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 IRK2_HUMAN at position 312 were found are listed after the table.

Point mutations at position R312 in IRK2_HUMAN

ProteinIRK2_HUMAN (P63252)    Gene: KCNJ2,HIRK    (other point mutations)Swiss-Prot
Cross-reference table
Family page
PositionR312
General numbering (KChannelDB) -
DomainC-term
Family alignments Inward rectifiers (Kir)
Potassium channels 2 TMs
Other point mutations at the same position Position 294 in Inward rectifiers (Kir) family
Position 294 in Potassium channels 2 TMs family
Reference #1Lopes CM, Zhang H, Rohacs T, Jin T, Yang J, Logothetis DE
Neuron 2002 Jun 13;34(6):933-44.		Medline
Text sourceHTML full text
Point mutationR312C (Not yet checked)
Point mutationR312K (Not yet checked)
Point mutationR312Q (Not yet checked)
Reference #2Donaldson MR, Jensen JL, Tristani-Firouzi M, Tawil R, Bendahhou S, Suarez WA, Cobo AM, Poza JJ, Behr E, Wagstaff J, Szepetowski P, Pereira S, Mozaffar T, Escolar DM, Fu YH, Ptacek LJ
Neurology 2003 Jun 10;60(11):1811-6.		Medline
Text sourceHTML full text
Point mutationR312C (Not yet checked)
Reference #3Bendahhou S, Donaldson MR, Plaster NM, Tristani-Firouzi M, Fu YH, Ptacek LJ
J Biol Chem 2003 Dec 19;278(51):51779-85. Epub 2003 Oct 1.		Medline
Text sourceHTML full text
Point mutationR312C (Not yet checked)

Relevant sentences

Reference #1 (Lopes CM et al.): R312C
  • T50 for poly-Lys inhibition was 25 ± 5 s (R67K , n = 4) and 53 ± 11 s (R312K , n = 5) when compared to 4.7 ± 0.9 s (R67C , n = 4) and 20 ± 3 s (R312C , n = 11) for neutral amino acids mutations and 209 ± 49 s for wild-type channels

  • A similar strengthening of channel-PIP2 interaction was observed for the Kir2.1(R218C / R312C) mutants when MTSEA was applied (see Figure 3C )

Reference #2 (Donaldson MR et al.): R312C
  • These included six novel mutations (D71N , T75R , G146D , R189I , G300D , and R312C) as well as previously reported mutations R67W and R218W

  • Each mutation changed an amino acid of the Kir2.1 protein as follows: R67W (c427t) , D71N (g439a) , T75R (c452g) , G146D (g665a) , R189I (g794t) , R218W (c880t) , G300D (g1127a) , and R312C (c1162t)

  • R67W , R189I , R218W , G300D , and R312C alter residues demonstrated to bind phosphatidylinositol 4 , 5-bisphosphate (PIP2)

  • Six probands had mutations (R67W , R189I , R218W , G300D , and R312C) of residues that were shown , when mutated , to decrease affinity of Kir2.1 for PIP2 and to inhibit channel function.17 , 19 , 20 PIP2 is a membrane-bound second messenger shown to activate Kir2.1 and other inward-rectifying channels by facilitating the open channel state.20-22 Basic residues involved in binding likely have electrostatic relationships with the anionic head groups of the PIP2 molecule.23 Sites without charge , such as G300 , are thought to facilitate PIP2 binding through allosteric effects

  • Mutations R67W , D71N , T75R , G146D , R189I , R218W , G300V , and R312C are shown in bold italic type

Reference #3 (Bendahhou S et al.): R312C
  • All ATS missense mutations (filled circles , R67W , D71V / N , T75R , S136F , G144S , G146D , P186L , R189I , N216H , R218Q / W , G300V / D , V302M , E303K , R312C) and deletions (triangles , {Delta}95-98 and {Delta}314-315) are represented on the channel

  • Three of these mutations are located in the NH2 terminus (R67W , D71V / N , and T75R) , one deletion occurs in the first transmembrane segment M1 ({Delta}95-98) , three mutations occur in the pore region (S136F , G144S and G146D) , and the remaining mutations reside in the COOH terminus of the Kir 2.1 channel (P186L , R189I , N216H , R218Q / W , G300V / D , V302M , E303K , R312C , and {Delta}314-315)

Reference #1 (Lopes CM et al.): R312K
  • In order to assess whether this was due to either the inaccessibility of these residues to MTSEA or to the requirement of a particular residue at that position , we mutated these sites to other positive charged residues (R67K , R312K , H271K , H271R)

  • In the cases of R67K and R312K , the alternative positively charged residues increased PIP2-channel interaction , but the interaction was weaker than for the wild-type channel

  • T50 for poly-Lys inhibition was 25 ± 5 s (R67K , n = 4) and 53 ± 11 s (R312K , n = 5) when compared to 4.7 ± 0.9 s (R67C , n = 4) and 20 ± 3 s (R312C , n = 11) for neutral amino acids mutations and 209 ± 49 s for wild-type channels

  • Yet , all mutations that destroy the phosphorylation motif (R217 / R218K / Q and R311 / R312K / Q) weakened chanel-PIP2 interactions , suggesting complex interactions at these sites

Reference #1 (Lopes CM et al.): R312Q
  • We found that the mutant channels H53Q , K182Q , K185Q , R218Q , K219Q , R228Q , and R312Q have significantly faster PIP2Ab inhibition than the wild-type , suggesting that the interaction with PIP2 is weakened by each mutation

  • View larger version: [In this window] [In new window] We could not measure any currents from either the H271Q or the R312Q equivalent Kir1.1 mutants

  • Kir1.1 mutations in R312 (R312Q / W) are one of the genetic defects associated with the antenatal variant of Bartter's syndrome , a disease characterized by polyhydramnios , premature delivery , hypokalemic alkalosis , and hypercalciuria (Schulte et al. , 1999(image) )

  • We showed that generally , and in particular for R218Q and R312Q , neutralizing mutations that affect channel-PIP2 interactions affect whole-cell current and strength of interaction in a similar way

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