fig. 4, C and D). inhibiting ERK1/2 activity appears to negatively regulate the AKAP function of RSPH3.

SIGNOR-262839

O95817

Q8NEZ5

0

binding

down-regulates quantity by destabilization

0.2

We further demonstrated BAG3, a HSP70 co-chaperone, is a bona fide substrate of SCFFBXO22. FBXO22 mediates BAG3 ubiquitination and degradation that requires ERK-dependent BAG3 phosphorylation at S377.

SIGNOR-277319

O60603

P03217

0

post transcriptional regulation

down-regulates quantity by repression

0.2

The RNA degradation induced by EBV BGLF5 can affect immunologically relevant proteins, including TLR2. Alkaline exonuclease involved in host shutoff, downregulates TLR2.

SIGNOR-266741

Q9P0K8

Q9HC98

0

phosphorylation

up-regulates activity

0.2

Additionally, we found that NEK6 phosphorylated FOXJ2 at Thr23 and Ser254 ( xref , lanes 3 and 5), and NCOA5 at Ser21 and Ser151 ( xref , lanes 3 and 4).

SIGNOR-278965

Q96QB1

Q00535

0

phosphorylation

up-regulates activity

0.2

The CDK5 kinase phosphorylates four serines in DLC1 located N-terminal to the Rho-GAP domain. When not phosphorylated, this N-terminal region functions as an autoinhibitory domain that places DLC1 in a closed, inactive conformation by efficiently binding to the Rho-GAP domain. CDK5 phosphorylation reduces this binding and orchestrates the coordinate activation DLC1, including its localization to focal adhesions, its Rho-GAP activity, and its ability to bind tensin and talin.

SIGNOR-276444

Q13315

P48729

0

phosphorylation

down-regulates quantity by destabilization

0.2

Mechanistically, CK1α phosphorylates the serine residue S1270 and modulates the protein abundance of ataxia telangiectasia mutated (ATM), a primary initiator of DNA double-strand break (DSB)-response signaling, which is compromised in ENZA-resistant cells and patients. Inhibition of CK1α stabilizes ATM, resulting in the restoration of DSB signaling, and thus increases ENZA-induced cell death and growth arrest.

SIGNOR-277918

Q9Y6N7

Q14938

0

transcriptional regulation

up-regulates quantity

0.2

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

SIGNOR-268907

Q9BWW4

P06239

0

phosphorylation

up-regulates activity

0.2

The Src tyrosine kinase inhibitor PP2 blocked the nuclear translocation of Ssdp1. Western blot analysis showed that co-expression of Ssdp1 and Lck in 293T cells induces Ssdp1 phosphorylation. Mutation of the Ssdp1 N terminal tyrosine residues 23 and 25 markedly reduced both the phosphorylation and the nuclear localization of Ssdp1. Lck enhanced the transcriptional activity of Ssdp1 in the context of known components of a LIM-homeodomain (LIM-HD)/cofactor complex.

SIGNOR-273648

P03372

Q9H3C7

0

binding

down-regulates activity

0.2

We further demonstrate that GGNBP2 protein physically interacts with ERα, inhibits E2-induced activation of estrogen response element-driven reporter activity, and attenuates ER target gene expression in T47D cells.

SIGNOR-269076

P50549

Q13535

0

phosphorylation

up-regulates quantity by stabilization

0.2

Collectively, the results described above indicate that ATR phosphorylates ETV1 and stabilizes it from proteolytic degradation.

SIGNOR-279355

P68431

O94953

0

demethylation

down-regulates activity

0.2

The KDM4 family of Jumonj domain histone demethylases specifically target di- and tri-methylated lysine 9 on histone H3 (H3K9me3), removing a modification central to defining heterochromatin and gene repression. The majority of studies regarding its function describe it as an activator that removes repressive H3K9me3 and H3K9me2 at or near regulated promoters in order to facilitate expression of the indicated pathways.

