DP00062: Retinoic acid receptor RXR-alphaFASTA viewXML view

General information
DisProt:DP00062
Name:Retinoic acid receptor RXR-alpha
Synonym(s):RXRA_HUMAN
Retinoid X receptor alpha
Nuclear receptor subfamily 2 group B member 1
First appeared in release:Release 1.0 (08/01/2003)
UniProt:P19793
UniGene:Hs.590886
SwissProt: RXRA_HUMAN
TrEMBL:  
NCBI (GI): 133701
Source organism:Homo sapiens (Human)
Sequence length:462
Percent disordered:6%
Homologues: 


Native sequence

        10         20         30         40         50         60
         |          |          |          |          |          |
MDTKHFLPLD FSTQVNSSLT SPTGRGSMAA PSLHPSLGPG IGSPGQLHSP ISTLSSPING - 60
MGPPFSVISS PMGPHSMSVP TTPTLGFSTG SPQLSSPMNP VSSSEDIKPP LGLNGVLKVP - 120
AHPSGNMASF TKHICAICGD RSSGKHYGVY SCEGCKGFFK RTVRKDLTYT CRDNKDCLID - 180
KRQRNRCQYC RYQKCLAMGM KREAVQEERQ RGKDRNENEV ESTSSANEDM PVERILEAEL - 240
AVEPKTETYV EANMGLNPSS PNDPVTNICQ AADKQLFTLV EWAKRIPHFS ELPLDDQVIL - 300
LRAGWNELLI ASFSHRSIAV KDGILLATGL HVHRNSAHSA GVGAIFDRVL TELVSKMRDM - 360
QMDKTELGCL RAIVLFNPDS KGLSNPAEVE ALREKVYASL EAYCKHKYPE QPGRFAKLLL - 420
RLPALRSIGL KCLEHLFFFK LIGDTPIDTF LMEMLEAPHQ MT



Functional narrative    

Retinoid X receptor (RXR) is a member of the nuclear hormone receptor superfamily of transcription regulators. RXR plays a central role in the retinoid and non-steroid signaling pathways. RXR consists of three domains: an N-terminal region of unknown structure, a DNA binding domain (DBD) and a ligand-binding region. Binding occurs cooperatively as dimers to hormone response elements composed of two copies of the consensus half-site sequences of direct repeats of AGGTCA. When RXR binds 9-cis-retinoic acid it transactivates as a homodimer. The flexibility in the dimerization region allows different protein-protein interactions and response elements to be recognized. The order-disorder transition of the C-terminal DNA-binding domain extends the backbone to allow optimal interactions with the upstream DBD in the dimer. RXR is highly expressed in the liver and also found in the lung, kidney and heart.

Region 1: 172-176 Region 2: 178-187 Region 4: 181-187 Region 3: 169-189 Region 5: 202-206

Map of ordered and disordered regions







Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.


Region 1
Type:Disordered - Extended
Name:D-BOX
Location:172 - 176
Length:5
Region sequence:

RDNKD

Modification type: Engineered
PDB: 1RXR:1
Structural/functional type:  
Functional classes: Molecular assembly
Functional subclasses: Protein-protein binding
Protein-DNA binding
Detection methods:
  1. Nuclear magnetic resonance (NMR) (300 K; pH: 6.6; KH2PO4 (pH 6.7) 20 mM; KCl 100 mM; ZnCl2 0.3 mM; 2H2O 100 %)

  2. Nuclear magnetic resonance (NMR) (300 K; pH: 6.6; 2H2O 5 %; H2O 95 %; KCl 100 mM; KH2PO4 (pH 6.7) 20 mM; ZnCl2 0.3 mM)
References:
  1. Holmbeck SM, Dyson HJ, Wright PE. "DNA-induced conformational changes are the basis for cooperative dimerization by the DNA binding domain of the retinoid X receptor." J Mol Biol. 1998; 284(3): 533-9. PubMed: 9826495

  2. Holmbeck SM, Foster MP, Casimiro DR, Sem DS, Dyson HJ, Wright PE. "High-resolution solution structure of the retinoid X receptor DNA-binding domain." J Mol Biol. 1998; 281(2): 271-84. PubMed: 9698548
Comments:
 



Region 2
Type:Disordered - Extended
Name:Second Zinc Finger Binding Domain
Location:178 - 187
Length:10
Region sequence:

LIDKRQRNRC

Modification type: Engineered
PDB: 1RXR:1
Structural/functional type: Function arises via a disorder to order transition
Functional classes: Molecular assembly
Functional subclasses: Metal binding
Protein-DNA binding
Detection methods:
  1. Nuclear magnetic resonance (NMR) (300 K; pH: 6.6; 2H2O 100 %; KCl 100 mM; KH2PO4 (pH 6.7) 20 mM; ZnCl2 0.3 mM)

