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 ESR1_HUMAN at position 539 were found are listed after the table.
| Protein | ESR1_HUMAN (P03372) Gene: ESR1,ESR, NR3A (other point mutations) | Swiss-Prot
Cross-reference table
Family page |
| Protein isoforms | 2 | |
| Position | L539 | |
| General numbering (NucleaRDB) | 1247 |
| Domain | LBD HELIX 12 |
| Family alignments |
3A1 ER alpha
3A Estrogen (ER)
3 Estrogen like (ER,ERR,GR,MR,PR,AR)
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| Other point mutations at the same position |
Position 539 in 3A1 ER alpha family
Position 539 in 3A Estrogen (ER) family
Position 754 in 3 Estrogen like (ER,ERR,GR,MR,PR,AR) family
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| Reference #1 | Pearce ST, Liu H, Jordan VC
J Biol Chem 2003 Feb 28;278(9):7630-8. | Medline |
| Text source | HTML and PDF full texts |
| Point mutation | L539A (True positive) | |
| Reference #2 | Bai Y, Giguere V
Mol Endocrinol 2003 Apr;17(4):589-99. | Medline |
| Text source | HTML full text |
| Point mutation | L539A (Not yet checked) | |
| Reference #3 | Deblois G, Giguere V
J Steroid Biochem Mol Biol 2003 Jun;85(2-5):123-31. | Medline |
| Text source | HTML full text |
| Point mutation | L539A (Not yet checked) | |
Reference #1 (Pearce ST et al.): L539A
- The protein levels of the L539A / L540A double mutant remained constant upon E2 treatment , whereas 4-OHT induced degradation of the ER (38 )
- The mouse ER mutants L543A / L544A (L539A / L540A in human) and M547A / L548A (M543A / L544A in human) (26 ) as well as the human ER mutants L540Q , E542A / D545A , and L540Q / E542A / D545A (27 ) are not degraded by ICI 182 , 780
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Reference #2 (Bai Y et al.): L539A
- The transcriptionally inactive mutant ER alpha L539A showed no interaction with all three SRC RIDs
- For both ER alpha and ERß , coactivators are recruited to nuclei upon E2 treatment , whereas the transcription-defective ER alpha L539A mutant fails to promote coactivator movement to the nuclei and physical binding to ER alpha
- The 10 pairs are CFP-ER alpha , YFP-ER alpha without or with 10-8 M E2 treatment (lanes 1 and 2) , CFP-ER alpha , YFP-ERß , control or E2 (lanes 3 and 4) , CFP-ERß , YFP-ER alpha control or E2 (lanes 5 and 6) , CFP-ERß , YFP-ERß control or E2 (lanes 7 and 8) and CFP-ER alpha L539A , and YFP-ER alpha L539A control or E2 (lanes 9 and 10)
- As shown in Fig. 2B(image) (lanes 1-10) , the ER dimers are ER alpha homodimers in the absence or presence of 10-8 M E2 (lanes 1 and 2) , ER alpha / ß heterodimers (CFP-ER alpha and YFP-ERß , lanes 3 and 4 ; CFP-ER alpha and YFP-ER alpha , lanes 5 and 6) , ERß homodimers (lanes 7 and 8) , and ER alpha L539A mutant homodimers (lanes 9 and 10)
- ER alpha L539A is an ER alpha transcription-deficient mutant that is still capable of binding ligand but fails to activate gene expression (7 )
- As shown in Fig. 3C(image) , ER alpha L539A retains its ability to form homodimers independent of E2 and transcription activity
- Furthermore , the transcriptionally inactive ER alpha L539A mutant had no effect on the localization of the SRC-1 RID (Fig. 4A(image) )
- Furthermore , the transcription-defective ER alpha L539A mutant failed to recruit the SRC-1 RID in the presence of E2 (Fig. 4B(image) )
- In addition , the transcriptionally inactive ER alpha L539A mutant also failed to interact with the SRC-2 RID
- FRET Analysis of ER alpha Interactions with Coactivator RIDs A , An example of colocalization of donor CFP-ER alpha and acceptor YFP-SRC-1 images under various conditions , including in the presence of 10-8 M E2 and 10-6 M OHT on wild-type ER alpha and on the transcription-defective mutant ER alpha L539A
- Similarly , the transcriptionally inactive ER alpha L539A mutant still formed homodimers but failed to bind to any of the three SRC RIDs
- CFP-ER alpha L539A and YFP-ER alpha L539A were constructed in a similar manner with the exception that CMXhER alpha L539A was used as template
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Reference #3 (Deblois G et al.): L539A
- The ER alpha mutants used included CDEF alpha , which lacks the 'AB' portion (AF-1) of ER alpha , ABC alpha , which lacks the LBD (AF-2) of ER alpha and ER alpha L539A , a mutant in which leucine 539 was changed to an alanine
- The L539A mutation completely abolishes the AF-2 activity of the receptor by preventing helix 12 from interacting with coactivators [19 ]
- Cotransfection of SRA in the presence of ligand also increased the transcriptional activity of ERsmall alpha , GreekL539A mutant by two-fold , suggesting that SRA might also possess the ability to coactivate ER alpha through its AF-1 domain without requirement for the AF-2 domain (Fig. 3A )
- However , this AF-1 mediated effect of SRA on ABC alpha and ERsmall alpha , GreekL539A seems to require the presence of E2 , despite the fact that these mutants did not show any ligand-induced activity
- To determine whether the SRA-mediated coactivation observed on ABCsmall alpha , Greek and ER alpha L539A in the presence of ligand resulted solely from overexpression of SRA , or if this effect could also be observed upon overexpression of SRC-1 , COS-1 cells were transiently cotransfected with SRC-1 and ER alpha or the mutant receptors
- Overexpression of SRC-1 did not induce any ligand-dependent coactivation of ABC alpha or ER alpha L539A (Fig. 3C ) , suggesting that the SRA effect observed for these mutants in the presence of E2 is specific for the RNA coactivator
- The effect of SRA on ABC alpha and ER alpha L539A mutants was unexpected since SRA could mediate AF-1-induced coactivation of the mutant receptors only in the presence of E2 despite the fact that these mutants do not show estrogenic responses
- To further verify that the effect of SRA observed on ABCsmall alpha , Greek and ER alpha L539A in the presence of ligand was caused by MAPK activation , we used a MAPK inhibitor , PD98059 , and asked whether it abolishes this ligand-dependent effect of SRA on the two mutants
- The finding that SRA coactivation of ER alpha AF-1 was generated only upon E2 treatment was unexpected considering the fact that the two mutants used to investigate this effect (ABCsmall alpha , Greek and ER alpha L539A) did not possess the ability to generate a ligand response
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2005, NucleaRDB.
cmbi.kun.nl), 21-Apr-2005