SIGNOR-263734

P25098

P62166

0

binding

down-regulates activity

0.2

Here we show that the neuronal calcium sensor-1 (NCS-1) can mediate desensitization of D2 dopamine receptors. Analysis of D2 receptors expressed in human embryonic kidney 293 cells indicates that NCS-1 attenuates agonist-induced receptor internalization via a mechanism that involves a reduction in D2 receptor phosphorylation. Coimmunoprecipitation experiments from striatal neurons reveal that NCS-1 is found in association with both the D2 receptor and G-protein-coupled receptor kinase 2, a regulator of D2 receptor desensitization.

SIGNOR-263965

Q00987

Q9NQU5

0

phosphorylation

up-regulates activity

0.2

We also showed that PAK6 phosphorylates Mdm2 on Thr-158 and Ser-186, which is critical for AR ubiquitin-mediated degradation.

SIGNOR-276428

P68431

P83916

0

binding

up-regulates activity

0.2

A core characteristic of heterochromatin is its association with heterochromatin protein 1 (HP1) proteins, a highly conserved family of chromosomal proteins that bind to di- and trimethylated H3K9 via a conserved N-terminal domain called the chromodomain (CD) HP1 proteins are a highly conserved family of eukaryotic proteins that bind to methylated histone H3 lysine 9 (H3K9) and are required for heterochromatic gene silencing.

SIGNOR-264493

P40763

Q13188

0

phosphorylation

down-regulates activity

0.2

Hippo pathway component MST2 kinase phosphorylates STAT3 at T622, which is located in the SH2 domain of STAT3. This phosphorylation blocks the SH2 domain in one STAT3 molecule to bind with the phosphorylated Y705 site in another STAT3 molecule, which further counteracts IL6-induced STAT3 dimerization and activation.

SIGNOR-277599

P17252

Q9NPB6

0

binding

up-regulates activity

0.2

The Par complex member Par-6, previously thought to inhibit aPKC, is a potent activator of aPKC in our assays. Par-6 and aPKC interact via PB1 domain heterodimerization, and this interaction activates aPKC by displacing the pseudosubstrate, although full activity requires the Par-6 CRIB-PDZ domains.

SIGNOR-227489

Q8N752

Q9H4H8

0

binding

up-regulates quantity

0.2

We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.

SIGNOR-273757

P11912

Q9NRF2

0

dephosphorylation

down-regulates activity

0.2

SHP-1 is recruited by the phosphorylated ITIM-bearing receptors such as CD22 and it dephosphorylates proximal BCR signaling molecules such as CD79, SYK, BLNK.

SIGNOR-268457

P48539

P35398

0

transcriptional regulation

up-regulates quantity by expression

0.2

RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.

SIGNOR-266848

P31751

O60858

0

polyubiquitination

down-regulates quantity by destabilization

0.2

Here, we demonstrate that overexpression of RFP2 in cells induced apoptosis through proteasomal degradation of MDM2 and AKT. We observed that RFP2 formed a complex with MDM2, a negative regulator of the p53 tumor suppressor, and AKT, a regulator of apoptosis inhibition at the cellular level. Additionally, we found that the interaction of RFP2 with MDM2 and AKT resulted in ubiquitination and proteasomal degradation of MDM2 and AKT in vivo and in vitro.

SIGNOR-271853

Q9UK17

P06241

0

phosphorylation

up-regulates activity

0.2

These results indicate that Y108 (for Src-family kinases) and Y136 (for EGFR kinase) are involved in the tyrosine phosphorylation of hKv4.3 channels.

SIGNOR-276396

Q9UHD2

P06239

0

phosphorylation

down-regulates activity

0.2

The Src family kinases (SFKs) Lck, Hck, and Fgr directly phosphorylate TBK1 at Tyr354/394, to prevent TBK1 dimerization and activation.

SIGNOR-276724

O43623

O96013

0

phosphorylation

up-regulates quantity by stabilization

0.2

P21 activated kinase 4 (PAK4) directly phosphorylates Slug, resulting in pro malignant Slug stabilization.

