| + |
CSNK2A2 | up-regulates activity 
phosphorylation
|
SCN2A |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275754 |
Ser1112 |
VPIAVGEsDFENLNT |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19064667 |
We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275758 |
Ser1124 |
LNTEEFSsESDMEES |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19064667 |
We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275762 |
Ser1126 |
TEEFSSEsDMEESKE |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19064667 |
We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
CSNK2B | up-regulates activity
phosphorylation
|
SCN2A |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275752 |
Ser1112 |
VPIAVGEsDFENLNT |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19064667 |
We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275756 |
Ser1124 |
LNTEEFSsESDMEES |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19064667 |
We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275760 |
Ser1126 |
TEEFSSEsDMEESKE |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19064667 |
We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
CSNK2A3 | up-regulates activity
phosphorylation
|
SCN2A |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275751 |
Ser1112 |
VPIAVGEsDFENLNT |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19064667 |
We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275755 |
Ser1124 |
LNTEEFSsESDMEES |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19064667 |
We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275759 |
Ser1126 |
TEEFSSEsDMEESKE |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19064667 |
We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
CSNK2A1 | up-regulates activity
phosphorylation
|
SCN2A |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275753 |
Ser1112 |
VPIAVGEsDFENLNT |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19064667 |
We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275757 |
Ser1124 |
LNTEEFSsESDMEES |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19064667 |
We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275761 |
Ser1126 |
TEEFSSEsDMEESKE |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19064667 |
We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
GSK3B | down-regulates activity 
phosphorylation
|
SCN2A |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275748 |
Thr1966 |
TPEKTDMtPSTTSPP |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 32599005 |
Glycogen synthase kinase 3β (GSK3beta) phosphorylates the Nav1.2C-terminal tail at T1966, suppressing Na+ currents and channel trafficking to the plasma membrane |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FGF12 | down-regulates activity
binding
|
SCN2A |
0.315 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253428 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 20679355 |
Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FGF11 | down-regulates activity
binding
|
SCN2A |
0.255 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253430 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 20679355 |
Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RCOR1 | down-regulates quantity by repression 
transcriptional regulation
|
SCN2A |
0.274 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-220695 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 10449787 |
We show here that CoREST, a newly identified human protein, functions as a corepressor for REST. A single zinc finger motif in REST is required for CoREST interaction. Together, REST and CoREST mediate repression of the type II sodium channel promoter in nonneural cells, and the REST/CoREST complex may mediate long-term repression essential to maintenance of cell identity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
phenytoin | down-regulates activity
chemical inhibition
|
SCN2A |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258352 |
|
|
Rattus norvegicus |
|
| pmid |
sentence |
| 1658608 |
This study examined the actions of phenytoin, carbamazepine, lidocaine, and verapamil on rat brain type IIA Na+ channels functionally expressed in mammalian cells, using the whole-cell voltage-clamp recording technique. The drugs blocked Na+ currents in both a tonic and use-dependent manner. |
|
| Publications: |
1 |
Organism: |
Rattus Norvegicus |
| + |
FGF14 | down-regulates activity
binding
|
SCN2A |
0.384 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253429 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 20679355 |
Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TNF | up-regulates activity 
|
SCN2A |
0.261 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253489 |
|
|
Mus musculus |
Cerebral Cortical Neuron |
| pmid |
sentence |
| 26112872 |
TNF-α increases Na(+) currents by accelerating the channel activation as well as increasing the expression of VGSCs in a mechanism dependent upon NF-κB and p38 MAPK signal pathways in CNS neurons. TNF-α increased Na(+) currents by accelerating the activation of VGSCs. The threshold for action potential (AP) was decreased and firing rate were increased. VGSCs were up-regulated at both the mRNA and protein levels. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
verapamil | down-regulates activity
chemical inhibition
|
SCN2A |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258355 |
|
|
Rattus norvegicus |
|
| pmid |
sentence |
| 1658608 |
This study examined the actions of phenytoin, carbamazepine, lidocaine, and verapamil on rat brain type IIA Na+ channels functionally expressed in mammalian cells, using the whole-cell voltage-clamp recording technique. The drugs blocked Na+ currents in both a tonic and use-dependent manner. |
|
| Publications: |
1 |
Organism: |
Rattus Norvegicus |
| + |
IL10 | down-regulates quantity by repression
transcriptional regulation
|
SCN2A |
0.274 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253499 |
|
|
Rattus norvegicus |
|
| pmid |
sentence |
| 23357618 |
Interleukin-10 down-regulates voltage gated sodium channels in rat dorsal root ganglion neurons. Consistent with the electrophysiological results, real-time PCR and western blot revealed that IL-10 (200 pg/ml) down-regulated VGSCs in both mRNA and protein levels and reversed the up-regulation of VGSCs by TNF-α. |
