NucleaRDB: Extraction of mutation data from the literature

2005, NucleaRDB.

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 NR1I3_MOUSE at position 352 were found are listed after the table.

Point mutations at position L352 in NR1I3_MOUSE

Protein	NR1I3_MOUSE (O35627) Gene: Nr1i3,Ca (other point mutations)	Swiss-Prot Cross-reference table Family page
Protein isoforms	2
Position	L352
General numbering (NucleaRDB)	1247
Domain	LBD HELIX 12
Family alignments	1I3 Constitutive Androstane alpha (CAR1) 1I Vitamin D3-like (VDR,PXR,CAR) 1 Thyroid hormone like (TR,RAR,ROR,PPAR,VDR
Other point mutations at the same position	Position 352 in 1I3 Constitutive Androstane alpha (CAR1) family Position 412 in 1I Vitamin D3-like (VDR,PXR,CAR) family Position 400 in 1 Thyroid hormone like (TR,RAR,ROR,PPAR,VDR family
Reference #1	Ueda A, Kakizaki S, Negishi M, Sueyoshi T Mol Pharmacol 2002 Jun;61(6):1284-8.	Medline
Text source	HTML and PDF full texts
Point mutation	L352A (True positive)
Cited point mutation	Leu352Ala
Reference #2	Dussault I, Lin M, Hollister K, Fan M, Termini J, Sherman MA, Forman BM Mol Cell Biol 2002 Aug;22(15):5270-80.	Medline
Text source	HTML and PDF full texts
Point mutation	L352A (True positive)
Reference #3	Andersin T, Vaisanen S, Carlberg C Mol Endocrinol 2003 Feb;17(2):234-46.	Medline
Text source	HTML full text
Point mutation	L352A (True positive)

Relevant sentences

Reference #2 (Dussault I et al.): L352A

CMX-CAR L352A and CAR E355A were constructed by replacing the BspEI / NheI fragment of CAR with synthetic oligonucleotides corresponding to amino acids 329 to 358 of CAR , encoding an alanine at either position 352 or 355 of the H12 / AF2 domain
To address this question , we mutated conserved amino acid residues in H12 / AF2 (L352A and E355A) and H3 (K187A) that contribute to the hydrophobic coregulator cleft on the surface of ligand-bound nuclear receptors (8 , 11 , 37 , 43 )
In contrast , mutations in either the H12 / AF2 domain (L352A and E355A) or H3 (K187A) completely inhibited constitutive activity , and TCPOBOP failed to restore activity to wild-type levels (Fig. 1A )
Single point mutations in H12 / AF2 (L352A or E355A) or H3 (K187A) specifically resulted in the complete loss of both constitutive and ligand-induced SRC-1 recruitment (Fig. 1B , lanes 4 to 9)
Moreover , the ability to selectively abolish constitutive activity in this mutant but not others (K205 , L352A , and E355A) (Fig. 1A and B ; Fig. 5A and B ) implies that constitutive and agonist-inducible activity have both distinct and overlapping determinants
In contrast , mutations in either the H12 / AF2 domain (L352A and E355A) or H3 (K187A) completely inhibited constitutive ac
FIG

Reference #3 (Andersin T et al.): L352A

The panel of ligand inducibility on the DR4-type RE (Fig. 3A(image) , top) indicated that only L352A and the AF-2 deletion lost their responsiveness to TCPOBOP
The inverse agonistic effect of androstanol was completely lost with L352A , L353A , I356A , C357A , and the AF-2 deletion
Interestingly , with L352A , L353A , I356A , and the AF-2 deletion androstanol became slightly agonistic
The point mutants L352A , L353A , E355A , I356A , and C357A and the AF-2 deletion reduced the basal activity by 90% or more , S358A by 75% , and G354A by only 10%
A minor difference was found also concerning a responsiveness of L352A to TCPOBOP , which was found to be statistically significant on the PBREM but not to the DR4-type RE
Finally , L352A , L353A , I356A , and the AF-2 deletion showed no interaction with TIF2 irrespective of ligand presence
This indicates that the supershift assay may not be sensitive enough to detect the ligand modulation of the low basal activity of the mutants L352A , L353A , and I356A
This reduction was not as drastic as observed with the mutants L352A , L353A , I356A , and C357A and the AF-2 deletion (Fig. 3(image) )
For the second hypothesis C357 was mutated into serine and tyrosine , Y336 was mutated into alanine , cysteine , and phenylalanine , and the point- mutants Y336A / C357A , Y336C / C357Y , and L352A / C357A were created
All three double-point mutants , Y336A / C357A , Y336C / C357Y , and L352A / C357A , showed nearly abolished response to ligand , which was expected because of the profile of the individual mutants Y336C , C357Y , and L352
Interestingly , C357A / Y336A and L352A / C357A reduced the basal activity of CAR by 80-90% , whereas Y336C / C357Y did not influence it significantly

Reference #1 (Ueda A et al.): Leu352Ala

mCAR lost its constitutive activity after an AF2 mutation (Leu352Ala or Glu355Ala) or an AF2 deletion in a cell-based transfection assay (Choi et al. , 1997(image) )
mCAR lost its constitutive activity after an AF2 mutation (Leu352Ala or Glu355Ala) or an AF2 deletion in a cell-based transfection assay (Choi et al. , 1997)

F.Horn (nucleardbcmbi.kun.nl), 21-Apr-2005