SIGNOR-280057

P18846

Q00526

0

phosphorylation

up-regulates

0.2

Cyclin-dependent kinase 3-mediated activating transcription factor 1 phosphorylation enhances cell transformationwe found that cdk3 phosphorylates activating transcription factor 1 (atf1) at serine 63 and enhances the transactivation and transcriptional activities of atf1.

SIGNOR-180920

P05108

Q9NTG7

0

deacetylation

up-regulates quantity by stabilization

0.2

Resveratrol stimulates cortisol biosynthesis by activating SIRT-dependent deacetylation of P450scc.|Stable overexpression of SIRT3 abrogates the cellular content of acetylated P450scc, concomitant with an increase in P450scc protein expression and cortisol secretion. Mutation of K148 and K149 to alanine stabilizes the expression of P450scc and results in a 1.5-fold increase in pregnenolone biosynthesis.

SIGNOR-268718

P60321

Q99619

0

binding

down-regulates quantity by destabilization

0.2

We have identified SPRY domain-containing SOCS (suppressor of cytokine signaling) box protein 2 (SPSB2) as a novel negative regulator that recruits an E3 ubiquitin ligase complex to polyubiquitinate iNOS, resulting in its proteasomal degradation. A cell-free ubiquitination assay was established to demonstrate SPSB2-dependent ubiquitination of iNOS. LPS/IFN-γ–stimulated macrophage lysates from Spsb2−/− mice were used as a source of iNOS and incubated with ubiquitin and a trimeric SPSB2/elongin BC complex in the presence of E1 and E2 (UbcH5a) enzymes, Rbx2, and Cullin5 for various times.

SIGNOR-271901

P04001

Q92753

0

transcriptional regulation

up-regulates quantity by expression

0.2

These observations indicate that RORβ is required for the induction of S opsin and support the conclusion that RORβ regulates Opn1sw transcription in a direct manner through ROREs within its proximal promoter region. In addition, they explain the greatly diminished expression of Opn1sw observed in the retina of RORβ-/- mice.

SIGNOR-266851

P14210

P08047

0

transcriptional regulation

up-regulates quantity by expression

0.2

Furthermore, in transient cotransfection assays, overexpression of Sp1 and/or Sp3 stimulated HGF promoter activity independently and additively through binding to the Sp1 binding site in the HGF gene promoter region.

SIGNOR-251739

Q6NXT1

Q05655

0

phosphorylation

up-regulates activity

0.2

The mechanism by which phosphorylation of Ankrd54 by PKC\u03b4 enhances cytoplasmic accumulation of Ankrd54 and its interaction with Lyn remains to be determined.|This revealed, in agreement with the biochemical analysis, that PKCdelta significantly promotes cytoplasmic accumulation of Ankrd54.

SIGNOR-279259

P78357

Q05655

0

phosphorylation

down-regulates activity

0.2

Inhibition of PKCdelta increased p190 activity, while PKCdelta overexpression diminished p190 activity.|We further show that PKC\u03b4 was able to phosphorylate and bind distinct domains of p190.

SIGNOR-279260

P55211

Q6UXS9

0

cleavage

up-regulates

0.2

Caspase-12 specifically cleaves and activates procaspase-9 in cytosolic extracts. Results suggest that caspase-12 can activate caspase-9 without involvement of cytochromec.

SIGNOR-90318

P23246

P49840

0

phosphorylation

down-regulates

0.2

Psf is directly phosphorylated by gsk3, thus promoting interaction of psf with trap150, which prevents psf from binding cd45 pre-mrna. / threonine phosphorylation of psf by gsk3 primarily occurs on residue t687

SIGNOR-168385

Q01860

Q6U7Q0

0

transcriptional regulation

up-regulates quantity by expression

0.2

Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays revealed that Zfp322a binds to Pou5f1 and Nanog promoters and regulates their transcription.