|
| Publications: |
1 |
Organism: |
Rattus Norvegicus |
| + |
PKA | down-regulates activity
phosphorylation
|
SCN2A |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275749 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 32599005 |
For example, protein kinase A (PKA) and protein kinase C (PKC) have been shown to phosphorylate multiple serine residues on the interdomain I-II and III-IV linkers of Nav1.2, significantly reducing current and increasing firing thresholds |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SCN2A | up-regulates quantity
relocalization
|
sodium(1+) |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253404 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 27262167 |
Voltage-gated Na1 channels (NaV channels) drive the rapid upstroke of action potentials in cardiac and skeletal muscle and in most neurons, thereby serving as initiators of electrical activity in excitable tissue. Nine genes encode a family of homologous of NaV channel pore-forming a subunits. While channels are open, Na1 ions flux through the central pore down an electrochemical gradient, further depolarizing the membrane and triggering an action potential. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KDM5C | down-regulates quantity by repression
transcriptional regulation
|
SCN2A |
0.336 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-264313 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 31691806 |
The KDM5C decrease was associated with a lack of repression of downstream target genes Scn2a, Syn1 and Bdnf in the embryonic brain of Arx-null mice. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
TNF | up-regulates quantity by expression
transcriptional regulation
|
SCN2A |
0.261 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253480 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 26112872 |
TNF-α increases Na(+) currents by accelerating the channel activation as well as increasing the expression of VGSCs in a mechanism dependent upon NF-κB and p38 MAPK signal pathways in CNS neurons. TNF-α increased Na(+) currents by accelerating the activation of VGSCs. The threshold for action potential (AP) was decreased and firing rate were increased. VGSCs were up-regulated at both the mRNA and protein levels. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
FGF13 | down-regulates activity
binding
|
SCN2A |
0.273 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253427 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 20679355 |
Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
lidocaine | down-regulates activity
chemical inhibition
|
SCN2A |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258354 |
|
|
Rattus norvegicus |
|
| pmid |
sentence |
| 1658608 |
This study examined the actions of phenytoin, carbamazepine, lidocaine, and verapamil on rat brain type IIA Na+ channels functionally expressed in mammalian cells, using the whole-cell voltage-clamp recording technique. The drugs blocked Na+ currents in both a tonic and use-dependent manner. |
|
| Publications: |
1 |
Organism: |
Rattus Norvegicus |
| + |
REST | down-regulates quantity by repression
transcriptional regulation
|
SCN2A |
0.297 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-220698 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 10449787 |
We show here that CoREST, a newly identified human protein, functions as a corepressor for REST. A single zinc finger motif in REST is required for CoREST interaction. Together, REST and CoREST mediate repression of the type II sodium channel promoter in nonneural cells, and the REST/CoREST complex may mediate long-term repression essential to maintenance of cell identity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CoREST-HDAC complex | down-regulates quantity by repression
transcriptional regulation
|
SCN2A |
0.277 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268541 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 16140033 |
This suggests that the HDACs in the LSD1 complex are likely to function upstream of CoREST/LSD1, generating a hypoacetylated histone substrate, which can then be better recognized by CoREST/LSD1. Further supporting this model, we found that inhibition of HDAC activity by TSA resulted in derepression of two LSD1 target genes, the human neuronal-specific sodium channel (SCN) genes, SCNA2 and SCNA3 (Figure 1H). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SCN2A | up-regulates
|
Action_potential |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253450 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 26043074 |
The expression of voltage-gated sodium channels (NaVs) is a key feature for initiation and conduction of action potentials in excitable tissues and cells such as cardiac and skeletal muscle and neurons. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PKC | down-regulates activity
phosphorylation
|
SCN2A |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275750 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 32599005 |
For example, protein kinase A (PKA) and protein kinase C (PKC) have been shown to phosphorylate multiple serine residues on the interdomain I-II and III-IV linkers of Nav1.2, significantly reducing current and increasing firing thresholds |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
carbamazepine | down-regulates activity
chemical inhibition
|
SCN2A |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258353 |
|
|
Rattus norvegicus |
|
| pmid |
sentence |
| 1658608 |
This study examined the actions of phenytoin, carbamazepine, lidocaine, and verapamil on rat brain type IIA Na+ channels functionally expressed in mammalian cells, using the whole-cell voltage-clamp recording technique. The drugs blocked Na+ currents in both a tonic and use-dependent manner. |
|
| Publications: |
1 |
Organism: |
Rattus Norvegicus |
| + |
NEDD4L | down-regulates quantity by destabilization
ubiquitination
|
SCN2A |
0.323 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253459 |
|
|
Mus musculus |
Neuron |
| pmid |
sentence |
| 23778145 |
The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
3.0
SCN2A
- 
- 