NucleaRDB: 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 NR1I3_MOUSE at position 336 were found are listed after the table.

Point mutations at position Y336 in NR1I3_MOUSE

ProteinNR1I3_MOUSE (O35627)    Gene: Nr1i3,Ca    (other point mutations)Swiss-Prot
Cross-reference table
Family page
Protein isoforms2
PositionY336
General numbering (NucleaRDB) 1057
DomainLBD HELIX 10-11
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 336 in 1I3 Constitutive Androstane alpha (CAR1) family
Position 392 in 1I Vitamin D3-like (VDR,PXR,CAR) family
Position 381 in 1 Thyroid hormone like (TR,RAR,ROR,PPAR,VDR family
Reference #1Andersin T, Vaisanen S, Carlberg C
Mol Endocrinol 2003 Feb;17(2):234-46.		Medline
Text sourceHTML full text
Point mutationY336A (True positive)
Cited point mutationY336A,Y336
Point mutationY336C (True positive)
Point mutationY336F (True positive)

Relevant sentences

Reference #1 (Andersin T et al.): Y336
  • We showed that this blockade is not due to an intramolecular disulfide bridge , but is probably caused by an interaction between C357 and Y336

  • Alternatively , the sulfhydryl group of C357 could interact with Y336 , which is homologous to the F422-H397 interaction in VDR (24 ) (see Fig. 7(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

  • Interestingly , in comparison to wild-type CAR , Y336A showed an increased TCPOBOP inducibility and a nearly abolished response to androstanol

  • The reduction in basal activity and increase in agonist response of Y336A was not as drastic as with C357A , but showed the same tendency

  • In contrast , Y336C behaved similar to wild-type CAR , but showed lower ligand responsiveness and slightly reduced basal activity

  • The mutant Y336F lost inducibility by TCPOBOP , kept some responsiveness to androstanol , and did not affect the basal activity

  • This indicates that both the polar hydroxyl group as well as the large volume of Y336 are important for the full ligand responsiveness of CAR , but not very critical for the basal activity of the receptor

  • 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

  • Taken together , the functional profiles of all three double-point mutants suggest that C357 , Y336 , and the CoA interacting amino acid L352 are functionally linked , such as F422 , H397 , and L417 in VDR (24 , 25 , 26 )

  • Model for Stabilization of Helix 12 in CAR Compared with VDR The structural relation of helices 11 and 12 in mouse CAR (left) and human VDR (right) and their link via an interaction between Y336 and C357 (CAR) or H397 and F422 (VDR) is indicated by a dashed line

  • C357 appears to be very specific in its interaction with Y336 and is not involved in the formation of disulfide bridges

  • A modeling of the structure of helices 11 and 12 on the basis of the VDR structure (Fig. 7(image) ) predicts that C357 interacts with Y336

  • In fact , mutagenesis of Y336 alone and in combination with C357 suggests that both amino acids are functionally linked , such as F422 and H397 in VDR

  • The specificity of the interaction between these two amino acids is supported by the observation that the double mutant Y336C / C357Y showed no effect on the basal activity of CAR , i.e. that these two residues stabilize helix 12 independent of their orientation

  • In contrast to VDR , in CAR the stabilization of helix 12 by the C357-Y336 interaction occurs even in the absence of ligand

  • A mutation of C357 or Y336 allows a free movement of helix 12 in the absence of ligand and provides CAR with a functional profile comparable to classical endocrine NRs , i.e. low basal activity and high ligand inducibility

  • The C357-Y336 interaction seems to be reinforced and optimized by the agonist TCPOBOP , whereas the Y336C / C357Y double mutant of CAR has lost its responsiveness to ligand

  • The principal role of C357 seems to be the stabilization of helix 12 via an interaction with Y336 , but it is possible that Y336 directly contacts the ligand in the way that H397 does in VDR

  • Within the adopted orphan receptor , movement of helix 12 seems to be reduced via an interaction between C357 and Y336 , which is only optimized by contact with a ligand

  • The amino acid sequences of VDR and CAR were aligned and the amino acid residues V418 , L419 , V421 , F422 , G423 , and H397 of VDR were mutated in silico to the respective amino acid residues of mouse CAR (L353 , G354 , I356 , C357 , S358 , and Y336 , respectively) by using the mutation command of Swiss PDB Viewer (v.3.7b2)

  • The torsion angles of the side chain of Y336 were adjusted manually

Reference #1 (Andersin T et al.): Y336A
  • 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

  • Interestingly , in comparison to wild-type CAR , Y336A showed an increased TCPOBOP inducibility and a nearly abolished response to androstanol

  • The reduction in basal activity and increase in agonist response of Y336A was not as drastic as with C357A , but showed the same tendency

  • 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 (Andersin T et al.): Y336C
  • 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

  • In contrast , Y336C behaved similar to wild-type CAR , but showed lower ligand responsiveness and slightly reduced basal activity

  • 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

  • The specificity of the interaction between these two amino acids is supported by the observation that the double mutant Y336C / C357Y showed no effect on the basal activity of CAR , i.e. that these two residues stabilize helix 12 independent of their orientation

  • The C357-Y336 interaction seems to be reinforced and optimized by the agonist TCPOBOP , whereas the Y336C / C357Y double mutant of CAR has lost its responsiveness to ligand

Reference #1 (Andersin T et al.): Y336F
  • The mutant Y336F lost inducibility by TCPOBOP , kept some responsiveness to androstanol , and did not affect the basal activity

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