KChannelDB: Extraction of mutation data from the literature

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

The table below describes different point mutations at a given position and provides links to other documents. The sentence(s) where the point mutations in IRK3_RAT at position 137 were found are listed after the table.

Point mutations at position F137 in IRK3_RAT

ProteinIRK3_RAT (P63251)    Gene: Kcnj3,Girk1, Kg    (other point mutations)Swiss-Prot
Cross-reference table
Family page
PositionF137
General numbering (KChannelDB) -
DomainLoop 1-2
Family alignments Inward rectifiers (Kir)
Potassium channels 2 TMs
Other point mutations at the same position Position 118 in Inward rectifiers (Kir) family
Position 118 in Potassium channels 2 TMs family
Reference #1Mao J, Li L, McManus M, Wu J, Cui N, Jiang C
J Biol Chem 2002 Nov 29;277(48):46166-71.		Medline
Text sourceHTML full text
Point mutationF137S (Not yet checked)
Cited point mutationPhe137Ser,Phe-137
Reference #2Mao 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
Text sourceHTML full text
Point mutationF137S (Not yet checked)
Reference #3Milovic S, Steinecker-Frohnwieser B, Schreibmayer W, Weigl LG
J Biol Chem 2004 Aug 13;279(33):34240-9. Epub 2004 Jun 2.		Medline
Text sourceHTML full text
Point mutationF137S (Not yet checked)
Reference #4Ramu Y, Klem AM, Lu Z
Biochemistry 2004 Aug 24;43(33):10701-9.		Medline
Text sourceHTML full text
Point mutationF137S (Not yet checked)

Relevant sentences

Reference #1 (Mao J et al.): F137S
  • We found that homomeric GIRK1-F137S and GIRK4-S143T channels were activated at pH o 6.2 by ~20 and ~70% , respectively

  • Therefore , we constructed the GIRK1 with Phe-137 mutated to serine (GIRK1-F137S) and GIRK4 with Ser-143 mutated to threonine (GIRK4-S143T) as shown previously by Vivaudou et al. (35 )

  • Homomeric expressions of GIRK1 and GIRK4 channels were achieved by F137S mutation in GIRK1 and S143T mutation in GIRK4

  • The GIRK1-F137S was moderately stimulated at pH o 6.2 (A) , whereas the GIRK4-S143T currents were strongly augmented (B)

  • We found that the histidine mutation totally abolished the pH o sensitivity in both homomeric GIRK1-F137S and GIRK4-S143T channels (Figs

  • Because the homomeric GIRK4-S143T is more sensitive to pH o than the GIRK1-F137S , it is possible that the His-120 in GIRK4 plays a more important role in the pH o sensitivity of the heteromeric GIRK1 / GIRK4 channels

Reference #2 (Mao J et al.): F137S
  • Therefore , the F137S mutation was constructed in GIRK1 (GIRK1F137S , GIRK1*) and the S143T in GIRK4 (GIRK4S143T , GIRK4*) by using the site-directed mutagenesis technique

  • The GIRK1F137S currents were markedly inhibited by 30 nM PMA

  • Similar results were found in the GIRK1F137S-S185A mutant (D) and heteromeric GIRK1S185A / GIRK4S191A channel (E)

  • GIRK1* , GIRK1F137S ; GIRK4* , GIRK4S143T

Reference #3 (Milovic S et al.): F137S
  • When coexpressed with the m2 acetylcholine (ACh) receptor in Xenopus oocytes , agonist-activated GIRK1F137S- and GIRK2-mediated currents are inhibited by halothane , whereas in the absence of ACh , high concentrations of halothane induce GIRK1F137S-mediated currents

  • To elucidate the molecular mechanism of halothane action on GIRK currents of different subunit compositions , we constructed deletion mutants of GIRK1F137S (GIRK1{Delta}363*) and GIRK2 (GIRK2{Delta}356) lacking the C-terminal ends , as well as chimeric GIRK channels

  • GIRK1 F137S or GIRK1 containing heteromeric channels such as GIRK1 / GIRK4 , but not homomeric GIRK4 channels , are activated by high concentrations of halothane in the absence of an agonist (14 )

  • GIRK2 / 1 / 2 and GIRK2 / 1 / 2 / 1 are chimeric GIRK proteins with the transmembrane domains of GIRK1F137S between aa 88 and aa 202 inserted into the core of GIRK2 and GIRK2 / 1356 , respectively

  • To elucidate the mechanism of halothane action on GIRK channels on the molecular level and to investigate the structural requirements for the modulation by halothane , we performed single channel experiments and used deletion mutants of GIRK1 F137S (the substitution of a serine for a phenylalanine in GIRK1 is necessary to get conductive homooligomeric GIRK1 channels ; Ref

