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DrugBank target: P10276

DrugBank target: P10276 (RARA_HUMAN)     

Example structure of target: 1dkf

( There are 6 structures corresponding to this UniProt sequence in the PDB. Click the orange, plus icon above for a list. )

Retinoic acid receptor alpha

Nuclear receptor subfamily 1 group B member 1, RAR-alpha.

Function

Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Regulates expression of target genes in a ligand- dependent manner by recruiting chromatin complexes containing KMT2E/MLL5. Mediates retinoic acid-induced granulopoiesis..

Disease(s)

Note=Chromosomal aberrations involving RARA are commonly found in acute promyelocytic leukemia. Translocation t(11;17)(q32;q21) with ZBTB16/PLZF; translocation t(15;17)(q21;q21) with PML; translocation t(5;17)(q32;q11) with NPM. The PML-RARA oncoprotein requires both the PML ring structure and coiled-coil domain for both interaction with UBE2I, nuclear microspeckle location and sumoylation. In addition, the coiled- coil domain functions in blocking RA-mediated transactivation and cell differentiation.

Schematic diagram of Pfam domains in target sequence plus wiring diagrams of PDB structures of target.

1dkf
1dsz
3a9e
3kmr
   more ...

Key:    PfamA domain

Sequence length: 461 a.a.

Approved drugs targeting this protein

The DrugBank database identifies 6 drugs for this target protein:

 

 
Generic name: DB00799 tazarotene
Formula: C21H21No2S
Structure: There are no structures of this molecule in the PDB.
Generic name: DB04942 tamibarotene
A80
Formula: C22H25No3
Structure: There is one PDB structure containing this molecule but it is not bound to the above target protein.
 
Generic name: DB00210 adapalene
Formula: C28H28O3
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB00982 isotretinoin
Formula: C20H28O2
Structure: There are no structures of this molecule in the PDB.
Generic name: DB00523 alitretinoin
9CR
Formula: C20H28O2
Structure: There are 3 PDB structures containing this molecule although none are bound to the above target protein.
 
Generic name: DB00459 acitretin
Formula: C21H26O3
Structure: There are no structures of this molecule in the PDB.

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