Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

AR

contributors: mct/npt/pgu - updated : 27-06-2019

HGNC name	androgen receptor (dihydrotestosterone receptor; testicular feminization; spinal and bulbar muscular atrophy; Kennedy disease)
HGNC id	644

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain diencephalon hypothalamus   highly Reproductive female system breast mammary gland       female system ovary         male system prostate

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow       Connective bone       Nervous central

cells

System Cell Pubmed Species Stage Rna symbol Reproductive epithelial 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
	AR is colocalized with NR4A1 in the nucleus in an androgen-dependent manner

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
	BCAS2 can form a complex with AR and HSP90AB1, it may function with HSP90 to stabilise AR protein from being degraded by proteasome

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
	AR protein, translocated into the nucleus in the presence of androgen, modulates likely NR4A1 transactivation
	ATF3 can directly bind the androgen receptor (AR) and consequently repress AR-mediated gene expression (
	specific interaction between the mutant androgen receptor (AR), a protein associated with spinal and bulbar muscular atrophy (SBMA), and the nuclear protein PAXIP1
	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
	MAZ and AR are interrelated and MAZ plays an important role in Prostate cancer (PCa) pathogenesis
	WDR77 is a coactivator of androgen receptor (AR), with distinct growth suppression and promotion function in gender specific endocrine organs and their malignancies
	UBE2B is a critical target gene of AR in Sertoli cells, mediating the function of AR in spermatogenesis by promoting H2A ubiquitylation
	AR-CCL4-STAT3 axis is key regulator during prostate tumor initiation, suggesting important roles of infiltrating macrophages and inflammatory cytokines for the prostate tumorigenesis
	acts in a pro-proliferative manner by stabilizing AR and enhancing its cellular function
	IPO7 binding to AR, however, inhibits import by shielding the bipartite nuclear localization signal (NLS)
	MLXIPL interacts with AR and regulates its transcriptional activity
	CACUL1 directly associates with AR and suppresses AR transcriptional activity
	ING2 interacts with AR and hampers the AR transcriptional activation, causes growth arrest, and induces cellular senescence
	potential crosstalk between ING1 and ING2 tumor suppressors to inhibit AR signaling and induce cellular senescence in PCa cells
	FOXA1 is a negative regulator of SEMA3C and SEMA3C is a novel target of AR, GATA2, and FOXA1
	DHX15 regulates AR activity by modulating E3 ligase SIAH2-mediated AR ubiquitination independent of its ATPase activity
	functional interplay between AR and SRARP in breast cancer
	SUMO3 modification of PIAS1 modulates AR cellular distribution and stability
	AR cooperates with SMAD4 to maintain skeletal muscle homeostasis

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cancer reproductive prostate modulation of ELF3 expression and/or AR/ELF3 interaction may have utility in the treatment of prostate carcinoma cancer reproductive prostate . 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