  • Oocytes were prepared as described (26 ) , and 50 nl of cRNA solutions were injected (concentrations in ng / µl given in parenthesis): m2 receptor (30 ) , GIRK1F137S (0.3) , GIRK1{Delta}363* (0.3) , GIRK2 WT (30) , GIRK2{Delta}356 (3) and GIRK2 / 1356 (0.25-0.85) , GIRK2 / 1 / 2 (250) , GIRK2 / 1 / 2 / 1 (3)

  • The following DNAs were used: m2 receptor (29 ) , rat GIRK1F137S from atrium , and GIRK2 WT from mouse testis cloned into pBS-mxt

  • For exchange of the transmembrane domains of GIRK2 and GIRK2 / 1356 by the homologous domain of GIRK1F137S (aa 88-202) , restriction sites for AflII and EheI were introduced by site-directed mutagenesis

  • The difference in currents was less pronounced for GIRK1F137S and GIRK1{Delta}363* channels ; the truncated channels showed an increase in the current amplitude by a factor of about 4.5 and no change in the current ratios (Fig. 1B ) when the same amount of cRNA was injected

  • Effect of Halothane on Currents through Homooligomeric Wild Type GIRK Channels—As exemplified in Fig. 2A , halothane was able to modulate the current through homooligomeric GIRK1 F137S channels in Xenopus oocytes , corroborating our previous results (14 )

  • Halothane activates basal currents but inhibits IACh through GIRK1F137S channels

  • A , time course of a GIRK1F137S-mediated current expressed in a Xenopus oocyte measured with the two-electrode voltage clamp technique

  • Addition of 50 nM ACh to the pipette solution activated GIRK1 F137S channels in cell-attached patches

  • The effects of halothane on the agonist-induced activity of GIRK1 F137S channels

  • Agonist-induced currents were more sensitive against halothane than currents through GIRK1 F137S channels

  • The halothane-induced activation of background currents that were mediated by truncated GIRK1 {Delta}363* channels was more pronounced than with GIRK1 F137S currents (Fig. 5 , A and B )

  • Lower concentrations were less effective , but still 300 µM halothane induced 104 ± 14% (n = 17 , p < 0.001) augmentation of the current , a value reached with GIRK1 F137S-mediated currents only at concentrations of more than 1 mM

  • The deletion of the C terminus of GIRK1 F137S altered its halothane sensitivity

  • B , current activation by halothane was more pronounced in GIRK1 {Delta}363*-injected oocytes than with GIRK1 F137S currents

  • The agonist-induced currents of GIRK1 {Delta}363* were similarly sensitive to inhibition by halothane when compared with GIRK1 F137S channels

  • Single channel experiments of the halothane effect on GIRK1 {Delta}363* yielded similar results compared with GIRK1 F137S channels

  • The single channel conductivity was determined to be 14.5 ± 0.18 picosiemens and , therefore , the same as for GIRK1 F137S channels

  • As expected from the two-electrode voltage clamp experiments , halothane at a concentration of 1 mM had no effect on the open probability of ACh-activated GIRK1 {Delta}363* channels , but similar to GIRK1 F137S channels , it propagated channel openings with longer open times (Table I and Fig. 5 , F and G )

  • In contrast to GIRK1F137S or GIRK2{Delta}356 channels , the basal current of the chimera was inhibited instead of being activated by halothane (data not shown)

  • Therefore , we substituted the region between aa 88 and aa 202 of the GIRK2 channel and the GIRK2 / 1356 channel for the homologous region of GIRK1F137S

  • In the absence of an agonist , halothane induced activity of GIRK1 F137S and GIRK1 {Delta}363* channels

Reference #4 (Ramu Y et al.): F137S
  • Interestingly , a single mutation located distally to the variable region (F137S in GIRK1 or S143T in GIRK4 ; Figure 10A) causes them not only to express functional homotetrameric channels , but also to conduct K + current constitutively (42)

  • Parts B-D of Figure 10 show current records of GIRK1 / 4 , GIRK1-F137S , and GIRK4-S143T channels in the absence or presence of TPN Q at the concentrations indicated

  • Analysis of dose-inhibition curves yields K d values of 12 nM , 20 (image)M , and 2 nM for GIRK1 / 4 , GIRK1-F137S , and GIRK4-S143T channels , respectively (Figure 10E)

  • (B-D) Currents of GIRK1 / 4 , GIRK1-F137S , and GIRK4-S143T , recorded in the absence or presence of TPN Q at the concentrations indicated

  • The curves through the data are fits of the equation described in Figure 2 , yielding K d values of 12.2 ± 0.1 nM , 20.0 ± 0.2 (image)M , and 2.1 ± 0.2 nM for GIRK1 / 4 , GIRK1-F137S , and GIRK4-S143T , respectively

Reference #1 (Mao J et al.): Phe-137
  • Therefore , we constructed the GIRK1 with Phe-137 mutated to serine (GIRK1-F137S) and GIRK4 with Ser-143 mutated to threonine (GIRK4-S143T) as shown previously by Vivaudou et al. (35 )

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