SIGNOR-264900

Q13131

Q13554

0

phosphorylation

up-regulates

0.2

These data indicate that the camkks function in intact cells as ampkks, predicting wider roles for these kinases in regulating ampk activity in vivo.

SIGNOR-138360

P68431

P51812

0

phosphorylation

down-regulates activity

0.2

Phosphorylation at ser-11 (h3s10ph) by rps6ka4 and rps6ka5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or uv irradiation and result in the activation of genes, such as c-fos and c-jun.

SIGNOR-119229

Q6DN90

O95819

0

phosphorylation

up-regulates activity

0.2

Together, our results provide compelling evidence that MAP4K4 promotes FA dynamics by regulating IQSEC1 and Arf6 pathway and controlling endocytosis of integrin.|Upon targeting to FAs via MTs, MAP4K4 can bind and phosphorylate IQSEC1, which in turn activates Arf6 and endocytosis, leading to turnover of FAs.

SIGNOR-280020

P26367

O00330

0

binding

down-regulates activity

0.2

In the heterologous cell line BHK-21, Pdx1 inhibited by 60 to 80% the activation of the alpha-cell specific element G1 conferred by Pax-6 and/or Cdx-2/3. Although Pdx1 could bind three AT-rich motifs within G1, two of which are binding sites for Pax-6 and Cdx-2/3, the affinity of Pdx1 for G1 was much lower as compared to Pax-6. In addition, Pdx1 inhibited Pax-6 mediated activation through G3, to which Pdx1 was unable to bind. Moreover, a mutation impairing DNA binding of Pdx1 had no effect on its inhibition on Cdx-2/3. Since Pdx1 interacts directly with Pax-6 and Cdx-2/3 forming heterodimers, we suggest that Pdx1 inhibits glucagon gene transcription through protein to protein interactions with Pax-6 and Cdx-2/3.

SIGNOR-254903

Q9UGP8

P67870

0

phosphorylation

up-regulates activity

0.2

Sec63 was identified as a novel substrate and binding partner of protein kinase CK2. We identified serine 574, serine 576 and serine 748 as CK2 phosphorylation sites. Phosphorylation of Sec63 by CK2 enhanced its binding to Sec62.

SIGNOR-265270

O43781

P18848

0

transcriptional regulation

down-regulates quantity by repression

0.2

Interestingly, the promoter activity of Dyrk3 was negatively regulated by ATF4, indicating a double-negative feedback loop.

SIGNOR-275453

Q16206

Q05655

0

phosphorylation

up-regulates

0.2

Tnox is phosphorylated by protein kinase c_ (pkc_) both in vitro and in vivo. Replacement of serine-504 with alanine significantly reduces phosphorylation by pkc_. C. overexpression of the s504a tnox mutant leads to diminished cell proliferation and migration, reflecting reduced stability of the unphosphorylatable tnox mutant protein.

SIGNOR-197706

Q9GZY8

O94806

0

phosphorylation

up-regulates activity

0.2

The mitochondrial fission factor (MFF), the main mitochondrial receptor for the Dynamin-related protein 1 (DRP1), is directly phosphorylated by Protein Kinase D (PKD) specifically during mitosis. PKD-dependent MFF phosphorylation is required and sufficient for mitochondrial fission in mitotic but not in interphasic cells.|PKD directly phosphorylates MFF on serines 155, 172, and 275

SIGNOR-275945

P16401

P49841

0

phosphorylation

up-regulates

0.2

We found that threonine 10 of h1.5 can be phosphorylated by glycogen synthase kinase-3 in vitro. We have generated an antiserum specific for human h1.5 phosphorylated at threonine 10. Immunofluorescence labeling of hela cells with this antiserum revealed that the phosphorylation at this site appears in prometaphase and disappears in telophase, and that this hyperphosphorylated form of h1.5 is mainly chromatin-bound in metaphase when chromatin condensation is maximal.

