KChannelDB: Extraction of mutation data from the literature

2005, KChannelDB.

This data was extracted from Medline abstracts and full texts (when available) in an automated manner.

The table below describes the selected point mutation and provides links to other documents. The sentence(s) where the point mutation S191A was found are listed after the table.

The mutated residues are also indicated in the family sequence alignments and hyperlinked to the corresponding mutation pages.

Point mutation S191A in IRK5_RAT

Point mutation:	S191A
Cited point mutation:	Ser191Ala,Ser-191
Domain:	C-term
General numbering (KChannelDB):	-
Protein:	IRK5_RAT (Kcnj5,Girk)	Swiss-Prot Cross-reference table Family page
Other point mutations / same protein	List of mutations in IRK5_RAT
Family alignments	Inward rectifiers (Kir) Potassium channels 2 TMs
Other point mutations / same position	Position 166 in Inward rectifiers (Kir) family Position 166 in Potassium channels 2 TMs family
Reference:	Molecular basis for the inhibition of G protein-coupled inward rectifier K(+) channels by protein kinase C. Mao J, Wang X, Chen F, Wang R, Rojas A, Shi Y, Piao H, Jiang C Proc Natl Acad Sci U S A 2004 Jan 27;101(4):1087-92. Epub 2004 Jan 19.	Medline
Other point mutations / same article	List
Text source	HTML full text
Validation status	Not yet checked

Relevant sentences:

Ser-191

This inhibition was greatly eliminated by mutation of Ser-185 in GIRK1 and Ser-191 in GIRK4 that remained G protein sensitive
Thus , these results indicate that the PKC-dependent phosphorylation underscores the inhibition of GIRK channels by SP , and Ser-185 in GIRK1 and Ser-191 in GIRK4 are the PKC phosphorylation sites
Our results indicate that Ser-185 in GIRK1 and Ser-191 in GIRK4 are likely to be the PKC sites critical for the inhibition of GIRK channels by the excitatory neurotransmitter SP
(C) When Ser-191 was substituted with an alanine in GIRK4S143T , the GIRK4S143T-S191A currents were barely inhibited by 30 nM PMA
Ser-185 in the GIRK4 and Ser-191 in the GIRK4 were shown to affect the PMA sensitivity
If the Ser-191 in GIRK4 is a phosphorylation site , mutation of Ser-185 at the corresponding site in GIRK1 may also affect the PKC-induced channel inhibition
To understand whether the Ser-191 in GIRK4 and Ser-185 in GIRK1 indeed mediate the PMA-induced inhibition of the heteromeric GIRK1 / GIRK4 channel , GIRK1S185A and GIRK4S191A mutations were constructed in the WT GIRK1 and GIRK4 , and coexpressed in the oocytes
(B) Mutation of Ser-185 in the GIRK4 and Ser-191 in the GIRK4 to alanine eliminated the SP- and PMA-induced channel inhibition
The PKC-dependent inhibition of GIRK channels relies on Ser-185 in GIRK1 and Ser-191 in GIRK4

S191A

(A) Exposure of the internal patch membrane to the catalytic subunit of PKC (0.1 unit / ml for 20 s) strongly inhibited the WT channels (* , P < 0.05 in comparison with the control group WT without PKC) whereas PKC did not significantly reduce activity of the GIRK1S185A / GIRK4S191A mutant in comparison with that in the absence of PKC (P > 0.05 , n = 4-10)
(B) A 20-s exposure of the internal patch membranes to 20 nM G beta gamma markedly enhanced channel activity of the GIRK1S185A / GIRK4S191A mutant in comparison with the WT GIRK1-GIRK4 in the absence of G protein in A
(C) When Ser-191 was substituted with an alanine in GIRK4S143T , the GIRK4S143T-S191A currents were barely inhibited by 30 nM PMA
Similar results were found in the GIRK1F137S-S185A mutant (D) and heteromeric GIRK1S185A / GIRK4S191A channel (E)
The S191A mutation significantly diminished the PMA-induced channel inhibition (11.1 ą 4.8% , n = 14 ; P < 0.01) (Fig. 3C ) whereas no significant change in the PMA effect was found in other mutants (Fig. 3F )
To understand whether the Ser-191 in GIRK4 and Ser-185 in GIRK1 indeed mediate the PMA-induced inhibition of the heteromeric GIRK1 / GIRK4 channel , GIRK1S185A and GIRK4S191A mutations were constructed in the WT GIRK1 and GIRK4 , and coexpressed in the oocytes
The GIRK1S185A / GIRK4S191A showed baseline currents 3.7 ą 0.4 ľA (n = 14) and were inhibited by 30 nM PMA by 17.8 ą 2.0% , which was significantly smaller than that of the WT GIRK1 / GIRK4 (P < 0.01) (Fig. 3 E and F )
Because the GIRK1S185A / GIRK4S191A did not completely eliminate the current inhibition by PMA , there may be another unidentified PKC site that could be the Ser-221 in GIRK1 and Ser-227 in GIRK4
The sensitivity of the GIRK1S185A / GIRK4S191A to the catalytic subunit of PKC was studied in inside-out patches
Like its WT counterpart , the GIRK1S185A / GIRK4S191A remained to be sti mulated by the G beta gamma subunit in excised patches although the channel rundown seemed to be faster than the WT channels (Fig. 4B )
Neither the GIRK1S185A / GIRK4S191A nor the GIRK1S185D / GIRK4S191D was inhibited by SP (1.1 ą 2.3% , n = 12 ; and 4.7 ą 0.8% , n = 6 , respectively)
We have noticed that the GIRK1S185A / GIRK4S191A mutant is still modestly inhibited by PMA

F.Horn (kchanneldbcmbi.ru.nl), 17-Aug-2005