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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
Corresponding disease
AIS androgen insensitivity syndrome
SBMA spinal and bulbar muscular atrophy
Location Xq12      Physical location : 66.763.873 - 66.944.119
Synonym name
  • dihydrotestosterone receptor
  • nuclear receptor subfamily 3 group C member 4
  • Synonym symbol(s) DHTR, NR3C4, KD, AIS, TFM, HUMARA, SBMA, SMAX1
    EC.number 3.1.3.48
    DNA
    TYPE functioning gene
    SPECIAL FEATURE arranged in tandem
    STRUCTURE 180.24 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence cytosine-phosphate-guanine/HTF
    Binding site   transcription factor   HRE
    motif repetitive sequence   triplet
    text structure
  • two polymorphic trinucleotide repeat segments encoding polyglutamine and polyglycine tracts in the N terminal transactivation domain
  • the major site of transcription initiation is approximately 1.1 kb upstream of the initior methionine of AR protein lying in a GC rich region and containing a putative Sp1 binding site characteristic of a "housekeeping" promoter and a 44 base segment composed of alterning adenosine and guanosine residues
  • HRE interacting with an auxiliary factor to elicit androgen-specific regulation of ARNm
  • MAPPING cloned Y linked Y status confirmed
    Map cen - DXS1 - AR /SBMA - DXS159 - DXS106 ,DXS132 - qter
    Physical map
    LOC389863 X hypothetical gene supported by BC000228; NM_005077 LOC286449 Xq12 hypothetical gene supported by NM_005077; BC010100 LOC340554 Xq12 similar to KIAA1726 protein FLJ12525 Xq12-q13 hypothetical protein FLJ12525 FKSG43 Xq12 FKSG43 MSN Xq11.21-q12.1 moesin LOC392484 X similar to Nanog homeobox; homeobox transcription factor Nanog LOC347421 Xq12 similar to hypothetical protein FLJ40432 LOC389864 X hypothetical gene supported by AK091520; BC006550; BC007435; NM_002139 LOC389865 X LOC389865 Z39IG Xp11-q11 Homo sapiens Ig superfamily protein (Z39IG), mRNA. LOC392485 X similar to CG13379-PA LOC139272 Xq12 similar to eukaryotic initiation factor 4B HEPH Xq11-q12 hephaestin LOC392486 X similar to Probable G protein-coupled receptor GPR83 precursor LOC139270 Xq12 similar to Pyruvate kinase, M1 isozyme (Pyruvate kinase muscle isozyme) (Cytosolic thyroid hormone-binding protein) (CTHBP) (THBP1) XEDAR Xp22 similar to Pyruvate kinase, M1 isozyme (Pyruvate kinase muscle isozyme) (Cytosolic thyroid hormone-binding protein) (CTHBP) (THBP1) AR Xq11.21-q12.1 androgen receptor (dihydrotestosterone receptor; testicular feminization; spinal and bulbar muscular atrophy; Kennedy disease) OPHN1 Xq12 oligophrenin 1 PGK1P1 Xq12 phosphoglycerate kinase 1, pseudogene 1 MGC21416 Xq12 hypothetical protein MGC21416 LOC392487 X similar to ribosomal protein L31 STARD8 Xq12 START domain containing 8 LOC389866 X similar to PAI-1 mRNA-binding protein; chromodomain helicase DNA binding protein 3 interacting protein EFNB1 Xq12 ephrin-B1 LOC389867 X LOC389867 PJA1 Xq12 praja 1 FLJ33610 Xq13.1 hypothetical protein FLJ33610 HCP43 Xq13.1 cytochrome c, somatic pseudogene TED Xq13.1 TED protein ED1 Xq12-q13.1 ectodermal dysplasia 1, anhidrotic
    RNA
    TRANSCRIPTS type messenger
    text at least 2
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    - - - 10000 - - major in human prostate 1988 3216866
    - - - 7000 - - less abundant in human prostate 1988 3216866
    - - - 87 - - 1988 3216866
    lacking the normal N terminus found in AR-B
    - - - 110 - - 1988 3216866
    - - - 11000 - - prostate, cancer cell lines 1988 3377788
    - - - 8500 - - prostate, cancer cell lines 1988 3377788
    - - - 4700 - - prostate, cancer cell lines 1988 3377788
    8 - 4314 - 920 - 2002 12015328
    8 - 1765 - 388 - 2002 12015328
    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
  • MAGEA11 links N-terminal domains of AR and EP300 to promote transcriptional synergy through a cadre of FXXLF-related interacting motifs
  • 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
  • coregulator effects of MAGEA11 on the AR N and C-terminal interaction amplify the androgen-dependent transcriptional response to EP300 required for normal human male sex development in utero
  • 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
  • MAGEA11 increases AR transcriptional activity by forming a molecular bridge between transcriptionally active AR dimers
  • 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