Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

AR (P10275) - Overview - Molecular Target Synopsis

Protein


AR, Androgen receptor
UniProt P10275

Also Known as ANDR_HUMAN, AR, DHTR, NR3C4

Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3., Isoform 3 and isoform 4 lack the C-terminal ligand-binding domain and may therefore constitutively activate the transcription of a specific set of genes independently of steroid hormones. Binds DNA as a homodimer. Part of a ternary complex containing AR, EFCAB6/DJBP and PARK7. Interacts with HIPK3 and NR0B2 in the presence of androgen. The ligand binding domain interacts with KAT7/HBO1 in the presence of dihydrotestosterone. Interacts with EFCAB6/DJBP, PELP1, PQBP1, RANBP9, RBAK, SPDEF, SRA1, TGFB1I1 and RREB1. Interacts with ZMIZ1/ZIMP10 and ZMIZ2/ZMIP7 which both enhance its transactivation activity. Interacts with SLC30A9 and RAD54L2/ARIP4. Interacts via the ligand-binding domain with LXXLL and FXXLF motifs from NCOA1, NCOA2, NCOA3, NCOA4 and MAGEA11. The AR N-terminal poly-Gln region binds Ran resulting in enhancement of AR-mediated transactivation. Ran-binding decreases as the poly-Gln length increases. Interacts with HIP1 (via coiled coil domain). Interacts (via ligand-binding domain) with TRIM68. Interacts with TNK2. Interacts with USP26. Interacts with RNF6. Interacts (regulated by RNF6 probably through polyubiquitination) with RNF14; regulates AR transcriptional activity. Interacts with PRMT2 and TRIM24. Interacts with RACK1. Interacts with RANBP10; this interaction enhances dihydrotestosterone-induced AR transcriptional activity. Interacts with PRPF6 in a hormone-independent way; this interaction enhances dihydrotestosterone-induced AR transcriptional activity. Interacts with STK4/MST1. Interacts with ZIPK/DAPK3. Interacts with LPXN. Interacts with MAK. Part of a complex containing AR, MAK and NCOA3. Interacts with CRY1. Interacts with CCAR1 and GATA2. Interacts with ZNF318 (By similarity). Interacts with BUD31 (PubMed:25091737). Interacts with ARID4A (PubMed:23487765). Interacts with ARID4B (By similarity). Interacts (via NR LBD domain) with ZBTB7A; the interaction is direct and androgen-dependent (PubMed:20812024). Interacts with NCOR1 (PubMed:20812024). Interacts with NCOR2 (PubMed:20812024).

5VO4
CRYSTAL STRUCTURE OF THE ANDROGEN RECEPTOR LIGAND BINDING DOMAIN IN COMPLEX WITH 5-(2-FLUORO-4-HYDROXYPHENYL)-1-METHYL-1H-PYRROLE-2- CARBONITRILE
RCSB/PDB
Inspect Structure
See all 3D Structures for AR

Isoforms / Transcripts (Protein Coding)


Drugs


AR is targeted by Approved Drugs Oxymetholone, Dromostanolone Propionate, Ethylestrenol, Nilutamide, Alitretinoin, Etretinate, Enzalutamide, Fluoxymesterone, Testosterone Cypionate, Bexarotene, Testosterone Undecanoate, Nandrolone Decanoate, Testosterone Enanthate, Testosterone Propionate, Stanozolol, Oxandrolone, Bicalutamide, Nandrolone Phenpropionate, Flutamide, Testosterone, Tazarotene, Methyltestosterone, Danazol. (see details)
Oxymetholone
Dromostanolone Propionate
Ethylestrenol
Nilutamide
Alitretinoin
Etretinate
Enzalutamide
Fluoxymesterone
Testosterone Cypionate
Bexarotene
Testosterone Undecanoate
Nandrolone Decanoate
Testosterone Enanthate
Testosterone Propionate
Stanozolol
Oxandrolone
Bicalutamide
Nandrolone Phenpropionate
Flutamide
Testosterone
Tazarotene
Methyltestosterone
Danazol

Sub-cellular localization


UniProt: AR is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: AR is active in the following subcellular-locations: cytoplasm, cytosol, nuclear chromatin, nuclear speck, nucleoplasm, nucleus, plasma membrane, protein-containing complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project AR has gain in 2 cell-lines, loss in 31 cell-lines and no signal in 972 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MCF7, T47D, BT_549

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: LNCAP, MDA-MB-453, MFM-223

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HSMM, NHLF, BJ

(see details)

3D Structures


For AR there are:
95 structures (104 chains) solved
94 are solved in complex with at least one small molecule ligand
16 are solved with an approved drug

AR is solved in complex with the approved drug(s):

TES/TESTOSTERONE (2AM9_A, 2Q7I_A, 2Q7J_A, 2Q7K_A, 2Q7L_A, 2YHD_A, 2YLO_A, 2YLP_A, 2YLQ_A, 3ZQT_A, 4HLW_A),
T3/LIOTHYRONINE (2PIV_A, 2PIW_A),
FLF/FLUFENAMIC ACID (2PIX_A),
MXD/MINOXIDIL (4K7A_A),
CA4/CYPROTERONE ACETATE (2OZ7_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


AR has been screened with compounds ( bioactivities). (see details)