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 VDR_HUMAN at position 284 were found are listed after the table.

Point mutations at position M284 in VDR_HUMAN

ProteinVDR_HUMAN (P11473)    Gene: VDR,NR1I    (other point mutations)Swiss-Prot
Cross-reference table
Family page
PositionM284
General numbering (NucleaRDB) -
DomainLoop 5-6
Family alignments 1I1 Vitamin D3 (VDR)
1I Vitamin D3-like (VDR,PXR,CAR)
1 Thyroid hormone like (TR,RAR,ROR,PPAR,VDR
Other point mutations at the same position Position 284 in 1I1 Vitamin D3 (VDR) family
Position 279 in 1I Vitamin D3-like (VDR,PXR,CAR) family
Position 272 in 1 Thyroid hormone like (TR,RAR,ROR,PPAR,VDR family
Reference #1Mohr SC, Swamy N, Xu W, Ray R
Steroids 2001 Mar-May;66(3-5):189-201.		Medline
Text sourceHTML and PDF full texts
Point mutationM284A (True positive)
Cited point mutationMet284Ala,Met284
Point mutationM284S (True positive)

Relevant sentences

Reference #1 (Mohr SC et al.): M284A
  • Table 1 Natural* and designed mutations in VDR-LBD and their effects Change Effect (Reference) C190W* Familial VDRR-II [57] S225A Kd for ligand unchanged [44] H229A Kd for ligand increased by 27X [44] D232A Kd for ligand increased by 30X [44] V234A Kd for ligand almost unchanged [44] S235A Kd for ligand almost unchanged [44] Y236A Kd for ligand increased by 3.5X [44] S237A Kd for ligand increased by 27X [44] K240A Kd for ligand increased by 27X [44] I242A Kd for ligand increased by 27X [44] F244G Impaired transactivation [54] K246A Kd for ligand increased by 2X [44] L254G Impaired transactivation ; no RXR heterodimer formed [54] R274L* Ligand binding severely decreased ; VDRR-II [43] S275A Kd for ligand increased by 5.3X [44] M284A Ligand binding significantly reduced (Ray et al. , unpublished) M284S Ligand binding significantly reduced (Ray et al. , unpublished) W286A No ligand binding (Ray et al. , unpublished) W286F No ligand binding (Ray et al. , unpublished) C288G Ligand binding 'attenuated severely' at 37°C ; decreased 3X at 4°C , [25] Y295STOP* No ligand binding [55] D299A No ligand-binding (Ray et al. , unpublished) K302A No change in ligand-binding (Ray et al. , unpublished) H305Q* Ligand binding decreased 5X [55] I314S* Reduced transactivation ; high ligand concentration restores it ; RXR interaction diminished [53] C337G Ligand binding moderately decreased at 37°C [25] C369G Ligand binding only mildly affected at 37°C [25] K386Q Very slight decrease in ligand binding [52] L387STOP No ligand binding [52] R391C* Transactivation decreased together with RXR binding [53] L404STOP Kd for ligand increased by 10X [52] L417A No change in ligand binding ; transcriptional activation eliminated [56] L417S Ligand binding normal ; transactivation abolished (also coactivator binding) [52] V418S Significant reduction in ligand-binding (Ray et al. , unpublished) E420A No change in ligand binding ; transcriptional activation eliminated [56] E420Q Ligand binding normal ; transactivation abolished (also coactivator binding) [52] E425Q No effect on ligand binding or transactivation [52] S.C

Reference #1 (Mohr SC et al.): M284S
  • Table 1 Natural* and designed mutations in VDR-LBD and their effects Change Effect (Reference) C190W* Familial VDRR-II [57] S225A Kd for ligand unchanged [44] H229A Kd for ligand increased by 27X [44] D232A Kd for ligand increased by 30X [44] V234A Kd for ligand almost unchanged [44] S235A Kd for ligand almost unchanged [44] Y236A Kd for ligand increased by 3.5X [44] S237A Kd for ligand increased by 27X [44] K240A Kd for ligand increased by 27X [44] I242A Kd for ligand increased by 27X [44] F244G Impaired transactivation [54] K246A Kd for ligand increased by 2X [44] L254G Impaired transactivation ; no RXR heterodimer formed [54] R274L* Ligand binding severely decreased ; VDRR-II [43] S275A Kd for ligand increased by 5.3X [44] M284A Ligand binding significantly reduced (Ray et al. , unpublished) M284S Ligand binding significantly reduced (Ray et al. , unpublished) W286A No ligand binding (Ray et al. , unpublished) W286F No ligand binding (Ray et al. , unpublished) C288G Ligand binding 'attenuated severely' at 37°C ; decreased 3X at 4°C , [25] Y295STOP* No ligand binding [55] D299A No ligand-binding (Ray et al. , unpublished) K302A No change in ligand-binding (Ray et al. , unpublished) H305Q* Ligand binding decreased 5X [55] I314S* Reduced transactivation ; high ligand concentration restores it ; RXR interaction diminished [53] C337G Ligand binding moderately decreased at 37°C [25] C369G Ligand binding only mildly affected at 37°C [25] K386Q Very slight decrease in ligand binding [52] L387STOP No ligand binding [52] R391C* Transactivation decreased together with RXR binding [53] L404STOP Kd for ligand increased by 10X [52] L417A No change in ligand binding ; transcriptional activation eliminated [56] L417S Ligand binding normal ; transactivation abolished (also coactivator binding) [52] V418S Significant reduction in ligand-binding (Ray et al. , unpublished) E420A No change in ligand binding ; transcriptional activation eliminated [56] E420Q Ligand binding normal ; transactivation abolished (also coactivator binding) [52] E425Q No effect on ligand binding or transactivation [52] S.C

Reference #1 (Mohr SC et al.): Met284
  • Combination of techniques: affinity labeling , point mutation and hormone-binding analysis to identify a contiguous area in VDR-LBD comprising Met284 , Trp286 and Cys288 4.1

  • Role of Met284 in 1small alpha , Greek , 25(OH)2D3-binding 4.3

  • Role of Met284 in 1small alpha , Greek , 25(OH)2D3-binding Met residues , containing an apolar mercaptomethyl side chain , are usually involved in nonbonding hydrophobic interactions with the non-polar area of a ligand

  • In the case of VDR , presence of Met284 in close proximity with Trp286 and Cys288 propelled us to investigate its potential role in hormone binding

  • Site-directed mutagenesis of Met284 to Ala or Ser ; and subsequent binding analysis with 3H-1 , 25(OH)2D3 revealed a 78% and 70% loss of 3H-1 , 25(OH)2D3-binding respectively by these mutants compared to the wild type protein

  • These results strongly suggested that Met284 , in addition to Trp286 and Cys288 , participates in hormone-binding in a significant way , possibly providing non-bonding , hydrophobic interaction

  • The data also indicates that the A-ring fits tightly inside the general area consisting of Met284 , Trp286 and Cys288

  • Met284 (shown in blue) functions to provide hydrophobic contacts that buttress Trp286 / ligand interaction

  • In addition to Met284 , Trp286 and Cys288 , our model identifies other residues contacting the ligand , i.e. , Arg274 and Ser275 (1-OH contact) , Ser237 (3-OH contact) , Asp299 (25-OH contact) , Lys302 and Val418 (hydrophobic interaction with the side chain)

  • Role of Met284 in 1 , 25(OH)2D3-binding Met residues , containing an apolar mercaptomethyl side chain , are usually involved in nonbonding hydrophobic interactions with the non-polar area of a ligand

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