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FLASH GENE
Symbol AR contributors: mct/npt/pgu - updated : 27-03-2013
HGNC name androgen receptor (dihydrotestosterone receptor; testicular feminization; spinal and bulbar muscular atrophy; Kennedy disease)
HGNC id 644
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Nervousbraindiencephalonhypothalamus highly
Reproductivefemale systembreastmammary gland  
 female systemovary   
 male systemprostate   
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow   
Connectivebone   
Nervouscentral   
cells
SystemCellPubmedSpeciesStageRna symbol
Reproductiveepithelial cell
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES Hydrophobic
STRUCTURE
motifs/domains
  • a modulating N-terminal domain with glutamine (poly CAG), proline and glycine (GGC) homopolymeric sequences, motif FXXLF
  • a DNA-binding domain
  • a NLS region that functions as mitotic chromatin binding-determining region and has a novel role in the regulation of the AR association with mitotic chromatin
  • a nuclear export signal (NES)(AR), a nuclear export signal in the ligand binding domain (LBD), playing a key role in AR ubiquitination and proteasome-dependent degradation in prostate cancer cells.
  • a C-terminal steroid-binding domain
  • hydrophobic ligand binding domain, and activation function 2 (AF2)
  • a central bipartite (class II) zinc finger DNA binding domain
  • mono polymer homomer , dimer
    HOMOLOGY
    interspecies ortholog to murine Ar
    ortholog to C.elegans Y73b6a.5
    Homologene
    FAMILY
  • steroid/thyroid hormone receptor superfamily
  • nuclear hormone receptors family
  • NR3 subfamily
  • CATEGORY enzyme , transcription factor , protooncogene , receptor nuclear , transport
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,chromatin/chromosome
    text
  • translocation into the nucleus upon binding the hormone ligand
  • GLI1 could be colocalized in the nucleus with AR in the absence of appropriate ligands
  • basic FUNCTION
  • regulation of androgen action (cellular proliferation and differentiation in target tissues)
  • steroid hormone activated transcription factor
  • stimulating transcription of androgen responsive genes
  • may function as both a suppressor and a proliferator to suppress or promote prostate cancer metastasis
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    text
  • sex differentiation
  • small molecule transport
  • PATHWAY
    metabolism
    signaling hormonal
    cell-cell signaling
    a component
  • dimerized upon binding the hormone ligand
  • INTERACTION
    DNA binding
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • MADH3
  • HBOA (modulation of AR activity)
  • androgens
  • RAN
  • with RANBP9, interaction mediated by both the N-terminal domain and the DNA-binding domain
  • interacting with PMEPA1 (negatively regulates the stability of AR protein by enhancing AR ubiquitination and proteasome-mediated degradation through NEDD4)
  • AES physically interacts with the N-terminal domain of AR and inhibits AR-driven transcription
  • substrate of Aurora-A and elevated AURKA could contribute to androgen-independent cell growth by phosphorylation and activation of AR
  • physical interaction between GLI1 and AR
  • BTG2 complexing with AR via an LxxLL-dependent mechanism and may play a role in prostate cancer via modulating the AR signaling pathway
  • GLI1 play a central role in SHH signaling in prostate cancer, and can act as a co-repressor to substantially block AR-mediated transactivation, at least in part, by directly interacting with AR
  • DNMT1 operates either as a functional intermediary or in cooperation with E2F1 inhibiting AR gene expression in a methylation independent manner
  • ZEB1 binds to an E-box sequence in the AR gene promoter, and physically interacts with AR in human foreskin cells
  • ATF3 can directly bind the androgen receptor (AR) and consequently repress AR-mediated gene expression (
  • CCT6A interacts with androgen receptor (AR)
  • DDB2 is a novel androgen receptor (AR)-interacting protein, mediating contact with AR and CUL4A-DDB1 complex for AR ubiquitination/degradation
  • ERG redirects AR to a set of genes including SOX9 that are not normally androgen stimulated, and SOX9 is a critical downstream effector of ERG in TMPRSS2:ERG fusion-positive prostate cancer (PCa)
  • ELF3 is a repressor of AR transcriptional activity
  • KDM4B enzymatic activity is required to enhance AR transcriptional activity
  • UBE2B is a critical target gene of AR in Sertoli cells, mediating the function of AR in spermatogenesis by promoting H2A ubiquitylation
  • IPO7 binding to AR, however, inhibits import by shielding the bipartite nuclear localization signal (NLS)
  • cell & other
    REGULATION
    activated by DAPK3 (interaction of DAPK3 with AR seems to be mediated in part by apoptosis antagonizing transcription factor and in part by direct binding)
    induced by FOXO3A
    repressed by MADH3 (repression of AR mediated transcription)
    Phosphorylated by CDK9 (phosphorylation of AR S81 is an important step in regulating AR transcriptional activity and prostate cancer cell growth)
    Other coregulated by SMAD3 in prostate cancer cells
    androgen induces SUMO2 and SUMO3 modification (SUMOylation) of the endogenous AR in prostate cancer cells, which is also reflected in the chromatin-bound receptor
    ASSOCIATED DISORDERS
    corresponding disease(s) AIS , SBMA
    related resource Androgen receptor
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification    
    in prostate and breast cancers
    tumoral     --over  
    of both AR and ZNF652 in clinically organ-defined prostate cancer are associated with a statistically increased risk of relapse (Pubmed 20204290)
    constitutional     --over  
    in patients with severe hypospadias
    Susceptibility
  • to prostate cancer and uterine endometrial carcinoma with expansion of CAG repeat
  • early-onset androgenetic alopecia(AGA)
  • to Polycystic Ovary Syndrome (PCOS)
  • to postmenopausal breast cancer risk
  • to idiopathic male infertility
  • to isolated hypospadias
  • Variant & Polymorphism repeat , other
  • expansion of polyglutamine tract causes SBMA (Kennedy disease)
  • a smaller size of the polyGLN region may be associated with the development of prostate cancers or with PCOS
  • GGN repeats variation increasing the risk of AGA
  • variants may modify hormone therapy associated postmenopausal breast cancer risk
  • association between increased androgen receptor CAG length and idiopathic male infertility, suggesting that even subtle disruptions in the androgen axis may compromise male fertility
  • boys with isolated hypospadias have longer CAG alleles in AR, which may be related with the development of this congenital malformation
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveprostate
    modulation of ELF3 expression and/or AR/ELF3 interaction may have utility in the treatment of prostate carcinoma
    cancerreproductiveprostate
    . ideal therapeutic approach(es) could be to target the proliferative function or suppressive function of AR separately, which could be achieved by development of specific vehicles that carry androgens only to those prostate cells with AR suppressive func
    ANIMAL & CELL MODELS
    transgenic mice developing many of the motor sympltoms of SBMA