SIGNOR-183325

O15084

Q13557

0

phosphorylation

down-regulates activity

0.2

We provide evidence for a dual kinase-mediated regulation of the PITK holoenzyme whereby PITK phosphorylation at S1017 is catalyzed by calcium/calmodulin-dependent kinase II-delta (CaMKIIdelta), promoting the subsequent phosphorylation of S1013 by glycogen synthase kinase-3 (GSK3) in vitro.|the phosphorylation of PITK at these specific residues altered PP1 binding and subsequent PITK-directed dephosphorylation of hnRNP K

SIGNOR-264793

Q15811

Q96CN9

0

relocalization

up-regulates activity

0.2

GFP-GCC88 was immunoprecipitated by both the short and long form of ITSN-1 but not with FLAG-Rheb (Figure 4A). These data demonstrate that both GCC88 and ITSN-1 are part of a complex. We propose that GCC88 recruits ITSN-1-L to the TGN, which in turn activates Cdc42 at the trans-face of the Golgi (Figure 9A).

SIGNOR-260600

Q96F24

P42345

0

phosphorylation

up-regulates activity

0.2

Human NRBF2 is phosphorylated by MTORC1 at S113 and S120. Upon nutrient starvation or MTORC1 inhibition, NRBF2 phosphorylation is diminished. Phosphorylated NRBF2 preferentially interacts with PIK3C3/PIK3R4. Suppression of NRBF2 phosphorylation by MTORC1 inhibition alters its binding preference from PIK3C3/PIK3R4 to ATG14/BECN1, leading to increased autophagic PtdIns3K complex assembly, as well as enhancement of ULK1 protein complex association.

SIGNOR-265875

Q9UGI0

P31749

0

phosphorylation

up-regulates activity

0.2

Our findings also identify an essential role for activation of Trabid by AKT-mediated phosphorylation at Ser78/Thr117 in negatively regulating Twist1 signaling, which further provides insights into the mechanisms by which Trabid regulates Twist1 ubiquitination.

SIGNOR-273484

Q9Y4G8

O14920

0

phosphorylation

down-regulates quantity by destabilization

0.2

Taken together, these results indicate that IKK\u03b2-dependent phosphorylation of RAPGEF2 is required for RAPGEF2 degradation induced by HGF and mediated by \u03b2TrCP.

SIGNOR-279807

P09211

Q05513

0

phosphorylation

up-regulates activity

0.2

Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently

SIGNOR-276017

P54274

P68400

0

phosphorylation

up-regulates

0.2

Regulation of telomeric repeat binding factor 1 binding to telomeres by casein kinase 2-mediated phosphorylation. Mapping of the ck2 target site identified threonine 122 as a substrate in trf1. A threonine to alanine change at this position led to a diminished dna binding due to reduced dimerization of trf1.

SIGNOR-178034

P19447

P68400

0

phosphorylation

down-regulates activity

0.2

Phosphorylation of S751 by CKII inhibits 5′ incision.

SIGNOR-276013

P46527

P49792

0

relocalization

down-regulates quantity

0.2

RanBP2 can increase the sumoylation of p27kip1. In our study, the target protein p27kip1 mainly acts as a tumor-suppressor gene in the nucleus, RanBP2 and SUMO1 act as oncogenes by promoting the nuclear-cytoplasmic translocation and debilitate the G1-arrest brought by p27kip1 accumulation in the nucleus.

SIGNOR-259115

Q13671

P55196

0

binding

up-regulates activity

0.2

Rit and Rin were found to interact with the known Ras binding proteins RalGDS, Rlf, and AF-6/Canoe. These interactions were GTP and effector domain dependent and suggest that RalGDS, Rlf, and AF-6 are Rit and Rin effectors.

SIGNOR-220926

O43318

Q13555

0

phosphorylation

up-regulates

0.2

Camkii interacts with and phosphorylates tak1.

SIGNOR-96422

O94826

Q13627

0

phosphorylation

up-regulates activity

0.2

Phosphorylation of TOM70 Ser91 by DYRK1A stimulates interaction of TOM70 with the core TOM translocase.

