TABLE 4

Mutant lesions in daf-2 alleles

AlleleClassaMutation location location (domain)DNA changeAmino acid changeReferencePredicted outcome of mutationb
e9792DL1TGC-TACC146YThis studya
m631NCL1CGA-TGAR281STOPThis studyb
m411BCys-RichGGA-GAAG383EYu et al. (2002)c
mg43cNCCys-RichTGT-TATC401YKimura et al. (1998)a
m5792BCys-RichCGT-TGTR437CScott et al. (2002)d, h, i
sa1872CCys-RichTGT-AGTC469SKimura et al. (1998)a
mg43cNCCys-RichCCC-CTCP470LKimura et al. (1998)d
m596d1EL2GGC-AGCG547SScott et al. (2002)e, h
e13681AL2TCA-TTAS573LKimura et al. (1998)e
e1365/sa193e,f1AL2TGC-TACA580TKimura et al. (1998); this studyf
sa2291AFnIII1GAT-AATD648NKimura et al. (1998)g
mu1501AFnIII1GGC-GACG682DThis studyf
e13711AFnIII2αGGA-GAAG803EThis studyd
m2121DFnIII2IDTGT-TATC883YThis studya, h
m577f1CFnIII2βTGC-TACC1045YThis studya, h
m646NCPrekinaseCAA-TAAQ1223STOPThis study; K. Kimura and G. Ruvkun (personal communication)b
sa2192CKinaseGAT-AATD1374NKimura et al. (1998)d
sa2232EKinaseCGA-CAAR1430QThis studyd, h, i
e13912DKinaseCCC-CTCP1434LKimura et al. (1998)d, i
m65NCKinaseTGG-TAGW1449STOPThis studyb
e13702CKinaseCCA-TCAP1465SKimura et al. (1998)d
m633NCKinaseCGT-CATR1510HK. Kimura and G. Ruvkun (personal communication)d
tm1236NCKinaseDeletion (see text)This study
  • a Classes as defined in Gems et al. (1998). NC, nonconditional Daf-c.

  • b a: Residue affected is a disulfide-bonded cysteine. Substitution is likely to disrupt fold stability. b: Nonsense mutation implying truncation of the polypeptide chain. Mutant protein is expected not to be functional. c: Residue affected is in a part of the sequence present only in nematodes. We were unable to predict the effect of substitution on the basis of homology to mammalian receptors. d: Residue affected is highly conserved in all phyla. Substitution is likely to affect stability of the structure or aspects of the receptor mechanism. e: Residue affected is solvent inaccessible and not highly conserved across phyla. The conservative nature of the substitution means that it is not predicted to have major detrimental effects. f: Residue affected is solvent inaccessible and not highly conserved across phyla. The nonconservative nature of the substitution suggests that it is likely to disrupt fold stability. g: Residue affected is solvent accessible and not highly conserved across phyla. Currently unable to predict effect of substitution. h: A nonidentical, naturally occurring, or engineered mutation in the equivalent hInsR position has been reported. i: An identical, naturally occurring, or engineered mutation in the equivalent hInsR position has been reported. For further details, see http://www.biochem.ucl.ac.uk/rilm.

  • c The mg43 allele has two lesions, both affecting the CR domain.

  • d Previously defined as class 2A (Gems et al. 1998). Given that this allele is suppressed by daf-12(m20), we have redesignated it as a class 1 allele.

  • e The e1365 and sa193 alleles were isolated in different labs but contain identical sequence changes.

  • f Sequence analysis revealed that the allele identified as e1365 in Gems et al. (1998) was in fact daf-2(m577). The real e1365 (Kimura et al. 1997) is a class 1A allele.