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 IRK11_MOUSE at position 127 were found are listed after the table.

Point mutations at position V127 in IRK11_MOUSE

ProteinIRK11_MOUSE (Q61743)    Gene: Kcnj1    (other point mutations)Swiss-Prot
Cross-reference table
Family page
PositionV127
General numbering (KChannelDB) -
DomainLoop 1-2
Family alignments Inward rectifiers (Kir)
Potassium channels 2 TMs
Other point mutations at the same position Position 121 in Inward rectifiers (Kir) family
Position 121 in Potassium channels 2 TMs family
Reference #1Proks P, Capener CE, Jones P, Ashcroft FM
J Gen Physiol 2001 Oct;118(4):341-53.		Medline
Text sourceHTML full text
Point mutationV127A (Not yet checked)
Point mutationV127D (Not yet checked)
Point mutationV127K (Not yet checked)
Point mutationV127S (Not yet checked)
Point mutationV127T (Not yet checked)

Relevant sentences

Reference #1 (Proks P et al.): V127A
  • The following mutations did not produce functional channels: V127K , V127S , V127A , V127D , E126Q , E126D , F133Y , and the double mutants F133Y + M137C , F133Y + G135F , and V127T + W83F

  • We attempted to explore the effect of mutating V127 to a range of other amino acids including both charged (V127K , V127D) and uncharged (V127S , V127A) residues , but none of these mutations expressed functional channels

Reference #1 (Proks P et al.): V127D
  • The following mutations did not produce functional channels: V127K , V127S , V127A , V127D , E126Q , E126D , F133Y , and the double mutants F133Y + M137C , F133Y + G135F , and V127T + W83F

  • We attempted to explore the effect of mutating V127 to a range of other amino acids including both charged (V127K , V127D) and uncharged (V127S , V127A) residues , but none of these mutations expressed functional channels

Reference #1 (Proks P et al.): V127K
  • The following mutations did not produce functional channels: V127K , V127S , V127A , V127D , E126Q , E126D , F133Y , and the double mutants F133Y + M137C , F133Y + G135F , and V127T + W83F

  • We attempted to explore the effect of mutating V127 to a range of other amino acids including both charged (V127K , V127D) and uncharged (V127S , V127A) residues , but none of these mutations expressed functional channels

Reference #1 (Proks P et al.): V127S
  • The following mutations did not produce functional channels: V127K , V127S , V127A , V127D , E126Q , E126D , F133Y , and the double mutants F133Y + M137C , F133Y + G135F , and V127T + W83F

  • We attempted to explore the effect of mutating V127 to a range of other amino acids including both charged (V127K , V127D) and uncharged (V127S , V127A) residues , but none of these mutations expressed functional channels

Reference #1 (Proks P et al.): V127T
  • Mutations within the pore loop of Kir6.2 (V127T , G135F , and M137C) dramatically affected the mean open time ({tau} o) and the short closed time ({tau} C1) within a burst , and the number of openings per burst , but did not alter the burst duration , the interburst closed time , or the channel open probability

  • Thus , the V127T and M137C mutations produced longer {tau} o , shorter {tau} C1 , and fewer openings per burst , whereas the G135F mutation had the opposite effect

  • All three mutations also reduced the single-channel conductance: from 70 pS for the wild-type channel to 62 pS (G135F) , 50 pS (M137C) , and 38 pS (V127T)

  • The following mutations did not produce functional channels: V127K , V127S , V127A , V127D , E126Q , E126D , F133Y , and the double mutants F133Y + M137C , F133Y + G135F , and V127T + W83F

  • Therefore , we examined the effect of mutating the four different residues , one at a time , to those found in Kir2.1 (i.e. , V127T , F133Y , G135F , and M137C)

  • (B) Mean current-voltage relations measured for Kir6.2 / SUR1 (O , n = 3) , Kir6.2-V127T / SUR1 ({blacksquare} , n = 3) , Kir6.2-G135F / SUR1 (• , n = 3) , and Kir6.2-M137C / SUR1 ({square} , n = 3) channels in symmetrical 140-mM K +

  • The lines are fitted to either one exponential (WT , G135F) or the sum of two exponentials (V127T and M137C) with the time constants indicated

  • (A) Single-channel currents recorded at -60 mV from an inside-out patch excised from oocytes expressing SUR1 and either Kir6.2 , Kir6.2-V127T , or Kir6.2-V127T + F133Y

  • (B) Mean current-voltage relations measured for Kir6.2 / SUR1 ({circ} , n = 3) , Kir6.2-V127T / SUR1 ({blacksquare} , n = 3) , or Kir6.2-V127T+F133Y / SUR1 (• , n = 3)

  • The ability of the channel to discriminate against Na + ions was unaffected , however: the relative permeability to intracellular Na + , P Na / P K , was 0.27 ± 0.03 (n = 5) and 0.28 ± 0.02 (n = 5) for the wild-type and V127T mutant channels , respectively

  • In both the wild-type channel and the G135F mutant , the open time histogram at -60 mV was best fit with a single exponential , whereas for both the V127T and M137C mutants , it was best fit by the sum of two exponentials (Fig 4 A ; see Fig 6 )

  • First , the V127T and M137C mutations may increase the number of open states

  • If the data for the pore mutants are fit with only a single exponential , for comparative purposes , the mean open time at -60 mV increased from 2.25 ± 0.15 ms (n = 5) for the wild-type channel , to as much as 6.49 ± 0.93 ms (n = 5) in the case of the V127T mutant

  • These are the measured values of {tau} o ; the values corrected for missed events are given in Table 1 , as are the results of fitting the V127T and M137C pore mutants with two open times

  • All three mutations significantly altered the short closed time ({tau} C1) , with V127T and M137C increasing , and G135F decreasing , its duration (Fig 4 B , 6)

  • Thus , the V127T and M137C mutations produced longer {tau} O and fewer openings per burst ; and , conversely , the G135F mutation reduced {tau} O and increased the number of openings per burst (see Fig 6 )

  • Double Mutants Although mutation of F133 did not result in functional channels , we were able to record currents when the F133V mutation was combined with the V127T mutation

  • Fig 5 compares single-channel currents and current-voltage relations for the double mutant V127T + F133Y with those of the V127T mutant alone

  • The double mutant showed a further reduction in conductance , being 30.6 ± 1.8 pS (n = 3) as compared with 38 pS for V127T and 70 pS for the wild-type channel

  • In particular , there was a further increase in the mean open time for V127T + F133Y mutant channels ({tau}O = 7.45 ± 1.29 ms , n = 4)

  • However , unlike the V127T mutant , {tau}C1 was not significantly different from that of the wild-type channel , suggesting that the F133Y mutation can compensate for the effect of the V127T mutation on the short closed time

  • Effects of P-loop Mutations on the Single-channel Conductance One explanation for the reduced single-channel conductance of the V127T , M137C , and W83F mutants is that the channel kinetics are too fast to be resolved , resulting in a time-averaged conductance of apparently smaller amplitude

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