SIGNOR-279994

Q9P0L9

P17612

0

phosphorylation

up-regulates activity

0.2

PKD2L1 channel activation by PKA phosphorylation. In this study, we observed the activity of PKD2L1 channel increased by the downstream cascades of β2AR and found the clustered phosphorylation sites, Ser-682, Ser-685, and Ser-686 that are significant in the channel regulation by phosphorylation.

SIGNOR-273562

P48729

Q9BQN1

0

binding

up-regulates quantity

0.2

We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.

SIGNOR-273752

Q71DI3

Q9UIF8

0

binding

down-regulates activity

0.2

The BAZ2B bromodomain has been shown to bind to acetylated H3K14 (H3K14ac), whose presence at promoter regions is generally associated with gene activation. This suggests a potential role for BAZ2B in transcriptional activation.

SIGNOR-266623

Q9BX84

P63244

0

binding

down-regulates activity

0.2

We identified RACK1 as the first TRPM6-associated protein and demonstrated that RACK1 inhibits TRPM6 channel activity depending on the phosphorylation state T1851 in the α-kinase domain.

SIGNOR-260921

O43524

O43638

0

transcriptional regulation

down-regulates quantity by repression

0.2

Fkhl18 suppressed the transcriptional activity of FoxO3a and FoxO4.

SIGNOR-261610

P69905

P15169

0

cleavage

down-regulates activity

0.2

Both human plasma carboxypeptidase N (CPN) and membrane-bound carboxypeptidase M (CPM) released the C-terminal arginine (alpha-Arg141) of the alpha chain of human adult hemoglobin. Thus, the hydrolysis of hemoglobin by CPM and CPN demonstrated the contribution of the alpha-Arg141 residue to sustaining the tetrameric structure of hemoglobin and its normal oxygen affinity and vasoactivity.

SIGNOR-256508

Q12800

P27361

0

phosphorylation

down-regulates

0.2

We previously established that phosphorylation of lsf in early g1 at ser-291 and ser-309 inhibits its transcriptional activity and that dephosphorylation later in g1 is required for its reactivation. At the peak activities of erk and cyclin c/cdk2 in early g1, lsf is efficiently phosphorylated on ser-291 and ser-309.

SIGNOR-184176

P52292

P0DTC6

0

binding

down-regulates activity

0.2

The results from Figure 1C suggest that ORF6 inhibits IFN-β production through IRF3 or a component downstream of IRF3. Thus, we examined the effect of ORF6 on IRF3 nuclear translocation. Upon poly(I:C) treatment, IRF3 translocated to the cell nucleus in the absence of ORF6, whereas the expression of ORF6 blocked its nuclear translocation (Figure 2D). Karyopherin α 1–6 (KPNA1–6) are importing factors for nuclear translocation of cargos, including IRF3, IRF7, and STAT1 (Chook and Blobel, 2001). Co-immunoprecipitation showed that ORF6 selectively interacted with KPNA2, but not the other KPNAs (Figure 2E), suggesting that ORF6 inhibits IFN-β production by binding to KPNA2 to block IRF3 nuclear translocation (Figure 2F).

SIGNOR-262513

P52292

Q19QW5

0

relocalization

down-regulates activity

0.2

Taken together, these data support a direct interaction between KPNA2 and ORF6 in the context of virus infection.|SARS-CoV, but not SARSdeltaORF6, retains KPNA2 at the ER/Golgi membrane.

SIGNOR-260272

Q9NZQ7

Q9Y2A9

0

glycosylation

up-regulates activity

0.2

These results further suggested that B3GNT3 mediates PD-L1 and PD-1 interaction through N-linked glycosylation instead of O-linked glycosylation

SIGNOR-275389

Q13586

Q13131

0

phosphorylation

down-regulates activity

0.2

STIM1 is a novel exercise‐regulated AMPK substrate. Phosphorylation of STIM1 by AMPK suppresses SOCE

SIGNOR-277299

Q03135

O60260

0

ubiquitination

down-regulates quantity

0.2

Parkin induces the degradation of cav-1 through the proteasome dependent pathway.|We also demonstrated that WT parkin ubiquitinates cav-1 for degradation.