  2. Nuclear magnetic resonance (NMR) (300 K; pH: 6.6; 2H2O 5 %; H2O 95 %; KCl 100 mM; KH2PO4 (pH 6.7) 20 mM; ZnCl2 0.3 mM)
References:
  1. Holmbeck SM, Dyson HJ, Wright PE. "DNA-induced conformational changes are the basis for cooperative dimerization by the DNA binding domain of the retinoid X receptor." J Mol Biol. 1998; 284(3): 533-9. PubMed: 9826495

  2. Holmbeck SM, Foster MP, Casimiro DR, Sem DS, Dyson HJ, Wright PE. "High-resolution solution structure of the retinoid X receptor DNA-binding domain." J Mol Biol. 1998; 281(2): 271-84. PubMed: 9698548
Comments:
 



Region 3
Type:Disordered - Extended
Name: 
Location:169 - 189
Length:21
Region sequence:

YTCRDNKDCLIDKRQRNRCQY

Modification type: Engineered
PDB: IRXR:1
Structural/functional type: Function arises via a disorder to order transition
Functional classes: Molecular assembly
Functional subclasses: Metal binding
Protein-DNA binding
Detection methods:
  1. Nuclear magnetic resonance (NMR) (300 K; pH: 6.6; 2H2O 100 %; KCl 100 mM; KH2PO4 (pH 6.7) 20 mM; ZnCl2 0.3 mM)

  2. Nuclear magnetic resonance (NMR) (300 K; pH: 6.6; 2H2O 5 %; H2O 95 %; KCl 100 mM; KH2PO4 (pH 6.7) 20 mM; ZnCl2 0.3 mM)
References:
  1. Holmbeck SM, Dyson HJ, Wright PE. "DNA-induced conformational changes are the basis for cooperative dimerization by the DNA binding domain of the retinoid X receptor." J Mol Biol. 1998; 284(3): 533-9. PubMed: 9826495

  2. Holmbeck SM, Foster MP, Casimiro DR, Sem DS, Dyson HJ, Wright PE. "High-resolution solution structure of the retinoid X receptor DNA-binding domain." J Mol Biol. 1998; 281(2): 271-84. PubMed: 9698548
Comments:
This region contains the D-box as well as the second zinc binding domain and lies between the first and second helices.




Region 4
Type:Disordered - Extended
Name:Second Zinc binding domain
Location:181 - 187
Length:7
Region sequence:

KRQRNRC

Modification type: Engineered
PDB: 1RXR:1
Structural/functional type: Function arises via a disorder to order transition
Functional classes: Molecular assembly
Functional subclasses: Metal binding
Protein-DNA binding
Detection methods:
  1. Nuclear magnetic resonance (NMR) (300 K; pH: 6.8; )
References:
  1. Holmbeck SM, Dyson HJ, Wright PE. "DNA-induced conformational changes are the basis for cooperative dimerization by the DNA binding domain of the retinoid X receptor." J Mol Biol. 1998; 284(3): 533-9. PubMed: 9826495

  2. Holmbeck SM, Foster MP, Casimiro DR, Sem DS, Dyson HJ, Wright PE. "High-resolution solution structure of the retinoid X receptor DNA-binding domain." J Mol Biol. 1998; 281(2): 271-84. PubMed: 9698548
Comments:
 



Region 5
Type:Disordered - Extended
Name:C-terminal helix
Location:202 - 206
Length:5
Region sequence:

REAVQ

Modification type: Engineered
PDB: 1RXR:1
Structural/functional type: Function arises via an order to disorder transition
Functional classes: Molecular assembly
Functional subclasses: Protein-DNA binding
Substrate/ligand binding
Protein-protein binding
Detection methods:
  1. Nuclear magnetic resonance (NMR) (300 K; pH: 6.6; 2H2O 100 %; KCl 100 mM; KH2PO4 20 mM; ZnCl2 0.3 mM)

  2. Nuclear magnetic resonance (NMR) (300 K; pH: 6.6; 2H2O 5 %; H2O 95 %; KCl 100 mM; KH2PO4 20 mM; ZnCl2 0.3 mM)
References:
  1. Holmbeck SM, Dyson HJ, Wright PE. "DNA-induced conformational changes are the basis for cooperative dimerization by the DNA binding domain of the retinoid X receptor." J Mol Biol. 1998; 284(3): 533-9. PubMed: 9826495

  2. Holmbeck SM, Foster MP, Casimiro DR, Sem DS, Dyson HJ, Wright PE. "High-resolution solution structure of the retinoid X receptor DNA-binding domain." J Mol Biol. 1998; 281(2): 271-84. PubMed: 9698548
Comments:
The C-terminal helix undergoes an order to disorder transition upon binding to DNA. The unwinding of the helix most likely facilitates homodimer formation by maximizing interactions between the two DNA-bound RXR proteins.


References

  1. Mangelsdorf DJ, Ong ES, Dyck JA, Evans RM. "Nuclear receptor that identifies a novel retinoic acid response pathway." Nature. 1990; 345(6272): 224-9. PubMed: 2159111


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