+ |
PRKG2 | down-regulates activity
phosphorylation
|
HCN2 |
0.2 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-263185 |
Ser668 |
DRIGKKNsILLHKVQ |
Mus musculus |
Brain |
pmid |
sentence |
21347269 |
Here, we show for the first time that in the HCN2 channel cGMP can also exert an inhibitory effect on gating via cGMP-dependent protein kinase II (cGKII)-mediated phosphorylation.We identify the proximal C-terminus of HCN2 as binding region of cGKII and show that cGKII phosphorylates HCN2 at a specific serine residue (S641) in the C-terminal end of the CNBD. The cGKII shifts the voltage-dependence of HCN2 activation to 2-5 mV more negative voltages and, hence, counteracts the stimulatory effect of cGMP on gating. |
|
Publications: |
1 |
Organism: |
Mus Musculus |
+ |
SRC | up-regulates activity
phosphorylation
|
HCN2 |
0.27 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-263199 |
Tyr476 |
LDSSRRQyQEKYKQV |
Homo sapiens |
HEK-293 Cell |
pmid |
sentence |
26280531 |
We identified a highly conserved tyrosine residue in the C-linker of HCN channels (Tyr476 in HCN2) that confers modulation by Src. Replacement of this tyrosine by phenylalanine in HCN2 or HCN4 abolished sensitivity to Src inhibitors. Mass spectrometry confirmed that Tyr476 is phosphorylated by Src. Our results have functional implications for HCN channel gating. Furthermore, they indicate that tyrosine phosphorylation contributes in vivo to the fine tuning of HCN channel activity. |
|
Publications: |
1 |
Organism: |
Homo Sapiens |