SIGNOR-278710

P10912

P54764

0

phosphorylation

up-regulates activity

0.2

EphA4 binds to growth hormone receptor at both its extracellular and intracellular domains and phosphorylates growth hormone receptor when stimulated with a ligand.|These findings suggest that EphA4 activates not only GHR, as shown above, but also JAK2 by direct phosphorylation.

SIGNOR-279461

P05771

P54792

0

binding

up-regulates

0.2

Taken together, these results suggest that site-specific dvl2 phosphorylation is required for dvl2 association with pkc_. This interaction is likely to be one of the mechanisms essential for wnt3a-dependent neurite outgrowth.

SIGNOR-199457

P49841

Q9UK32

0

phosphorylation

down-regulates activity

0.2

Moreover, RSK4 stabilized Beta-catenin in the presence of GSK-3Beta WT but not RSK4 stabilizes Beta-catenin through phosphorylation of GSK-3Beta (Ser9) in ESCC cells|GSK-3Beta S9A in ESCC cells, which was similar to overexpression of GSK3Beta S9D|

SIGNOR-275801

Q15652

P22415

0

binding

up-regulates activity

0.2

We show that, by direct interaction with USF-1, JMJD1C is recruited to lipogenic promoters. We also show that JMJD1C is phosphorylated at T505 by mammalian target of rapamyci (mTOR) to be recruited to lipogenic genes in response to insulin/feeding.

SIGNOR-265167

Q5XUX0

P12830

0

binding

down-regulates quantity by destabilization

0.2

Here we show that the low levels of FBXO31 are maintained through proteasomal degradation by anaphase-promoting complex/cyclosome (APC/C). We find that the APC/C coactivators CDH1 and CDC20 bind to a destruction-box (D-box) motif present in FBXO31 to promote its polyubiquitination and degradation in a cell-cycle-regulated manner, which requires phosphorylation of FBXO31 on serine-33 by the prosurvival kinase AKT.

SIGNOR-277377

Q02447

P62136

0

dephosphorylation

down-regulates activity

0.2

Transcription factors Sp1 and Sp3 activate alpha-ENaC2 transcription through a GC-rich element (Sp1-binding site) in the promoter. Sp1 and Sp3 are essential for alpha-ENaC2 transcription in lung epithelial cells and that dephosphorylation of the Sp transcription factors by PP1 suppresses alpha-ENaC2 expression.

SIGNOR-251953

P09471

P25103

0

binding

up-regulates activity

0.2

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257249

P27816

O14757

0

phosphorylation

down-regulates quantity by destabilization

0.2

MAP4 is a novel target of FBXW7 via the phosphorylated threonine T521 modified by CHEK1 in ESCC. The threonine T521 of MAP4, which was phosphorylated by CHEK1, played a key role in the FBXW7-related degradation system.

SIGNOR-277846

Q9UJT1

Q14980

0

binding

up-regulates

0.2

Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules.

SIGNOR-117159

Q9UHC6

Q6ZVD7

0

transcriptional regulation

down-regulates quantity by repression

0.2

In this study we performed chromatin immunoprecipitation coupled to shotgun cloning to discover novel STOX1A target genes. Our results show that CNTNAP2, a member of the neurexin family, is directly downregulated by STOX1A.

SIGNOR-269065

Q01668

Q9UJD0

0

binding

up-regulates activity

0.2

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-264357

P0C0S8

O75582

0

phosphorylation

up-regulates

0.2

We found that msk1 phosphorylated histone h2a on serine 1, and mutation of serine 1 to alanine blocked the inhibition of transcription by msk1.

SIGNOR-123383